First Aid 2013 PDF

A STUDENT-TO-STUDENT GUIDE
..,.. Advice from students who aced the 2012 exam
..,.. 1200+ frequently tested facts and mnemonics
..,.. Hundreds of high-yield color images and diagrams throughout
..,.. Student ratings of more than 300 review products

TAO LE, MD, MHS
Associate Clinical Professor of Medicine and Pediatrics
Chief, Section of Allergy and Immunology
Department of Medicine
University of Louisville
VIKAS BHUSHAN, MD
Diagnostic Radiologist
Los Angeles
VIVEK T. KULKARNI
Yale School of Medicine
Class of 2014
MAT THEW M. S OCHAT

Warren Alpert Medical School of Brown University
Class of 2013
ID Medical
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The McGrawHill Companies 'ii'll
, ,.
First Aid for the USMLE Step 1 2013: A Student-to-Student Guide
Copyright 2013 by Tao Le and Vikas Bhushan. All rights reserved. Printed in the United States of America. Except as per
mitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any
form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher.
Previous editions copyright 1991 through 2012 by Vikas Bhushan and Tao Le. First edition copyright 1990, 1989 by
Vikas Bhushan, Jeffrey Hansen, and Edward Hon.
Photo credits for this book begin on page 633 and are considered an extension of this copyright page.
First Aid for the is a registered trademark of The McGraw-Hill Companies, Inc.
1 2 3 4 5 6 7 8 9 0 DOW/DOW 14 13 12
ISBN 978-0-07-180232-1
MHID 0-07-180232-0
ISSN 1532-6020
Notice
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes
in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources
believed to be reliable in their efforts to provide information that is complete and generally in accord with the stan
dards accepted at the time of publication. However, in view of the possibility of human error or changes in medical
sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or pub
lication of this work warrants that the information contained herein is in every respect accurate or complete, and they
disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained
in this work. Readers are encouraged to confirm the information contained herein with other sources. For example
and in particular, readers are advised to check the product information sheet included in the package of each drug
they plan to administer to be certain that the information contained in this work is accurate and that changes have
not been made in the recommended dose or in the contraindications for administration. This recommendation is of
particular importance in connection with new or infrequently used drugs.
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Dedication
To the contributors to this and past editions, who took time to share
their knowledge, insight, and humor for the benefit of students.
Contents
Contributing Authors vii How to Contribute XVII
Associate Authors viii How to Use This Book xix
Faculty Reviewers ix Common USMLE Laboratory Values XXI
Preface xi Basic Science Discipline Cross-Reference

Table for High-Yield Facts xxiii
Special Acknowledgments xii
First Aid Checklist for the USMLE Step 1 xxiv
Acknowledgments for Online Contributors xiii
SECTION I G UIDE TO EFFICIE NT E XAM PREPAR ATIO N 1
Introduction 2 Clinical Vignette Strategies 21
USMLE Step 1-The Basics 2 If You Think You Failed 22
Defining Your Goal 12 If You Failed 22
Timeline for Study 12 Testing Agencies 23
Study Materials 17 References 23
Test-Taking Strategies 19
SECTION I SUPPLEMENT SPECIAL SIT UATIO NS 25
First Aid for the International Medical Graduate 26 First Aid for the Podiatric Medical Student 41
First Aid for the Osteopathic Medical Student 36 First Aid for the Student with a Disability 43
SECTION II HIGH-YIELD GE NERAL PRI NCIPLES 45
How to Use the Database 46 Immunology 191
Behavioral Science 49 Pathology 211
Biochemistry 63 Pharmacology 225
Microbiology 117
v
SECTION Ill HIGH-YIELD ORGA N SYSTE MS 245
Cardiovascular 249 Psychiatry 457
Endocrine 285 Renal 477
Gastrointestinal 307 Reproductive, 503
Hematology and Oncology 343 Respiratory 543
Musculoskeletal, Skin, and Connective Tissue 377 Rapid Review 565
Neurology 407
SECTION IV TOP-RATED REVIEW RESO URCES 583
How to Use the Database 584 Microbiology and Immunology 601

IJ
Question Banks 586 Pathology 605
Question Books 587 Pharmacology 610
Internet Sites 588 Physiology 614
Comprehensive 589 Commercial Review Courses 619
Anatomy, Embryology, and Neuroscience 591 Publisher Contacts 624
Behavioral Science 595 Abbreviations and Symbols 625
Biochemistry 597 Photo Acknowledgments 633
Cell Biology and Histology 599
Index 641 About the Authors 695
VI
Contri b uti ng Authors
JACOB BARANOSKI MAX C. PETERSEN

Medical Scientist Training Program
Class of 2014
ROBERT STRETCH
VICKI Z. J. BING
Class of 2014
Class of 2014
GARTH STROHBEHN
JEFFREY S. FUTTERLEIB Yale School of Medicine
Yale School of Medicine Class of 2014
Class of 2013
NICHOLAS THEODOSAKIS
ABHIJEET GUMMADAVELLI Medical Scientist Training Program
Yale School of Medicine Yale School of Medicine
Class of 2014
RICHARD P. USATINE, MD
LAUREN HIBLER Dermatology Images Contributor
Professor, Dermatology and Cutaneous Surgery
Professor, Family and Community Medicine
Class of 2014
University of Texas Health Science Center San Antonio
JEFFREY HOFMANN CAROLINE A. WALKER

Warren Alpert Medical School of Brown University Yale School of Medicine
Class of 2016 Class of 2014
OLGA LAUR SAMANTHA X. Y. WANG

WALTER F. WIGGINS, PhD

KELSEY B. LOELIGER
Editor, firstaidteam.com
Medical Scientist Training Program
Wake Forest School of Medicine
Class of 2014
GORAN MICEVIC PETER ZHAO

Medical Scientist Training Program Yale School of Medicine
Yale School of Medicine Class of 2014
VI I
Associate Authors
FADY AKLADIOS AMY MORENO

Medical University of the Americas Yale School of Medicine
ADITYA BARDIA, MD, MPH

AYESHA NZERIBE
Attending Physician, Massachusetts General Hospital Cancer Center
Instructor in Medicine, Harvard Medical School Warren Alpert Medical School of Brown University
Class of 2013
MICHELLE M. BRAVO
Warren Alpert Medical School of Brown University KEZIA SPENCE
Class of 2013 Warren Alpert Medical School of Brown University
Class of 2013
RAFAEL A. BUERBA
Class of 2014
RANY WOO
Class of 2013
JONATHAN FU
Class of 2013 ANDREW HANOI WU
Boston University School of Medicine
ALEJANDRO RAFAEL GENER Class of 201 5
Universidad Central del Caribe

Class of 201 5
MICHAEL XIONG
Warren Alpert Medical School of Brown University
ASHWANI GORE
Class of 201 5
St. George's University School of Medicine
Class of 201 5
PATRICIA ZADNICK
JAMES M. GRAY Johns Hopkins School of Medicine
University College Dublin School of Medicine and Medical Science Class of 2014
Class of 2014
CHRISTINE ZENDER-PRINCETON, DO
WILLIAM L. HWANG, MSc
Resident Physician, Lakeland Regional Healthcare
Health Sciences & Technology and Biophysics Programs
Adjunct Professor, Clinical
Harvard University/Massachusetts Institute of Technology
Michigan State University College of Medicine
MD/PhD candidate
KATHARINE JOO JINYU (JANE) ZHANG

Warren Alpert Medical School of Brown University Warren Alpert Medical School of Brown University
VI I I
Faculty Reviewers
CHARLES DELA CRUZ, MD SHANTA KAPADIA, MD
Assistant Professor, Department of Pulmonary and Critical Care Medicine Lecturer, Department of Surgery
EMILY R. ESPOSITO, PhD BERTRAM KATZUNG, MD, PhD

Assistant Professor Professor Emeritus
Sullivan University College of Pharmacy University of California, San Francisco
CONRAD FISCHER, MD
GERALD LEE, MD
Associate Professor of Physiology, Medicine, and Pharmacology
Assistant Professor, Section of Allergy and Immunology
Touro College of Medicine, New York City
Department of Internal Medicine
University of Louisville School of Medicine
STUART FLYNN , MD
Dean, College of Medicine
WARREN LEVINSON, MD, PhD
The University of Arizona, Phoenix
Professor, Department of Microbiology and Immunology
University of California, San Francisco
ANUJ GAGGAR, MD
Clinical Fellow
Department of Infectious Disease N ICHOLAS MAHONEY, MD
University of San Francisco School of Medicine Assistant Professor, Department of Ophthalmology
Wilmer Eye Institute/Johns Hopkins University
MATTHEW GARABEDIAN, MD
Division of Maternal-Fetal Medicine PETER MARKS, MD, PhD
Department of Obstetrics and Gynecology
Associate Professor, Department of Internal Medicine
Santa Clara Valley Medical Center
ANTHONY GLASER, MD, PhD

Assistant Professor, Department of Family Medicine
PATRICIA J. MElTING, PhD
Medical University of South Carolina Professor of Physiology & Pharmacology and of Medicine
Vice Chancellor and Senior Associate Dean for Student Affairs
The University of Toledo College of Medicine and Life Sciences
RYAN C. W. HALL, MD
Assistant Professor, Department of Medical Education
University of Central Florida, Orlando AFSOON MOKTAR, PhD
Affiliate Assistant Professor, Department of Psychiatry
Assistant Professor
University of South Florida, Tampa
Sullivan University College of Pharmacy
RAJESH JARI, MD, MBA

ROBERT NOVAK, MD
Spine, Medicine, and Rehabilitation Therapies-SMART Pain Management
Westminster and White Marsh, Maryland Chair, Department of Pathology and Laboratory Medicine
Akron Children's Hospital
KURT JOHNSON , PhD

Professor, Department of Anatomy and Regenerative Biology and DAVID PERRY, PhD
Department of Obstetrics and Gynecology Professor, Department of Pharmacology and Physiology
George Washington University School of Medicine George Washington University School of Medicine
IX
MICHAEL S. RAFII, MD, PhD HOWARD STEINMAN, PhD
Director, Memory Disorders Clinic Professor, Department of Biochemistry
Assistant Professor of Neurosciences Assistant Dean of Biomedical Science Education
University of California San Diego Health System Albert Einstein College of Medicine
STEPHEN THUNG, MD
DANIEL J. RUBIN, MD, MSC Associate Professor, Department of Obstetrics/Gynecology
Ohio State University
Assistant Professor of Medicine, Division of Endocrinology
Associate Program Director, Endocrinology Fellowship
Temple University School of Medicine RICHARD P. USATINE, MD
Professor, Dermatology and Cutaneous Surgery
Professor, Family and Community Medicine
University of Texas Health Science Center San Antonio
JOSEPH SCHINDLER, MD
Assistant Professor, Department of Neurology and Neurosurgery
Clinical Director, Yale New Haven Stroke Program HILARY VERNON, MD
Yale School of Medicine Assistant Professor, McKusick-Nathans Institute of Genetic Medicine
Johns Hopkins University
SANJIV SHAH, MD ADAM WEINSTEIN, MD

Assistant Professor, Division of Cardiology Assistant Professor, Section of Pediatric Nephrology
Department of Medicine Department of Pediatrics
Northwestern University Geisel School of Medicine at Dartmouth
X
Preface
With this edition o f First Aid for the USMLE Step 1, we continue our commitment to provide students with the most
useful and up-to-elate preparation guide for the USMLE Step 1 . Th is edition represents a comprehensive revision in
many ways and includes:
An updated, full-color design with new color photos, enhanced illustrations, and improved formatting of tabular
material and mnemonics integrated throughout the text.
Extensive text and image revisions, clarifications, errata corrections, and new material based on student
experience with the 2 0 1 2 administrations of the USMLE Step 1 .
A revised and updated exam preparation guide for the U SMLE Step 1 with updated data from the NBME and
NRMP. Includes student feedback as well as study and test-taking strategies for the current exam format.
Thoroughly revised U S M LE advice for international medical graduates and osteopath ic medical students.
More than 1 200 frequently tested facts and useful mnemonics, including hundreds of new or revised entries and
tables.
An updated guide to recommended U SMLE Step 1 review resources, based on a nationwide survey of randomly
selected th ird-year medical students.
Bm1us Step 1 h igh-yield facts, cases, video lectures, corrections, and updates can be found exclusively on our
blog at www.firstaidteam . com.
The improvements in th is edition would not have been possible without the help of the thousands of medical
students, graduates, and faculty members who contributed their feedback, suggestions, and error corrections. We
invite students and faculty to continue sharing their thoughts and ideas to help us i mprove First Aid for the USMLE
Step 1. ( See How to Contribute, p. xvi i . )
Lou isville Tao Le

Los Angeles Vikas Bhushan
New Haven Vivek T. Kulkarni
Providence Matthew M. Sochat
XI
Specia l Acknowledgments
Th is has been a collaborative project from the start. We gratefully acknowledge the thousands o f thoughtful
comments, corrections, and advice of the many medical students, international medical graduates, and faculty who
have supported the authors in the continuing development of First Aid for the USMLE Step 1.
We provide special acknowledgment and thanks to the following students who contributed on many l evels: Peter
Gayed, Ch ika Anekwe, Ashleigh Bouchelion, Jack Cossman, Rahul Dalal, Abdelaziz Farhat, Yun Rose Li, E l izabeth
Marshal l , Sean Martin , and Aj it Rao.
For help on the Web , thanks to Jaysson Brooks, Molly Lewis, Sean Martin , Luke M urray, Sarah-Grace Wesley, and
Vamsi Kancherla.
Thanks to the First Aid Step 1 Express team: Jeffrey Hofmann, Will iam Hwang, Stephen A. Allsop, Karolina Brook,
Aaron Feinstein, Adrian I-laimovich, Katie Lee Hwang, Vivek Kulkarni, Mihan Lee, ilay Patel, Max Petersen , N ick
Theodosakis, and Rany Woo.
For support and encouragement throughout the process, we are grateful to Thao Pham and Jonathan Kirsch , Esq.
Thanks to Selina Frankl in and Lou ise Petersen for organizing and supporting the proj ect. Thanks to our publ isher,
McGraw-H ill, for the valuable assistance of its staff, including M idge Haramis, Jeffrey H e rzich, and John Wil l iams.
For enthusiasm, support, and commitment for this ongoing and ever-challenging project, thanks to our editor,
Catherine Johnson .
For editorial support, enormous thanks to Emma D. Underdown , Linda Bradford, and Linda Davoli . We are also
grateful to Tara Price for the interior design of the book and to the medical illustrators, Diana Kryski and Hans
euhart, for their great work on the new and updated illustrati ons. Special thanks to Jan Beclnarczuk for a greatly
improved index. Many thanks to Dr. Richard Usatine of Usatine Media for his outstanding clermatologic image and
editorial contributions. We are also very thankful to Freel Howell and Robert Cannon of Textensor for providing
access and support to their Annotate collaborative platform, wh ich will allow us to more efficiently manage
contributions from thousands of medical students and graduates . Lastly, tremendous thanks to Rainbow Graphics,
especially David Hommel and Tina Castle, for remarkable ongoing editorial and production work under time
pressure .
Louisville Tao Le
Los Angeles Vikas Bhushan
New Haven Vivek T. Kulkarni
Providence Matthew M. Sochat
XI I
Acknowl edgments
for On l i n e Contri butors
This year we were fortunate t o receive the input of thousands of medical students and graduates who provided new material, clarifications,
and potential corrections through our Web site and our new collaborative editing platform. This has been a tremendous help in clarifying
difficult concepts, correcting errata from the previous edition, and minimizing new errata during the revision of the current edition.
This reflects our long-standing vision of a true student-to-student publication. We have done our best to thank each person individually
below, but we recognize that errors and omissions are likely. Therefore, we will post an updated list of acknowledgments at our Web site
www.firstaidteam.com under the Errata and Updates tab. We will gladly make corrections if they are brought to our attention.
For submitting contributions and corrections, many thanks to Solomon Abay, Hussein Abbas, Ramzi Abboud, Assya Abdallah, Mohamad Abdelfattah,
George Abdelmessieh, Salwan Abdullah, Yazan Abou-lsmail, Khalil Abusabha, Stacy Achdjian, Ebele Achebe, James Ackerman, Nivia Acosta, lance
Adams, Robert Adams, Carson Adams, Adebanke Adebayo, Jessica Adefusika, Mona Adeli, Mishuka Adhikary, Amina Adil, Brandon Adler, David Adler,
Sumit Agarwal, Deepak Agarwal, Manik Aggarwal, Neha Agnihotri, Nupur Agrawal, Cynthia Aguirre, Daniel Ahmad, Michele Ahmadi, Tina Ahmadinejad,
Rabia Ahmed, Kamran Ahmed, Mushfique Ahmed, Annie Ahn, Sahir Ahsan, Zahab Ahsan, Jared Aida, Carol Akers, Oyinade Akinyede, Fady Akladios,
Danso Ako-Adjei, Ani! Akoon, Erik Akopian, Oluronke Alate, Mahdi Alajaj, Mohammad Alam, Ridwaan Albeiruti, Carlos Albrecht, Anas Albrejawi Alhomsi,
Austin Albright, Carmen Alcala, Tiara Aldridge, Samia Aleem, Michail Alevizakos, Sheby Alexander, Eirene Alexandrou, Shad Ali, Mohammad Ali, Huzair
Ali, Munni Ali, Mariam Ali, Zahra Alibrahim, Evan Alicuben, Narges Alipanah, Atush Alipuria, Niloo Allahyari, laura Almquist, Raed Alnaji, Brock Alonzo,
Omar AI-Qudsi, Zina AI-Sakini, Aileen Alviar, Saif Alzoobaee, Chelsey Amer, Kunal Amin, Alec Amram, Keshav Anand, Kayley Ancy, Carl Andersen,
Thomas Anderson, Dallin Anderson, Daniel Anderson, Mark Anderson, David Andrews, Zubair Ansari, Ali Ansary, Chase Ansok, Ahmed Antably, Emeka
Anyanwu, Dillon Arando, Chris Arbonies, Saeed Arefanian, Alejandro Arenas, Nkiruka Arinze, Anne Armstrong, Grayson Armstrong, Jonathan Arnold,
Mack Arroliga, Praag Arya, Rozana Asfour, Derrick Ashong, Karam Asmaro, Ricardo Aulet, Rik Austin, Meghan Auten, liezl Avila, Shiri Avraham, Temitope
Awosogba, Gabriel Axelrud, Derek Axibal, Reed Ayabe, Giselle Ayala, Ndang Azang-Njaah, Ali Ahsan Azeem, Eisha Azhar, Corneliu Bacauanu, Becca
Bacharach, Warren Backman, Karam Badran, Javier Baez, Kandy Bahadur, Sara Bahraini, Mirza Baig, Ursula Bailey, Erin Bailey, Mayank Bajpai, Joshua
Bakhsheshian, Maria Bakkal, Asha Balakrishnan, Jill Balala, Rajinder Balasuriya, Zach Balest, Rebekah Baltz, Gaurav Bansal, Aiyush Bansal, Faustino
Banuelos, Daniel Bar, Nicholas Barasch, Mike Barca, Nicolas Barcelo, Ayse Dalsu Baris, Anne Barnard, Morgan Barnell, Kyle Bartlett, Joshua Barzilai, Bruce
Bassi, Bennett Battle, Marianne Bauer, Mark Bauernfeind, Harinder K. Bawa, Omkar Baxi, Michael Baxter, Ahmad Najdat Bazarbashi, Joel Beachey, Tyler
Beals, Ryan Beck, Jessica Beckerman, Nic Beckmann, Angela Beckon, Sumeer Bedi, Rachel Beekman, Ryan Begley, Jordan Bell, Joseph Benedict,
Nontawan Benja-Athonsirikul, Krista Bergman, Justin Berkowitz, Elizabeth Berry, Adam Berry, Marina Bessel, Adam Betz, Anita Bharath, Suraj Bhargav,
Vijay Bhat, Ankit Bhatia, Nita Bhatt, Sajjad Akbar Bhatti, Osman Bhatty, Nora Biary, Charlotte Bibbee, Alexander Bick, David Bishop, Rohan Biswas, Rachel
Blair, Max Blanter, Jessamyn Blau, Greg Bligard, David Bluhm, Sarah Bly, Raymond Boakye, Satish Babu Bodapati, Joanne Boisvert, Craig Bollig, Romin
Bonakdar, Jeffrey Bonenfant, Valentina Bonev, Namrita Boparai, Nicholas Bope, Sanket Borgaonkar, Joshua Borsook, Tarrah Bowen, Anthony Bowen,
Grace Boynton, Hemal Brahmbhatt, Mike Bramati, James Brann, Steve Braun, Kathryn Breidenbach, Jennifer Bress, Jamie Brett, Betsy Breuker, Elizabeth
Brezinski, Valerie Brice, Bryan Broach, Benjamin Brockbank, Frank Brodie, Karolina Brooks, Aaron Brown, Sareena Brown, Blair Brown, Gabrielle Brown,
Ronnie Brown, Christopher Brown, Will Brubaker, Nataly Bruk, Tina Bruno, Jason Brustein, Daniel Bryan, Campbell Bryson, Rob Buchanan, Floyd Buen,
Antiem Bui, John Bui, Jaclyn Burch, Ross Burge, Katelyn Burgess, Adrian Burgos, Colin Burke, Stephen Burks, Bradley Burmeister, Sharlena Burnett,
lauren Burtz, Cathleen Bury, Aaron Bush, Alex Buss, Steve Butala, Emran Butt, Matt Byun, Armando Cabrera, Melissa Cain, Nora Callinan, Sean Campbell,
Andrew Campbell, Melissa Campos, Adam (anion, David Capaldi, lindsay Capron, Jordan Carl, Tyler Carllee, Silva Carlos, Harris Carmichael, Nathan
Carpenter, leah Carr, Madeline Carroll, Evan Carstensen, Phil Carullo, Priscilla Carvalho, Alan Casciola, Ryan Casserly, leon Castaneda, Crystal
Castaneda, Jonas Castaneda, Brandi Castro, Alexander Cavalea, Garrett Cavanaugh, Thomas Cayce, Alberto Cerra, Esther Cha, Ausim Chaghtai, Gaurab
Chakrabarti, Jason Chan, Daniela Chan, Maria Chancay, Anisha Chandiramani, Sidharth Chandra, Mahesh Chandrasekhar, Sunny Chang, Khalid Hamid
Changal, David Charles, Mubeen Sultan Cheema, Alice Chen, Thomas Chen, lu Chen, Joanna Chen, Frank Chen, Eric Chen, Andrew Chen, Daniel Cheng,
Jacklyn Cheng, Julie Cheng, Esther Cheng, Chris Chesnut, Monica Cheung, Michael Chevinsky, Sharon Chi, Tiffany Chi, Kelly Chien, Jordan Chinai, Cathy
Patricia Lee Ching, Anny Ching, Shideh Chinichian, Allen Chiou, Lironn Chitayat, Megan Chock, Michael Choe, Mohammad Rizwan Chaudhary, Ahmad
Chaudhry, Ryan Choudhury, Mohsin Chowdhury, laura Christensen, Andrew Christiansen, Amy Chu, Kai Chu, Philip Chu, Jonathan Chun, Jina Chung,
XIII
Andrew Cichowski, Anthony Cipriano, Dave Ciufo, Andrew Clair, Michael Clark, Summer Clark, Danielle Clark, Emily Clemetson, Michael Cloud, Sarah
Codrea, Steven Cogorno, Alex Cohen, Rachel Cohen-Shohet, Elizabeth Collins, Amy Collins, Xavier Colon, Jennifer Colon, Hadassah Consuegra Anderson,
Jonathan Copp, Nikhil Cordeiro, Samuel Cordeiro, Elizabeth Cordie, Sarah Cormie, Amarilis Cornejo, Eva Corona, Matthew Cossack, Ryan Cotter, Jennifer
Cottral, Molly Cowdrey, Laurel Cox, Katherine Cox, Gordon Crabtree, Paul Craig, Matthew Craig, Crystal Craig, Elizabeth Cramer, Teela Crecelius,
Katherine Crifasi, Brian Cripe, Michael Cronin, Nick Crowley, Niall Crowley, Daniel Croymans, Allison Cruse, John Cummins, William Currie, Eileen Curry,
Brian Curry, Carl D, Howard Dai, Jessica Dai, David Dai, Thomas Dailey, Pavan Dalal, Mariaana Dalangin, Erika Daley, Keren Dallalzadeh, Thuan Dang,
Avace Dani, Gabrielle Daniel, Ameesh Dara, Tyler Darnell, Ryan Daro, Tony Darrington, Alvin Das, Shayna Dattani, Neil Dattani, Shravan Dave, Joshua
Davidson, Kerri Davis, Andrew Davis, Chelsea Davis, Michael Davis, Noor Dawood, Solomon Dawson, Andrew Daya, Daniel Dayan, Charles De Jesus,
Hector De Jesus, Ivan De Jesus, Nastassia De Souza, Nakyda Dean, Nakydadean Dean, Malcolm Debaun, Cory Deburghgraeve, Johannes Decker, Jennifer
Decoste-Lopez, Alison Dedent, Raj Dedhia, Mhair Dekmezian, Henry Del Rosario, Ritchie Mae Delara, Sara Delarosa, Steven Delbello, James Delgadillo,
Joseph Delio, Samantha Demar, Dawit Demissie, Kathryn Demitruk, John Demuth, Kara Denby, Vedant Desai, Danielle Desjardins, Danielle Detelich,
Andrew Deutsch, Anjan Devaraj, Ryan Devenyi, David Deyoung, Trisha Dickey, Marine Dididze, Christine Dillingham, Bill Diplas, Ebony Dix, Erin Dizon,
Teresa Do, Chris Dobson, Taylor Dodgen, Natasha Dolgin, Sarah Donaldson, Patrick Dooling, Amy Dora, Bradleigh Dornfeld, Heather Douthitt, Dr Munaf,
Alex Drake, Mariah Dreisinger, Maggie Driscoll, lan Dryden, Xi Du, Milap Dubal, Genia Dubrovsky, Brittany Duchene, Matthew Duda, Sarah Duhon, Mark
Dukshtein, Rachelle Duquette, Zachary Dureau, Jonathan Dutt, Alison Dzwonczyk, Micah Eades, John Eager, Anas Easa, Christian Eckmann, Colin
Edwards, Jared Ee, Nima Eftekhary, Ashley Egan, Badi Eghterafi, Nick Eglitis, Ehren Ekhause, Lindsay Elbaum, Justen Elbayar, llyas Eli, Tyler Ellington,
Alexis Elliott, Alejandra Ellison-Barnes, Sora Ely, Matthew Emerich, Drew Emge, Trine Engebretsen, Christopher English, Chris English, Feras Entabi, Esther
Enuanwa, Elizabeth Ernst, Rito Escareno, Michael Esparza, Diego Espinoza, Chris Ethridge, Clay Evans, Brendan Everett, Abieyuwa Eweka, Cyril Eyadiel,
Nnenna Ezeilo, Abayomi Fabunmi, Eric Faden, Josh Fage, Laura Fagen, Kerolos Fahmi, Falcon Falcon, Kimberly Faldetta, Lu Fan, Hang Fang, Hongfei Fang,
Lawrence Fannon, Joseph Farahany, Abdelaziz Farhat, Bilal Farhat, Amy Farkas, Amanda Farris, Michael Fay, Alicia Febles De Lorow, ldo Feferkorn,
Rebecca Fega, Leah Feldman, Robert Feng, Jenny Feng, Yaniv Fenig, Elizabeth Fenstermacher, Agha Hassan Feroze, Abdullah Feroze, Michael Ferro,
Michael Fickes, Vikram Fielding-Singh, Tucker Fischbeck, Juliya Fisher, Alex Fisher, Mark Fisher, Erin Fitzgerald, Heidi Fjeldstad, Jason Flamendorf, Kenneth
Flax, Mario Flores, Katy Flynn-Meketon, Kelly Fong, Christopher Foote, Jon Forbes, Lisa Fosnot, Andrew Fouche, Nyssa Fox, Loren Fox, Sarah Franjoine,
Harris Frank, Miguel Frau, Rob Freeman, Monika Freiser, Appolinia Frey, Yev Freyvert, Martin Fried, Robin Friedman, Jamie Friedmanjamief, Melanie
Friess, Jason Frischhertz, Nathan Frogge, Simona Frunza-Stefan, Alicia Fuhrman, Tim Fuller, Tracy Fulton, Brian Fung, August Funk, Nicholas Furlani, Bob
Furlong, Michael Gabbard, Alex Gaidarski, James Gallagher, Sylvia Bea Galvan, Nikita Ganatra, Anjalika Gandhi, Niral Gandhi, Niket Gandhi, Abby
Gandolfi, Milan Ganger, Akshay Ganju, Jared Gans, lan Gao, Jennifer Gao, Maria Victoria Garcia, Heidy Garcia, Benjamin Garden, Michael Garitty, John
Garlich, Michael Gazes, Daniel Gealy, Alison Gegios, Steven Gelb, Scott Gelman, Alejandro Gener, Douglas George, Ramez Ghabour, Marcel Ghanem,
Saad Ghazipura, Alexander Ghobadimanesh, Martin Gibbs, David Gill, Harrison Gimbel, Will Gionfriddo, Jacob Gire, Christine Glendon, Steven Glenn,
Joshua Glick, Chad Glisch, Catherine Go, Shanette Go, Michelle Go, Nikhil Godbole, Melanie Goebel, Aneesh Goel, George Gold, Andrew Goldman,
Whitney Goldsberry, lan Goldstein, Greg Goldstein, Aaron Goldstein, Nicholas Golinvaux, Anurekha Gollapudi, Jane Golub, Charles Gonzales, Lillian
Gonzalez, Wilfreda Gonzalez, Javier Gonzalez, Abigail Goodman, Avi Goodman, Ashwani Gore, Shaun Gould, Morgen Govindan, Indira Gowda, Daniel
Grabell, Trevor Grace, Cynthia Grady, Jaykumar Grandhi, Rebecca Graves, James Gray, Emily Gray, Christian Greco, Clifton Green, Ari Greenbaum, Steven
Greenstein, Alexander Greenstein, Tobin Greensweig, Char Grif, Gabriel Griffin, Ashley Grigsby, Brian Grisez, Nathan Grohmann, Britt Gros, Bridget Gro s,
Kelli Gross, Daniel Grosser, Andrea Grosz, Alan Groves, Joanna Grzadziel, Allen Guehl, Arthur Guepe, Jonah Gunalda, Robin Guo, Ling Guo, Jessie Guo,
Akash Gupta, Sheena Gupta, Abhishek Gupta, Gita Gupta, Ankur Gupta, Apar Gupta, Kiran Guthikonda, Kai Ha, lnna Hadass, Cathryn Haeffele, Kevin
Hageman, Sue Hahn, Moosa Haider, Adrian Haimovich, Angie Hairrell, Mark Hall, Sarah Hall, Charles Hall, Jeremy Hall, Alexander Hallac, Akbar Hamid,
Kam Hanamaikai, John Hanks, Jesse Hansen, Stephanie Harbison, Brian Harms, Jessica Harrell, David Harrington, Holly Harris, Frank Harris, Jennifer
Harris, Cynthia Hart, Bridget Hartman, Heather Hartman, Becca Hartog, Georgina Hartzell, Zach Harvanek, Connor Hasbrook, Hasnain Hasham, Omar
Hashmi, Jordan Haskins, Ammar Hassan, John Hassani, Kai Hata, Mike Hausberger, Andriy Havrylyan, Liz Haworth, Shane Hawthorne, Shakaib Hayat,
Lisa Hayman, George Hayward, Sindalisa Hean, Jason Hedge, Elise Heeringa, Jeff Heimiiler, Christine Helou, Krista Hemmesch, Martha Henao, Phi lip
Hendley, Whitney Hendrickson, Rachel Henrickson, Eduardo Hernandez, Matthew Hernandez, Miriam Herschman, Anthony Herzog, Matthew Hess,
Amber Hetrick, Jarred Hicks, Andrew Higdon, David Hilburn, Derek Hill, Graham Hill, Julia Hiner, Jonathan Hirshberg, Whitney Hitchcock, Yoona Ho,
Marjorie Ho, Alan Hoang, Sandra Hobson, Max Hockstein, Evan Hodell, Aaron Hodes, Erika Hoenke, Zach Hoffman, Martin Hofmann, Kaitlin Holdstem,
Charles Hong, Michael Hong, Chris Hong, Austin Horrocks, Wendy Hosin, Elika Hoss, Reza Hosseini Ghomi, Pearl Houghteling, Nicholas Hountras, L.
Mclean House li, Kara Hoverson, Lee Howard, Ryan Howard, Tifany Hoyne, Ahmed Hozain, Ruth Hsiao, Jenmfer Hsu, Wei-Chun Hsu, Anna Hsu, Annie
Hsu, Jen Hsu, Derek Hsu, Peifen Hu, Jessie Hu, Cindy Hu, Charles Hua, Linda Huang, Hanwei Huang, Christopher Huelsman, Brandon Huffman, Myriam
Hughes, Hayley Hunt, Nakia Hunter, Jennie Huo, Lara Hurlburt, Irene Hurst, Mustafa Husaini, Adnan Hussain, Hanif Hussaini, Monica Huynh, Daniel
Hwang, Michael Hwang, Patrick Hyppolite, Adaora lfeanyi, Kevan lffrig, Atanas lliev, Hasan IMANLI, Peter lp, Neil Issar, Kilali lyalla, Mangala Iyengar, Lee
Jablow, Deidrya Jackson, Lishan Jackson, Robert Jackson, Joshua Jackson, Jacoby Jacobsen, Asif Jafferani, Syed Jaffery, Ariba Jahan, Supriya Jam, Amita
Jain, Sechin Jain, Christopher Jakubowski, Asha Jamzadeh, Samantha Jamga, Daniel Javaherian, Matthew Jaykel, Tim Jaykel, Isaac Jenabi, Jack Jeng,
Kimberly Jenkins, Kim Jenna, Brett Jensen, Jonathan Jerkins, Forrest Jespersen, Krishan Jethwa, Shiel Jhaveri, Lunan Ji, Rui Jiang, Yike Jiang, Ahce Jiang,
William Jiang, Ying Jin, Peter Jin, Bennett Johnson, Ben Johnson, Linda Johnson, Wcs Johnson, Stacey Johnson, I real Johnson, Brianna Johnson-Rabbett,
Benjamin Jones, Roger Jones, Tyler Jones, Chelsea Jones, Andrew Jones, Nate Jones, Patrick Jorda, Mary Kate Jordan, Lia Jordana, Walter Joseph, Claire
Joseph, Rahul Joy, Alexander Juhn, Jenny Jun, Sarah Jung, Michael Jung, Sam K, Nida K, Payal Kadakia, Clhan Kadipasaoglu, Jessica Kafer, Jodi Kagihara,
Rachel Kahn, Adam Kahn, Charissa Kahue, Mehboob Kalani, Mowffaq Kalantan, Shana Kalaria, Mariya Kalashnikova, Sudhir Kalaskar, Zach Kalb, Omar
Kallas, Kunal Kambli, Caroline Kan, Pridvi Kandagatla, Sean Kandel, Ravinder Kang, David Kang, Sarv Kannapiran, Ro er Kanumuri, Jordan Kapper, Ni a
Karamooz, Peter Karempelis, Syed Karim, Justin Karlin, Joshua Karlin, Krupa Karnik, Anthony Kasch, Stephen Kasteler, Kenan Katranji, Igor Katsyv, Leah
Katta, Monica Katz, Matthew Katz, Benjamin Kaufman, Anatoly Kazakin, Amir Ka erouninia, Matthew Kelley, Sandra Kellum, Jonathan Ken, Donan
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Kenleigh, Daniel Kennedy, Kristen Kent, Kyle Kern, Amanda Kern, Rohit Kesarwani, Briana Ketterer, Ryan Key, Andrew Keyser, Phue Khaing, Mazen Khan,
Rabnawaz Khan, ldrees Khan, Aimal Khan, Muhammad Zubair Khan, Shadab Khan, Rabeea Khan, Tamer Khashab, Sameer Khatri, Ben Khazan, Ali
Khiabani, Akhil Khosla, Gohar Khosravi, Michal Kidacki, Zachariah Kidman, Crystal Kiewert, Daniel Kil, David Kim, Ellen Kim, Grace Kim, Jenna Kim, Jun
Kim, Kristin Kim, Christopher Kim, Soo Jeong Kim, Phillip Kim, Ajin Kim, Julie Kim, Samuel Kim, David Kimball, Jonathan King, Eric King, Nikhar Kinger,
Kathleen Kirkland, Annah Kirkley, Drew Kiser, Joshua Kiss, Wissam Kiwan, Maximilian Klein, Nicole Klekowski, Kris Klem, Isaiah Kletenik, Dane Klett,
Bradley Kliewer, Michelle Knoll, Pin-Vi Ko, Brett Kadish, Kristin Koenig, Aaron Kofman, Lauren Kohan, Pratistha Koirala, Nadeem Kolia, Franchesca Konig
Toro, Matthew Koo, Hannah Kooperkamp, Yelena Korotkaya, Jacqueline Korpics, Karthik Kota, Uzma Kothawala, Yann-Fuu Kou, Adam Kowalski, David
Kraft, Scott Kramer, Landon Krantz, Sarah Krantz, Brad Krasnick, Carl Kraus, Vijay Krishna, Ross Krista!, Malgorzata Krzyszczak, Paul Kuder, Elizabeth
Kuilanoff, Nishat Kulkarni, Robret Kulwin, Keerthana Kumar, Anupam Kumar, Sanjay Kumar, Aashish Kumar, Hanesh Kumar, Preethi Kumar, Hiren
Kunadia, Joseph Kundukulam, Edward Kuoy, Daniel Kurbanov, Vadim Kurbatov, Ashleigh M. Kussman, Levon Kuypelyan, Melissa Kwan, Rui Kwan, Janet
Kwok, Levon Kyupelyan, Tiffany L, Alison La, Jennifer Ladd, Carlos Lago, Hamed Lahijani, Erica Lai, Isabella Lai, Kuan-Chi Lai, Bryan Lai, Rosalind Lai,
Charlene Lai, Chandru Jay Lalwani, Lauren Lambeth, Jon Lamee, Rongpei Lan, Megan Land, Kristen Landry, Maria Lapchenko, Marissa Lapedis, Caroline
Larosa, Derek Laskar, Joe Lau, Wincie Lau, Samantha Lavergne, John Le, Jessica Lee, Kacia Lee, Paul Lee, Raymond Lee, Dane Lee, Dianne Lee, Yungah
Lee, Jisoo Lee, Christina Lee, Katherine Lee, Joo Yeon Lee, Michelle N Lee, Eunjoo Lee, Anna Lee, Michelle Lee, Jason Lee, Jennifer Lee, Katie Lees, Lucas
Lenci, Kyle Leneweaver, Mike Leonard, Scott Lester, Stephanie Leung, Peggy Leung, Celine Leung, Steven Leung, Seth Levin, Matthew Levine, Kate Levy,
Vivian Levy, Natashia Lewis, Molly Lewis, Lei Li, Luming Li, Yun Li, Li Li, Angela Li, Kai Li, Carol Li, Bin Li, Qiansheng Liang, Emily Liebling, Sofia Ligard,
Caitlin Lim, Simon Lim, Lian Lim, Geoffrey Lim, David Lin, Alex Lin, Tsung Hsien Lin, Jennifer Ling, Matthew Listo, Alison Little, Amy Liu, Kevin Liu,
Emberlynn Liu, Lars Logdberg, Kevin Loh, Paula Lomba, David Long, Cesar Lopez Angel, Christopher Lops, Jaime Loso, Kristian Loveridge, Dylan Lovin,
Michele Luhm Vigor, Jason Luijasonl, Karen Luk, Chris Lunt, Leo Luo, David Luu, Ying Luu, Catherine Ly, Blair M, E M, Nilam M, Andrea Ma, Stephanie
Ma, Ashlee Macdonald, Andrew Macquarrie, Mahesh Madhavan, Jai Madhok, Selena Magalotti, Paula Magee, lsha Mahamud, Michael Mahan, Val
Maharaj, Mithu Maheswaranathan, Mithunan Maheswaranathan, Hadi Mahmaljy, Mhd Abdallah Mahrous, Herman Mai, Thi Mai, Leann Mainis, Vivian
Mai-Tran, Gary Mak, Lindsay Makara, Vyacheslav Makler, Slava Makler, Mona Malakouti, Veshal Malhotra, William Malins, llir Manaj, Sarah Mancini,
Jason Mandell, Morgan Mandigo, Nicole Mangiboyat, Christopher Manieri, Alexandra Mannix, Abdallah Mansour, Soohan Mansuri, David Mao,
Marnonette Marallag, Leanna Marderian, Fernando Mariz, Dan Marks, Benjamin Marsh, Kerry Marshall, Daniel Martig, Kent Martin, Pablo Martinez, Luis
Martinez, Ryan Martinez, Jaime Martinez, Pablo F. Martinez, Jessica Mason, Sunil Mathew, Gladcy Mathew, Irene Mathieu, Sandy Mazzoni, Jamie
Mazzurco, Ositadinma Mbadugha, Ndi Mbride, Tom Mcbride, Alexis Mccabe, Heather Mccain, Marissa Mccay, Brittani Mcclain, James Mcclurg, Jonathan
Mcgovern, Sarah Mcguffin, Caitlin Mcintyre, Nicholas Mckenna, Tina Mckenzie, Tyler Mckinnon, Lance Mcleroy, Jake Mcmillin, Colton Mcnichols, Casey
Means, Oren Mechanic, James Medley, Britton Mehr, Hirai Mehta, Komal Mehta, Dillon Meier, Chris Meinzen, Maayan Melamed, Joshua Melito, Clay
Merritt, Phoebe Mesiha, Andrew Meyers, Okechukwu Mgbemena, Erik Miguel, Amir Mikhchi, Mark Mikhly, Brian Miller, Moshe Miller, Andrew Miller,
Tom Miller, Chris Millhouse, Steven Mills, Daniel Miranda, Leonidas Miras, Anne Misiura, Stuart Mitchell, Kevin Mitchell, Todd Miyake, Takudzwa
Mkorombindo, Lauren Moak, Sarah Mohajeri, Abdirahman Mohamed, Girish Mohan, Desh Mohan, Chaitra Mohan, Shifa Mohiuddin, Ghulam Rehman
Mohyuddin, Jeffrey Mojica, Richard Molena, Domingo Molina, Daniel Mollengarden, Ryan Moore, Lindsay Morgenstern, Marina Morie, Andrew Morris,
Elizabeth Morris, Gregory Morris, Aimee Morris, Tyler Morrison, Daniel Mortensen, Chris Morton, Shawn Moshrefi, Natalie Mota, Saba Motakef, Moustafa
Moustafa, Murali Mukkamala, Benjamin Mullenbach, Katherine Mun, Marlon Munian, Jacob Murphree, Tim Murphy, Praveen Murthy, Raza Mushtaq,
John Muzic, Kledia Myrtolli, Jennifer Mytar, Lucy Na, Elizabeth Nadal, Diana Naderi, Hodad Naderi, Navid Nafissi, Jonathan Nahas, Kiran Naidoo, Neil
Naik, Yuree Nam, Hiroya Nambu, Yuree Namyureen, Ashwin Narayana, Dustin Nash, Daniel Nassau, Neelima Navuluri, Shariq Nawab, Giseli Nazmi, Ryan
Neeley, Steven Neeley, Anoop Nehra, Steven Nelson, Joseph Nelson, Mithun Neral, Craig Ness, Kevin Nethers, Jordan Newman, Natalie Ngai, Quoc Ngo,
Julius Ngu, Bao Nguyen, Mai Trang Nguyen, Jennifer Nguyen, Brian Nguyen, Angeline Nguyen, Nga Nguyen, Vy Nguyen, Andrew Nguyen, Christine
Nguyen, Phi Nguyen, Peter Nguyen, Ronald Nguyen, Anthony Nguyen, Hung Nguyen, Sheena Nguyen, Alexandre Nguyen, Dan Nguyen, Janie Nguyen,
Tram Nguyen, Ruba Nicola, Carl Nieweld, Lena Ning, Isabella Niu, Conway Niu, Leila Njimoluh, Mark Noble, Tomoki Nomakuchi, Adrian Nugent, Drew
Nunziat, Aisulu Nurgozha, Tarik Nurkic, Emmanuel Nwelue, Ada Nwozuzu, Ernestina Nyarko, Kunal Oak, Souzana Obretenova, James O'Dowd, Florence
Odufalu, Michael Ofori, Ben Oglivie, Oladoyin Ogunbayo, Kyle Oholendt, Kene Okeke, Michelle Okoronkwo, Bunmi Olaloye, John O'laughlin, Elizabeth
Oler, Edgar Olivas, Cara Olsen, Joseph Omlor, Sina Salehi Omran, Neil Onizuka, Abimbola Orisamolu, Christopher Orr, Kenneth Ortiz, Vedran Oruc, Lais
Osmani, Erik Ostler, Adetola Otesile, Robert Oubre, Xiaoxi Ouyang, Steve Ovada, Jordan Owens, Kolawole Oyewole, Rudy P, Sigmund Paczkowski, Kevin
Padrez, Alyssa Pagliere, Allyson Palmer, Jd Palmer, Brian Palmisano, Jason Pan, Qinshi Pan, Saman Panahipour, Prakash Panchani, Gabrielle Paoletti, Amit
Parekh, Ruby Parikh, Sneha Parikh, Sonal Parikh, Jong Park, Anthony Park, Braden Parmer, Christian Parobek, James Parris, Scott Pascal, Vanessa Pascoe,
Janaki Paskaradevan, Parimal Patel, Ronak Patel, Suketu Patel, Amy Patel, Satya Patel, Sagar Patel, Shyam Patel, Tariq Patel, Hasita Patel, Parin Patel, Devin
Patel, Neal Patel, Hiren Patel, Priya Patel, Maharsh Patel, Kinner Patel, Gaurav Patel, Lance Patel, Tejas Patel, Manisha Patel, Vishal Patel, Krupa Patel,
Nilam Patel, Mahesh Patel, Mita Patel, Kershaw Patel, Romy Patel, Janus Patel, Tejas Patil, Rajesh Patnaik, Melissa Patterson, Kelly Paulk, Brit Payton, Justin
Peacock, Katherine Pederson, Alia Pekareva, Andrew Pelikan, Andrew Peranteau, Alex Perelman, Enmanuel Perez, Rafael Perez, Mari Perez-Rosendahl,
Tiffany Perkins, Liz Perkins, Barry Perlman, Michael Perone, David Perry, Asad Pervez, Max Petersen, Ashley Peterson, Sarah Peterson, Camille Petri, Tracy
Pham, Andrew Pham, Tiffany Phanhdone, Douglas Phelan, Adam Phillips, Carson Phillips, Nick Piazza, Michael Pierce, Allison Pierce, Sara Pike, Meredith
Plant, Alex Podolsky, Marc Polacca, Quiana Pollock, Kathleen Polonchek, Kristina Pontarelli, Francesco Pontoriero, Adrienne Poon, Nicole Pope, Jeremy
Porter, Lesley Portugal, Michael Posch, Emily Pospiech, Thomas Powell, Catherine Powell, Jamila Power, Shrestha Prajib, Tyler Prestwood, Andrea Price,
Jason Primus, Emilie Prot, Caroline Protin, Liese Pruitt, Kristina Prus, Alena Prystupa, Ramya Punati, Ashvin Punnyamurthi, David Purger, Anthony
Purgianto, Raghuveer Puttagunta, H Q, Zuhab Qamar, Seema Qayum, Hazeeb Qazi, Xiaoming Qi, Ann Qiu, Ming Vi Qiu, Nabila Quadri, Cara Quant, Jose
Quesada, Nick Quinn, Thomas Quinn, Sidra Qureshi, Jenn Raab, Amanda Rabideau, Ashwinee Ragam, Preethi Raghu, Vikram Raghu, Christina Ragland,
Roxana Rahmanian, Samira Rahmanian, Asirna Raja, Akriti Raju, Charles Ramkishun, Josean Ramos, Jonathan Ramsey, Neerva Rana, Jessica Randell, Ajit
Rao, Justin Raper, Ken Rapp, Rita Raturi, Rebecca Raub, Curtis Read, Alan Reagan, David Rebedew, Joshua Reber, Matthew Rebesco, Thomas Reher,
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Daniel Reid, Joshua Reid, Rebecca Reimers, Steven Reinhart, Michael Reinsbach, Brock Reiter, Sonia Replansky, David Retamar, Monica Rettenmier,
Joshua Reuss, Wissam Rhayem, Jamie Rhodes, Fady Riad, Andrew Richardson, Aaron Richler, Sabah R'id, John Riester, Catherine Rim, Ryan Rimer,
Kathryn Rimmer, Dalianne Rivera, Alicia Rizzo, Kris Roach, Joshua Roark, Michael Robers, Leslie Robin, Michelle Robinette, Monica Roca, Will Roche, Ellis
Rochelson, Alejandro Rodriguez, Jesus Rodriguez, Carmen Rodriguez, Javier Rodriguez Kovacs, Jackeline Rodriguez-Smith, Samuel Rogers, Ben Rogers,
Eric Rohman, Sarah Rollins, Christine Rollins, Brice Rolston, Vladimir Romannikov, Bobby Rombola, David Roraff, Javier Rosales, Evan Rosenbaum,
Matthew Rosenbaum, Elizabeth Rosenberger, Eric Rosenfeld, Jared Ross, Joshua Ross, Lela Ross, Bryan Roth, Ryan Roth, Ben Roth, Kara Rothenberg,
Steven Rothenberg, Zach Rottmann, Jonathan Roy, David Roy, David Rubins, Sharmistha Rudra, Chloe Rugut, Eric Rupe, William Rusnak, Meghan Rutgers,
Nidia Ryan, Yamaan Saadeh, Janany Sabescumar, Sandeep Sabhlok, Michael Saco, Radha Sadacharan, Ahmed Sadek, Cameron Saffer, Abigail Sage, Atith
Saheba, Sachin Sahni, S M Nazmus Sakib, Yusuf Salah, Mohamad Saleh, Ramy Saleh, Dr. Salway, Diana Samberg, Yoni Samocha, Glenn San Agustin,
Christopher Sanchez, Juan Sanchez, Evan Sander, Britt Sandier, Kiri Sandier, Kenneth Sands, Jake Sanning, Margarita Santiago, Nishtha Sareen, Joyatee
Sarker, Luay Sarsam, Milan Satcher, Alexander Satin, Alexandra Satty, Christopher Schaefer, William Schaffenburg, Jessica Schancupp, Matthew Schear,
Sid Schechet, Eli Scher, Kai Schlingmann, Megan Schmidt, Amanda Schmitt, Drew Schmucker, Sam Schroeder, Adam Schwalje, Dan Schwartz, Brandon
Schwartz, Kristopher Schwebler, Sarah Scott, Elliot Scott, Eric Seachrist, Derek Seehausen, Nilmaris Segarra, Tracy Seimears, Jackie Selbst, Philip Senger,
Gina Sequeira, Nikhil Seth, Sajiv Sethi, Tasneam Shagroni, Raju Shah, Halie Shah, Rusha Shah, Manan Shah, Kinchit Shah, Bijal Shah, Tejal Shah, Ankur
Shah, Anna Shah, Arpeet Shah, Vishal Shah, Anand Shah, Archana Shah, Zoheb Shaikh, Berje Shammassian, Angela Shan, Brett Shannon, Ayesha Shariff,
Amal Shariff, Anil Sharma, Aarti Sharma, Allison Shatz, Brian Shayota, Mike Shelton, Kartik Shenoy, Rashna Shetty, Johanna Sheu, Eugenia Shevchenko,
Sandra Shi, James Shi, Kyle Shibuya, Jessica Shie, Matthew Shiel, Yushane Shih, John Shin, Mackenzie Shindorf, Justine Shum, Thomas Shum, Erik
Shwarts, Shan Siddiqi, Ashhad Siddiqui, Eliud Sifonte, Nathan Silvestri, Aaron Sin, Vikal Singh, Shashank Singh, Harmandeep Singh, Amteshwar Singh,
Vikram Singh, Melissa Singh, Punit Singh, Arindam Singha, Varsha Sinha, Mark Sittig, Tim Sitton, Stephanie Skala, Ahalya Skandarajah, David Skoglund,
Racquel Skold, Ernest Sliwinski, Justin Sloane, Emily Smergel, Nicholas Smith, Amanda Smith, Justin Smith, Kyle Smith, Craig Smith, Kendall Snyder,
Kunmi Sobowale, Matthew Sochat, Jae Ho Sohn, Shantanu Solanki, Sanaa Somalya, David Somsen, Raku Son, Daniel Son, Joohyun Song, Yohan Song,
Jasen Sood, Sufian Sorathia, Brett Sorge, Juan Sosa, Michael Sotiriou, Mario Soto, Yehuda Julian Spector, Julian Spector, Cory Spicer, Daniel Spiegel,
Lauren Spiegel, Adam Spjute, Kathryn Stadeli, Irina Staicu, Michael Stanaek, Anna-Bianca Stashak, Jake Steel, Christopher Steele, Ruth Stefanos, Mike
Stengel, Kevin Stephens, Scott Stiles, Blair Stocks, Jon Stoever, IIana Stol, Timothy Stooksberry, Tony Stover, Michelle Stram, Alyssa Stram, Jehu Strange,
Marshall Strother, Daphna Stroumsa, Sean Sturm, Maham Subhani, Mark Suguitan, Matthew Sullivan, Farheen Sultana, Lishi Sun, Cliff Sung, Srinivas
Sunkara, Matthew Surdel, Tyler Surma, Ryan Sutherland, Alex Swan, Christopher Sweat, Adam Sweeney, Tyler Swiss, Ali Syed, David Symister, Ariana
Tabing, Hannah Taft, Shahein Tajmir, James Tak, Brandon Takase, Malia Takeuchi, Selorm Takyi, Afsaneh Talai, Sejal Tamakuwala, Neal Tambe, Tanya Tan,
Amit Tandon, Lynda Tang, Mengyao Tang, Frances Tangherlini, Dantera Tangpisuthipongsa, Jackie Tanios, Kathryn Tapper, Karen Tart, Christine Tat, Elias
Taxakis, Rachel Taylor, Scott Taylor, Miguel Teixeira, Kara Teruya, Zach Testo, Mazell Tetruashvily, Yana Thaker, Prakash Thapa, William Thieu, Aaron
Thomas, Jerry Thomas, Taryn Thomas, Barrett Thomas, Alexandra Thomas, Ashley Thompson, Jason Thompson, Sibo Tian, Wayne Tie, Tom Tielleman,
Thomas Tielleman, Connie Tien, Meghan Tierney, Tonia Tiewul, Andrew Timmons, Corey Tingey, Joanne Tisak, Wissam Tobea, Marko Todorovic, Josef
Tofte, Thomas Tolbert, Justin Tomal, Jimmy Ton, Corey Tong, Olivia Tong, Gabriel Tonkin, Nevkeet Toor, Thalia Torres, Bela Toth, Jamie Totman, Lauren
Towne, Jorge Trabanco, Albert Train, Patrick Tran, Bao Tran, Sunyu Tran, Darrell Tran, Pat Tran, Norris Tran Due, Daniel Treister, Hung Trinh, Adrian Tripp,
Chelsea Troiano, Ryan Trowbridge, Kim Truong, Cindy Tsai, Valerie Tsang, Brian Tse, Victor Tseng, Pei-Yuan Tsou, Brian Tu, Alex Turin, Sergey Turin, Stefan
Turkula, Alison Ullman, Sphoorti Umarjee, Chelsea Dawn Unruh, Krishna Upadhyaya, Oleg Uryasev, Eric Uzoma, Nataly Vadasz, Kimaya Vaidya, Jason
Valadao, Erik Valenti, Kippie Valentine, Carla Valenzuela, Tina Varghese, Ross Varma, Matthew Varner, Bradley Varner, Jacob Varney, Ashley Vaughn, Aria
Vazirnia, Christine Velazquez, Laura Veras, Christopher Verdick, Saurabh Verma, Marissa Versalle, Benjamin Vidalis, Albert Vien, Anita Vijapura, Liliana
Villamil-Nunez, David Villanueva, Tomas Villarreal, Howard Vo, Peter Vu, Charles Vu, John Vu, Elizabeth W, Christianne Wa, Cherisse Wada, Jacob Wagner,
Brittany Wagner, John Wainwright, Kevin Walker, Brandon Walker, Sean Wallace, Scott Walter, Joseph Wan, Tony Wang, Bo Wang, Jessica Wang,
Jonathan Wang, Vivian Wang, Wendy Wang, Lindsay Warner, James Warren, Joshua Wasmund, Ryan Watson, Dovie Watson, Daniel Watson, Kathleen
Weber, Katie Weber, Catherine Wei, Sam Weimer, Frank Weinberg, Candice Weiner, Ken Weinlander, Mark Weinreich, Lindsay Weiss, Claire Welteroth,
Nick Wendling, Michael West, Kyle Westerholt, Derek Weyhrauch, Matthew Wheelwright, Natalie White, lan Whiteside, Rachel Whynott, Jenna
Wickersham, Shira Wieder, Renee Wierz, Olivia Wilcox, Nicholas Wilkie, Sara Williams, Elbert Williams, Emily Willner, Erika Wilson, Brant Wilson, Rachael
Winchester, Daniel Wingo, Lee Winkler, Paul Winograd, Keith Wirth, Lauren Wiznia, Sean Wo, Lindsey Woeste, William Wojtusiak, Amanda Wolf, Tiana
Won, Christina Wong, Anthony Wong, Kimberly Wong, Stephanie Wong, Linda Wong, James Wong, Christopher Wood, Jennifer Wootton, Megan
Worthley, Xinyu Wu, Sarah Wu, Gregory Wu, Wayland Wu, Susan Wu, Chester Wu, Daniel Wu, Andrew Wu, Andrew Wuenstel, Rachel Wurmser, Kirk
Wyatt, Jonathan Xia, Michael Xiong, Willa Xiong, Baogang Xu, Ron Yalon, Tarek Yamany, Xiaofeng Van, Jennifer Van, Debby Yanes, Kimberly Yang,
Jonathan Yang, Christine Yang, Jimmy Yao, Gokul Yaratha, Golsa Yazdy, Allen Ye, Brittany Vee, James Yeh, Emily Yeh, John Yeh, Aleksandr Yelenskiy,
Amanda Yen, Albert Yen, Johnny Yep, Nury Vim, Kathleen Yip, Michael Yip, Yin Yiu, Stella Yoo, Jane Yoon, Kei Yoshimatsu, Makoto Yoshino, Jae You,
Jovante Young, Andrew Young, Michael Youssef, Xin Yu, Connie Yu, Mary Yu, Hana Yu, Cathy Yu, Michael Yuan, Marshall Yuan, Michael Yudelevich, Etana
Zack, Muhammad Usman Zafar, Lisansha Zahirsha, Andreina Zambrano, Ferdous Zannat, Helio Zapata, Katherine Zappia, Rolla Zarifa, Debra Zauner,
Mariam Zeini, Jennifer Zhan, Jinmeng Zhang, Steven Zhang, Jane Zhang, Yingtao Zhang, Bingnan Zhang, Qian Zhang, Wency Zhao, Shuang Zhao, Betty
Zhao, Ludan Zhao, Sherry Zhao, Theresa Zhou, Xun Zhou, Shira Ziegler, Nicole Zimmerman, Mark Zobeck, Adnan Zubair, and Michael Zumwalt.
For submitting book reviews, thanks to Rami Abukamil, Kristen Anderson, Maureen Ayers Looby, Glorilee Balistrieri, Emaad Basith, Matthew Bloom,
Pierre Bueser, Elspeth Call, Hector Casiano, Edgie-Mark Co, Loren Colson, Alex Doudt, Clinton Ezekiel, Kendell Felker, Michael Flores, Cynthia Gee,
Michael Greff, Lindsay Henderson, Ryan Tyler Hoff, Sebastian Jacobi, Priyanka Jagar, Kunal Kamboj, Harris Khan, Sameer Lakha, Tsung Hsien Lin, Michelle
Liu, Lyndon Luk, Neil Majithia, Vanessa Mallol, Shane Mandalia, Gretchen Metzenberg, Naila Mirza, Steven Mong, Yen Nguyen, Fernando Ovalle, Nirav
Patel, Jason Pesqueira, Alison Petrie, Hassan Qadir, Yujie Qiao, Faith Quenzer, Monique Roberts, Jasjeet Sekhon, Gabriel Soto, Kazuhiro Takahashi,
Richard Tapnio, Jasmine Toor, Trung Tran, Michael Tran, Dana Turker, Sierra Witte, and Betty Zhao.
XVI
How to Contri bute
Th is version of First Aid for the USMLE Step 1 incorporates hundreds of contributions and changes suggested by
faculty and student reviewers. We invite you to participate in th is process. We also offe r paid internships in medical
education and publ ishing rangi ng from three months to one year. Please send us your suggestions for:
Study and test-taking strategies for the U S M LE Step 1
New facts, mnemonics, diagrams, and illustrations
High-yield topics that may appear on future Step 1 exams
Personal ratings and comments on review books, online question banks, videos, and courses
For each new entry incorporated into the next edition, you will receive up to a $20 Amazon .com gift certificate
per entry from the author group, as well as personal acknowledgment in the next edition. Diagrams, tables, partial
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The preferred way to submit new entries, clarifications, mnemonics, or potential corrections with a val id, authoritative
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www. firstaidteam . com
This Web site will be continuously updated with val idated errata, new h igh-yield content, and a new online platform
to contribute suggestions, mnemonics, diagrams, clinical images, and potential errata.
Alternatively, you can e-mail us at: firstaidteam@yahoo . com.
Contributions submitted by June 1 5 , 2 0 1 3 , receive priority consideration for the 2 0 1 4 edition of First Aid for the
USMLE Step 1. We thank you for taking the time to share your experience and apologize in advance that we cannot
individually respond to all contributors as we receive hundreds of contributions each year.
XVI I
N O T E TO C O N T R I B U T O R S
All contributions become property of th e authors and are subj ect to editing and reviewing. Please verify all data and
spellings carefully. In the event that similar or duplicate entries are received, only the fi rst complete entry received
with a val id, authoritative reference will be used. Please follow the style, punctuation, and format of th is edition as
much as possible.
J O I N TH E F I RST AI D TEAM
The First Aid author team i s pleased to offer part-time and full-time paid internships i n medical education and
publishing to motivated medical students and physicians. Internships may range from a few months ( e .g. , a summer)
up to a full year. Participants will have an opportunity to author, edit, and earn academic c redit on a wide variety of
projects, including the popular First Aid series.
In 20 1 3 , we are actively seeking passionate medical students and graduates with a specific interest in improving
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and summary of your interest or sample work.
XVI I I
How to U se This Book
Medical students who have used previous editions of this guide have given us feed back o n how best to make use of
the book.
It is recommended that yo u begin using this book as early as possible wh ile learning the basic medical scienc s .
You can use Section IV to select fi rst-year course review books and Internet reso urces and the n use thos books for
review while taking your medical school classes.
Use differ nt parts of the book at different stages in your preparation for the USMLE Step l . Before you b gm
to study for the U SMLE Step l , we suggest that you read Section I: Guide to EHicient Exam Pr e p a rat i o n nd
Section IV: Top-Rated Review Resources. If you are an international medical raduate s t u dent, an o t o p athi
medical student, a podiatry student, o r a student with a disabil ity, refer to the appropriate Section I s upplem nt
for additional advice. Devise a study plan and decide what resources to buy. We tr ongly recommend that y u inv st
in the latest edition of at least one or two top-rated review books on each subj ect.
First Aid is not a comprehensive review book, and it is not a panacea for i nadequate preparation during the first
two years of medical school . Scanning Sections I I and III will give you an i nitial idea of the diverse ran e of topics
covered on the U SMLE Step 1 .
As you study each discipline, use the cor sponding high-yield-fact section in Firs t Aid for the USMLE Step 1 as a
means of consolidating the mate ial and tes ting yourself to see if you have mastered w m e of the fr qu ntly t s t d
items. Actively work with i n the book to integrate important facts i nto your fund of knowledge . U s i ng First Aid for th
USMLE Step 1 as a review can serve as both a self-test of your knowledge and a repetJtion o f imp rta n t fa ts t o learn.
The Rapid Review section includes h igh-yield topics and vignettes are a bstracted from 1 cent e a m s to h lp guicl
your preparation.
To broad n your learning stratee,ry, yo u can i n t ate your First Aid study with First Aid Cases for the USMLE St p 1 ,
First Aid Q6A for the USMLE tep 1 , and the USMLE-Rx Qmax Step l test bank. First Aid Cases and First Aid
Q6A are organized to match First Aid for the USMLE Step 1 chapt r for c h a pt r. After r viewmg a dtscipl in r
organ system chapter with i n First Aid, yo u can r view c ses on the same topics and then test yo u r kn ledge in
the corresponding chapters of First Aid Cases and Fin;t Aid Q6A and with U S M LE-Rx Qma Step 1 . If y u want a
d per revi w of the h igh-yield topics, consider adding First Aid for the Basic Sciences: Genera l Prin ipl s nd Organ
Systems and the First Aiel Express or Ulti mate video courses (vvww. usmle-rx.com ) to your study plan.
Return t o Sections I I a n d I I I frequ n t ly during yo ur preparation a n d fi l l yo ur shurt-te m memory w it h remaining

high-yield facts a fe v days before the U S MLE Step l . The book can serve as a useful way of retai ning key
associations and keeping high-yield fac ts fresh in your memory j ust prior to the examination . Reviewing the book
immediately after the exam is probably the best way to help us improve the next edition. Decide what was truly h igh
and low yield and send in your com ments , post them on our Web site, or send us a s anned copy of your e tir
a nnota te d book. Remem ber th a t yo u cannot disclose any exam material from the lJ SMLE.
IX
Com m o n U SM LE La boratory Va l ues
* = Incl uded i n the B iochemical Profile ( S MA- 1 2 )
Blood, Plasma, Serum Reference Range Sl Reference Intervals
* Alanine a m i notransferase (ALT, CPT at 3 0 C ) 8-20 U/L 8-20 U/L
Amylase, seru m 2 5 - 1 2 5 U/L 2 5 - 1 2 5 U/L
* Aspartate a m i notransferase (AST, GOT at 3 0 C ) 8-20 U/L 8-20 U / L
B i l i ru b i n , serum (adult)
Total II D i rect 0 . 1 - l . O mg/d L // 0 . 0 -0 . 3 m g/d L 2 - 1 7 pmoi!L / / 0-5 pmol/L
* Calcium, seru m ( Total) 8 .4- 1 0 . 2 m g/d L 2 . 1 -2 . 8 m moi!L
* Cholesterol , serum (Tota l ) 140-200 m g/d L 3 . 6 -6 . 5 m mol /L
* Creatinine, s e r u m (Total) 0 . 6 - 1 . 2 mg/d L 5 3 - 1 0 6 pmoi!L
Electrolytes, serum
Sodium 1 3 5 - 147 m E q / L 1 3 5 - 1 47 mmol/L
Chloride 9 5 - 1 0 5 m E q /L 9 5 - 1 0 5 m m oi !L
* Potassium 3 . 5 - 5 . 0 mEq/L 3 . 5 -5 . 0 m m oi !L
B icarbonate 2 2-28 m E q /L 2 2 -2 8 m moi !L
Gases, arteri a l blood ( room a i r)

P oz 7 5 - 10 5 m m H g 1 0 . 0 - 1 4 . 0 k Pa
P coz 3 3 -44 m m i-Ig 4.4-5 .9 k Pa
pH 7. 3 5 -7.4 5 [1--J+ ] 3 6 -44 nmoi!L
* Glucose, seru m Fasting: 70-1 1 0 mg/d L 3 . 8 - 6 . 1 m moi!L

2-h postprand i a l : < 1 20 m g/d L < 6.6 m moi!L
Growth hormone - arg i n i n e sti mulation Fasting: < 5 ng/m L < 5 pg/L
provocative stimu l i : > 7 n g/m L > 7 pg/L
Osmol a l i ty, seru m 2 7 5-295 mOsm /kg 2 7 5 -2 9 5 m O s m /kg
* Phosphatase (alka l i n e ) , serum (p-NPP at 3 0 C ) 20-70 U/L 2 0 -70 U /L
* Phosphorus ( i norga n ic) , serum 3 . 0-4. 5 mg/d L l . 0 - 1 . 5 m mol/L
* Proteins, serum
Total (recumbent) 6 . 0-7. 8 g/d L 60-7 8 g/L
Albu m i n 3 . 5 - 5 . 5 g/d L 3 5 - 5 5 g/L
Globul i ns 2 . 3 -3 . 5 g/d L 23-35 g/L
* Urea n itrogen , seru m ( B U N ) 7- 1 8 mg/d L 1 . 2-3 . 0 mmol/L
* Uric a c i d , seru m 3 . 0 - 8 . 2 mg/dL 0 . 1 8 - 0 .48 m m o i ! L

Cerebrospinal Fluid
Glucose 40-70 mg/d L 2 . 2-3 .9 m mol/L
(continues)
XX I
Hematologic
Eryth rocyte count Male : 4 . 3 - 5 .9 m i l l ion/mm 3 4 . 3 - 5 .9 X 1 0 1 2 /L

Female : 3 . 5 - 5 . 5 m i l l ion/mm 3 3 . 5 - 5 . 5 X 1 0 1 2 /L
Hematocrit Male : 41-5 3 % 0.4 1 - 0 . 5 3

Female : 36-46% 0 . 3 6 - 0 .46
Hemoglob i n , blood Male : 1 3 . 5 - 1 7. 5 g/d L 2 . 09-2 .7 1 m mol /L

Fem a l e : 1 2 . 0 - 1 6 . 0 g/d L 1 . 86-2 .4 8 m moi!L
Reticulocyte count 0 . 5 - 1 . 5 % of red cells 0.005-0.0 1 5
Hemoglob i n , plasma l -4 mg/d L 0 . 1 6- 0 . 62 J.Imoi!L
Leukocyte count and d i fferential

Leukocyte count 4 5 0 0 - l l , O O O /m m 3 4. 5 - 1 1 . 0 X 1 0 9 /L
Segmented neutroph i l s 54-62 % 0 . 54-0.62
Band forms 3-5% 0.03-0.05
Eosi noph i l s 1-3% 0.01-0.03
Basoph i l s 0-0.7 5 % 0-0 . 0 0 7 5
Lymphocytes 2 5 -3 3 % 0.2 5-0.33
Monocytes 3 -7% 0.03-0.07
M e a n corpuscular hemoglobin 2 5 .4-34.6 pg/cell 0 . 39-0 . 5 4 fmol!cell
Mean corpuscul ar volume 80-100 11m 3 80-1 0 0 fL
Platelet count 1 5 0,00 0-40 0 , 0 0 0 /m m 3 1 5 0-400 X 1 0 9 /L
Proth rombin time 1 1 - 1 5 seconds 1 1 - 1 5 seconds
Activated partial thromboplastin time 2 5 -40 seconds 2 5 -40 seconds
Sedimentation rate , erythrocyte M a l e : 0-1 5 m m /h 0 - 1 5 m m /h

(Westergren) Female : 0-20 m m /h 0-20 m m /h
Proteins in u r ine, total < 1 5 0 mg/24 h < 0 . 1 5 g/24 h
XXI I
Basic Scie n ce Discipl i n e
Cross- Referen ce Ta ble
for H igh-Yield Facts
Hema-
Cardio- Endocri- Gastro- tology/ lmmu- Musculo- Repro- Respira-
vascular nology intestinal Oncology no logy skeletal Neurology Psychiatry Renal ductive tory
Behavioral 6 1 -6 2 60, 6 2 5 9-60

Science
Embryology 2 5 0-2 5 2 286 3 0 8- 3 0 9 251 408-4 1 0 478 5 04- 5 1 4
Anatomy 253 2 86-2 89 3 09-3 1 8 344-347 3 7 8- 3 8 6 4 1 1 -442 479 5 1 4- 5 1 7 5 44- 546
Biochemistry l !O 1 1 0- 1 1 1 , 77-79, 8 2-89

115 86, 1 1 4
Microbiology 1 24, 1 49 20 1 -202 1 44, 1 69, 1 48 , 1 62 , 1 69- 1 70 1 3 8- 1 4 1 , 1 3 1-1 32,

1 3 5- 1 3 7 , 1 7 2 , 1 74 1 66- 1 67 , 1 50, 1 56, 1 6 8 , 1 74
1 47 , 1 69 , 1 74 1 7 1 , 1 73
1 5 1-1 52,
1 67- 1 68
Pathology 2 6 5-2 7 8 223, 3 24- 340 2 1 8-2 24, 200, 3 8 7-40 3 4 1 6-4 1 7 , 4 5 9-47 2 4 8 8-49 8 5 2 4- 5 3 7 5 5 3- 5 6 1
296- 3 04 3 5 0- 3 66 20 3-208 4 1 9-4 2 0 ,
42 2-448
Pharmacology 2 79-2 84 3 0 5-306 340-342 367-3 7 5 209-2 1 0 404-406 449-4 5 6 47 2-476 499- 5 0 2 5 3 8- 5 4 1 5 6 2 - 5 64
Physiology 2 5 3-2 6 5 2 89-29 5 3 1 9-3 2 3 347-349 3 7 8-3 8 6 4 1 1 -442 480-4 8 8 5 1 8- 5 2 3 546- 5 5 2
XXI I I
First Aid Checklist for the USMLE Step 1
Th i s is a n exa m p l e of how yo u m i ght use the i nfo rmation i n Section I to p repa re fo r the U S M LE Step 1 .
Refer to correspon d i n g to p i cs i n Secti o n I for m o re deta i l s.
Years Prior
0 Sel ect top-rated revi ew books a s stu dy g u i d es for fi rst-yea r m e d i ca l school cou rses.
0 Ask for a dvice from those who h ave recently taken the U S M LE Ste p 1 .
Months Prior
0 Revi ew co m p uter test fo rmat a n d registrati on i nfo rmati o n .
0 Reg ister six m o nths i n a dva nce. Ca refu l ly verify n a m e a n d a d d ress pri nted o n sched u l i n g perm it. C a l l
Pro m etric o r go o n l i n e f o r test d ate ASAP.
0 Defi ne goa ls fo r the U S M LE Ste p 1 (e.g., comfo rta bly pa ss, beat the m e a n , a ce the test) .
0 Set u p a rea l istic t i m e l i n e for stu dy. Cove r less cra m m a b l e su bj ects fi rst. Review su bj ect-by-su bj ect
e m p h a s i s a n d c l i n ical vignette format.
0 S i m u l ate the U SM L E Step 1 to p i n p o i nt strengths and wea knesses i n knowl edge and test-ta ki n g ski l ls.
0 Eva l u ate and choose study m ethods and materi a l s (e.g., revi ew boo ks, p ra ctice tests, softwa re) .
Weeks Prior
0 S i m u l ate the U S M LE Step 1 a ga i n . Assess how close yo u a re to yo u r goa l .
0 P i n p o i n t rema i n i ng wea kn esses. Stay hea lthy (exe rcise, sleep) .
0 Ve rify i nfo rmation o n a d m issi o n ticket (e.g., l ocation, d ate) .
One Week Prior

0 Rem e m b e r comfo rt measu res (loose cloth i n g, earpl ugs, etc.) .
0 Wo rk out test site logistics such as l ocati on, tra n sportation, pa rki ng, a n d l u n c h .
0 Ca l l Pro m etric a n d confirm yo u r exa m a p poi ntment.
One Day Prior

0 Relax.
0 Lightly revi ew short-term m ateri a l if n ecessa ry. Skim h i gh-yi e l d fa cts.
0 Get a good n ight's sleep.
0 M a ke s u re the name pri nted o n yo u r photo ID a p p e a rs EXACTLY the sa m e a s the name p ri nted on yo u r
sched u l i n g perm it.
Day of Exam
0 Rel ax. Eat b rea kfa st. M i n i m ize bath room b rea ks d u ri n g the exa m by avo i d i n g excessive m o r n i n g caffei n e.
0 Ana lyze a n d m a ke adjustm ents i n test-ta king tech n i q u e . Yo u a re a l l owed to revi ew n otes/study m ateri a l
d u ri n g b rea ks o n exa m day.
After the Exam

D Celebrate, rega rd l ess.
D Send feed back to u s on o u r Web site at www. firstaidtea m.com.
XXIV
S ECT I O N I
G u ide to Efficient
Exa m Prepa ration
I ntro d u ction 2
U S M LE Ste p 1 -Th e
Basics 2
D efi n i ng You r G o a l 12
Ti m e l i n e fo r Stud y 12
Study Materi a l s 17
Test-Ta k i n g
Strategies 19
C l i n i ca l Vig nette
Strategies 21
If You Th i n k You
Fa i l e d 22
If You Fa i l ed 22
Testi ng Age n c i es 23
References 23
1
2 SECTION I G U I D E T O E F F I C I E N T E X A M P R E PA R AT I O N
I NTRO D U CT I O N
Relax.
Th is section is intended to make your exam preparation easier, not harder.

O u r goal is to reduce your l evel of anxiety and help you make the m ost of
your efforts by helping you understand more about the United States Medical
Licensing Examination, Step 1 ( U SMLE Step 1 ). As a medical student, you
are no doubt familiar with tak i ng standardized exa m i n ations and qui ckly
absorb i ng large amounts of material . Whe n you fi rst confront the U S MLE
Step 1 , however, you may find it all too easy to become sidetracked from your
goal of studying with maximal effectiveness. Common mistakes that students
make when studying for Step 1 include the following:
Not understanding how scoring is performed or what the score means

Starting to study ( including First Aid) too late
Starting to study intensely too early and burning out
Using inefficient or inappropriate study methods
Buying the wrong books or buying more books than you can ever use
Buying only one publ isher's review series for all subj ects
ot using practice examinations to maximum benefit
Not using review books along with your classes
The test at a glance: Not analyzing and improving your test-taking strategies
8-hour exam Getting bogged down by reviewing difficult topics excessively
Total of 322 multiple choice items Studying material that is rarely tested on the U SMLE Step 1
7 test blocks (60 min/block) Failing to master certai n high-yield subj ects owing to overconfidence
46 test items per block Using First Aid as your sole study resource
45 minutes of break time, plus another Tryi ng to do it all alone
15 if you skip the tutorial
In th is section , we offer advice to help you avoid these pitfalls and be more
productive in your studies.
U S M L E S T E P 1 -T H E BAS I C S
The U SMLE Step 1 i s the fi rst o f three examinations that you must pass i n
o r d e r t o become a l i c e nsed phys i c i a n i n th e U nited States. T h e U S M LE
is a j oint endeavor of the ational Board of Medical Exa m i n e rs ( N B M E )
and the Federation o f State Medical Boards ( F S M B ) . Th e U S M LE serves
as the single examination system for U . S . medical students and international
medical graduates ( I MGs) seeking medical licensure i n the United States.
The Step 1 exam includes test items drawn from the following content areas :
Anatomy
Behavioral sciences
B iochemistry
M icrobiology and immunology
Patholo gy
G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N SECTION I 3
Pharmacology
Physiology
Interdisciplinary topics such as nutrition, genetics, and aging
How Is the Computer-Based Test (CBT) Strudured?
The C BT Step 1 exam consists of one "optional" tutorial/simulation block

and seven "real" question blocks of 46 questions each (see Figure 1 ) for a total
of 3 2 2 questions, timed at 60 minutes per block. A short 1 1 -question survey
follows the last question block. The computer begins the survey with a prompt
to proceed to the next block of questions .
Once an examinee finishes a particular question block on the CBT, he or she

must cl ick on a screen icon to conti nue to the next block. Examinees cannot
go back and change their answers to questions from any previously completed
block. H owever, changi ng ans wers is allowed within a block of questions as
long as time permits - unless the questions are part of a sequential item test
set (see p. 4) .
What Is the CBT Like?
Given the unique environment of the C BT, it's important that you become
familiar ahead of time with what your test-day conditions will be l ik e . In
fact, you can easily add 1 5 minutes to your break time ! This is because the
I S-minute tutorial offered on exam day may be skipped if you are al ready
familiar with the exam procedures and the testing interface. The 1 5 minutes
is then added to your allotted break time of 45 minutes for a total of 1 hour of
If you know the format you
potential break time. You can download the tutorial from the U SMLE Web
can skip the tutorial and add 15
site and do it before test day. This tutorial is the exact same interface you will
minutes to your break time!
use in the exa m ; learn it now and you can skip taking it duri ng the exam,
giving you 1 5 extra minutes of break ti me. You can also gain experience with
the CBT format by taking the 1 5 0 practice questions available online or by
FIGURE 1 . Schematic of CBT Exam.
AM
Exam
Su rvey
4 S E CT I O N I G U I D E T O E F F I C I E N T E X A M P R E PA R AT I O N
signing up for a practice session at a test center ( for details, see What Does the
C BT Format Mean to Me? ) .
For s e c ur i ty reasons, exa m i n e es are not a l l owed t o b r i ng a n y p e rsonal

electronic equ ipment into th e testing area. Th is includes both digital and
analog watches, cellular telephones, and electronic pagi ng devices. Food and
beverages are also prohibited. The testi ng centers are monitored by audio
and video surveillance equipment. H owever, most testing centers allot each
examinee a small locker outside the testing area i n wh ich he or she can store
snacks, beverages, and personal items.
The typical question screen i n the C BT consists of a question followed by

Keyboard shortcuts:
a number of choices on which an examinee can click, together with several
A, 8, etc. -letter choices
navigational buttons on the top of the screen . There is a countdown timer on
Enter or spacebar-move to next
the upper left-hand corner of the screen as well . There is also a button that
question
allows the examinee to mark a question for review. If a given question happens
Esc-exit pop-up Lab and Exhibit
to be longer than the screen (which occurs very rarely) , a scroll bar will appear
windows
on the right, allowing the examinee to see the rest of the question. Regardless
Alt-T-countdown timers for current
of whether the examinee clicks on an answer choice or leaves it blank, h e or
session and overall test
she must click the "Next" button to advance to the next question.
The U S MLE features a small number of media clips i n the form of audio
and/or video. There may even be a question with a multimedia h eart sound
simulation. In these questions, a digital image of a torso appears on the screen,
and the examinee directs a digital stethoscope to various auscultation points
Heart sounds are tested via media to l isten for heart and breath sounds. No more than five media questions
questions. Make sure you know will be fo und on any given exa mination, a n d the U S M L E orie ntation
how different heart diseases materials now include several practice questions in these new formats. During
sound on auscultation. th e exam tutorial, examinees are give n an opportunity to ensure that both
the audio headphones and the vol ume are functioning properly. If you are
already familiar with the tutorial and planning on skippi ng it, fi rst skip ahead
to the section where you can test your h eadphones. After you are sure the
headphones are working properly, proceed to the exa m .
Recently t h e U S MLE i n trod uced a sequential item t e s t format for s o m e

questi o n s . Sequential i t e m questi ons a re grouped togeth e r i n the l i st o f
questions on the left-hand s i d e of the screen . Questions i n a sequential item
set must be completed in order. After an examinee answers the fi rst question,
h e or she will be given the option to proceed to the next item but will be
warned that the answer to the first question will be locked. After proceeding,
examinees will not be able to change the answer selected for that question .
The question stem and the answer chosen will be available to the examinee
Test illustrations include: as he or she answers the next question(s) i n the sequence. No more than five
Gross photos sets of sequential item questions will be found in any given examination.
Histology slides
Some Step l questions may also conta i n figures or illustrations. These are
Radiographs
typ i cally s i tuated to the right of th e question . Al though the contrast and
Electron micrographs
brightness of the screen can be adj usted, there are no other ways to manipulate
Line drawings
the picture (e.g., there is no zooming or panning) .
The examinee can c a l l up a wi ndow displayi ng normal laboratory val u e s .

In order t o do so, h e or she m u s t c l i ck t h e " L a b " icon on t h e top part of
Familiarize yourself with the
the screen. Afterward , the examinee will have the option to choose between
commonly tested lab values.
"Blood," "Cerebrospinal," "Hematologic," or " Sweat and Urine." The normal
values screen may obscure the question if it is expanded. The examinee may
have to scroll down to search for the needed lab values. You might want to
memorize some common lab values so you spend less time on questions that
requ ire you to analyze these.
The CBT interface provides a running l ist of questions on the left part of the
screen at all times. The software also permits examinees to highlight or cross
out information by using their mouse. Finally, there is an "Annotate" icon on Ctri-Ait-Delete are the keys of death
the top part of the screen that allows students to write notes to themselves for during the exam. Don't touch them!
review at a later time. Being famil iar with these features can save time and
may help you better organize the information you need to answer a question.
What Does the CBT Format Mean to Me?
The significance of the C BT to you depends on the requirements of you r

school and y o u r l evel of computer knowl edge . If you a r e a Mac u s e r , you
might want to spend some time using a Windows-based system and pointing
and clicking icons or buttons with a mouse .
For those who feel they might benefit, the U S MLE offers an opportu nity
to take a simulated test, or " C BT Practice Session at a Prometric ce nter."
Students are e l igible to register for th i s thre e-and-one-half-hour practice
session after they have received their schedul ing permit.
The same U S MLE Step 1 sample test items ( 1 5 0 questions) available on

You can take a shortened CBT
the U S MLE Web site, www. usml e . org, are used at these sessions. No new
practice test at a Prometric center.
items will be presented. The session is divided into three one-hour blocks of
50 test items each and costs about $42 . Students receive a printed percent
correct score after completing the session . No explanations of questions are
provided .
You may register for a practice session online at www. usmle .org. A separate
scheduling permit is issued for the practice session. Students should allow two
weeks for receipt of th is permit.
How Do I Register to Take the Exam?
Prometric test centers offer Step 1 on a year-round basis, except for the fi rst
two weeks in January and major holidays . The exam is given every cl a y except
Sunday at most c enters . Some schools admi nister the exam on th e i r own
campuses . Check with the test center you want to use before making your
exam plans.
U . S . students can apply to take Step 1 at the NBME Web site. Th is appl ication
allows you to select one of 1 2 overlapp i ng three-month blocks in wh ich to be
6 SECT I O N I G U I D E T O E F F I C I E N T E X A M P R E PA R AT I O N
tested ( e .g. , April-May-June, June-July-August) . C hoose your three-month

el igibil ity period wisely. If you need to reschedule outside your i nitial three
month period, you can request a one-time extension of eligibil ity for the next
contiguous three-month period, and pay a rescheduling fee . The appl ication
also incl udes a photo I D form that must be certified by an official at your
medical school to verify your enr o l l ment. After the N B M E processes your
appl ication, it will send you a schedul ing permit.
The s c h e d u l i n g permit you receive fro m the N B M E w i l l c o n t a i n your

The Prometric Web site will display
U S MLE identification number, the el igibil ity period in which you may take
a calendar with open test dates.
the exam , and two additional numbers . The fi rst of these is known as your
"scheduling number." You must have this number in order to make your exam
appointment with Prometric . The second number is known as the "candidate
identifi cation number," or C I N . Examinees must enter the i r C I N s at the
Prometric workstation in order to access their exams. Prometric has no access
to the codes. Do n ot lose your permit! You will not be allowed to take the
exam unless you present th is permit along with an unexpired , government
issued ph oto I D that includes your signatu re (such as a driver's l icense or
passport) . Make sure the name on your photo I D exactly matches the name
that appears on your scheduling permit.
Once you receive your schedul ing permit, you may access the Prometric Web
The confirmation emails that
Prom .tric and NBME send are not

site or call Prometric's toll-free number to arrange a time to take the exam. You
may contact Prometric two weeks before the test elate if you want to confirm
the same as the scheduling permit.
identification requ irements. Although requests for taking the exam may be
completed more than six months before the test elate, examinees will not
receive their scheduling permits earl ier than six months before the el igibil ity
period. The eligibil ity period is the three-month period you have chosen to
take the exam. Most medical students choose the April-June or June-August
period. Because exams are scheduled on a "first-come, fi rst-served" basis, it is
recommended that you contact Prometric as soon as you receive your permit.
Te5t scheduling is done on a "first-come,
After you 've scheduled your exa m , i t's a good idea to confirm your exam
first-served" basis. It's important to col/
appointment with Prometric at least one week before your test elate . Prometric
and sch edule an exam date as soon as
does not provide written confirmation of exam elate, time, or location. Be sure
you receive your scheduling p rmit.
to read the 2 0 1 3 USMLE Bu lletin o{ Infonnation for further details.
What If I Need to Reschedule the Exam?
You can change your test elate a nd/o r c enter by contacting Prometric at
1 -800-MED-EXAM ( l -800-6 3 3-3926) or www.prometric. com . Make sure to
have your CIN wh en rescheduling. If you are reschedul ing by phone, you
must speak with a Prometric representative ; leaving a voice-mail message will
not suffice. To avoid a rescheduling fee , you will need to request a change
at l east 3 1 calendar days before you r appoi ntment. Please note that your
rescheduled test elate must fal l with i n your assigned th ree-month el igibil ity
period.
G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N S ECTI O N I 7
When Should I Register for the Exam?

Register six months in advance for
Although there are no deadlines for registering for Step 1 , you should plan to seating and scheduling preference.
register at l east six months ahead of your desired test elate . Th is will guarantee
that you w i l l get eith e r your test center of choice or one with i n a 5 0-mile
radius of your first choice. For most U. S . medical students, the desired testing
window is in June, since most medical school c urricula for the second year
end in May or June. Thus, U . S . medical students should plan to register before
January in anticipation of a June test elate . The timing of the exam is more
flexible for IMGs, as it is related only to when they finish exam preparation.
Talk with upperclassmen who have al ready taken the test so you have real
life experience from students who went through a similar curriculum, then
formulate your own strategy.
Where Can I Take the Exam?
Your testing l ocation i s arranged with Prometric when you call fo r your
test elate (after you receive your scheduling permit) . For a l ist of Prometric
locations nearest you , visit www. prometric.com.
How Long Will I Have to Wait Before I Get My Scores?
The U SMLE reports scores th ree to four weeks, unless there are delays i n
score processing. Examinees w i l l be notified v i a email when their scores are
available. By following the online instructions, examinees will be able to view,
clownloacl, and print their score report. Additional information about score
timetables and accessibility is available on the official USMLE Web site .
What About Time?

Gain extra break time by skipping the
Time is of special interest on the CBT exam. Here's a breakdown of the exam tutorial or finishing a block early.
schedule:
1 5 minutes Tutorial (skip if famil iar with test format and features)
7 hours Seven 60-minute question blocks
45 minutes B reak time ( i ncludes time for lunch)
The computer will keep track of how much time has elapsed on the exa m .
H oweve r, the c o m p u te r w i l l show you o n l y how mu c h t i m e you have
rema ining i n a given block. Therefore, it is up to you to determine if you
are pacing yourself properly (at a rate of approximately one question per 7 7
seconds) .
The computer will not warn you if you are spending more than your allotted
time for a break. You should therefore budget your time so that you can take
a short break when you need one and have time to eat. You must be especially
careful not to spend too much time in between blocks (you should keep track
of how much time elapses from the time you finish a block of questions to the
time you start the next block). After you finish one question block, you'll need
to click on a button to proceed to the next block of questions. If you do not

click to proceed to the next question block, you will automatically be entered
into a break period .
Forty-five minutes is the minimum break time for the clay, b ut you are not
requ ired to use all of it, nor are you requ ired to use any of it. You can gain
extra break time (but not time for the question blocks) by skippi ng the tutorial
Be careful to watch the clock
or by finish ing a block ahead of the allotted time. Any time remaining on the
on your break time. clock when you finish a block gets added to your remaining break time . Once
a new question block has been started, you may not take a break until you
have reached the end of that block. If you do so, th is will be recorded as an
"unauthorized break" and will be reported on your final score report.
Finally, be aware that it may take a few minutes of your break time to "check
out" of the secur e resting room and then "check in" again to resume testing,
so plan accordi ngly. The "check-i n " process may include fi ngerprints and
pocket checks. Some students recommend pocketless cloth i ng on exam clay
to streaml ine the process.
If I Freak Out and Leave, What Happens to My Score?
Your schedul ing permit shows a CIN that you will enter onto your computer
screen to start your exam. Entering the CIN is the same as breaking the seal
on a test book, and you are considered to have started the exam when you
do so. However, no score will be reported if you do not complete the exam.
In fact, if you leave at any time from the start of the test to the last block, no
score will be reported . The fact that you started but did not compl ete the
exam, however, will appear on your U S MLE score transcript. Even though a
score is not posted for incomplete tests, examinees can still request that their
scores be calculated and reported if they desire; unanswered questions will be
scored as incorrect.
The exam ends when all question blocks have been completed or when their
time has expired. As you l eave the testing center, you will receive a printed
test-completion notice to document your completion of the exam. To receive
an official score, you must finish the entire exam.
What Types o f Questions Are Asked?
One-best-answer multiple-choice items (either singly or as part of a sequential

Nearly three-fourths of Step 1 questions
item set) are the only question type on the exam. Most questions consist of a
begin with a description of a patient.
clinical scenario or a direct question followed by a l ist of five or more options.
You are requ ired to select the s i ngl e best a nswer among the options give n .
There are no "except," "not," or matching questions on t h e exam. A number
of options may be partially correct, i n which case you must select the option
that best answers the question or completes the statement. Additionally, keep
in mind that experimental questions may appear on the exam, which do not
affect your score (see Difficult Questions, p. 2 0 ) .
How Is the Test Scored?
Each Step 1 examinee receives an electronic score report that includes the
examinee's pass/fa i l status, two test scores, and a graphic depiction of the
examinee's performance by discipl i n e and organ system or s u b j e c t area.
The actual organ system profi l e s reported may depend on the statisti cal
characteristics of a given administration of the examination .
The N B M E provides two overall test scores based on the total number of
items answered correctly on the examination (see Figure 2). The first score,
the three-digit score, is reported as a scaled score in which the mean is 2 2 5
and the standard deviation i s approximately 2 1 . Th is i s the only score that gets
reported to residency program directors. The second score scale, the two-digit
score, defines 75 as the minimum passing score (equ ivalent to a score of 1 8 8
on the fi rst scal e ) . Th is score is only reported to state l icensing boards that
may have statutory requ irements that the score scale have 75 as the minimum
The mean Step 1 score for U. S.
passing score . In 2 0 1 1 , the U SMLE stopped reporting the two-digit score to
medical students continues to rise,
score users ( e . g . , residency programs) and now reports only the three-digit
from 200 in 1991 to 225 in 201 1.
score . Throughout this book we refer to scores using the three-digit scale only.
A score of 1 88 or h igher is required to pass Step 1 . The NBME does not report
the minimum number of correct responses needed to pass, but estimates that
it is roughly 60-70%. The NBME may adj ust the minimum passing score in
the future , so please check the U S MLE Web site or www. firstaidteam . com
for updates.
According to the U S M L E , medical schools receive a l isting of total scores

and pass/fail results plus group summaries by discipl ine and organ syste m .
Students c a n withhold their scores from their medical school if they wish .
Official U S MLE transcripts , w h i c h c a n be sent on request to res i d e n cy
programs, include only total scores, not performance profiles.
Consult the USMLE Web site or your medical school for the most c urrent
and accurate information regarding the examination.
FIGURE 2 . 201 1 Scoring Sca les for t h e U S M L E Step 1 .
3-digit score
160 170 180 188 190 200 210 220 230 240 250 260
(-2 SD) (-1 SD) (x) (+ 1 SD) (+2 SD)
T A B L E I . Passing Rates for the 201 0-201 1 USMLE Step 1 .
20 1 0 201 1
No. Tested % Passing No. Tested % Passing
Allopath ic l st takers 1 8, 1 1 6 92% 1 8, 3 1 2 94%
Repeaters 1 ,7 2 6 61% 1 ,498 70%
Allopath ic total 1 9, 842 90% 1 9,8 1 0 93%
Osteopath ic 1 st takers 1 ,964 82% 2,145 89%
Repeaters 75 41% 66 65%
Osteopath ic total 2,039 80% 2 ,2 1 1 88%
Total U. S . /Canadian 2 1 ,8 8 1 89% 2 2 ,02 1 92%

I M G 1 st takers 1 4, 2 0 3 70% 1 4, 8 5 5 73%
Repeaters 4,6 5 6 33% 4,62 1 36%
IMG total 1 8, 8 5 9 61% 1 9,476 64%
Total Step 1 examinees 40,740 76% 4 1 ,497 79%
What Does My Score Mean?
The most important point with the S tep 1 score is pass i n g versus fa i l i ng.
Pass ing essentially means, " H ey, you 're o n your way to becoming a fully
l i c ensed doc." As Table 1 shows, the maj ority of students pass the exam, so
remember, we told you to relax.
Beyond that, the main point of having a quantitative score is to give you a sense
of how well you've clone on the exam and to help schools and residencies rank
their students and appl icants, respectively.
Official N B M E/USMLE Resources
We strongly encourage students to use the materials provided by the testi ng

agencies (see p. 2 3 ) and to study in detail th e fol l owing B M E resour ces,
all of wh ich are available at the U SMLE Web site, www. usmle .org:
USMLE Step 1 Computer-based Content and Sample Test Questions (free

to all examinees)
Practice questions may be easier
2 0 1 3 USMLE Bu lletin of lnformation (free to all examinees)
than the actual exam.
Comprehensive Basic Science Self-Assessment
The USMLE Step 1 Compu ter-based Conten t and Sample Test Questions
contains approximately 1 5 0 questions that are similar in format and content
to the questions on the actual U SMLE Step 1 exam. Th is practice test offers
one of the best means of assessing your test-taking skills. H owever, it does not
contain enough questions to simulate the ful l length of the examination, and
its content represents a l i mited sampl ing of the basic science material that
may be covered on Step l . Moreover, most students felt that the questions on
the actual 2 0 1 2 exam were more challenging than those contained in that
G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N S ECTIO N I 1 1
year's sample questions. Interestin g ly, some stu dents reported that they had TA B L E 2 . CBSSA to U S M L E Score
Prediction.
encountered a few near-duplicates of these sample questions on the actual
Step l exam. Presumably, these are "experimental " questions, but who knows? CBSSA Approximate
Score USMLE Step 1 Score
So the bottom line is, know these questions!
200 151
The extremely detailed Step 1 Content Outline provided by the U SMLE has 250 163
not proved useful for students studying for the exam. The U S MLE even states
300 175
that " . . . the content outl ine is not intended as a curriculum development or
study gu ide." 1 We concur with th is assessment. 350 1 86
400 198
The 2 0 1 3 USMLE B u lletin of Info rm a tion contains deta i l e d procedur al
450 210
and policy information regarding the C B T, including desc ripti o ns of all
500 221
three Steps, scoring of th e exa m s , reportin g of scores to medical schools
and residency programs, procedures for score rechecks and other inquiries, 550 233
pol icies for irregular behavior, and test dates. 600 245
650 257
The NBME also offers th e C omprehensive Basic Science Self-Assessment
( C B S SA) , wh ich tests users on topics covered during basic science courses 700 268
in a format similar to that of the U SMLE Step l examination. Students who 750 280
prepared for the examination using th is Web-based tool reported that th ey 800 292
found the format and content h ighly i ndicative of questions tested on the
Step l examination. I n addition, the C B S SA is a fa ir predictor of U S M LE
performance (see Table 2 ) .
The C B S SA exists i n two forms: a sta ndard-paced a n d a self-paced format,

both of wh ich consist of four sections of 50 questions each (for a total of 200
multiple-choice items) . The standard-paced format allows the user up to one
hour to complete each section, reflecting the time l i mits of the actual exam.
By contrast, the self-paced format places a four-hour time limit on answering
the multiple-choice questions. Keep i n mind that this bank of questions is
available only on the Web . The N B M E requ ires that users log on, register,
and start the test with i n 30 clays of registra tion. Once the assessment has
begun, u sers are required to complete the sections within 20 clays . Following
completion of the questions, the C B S SA will provide a performance profile
indicating each user's relative strengths and weaknesses, much l ike the report
profile for the U SMLE Step l exam. It is scaled with an average score of 5 0 0
a n d a standard deviation of l 0 0 . Please n ote that C B S SAs do n o t provide
correct answers to th e questions at the end of the session. H owever, some
forms can be purchased with an extended feedba ck option; these tests show
you which qu estions you a n swered i n c o rrectly, but do not show you the
correct answer or explain why your choice was wron g . Feedback from the self
assessment takes the form of a performance profile and nothing more. The
NBME charg es $ 5 0 for assessments without feedback and $60 for assessments
with feedback. The fees are payabl e by credit card or money order. For more
information regarding the C B S SA, please visit the NBME's Web site at www.
nbme . org and click on the link labeled "NBME Self-Assessment Services."
12 SECTI O N I G U I D E T O E F F I C I E N T E X A M P R E PA R AT I O N
D E F I N I N G YO U R G O A L
I t i s useful to define your own personal performance goal when approach ing
Fourth-year medical students have the
the U S MLE Step l . You r styl e a n d i n tensity of preparati o n c a n th en be
best feel for how Step 1 scores factor
matched to your goal . Furthermore, your goal may depend on your school 's
into the residency application process.
requ irements, your specialty choice, your grades to date , and your personal
assessment of the test's i mportance. Do your best to define your goals early so
that you can prepare accordingly.
C e rt a i n h ighly competitive res i d e n c y programs, s u c h as th ose in plastic

surgery and orthopedic surgery, have acknowledged their use of Step 1 scores
in th e selection process. In such residency programs, greater e mphasis may be
placed on attaining a h igh score, so students who seek to enter these programs
may wish to cons ider aiming for a very h igh score on the Step 1 exam (see
Figure 3 ) . At the same time, your Step 1 score is only one of a number of
factors that are assessed when you apply for residency. In fact, many residency
Some competitive residency programs programs value other criteria such as letters of recommendation, th i rd-year
place more weight on Step 1 clerkship grades, honors, and research experience more than a h igh score
scores in their selection process. on Step l . Fourth-year medical students who have recently completed the
residency application process can be a valuable resource in th is regard .
T I M E L I N E F O R STU DY
Before Starting
Your preparation for the USMLE Step 1 starts with entering medical school .
Organize your studying so that wh e n th e time comes to prepare for the
U S MLE , you will be ready with a strong background .
F1GuRE l . Median USMLE Step 1 Score by Specia lty for Matched U.S. Seniors. a
260
250 ...:c. ..I. T-
1 l
249
240 T 1 1 1
2 0- 2 0- 2 0-
2 3 2 4
l.
.L
230 T T I I T T I 1 I 1 1
220 T T T !
2 0 - 2 1 1
2 3
225 T
2 6 T
2 6 T
2 6 2
f
2 0
I
h T I I 1 I 1
.L .L

2 214 214
210
.L .J..
200 I 1
190
a
Vertical lines show 1nterquartile range Source: wwwnrmp.org
Make a Schedule
After you have defined your goals, map out a study schedule that is consistent
with your o b j ectives, your vacati o n t i m e , th e diffi c u l ty of your ongoi ng
c o ur sework, a n d your fa m i l y a n d s o c i a l c o m m i tm e nts ( s e e F i gu r e 4 ) .
Determine whether you want to spread out your study time o r concentrate it
into 1 4-hour study days i n the fi nal weeks . Then factor in your own h istory in
preparing for standardized examinations ( e .g. , SAT, MCAT) . Talk to students
at your school who have recently taken Step 1 . Ask th em for the i r study
schedules, especially those who have study habits and goals similar to yours.
Typ ical ly, U . S . medical stu d e n ts a l l o t betwee n five and seven weeks for
dedicated preparation for Step 1 . The time you dedicate to exam preparation
will depend on your target score as well as your success in preparing yourself
dur i n g the fi rst two years of medical school. Some students reserve about a
week at the end of their study period for final review; others save j ust a few
Customize your schedule. Tackle
days. When you have scheduled your exam date , do your best to adhere to it.
your weakest section first.
Studies show that a later testi ng elate does not translate into a higher score, so
avoid pushing back your test date without good reason . 2
Another important consideration is when you will study each subj ect. Some
subj ects lend themselves to cramming, whereas others demand a substantial
long-term commitment. The "crammable" subj ects for Step 1 are those for
which concise yet relatively complete review books are available. ( See Section
FIGURE 4 . Typical Timeline f o r the U S M L E Step 1 .
201 2 Nov
Dec
201 3 Jan ----1f--- Schedule test date and

locatio n
Feb
Mar
Apr
May
June
July
Aug
f----- Expect scores 4-6 weeks
after exam
Sept
IV for h ighly rated review and sample exa m i nation materials . ) B e h avioral
science and physiol ogy are two subj ects with concise review books . Three
subj ects with longer but qu ite comprehensive review books are microbiology,
pharmacology, and biochemistry. Thus, th ese s u b j e c ts c o u l d be c overed
towa rd the end of your s c h e d u l e , w h e reas oth e r s u b j e c ts ( a natomy and
pathology) requ ire a longer time commitment and could be studied earl ier.
Many students prefer u s i ng a " syste ms-based" approach ( e . g. , G I , renal ,
cardiovascular) to integrate th e material ac ross basic science subj ects. See
Section III to study anatomy, pathology, physiology, and pharmacology facts
by organ system. Each subject may make up a different percentage of the test.
For example, although anatomy may requ i re a longer time commitment to
review, you may encounter fewer anatomy questions on the test than questions
on pharmacology. You can find more details of the breakdown of the test at
the NBME's Web site.
Make your schedule real istic, and set achievable goals. Many students make
"Crammable" subjects should
the mistake of studying at a l evel of detail that requires too much time for a
be covered later and Jess
comprehensive review - reading Gra y 's Ana tom y i n a couple of clays is not a
crammable subjects earlier.
real istic goal ! Have at least two catch-up clays i n your schedu l e . No matter
how well you stick to your schedule, unexpected events happen . But don't let
yourself procrastinate because you have catch-up clays; stick to your schedule
as closely as possible and revise it regularly on the basis of your actual progress.
Be careful not to lose focus. Beware of feelings of inadequacy when comparing
study schedules and progress with your peers. Avoid others who stress you
out. Focus on a few top-rated resources that suit you r learning style - not on
some obscure books your friends may pass clown to you . Accept the fact that
you cannot learn it all .
You will need time for uninterrupted and focused study. Plan your personal
Avoid burnout. Maintain proper
affairs to minimize crisis situations near the elate of the test. Allot an adequate
diet exercise, and sleep habits.
number of breaks in your study schedule to avoid burnout. Maintain a healthy
lifestyle with proper diet, exercise, and sleep.
Another important aspect of your preparation is your studying environment.

Study where you have always been comfortable studying. Be sure to include
everyth ing you need close by ( review books, notes, coffe e , snacks, etc . ) . If
you 're the kind of person wh o cannot study alone, form a study group with
other students taking the exam. The main point here is to create a comfortable
environment with minimal distractions.
Year(s) Prior
Although you may be tempted to rely solely on cramming in the weeks and
months before the test, you should not h ave to do so. The knowledge you
gained dur i ng your fi rst two years of medical school and even d ur i ng your
undergraduate years should provide the groundwork on which to base your
test preparation. Student scores on NBME subj ect tests (commonly known as
"shelf exams") have been shown to be h ighly correlated with subsequent Step
1 scores. 3 Moreover, undergraduate science GPAs as well as MCAT scores are Buy review books early (first year)
strong predictors of performance on the Step 1 exam.4 and use while studying for courses.
We also recommend that you buy h i ghly rated review books early in your fi rst
year of medical school and use them as you study throughout the ho years.
When Step 1 comes along, these books will be familiar and personalized to the
way in wh ich you learn . It is risky and inti midating to use unfamiliar review
books in the final wo or three weeks preceding the exam. Some students find
it helpful to personalize and annotate First Aid through out the curriculum.
Months Prior
Review test elates and the appl ication procedur e . Testing for the U S M L E
Step 1 is clone on a year-round basis. If you h ave a n y disab il ities or "special
circumsta n c es," c o n t a c t th e N B M E as e a rly as possible to discuss test
accommodations (see p . 43, First Aiel for the Student with a Disabil ity) .
Before you begin to study earn estly, simulate the US MLE Step 1 under Simulate the USMLE Step 1
" real " conditions to pi npoint strengths and weaknesses in your knowledge , under "real" conditions before
test endur a n c e , and test-taking ski l l s . B e sure th at you are well informed beginning your studies.
about the examination and that you have planned your strategy for studying.
Consider what study methods you will use, the study materials you will need,
and how you will obta i n you r material s . Plan ahead . Do a lot of practic e
questions. Get advice from th ird- a n d fou rth-year medical students who have
recently taken the U SMLE Step 1 . There might be strengths and weaknesses
in your school's c u rriculum that you should take into account in deciding
where to focus your efforts . You might also choose to share books, notes, and
study hints with classmates. That is how th is book began.
Three Weeks Prior
Two to fou r weeks before the exa m i nation is a good time to resi mulate the
USMLE Step 1 . You may want to do th is earl ier d epending on the progress
of your review, but be sure not to do it later, when there will be littl e time
to remedy gaps i n your knowledge or test-taking ski l l s . Make use of any
remaining good-quality sample U S MLE test questions, and try to simu late
the computerized test conditions so that you can adequately assess your test In the final two weeks, focus on
performance. One way to simulate a ful l-l ength exam is doing a ful l , timed review, practice questions, and
NBME C B S SA fol l owed by three 46-question bl ocks from your question endurance. Stay confident!
bank or the free 1 5 0 questions from the U S M LE Web site. Recogn ize, too,
that time pressu re is inc reas ing as more and m ore questions are framed as
cl inical vignettes. Most sample exam questions are shorter than the real th ing.
Focus on reviewing the high-yield facts, your own notes, clinical images, and
very short review books . Do not fall into the trap of reviewing your strengths
repeatedly; spend time on your weaknesses.
16 SECT I O N I G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N
One Week Prior
Make sure you have your C I N ( found on your s c h e d u l i ng permit) as well

as other items necessary for the day of the examination, includi ng a current
driver's l icense or another form of photo ID with your signatu re ( make sure
the name on your I D exactly matc h e s that o n your schedul i ng permit) .
Confirm the Prometric testing center location and test time. Work out how
you will get to the testing center and what parking and traffi c problems you
One week before the test:
might encounter. If possible, visit the testing site to get a better idea of the
Sleep according to the same schedule
testing conditions you will face. Determine what you will do for lunch. Make
you'll use on test day
sure you have everything you need to ensure that you will be comfortable and
Review the CBT tutorial one last time
alert at the test site. It may be beneficial to adj ust your schedule to start waking
Call Prometric to confirm test date and
up at the same time that you will on your test day. And of course, make sure
time
to maintain a healthy lifestyle and get enough sleep.
One Day Prior
Try your best to relax and rest the night before the test. Double-check your
admissions and test-taking materials as well as the comfort measures discussed
earl ier so that you will not have to deal with such details on the morning of
the exam. At th is point it will be more effective to review short-term memory
material that you're already familiar with than to try to learn new material .
The Rapid Review section at the end of th is book is h igh yield for last-minute
studying. Remember that regardless of how hard you have studied, you cannot
know everyth ing. There will be th ings on the exam that you have never even
seen before, so do not panic. Do not underestimate your abilities.
Many students report difficulty sleeping the night prior to the exam. Th is is
often exacerbated by going to bed much earl ier than usual . Do whatever it
takes to ensure a good night's sleep ( e . g . , massage , exercise, warm milk, no
back-l it screens at night) . Do not change your daily routi ne prior to the exam.
Exam clay is not the clay for a caffeine-withdrawal headache.
Morning of the Exam

No notes, books, calculators, pagers, cell
phones, recording devices, or watches On the morning of the Step 1 exa m , wake up at your regu l a r time and
of any kind are allowed in the testing eat a normal breakfast. If you th ink it will help you , h ave a close friend or
area, but they are allowed in lockers. family member check to make sure you get out of bed. Make sure you have
your scheduling permit admission ticket, test-taking materials, and comfort
measu res as discussed earl ier. Wear loose, comfortable cloth ing. Plan for a
variable temperature in the testing center. Arrive at the test site 3 0 minutes
before the time designated on the admission ticket; however, do not come
too early, as doing so may i ntensify your anxiety. Wh e n you a rrive at th e
test site, the proctor should give you a U S MLE information sheet that will
explain critical factors such as th e proper use of break ti m e . Th e U SM LE
uses the B iometric Identity Management System ( B I M S ) at some test cente r
locations. B I M S converts a fi ngerprint, taken on test clay, to a digital i mage
used for identification of examinees during the testing process. Seating may be
assigned, but ask to be reseatecl if necessary; you need to be seated in an area
G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N SECTI O N I 17
that will allow you to remain comfortable and to concentrate . Get to know Arrive a t the testing center
your testing stati o n , especially if you have never been in a Prometric testi ng 30 minutes before your scheduled
center before . Listen to your proctors regarding any changes in instructions or exam time. If you arrive more
testing procedures that may apply to your test site. than half an hour late, you will
not be allowed to take the test.
Finally, remember that it is natural (and even beneficial) to be a little nervous.
Focus on being mentally clear a n d alert. Avoid pan i c . Avoid panic. Avoi d
panic. When you are asked t o begin the exam, take a deep breath, focus o n
the screen, and th en begi n . Keep a n eye on th e timer. Take advantage o f
breaks between blocks t o stretch, maybe do some j umping jacks, a n d relax for
a moment with deep breath i ng or stretching.
After the Test
After you have completed the exam, be sure to have fun and relax regardless
of how you may feel. Taking the test is an achievement in itself. Remember,
you are much more l ikely to have passed than not. E n j oy the free time you
have before your clerkships. Expect to experience some "reentry" phenomena
as you try to regain a real life . Once you have recovered sufficiently from the
test (or from partyi ng) , we i nvite you to send us your feedback, corrections,
and suggestions for entries, facts, mnemonics, strategies, resource ratings, and
the l ike (see p. xvii , How to C ontribute ) . Sharing your experience will benefit
fellow medical students and IMGs.
S T U D Y M AT E R I A L S
Quality and Cost Considerations
Although an ever-increasing number of review books and software are now

available on the market, the qual ity of such material is h ighly variable. Some
common problems are as follows :
Certain review books are too detailed to allow for review in a reasonable
amount of time or cover subtopics that are not emphasized on the exam.
Many sample question books were originally written years ago and have
not been adequately updated to reflect recent trends.
Many sample question books use poorly written questi ons or contain
factual errors in their explanations.
Explanations for sample questions vary in qual ity.
If a given review book is not working for
Basic Science Review Books you, stop using it no matter how highly
rated it may be or how much it costs.
In selecting review books, be sure to weigh different opinions against each
other, read the reviews and ratings i n Section IV of th is guide, examine the
books cl osely i n the bookstore, and choose carefully. You are i nvesting not
only money but also your l i mited study time. Do not worry about finding
the "perfect" book, as many sub j ects s imply do not have one, and different
students prefer different formats. Supplement your chosen books with personal
notes from other sources, including what you learn from question banks .
There are two types of review books : those that are stand-a l o n e titl es and
Charts and diagrams may be
those that are part of a series. Books in a series generally have the same style ,
the best approach for physiology
a n d you must decide if that style works for you . However, a given style is not
and biochemistry, whereas
optimal for every subj ect.
tables and outlines may be
You should also find out which books are up to date . Some recent editions
preferable for microbiology.
reflect major improvements , whereas others contain only cursory changes.
Take into consideration how a book reflects the format of the U SMLE Step 1 .
Pradice Tests
Taking practice tests provides valuable information about potential strengths

a n d weaknesses in your fu n d of knowl e dge a n d test-taking s k i l l s . Some
students use practice exami nations s imply as a means of break i ng up the
monotony of studying and adding variety to the i r study schedule, whereas
other students rely almost solely on practice tests . Your best preview of the
Most practice exams are shorter and
computerized exam can be found in the practice exams on the U SMLE Web
less clinical than the real thing.
site . Some students also recommend u s i ng c o mputerized test s i mulation
programs. In addition, students report that many current practice-exam books
have questions that are, on average , shorter and less cl inically oriented than
those on the current U SMLE Step l .
After taking a practice test, try to identify concepts and areas of weakness, not
j ust the facts that you missed . Do not panic if you miss a lot of questions on a
Use practice tests to identify
practice examination; instead, use the experience you have gained to motivate
concepts and areas of weakness,
your study and prioritize those areas in which you need the most work. Use
not just fads that you missed.
quality practice examinations to i mprove your test-taki ng skills. Analyze your
abil ity to pace yourself.
Clinical Review Books
Keep your eye out for more clinically oriented review books; purchase them
early and begin to use them. A number of students are turning to Step 2 books,
pathophysiology books, and case-based reviews to prepare for the cl i n ical
vignettes. Examples of such books include:
First Aid Cases for the USMLE Step 1 ( McGraw-H ill)

First Aid for the Wards (McGraw-H ill)
First Aid Clerkship series (McGraw-H ill)
B lueprints clinical series ( Lippincott Williams & Wilkins)
PreTest Ph ysica l Diagnosis ( McGraw-H i l l )
Washington Manual ( Lippincott Wil l iams & Wilkins)
Various USMLE Step 2 review books
Ci U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N S ECTI O N I 19
Texts, Syllabi, and Notes
Limit your use of textbooks a n d course syl l a b i for Step 1 review. Many
textbooks are too deta i l ed for h igh-yield review and include material that
is generally not tested on the U S M LE Step 1 ( e .g. , dru g dosages, complex
chemical structure s ) . Syl l a b i , a l th o ugh fa m i l iar, are incons istent ac ross
medical schools and frequently reflect th e emphasis of individual fac u l ty,
wh ich often does not correspond to that of the U SMLE Step 1 . Syllabi also
tend to be l ess organized than top-rated books and generally conta in fewer
diagrams and study questions.
T E S T-TA K I N G S T R AT E G I E S
Your test performance will be influenced by both your knowledge and your
Practice and perfect test-taking skills
test-taking skills. You can strengthen your performance by considering each
and strategies well before the test date.
of these factors . Test-taking skil l s and strategies should be devel oped and
perfected well i n advance of the test elate so that you can concentrate on the
test itself. We suggest that you try the following strategies to see if they might
work for you .
Pacing
You have seven hours to compl ete 3 2 2 questi o n s . Note that e a c h one
hour block contains 46 questions. Th is works out to about 7 7 seconds per
question. If you find yourself spending too much time on a question, mark the
question, make an educated guess, and move on. If time permits, come back
to the question later. In the past, pacing errors have been detrimental to the
Time management is an important
performance of even h ighly prepared examinees. The bottom line is to keep
skill for exam success.
one eye on the clock at all times !
Dealing with Each Question
Th ere a re several e s t a b l i s h e d te c h n i qu e s fo r effi c i e n tl y appro a c h i n g

multiple-choice questions; fi n d what works for you . One technique begins
with identifying each question as easy, workable, or i mpossible. You r goal
should be to answer all easy questions, resolve all workable questions i n a
reasonable amount of ti m e , and make qu ick and intell igent guesses on a l l
impossible questions. M o s t students read the stem, think o f the answer, a n d
turn immediately t o t h e choices. A second technique is to first skim the answer
choices and the last sentence of the question and then read through the
passage quickly, extracting only relevant information to answer the question.
Try a variety of techniques on practice exams and see what works best for you .
Difficult Questions
Because of the exam 's c l i nical emphasis, you may fi n d that many of th e
questions on th e Step l exam appear workable but take more time than
is available to you . It can be tempting to dwell on such questions because
you feel you are on the verge of " figuring it out," but resist th is temptation
Do not dwell excessively on and budget your time . Answer difficult questions with you r best guess, mark
questions that you are on the them for review, and come back to them only if you have time after you have
verge of "figuring out. " Make completed the rest of the questions in the block. This w i l l keep you from
your best guess and move on. i nadvertently leaving any questions blank i n your efforts to "beat the clock."
Another reason for not dwell i ng too long on any one question is that certain
questions may be experimental or may be incorrectly phrased. Moreover, not
Remember that some questions all questions are scored . Some questions serve as "embedded pretest items"
may be experimental. that do not count toward your overall score . I n fact, anywhere from l 0% to
20% of exam questions have been designated as experimental on past exams.
Guessing
There is no penalty for wrong answers . Thus, no test block should be left
with unanswered questions. A hunch is probably better than a random guess .
If you have to guess, we suggest selecting an answer you recognize over one
with wh ich you are totally unfamil iar.
Changing Your Answer
The conventional wisdom is not to change answers that you have al ready
marked unless there is a convincing and logical reason to do so - i n other
words, go with your "first hunch." H owever, studies show that if you change
Your first hunch is not always correct.
your answer, you are twice as l ikely to change it from an incorrect answer to a
correct one than vice versa. So if you have a strong "second hunch," go for it!
Fourth-Quarter Effed (Avoiding Burnout)
Pacing and endurance are i mportant. Practice helps d evelop both . Fewer
and fewer examinees are leaving the examination session early. Use any extra
time you might have at the end of each block to return to marked questions
or to recheck your answers; you cannot add the extra time to any remaining
blocks of questions. Do not be too casual in your review or you may overlook
Do not terminate a question
serious mistakes. Remember your goals, and keep in mind the effort you have
block too early Carefully review
devoted to studyi ng compared with the small additional effort you will need
your answers if possible.
to maintain focus and concentration throughout the examination. Never give
up. If you begin to feel frustrated, try taking a 3 0-second breather.
G U I D E TO E F F I C I E N T E X A M P R E PA R AT I O N SECTI O N I 21
C L I N I C A l V I G N E T T E S T R AT E G I E S
I n recent yea rs , th e U S M L E Step l has become i n c reasingl y c l i ni c a l l y

Be prepared to read fast
oriente d . Th i s c h a nge m i rrors the tre n d i n m e d i c a l e d u c a t i o n towa rd
and think on your feet!
introducing students to c l i nical problem solving dur i ng the basi c science
years. The increasing clinical emphasis on Step l may be challenging to those
students who attend schools with a more traditional curriculum.
What Is a Clinical Vignette?
A cli nical vignette is a short ( usually paragraph-long) description of a patient,

including demograph ics, presenting symptoms, signs, and other information
concerning the patient. Sometimes th i s paragraph is fol l owed by a b r i e f
l isti ng of i mportant physical findings and/or laboratory results. T h e task o f
Practice questions that include case
assimilating a l l th is information and answering the associated question in the
span of one minute can be intimidating. So be prepared to read quickly and histories or descriptive vignettes are
critical for Step I preparation.
th ink on your feet. Remember that the question is often i ndi rectly ask i ng
something you already know.
Strategy
Remember that Step l vignettes usually describe diseases or disorders in their

most classic presentation. So look for buzzwords or cardinal signs ( e .g. , malar
rash for SLE or nuchal rigidity for meningitis) i n the narrative h istory. Be
aware , however, that the questi on may contain classic signs and symptoms
Step T vignettes usually describe
instead of mere buzzwords . Sometimes the data from labs and the physical
diseases or disorders in their
exam will help you confirm or rej ect possible diagnoses, thereby helping you
most classic presentation.
rule answer choices in or out. In some cases, they will be a dead giveaway for
the diagnosis.
Making a diagnosis from the h istory and data is often not the final answer. Not
infrequently, the diagnosis is divulged at the end of the vignette, after you have Sometimes making a diagnosis
just struggled through the narrative to come up with a diagnosis of your own .
is not necessary at all.
The question might then ask about a related aspect of the diagnosed disease .
One strategy that many students suggest is to skim the questions and answer
choices before reading a vignette, especially if the vignette is lengthy. Th is
focuses your attention on the relevant information and reduces the time spent
on that vignette . Sometimes you may not need much of the information in
the vignette to answer the question. However, be careful with skimming the
answer choices; going too fast may warp your perception of what the vignette
is asking.
I F Y O U T H I N K Y O U FA I L E D
After the test, many examinees feel that they have failed, and most are at the
very least unsure of their pass/fail status. There are several sensible steps you
can take to plan for the future in the event that you do not achi eve a passing
score . First, save and organize all your study mate ri als, i n c l u d i ng review
books, practice tests, and notes. Famil iarize yourself with the reappl ication
procedures for Step l , incl uding appl ication deadl ines and upcoming test
If you pass Step 1, you are not
elates. The CBT format allows an examinee who has failed the exam to retake
allowed to retake the exam.
it no earl ier than the first clay of the month after 60 clays have elapsed since
the last test elate . Examinees will, however, be allowed to take the Step l exam
no more than four times within a 1 2-month period should they repeatedly fail.
The performance profiles on the back of the U S MLE S tep l score report
provide valuable feedback concerning your relative strengths and weaknesses.
Study these profiles closely. Set up a study ti meline to strength e n gaps in
your knowledge as well as to maintain and improve what you already know.
Do not neglect high-yield subj ects . It is normal to feel somevvhat anxious
about retaking the test, but if anxiety becomes a problem, seek appropriate
counsel ing.
Although the NBME allows an unlimited number of attempts to pass Step l ,

they recommend that l icensing authorities allow a maximum of six attempts
for each Step examination . 5 Aga i n , review your school's pol icy regarding
retakes.
I F Y O U FA I L E D
Even i f you came out of the exam room fee l i ng that you fa iled, seeing that
failing grade can be traumatic, and it is natural to feel upset. Different people
react in different ways : For some it is a stimulus to buckle clown and study
harder; for others it may "take the wind out of their sails" for a few clays; and
Near the failure threshold, each point
it may even lead to a reassessment of individual goals and abilities. In some
on the three-digit scale is equivalent to
instances, however, failure may trigger weeks or months of sadness, feelings of
about 1.5 questions answered corredly. 6
hopelessness, social withdrawal, and inability to concentrate - in other words,
true clinical depression. If you th ink you are depressed, please seek help.
TESTI N G AG E N C I E S
National Board of Medical Examiners (NBME)

Department of Licensing Examination Services
3 7 5 0 Market Street
Philadelph ia, PA 1 9 1 04-3 1 02
( 2 1 5 ) 5 90-9700
Fax: ( 2 1 5 ) 590-94 5 7
Email : webmail@nbme . org
www. nbme . org
Educational Commission for Foreign Medical Graduates (ECFMG)

3624 Market Street
Philadelph ia, PA 1 9 1 04-268 5
( 2 1 5 ) 3 86- 5900
Fax: ( 2 1 5 ) 3 86-9 1 96
Ema i l : info@ecfmg. org
www. ecfmg.org
Federation of State Medical Boards (FSMB)

400 Fuller Wiser Road , Suite 3 0 0
Euless, TX 760 3 9-3 8 5 6
( 8 1 7) 868-4000
Fax: ( 8 1 7) 868-4099
Emai l : usmle@fsmb .org
www.fsmb .org
USMLE Secretariat
Philadelph ia, PA 1 9 1 04- 3 1 90
( 2 1 5 ) 5 90-9700
Fax: ( 2 1 5 ) 590-94 5 7
Ema i l : webmail@nbme .org
www. usmle .org
REFERENCES
l . Un ited States Medical Licensing Exa m ination. Step 1 C ontent Description

Online. Ava i l able at: http : //www.usmle.org/pdfs /step- 1 /2 0 1 2content_step 1 .pdf.
Accessed S eptember 2 6 , 2 0 1 2 .
2 . Poh l , Charles A . , Robeson, Mary R . , H ojat, Mohammadreza, and Velosk i , J .
Jon, " S ooner or Later? U S M L E Step 1 Performance a n d Test Ad m i n istration
Date at the End of the Second Year," Academic Medicine, 2002 , Vol . 7 7, No.
10, pp. S 1 7- S 1 9.
3. Holtman, Matthew C . , Swanson, David B . , R ipkey, Douglas R . , and Case,
Susan M . , " U s i n g Basic S c ience Subject Tests to Identify Students at R i sk for
Fa i l i ng Step 1 ," Academic Medicine, 2 0 0 1 , Vol . 76, No. 10, pp. S48-S 5 l .
4 . Basco, Will iam T., Jr., Way, David P. , G i l b e rt, Gregory E . , and Hudson,
Andy, "Undergraduate Institutional MCAT S cores as P re d i c tors of U S M LE
Step 1 Performance," Academic Medicine, 2 0 02 , Vol . 7 7, No. 1 0 , pp. S 1 3 -
S16.
5 . United States Medical Licensing Exa m i nation . 2 0 1 3 U S M LE B u l l e ti n :
El igibibii lty. Ava i l able at: http : //www.usm l e . org/b u l l eti n /e l igibil ity. Accessed
September 26, 2 0 1 2 .
6 . O'Donnel l , M . J . , Obensha i n , S . Scott, and E rd m a n n , James B . , " 1 :
Background Essential to the Proper Use o f Results o f Step 1 and Step 2
of the U S M L E ," Academic Medicine, October 1 9 9 3 , Vol . 6 8 , No. 1 0 , pp.
7 3 4-7 39.
S ECTI O N I S U P P LE M E NT
Specia l Situations
26 SECTION I S P E C I A L S I T U AT I O N S
F I R S T A I D F O R T H E I N T E R N AT I O N A L M E D I C A L G R A D U AT E
" International medical graduate" ( I M G ) i s the accepted term n ow used to

describe any student or graduate of a non-U . S . , non-Canadian, non-Puerto
IMGs make up approximately 25%
Rican medical school , regardless of wheth e r he or she is a U. S . citizen or
of the U.S. physician population.
resident. Technically the term IMG encompasses FMGs (foreign medical
graduates; i . e . , medical graduates from medical schools outside the United
States who are not residents of the U nited States - that is, U. S . citizens or
green-card holders ) , although the terms I M G and FMC are ofte n used
interchangeably.
I M G's Steps to Licensure in the United States
To be eligible to take the U S MLE Steps, you (the appl icant) must be officially
Mare detailed information
enrolled in a medical school located outside the United States and Canada
can be found in the ECFMG
th at is l i s ted i n the International Medical E d u cation D irectory ( I M E D ;
Information Booklet, available at
http : //www.faimer. org/resources/i m e cl . html ) , both at the time you apply for
www. edmg.argjpubshome.html.
examination and on your test clay. In addition, your "Graduation Year" must
be listed as "Current" at the time you apply and on you r test clay.
If you are an IMG, you must go through the following steps (not necessarily
in this order) to apply for residency programs and become licensed to practice
in the United States. You must complete these steps even if you are already
a practicing physician and have completed a residency program i n your own
country.
Pass U S MLE Step 1 , Step 2 C K, a n d Step 2 C S , as well as obta i n a

Applicants may apply online
medical school diploma ( n ot necessarily i n th is order) . All three exams
for USMLE Step 1, Step 2 CK, or
can be taken dur i ng medical school .
Step 2 CS at www. edmg.org.
Apply for certification from the Educational C o mmission for Foreign
M e d i c a l Graduates ( E C FM G ) after above steps are s u c c essfu l l y
completed. There w i l l be a delay o f 4-8 weeks between your E C FMG
application and your receipt of the ECFMG certificate ; the EC FMG will
not issue a certificate (even if all the U SMLE scores are submitted ) u ntil
it verifies your medical diploma with your medical school .
You must have a val id ECFMG certificate before entering an accredited
residency program in the United States, although you can begi n th e
E l e ctroni c Resi d e n c y Appl i c a t i o n S e rv i c e ( E RA S ) appl i c a t i o n a n d
interviews before you receive t h e certificate . H owever, m a n y programs
prefer to interview IMGs who have an EC FMG certificate, so obtaining
it by the time you submit your E RAS application is ideal .
Apply for residency positions i n your fields of i nterest, either di rectly
or th rough the E RAS and the National Residency Match i ng Program
(NRMP) , otherwise known as "the Match ." To be entered into the Match ,
you need to have passed all the exa m inations necessary for EC FMG
certification ( i . e . , Step 1 , Step 2 C K, and Step 2 C S ) by the rank order l ist
deadl ine ( usually in late February before the Matc h ) . If you do not pass
these exams by the deadl ine, you will be withdrawn from the Matc h .
S P E C I A L S I T U AT I O N S SECTION I 27
I f you are not a U . S . citizen o r green-card holder (permanent resident) ,

obtain a visa that will allow yo u to enter and work in the United Stat s .
Sign up t o receive the EC FMG a n d E RAS email newsletter t o keep up to
elate with their most current policies and deadl ines.
If required by the state in which your residency program is located, obtain
an educational/training/l imited medical license. Your residency program
may a5sist you with th is appl ication . Note that medical l icensing i5 the
prerogative of each i n dividual state , not of the federal government, and
that states vary with respect to their laws a bout licensing.
Once you have the ECFMG certification, take the USMLE Step 3 dur i n g
your residency, and then obtain a full medical license . Once you have a
state-issued l icense, you are permitted to practice in federal i nstitutions
such as Veterans Affairs (VA) hospitals and Indian Health Service facil ities
i n any state. Thi5 can open the door to "moonl ighting" opportunities
and possibil ities for an H 1 B visa appl ication if relevant. For deta ils on
individual state rules, write to the l icensing board in the state in question
or contact the Federation of State Medical Boards ( FSMB ) . If you need
to apply for an H 1 B visa for starting residency, yo u will need to take and
pass the USMLE Step 3 exam, preferably before you Match.
Complete yo ur residency and then take the appropriate specialty board
exams if you wish to become board certified ( e .g. , in internal medicine or
surgery) . If you already have a specialty certification in another country,
some specialty boards may grant you six months' or one year's c redit
toward your total residency time.
C urrently, most residency programs are accepting appl ications thro ugh
ERAS. For more i nf01 mation, see First Aid for the Match or contact:
ECFMG/ERAS Program
3624 Market Street
Philadelphia, PA 1 9 1 04-268 5 U SA
( 2 1 5 ) 3 86-5900
Email : eras-support@ecfmg.org
www.ecfmg.org/eras
For deta iled information on the U SMLE Steps, visit the U S MLE Web
site at http://www. usmle.org.
The USMLE and the I M Ci
The U S M L E is a s e r i e s of standardized exams that give I M G s and U . S .

medical graduates a level playing field. The passing marks for IMGs for Step IMGs ha ve a maximum of s1x attempts
l , Step 2 CK, and Step 2 CS are determined by a statistical distribution that to pass any USMLE Seep, and must pass
is based on the scores of U. S . medical school students. For example , to pas the USMLE Steps requtred for t.CJ-MG
Step 1 , you will probably have to score h igher than the bottom 8- 1 0% of U . S . certification wtlhm a seven-year pc::ll d.
and Canadian graduates.
U nder new U S MLE program rul e s , a maximum of six atte mpts will be
permitted to pass any U SMLE S tep or component exam starting January l ,
20 1 2 for new examinees, and J anuary 1 , 2 0 1 3 for previous examinees. There
I
28 SECTION I S P E C I A L S IT U AT I O N S
is a l imit of three attempts with in a 1 2-month period for any of the U SMLE
Steps.
Timing of the USMLE
For an IMG, the timing of a complete application is critical . It is extremely

i mportant that you send i n your appl ication early if you are to obtai n the
maximum number of interviews . C omplete all exam requi rements by August
of the year in wh ich you wish to apply. C h e c k the E C FM G Web site for
deadl ines to take and pass the various Step exams to be eligible for the NRMP
Match.
I M G appl i c a nts must pass th e U S M L E Steps requ i re d fo r E C FMG

certification within a seven-year period . The U SMLE program recommends,
although not all j ur isdictions impose, a seven-year limit for completion of the
three-step U SMLE program .
If your clinical experience is recent,

In terms of U SMLE exam order, arguments can be made for taking the Step
consider taking the Step 2 CK
1 or the Step 2 CK exam fi rst. For example, you may consider taking the
first, followed by the Step 1.
Step 2 CK exam first if you have j ust graduated from medical school and
the cl inical topics are stil l fresh in your mind. H owever, keep i n mind that
th ere is substantial overlap between Step 1 and Step 2 CK topics in areas
such as pharmacology, pathophysiology, and biostatistics. You might therefore
consider taking the Step 1 and Step 2 C K exams c l ose togeth er to take
advantage of th is overlap in your test preparation.
USMLE Step 1 and the I M G
S ignificance of the Test. Step 1 is requ ired for the E C FMG certificate as
well as for registration for th e Step 2 C S . S i nce most U. S . graduates apply
to residency with their Step 1 scores only, it may be the only objective tool
available with which to compare IMGs with U . S . graduates.
El igibility Period. A three-month period of your choice.
Fee. The fee for Step 1 is $790 plus an international test delivery surcharge (if
you choose a testing region other than the United States or Canada ) .
Statistics. In 20 1 1 -20 1 2 , 7 3 % of iMG examinees passed Step 1 o n their first

attempt, compared with 94% of those from the United States and Canada.
Tips. Although few if any students feel totally prepared to take Step 1 , IMGs
A higher Step 1 score will improve
in particular requ ire serious study and preparation in order to reach their full
your chances of getting into a
potential on this exam. It is also imperative that IMGs do their best on Step
highly competitive specialty.
l , as a poor score on Step 1 is a distinct disadvantage i n applying for most
res idencies. Remember that if you pass Step 1 , you cannot retake it i n an
attempt to improve your score . You r goal should thus be to beat the mean ,
because you can then assert with confidence that you have clone better than
average for U . S . students . H igher Step 1 scores will also l e n d c redi b i l i ty to
S P E C I A L S I T U AT I O N S S E CT I O N I 29
your residency application and help you get into h ighly competitive specialties
such as radiology, orthopedics, and dermatology.
Do c o m m e rc i a l review c o ur s e s h e l p
C o m m e r c i a l Review C o u r s e s .
i mprove your scores? Reports va ry, a n d s u c h courses c a n be expen s i ve .
For some students these programs c a n provide a more structured learning
environment with professional support. H owever, review courses consume
a significant c h u nk of time away from i ndependent study. Many I M G s
decide t o prepare fo r S t e p 1 o n th e i r o w n a n d th en c o ns i d e r a review
course only if th ey fa i l . ( For more i n formation on review c o u r s e s , see
Section IV. )
USM LE Step l CK and the I MG
What Is the Step 2 It is a computerized test of the c l i nical sciences

C K?
consisti ng of up to 3 5 5 multiple-choice questions divided into eight blocks.
It can be taken at Prometric centers in the U nited States and several other
countries.
Content. The Step 2 C K includes test items in the following content areas :
The areas tested o n the Step 2 CK
relate to the clerkships provided
Internal medicine
at U. S. medical schools.
Obstetrics and gynecology
Pediatrics
Preventive medicine
Psych iatry
Surgery
Other areas relevant to the provision of care under supervision
Significance o f the Te st. The Step 2 CK i s requ i red for th e E C F M G

certificate . It reflects the level o f clinical knowledge o f the appl icant. It tests
clinical subjects, primarily i nternal medicine. Other areas that are tested are
surgery, obstetrics and gynecology, pediatrics, orthopedics, psychiatry, E NT,
ophthalmology, and medical ethics.
Eligibility.Students and grad uates from medical schools that are l isted in
IMED are e l igible to take th e Step 2 C K. Students must have completed
at least two years of medical school. This means that students must have
completed the basic medical s c i e n c e component of th e medical school
curriculum by the beginning of the el igibil ity period selected .
Eligibility Period. A three-month period of your choice .
Fee. The fee for th e Step 2 C K is $790 plus an i nternational test del ivery
surcharge ( i f you ch oose a testing region oth e r than the United States or
Canada) .
Statistics. In 20 l l -20 1 2 , 84% o f E C FMG candidates passed the Step 2 C K

o n their first attempt, compared with 96% o f U . S . and Canadian candidates.
30 S ECTI O N I S P E C I A L S I T U AT I O N S
Tip s . It's better to take the Step 2 C K after your i n ternal medicine rotation
Be familiar with topics that are
because most of the questions on the exam give c l i nical scenarios and ask
heavily emphasized in U.S. medicine,
you to make medical diagnoses and cl inical decisions. I n additio n , because
such as cholesterol screening.
th is is a cli nical sciences exam, cultural and geograph i c considerations play
a greater role than is th e case with Step l . For exampl e , i f your medical
education gave you ample exposure to malaria, bru cellosis, and mal nutrition
but l i ttle to alcohol withdrawal , child abuse, and cholesterol screening, you
must work to familiarize yourself with topics that are more heavily emphasized
in U. S . medicine. You must also have a basic understanding of the l egal and
social aspects of U . S . medici n e , because you will be asked questions about
communicating with and advising patients.
USMLE Step l C S and the I M G
What I s the Step 2 C S ? The Step 2 C S is a test of clinical and communication

skills administered as a on e-day, eight-hour exa m . It i n c l udes 1 0 to 1 2
encounters with standardized patients ( 1 5 minutes each , with l 0 minutes to
write a note after each encounter) .
C ontent. The Step 2 C S tests the ability to communicate in E ngl ish as well
as interpersonal skills, data-gathering skills, the ability to perform a physical
exam, and the ability to formulate a brief note , a differential diagnosis, and a
l ist of diagnostic tests . The areas that are covered in the exam are as follows:
Internal medicine
Surgery
Obstetrics and gynecology
Pediatrics
Psychiatry
Family medicine
Unl ike the U S MLE Step l , Step 2 C K, or Step 3, there are no numerical
The Step 2 CS is graded as passjfail.
grades for the Step 2 C S - it's si mply either a "pass" or a "fa i l ." To pass, a
candidate must attain a passing performance i n each of the following three
components:
Integrated Cl inical Encounter (ICE): includes Data Gathering, Physical

Exam, and the Patient Note
Spoken Engl ish Proficiency ( S E P )
Communication a n d Interpersonal Skills ( C I S )
According to the NBME, the most commonly failed component for I M G s is

the C I S .
S ignificance o f the Test. T h e Step 2 C S assesses spoken E ngl ish language

proficiency and is requ ired for the ECFMG certificate . The Test of English
as a Foreign Language (TOEFL) is no longer requ i red.
El igibility.Students must have completed at least two years of medical school

i n order to take the test. That means students must have completed the basic
medical science component of the medical school curriculum at the time

they apply for the exam.
Fee. The fee for the Step 2 C S is $ 1 3 7 5 .
Scheduling. You must schedule the Step 2 C S with i n four months o f the
Try to take the Step 2 CS the year
date indicated on your noti fication of registratio n . You must take the exam
before you plan to Match.
within 1 2 months of the elate indicated on your notification of registration. It is
generally advisable to take the Step 2 CS as soon as possible in the year before
your Match, as often the results either come in late or arrive too late to allow
you to retake the test and pass it before the Match.
Test Site Locations. The Step 2 C S is currently administered at the following

five locations :
Ph iladelph ia, PA
Atlanta, GA
Los Angeles, CA
Chicago, IL
Houston, TX
For more information about the Step 2 C S exam, please refer to First Aid for
the Step 2 CS.
USMLE Step l and the I M G
What Is the U S M L E Step 3 ? It is a two-clay computerized test in c l i nical

medicine consisti ng of 480 multiple-choice questi ons and nine compute r
based case simulations (CC S ) . The exam aims at testing your knowledge and
its application to patient care and clinical decision making ( i . e . , th is exam tests
if you can safely practice medicine independently and without supervision ) .
Significance o f the Test. Taking Step 3 before residency i s critical for IMGs Complete the Step 3 exam before
seeking an H 1 B visa and is also a bonus that can be added to the residency you apply for an H 18 visa.
appl ication. Step 3 is also requ ired to obta i n a full medical l icense i n the
United States and can be taken dur i ng residency for th is purpose .
Fee. The fee for Step 3 is $780 in all states except Iowa ( $ 8 3 0 ) , South Dakota
($9 3 0 ) , and Vermont ( $8 1 5 ) .
Most states requ i re that appl icants have completed one, two, or
El igibil ity.
three years of postgraduate training ( residency) before they apply for Step 3
and permanent state l i censur e . The excepti ons are the 1 3 states mentioned
below, wh ich allow IMGs to take Step 3 at the begi nning of or even before
residen cy. So if you don't ful fi l l the prerequ isites to taking Step 3 in your
state of choice, si mply use the name of one of the 1 3 states in your Step 3
application. You can take the exam in any state you choose regardless of the
state that you mentioned on your appl ication . Once you pass Step 3, it will be
recognized by all states. Basic eligibil ity requ irements for the USMLE Step 3
are as follows :
32 SECTI O N I S P E C I A L S I T U AT I O N S
Obta ining a n M D o r D O degree ( o r i ts equ ivalent) b y the app l ication

deadl ine.
Obta i n i ng an EC FMG ce rtifi cate if you are a grad uate of a foreign
medical school or are successfully completing a "fifth pathway" program
(at a elate no later than the appl ication deadl i n e ) .
M eeting t h e requ irements i mposed by t h e i n dividual state l ic e n s i ng
authority to which you are applying to take Step 3 . Please refer to www.
fsmb.org for more information.
Th e fol l ow i ng states do not h ave postgraduate tra i n i ng as a n e l i g i b i l i ty

requ irement to apply for Step 3 :
Arkansas
California
Connecticut
Florida
Lou isiana
Maryland
Nebraska
New York
South Dakota
Texas
Utah *
Washington
West Vi rginia
* Requ ires that IMGs obtain a "valid indefinite" E C FMG certificate .
The Step 3 exam is not available outside the United States. Applications can
be found online at www.fsmb. org and must be submitted to the F S M B .
In 20 l l -20 1 2 , 84% of iMG candidates passed the Step 3 on their first attempt,
compared with 97% of U . S . and Canadian candidates.
Residencies and the I M G
In the Match, the number of U . S .-citizen IMG applications has grown over
the past few years, while the percentage accepted has remained constant (see
Table 4 ). More information about residency programs can be obtained at
www.ama-assn .org.
The Match and the IMG
Given the growing number of IMG candidates with strong appl ications, you
should bear in mind that good U SMLE scores are not the only way to gain a
competitive edge . However, U SMLE Step l and Step 2 C K scores continue
to be used as the initial screening mechanism when candi dates are being
considered for interviews.
TA B L E 4 . IMGs in the Match.
Applicants 201 0 201 1 20 1 2
U . S .-citizen I MCs 3,695 3,769 4,279
% U. S .-citizen I MCs accepted 47 50 49
Non-U . S .-citi zen I MCs 7, 246 6,659 6,828
% non- U . S .-citizen I M C s 40 41 41
accepted
U. S . sen i ors (non-I M Cs) 1 6 ,070 1 6, 5 59 16, 527
% U . S . sen i ors accepted 93 94 95

Source: www. n rmp.org.
Based on accumulated IMG Match experiences over recent years, here are a
few pointers to help IMGs maximize their chances for a residency interview:
Apply early. Programs offer a l i mited number of interviews and often

select candidates on a fi rst-come, fi rst-served basis. Because of th is, you
should aim to complete the entire process of applying for the ERAS token ,
registering with the Association of American Medical Colleges (MM C ) ,
mailing necessary documents t o E RA S , and completing the E RAS ap
plication before September (see Figure 5 ) . Community programs usually
send out interview offers earlier than do university and university-affiliated
programs.
U. S . clinical experience helps. Externsh ips and observersh ips in a U. S .

Most U. S. hospitals allow externship
hospital setting have emerged a s a n i mportant credential o n an I M G ap
only when the applicant is
plication. Externships are l ike short-term medical school internsh ips and
actively enrolled in a medical
offer hands-on clinical experi ence. Observerships, also called "shadow
school, so plan ahead.
ing," involve following a phys i cian and observing how he or she manages
patients . Some progra ms requ i re students to have parti cipated in a n
externsh ip or observership before applying. It is best t o gain such an expe
rience before or at the time you apply to various programs so that you can
mention it on your E RAS application. If such an experience or opportu
nity comes up after you apply, be sure to inform the programs accordingly.
Cl inical research helps. U niversity programs are attracted to candidates

who show a strong interest in clinical research and academics. They may
even relax their appl ication c riteria for i ndividuals with unique back
grounds and strong research experie n c e . Publications in well-kn own
journals are an added bonus.
Time the Step 2 C S well . E C F M G has publ ished the new Step 2 C S
score-reporting schedule for 2 0 1 2-2 0 1 3 a t http : //www. ecfmg.org/news/
category/step-2-cs . Most program di rectors would l ike to see a passi n g
score on the Step 1 , Step 2 C K, and Step 2 C S exams before they rank an
IMG on their rank order l ist in mid-February. There have been many i n
stances in which candidates have lost a potential Match - either because
of delayed CS results or because they have been unable to retake th e
F1GuRE s . I M G Ti meline for Application.
June Obta i n E RAS token and obtai n AAMC I D

I f U S M L E Steps 1, 2 C S , and 2 C K completed : req u est
E C F M G certification
July Send docu ments to E R A S

Request l ette rs of recom m e n dation be u ploaded
Complete CAF and p e rson a l statement on M y E RAS
Aug ust
September
Select and apply to programs t h ro u g h MyE RAS
October
Sched u l e and attend i nterviews
Complete any p e n d i n g U S M L E Step exams
November
December
January
Obta i n E C F M G certification ( i f not done e a r l i e r)
February
S u b m i t ran k order l i st
Complete U S M L E Step 3 (if i n t e rested in H 1 B)
March Match resu lts (day 1)

SOAP (days 3-5)
Matched p rogram resu lts (day 5)
exam on time following a failur e . It is difficult to predict a result on the

Step 2 C S , since the grading process is not very transparent. Therefore ,
it is advisable to take the Step 2 C S as early as possible in the appl ication
year.
U. S . letters of recommendation help. Letters of recommendation from

clinicians practicing in the United States carry more weight than recom
mendations from home countries.
Step up the Step 3 . If H l B visa sponsorship is desired, a i m to have Step

A good score on the Step 3 may
3 results by January the Match year. In addition to the visa advantage
of
help offset poorer scores on
you will gain, an early and good Step 3 score may benefit IMGs who have
the Step 1 or 2 CK exams.
been away from clinical medicine for a wh ile as well as those who have
low scores on Step 1 and the Step 2 C K .
Verify medical credentials in a timely manner. Do not overlook the

medical school credential verification process. The EC FMG certificate
arrives only after credentials have been verified and after you have passed
S P E C I A L S I T U AT I O N S S E CTION I 35
Step 1 , the Step 2 C K, and the Step 2 C S , so you should keep track of the
process and check with the ECFMG from time to time about your status.
Of note , as of the 20 1 3 Match, programs

Don't count on a pre-Matc h .
participating in NRMP Match can no longer offer a pre-Match.
What if You Do Not Match?
For appl icants who do not Match into a residency program, there's SOAP
( Supplemental Offer and Acceptance Progra m ) . Under SOAP, unmatched
The Scramble has been replaced
appl icants will have access to the l ist of unfilled programs at noon Eastern
by SOAP (Supplemental Offer
time on th e M onday of Match week. The unfilled programs electi n g to
and Acceptance Program).
participate in SOAP will offer positions to unmatched appl icants through the
Registration, Ranking, and Results ( R 3 ) system. A series of "rounds" will begin
at noon Eastern time on Wednesday of Match week until 5 : 00 P . M . Eastern
time on Friday of Match week. Detailed information about SOAP can be
found at the NRMP Web site at h ttp : //www. n rmp .org/res_match/pol icies/
map_mai n . html .
Resources for the I MCi
EC FMG
3 624 Market Street
( 2 1 5 ) 3 86- 5900
Fax: ( 2 1 5 ) 3 8 6-9 1 96
www. ecfmg.org
The ECFMG telephone number is answered only between 9:00 A. M . and

1 2 : 3 0 P . M . and between 1 : 3 0 P.M. and 5 : 00 P . M . Monday through Friday
EST. The ECFMG often takes a long time to answer the phone, wh ich
is frequently busy at peak times of the year, and th en gives you a long
voice-mail message - so it is better to write or fax early than to rely on
a last-minute phone cal l . Do not contact the NBME, as all IMG exam
matters are conducted by the E C F M G . The EC FMG also publishes an
information booklet on ECFMG certification and the U SMLE program,
wh ich gives details on the elates and locations of forthcoming Step tests
for IMGs together with appl ication forms. It is free of charge and is also
available from the public affairs offices of U. S . embassies and consulates
worldwide as well as from Overseas Educational Advisory Centers . You
may order single copies of the handbook by calling ( 2 1 5 ) 3 86- 5 900, pref
erably on weekends or between 6 P . M . and 6 A. M . Philadelphia time, or by
faxing to ( 2 1 5 ) 386-9 1 96 . Requests for multiple copies must be made by
fax or mail on organizational letterhead . The full text of the booklet is also
available on the EC FMG's Web site at www. ecfmg.org.
36 SECT I O N I S P E C I A L S I T U AT I O N S
FSMB
400 Fuller Wiser Road, Su ite 300
Euless, TX 760 39
( 8 1 7 ) 868-4000
Fax: ( 8 1 7) 868-4099
www.fsmb . org
The FSMB has a number of publications availabl e , including free policy

documents . To obtain these publ ications, print and mail the order form
on the Web site listed above . Alternatively, write to Federation Publ ica
tions at the above address . All orders must be prepai d with a personal
check drawn on a U . S . bank, a cash ier's check, or a money order payable
to the FSMB. Foreign orders must be accompanied by an i nternational
money order or the equivalent, payable i n U. S . dollars th rough a U. S .
bank o r a U. S . affil iate o f a foreign bank. For Step 3 inquiries, the tele
phone number is ( 8 1 7 ) 868-404 1 . You may e-mail the FSMB at usmle@
fsmb.org or write to Examination Services at the address above .
The AMA has dedicated a portion of its Web site to information on IMG
demograph ics, residencies, immigration, and the l ike. This i n formation can
be found at www. ama-ass n . o rg/ama/pub/about-a ma/our-people/member
groups-sections/international-medical-graduates.shtm l .
Other resources that m a y be useful a n d of i nterest t o IMGs i n c l u d e the

following:
The Inte rn a tio n a l Medic a l G ra du a te 's G u ide to US Medicine and

Residency Training, by Patrick C. Alquire, Gerald P. Whelan, and Vi jay
Rajput ( 2 009; ISBN 978 1 9 3446 5 080) .
The International Medical Graduate 's Best Hope, by Franck Belibi and
Suzanne Bel ibi ( 2009; ISBN 978097987 7 3 0 8 ) .
F I R S T A I D F O R T H E O S T E O PAT H I C M E D I C A L S T U D E N T
What I s the COM LEX-USA Level l ?
T h e National Board o f Osteopath i c M e d i c a l E xa m i n e rs ( B O M E )

administers the Comprehensive Osteopath ic Medical Licensing Examination ,
or COMLEX-U SA. Like the U S MLE, the COMLEX-U SA is administered
over three levels.
The COMLEX-U SA series assesses osteopath i c medical knowledge an d

clinical skills using clinical presentations and physician tasks . A description
of the COMLEX-U SA Written Examination Blueprints for each level , wh ich
outline the various clinical presentations and physician tasks that examinees
will encounter, is given on the NBOME Web site . Another stated goal of the
COMLEX-U SA Level 1 is to create a more primary care-oriented exam th at
integrates osteopathic principles i nto clinical situations.
To be eligible to take the COMLEX-USA Level 1 , you must have satisfactorily

completed your fi rst year in an American Osteopath ic Association (AOA)
approvecl medical school . The office of the clean at each school informs the
NBOME that a student has completed his or her first year of school and is in
good standing. At th is point, the NBOME sends out an email with detailed
instructions on how to register for the exam.
For all th ree levels of the C O MLEX-U SA, raw scores are converted to a
percentile score and a score ranging from 5 to 800. For Levels 1 and 2 , a score
of 400 is required to pass; for Level 3 , a score of 3 5 0 is needed. COMLEX
U SA scores are posted at the NBOME Web site 4-6 weeks after the test and
usually mailed with i n 8 weeks after the test. The mean score is always 5 0 0 .
If you pass a COMLEX-USA exami nation, you a r e n o t allowed t o retake i t

to improve your grade. If you fai l , there is no specific l i m i t t o the number o f
times you c a n retake it i n order t o pass . However, a student may n o t take the
exam more than four times in one year. Levels 2 and 3 exams must be passed
in sequential order with i n seven years of passing Level 1 .
What Is the Strudure of the COM LEX-USA Level l ?
The COMLEX-USA Level 1 is a computer-based examination consisting of

400 questions over an eight-hour period i n a s ingle clay ( n i ne hours if you
count breaks). Most of the questions are in one-best-answer format, but a small
number are matching-type questions. Some one-best-answer questions are
bundled together around a common question stem that usually takes the form
of a clinical scenario. Every section of the COMLEX-U SA Level 1 ends with
either matching questions, multiple questions around a single stem, or both .
ew question formats may gradually be introduced, but candidates will be
notified if this occurs. In 20 1 2 , the NBOME introduced multimedia questions
and have stated that multimedia questions will continue to be a larger part of
the exam.
Questions are grouped into eight sections of 5 0 questions each in a manner

similar to the U S MLE . Reviewing and changing answers may be clone only
in the current section. A " review page" is presented for each block in order to
advise test takers of questions completed, questions marked for further review,
and incomplete questions for which no answer has been given.
Breaks are even more structured with COMLEX-USA than they are with the
USMLE. Students are allowed to take a 1 0-minute break at the end of the
second and sixth sections. Students who do not take these l 0-minute breaks
can apply the time toward their test tim e . After section 4, students are given
a 40-minute lunch b reak. These are the only times a student is permitted
a break. M ore i n formation about the c o m p u te r-based C O M LEX-U SA
examinations can be obtained from www. nbome . org.
What Is the Difference Between the U S M LE and the COM LEX-USA?
According to the NBOME, the COMLEX-USA Level 1 focuses broadly on

the following categories, with osteopath i c principles and practices integrated
into each section :
Health promotion and disease prevention

Th e h istory and physical
Diagnostic technologies
Management
Scientific understanding of mechanisms
Health care d el ivery
The tPt intf'rfoce for the COML FX

Althou gh the COMLEX-U SA and th e U SMLE are similar in scope, content,
USA L evel 1 is not the same as
and empha sis, some differences a re worth noting. For example, the i nterfa ce
the U Ml E StPp 1 interfacP.
i s different; you cannot search for lab val ues. The expectation is tha t you
can make a diagnosis with out having performed testi ng. Fewer deta ils are
given a bout a patient's conditi on , so a savvy student needs to know how to
differentiate between similar pathol ogies. Al so, age, gender, and ra ce are key
factors for diagnosis on th e COMLEX-U S A . I mages are e mbedd ed in the
question stem and the exa m i n ee h a s to click an attac h m ent bu tton to see the
image. If you don't rea d th e question carefu l ly, the attachment buttons a re
very easy to miss.
C O M LEX- U SA Level 1 tests osteopath i c principles i n a d d i ti o n to b a s i c

s c i e n c materials b u t d oes not emph a s i z e l a b techniques. Alth o u gh both
exa m often requ ire that you apply and integrate knowledge over several a reas
of baic science to answer a given qu estion, many stu dents wh o took both tests
reported that th e questions differed somewh at in styl e . Stud ents reported, for
e ample, that U SMLE qu estions genera l ly requ i red tha t the test taker reason
and d raw from the i nformation given (often a two-step process ) , whereas those
on the CO 1LEX-USA exam tended to be more straigh tforward . Furth ermore,
U S MLE questions were on average fou n d to be cons i d e rably l onger than
tho'le on the COMLEX-USA.
C O M LEX- U S A test takers can expect to h a ve only a few qu sti o n s o

b i o c h emistry, molec u l a r b i o l ogy, o r l a b tec h n i qu e . O n th e oth er h a n d ,
mi c robi ology i s very heavi l y tested by c l i n i ca l presentati o n a n d by l ab
identi fication . Another m ai n d i ffe re n c e i s that the C O M LEX- U SA exa m
stresses osteopath ic manipulative medicine. Th erefore, qu esti on banks specific
to the U SMLE will not be ad equate, and supplementation with a question
bank specific to the COMLEX-U SA i h ighly recommen d e d .
Stud ents a l s o comm e n ted th a t t h e C O M LEX- US A u t i l i z e d "buzzwords,"

a l though l i mited i n their use ( e . g . , "rose spots" i n typhoid fever ) , whereas
the U SMLE avoided buzzwords i n favor of descriptions of c l i nical findings
or symptoms ( e . g . , rose-colored pap u l e s on the abd omen rather than ro e
spots ) . Finally, U S MLE appeared to have m o re photograph s tha n did th e
COMLEX-USA. In general, the overall impression wa s th at the U SMLE was
S P E C I A L S I T U AT I O N S S E CT I O N I 39
a more "thought-provoking" exam, wh ile the COMLEX-USA was more o f a

"knowledge-based" exam.
Who Should Take Both the U S M LE and the COM LEX-USA?
Aside from facing the COMLEX-U SA Level l , you must decide if you will
also take the U SMLE Step l . We recommend that you consider taking both
the USMLE and the COMLEX-U SA under the following circumstances:
If y o u a r e applying t o allopath i c residencies. Although there is growing

acceptance of C O M LEX- U SA c e rtification on th e part of all opath i c
residencies, some all opath ic p rogra ms prefer or even requ ire passage
of the U S M L E Step l . These i n c l u d e m a n y a c a d e m i c progra m s ,
programs i n competi tive specialties ( e . g. , orthopedics, ophthalmology,
or dermatology) , and programs in competitive geograph i c areas (such as
Vermont, Utah , and California ) . Fourth-year doctor of osteopathy ( DO )
students who have already Matched m a y be a good source o f information
about wh i c h programs and specialties look for U S MLE scores . I t is
also a good idea to contact program di rectors at the i ns titutions you are
interested in to ask about their policy regarding the COMLEX-U SA versus
the USMLE.
Successful
If you a r e unsure about y o u r p ostgrad uate training p l a n s .
If you're not sure whether you need to
passage of both the COMLEX- U SA Level l and the USM LE Step l is take either the COMLEX-USA Level l
certain to provide you with the greatest possible range of options when or the USMLE Step 1, consider taking
you are applying for internship and residency training. both to keep your Match options open.
In addition , the COMLEX-U SA Level l has i n recent years placed increasing

emphasis on questi ons related to primary care medicine and prevention .
Having a strong background in family or primary care medicine can help test
takers when they face questions on prevention.
How Do I Prepare for the COM LEX-USA Level 1 ?
Student experience suggests th at you should start studying for the COMLEX
USA four to six months before the test is give n , as an early start will allow
you to spend up to a month on each subj ect. The recommendations made
in Section I regarding study and testing methods, strategies, and resources, as
well as the books suggested i n Section IV for the U SMLE Step l , hold true
for the COMLEX-USA as wel l .
Another important source of information is i n the Examination Guidelines

and Sample Exam, a booklet that discusses the breakdown of each sub j ect
wh ile also providing sample questi ons and corresponding an swers . Many
students, however, felt that th is breakdown provided only a general gu idel ine
and was not representative of the level of difficulty of the actual COMLEX
USA. The sample questions did not provide examples of clinical vignettes,
wh ich made up approximately 2 5 % of th e exa m . Yo u w i l l receive th i s
40 SECTI O N I S P E C I A L S I T U AT I O N S
publication with registration materials for the C O MLEX-U SA Level 1 , but

you can also receive a copy and additional i n formation by writing:
NBOME
876 5 W. H iggins Road, Su ite 200
C h icago, IL 606 3 1 -4 1 7 4
( 7 7 3 ) 7 1 4-0622
Fax: (77 3 ) 7 1 4-06 3 1
or by visiting the NBOME Web page at www. nbome.org.
T h e N B O M E deve l o p e d t h e C o m p re h e n s ive O s t e o p a th i c M e d i c a l
S el f-Assessment Exami nation ( C O M SAE ) series t o fi l l t h e n e e d for self
assessment on the part of osteopath ic medical students . Many students take
the COMSAE exam before the COMLEX-U SA in addition to using test-bank
questions and board review books. Students can purchase a copy of this exam
at www. nbome .org/comsae.asp.
I n recent years, students have reported a n emphasis i n certai n areas . For

example:
There was an increased emphasis on upper l i mb anatomy/brachial plexus .

Specific top ics were repeatedly tested o n the exa m . These i n c l uded
cardiovascular physiology and pathology, acid-base physiology, diabetes,
benign prostatic hyperplasia, sexually transmitted diseases, measles, and
rubella. Thyroid and adrenal function, neurology ( head i n j ury) , specific
drug treatments for bacterial infection, migraines/cluster headaches, and
drug mechanisms also received heavy emphasis.
You must know the Chapman Behavioral science questions were based on psychiatry.
reflex points and the obscure H igh-yield osteopath ic manipulative technique ( OMT) topics included
names ofphysical exam signs. an emphasis on the sympathetic and parasympathetic i n n e rvations of
viscera and nerve roots, rib mechanics/diagnosis, and basic craniosacral
theory. Students who spend time reviewing basic anatomy, studying nerve
and dermatome innervations, and understanding how to perform basic
OMT techniques (e.g., muscle energy or counterstrai n ) can improve thei r
scores.
The COMLEX-USA Level 1 also includes multimedia-based questions. Such

questions test the student's ab i l i ty to perform a good phys i cal exam and to
elicit various physical diagnostic signs ( e . g. , Murphy's sign ) .
Since topics that were repeatedly tested appeared in a l l four booklets, students
found it useful to review them in between the two test clays . It is important
to understand that the topics emphasized on the c urrent exam may not be
stressed on future exams. However, some topics are heavily tested each year,
so it may be beneficial to have a sol id fou ndation i n the above-mentioned
topics.
S P E C I A L S I T U AT I O N S SECTI O N I 41
F I R S T A I D F O R T H E P O D I AT R I C M E D I C A L S T U D E N T
The National B oard of Podiatric Medical Examiners ( N B P M E ) tests are

designed to assess whether a candidate possesses the kn owl edge requ i red
to practice as a m i n i mally competent entry-level podiatrist. The N B PM E
examinations are used a s part o f the l icensing process governing the practice
of podiatric medicine. The NBPME exam is recognized by all 5 0 states and
the District of Columbia, the U. S . Army, the U . S . avy, and the Canadian
provinces of Alberta, British Columbia, and Ontario . Individual states use
the exami nation scores differently; therefore, doctor of podiatric medicine
(DPM) candidates should refer to the NBPME B ulletin of information: 2 0 1 2
Examinations.
The NBPME Part I is generally taken after the completion of the second
Areas tested on the NBPME Part 1:
year of podiatric medical education. Unl ike the U S MLE Step 1 , there is no
General anatomy
behavioral science secti o n , nor i s biomechanics tested. The exam samples
Lower extremity anatomy
seven basic science discipl i n e s : ge n e ral a natomy ( 1 0 % ) ; lower extre m i ty
Biochemistry
anatomy ( 2 2 % ) ; biochemistry ( 1 0% ) ; physiology ( 1 2 % ) ; medical microbiology
Physiology
and immunol ogy ( 1 5 % ) ; pathol ogy ( 1 5 % ) ; a n d pharmacol ogy ( 1 6 % ) . A
Medical microbiology & immunology
detailed outline of topics and subtopics covered on the exam can be found
Pathology
in the NBPME Bulletin of Information, available on the NBPME Web site .
Pharmacology
Your N BPME Appointment
In early spring, your college registrar will have you fill out an appl ication for
the NBPME Part I . After your appl ication and registration fees are received,
you will be mailed the NBPME B ulletin of infomwtion: 2 0 1 2 Examinations.
The exam will be offered at an independent location in each city with a
podiatric medical s c h ool ( New Yo rk, P h i l adel p h i a , M i a m i , C l evel a n d ,
Chicago, Des Moines, Phoenix, a n d S a n Francisco ) . You may take the exam
at any of these locations regardless of which school you attend. However, you
must designate on your application wh ich testing location you desire . Specific
instructions about exam elates and registration deadlines can be found in the
NBPME Bu lletin.
Exam Format
The BPME Part I is a written exam consisting of 2 0 5 questions. The test

consists entirely of multiple-c h o i c e questions with fou r answer c h o i c e s .
Examinees have three hours in wh ich t o take t h e exam a n d a r e given scratch
paper and a calculator, both of wh ich must be tu rned in at the end of the
exam. Some questions on the exam will be "trial questions." These questions
are evaluated as future board questions but are not counted in your score .
42 SECTIO N I S P E C I A L S I T U AT I O N S
Interpreting Your Score
Three to four weeks following the exam elate, test takers will receive their
scores by mail . NBPME scores are reported as pass/fai l , with a scaled score of
at least 7 5 needed to pass. E ighty-five percent of first-time test takers pass the
N B PME Part I. Failing candidates receive a report with one score between 5 5
and 74 in addition to diagnostic messages intended to help identify strengths
or weaknesses in specific content areas . If you fail the N B P M E Part I , you
must retake the entire examination at a later elate . There is no l i m i t to the
number of times you can retake the exa m .
Preparation for the N BPM E Part I
Students suggest that you begin studying for the NBPME Part I at least three
months prior to the test elate . The suggestions made in Section I regarding
study and testing methods fo r th e U S MLE Step l can be applied to the
NBPME as wel l . Th is book should, however, be used as a supplement and
not as the sole source of informati o n . Keep in mind that you need only a
passing score . Neither you nor your school or futur e residency will ever see
your actual numerical score . Competing with colleagues should not be an
issue, and study groups are beneficial to many.
A potential study method that helps many students is to copy the outline of the
Know the anatomy of the
material to be tested from the NBPME Bu lletin. Check off each topic during
lower extremity!
your study, because doing so will ensure that you have engaged each topi c . lf
you are pressed for time, prioritize subj ects on the basis of their weight on the
exam. Approxi mately 2 2 % of the NBPME Part I focuses on l ower extremity
anatomy. In th is area, students should rely on the notes and material that they
received from their class . Remember, lower extremity anatomy is the podiatric
physician's specialty - so everyth ing about i t i s i mportant. Do not forget t
study osteology. Keep your old tests and look through old lower extremity clas
exams, since each of the podiatric coll eges submits questions from its own
exams. Th is strategy will give you an u nderstanding of the types of questions
that may be asked. On the N B P M E Part I , you will see some of the same
classic lower extremity anatomy questions you were tested on in school .
The N B P M E , l ike the U S M L E , requ i res that you apply a n d i n tegrate

knowl edge over several areas of b a s i c science i n order to answer exa m
q u e s t i ons . S t u d e n ts report t h a t m a n y q u e s t i o n s e m p h a s i z e c l i n i c a l
presentati ons; h owever, the facts i n th i s book are ve ry usefu l i n h e l p i ng
students recall the various diseases and organisms. DPM candidates should
expand on the high-yield pharmacol ogy section and study antifungal drugs
and treatments for Pseudomonas, methicillin-resistant S. aureus, candidiasi s,
and erythrasma. The high-yield section focusing on pathology is very useful ;
however, additional emphasis on diabetes m e l l itus a n d a l l i ts secondary
manifestations, particularly peripheral neuropathy, should not be overlooked.
Students should also focus on renal physiology a n d d ru g e l i m i nati on, the
biochemistry of gout, and neur ophysiology, all of which have been noted to
be important topics on the NBPME Part I exa m .
S P E C I A L S I T U AT I O N S S E CTI O N I 43
A sample set o f questions is found i n the NBPME B u lletin o f Informatio n :

2 0 1 2 Examinations. These samples a r e s i m i l a r in difficulty t o actual board
questions. If you do not receive a n NBPME B u lletin or i f you h ave any
questions rega rdi ng registration, fees, test c enters , authorization forms, or
score reports, please contact your college registrar or:
NBPME
P.O. Box 5 1 0
Bellefonte, PA 1 68 2 3
(8 1 4) 3 5 7-0487
Email: NBPMEOfc@aol .com
or visit the NBPME Web page at www. nbpme . info.
F I RST A I D FO R TH E STU D E N T WITH A D I SA B I LITY
The U S M L E provides a c c o m modations for students with d o c u m e n ted

disab i l ities. The basis for s u c h a c c o m m odations is the Americans w i th
Disabilities Act (ADA) of 1 990. The ADA defines a disability as "a significant
limitation in one or more major life activities." This includes both "observable/
physical" disabil ities (e.g. , blindness, hearing loss, narcolepsy) and "h idden/
mental disab il ities" ( e . g. , attention-deficit hyperactivity disorder, chronic
fatigue syndrome, learning disabil ities ) .
To provide appropriate support, t h e administrators of the U S MLE must b e U. S. students seeking ADA
informed o f both the nature a n d the severity o f an examinee's disability. Such
compliant accommodations
documentation is required for an examinee to receive testing accommodations.
must contad the NBME directly;
Accommodations include extra time on tests, low-stimulation environments,
IMGs, contad the ECFMG.
extra or extended breaks, and zoom text.
Who Can Apply for Accommodations?
Students or graduates of a school in th e U nited States or Canada that i s

accredited b y the Liaison Committee on Medical Education ( LCME) or the
AOA may apply for test accommodations directly from the NBME. Requests
are granted only if they meet the ADA definition of a disability. If you are a
disabled student or a disabled graduate of a foreign medical school , you must
contact the EC FMG (see below) .
Who Is Not Eligible for Accommodations?
Individuals who do not meet the ADA definition of disabled are not eligible
for test accommodations. D i ffi c ulties not eligible for test accommodations
include test anxiety, slow reading without an identified underlying cognitive
deficit, Engl ish as a second language, and learning difficulties that have not
been diagnosed as a medically recognized disability.
Understanding the Need for Documentation
Although most learni ng-disabled medical students are all too familiar with
the often exhausting process of providing documentation of their disab i l i ty,
you should realize that applying for U S M L E accommodation is different
from these previous experiences. Th i s is because the N B M E d etermines
whether an i ndividual is disabled solely on the basis of the guidelines set by
the ADA. Previous accommodation does not in itself j ustify provision of an
accommodation, so be sure to review the NBME gu idelines carefully.
Getting the Information
The first step in applying for U SMLE special accommodations is to contact

the NBME and obtain a guidelines and questionnaire booklet. Th is can be
obtained by calling or writing to :
Testing Coordinator
Office of Test Accommodations
National Board of Medical Examiners
Philadelph ia, PA 1 9 1 04-3 1 02
( 2 1 5 ) 590-9 5 09
Internet access to this information is also available at www. nbme. org. Th is

information is also relevant for IMGs, since the information is the same as
that sent by the ECFMG.
Foreign graduates should contact the EC FMG to obtai n i n formation on

special accommodations by calling or writing to :
EC FMG
3 624 Market Street
( 2 1 5 ) 3 86- 5900
Wh en you get th is informatio n , take some time to read i t carefu l ly. The
gu i d e l i nes are clear and expl i c i t about what you n e e d to d o to obta i n
accommodations.
SECTION II
High-Yield
General Principles
"There comes a time when for every addition of knowledge you forget
something that you knew before. It is of the highest importance, therefore,
not to have useless facts elbowing out the useful ones."
-Sir Arthur Conan Doyle, A Study in Scarlet
"Never regard study as a duty, but as the enviable opportunity to leam."

-Albert Einstein
"Live as if you were to die tomorrow. Leam as if you were to live forever."
-Gandhi
46 SECTION II HIGH-YIELD GENERAL PRINCIPLES
HOW TO USE THE DATABASE
The 2013 edition of First Aid for the USMLE Step 1 contains a revised and
expanded database of basic science material that student authors and faculty
have identified as high yield for board review. The information is presented
in a partially organ-based format. Hence, Section II is devoted to pathology
and the foundational principles of behavioral science, biochemistry,
microbiology, immunology, and pharmacology. Section III focuses on organ
systems, with subsections covering the embryology, anatomy and histology,
physiology, pathology, and pharmacology relevant to each. Each subsection
is then divided into smaller topic areas containing related facts. Individual
facts are generally presented in a three-column format, with the Title of the
fact in the first column, the Description of the fact in the second column,
and the Mnemonic or Special Note in the third column. Some facts do not
have a mnemonic and are presented in a two-column format. Others are
presented in list or tabular form in order to emphasize key associations.
The database structure used in Sections II and III is useful for reviewing
material already learned. These sections are not ideal for learning complex
or highly conceptual material for the first time.
The database of high-yield facts is not comprehensive. Use it to complement

your core study material and not as your primary study source. The facts and
notes have been condensed and edited to emphasize the essential material,
and as a result, each entry is "incomplete" and arguably "over-simplified."
Often the more you research a topic, the more complex it gets, and certain
topics resist simplification. Work with the material, add your own notes and
mnemonics, and recognize that not all memory techniques work for all
students.
We update the database of high-yield facts annually to keep current

with new trends in boards content as well as to expand our database of
information. However, we must note that inevitably many other very high
yield entries and topics are not yet included in our database.
We actively encourage medical students and faculty to submit entries and

mnemonics so that we may enhance the database for future students. We
also solicit recommendations of alternate tools for study that may be useful
in preparing for the examination, such as diagrams, charts, and computer
based tutorials (see How to Contribute, p. xvii).
Image Acknowledgments
Images marked with are reproduced with permission of USMLE-Rx.com.

Images marked with lil!l are reproduced with permission of Dr. Richard P.
Usatine and the Color Atlas of Family Medicine (www.usatinemedia.com).
Images marked with c are reproduced with permission of other sources.
Citations are listed on page 633.
HIGH-YIELD GENERAL PRINCIPLES SECTION II 47
Disclaimer
The entries in this section reflect student opinions of what is high yield.
Because of the diverse sources of material, no attempt has been made
to trace or reference the origins of entries individually. We have regarded
mnemonics as essentially in the public domain. Errors and important
omissions will gladly be corrected if brought to the attention of the authors,
either through our online errata process or directly by e-mail.
48 SECTION II HIGH-YIELD GENERAL PRIN CI PLES
NOTES
HIGH-YIELD PRINCIPLES IN
Behavioral Science
"It's psychosomatic. You need a lobotomy. I'll get a saw."

-Calvin, "Calvin & Hobbes"
A heterogeneous mix of epidemiology, biostatistics, ethics, psychology,

sociology, and more falls under the heading of behavioral science. Many
medical students do not study this discipline diligently because the
material is felt to be easy or a matter of common sense. In our opinion,
this is a missed opportunity.
Behavioral science questions may seem less concrete than questions

from other disciplines, requiring an awareness of the social aspects
of medicine. For example, if a patient does or says something, what
should you do or say in response? These so-called quote questions now
constitute much of the behavioral science section. Medical ethics and
medical law are also appearing with increasing frequency. In addition,
the key aspects of the doctor-patient relationship (e.g., communication
skills, open-ended questions, facilitation, silence) are high yield, as are
biostatistics and epidemiology. Make sure you can apply biostatistical
concepts such as specificity and predictive values in a problem-solving
format.
50 SECTION II BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-EPIDEMIOLOGY/BIOSTATISTICS
BEHAVIORAL SCIENCE-EPIDEMIOLOGY/BIOSTATISTICS
Types of studies
STUDY TYPE DESIGN MEASURES/EXAMPLE
Case-control study Compares a group of people with disease to a Odds ratio (OR).
Observational and group without disease. " Patients with CO PD had higher odds of a
retrospective Looks for prior exposure or risk factor. history of smoking than those without CO PD
Asks, "What happened?" had."
Cohort study Compares a group with a given exposure or risk Relative risk (RR).
Observational and factor to a group without such exposure. "Smokers had a higher risk of developing CO PD
prospective or Looks to see if exposure t the likelihood of than nonsmokers had."
retrospective disease.
Can be prospective (asks, "Who will
develop disease?") or retrospective (asks,
"Who developed the disease [exposed vs.
nonexposed]?").
Cross-sectional study Collects data from a group of people to assess Disease prevalence.
Observational frequency of disease (and related risk factors) Can show risk factor association with disease, but
at a particular point in time. does not establish causality.
Asks, "What is happening?"
Twin concordance Compares the frequency with which both Measures heritability.
study monozygotic twins or both dizygotic twins
develop same disease.
Adoption study Compares siblings raised by biological vs. Measures heritability and influence of
adoptive parents. environmental factors.
Clinical trial Experimental study involving humans. Compares therapeutic benefits of 2 or more treatments,
or of treatment and placebo. Study quality improves when study is randomized, controlled, and
double-blinded (i.e., neither patient nor doctor knows whether the patient is in the treatment or
control group). Triple-blind refers to the additional blinding of the researchers analyzing the data.
STUDY SAMPLE PURPOSE
Phase I Small number of healthy volunteers. Assesses safety, toxicity, and pharmacokinetics.
Phase II Small number of patients with disease of Assesses treatment efficacy, optimal dosing, and
interest. adverse effects.
Phase Ill Large number of patients randomly assigned Compares the new treatment to the current
either to the treatment under investigation or standard of care.
to the best available treatment (or placebo).
Phase IV Postmarketing surveillance trial of patients after Detects rare or long-term adverse effects.
approval.
BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-EPIDEMIOLOGY/BIOSTATISTICS SECTION II 51
Evaluation of Uses 2 x 2 table comparing test results with the Disease

e
:1
diagnostic tests actual presence of disease. TP =true positive;
FP=false positive; TN=true negative; F = TP FP
false negative.
FN TN
Sensitivity and specificity are fixed properties
of test; however, PPV and NPV vary with
prevalence or pretest probability.
Sensitivity (true Proportion of all people with disease who test = T P I (TP + FN)
positive rate) positive, or the probability that a test detects = 1 -false-negative rate
disease when disease is present. PID=Positive In Disease
Value approaching 100% is desirable for ruling SNOUT= SeNsitivity rules OUT
out disease and indicates a low false-negative If 100% sensitivity, TP I (TP + F )= 1, F =0,
rate. Used for screening in diseases with low and all negatives must be TNs
prevalence.
Specificity (true Proportion of all people without disease who =T N I (TN + FP)
negative rate) test negative, or the probability that a test = 1 false-positive rate
-
indicates non-disease when disease is absent. NIH=Negative In Health

Value approaching 100% is desirable for ruling SPIN= SPecificity rules IN
in disease and indicates a low false-positive If 100% specificity, T N I (TN+ FP) = 1, FP=0,
rate. Used as a confirmatory test after a positive and all positives must be TPs
screening test.
Example: HJV testing. Screen with ELISA
(sensitive, high false-positive rate, low
threshold); confirm with Western blot
(specific, high false-negative rate, high
threshold).
Positive predictive Proportion of positive test results that are true = TP I (TP + FP)
value (PPV) positive. PPV varies directly with prevalence or pretest
Probability that person actually has the disease probability: high pretest probability-+ high PPV
given a positive test result.
Negative predictive Proportion of negative test results that are true =TN I (FN + TN)
value (NPV) negative. NPV varies inversely with prevalence or pretest
Probability that person actually is disease free probability: high pretest probability-+ low NPV
given a negative test result.
<1.>
a.
0
<1.>
0.. A 100% sensitivity
0 B practical compromise between specificity and sensitivity
Q;
..0 C 100% specificity
E
:::>
z
Test results
Incidence vs. # of new cases Incidence looks at new incidents.

prevalence in a specified time period
Incidence rate =
Population at risk during

same time period
# of existing cases Prevalence looks at all current cases.
I)reva 1ence = ..,-------o------"'-----o-
--
Population at risk
Prevalence"" incidence rate x average disease
duration.
Prevalence> incidence for chronic diseases
(e.g., diabetes).
Quantifying risk
Odds ratio {OR) Typically used in case-control studies. Odds that . ale ad
Odds rat1o = - = -
the group with the disease (cases) was exposed b/d be

to a risk factor (a/c) divided by the odds that
the group without the disease (controls) was
exposed (b/d).
Relative risk (RR) Typically used in cohort studies. Risk of a/(a t b)
Relative risk ---,-
developing disease in the exposed group
=
e/(e t d)
divided by risk in the unexposed group (e.g., if
2 1% of smokers develop lung cancer vs. 1% of
nonsmokers, RR 2 1/ 1 2 1) . If prevalence is
= =
low, RR"" OR.

Attributable risk The difference in risk between exposed and
Attributable risk _a_ - _e_
unexposed groups, or the proportion of =
atb etd
disease occurrences that are attributable to the
exposure (e.g., if risk of lung cancer in smokers
is 21% and risk in nonsmokers is 1%, then 20%
of the 2 1% risk of lung cancer in smokers is
attributable to smoking).
Absolute risk Absolute reduction in risk associated with a

reduction {ARR) treatment as compared to a control (e.g., if
Disease
I
8% of people who receive a placebo vaccine 8
develop flu vs. 2% of people who receive a flu
a b
vaccine, then ARR 8%-2% 6%).= =
Number needed to Number of patients who need to be treated for 1 ci18 c d
treat patient to benefit. Calculated as !/absolute risk

reduction.
Number needed to Number of patients who need to be exposed
harm to a risk factor for 1 patient to be harmed.
Calculated as 1/attributable risk.
Precision vs. accuracy

Precision The consistency and reproducibility of a test Random error-reduces precision in a test.
(reliability). t precision ! standard deviation.
-+
The absence of random variation in a test.

Accuracy The trueness of test measurements (validity). The Systematic error-reduces accuracy in a test.
absence of systematic error or bias in a test.
X
Accurate Precise Accurate and Not accurate,
precise not precise
Bias Occurs when there is systematic error or favor in a particular direction.

Selection bias Nonrandom assignment to participation in Ways to reduce bias:
a study group (e.g., Berkson's bias, loss to Blind studies to limit influence of
follow-up) participants and researchers on

Recall bias Knowledge of presence of disorder alters recall interpretation of outcomes
Placebo control groups
by subjects; common in retrospective studies
Crossover studies (each subject acts as own
Sampling bias Subjects are not representative of the general control) to limit confounding bias
population; therefore, results are not Randomization to limit selection bias and
generalizable. A type of selection bias. confounding bias
Late-look bias Information gathered at an inappropriate Matching to reduce confounding bias
time-e.g., using a survey to study a fatal

disease (only those patients still alive will be
able to answer survey)
Procedure bias Subjects in different groups are not treated the
same-e.g., more attention is paid to treatment
group, stimulating greater adherence
Confounding bias Occurs when factor is related to both exposure
and outcome, but is not on the causal pathway;
factor distorts or confuses effect of exposure on
outcome
Lead-time bias Early detection confused with t survival; seen
with improved screening (natural history of
disease is not changed, but early detection
makes it seem as though survival t)
Observer-expectancy Occurs when a researcher's belief in the efficacy
effect of a treatment changes the outcome of that
treatment
Hawthorne effect Occurs when the group being studied changes Dr. Hawthorne is watching you
its behavior owing to the knowledge of being
studied
I
Statistical distribution Measures of central tendency=mean, median, mode.

Measures of dispersion=standard deviation (SD), standard error of the mean (SEM), Z-score,
confidence interval.
Normal distribution Gaussian, also called bell-shaped.
Mean=median=mode.
SO and SEM cr=SD; n=sample size.
SEM= a!-Vn..
SEM as n t.
Positive skew Typically, mean > median > mode.

Asymmetry with longer tail on right.
Mode is least affected by outliers in the sample.
Negative skew Typically, mean<median <mode.

Asymmetry with longer tail on left.
Statistical hypotheses
Null (H0) Hypothesis of no difference (e.g., there is no
association between the disease and the risk
factor in the population). Power
H,
"'
a
Alternative (H1) Hypothesis of some difference (e.g., there is (1-)

>-
some association between the disease and the ""0
.a
risk factor in the population).
V>
Ho Correct
Statistical error types

Type I error (a) Stating that there is an effect or difference Also known as false-positive error.
when none exists (to mistakenly accept the If p < .05, then there is less than a 5% chance
alternative hypothesis and reject the null that the data will show something that is not
hypothesis). really there.
a is the probability of making a type I error. a= you saw a difference that did not exist-e.g.,
p is judged against a preset a level of convicting an innocent man.
significance (usually<.05).
Type II error () Stating that there is not an effect or difference Also known as false-negative error.
when one exists (to fail to reject the null p=you were blind to a difference that did
hypothesis when it is in fact false). exist-e.g., setting a guilty man free.
p is the probability of making a type II error.
Power (1- p) Probability of rejecting null hypothesis when If you t sample size, you t power. There is
it is in fact false, or the likelihood of finding power in numbers.
a difference if one in fact exists. It increases
with:
t sample size
t expected effect size
t precision of measurement
Meta-analysis Pools data and integrates results from several Limited by quality of individual studies or bias
similar studies to reach an overall conclusion. in study selection.
t statistical power.
Confidence interval Range of values in which a specified probability If the 95% CI for a mean difference between 2
of the means of repeated samples would be variables includes 0, then there is no significant
expected to fall. difference and H0 is not rejected.
CI= confidence interval. If the 95% CI for odds ratio or relative risk
CI=range from (mean- Z(SEM)] to (mean+ includes l, I-I0 is not rejected.
Z(SEM)]. If the Cis between 2 groups do not overlap
The 95% CI (corresponding top=.05) is often --+ significant difference exists.
used. If the Cis between 2 groups overlap--+ usuaiJy
For the 95% CI, Z= 1.96. no significant difference exists.
For the 99% CI, Z= 2.58.
t-test vs. ANOVA vs. X1

t-test Checks difference between the means of 2 Mr. T is mean.
groups.
ANOVA Checks difference between the means of 3 or ANOVA=ANalysis Of VAriance of 3 or more
more groups. groups.
Chi-square (Xl) Test checks difference between 2 or more X2=compare percentages (%) or proportions.
percentages or proportions of categorical
outcomes (not mean values).
Pearson's correlation always between -1 and +l. The closer the absolute value of r is to l, the stronger the linear
r is
coefficient (r) correlation between the 2 variables.
Coefficient of determination= r2 (value that is usually reported).
Disease prevention
Primary Prevent disease occurrence (e.g., HPV PDR:
vaccination). Prevent
Secondary Early detection of disease (e.g., Pap smear). Detect
Reduce disability
Tertiary Reduce disability from disease (e.g.,
chemotherapy).
56 SECTION II BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-ETHICS
Medicare and Medicare and Medicaid-federal programs that MedicarE is for Elderly.
Medicaid originated from amendments to the Social MedicaiD is for Destitute.
Security Act.
Medicare is available to patients 65 years of
age,< 65 with certain disabilities, and those
with end-stage renal disease.
Medicaid is joint federal and state health
assistance for people with very low income.
BEHAVIORAL SCIENCE-ETHICS
Core ethical principles

Patient autonomy Obligation to respect patients as individuals and to honor their preferences in medical care.
Beneficence Physicians have a special ethical (fiduciary) duty to act in the patient's best interest. May conflict
with autonomy. If the patient can make an informed decision, ultimately the patient has the right
to decide.
Nonmaleficence " Do no harm." However, if the benefits of an intervention outweigh the risks, a patient may make
an informed decision to proceed (most surgeries and medications fall into this category).
Justice To treat persons fairly.
Informed consent Legally requires: Patients must have an intelligent understanding

Discussion of pertinent information of the risks, benefits, and alternatives, which
Patient's voluntary agreement to the plan of include no intervention
care Written consent can be revoked by the patient at
Freedom from coercion any time, even orally.
Exceptions to informed consent:
Patient lacks decision-making capacity or is
legally incompetent
Implied consent in an emergency
Therapeutic privilege-withholding
information when disclosure would severely

harm the patient or undermine informed
decision-making capacity
Waiver-patient waives the right of informed
consent
Consent for minors A minor is generally any person< 18 years of age. Parental consent laws in relation to health care
vary state by state. Generally, consent must be obtained unless minor is emancipated (e.g., is
married, is self-supporting, has children, or is in the military). Parental consent is not required
in ( 1) emergency situations, (2) prescribing contraceptives, (3) treating STDs, (4) medical care of
pregnancy, and (5) treatment of drug addiction.
BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-ETHICS SECTION II 57
Decision-making Physician must determine whether the patient The patient's family cannot require that a doctor
capacity is psychologically and legally capable of withhold information from the patient if
making a particular health care decision. patient demonstrates decision-making capacity.
Components:
Patient makes and communicates a choice
Patient is informed (knows and understands)
Decision remains stable over time
Decision is consistent with patient's values
and goals, not clouded by a mood disorder

Decision is not a result of delusions or
hallucinations
Advance diredives Instructions given by a patient in anticipation of the need for a medical decision. State-specific.
Oral advance directive Incapacitated patient's prior oral statements commonly used as guide. Problems arise from variance
in interpretation. If patient was informed, directive was specific, patient made a choice, and
decision was repeated over time to multiple people, the oral directive is more valid.
Living will (written Describes treatments the patient wishes to receive or not receive if he/she loses decision-making
advance directive) capacity. Usually, patient directs physician to withhold or withdraw life-sustaining treatment if he/
she develops a terminal disease or enters a persistent vegetative state.
Medical power of Patient designates an agent to make medical decisions in the event that he/she loses decision-making
attorney capacity. Patient may also specify decisions in clinical situations. Patient can revoke anytime patient
wishes (regardless of competence). More flexible than a living will.
Surrogate decision If an incompetent patient has not prepared an advance directive, individuals (surrogates) who know
maker the patient must determine what the patient would have clone if he/she were competent. Priority
of surrogates: spouse, adult children, parents, adult siblings, other relatives.
Confidentiality Confidentiality respects patient privacy and autonomy. If patient is not present or is incapacitated,
disclosing information to family and friends should be guided by professional judgment of
patient's best interest. The patient may waive the right to confidentiality (e.g., insurance
companies).
General principles for exceptions to confidentiality:
Potential harm to others is serious
Likelihood of harm to self is great
No alternative means exists to warn or to protect those at risk
Physicians can take steps to prevent harm
Examples of exceptions (many are state-specific) include:

Reportable diseases (STDs, TB, hepatitis, food poisoning)-physicians may have a duty to warn
public officials, who will then notify people at risk

The Tarasoff decision-California Supreme Court decision requiring physician to directly
inform and protect potential victim from harm; may involve breach of confidentiality
Child and/or elder abuse
Impaired automobile drivers
Suicidal/homicidal patients
58 SECTION II BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-ETHICS
Ethical situations
SITUATION APPROPRIATE RESPONSE
Patient is not adherent. Attempt to identify the patient's reason for nonadherence and determine his/her
willingness to change; do not attempt to coerce the patient into adhering or refer the
patient to another physician.
Patient desires an unnecessary Attempt to understand why the patient wants the procedure and address underlying
procedure. concerns. Do not refuse to see the patient or refer him/her to another physician. Avoid
performing unnecessary procedures.
Patient has difficulty taking Provide written instructions; attempt to simplify treatment regimens; use teach-back
medications. method (ask patient to repeat medication regimen back to physician) to ensure patient
comprehension.
Family members ask for information Avoid discussing issues with relatives without the permission of the patient.
about patient's prognosis.
A child wishes to know more about Ask what the parents have told the child about his/her illness. Parents of a child decide
his/her illness. what information can be relayed about the illness.
A 17-year-old girl is pregnant and Many states require parental notification or consent for minors for an abortion. Unless
requests an abortion. she is at medical risk, do not advise a patient to have an abortion regardless of her age
or the condition of the fetus.
A 15-year-old girl is pregnant and The patient retains the right to make decisions regarding her child, even if her parents
wants to keep the child. Her disagree. Provide information to the teenager about the practical issues of caring for
parents want you to tell her to give a baby. Discuss the options, if requested. Encourage discussion between the teenager
the child up for adoption. and her parents to reach the best decision.
A terminally ill patient requests In the overwhelming majority of states, refuse involvement in any form of physician
physician assistance in ending assisted suicide. Physicians may, however, prescribe medically appropriate analgesics
own life. that coincidentally shorten the patient's life.
Patient is suicidal. Assess the seriousness of the threat; if it is serious, suggest that the patient remain in the
hospital voluntarily; patient can be hospitalized involuntarily if he/she refuses.
Patient states that he/she finds you Ask direct, closed-ended questions and use a chaperone if necessary. Romantic
attractive. relationships with patients are never appropriate. Never say, "There can be no
relationship while you are a patient," because this implies that a relationship may be
possible if the individual is no longer a patient.
A woman who had a mastectomy Find out why the patient feels this way. Do not offer falsely reassuring statements (e.g.,
says she feels "ugly" when she "You still look good.").
undresses.
Patient is angry about the amount Acknowledge the patient's anger, but do not take a patient's anger personally. Apologize
of time he/she spent in the waiting for any inconvenience. Stay away from efforts to explain the delay.
room.
Patient is upset with the way he/she Suggest that the patient speak directly to that physician regarding the patient's
was treated by another doctor. concerns. If the problem is with a member of the office staff, tell the patient you will
speak to that individual.
A drug company offers a "referral Eligible patients who may benefit from the study may be enrolled, but it is never
fee" for every patient a physician acceptable for a physician to receive compensation from a drug company. Patients
enrolls in a study. must be told about the existence of a referral fee.
A physician orders an invasive test No matter how serious or trivial a medical error, a physician is ethically obligated to
for the wrong patient. inform a patient that a mistake has been made.
A patient requires a treatment not Never limit or deny care because of the expense in time or money. Discuss all treatment
covered by his/her insurance. options with patients, even if some are not covered by their insurance companies.
BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-DEVELOPMENT SECTION II 59
BEHAVIORAL SCIENCE-DEVELOPMENT
Apgar score Assessment of newborn vital signs following labor via a 10-point scale evaluated at l minute and
5 minutes. Apgar score is based on Appearance, Pulse, Grimace, Activity, and Respiration (
7 =good; 4-6 =assist and stimulate;< 4 =resuscitate). If Apgar score remains< 4 at later time
points, there is t risk that the child will develop long-term neurological damage.
Low birth weight Defined as< 2500 g. Caused by prematurity or intrauterine growth retardation. Associated with
t risk of SIDS, and with t overall mortality. Other problems include impaired thermoregulation
and immune function, hypoglycemia, polycythemia, and impaired neurocognitive/emotional
development. Complications include infections, respiratory distress syndrome, necrotizing
enterocolitis, intraventricular hemorrhage, and persistent fetal circulation.
Early developmental milestones

AGE MOTOR SOCIAL VERBAL/COGNITIVE
Infant
Birth-3 mo Rooting reflex, holds head up, Social smile Orients and responds to voice
Mora reflex disappears
7-9 mo Sits alone, crawls, transfers toys Stranger anxiety Responds to name and simple
from hand to hand instructions, uses gestures,
plays peek-a-boo
12-15 mo Walks, Babinski sign disappears Separation anxiety Few words
Toddler
12-24 mo Climbs stairs; stacks 3 blocks at Rapprochement (moves away 200 words and 2-worcl phrases
l yr, 6 blocks at 2 yr (age x 3 from and then returns to at age 2
=no. of blocks) mother)
24-36 mo Feeds self with fork and spoon, Core gender identity, parallel Toilet training ("pee at age 3")
kicks ball play
Preschool
3 yr Rides tricycle (rides 3-cycle at Comfortably spends part of clay 900 words and complete
age 3); copies line or circle away from mother sentences
drawings
4 yr Uses buttons and zippers, Cooperative play, imaginary Can tell detailed stories and
grooms self (brushes teeth), friends use prepositions
hops on l foot, makes simple
drawings (stick figures)
60 SECTION II BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-PHYSIOLOGY
Changes in the Sexual changes: Sexual interest does not !.

elderly Men-slower erection/ejaculation, longer Intelligence does not-
refractory period
Women-vaginal shortening, thinning, and
dryness
Sleep patterns: REM and slow-wave sleep;
t latency and awakenings
t suicide rate (men 65-74 years of age have the
highest suicide rate in the United States)
vision, hearing, immune response, bladder
control
renal, pulmonary, Gl function
muscle mass, t fat
Cirief Normal bereavement characterized by shock, denial, guilt, and somatic symptoms. Can last up to
1 year. May experience illusions.
Pathologic grief includes excessively intense grief; prolonged grief lasting > 2-6 months; or grief
that is delayed, inhibited, or denied. May experience depressive symptoms, delusions, and
hallucinations.
BEHAVIORAL SCIENCE-PHYSIOLOGY
Sexual dysfundion Includes sexual desire disorders (hypoactive sexual desire or sexual aversion), sexual arousal
disorders (erectile dysfunction), orgasmic disorders (anorgasmia and premature ejaculation), and
sexual pain disorders (dyspareunia and vaginismus).
Differential diagnosis includes:
Drugs (e.g., antihypertensives, neuroleptics, SSRis, ethanol)
Diseases (e.g., depression, diabetes)
Psychological (e.g., performance anxiety)
Body-mass index {BMI) BMI is a measure of weight adjusted for height. < 18.5 underweight
18.5-24.9 normal weight
weight in kg 25.0-29.9 overweight
BMI =
(height in meters)2 > 30.0 obesity

> 35.0 severe obesity
> 40.0 morbid obesity
> 45.0 super obesity
BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-PHYSIOLOGY SECTION II 61
Sleep stages
STAGE (%OF TOTAL SLEEP DESCRIPTION EEG WAVEFORM
TIME IN YOUNG ADULTS)
Awake (eyes open) Alert, active mental concentration Beta (highest frequency, lowest amplitude)
Awake (eyes closed) Alpha
Stage Nl (5%) Light sleep Theta
Stage N2 {45%) Deeper sleep; bruxism Sleep spindles and K complexes
Stage N3 {25%) Deepest, non-REM sleep (slow-wave sleep); Delta (lowest frequency, highest amplitude)
sleepwalking; night terrors; bedwetting
REM (25%) Dreaming, loss of motor tone, possibly a Beta
memory processing function, erections,
t brain 02 use
Serotonergic predominance of raphe nucleus is At night, BATS Drink Blood
key to initiating sleep.
Sleep enuresis is treated with oral desmopressin
acetate (DDAV P), which mimics vasopressin
(ADH, antidiuretic hormone); preferred over
imipramine because of the latter's adverse
effects.
Alcohol, benzodiazepines, and barbiturates are
associated with reduced REM and delta sleep.
Benzodiazepines are useful for night terrors and
sleepwalking.
Awake Stage Nl Stage N2 Stage N3 REM
K- Sleep
complex spindle
(Adapted, with permission, from Barrett KE et al. Ganong's Review of Medical Physiology. 23rd ed. New York: McGraw-Hill, 20 I 0, Fig. 15-7.)
REM sleep Occurs every 90 minutes; duration REM sleep is like sex: t pulse, penile/clitoral
t through the night. ACh is the principal tumescence, ! frequency with age.
neurotransmitter in REM sleep. NE reduces Because REM sleep has the same EEC patterns
REM sleep. as wakefulness, it has been termed "paradoxical
Findings: t and variable pulse and blood sleep" and "desynchronized sleep."
pressure. Extraocular movements during
REM sleep due to activity of PPRF
(paramedian pontine reticular formation/
conjugate gaze center). Penile/clitoral
tumescence.
62 SECTION II BEHAVIORAL SCIENCE BEHAVIORAL SCIENCE-PHYSIOLOGY
Sleep patterns of Patients with depression typically have the following changes in their sleep stages:
depressed patients ! slow-wave sleep
! REM latency
t REM early in sleep cycle
t total REM sleep
Repeated nighttime awakenings
Early-morning awakening (important screening question)
Narcolepsy Disordered regulation of sleep-wake cycles; primary characteristic is excessive daytime

sleepiness. May include hypnagogic (just before sleep) or hypnopompic (just before awakening)
hallucinations. The patient's nocturnal and narcoleptic sleep episodes start off with REM sleep.
Cataplexy (loss of all muscle tone following a strong emotional stimulus) in some patients.
Strong genetic component. Treated with daytime stimulants (e.g., amphetamines, modafinil) and
nighttime sodium oxybate (GHB).
Circadian rhythm Driven by suprachiasmatic nucleus (SCN) of hypothalamus. Controls ACTH, prolactin, melatonin,
nocturnal NE release. SC NE release pineal gland melatonin. SCN is regulated by
-+ -+ -+
environment (i.e., light).
Sleep terror disorder Periods of terror with screaming in the middle of the night; occurs during slow-wave sleep. Most
common in children. Occurs during non-REM sleep (no memory of arousal) as opposed to
nightmares that occur during REM sleep (memory of a scary dream). Cause unknown, but
triggers may include emotional stress during the previous day, fever, or lack of sleep. Usually self
limited.
Biochemistry
"Biochemistry is the study of carbon compounds that crawl."

- M ike Adams
"We think we have found the basic mechanism by which life comes from
"
l z1 r.e.
- Fra ncis H . C . Crick
This high-yield material includes molecular biology, genetics, cell

biology, and principles of metabolism (especially vitamins, cofactors,
minerals, and single-enzyme-deficiency diseases). When studying
metabolic pathways, emphasize important regulatory steps and enzyme
deficiencies that result in disease, as well as reactions targeted by
pharmacologic interventions. For example, understanding the defect
in Lesch-Nyhan syndrome and its clinical consequences is higher yield
than memorizing every intermediate in the purine salvage pathway.
Do not spend time on hard-core organic chemistry, mechanisms, or
physical chemistry. Detailed chemical structures are infrequently tested;
however, many structures have been included here to help students
learn reactions and the important enzymes involved. Familiarity with
the biochemical techniques that have medical relevance-such as
enzyme-linked immunosorbent assay (ELISA), immunoelectrophoresis,
Southern blotting, and PCR-is useful. Beware if you placed out of
your medical school's biochemistry class, as the emphasis of the test
differs from that of many undergraduate courses. Review the related
biochemistry when studying pharmacology or genetic diseases as a way
to reinforce and integrate the material.
64 S E C TI O N I I B I O C H E M I ST RY B I O C H E M I S T R Y - M O L E CU L A R
B I O C H E M I ST R Y-M O L E CU L A R
Chromatin structure DNA exists in the condensed, chromatin form Think of beads on a string."
"
in order to fit into the nucleus. Negatively

charged DNA loops twice around positively
..
..

charged h istone octamer to form nucleosome o&
.
[]
I
"bead." H istones are rich in the amino acids
lysine and argin i ne. Hl ties nucleosome beads .. Nucleosome core
together in a string. .. histones H2A, H2B, H3, H4
In mitosis, DNA condenses to form (each x2)
chromosomes.
H l is the only h istone that is not in the
nucleosome core.
H eterochromatin Condensed, transcriptionally inactive, sterically HeteroChromatin = H igh ly Condensed .
inaccessible.
Euchromatin Less condensed, transcriptionally active, Eu = true, " truly transcribed."
sterically accessible.
DNA methylation Template strand cytosine and adenine are
methylated in DNA repl ication , wh ich allows
m ismatch repair enzymes to distinguish
between old and new strands in prokaryotes.
H istone methylation Inactivates transcription of DNA. Methylation makes DNA Mute.
H istone acetylation Relaxes DNA coiling, allowing for transcription. Acetylation m akes DNA Active.
Nucleotides PURines (A, G )-2 rings. PURe As Gold.

PYrimidines (C, T, U ) -1 ring. CUT the PY (pie) .
Guanine has a ketone . Thym ine has a methyl . Thymine has a met hyl .
Deamination of cytosine makes uracil.
Uracil found in RNA; thym ine in DNA.
G-C bond ( 3 H bonds) stronger than A-T bond
(2 H bonds ) . t G-C content - t melting
temperature.
Purine (A, G) Pyrimidine (C, T, U) GAG -Amino acids necessary for purine
Carbamoyl synthesis :
C02
y-I
phosphate
Glycine
Aspartate , ,-, G lycine
\ / c ......_ ;,- \--;.......
c, .: Aspartate
N :c; .... ' . N .
:' I ':
c Gluta m i ne
I :I: C+N 1 0-Formyl 1:'
c :;.c : / tetrahydrofolate :c : c: NucleoSide base + ribose ( Sugar) .
=
'-. N
',.
>-,. N : .. - =-- .: NucleoTides base + ribose + phosphaTe ;
=
' Gl utamine

N10_Formyl- . t l i nked by 3'-5' phosphodiester bond.

tetrahydrofolate Aspartate
B I O C H E M I STRY B I O C H E M I S T R Y- M O L E CUL A R SECTION II 65
De novo pyrimidine Purines Pyrimidines

and purine synthesis
Make temporary base (orotic acid)
Start with sugar + phosphate ( PRPP) Add sugar + phosphate ( PRPP)
Add base Modify base
Pyrimidine base production

(requires aspartate)
Carbamoyl
l
Ribo s e 5 - P
Purine base production or
reuse f rom salvage pathway
(de novo requires aspartate,
Ribonucleotides are synthesized first and
are converted to deoxyribonucleotides by
ribonucleotide reductase.
p hospha te glycine, glutamine, and THFJ
\t<\E
Carbamoyl phosphate is i nvolved in 2 metabol ic
pathways : de novo pyrim idine synthesis and
/ PRPP 6-MP the urea cycle. Ornithine transcarbamoylase
-
aod deficiency ( OTC , key enzyme in the urea
cycle) leads to an accumulation of carbamoyl
UMP

!f$ \
IMP phosphate, wh ich is then converted to orotic
# UDP / acid.
Hydroxyu rea -0-f
&!i
AMP GMP
Various anti neoplastic and antibiotic d ru gs

function by interfering with puri ne synthesis:
!
dUDP CTP

Hydroxyurea inh ibits ribonucleotide
NSNIO_ dUMP reductase

methylene T H F
L THF
r;;-t-0-5-FU
6-mercaptopurine (6-MP) blocks de novo
purine synthesis
DHF
- >-
Oihydrofolate
5 -Auorouracil ( 5 -FU) i n h ibits thymidylate

reductase dTMP
synthase ( deoxythymidine monophosphate
MTX/TMP [dTMP])
Methotrexate ( MTX) inh ibits d i hydrofolate
reductase ( dTM P)
Tri methopri m (TMP) inh ibits bacterial
dihydrofolate reductase (! dTMP)
Orotic aciduria Inabil ity to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect i n
U M P synthase (a bifunctional enzyme). Autosomal recessive.
FINDINGS t orotic acid in urine, megaloblastic anem ia (does not i mprove with administration of vitamin B12
or folic acid), failure to thrive. No hyperammonem ia (vs. OTC deficiency- t orotic acid with
hyperammonemia).
TREATMENT Oral uridine admin istration.
66 SECTION I I B I O C H E M I ST RY B I O C H E M I S T RY-M O L E CU L A R
Purine salvage deficiencies

N ucleic acids N ucleic acids
ll ll

Guanylic acid Inosinic acid Adenylic acid
(GMP) (IMP) (AMP)
0
I )"'""'"'
Guani n
J
; '"
o ))
xanthine
' ' "' !{. 1 e
(} Adenine,
/
Xanthine
0
f)
H G PRT t PRPP
t PRPP
eJ
APRT
E)
(}
Adenosine deaminase (ADA)
Uric acid Xanthine oxidase
Base from degra ded DNA/RNA
Adenosine deaminase Excess ATP and dATP imbalances nucleotide Severe C ombi ned Immunodeficiency Disease
deficiency pool via feedback inh ibition of ribonucleotide ( SCID ) happens to kids .
reductase prevents DNA synthesis and thus
-+ lst disease to be treated by experimental human
! lymphocyte count. One of the major causes gene therapy.
of SCID. Autosomal recessive.
Lesch-Nyhan Defective purine salvage owing to absence of He's Got Purine Recovery Trouble.
syndrome HGPRT, which converts hypoxanthine to IMP
and guanine to GMP. Results in excess uric
acid production and de novo purine synthesis.
X-l i nked recessive.
Findings : retardation , self-mutilation,
aggression, hyperuricemia, gout,
choreoathetosis.
Genetic code features

Unambiguous Each codon specifies only l amino acid.
Degenerate/ Most amino acids are coded by multiple codons . Exception s : meth ionine and tryptophan encoded
redundant by only l codon (AUG and UGG, respectively) .
Comma less, Read from a fixed starting point as a continuous Exception s : some viru ses.
nonoverlapping sequence of bases.
U n iversal Genetic code is conserved th roughout Exception in humans: m itochondria.
evolution .
B I O C H E M I STRY B I O C H E M I S T R Y - M O L E CU L A R S E CTI O N I I 67
Point mutations in DNA Severity of damage : silent< m issense< nonsense< framesh i ft.
Silent Same a m i no acid, often base change in 3rd
position of codon (tRNA wobble).
Missense Changed amino acid (conservative -new amino
acid is similar i n chemical structure) .
Nonsense Change resulting in early stop codon. Stop the nonsense!
Frameshift Change resulting i n misread ing of all
nucleotides downstream, usually resulting in a
truncated, nonfunctional protein.
68 SECTION I I B I O C H E M I ST R Y B I O C H E M I S T R Y - M O L E CU L A R
DNA replication Eukaryotic DNA repl ication is more complex than the prokaryotic process but uses many
enzymes analogous to those l isted below. In both prokaryotes and eukaryotes, DNA repl ication is
semiconservative and i nvolves both continuous and discontinuous ( Okazaki fragment) synthesis.
Origin of replication Particular consensus sequence of base pairs
in genome where DNA repl ication begins.
May be single (prokaryotes) or multiple
(eukaryotes).
Replication fork Y-shapecl region along DNA template where
lead ing and lagging strands are synthesized.
Helicase Unwinds DNA template at repl ication fork.
Single-stranded Prevent strands from reannealing.
binding proteins
DNA topoisomerases Create a n ick in the hel i x to relieve supercoils Fluoroqui nolones - i n h ibit DNA gyrase
created during repl ication. (prokaryotic topoisomerase I I ) .
Primase Makes an RNA primer on which DNA
polymerase I I I can i niti ate repl ication.
DNA polymerase I l l Prokaryotic only. Elongates leading strand DNA polymerase I I I h a s 5 ' 3 ' synthesis and
-+
by adding cleoxynucleoticles to the 3' encl. proofreads with 3' -+5' exonuclease.
Elongates lagging strand until it reaches
primer of preceding fragment. 3' 5' -+
exonuclease activity "proofreads" each aclclecl

nucleotide.
DNA polymerase I Prokaryotic only. Degrades RNA primer; Has same functions as DNA polymerase I I I
replaces it with DNA. b u t a l s o excises RNA primer with 5 '
-+ 3'
exonuclease.
DNA ligase Catalyzes the formation of phosphodiesterase Seals.
bond within a strand of double-stranded DNA
(i.e. , joins Okazaki fragments).
Telomerase Enzyme adds DNA to 3' ends of chromosomes
to avoid loss of genetic material with every
dupl ication.
DNA
La gging
stra nd
3'
s
B I O C H E M I ST R Y B I O C H E M I STRY- M O L ECULAR SECTION II 69
DNA repair
Single stran d
Nucleotide excision Specific endonucleases release the Mutated i n xeroderma pigmentosum, which
repair oligonucleotide-conta ining damaged bases; prevents repa ir of pyri midine cli mers because
DNA polymerase and ligase fill and reseal the of ultraviolet l i ght exposure.
gap, respectively. Repa irs bulky hel ix-distorting
lesions.
Base excision repair Specific glycosylases recogn ize and remove Important i n repai r of spontaneous/toxic
damaged bases, apur inic/apyrimidinic dea m i nation.
endonuclease cuts DNA at both apurinic and
apyrimidinic sites, empty sugar is removed,
and the gap is filled and resealed.
Mismatch repair Newly synthesized strand is recogn ized, Mutated in hered itary nonpolyposis colorectal
mismatched nucleotides are removed, and the cancer ( H N PC C ).
gap is filled and resealed.
D o u b l e stra n d
Nonhomologous end Bri ngs together 2 ends of DNA fragments to Mutated in ataxia telangiectasia.
joining repa i r double-stranded breaks. No requirement
for homology.
DNA/RNA/protein DNA and RNA are both synthesized 5' 3'.

-+ m RNA is read 5' to 3'.
synthesis direction Remember that the 5' of the incom ing Protein synthesis is N-term inus to C -terminus.
nucleotide bears the triphosphate (energy
source for bond).
The triphosphate bond is the target of the
3' hydroxyl attack. Drugs blocking DNA
repl ication often have modified 3' O H ,
preventing addition o f t h e next nucleotide
( "chain term i nation").
DNA replication
5'
0 0 0
" / 5'
.f'p'\...o-
0
OH H
DNA synthesis requ i res
0
a free 3' OH to add the
next nucleotide
)( )(-Q-P
\11 -Q
0-P-0-P
3' I I I
0 0 0
OH H
7Q SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y - M O L E CUL A R
Types of RNA rRNA is the most abundant type. rampant, massive, ti ny.
mR A is the longest type.
tRNA is the smallest type.
Start and stop codons

mRNA start codons AUG (or rarely GUG ) . AUG inAUGurates protein synthesis.
Euka ryotes C odes for meth ionine, which may be removed
before translation is completed.
P roka ryotes C odes for for myl methionine (f-met) .
mRNA stop codons UGA, UAA, UAG . UGA = U Go Away.
UAA = U Are Away.
UAG = U Are Gone.
Fundional organization Sta rt o f

transcription
of the gene Sense/coding
(+1)
3'
)
__,___,..__ -"-'-''--...r- 5'
Enhancer Promotor Coding reg ion Termination
signals
Template strand
Regulation of gene expression

Promoter S ite where RNA polymerase and multiple other Promoter mutation commonly results in
transcription factors bind to DNA upstream dramatic ! in amount of gene transcribed.
from gene locus (Kf-rich upstream sequence
with TKfA and CAAT boxes) .
Enhancer Stretch of DNA that alters gene expression by Enhancers and silencers may be located close to,
binding transcription factors. far from , or even with i n (in an i ntron) the gene
Silencer Site where negative regulators (repressors) bind. whose expression it regulates.
RNA polymerases
Euka ryotes RNA polymerase I makes rRNA (most I, I I , and I I I are numbered as their products are
numerous RNA, rampant) . used in protein synthesis.
RNA polymerase II makes mRNA (largest RNA, a-amanitin, found i n Amanita phalloides (death
massive) . cap mushrooms), i n h ibits RNA polymerase I I .
RNA polymerase I I I makes tR A (smallest Causes severe hepatotoxicity if ingested.
RNA, tiny) .
No proofread ing function, but can in itiate
chains. RNA polymerase I I opens DNA at
promotor site.
P roka ryotes l RNA polymerase (multisubunit complex)
makes all 3 kinds of RNA.
B I O C H E M I ST RY B I O C H E M I S T RY-M O L E CU L A R SECTION I I 71
RNA processing Initial transcript is called heterogeneous Only processed RNA is transported out of the
(eukaryotes) nuclear RNA (hnRNA) . hnRNA destined for nucleus.
translation is called pre-m R A.
Cap
Processing occurs i n nucleus. After
Coding
5' _____..._...., transcription:
Gppp
i)
Capping on 5' end (addition of
3' < c:::t::=
:::;; =::;_) 7-methylguanosine cap)
HO-AAAAA
.._____..,
Ta il Polyadenylation on 3' end ("" 200 1\s) Poly-A polymerase does not requ i re a template.
Splicing out of i ntrons AAUAAA polyadenylation signal.
=
Capped, ta iled, and spliced transcript is called

m RNA.
0 Primary transcript combines with snRNPs

Splicing of pre-mRNA intron
and other proteins to form spliceosome.

f) Lariat-shaped ( looped) intermediate is
snRNPs__....
generated. 0 -GU-A-AG
) Lariat is released to remove intron precisely lariat
intermediate
and join 2 exons.
Patients with lupus make antibodies to
spliceosomal snRNPs.
lntrons vs. exons Exons conta i n the actual genetic information lntrons are interveni ng sequences and stay
coding for protein. in the nucleus, whereas exons exit and are
lntrons are i ntervening noncoding segments of expressed.
DNA. Different exons can be combined by alternative
spl icing to make u nique proteins i n d i fferent
tissues (e.g., -thalassemia mutations) .
l ntrons
j
Exons
Transcription
and splicing
72 SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y - M O L E CU L A R
tRNA
Structure 7 5 -90 nucleotides, zo structure, cloverleaf form, CCA: Can Carry Am i no acids.
anticodon end is opposite 3' aminoacyl encl.
All tRNAs, both eukaryotic and prokaryotic,
have CCA at 3' end along with a high
percentage of chem ically modified bases. The
amino acid is covalently bound to the 3' end of
the tRNA.
Charging Aminoacyl-tRNA synthetase (l per amino Aminoacyl-tRNA synthetase and binding of
acid, "matchmaker," uses ATP) scrutin izes charged tRNA to the codon are responsible for
amino acid before and after it bi nds to tRNA. accuracy of a m i no acid selection.
I f i ncorrect, bond is hydrolyzed . T he amino Tetracycl i nes bind 30S subunit, preventing
acid-tRNA bond has energy for formation of attachment of a m inoacyl-tRNA.
peptide bond. A mischarged tRNA reads usual
codon but inserts wrong am ino acid.
Methionine
Methionine Methionine "-
"- "- Ace
Ace Aminoacyl-tRNA Ace 3'
3' 3'
synthetase
ATP
"""'..,r-\,.
AMP + PP
IF2
( i nitiation factor)
AC
Ill
Ill
AUG """"--
5' '--,-' 3'
mANA Codon
tRNA wobble Accurate base pairing is requ ired only in the first 2 nucleotide positions of an mR A codon, so
codons d i ffering in the 3rd "wobble" position may code for the same tRNA/a m i no acid (as a result
of degeneracy of genetic code).
B I O C H E M I S T RY B I O C H E M I S T R Y - M O L E CU L A R S E CTI O N I I 73
Protein synthesis
Initiation Activated by GTP hydrolysis, in itiation factors Eukaryotes: 40S + 60S 80S (Even) .
-+
(eukaryotic I Fs) help assemble the 40S PrOkaryotes: 30S + 50S --- 70S (Od d).
ribosomal subunit with the in itiator tRNA
ATP- tRNA Activation (charging) .
and are released when the mRNA and the
GTP- tRNA Gripping and Going places
ribosomal subunit assemble with the complex.
(translocation ) .
Elongation l. Aminoacyl-tRNA binds to A site (except for
in itiator meth ion ine) T h i n k of "going APE":
2. R ibosomal rRNA ( "ribozyme") catalyzes A site = i ncom ing Am i noacyl-tRNA.
peptide bond form ation , transfers growing P site = accommodates growing Peptide.
polypeptide to a m i no acid in A site E site = holds Empty tRNA as it Exits.
3 . Ribosome advances 3 nucleotides toward 3' Many antibiotics act as protein synthesis
end of m RNA, moving peptidyl tRNA to P inhibitors:
site (translocation) Aminoglyc;osides bind 30S and inh ibit
Termination Stop codon is recogn ized by release factor, and formation of i n iti ation complex and cause
completed protein is released from ribosome. m isread ing of m RNA
Tetracycl i nes bind 30S and block a m inoacyl
60S tRNA from entering the acceptor site
Eukaryotic
Chloramphenicol binds 50S and inh ibits
ribosome
peptidyl transferase
Macrolides bind 50S and prevent release
of uncharged tRNA after it has donated its

a m ino acid
3'
Posttranslational modifications
Trimming Removal of N- or C-term i nal propeptides from zymogens to generate mature proteins.
Covalent alterations Phosphorylation, glycosylation , hydroxylation , methylation , and acetylation .
Proteasomal Attachment of ubiguitin to defective proteins to tag them for breakdown.
degradation
74 SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y - C E L LU L A R
B I O C H E M I S T RY - C E L LU L A R
Cell cycle phases Checkpoints control transitions between phases of cell cycle. This process is regulated by cycl i ns,
CDKs, and tumor suppressors. M itosis (shortest phase): prophase-metaphase-anaphase-telophase.
G 1 and G 0 are of variable duration.
REGULATION OF CELL CYCLE
CDKs Cycli n-dependent kinases; constitutive and G Gap or Growth.

=
inactive. S = Synthesis.
Cyclins Regulatory proteins that control cell cycle
events; phase specific; activate CDKs.
Cyclin-CDK complexes Must be both activated and inactivated for cell
cycle to progress. Interphase
(G1, S, G2)
Tumor suppressors p 5 3 and hypophosphorylated Rb normally
i n h ibit G 1 -to-S progression ; mutations in these
genes result in unrestrained cell division.
CELL TYPES
Permanent Rem a i n in G 0 , regenerate from stem cells. Neurons, skeletal and cardiac muscle, RBCs.
Stable (quiescent) Enter G 1 from G 0 when stimulated. Hepatocytes, lymphocytes.
Labile Never go to G 0 , d ivide rapidly with a short G 1 . Bone m arrow, gut epithel ium, ski n, ha ir foll icles,
germ cells.
Rough endoplasmic S ite of synthesis of secretory (exported) proteins Mucus-secreting goblet cells of the small
reticulum and of N-l inked ol igosaccharide addition to i ntestine and antibody-secreting plasma cells
many protei ns. are rich in RER.
Nissl bodies ( RER in neurons) -
synthesize enzymes (e.g. , ChAT [chol ine
acetyltransferase] makes ACh) and peptide
neu rotra nsm i tters.
Free ribosomes-unattached to any membrane;
site of synthesis of cytosolic and organellar
protei ns.
Smooth endoplasmic Site of steroid synthesis and detoxification of Liver hepatocytes and steroid hormone
reticulum drugs and poisons. producing cells of the adrenal cortex are rich
in SER.
B I O C H E M I ST R Y B IOCHE M I S T RY- C E L L U L A R SECTION I I 75
Cell trafficking Golgi is the d istribution center for proteins and l ipids from the ER to the vesicles and plasma
membrane. Modifies N-ol igosaccharides on asparagine. Adds 0-ol igosaccharides on seri ne and
threon ine. Adds mannose-6-phosphate to protei ns for trafficking to lysosomes.
Endosomes are sorting centers for material from outside the cell or from the Golgi, send i n g it to
lysosomes for destruction or back to the membrane/Golgi for fur ther use.
1-cell disease ( inclusion cel l d isease) - inherited lysosomal storage d isorder; failure of addition
of mannose-6-phosphate to lysosome proteins (enzymes are secreted outside the cell i nstead of
being targeted to the lysosome). Results in coarse facial features, clouded corneas, restricted joint
movement, and h igh plasma levels of lysosomal enzymes. Often fatal i n ch ildhood .
Vesicu l a r t raffick i n g prote i n s
Key:
C O P I : Golgi Golgi (retrograde); Golgi

-+
- ER.
Clathrin
COPI I : Golgi - Golgi (anterograde); ER
'rO COPI
- Golgi.
Clath r i n : trans-Golgi - lysosomes; plasma
COPII
membrane endosomes (receptor
-+
mediated endocytosis).
Endoplasmic
reticulum
N u cl ear envelope
Peroxisome Membrane-enclosed organelle i nvolved in catabol ism of very long fatty acids and am ino acids.
Proteasome Barrel-shaped protei n complex that degrades damaged or unnecessary protei ns tagged for
destruction with ubiqu itin.
76 SECTI O N I I B I O C H E M I ST RY B I O C H E M I S T R Y - C E L LU L A R
Microtubule Cyl indrical structure composed o f a hel ical array Drugs that act on m icrotubules:
of polymerized climers of a- and -tubulin. Mebenclazole/th iabenclazole
Each climer has 2 GTP bound. Incorporated (antihel m inth ic)

into flagella, cilia, mitotic spindles. Grows Griseofulvin (antifungal)
slowly, collapses qu ickly. Also involved in slow Vi ncristine/vinblastine (anti-cancer)
a-Tu bulin
axoplasm ic transport in neurons. Pacl itaxel (anti-breast cancer)
-Tu bulin Molecula r motor proteins - transport cellular Colch icine (anti-gout)
cargo toward opposite ends of m icrotubule Chediak- H igashi syndrome - mutation in the
Protofilament tracks. lysosomal trafficking regulator gene (LYST),
Dyne in =retrograde to microtubule ( + ..... ). whose product is required for the m icrotubule
-
Negative Kinesin =anterograde to m icrotubule dependent sorting of enclosomal proteins into

end(-) ( ..... +) .
- late multivesicular enclosomes. Results in
recurrent pyogen ic infections, partial albin ism ,
and peripheral neuropathy.
Cilia structure 9 + 2 arrangement of m icrotubules. Kartagener's syndrome (primary ciliary

Axonemal clynein -ATPase that links peripheral dyskinesia ) immotile cil i a clue to a clynein
-
9 doublets and causes bend ing of cilium by arm defect. Results i n male infertil ity
d i fferential sl iding of doublets. (immotile sperm) and ! female ferti l ity,
bronch iectasis, and recurrent sinusitis (bacteria
and particles not pushed out); associated with
situs i nversus.
Cytoskeletal elements
Actin and myosin M icrovilli, muscle contraction , cytokinesis, aclherens junctions.
M icrotubule Movement. Cilia, flagella, mitotic spi ndle, axonal trafficking, centrioles.
Intermediate Structure. Vimentin, clesm in, cytokeratin, lamins, gl ial fibrillary acid proteins (GFAP),
filaments neurofilaments.
Plasma membrane Asym metric l ipid bilayer.

composition Contains cholesterol , phosphol ipids, sph ingol ipicls, glycol ipicls, and proteins.
STA I N CELL TYPE

Immunohistochemical
stains for intermediate Vimentin Connective tissue
filaments Desm in Muscle
Cytokeratin Epithel ial cells
GFAP NeuroGl i a
Neurofilaments Neurons
B I O C H E M I ST R Y B I O C H E M I S T R Y- C E L LU L A R SECTION I I 77
Sodium-potassium Na+-K+ ATPase is located i n the plasma Ouabain i n h ibits by binding to K+ site.
pump membrane with ATP site on cytosol ic side. Card iac glycosides (digoxi n and digitoxi n)
For each ATP consumed, 3 Na+ go out d irectly i n h ibit the Na+-K+ ATPase,
and 2 K+ come in. During cycle, pump is wh ich leads to indirect i n hibition of Na+f
phosphorylated. Ca 2 + exchange -+ t [Ca 2 +L - t card iac
contractility.
3Na+ (o
Extracel l ular
o 2K+
side
Cytosolic
side
Collagen Most abundant protein i n the human body. Be ( So Totally) Cool, Read Books.
Extensively modified by posttranslational
mod ification.
Organizes and strengthens extracellular matrix.
Type I Most common (90%)-Bone, Skin, Tendon, Type I: bone.
dentin , fascia, cornea, late wound repair. Defective i n osteogenesis i mperfecta.
Type I I Cartilage (including hyaline), vitreous body, Type II: cartwolage.
nucleus pulposus.
Type I l l Reticulin-ski n, blood vessels, uterus, fetal Type III: defective i n Ehlers-Danlos
tissue, granulation tissue. (ThreE D).
Type I V Basement membrane or basal lamina. Type IV: under the floor (basement membrane) .
Defective i n Alport syndrome.
78 SECTION I I B I O C H E M I ST RY B I O C H E M I S T RY - C E L LU L A R
Collagen synthesis a n d strudure

Inside fibroblasts
1. Synthesis (RER) Translation of collagen a cha ins
(preprocollagen) - usually Gly-X-Y (X and Y
are prol ine or lysine).
2. Hyd roxylation (ER) Hydroxylation of specific prol ine and lysine
Hydroxylation
residues (requires vitamin C; deficiency OH OH
..... scurvy). Inhibited

in scurvy
3. G l ycosylati o n ( ER) Glycosylation of pro-a-chain hyclroxylysine
residues and formation of procollagen via
Glycosylation
hydrogen and d isulfide bonds (triple helix of (pro a chain)
OH OH
3 collagen a chains). Problems form ing triple lr Osteogenesis
imperfecta
helix -+ osteogenesis i mperfecta.
4. Exocytosis Exocytosis of procollagen into extracellular
Triple helix (procollagen)
space.
Outside fibroblasts c(1)
+
Peptide cleavage
5. P roteolytic Cleavage of d isulfide-rich terminal regions of
Ehlers-Danlos
process i n g procollagen, transforming it into insoluble
tropocollagen.
1
Collagen fibrils
with cross-links
6 . Cross- l i nkin g Reinforcement of many staggered tropocollagen

molecules by covalent lysine-hyclroxylysine
cross-linkage (by Cu 2 + -containing lysyl
oxidase) to make collagen fibrils. Problems
with cross-l inking -+ Ehlers-Danlos.
Osteogenesis Genetic bone d isorder (brittle bone disease) May be confused with child abuse.
imperfeda caused by a variety of gene defects. I ncidence is 1 : 10,000.
Most common form is autosomal dom inant
with abnormal type I collagen, causing:
Multiple fractures with minimal trauma;
may occur during the birth process

Blue sclerae r.J clue to the translucency of
the connective tissue over the choroidal

vems
Hearing loss (abnormal m iddle ear bones)
Dental i mperfections clue to lack of dentin
Ehlers-Danlos Faulty col lagen synthesis causing Type I or Type V coll agen most frequently
syndrome hyperextensible skin, tendency to bleed (easy affected in severe classic Ehlers-Danlos
bru ising) , and hypermobile joints. syndrome.
6 types. Inheritance and severity vary. Can
be autosomal dom inant or recessive. May
be associated with joint d islocation , berry
aneu rysms, organ rupture.
B I O CHE M I S T RY B I O C H E M I S T R Y - L A B O R AT O R Y T E C H N I QU E S SECTION II 79
Alport syndrome Due to a variety o f gene defects resulting i n 1ype I V collagen i s an i mportant structural
abnormal type IV collagen. Most com mon component of the basement membrane of the
form is X-I inked recessive. kidney, ears, and eyes.
Characterized by progressive hered itary
nephritis and deafness. May be associated with
ocular d isturbances.
Elastin Stretchy protei n with i n skin, lungs, large M ad a n's syndrome - caused by a defect i n
arteries, elastic ligaments, vocal cords, fibri l l i n .
liga menta flava (connect vertebrae-+ relaxed Emphysema - can be caused b y a1-antitrypsin
and stretched conformations). deficiency, resulting in excess elastase activity.
Rich in prol ine and glycine, nonhyclroxylatecl
forms.
Tropoelastin with fibrillin scaffoldi ng.
Cross-l inking takes place extracellularly and Wri nkles of aging are clue to reduced collagen
gives elastin its elastic properties. and elastin production .
Broken clown by elastase, which is normally
inh ibited by a1-antitrypsin .
B I O C H E M I S T R Y -LA B O R AT O R Y T E C H N I QUE S
Polymerase chain Molecular biology laboratory procedure used to ampl i fy a desired fragment of DNA.
readion Steps:
1 . Denaturation-DNA is denatured by heating to generate 2 separate strands
2. Annealing- during cool ing, excess premacle DNA primers anneal to a specific sequence on
each strand to be amplified.
3. Elongation-heat-stable DNA polymerase repl icates the DNA sequence following each
pnmer.
These steps are repeated multiple times for DNA sequence ampl i fication.
Agarose gel electrophoresis- used for size separation of PCR products (smaller molecules travel
further); compared agai nst DNA ladder.
80 SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y - L A B O R AT O R Y T E C H N I QU E S
Blotting procedures
Southern blot A DNA sample i s electrophoresed o n a gel and SNoW DRoP:
then transferred to a filter. The filter is then Southern =D A
soaked i n a denaturant and subsequently Northern = RNA
exposed to a radiolabeled D A probe that Western =Protei n
recogn izes and anneals to its complementary
strand. The resulting double-stranded, labeled
piece of DNA is visualized when the filter is
exposed to fi l m .
Northern blot S i m i lar t o Southern blot, except that an RNA
sample is electrophoresed . Useful for studying
mRNA levels.
Western blot Sample protei n is separated via gel
electrophoresis and transferred to a filter.
Labeled antibody is used to bind to relevant
protein.
Southwestern blot Identifies DNA-binding proteins (e.g.,
transcription factors) using labeled
ol igonucleotide probes.
Microarrays Thousands o f nucleic acid sequences are arranged i n grids o n glass o r sil icon . DNA o r R N A probes
are hybrid ized to the ch ip, and a scanner detects the relative amounts of complementary binding.
Used to profile gene expression levels of thousands of genes simultaneously to study certa in
d iseases and treatments. Able to detect single nucleotide polymorph isms ( S N Ps) for a variety of
appl ications including genotyping, forensic analysis, pred isposition to d isease, cancer mutations,
and genetic l inkage analysis.
Enzyme-linked A rapid immunologic techn ique testing for Used in many l aboratories to determine whether
immunosorbent assay antigen-antibody reactivity. a particular antibody (e.g., anti-H I V) is present
Patient's blood sample is probed with either in a patient's blood sample. Both the sensitivity
l. Indirect E LISA: uses a test antigen to and the specificity of E LI SA approach 100% ,
see if a specific antibody is present in but both false-positive and false-negative
the patient's blood ; a secondary antibody results do occur.
coupled to a color-generating enzyme is
added to detect the first antibody; or
2 . Direct ELISA: uses a test antibody
coupled to a color-generating enzyme to
see if a specific antigen is present in the
patient's blood.
If the target substance is present in the sample,
the test solution will have an intense color
reaction, ind icating a positive test result.
B I O C H E M I STRY B I O C H E M I S T R Y - L A B O R AT O R Y T E C H N I QU E S S E C TI O N I I 8l
Fluorescence in situ Fluorescent DNA or RNA probe binds to specific gene site of interest on chromosomes.
hybridization (FISH) Used for speci fic locali zation of genes and d i rect visual ization of anomal ies (e.g., m icrodeletions) at
molecular level (when deletion is too small to be visual i zed by karyotype).
Fluorescence =gene is present; no fluorescence =gene has been cleletecl .
Cloning methods Clon ing i s the production o f a recombinant DNA molecule that is self-perpetuating.
Steps:
l. Isolate eukaryotic m RNA (post-RNA processing steps) of i nterest.
2. Expose m R NA to reverse transcriptase to produce eDNA.
3 . Insert eDNA fragments into bacterial plasm ids conta i n i n g antibiotic resistance genes.
4. Surviving bacteria on antibiotic medium produce eDNA l ibrary.
Gene expression Transgenic strategies in m ice involve: Knock-out = removing a gene, tak ing it out.
modifications Random i nsertion of gene into mouse Knock-in =inserting a gene.
genome
Targeted insertion or deletion of gene
through homologous recombination with
mouse gene
Cre-lox system-Can i nducibly manipulate
genes at specific developmental points usi ng
an antibiotic-controlled promoter (e.g., to
study a gene whose deletion causes embryon ic
death).
RNA interference (RNAi) - dsRNA is
synthesized that is complementary to the
m RNA sequence of interest. When transfected
into human cells, dsRNA separates and
promotes degradation of target mRNA,
knocking clown gene expression .
Karyotyping A process in wh ich metaphase chromosomes are sta ined, ordered, and numbered accord ing to
morphology, size, arm-length ratio, and band ing pattern . Can be performed on a sample of blood,
bone marrow, amn iotic fluid, or placental tissue. Used to d i agnose chromosomal imbalances (e.g.,
autosomal trisomies, sex chromosome d isorders).
82 SECTION I I B I O C H E M I ST RY B I O C H E M I S T RY - G E N E T I C S
B I O C H E M I STRY- G E N E T I C S
Genetic terms
TERM D E F I N ITION EXAMPLE
Codominance Both alleles contribute to the phenotype of the Blood groups A, B, A B .

heterozygote.
Variable expressivity Phenotype varies among individuals with same 2 patients with neurofibromatosis type 1 ( F l )
genotype. may have varying disease severity.
I ncomplete Not all individuals with a mutant genotype BRCA l gene mutations do not always result in
penetrance show the mutant phenotype. breast or ovarian cancer.
Pleiotropy One gene contributes to multiple phenotypic PKU causes many seemingly unrelated
effects. symptoms, ranging from mental retardation to
hair/ski n changes.
Imprinting Differences in gene expression depend on Prader-Wil l i and Angel man's syndromes.
whether the mutation is of maternal or
paternal origin.
Anticipation I ncreased severity or earlier onset of disease i n Huntington's d isease.
succeed ing generations.
loss of heterozygosity I f a patient inherits or develops a mutation in Retinoblastoma and the " two-h it hypothesis."
a tumor suppressor gene, the complementary
allele must be deleted/mutated before cancer
develops. This is not true of oncogenes.
Dominant negative Exerts a dominant effect. A heterozygote Mutation of a transcription factor i n its allosteric
mutation produces a nonfunctional altered protein that site. Nonfunctioning mutant can still bind
also prevents the normal gene product from DNA, preventing wild-type transcription factor
functioning. from binding.
Linkage Tendency for certain alleles at 2 l inked loci
disequilibrium to occur together more often than expected
by chance. Measured in a population, not
in a fam ily, and often varies in different
populations.
Mosaicism Occurs when cells i n the body differ in genetic Mutation in the embryonic precursor of the bone
makeup clue to postfertil ization loss or change marrow stem cell a hematologic mosaic
-+
of genetic information dur i n g m itosis. individual.

Can be a germ-l ine mosaic (gonadal A chimeric ind ividual is derived from 2 zygotes
mosaicism ) , which may produce disease that is that subsequently fuse.
not carried by parent's somatic cel ls.
locus heterogeneity Mutations at d i fferent loci can produce the Marfan's syndrome, M E N 2 B , and
same phenotype. homocystinuria; all cause marfanoicl habitus.
Albinism.
Heteroplasmy Presence of both normal and mutated
mtDNA, resulting in variable expression in
m itochondrial inherited disease.
B I O C H E M I STRY B I O C H E M I ST R Y - G E N E T I C S SECTION I I 83
Genetic terms (continued)

TERM D E F I N ITION EXAMPLE
Uniparental disomy Offspring receives 2 copies of a chromosome Uniparental is eUploid (correct number
from 1 parent and no copies from the other of chromosomes) , not aneuploid. Most
parent. Heteroclisomy ( heterozygous) indicates occurrences of UPD normal phenotype.
-+
a meiosis I error. I soclisomy (homozygous) Consider UPD i n an individual manifesting

indicates a meiosis II error or postzygotic a recessive disorder when only one parent is a
chromosomal duplication of one of a pair of earner.
chromosomes, and loss of the other of the
original pair.
Hardy-Weinberg If a population is in Hardy-Weinberg Hardy-Wei nberg law assumes:

population genetics equilibrium and if p and q are the frequencies No mutation occur r i n g at the locus
of separate al leles, then : p2 + 2pq + q 2 1 and

= No selection for any of the genotypes at the
p + q = 1, which implies that: locus

p 2 = frequency of homozygosity for allele p Completely random mating
q 2 = frequency of homozygosity for allele q No net migration
2pq = frequency of heterozygosity (carrier

frequency, i f an autosomal recessive d isease ) .
T h e frequency of an X-l i nked recessive disease
in males = q and in females = q 2 .
Imprinting At some loci, only 1 allele is active ; the Both Prader-Wil l i and Angel man's syndromes
other is inactive (imprinted/inactivated by cl u e to inactivation or deletion of genes on
methylation) . With 1 al lele i nactivated, chromosome 1 5.
deletion of the active allele - d isease. Can also occur as a result of un iparental cli somy.
Prader-Willi syndrome Paternal allele is not expressed. Mental retardation, hyperphagia, obesity,
hypogonad ism, hypoton ia.
AngeiMan's syndrome Maternal allele is not expressed . Mental retardation , seizures, ataxia, inappropriate
laughter.
84 SECTION I I B I O C H E M I ST RY B I O C H E M I STRY- G E N ET I C S
Modes of inheritance
Autosomal dominant Often due to defects i n structural genes. Many Often pleiotropic. Fam i ly history crucial to
generations, both male and female, affected. d iagnosis.
Autosomal recessive 25% of offspring from 2 carrier parents are Com monly more severe than dominant disorders ;
affected. Often due to enzyme deficiencies. patients often present in childhood.
Usually seen in only l generation.
X-linked recessive Sons of heterozygous mothers have a 50% Commonly more severe i n males. Females
chance of being affected. No male-to-male usually must be homozygous to be affected.
transm ission.
X-linked dominant Transmitted through both parents. Either male Hypophosphatemic rickets formerly known as
-
or female offspring of the affected mother may vitamin 0-resistant r ickets. Inherited d isorder
be affected, whereas all female offspring of the resulting in t phosphate wasting at proximal
affected father are affected. tubule. Results in rickets-l i ke presentation.
Mitochondrial Transm itted only through mother. All offspring Variable expression i n population due to
inheritance of affected females may show signs of heteroplasmy.
d isease. Often due to failures in oxidative
M itochondrial myopathies - group of rare
phosphorylation .
d isorders resulting from mutations affecting
m itochondrial function . Often present with
myopathy and CNS disease. Muscle biopsy
often shows "ragged red fibers."
B I O C H E M I ST R Y B I O C H E M I STRY-G E N ET I C S SECTION I I 85
Autosomal-dominant diseases
Achondroplasia Cell-signaling defect of fibroblast growth factor ( FGF) receptor 3 . Results in dwarfism ; short l imbs,
larger head, but trunk size is normal. Associated with advanced paternal age.
Autosomal-dominant Formerly known as adult polycystic kidney disease. Always bilateral , massive enlargement of kidneys
polycystic kidney clue to multiple large cysts . Patients present with flank pa in, hematuria, hypertension, progressive
disease (ADPKD) renal fa ilure. 8 5 % of cases are due to mutation in PKD1 (chromosome 16 ; 1 6 letters in "polycystic
kidney" ) . Associated with polycystic l iver disease, berry aneurysms, mitral valve prolapse. Infantile
form is recessive.
Familial adenomatous Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer un less
polyposis colon is resected. Mutations on chromosome 5 (APC gene) ; 5 letters in "polyp."
Familial Elevated LDL clue to defective or absent LDL receptor. Heterozygotes (l : 500) h ave cholesterol "' 300
hypercholesterolemia mg/c! L . Homozygotes (very rare) have cholesterol "' 700+ mg/d L , severe atherosclerotic d isease
(hyperlipidemia early in l i fe, and tendon xanthomas (classically in the Ach illes tendon) ; M l may develop before
type I IA) age 20.
Hereditary Inherited disorder of blood vessels. Findings : telangiectasia, recurrent epistaxis, ski n discolorations,
hemorrhagic arteriovenous malformations (AVMs ) .
telangiectasia
(Osler-Weber-Rendu
syndrome)
Hereditary Spheroid erythrocytes clue t o spectrin or ankyrin defect; hemolytic anem i a ; t M C H C . Splenectomy
spherocytosis is curative.
Huntington's disease Findings : depression, progressive dementia, choreiform movements, caudate atrophy, and ! levels of
GABA and ACh in the brain. Symptoms manifest in affected individuals between the ages of 20
and 50. Gene located on chromosome 4 ; trinucleotide repeat d isorder: ( CAG\ , . "Hunting 4 food."
Marfan's syndrome Fibrill in-1 gene mutation --+ connective tissue di sorder affecting skeleton, heart, and eyes. Findings:
tall with long extrem ities, pectus excavatum, hypermobile joints, and long, tapering fingers and
toes (arachnodactyly) ; cystic medial necrosis of aorta aortic incompetence and dissecting aortic
--+
aneurysms ; floppy m itral valve. Subluxation of lenses.

Multiple endocrine Several distinct syndromes ( 1 , 2A, 2B) characterized by famil ial tumors of endocrine glands,
neoplasias ( M E N ) including those of the pancreas, parathyroid, pituitary, thyroid, and adrenal medulla. MEN 2A and
2B are associated with ret gene.
Neurofibromatosis Findings : cafe-au-la it spots, neural tumors, Lisch nodules (pigmented iris hamartomas) . Also marked
type 1 (von by skeletal d isorders (e.g., scol iosis) and optic pathway gl iomas. On long arm of chromosome 17; 17
Recklinghausen's letters in "von Reck l inghausen."
disease)
Neurofibromatosis Bilateral acoustic schwannomas, j uvenile cataracts. NF2 gene on chromosome 22 ; type 2 = 22 .
type 2
Tuberous sclerosis Findings : facial lesions (adenoma sebaceum ) , hypopigmentecl "ash leaf spots" on skin, cortical and
retinal hamartomas, seizures, mental retardation , renal cysts and renal angiomyol ipomas, cardiac
rhabdomyomas, t incidence of astrocytomas. Incomplete penetrance, variable presentation.
von Hippei-Lindau Findings : hemangioblastomas of retina/cerebel lum/medul l a ; the majority of affected individuals
disease develop multiple bilateral renal cell carcinomas and other tumors. Associated with deletion of
VHL gene (tumor suppressor) on chromosome 3 (3p ). Results in constitutive expression of H I F
(transcription factor) and activation o f angiogenic growth factors. Von H ippel-Lindau 3 words for
=
chromosome 3 .
86 SECTION I I B I O C H E M I ST RY B I O C H E M I STRY- G E N ET I C S
Autosomal-recessive Albi nism, ARPKD (formerly known as infantile polycystic kidney d isease) , cystic fibrosis, glycogen
diseases storage d iseases, hemochromatosis, mucopolysaccharidoses (except Hunter's), phenylketonuria,
sickle cell anemias, sphingolipidoses (except Fabry's), thalassem ias.
Cystic fibrosis Autosomal-recessive defect in CFTR gene on Inferti l ity i n males due to bilateral absence of
chromosome 7, commonly deletion of Phe vas deferens. Fat-soluble vita m i n deficiencies
508. CFTR channel actively secretes CJ- in (A, D, E , K) . Can present as fa ilure to thrive in
lungs and Gl tract and actively reabsorbs C) infancy.
from sweat. Most common lethal genetic d i sease of white
Defective Cl- channel secretion of
--+ population .
abnormally th ick mucus that plugs lungs, t concentration of Cl- ions i n sweat test is
pancreas, and l iver recurrent pulmonary
--+ d iagnostic.
infections (Pseudomonas species and Treatment: N-acetylcysteine to loosen mucous
S. aureus), chronic bronch itis, bronch iectasis, plugs (cleaves disulfide bonds with in mucous
pancreatic insufficiency (malabsorption and glycoproteins) .
steatorrhea) , nasal polyps, and mecon ium ileus
in newborns.
Mutation often causes abnormal protein folding,
resulting in degradation of channel before
reaching cell surface.
X-linked recessive Bruton's agammaglobulinemia, Wiskott-Aidrich Be Wise, Fool 's GOLD Heeds Silly HOpe.
disorders syndrome, Fabry's disease, G6PD deficiency,
Ocular albinism, Lesch-Nyhan syndrome,
Duchenne's (and Becker's) muscular
dystrophy, Hunter's Syndrome, Hemoph ilia
A and B , Orn ith ine transcarbamoylase
deficiency.
Female carriers may be affected, and may
have less severe symptoms clue to random X
chromosome inactivation in each cell.
Muscular dystrophies
Duchenne's X-l i nkecl framesh ift mutation deletion
--+ Duchenne's = deleted dystroph i n .
of dystroph in gene - accelerated muscle Dystroph i n gene (DMD) i s t h e longest
breakdown. Weakness begins in pelvic known human gene --+t rate of spontaneous
girdle muscles and progresses superiorly. mutation. Dystrophin helps anchor muscle
Pseudohypertrophy of calf muscles clue to fibers, primarily i n skeletal and card iac
fibrofatty replacement of muscle; cardiac muscle.
myopathy. Use of Cowers' maneuver, requiring D iagnose muscular dystroph ies by t CPK and
assistance of the upper extremities to stand up, muscle biopsy.
is characteristic. Onset before 5 years of age.
Becker's X-linked mutated clystrophin gene. Less severe
than Duchenne's. Onset in adolescence or
early adulthood .
B I O C H E M I STRY B I O C H E M I S T R Y-G E N E T I C S S E C TI O N I I 87
Fragile X syndrome X-l inked defect affecting the methylation and Tri nucleotide repeat d isorder ( C G G ) 11
expression of the FMR I gene. The 2nd most Fragile X = eXtra large testes, j aw, ears.
common cause of genetic mental retardation
(after Down synd rome) . Findings: macro
orch idism (enlarged testes), long face with a
large jaw, large everted ears, autism, mitral
valve prolapse.
Trinucleotide repeat Huntington's disease, myoton ic dystrophy, Try (trinucleotide) huntin g for my fried
expansion diseases Friedreich 's ataxia, fragile X syndrome. e gg s (X) .
Fragile X syndrome = (C GG) 11 X-Gi rlfriend 's First Aiel Helped Ace My Test.
May show genetic anticipation (disease severity
Frieclreich 's ataxia = (GAA) 11
t and age of onset in successive generations) .
Huntington's d isease = (CAG) 11
Myotonic dystrophy = (CTG) 11

88 SECTION I I B I O C H E M I ST R Y B I O C H E M I ST RY-G E N ET I C S
Autosomal trisomies
Down syndrome Findings : mental retardation, flat facies, Drinking age (2 1 ) .
(trisomy 2 1 ), 1 :700 prominent epicanthal folds, simian crease, Most common viable chromosomal d isorder
gap between 1 st 2 toes, duodenal atresia, and most common cause of genetic mental
congenital heart d isease (most commonly retardation .
ostium primum-type ASD ) . Associated with Results of pregnancy quad screen :
t risk of ALL and Alzheimer's disease (> 35 ! a-fetoprotei n , t -hCG , ! estriol ,
years of age ) . t i n h ibin A.
9 5 % o f cases cl u e t o meiotic nond isjunction of Ultrasound shows t nuchal i n first tri mester
homologous chromosomes (associated with translucency.
advanced maternal age ; from 1 : 1 500 in women
< 20 to 1 : 2 5 i n women > 45).
4% of cases clue to Robertson ian translocation.
1% of cases clue to Down mosaicism (no
maternal association ) .
Edwards' syndrome Find ings : severe mental retardation , rocker Election age ( 1 8 ) .
(trisomy 1 8), 1 : 8000 bottom feet, m icrognath ia (small jaw) , low-set Most common trisomy resulting i n l ive bi rth
Ears, clenched hands, prom inent occiput, after Down syndrome.
congenital heart disease. Death usually occurs Results of pregnancy quad screen :
within 1 year of birth. ! a-fetoprotein, ! -hCG , ! estriol , normal
inhibin A.
Patau's syndrome Findings : severe mental retardation, rocker Puberty ( 1 3 ) .
(trisomy 1 3), bottom feet, m icrophthalmia, microcephaly, Results of first-trimester pregnancy screen : ! free
1 : 1 5,000 cleft l iP/Palate, holoProsencephaly, -hCG, ! PAPP-A, and t nuchal translucency.
Polydactyly, congenital heart disease. Death
usually occurs within 1 year of birth.
Meiotic nondisju nction
Anaphase I
X X
)\ )\ )\
Anaphase II
u u n
n+1 n+1 n-1 n-1 n-1 n+1 n n
Normal
Robertsonian Nonreciprocal chromosomal translocation that commonly i nvolves chromosome pairs 1 3, 14, 1 5,
translocation 2 1 , and 2 2 . One of the most common types of translocation . Occurs when the long anns of 2
acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere
and the 2 short arms are lost. Balanced translocations normally do not cause any abnormal
phenotype. Unbalanced translocations can result in m iscarriage, stillbirth, and chromosomal
i mbalance (e.g., Down syndrome, Patau's syndrome) .
B I O C H E M I STRY B I O C H E M I STRY-G E N ETI C S S E C TI O N I I 89
Cri-du-chat syndrome Congenital microcleletion of short arm of Cri d u chat = c r y of the cat.
chromosome 5 ( 46,XX or XY, 5p-) .
Find ings : m icrocephaly, moderate to
severe mental retardation, h igh-pitched
crying/mewin g , epicanthal folds, cardiac
abnormalities (VS D ) .
Williams syndrome Congenital m icrocl e letion of long arm of chromosome 7 (deleted region i ncludes elastin gene) .
Findings : distinctive "elfin" facies, intellectual disabil ity, hypercalcemia (t sensitivity to vitamin D ) ,
well-developed verbal skills, extreme friend l i ness w i t h stra ngers, card iovascular problems.
llq 1 1 deletion Variable presentation, including Cleft palate, CATC H-2 2 .

syndromes Abnormal facies, Thym ic aplasia -+ T-cell Due t o aberrant development of 3 r d and 4th
deficiency, Cardiac defects, Hypocalcemia zo branch ial pouches.
to parathyroid aplasia, clue to m icrocleletion at
chromosome 22g l l .
D iG e o rge syn d ro m e thym ic, parathyroid, and
-
card iac defects.

V e l o c a rd iofa c i a l synd ro m e palate, facial, and
-
cardiac defects.
90 SECTION II B I O C H E M I ST RY B I O C H E M I S T RY-NUT R I T I O N
B I O C H E M I S T R Y - N UT R I T I O N
Vitamins: fat soluble A, D, E, K. Absorption dependent on gut Malabsorption syndromes (steatorrhea), such as
(i leum) and pancreas. Toxicity more common cystic fibrosis and sprue, or m ineral oil intake
than for water-soluble vitam ins, because these can cause fat-soluble vita m i n deficiencies.
accumulate in fat.
Vitamins: water soluble B 1 (thiamine: TPP) All wash out easily from body except B 1 2 and
B 2 (riboflavin : FAD, FMN) folate (stored in l iver) .
B 3 (niacin : NAD+) B -complex deficiencies often result in
B 5 (pantothenic acid: CoA) dermatitis, glossitis, and d iarrhea.
B 6 (pyridoxine: PLP)
B 7 (biotin)
B 9 (folate)
B 1 2 (cobalamin)
C (ascorbic acid)
Vitamin A (retinol)
FUNCTION Antioxidant; constituent of visual pigments Retinol is vitamin A, so think retin-A (used
(retinal ) ; essential for normal differentiation topically for wrinkles and acne) .
of epithel ial cells into specialized tissue Found in l iver and leafy vegetables.
(pancreatic cells, mucus-secreting cells);
prevents squamous metaplasia. Used to treat
measles and AML, subtype M 3 .
DEFICIENCY Night blindness, d r y ski n .
EXCESS Arthralgias, fatigue, headaches, skin changes,
sore throat, alopecia. Teratogenic (cleft
palate, cardiac abnormal ities), so a negative
pregnancy test and rel iable contraception are
needed before isotretinoin is prescribed for
severe acne.
Vitamin B1 (thiamine)
FUNCTION I n thiamine pyrophosphate (TPP) , a cofactor for a-ketoglutarate DH, Transketolase, and
several enzymes in decarboxylation reactions: Pyruvate DH required for ATP synthesis.
Pyruvate dehydrogenase (l inks glycolysis to Spell beriberi as Beri Beri to remember vitamin
TCA cycle) Bl .
a-ketoglutarate dehydrogenase (TCA cycle) Wernicke- Korsa koff- confusion,
Transketolase ( H M P shunt) ophthal moplegia , ataxia (classic triad) +
Branched-chain amino acid dehydrogenase confabulation, personal ity change, memory
DEFICIENCY Impaired glucose breakdown ..... ATP depletion loss (permanent) . Damage to medial dorsal
worsened by glucose infusion ; highly aerobic nucleus of thalamus, mammillary bodies.
tissues (brain and heart) are affected first. D ry beri beri -polyneuritis, symmetrical muscle
Wern icke-Korsakoff syndrome and beriberi . wasting.
Seen in mal nutrition a s wel l a s alcohol ism (2 Wet beriberi - h igh-output cardiac fa i lure
to malnutrition and malabsorption) . (dilated cardiomyopathy) , edema.
B I O C H E M I ST R Y B I O C H E M I S T R Y - N UT R I T I O N SECTION I I 91
Vitamin B1 (riboflavin)
FUNCTION Cofactor in oxidation and reduction (e.g., FAD and FM N are derived from riboFlavin
FADH 2 ) . ( B 2 2 KfP) .
=
DEFICIENCY Chei losis (inflam mation o f l ips, scal ing and The 2 C 's of B 2 .
fissures at the corners of the mouth) , Corneal
vascularization.
Vitamin 83 (niacin)
FUNCTION Constituent of NAD+, ADP+ (used i n redox NAD derived from Niaci n ( B 3 = 3 ATP) .
reactions) . Derived from tryptophan. Synthesis
requ i res vitamin B 6 .
DEFICIENCY Glossitis. Severe deficiency leads to pellagra, The 3 D's of B 3 : Diarrhea, Dermatiti s,
which can be caused by Hartnup disease Dementia .
(! tryptophan absorption), malignant carcinoid
syndrome (t tryptophan metabol ism), and
INH U vitamin B 6 ) . Symptoms of pellagra :
Diarrhea, Dementia, and Dermatitis.
EXCESS Facial flush ing (clue to pharmacologic closes for
treatment of hyperl ipidem ia) .
Vitamin 85 (pantothenate)
FUN CTION Essential component of CoA (a cofactor for acyl B 5 is "pento" thenate.
transfers) and fatty acid synthase.
DEFICIENCY Dermatitis, enteritis, alopecia, adrenal
insufficiency.
Vitamin 86 (pyridoxine)
FUNCTION Converted to pyridoxal phosphate, a cofactor used in transamination (e.g., ALT and AST ) ,
decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathion i ne, heme, n iacin,
h ista m i ne, and neurotransmitters including serotonin, epineph rine, norepinephrine, and GABA.
DEFICIENCY Convulsions, hyperirritabi l ity, peripheral neuropathy (deficiency inducible by I N H and oral
contraceptives) , sicleroblastic anemias clue to impaired hemoglobin synthesis and iron excess.
92 SECTION I I B I O C H E M I S T RY B I O C H E M I STRY- N U T R I T I O N
Vitamin 87 (biotin)
FUN CTION Cofactor for carboxylation enzymes (wh ich add "Avid in i n egg wh ites avidly binds biot i n ."
a 1 -carbon group) :
Pyruvate carboxylase : pyruvate ( 3 C )
- oxaloacetate (4C )
Acetyl-CoA carboxylase : acetyl-CoA (2C)
- malonyl-CoA (3C)
Propionyl-CoA carboxylase : propionyl-CoA
( 3 C ) - methylmalonyl-CoA (4C )
DEFICIENCY Rel atively rare . Dermatitis, alopecia, enteritis.
Caused by antibiotic use or excessive ingestion
of raw eggs.
Vitamin 89 (folic acid)

FUNCTION Converted to tetrahydrofolate (THF), a Found in leafy green vegetables. Folate from
coenzyme for 1 -carbon transfer/methylation fol iage.
reactions. Small reserve pool stored primarily i n the liver.
Important for the synthesis of n itrogenous bases
i n DNA and RNA.
DEFICIENCY Macrocytic, megaloblastic anemia; no Deficiency can be caused by several drugs (e.g.,
neurologic symptoms (as opposed to vitamin phenytoin, sulfonamides, MTX) .
B 1 2 deficiency) . Most common vitam in Supplemental folic acid in early pregnancy
deficiency i n the United States. Seen in reduces neural tube defects.
alcohol ism and pregnancy.
B I O C H E M I STRY B I O C H E M I ST R Y - N UT R I T I O N SECTION I I 93
Vitamin 812 (cobalamin)

FUNCTION Cofactor for homocysteine methyltransferase Found i n animal products.
(transfers C H 3 groups as methylcobalamin) Synthesized only by m icro organisms. Very
and methylmalonyl-CoA mutase. large reserve pool (several years) stored
DEFICIENCY Macrocytic, megaloblastic anem ia, primarily i n the l iver. Deficiency is usually
hypersegmentecl PMNs, neurologic caused by malabsorption (sprue, enteritis,
symptoms (paresthesias, subacute combined Diphyllobothrium latu m ) , lack of intrinsic
degeneration) clue to abnormal myeli n . factor (pernicious anem ia, gastric bypass
Prolonged deficiency leads t o irreversible surgery) , or absence of term inal ileum
nervous system damage. (Crohn's d isease) .
Use Schilling test to detect the etiology of the
C H 3 for anabolic Odd #C deficiency.
reactions fatty acids
1
Methyl malonyl-GoA
5-adenosyl-methionine ATP + methionine -+ SAM. SAM the methyl donor man.

SAM transfers methyl un its. Requ ired for the conversion of N E to
Regeneration of meth ionine (and thus SAM ) is epinephrine.
dependent on vita m i n B 1 2 and folate.
Anabolic pathways
/f
ATP
\
CH
SAM 3
---------
Methionine Homocysteine
TH F
methyltransferase CH 3 T H F
B, 2
94 SECTION I I B I O C H E M I ST RY B I O C H E M I ST R Y - N UT R I T I O N
Vitamin C (ascorbic acid)

FUN CTION Antioxidant. Found i n fru its and vegetables.
Also fac i l itates i ron absorption by keepin g i ron Pronounce "absorbic" a c i d .
2
in Fe + reduced state .
Necessary for hyd roxylation of prol ine and
lysine i n collagen synthesis.
Necessary for dopa m i n e -hydroxylase, wh ich
converts dopa m i n e to N E .
DEFICIENCY Scu rvy- swollen gums, bru is i ng, hemarthrosi s , Vita m i n C deficiency c a u s e s sCurvy clue t o a
anemia, p o o r wound heal i ng. C ollagen synthesis defect.
Weakened i m mune response.
EXCESS Nausea, vom iting, d i a rrhea, fatigue, sleep

problems. Can t risk of i ron toxicity in
predisposed i ndividuals (e.g. , those with
transfusions, hereditary hemoch romatosi s ) .
Vitamin D D 2 = ergocalciferol - ingested from plants. D r i n k i n g milk (fortified with vita m i n D ) i s good
D3 = cholecalciferol - consumed i n m ilk, for bones.
formed i n su n-exposed sk i n .
2 5 -0H D3 = storage for m .
1 , 2 5 - ( 0 H ) 2 D3 (calcitriol) = active form.
FUNCTION t i ntestinal absorption of calcium and

phosphate, t bone m i neral ization .
DEFICIENCY Rickets fJ in children (bone pain and

deform ity) , osteomalacia in adults (bone pain
and muscle weakness) , hypocalcemic tetany.
Breast m i l k has ! vitam i n D (supplement i n
dark-skinned patients) .
EXCESS Hypercalcem i a , hypercalciur ia , loss of appetite,

stupor. Seen in sarcoidosis (t activation of
vita m i n D by epithel ioid macrophages) .
Rickets. X-ray of legs in toddler shows bowing of femurs

(genu varum). C
Vitamin E
FUNCTION Antioxidant (protects eryth rocytes and E is for Eryth rocytes.
membranes from free-rad ical damage ) .
DEFIC IENCY t frag i l ity of erythrocytes ( hemolytic anem i a ) ,

muscle weakness, posterior column and
spi nocerebel lar tract demyel in ation.
B I O C H E M I STRY B I O C H E M I ST RY- N U T R I T I O N SECTION II 95
Vitamin K
FUNCTION Catalyzes y-c a rboxylation of gluta m i c acid K i s for Koagulation. Necessary for the synthesis
res idues on various prote i n s concerned with of clotting factors II, VI I , IX, X, and prote i n s
blood clotting. Synthesi zed by intestinal Aora . C a n d S . Wa rfa r i n -vita m i n K a ntagonist.
DEFICIENCY Neonatal hemorrhage with t PT and t a PTT Not i n breast m i lk; neonates a re g iven vita m i n K
but normal bleed i n g time (neonates have i n j ection at bi rth to preve nt hemorrhage.
sterile intestines and a re unable to synthesize
vita m i n K). Can also occur after prolonged
use of broad-spectru m antibiotics.
Zinc
FUN CTION Essential for the activity of 100+ enzymes. I mportant in the formation of zinc fi n gers (transcription
factor motif) .
DEHCIENCY Delayed wound h e a l i ng, hypogon ad ism, ! adult h a i r (ax i l l a ry, fac i a l , pubic) , dysge us ia , a n o s m i a .
M a y pre d ispose t o alcohol ic c i rrhosis .
Ethanol metabolism
Fomepizol e - i n h ibits alcohol dehydrogenase
Cytoso l Mitochondria
and i s an a n tidote for methanol or ethylene
Alcohol dehyd roge na se Acetaldehyde dehydrogenase
Ethano I "'\ Ace ta lde hy d e 7 "'\
7
Acetate glycol poison i n g.
NAD' NADH NAD' NADH D i sulfiram (Antabuse) - i n h ibits acetaldehyde
dehydrogenase (acetaldehyde accumul ates,
NAD + is the l i m iting reagent. contribut ing to h a n gover symptom s) .
Alcohol dehydrogenase operates via zero-order
k inetics.
Ethanol hypoglycemia Ethanol metabol ism t NAD H /NAD+ ratio in l iver, causing d iversion of pyruvate to lactate
and OAA to m a l ate, thereby i n h ibiting gluconeogenesis and stimulating fatty acid synthes i s .
--+ hypoglyc e m i a and hepatic fatty change (hepatocel lula r steatosis) seen i n chron i c alcoholics.
Overproduction of lactate --+ acidosis. Depletion of oxaloacetate shuts down the TCA cycle,
shunting acetyl-CoA i nto ketone production . Breakdown of excess m a late t NADPH and thus
fatty acid synthesi s .
--"'----=-./'---)! --"----./--)1
NADH NAD+ NADH NAD+
Pyruvate lactate Oxaloacetate malate

Glycolysis TCA cycle
9G S E CT I O N I I B I O C H E M I ST RY B I O C H E M I ST RY - M ETA B O L I SM
Malnutrition
Kwashiorkor Prote i n malnutrition resulting in skin lesions, Kwa s h iorkor results from a protein-
edema, l iver m a l function (fatty change clue to deficient M EAL :
! apolipoprote i n synthesis) . Cl i n ical pictur e i s Mal nutrition
small child w i t h swollen belly. Edem a
An e m i a
Liver (fatty)
Marasmus E nergy m a lnutrition resulting in tissue and Marasmus results in Muscle wasti n g.
muscle wasting, loss of subcutaneous fat, and
variable edema.
B I O C H E M I ST RY - M E TA B O L I SM
Metabolism sites
Mitochondria Fatty acid oxidation ( -oxidation) , acetyl
G oA production , TCA cycle, oxidative
phosphorylation.
Cytoplasm Glycolysi s , fatty acid synthesis, HMP shunt,

prote i n synthesis ( RER), steroid synthesis
( SE R) , cholesterol synthesis.
Both Heme synthesis, Urea cycle, Gluconeogenesi s . H UGs take two ( i . e . , both ) .
Enzyme terminology A n enzyme's name often describes its fu nction. For example, glucok i nase i s a n e n zyme that
catalyzes the phosphorylation of glucose using a molecule of KrP. The following a re com monly
used enzyme descriptors .
Kinase Uses ATP to add h i gh-energy phosphate group onto substrate (e.g., phosphofructok inase)
Phosphorylase Adds i norga n i c phosphate onto substrate without using KrP (e.g., glycogen phosphorylase)
Phosphatase Removes phosphate group from substrate (e.g., fructose- 1 ,6-bisphosphatase)
Dehydrogenase Catalyzes oxidation-reduction reactions (e.g. , pyruvate clehycl rogenase)
Carboxylase Transfers C 02 groups with the help of biotin (e.g., pyruvate carboxylase)
B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M SECTION II 9}
Rate-determining enzymes of metabolic processes

PROCESS ENZYME REGU LATORS
Glycolysis Phosphofructo k i n a se - ] (PFK- 1 ) AMP EB, fructose-2 ,6-BP EB , ATP 8, citrate 8
Gluconeogenesis Fru ctose- 1 , 6- bi sphosphatase ATP EB , A M P 8, fructose-2 ,6-BP 8
TCA cycle l socitrate d e hydrogenase ADP EB , ATP 8, NAD H 8
Glycogen synthesis G l ycogen synthase Glucose EB , i ns u l i n EB , epinephrine 8,

glucagon 8
Glycogenolysis G lycogen p h o s p h o rylase A M P EB, epineph rin e EB, glucagon EB, i ns u l i n 8,

ATP 8
I-I M P shunt G l u cose-6- phosphate dehydrogenase (G6PD) NAD P+ EB, NADPH 8
De novo pyr i m i d i n e C a r b a m oyl phosph ate synthetase I I

synthesis
De novo purine G l ut a m i n e- PRPP a m idotra n sferase A M P 8, I M P 8, CMP 8

synthesis
Urea cycle Carba m oyl phosphate synthetase I N-acetylgluta m ate EB
Fatty acid synthesis Acetyl - CoA ca rboxylase (ACC) In sul i n EB, c itrate EB , glucagon 8,
palm itoyl-CoA 8
Fatty acid ox idation C a r n i t i n e acyltra n sfe rase I Malonyl-C oA 8
Ketogenesis H M G - CoA synth a se
Cholesterol synthesis H M G- CoA reductase In s ul i n EB , thyroxi n e EB , glucagon 8,

cholesterol 8
98 SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y- M E TA B O L I S M
Summary of pathways
!O
Galactose
------...__ !c.
Galactose- 1 -phosphate
i< e t e i< i<

i
G l ycogen G l ucose

6-phosphog l uconolactone --
1
U D P-gl ucose - G l ucose- 1 -phosphate Giucose-6-phosphate
0
@
Galactokinase ( m i l d galactosemia)
Galactose - 1 -phosphate uridyltransferase
(severe galactosemia)
A
\:1
. HMP shunt
j
i< OllO i<
Fructose-6-phosphate ......-.- R i b u l ose-5-phosphate ---
E)
C0
Hexok i nase/g l u coki nase
() G l u c ose-6-phosphatase (von G ierke's)
0 G l ucose-6-phosphate dehydrogenase ( G 6 P D ) Fructose-1 ,6-bi sphosphate
0 Transketolase
t
fj H

N

,, , /
Phosp hofructokinase-1
g Fructose-1 ,6-bisphosphatase
t
G lyceraldehyde-3-P DHAP

F 1 P +=-- Fructose
Fructokinase (essential fructosuria)
e Al dolase B (fructose intol erance) G lyceraldehyde
H
1 , 3-bis-phosphoglycerate
m Pyruvate kinase
Pyruvate dehydrogenase

H
3-phosphoglycerate
Glycolysis
H M G -CoA red uctase
Pyruvate ca rboxylase

H
PEP ca rboxyk i n ase 2-phosphoglycerate
C itrate synthase
Chol esterol
i< m
lsocitrate dehydrogenase Phosphoenolpyruvate ( P E P )

G=)
a.-ketogl utarate dehydrogenase
Ornithine transcarbamoylase f
i< i<
Pyruvate Lactate
.-1:'1 M evalonate
Gluconeogenesis (!) I
r t

Acetoacetyi-CoA -- H M G -CoA
<::
i<
\1;1 Acetyl-GoA .
i<
Acetoacetate - - hydroxybutyrate
\
B Malonyl-GoA Fatty ac1ds
N H 4+ + CO 2
\
Aspartate
Citra

L '\
Citru l l ine Oxaloacetate
@ Req u i res biotin cofactor
(f) Arg1n1n o succ1nate

(
Malate
i<fill l socitrate
G) Req u i res thiamine cofactor (TPP)
-tl I rreversible, i m porta nt point of reg ulation
\
T CA
" i< /;
Ornithine U rea
cycle
cycle
Fu mara ogl utarate
.
7-CoA
S ucc1nat;____ u ccinyi I .__..:.::.
12 8
t
Arg inine _ ... Methyl malonyi-CoA
Urea
Propionyi-CoA
t
Odd-chain fatty acids
and branched-chain
a m ino acids
B I O C H E M I STRY B I O C H E M I S T R Y - M E TA B O L I S M S E CTI O N I I 99
ATP produdion Aerobic metabol ism of glucose produces 32 ATP via malate-aspartate shuttle (heart a n d l iver) , 3 0
ATP via glycerol-3-phosphate shuttle (muscle ) .
Anaerobic glycolys i s produces o n l y 2 n e t ATP p e r glucose molecule.
ATP hydrolysi s c a n be coupled to energetically u n favorable reactions.
N N
.. _JL_)-
N
Base (adenine}
Mg 2
/ '
/ '
/ '
o- o- o-
1 I I
-o - P - O- P -O- P-O-CH 2 O
1 / ""-..
II
0
II
0
II
0 c c
]- .
l\1,...VI...;
R1bose
Triphosphate moiety
OH OH
Adivated carriers C A R R I E R MOLECULE C A R R I E D I N ACTIVATE D FORM
ATP Phosphoryl groups
NADH , NAD P I-I , FAD H 2 Electrons
Coenzyme A , l ipoam ide Acyl groups
Biotin C 02
Tetrahydrofolates 1-carbon u n its
SAM CH3 groups
TPP Aldehydes
Universal eledron Nicoti n a m ides (NAD+ from vita m i n B3, NADP H i s a product of the H M P shunt.
acceptors NAD P+) and flavin nucleotides ( FAD+ from NADPH i s used i n :
vita m i n B2 ) . An abol ic processes
NAD + i s generally used i n catabolic processes Respi ratory burst
to carry reduc i n g equ ivalents away as NAD H . P-45 0
NADPH i s u s e d i n anabolic processes (steroid Glutath ione reductase
and fatty acid synthesis) as a supply of reduc in g
equ ivalents.
Hexokinase vs. Phosphorylation of glucose to yield glucose-6-phosphate serves as the 1 st step of glycolysi s (also
glucokinase serves a s the l st step of glycogen synthesis i n the liver) . Reaction i s catalyzed by either hexoki nase
or glucok i nase, depen d i n g on the tissue.
Hexokinase Ubiqu itous. H igh affi n ity ( low K11) , low capacity Feedback i n h ibite d by glucose- 6-phosphate.
( low vm aJ , u n i nduced by insul i n .
Glucokinase Liver a n d cells o f pancreas. Low affi n ity ( h i gh At low glucose concentrations, hexok inase
Km ) , h igh capacity ( h i gh Vma J , i nduced by sequesters glucose i n the tissue. At h i gh glucose
i n s u l i n . ( glucok i n ase is a glutton . It has a h i gh concentrations, excess glucose i s stored i n the
vmax because it c a n not be satisfied.) l iver.
1 00 SECTION I I B I O C H E M I S T RY B I O C H E M I S T RY - M E TA B O L I S M
Glycolysis regulation, Net glycolysis (cytoplasm) :

key enzymes Glucose + 2 P; + 2 ADP + 2 NAD + - 2 pyruvate + 2 ATP + 2 NAD H + 2 H + + 2 HzO.
Equation not balanced chemically, and exact balanced equation depends on i o n i zation state of
reactants and products.
REQUI RE ATP G l ucose ------+ G l ucose-6-phosphate Glucose-6-P 8 hexokinase.

Hexokinase/glucokinase
Fructose-6-P 8 glucok i nase.
F ructose-6-P Fructose-1 ,6-BP ATP 8, A M P EB, c itrate 8, fructose-2 ,6-BP EB .
Phosphofructokinase- 1
(rate-limiting step)
Glucokinase in liver; hexokinase in all other tissues.
PRODUCE ATP 1 ,3-BPG :=:=:=:=:= 3-PG

Phosphoglycerate kinase
ATP 8, a l a n i n e 8, fructose- 1 ,6- B P EB .

Phosphoenol pyruvate Pyruvate
Pyruvate kinase
Regulation by Fl,6BP FBPase-1

G luconeogenesis +---- Fructose-6-phosphate F1 ,6B P ----+ G lycolysis
PFK-1
l
Fructose
bisphosphatase-2 Phosphofructokinase-2
(active in fasting (active i n fed state) (+ )
state)
Fructose-2,6-bisphosphate ------'
F B Pase-2 and PFK-2 are part of the same complex but respond i n opposite manners to
phosphorylation by prote in ki nase A.
Fasting state : t glucagon - t cAM P - t prote i n k i n ase A - t F B Pase-2 , ! PFK-2 , less glycolys is.
Feel state : t insulin -+ ! cAM P - ! prote in kinase A - ! F B Pase-2 , t PFK-2 , more glycolys i s .
Pyruvate Reaction : pyruvate + NAD+ + CoA - acetyl The complex is s i m i l a r to the a-ketoglutarate
dehydrogenase C oA + C 02 + NAD H . dehydrogenase complex (same cofactors,
complex T h e complex conta ins 3 enzymes that requ i re 5 s i m i l a r substrate and action ) , wh ich converts
cofactors : a-ketoglutarate - succi nyi-C oA (TCA cycle) .
l. Pyrophosphate ( B 1 , thiamine ; TPP) Arse n i c i n h ibits l ipoic a c i d . Find i n gs : vom iting,
2. FAD ( B 2 , riboflavin) rice water stool s , garl ic breath .
3 . NAD ( B 3 , n i a c i n )
4. C oA ( B 5 , pantothen ate)
5 . Lipoic acid
Activated by exerc i se :
t AD+/ ADH ratio
t ADP
2
t Ca +
B I O C H E M I STRY B I O C H E M I S T R Y - M E TA B O L I S M SECTION I I 1 01
Pyruvate Causes backup of substrate (pyru vate and Lys i n e a n d Leuci n e - the on Ly pureLy
dehydrogenase a l a n i ne) resulting i n lactic acidosis. Most cases ketoge n i c a m i n o acids.
complex deficiency a re clue to mutations in X-l i n kecl gene for E l -a
subun i t of PDC .
Findings: neurologic defects, usually starting i n
i n fa ncy.
Treatment: t i ntake of ketogenic nutrients (e.g.,
h i gh fat content or t lysine and leucine) .
Pyruvate metabolism Fu nctions of d i fferent pyruvate metabol i c

pathways :
Glucose
!
0 A l a n i n e a m i notra n sferase (B6) : alanine
Pyruvate
c a r r i e s a m i n o groups t o the l iver from
muscle
E) Pyruvate carboxylase (bioti n ) : oxaloacetate
0
can replenish TCA cycle or be used i n
Lactate
Cahill cycle Cytosol gluconeogenesis
M itochondria
Cori cycle E) Pyruvate dehyd rogenase ( B 1 , B 2 , B3, B 5 ,
l ipoic acid) : transition fro m glycolysis to
the TCA cycle
0 Lactic acid dehydrogenase ( B3 ) : end of
E)
Oxaloacetate
a naerobic glycolys i s (major pathway i n
E>
Acetyl-CoA
R B C s , leukocyte s , k i d ney medulla, lens ,
testes, and cornea)
TCA cycle (Krebs cycle) Pyruvate -+ acetyl-CoA produces l NAD H , The TCA cycle produces 3 NAD H , l FAD H 2 ,
l C 02 . 2 C 02 , l G T P per acetyl-C oA = l O ATP/
1-c
Pyruvate 13C)
acetyl-CoA (2x everyth i n g per glucose) . TCA
8 ATP cycle reactions occur in the m itochon dria.
5:
5' 8 Acetyl-CoA
a-ketoglutarate dehydrogenase complex
8 NADH
requ i res the same cofactors as the pyruvate
Acetyl-CoA I2C)
ATP
dehydrogenase complex ( B 1 , B 2 , B 3, B 5 , l ipoic
F
NADH y Oxalo-
acetate

Ot.-,
<at-
e s-
ynt,.
has
..
Citrate 16()

acid ) .
C itrate Is Krebs' Sta rt i n g Substrate For Making
-[
14C l
cis- onitate
"
Oxaloacetate.
t
Malate I4C) lsocitrate I6C)
%

C0 2 + NADH
Fumarate 14() %; e 8 ATP
g;
""'"
8 NADH
() ADP
FADHz a- KG ISC)
NADH
Succinate 14()
10 COz +
GTP + CoA '-.. ...--.. Suconyl-
.. . tC}>
<J."
V
8
Succinyi-CoA
CoA I4C) l 8 NADH
8 ATP
* Enzymes are irreversi b le.
l 02 SECTION I I B I O C H E M I S T RY B I O C H E M I S T R Y - M E TA B O L I S M
Eledron transport NAD H electrons from glycolys is enter m i tochondria v i a the m a late-aspartate or glycerol-3 -
chain and oxidative phosphate shuttle. FAD H 7 electrons are transferred to complex I I (at a lower energy level than
phosphorylation NADH ) . The passage of electrons results i n the formation of a proton grad ient that, coupled to
oxidative phosphorylation, dr ives the production of ATP.
ADP t P, ATP t Hp
Mitochondrial
matrix
I n n e r mitochondrial
mem brane
I ntermembranous
space
ATP PRODUCED VIA ATP SYNTHASE
l NAD H - 3 ATP; l FADH2 - 2 ATP.

OXI DATIVE PHOSPHORYlATION POISONS
Electron transport D i rectly i n h ibit electron transport, caus i n g a Rotenone, cya n ide, antimyc i n A, CO.
inhibitors proton gradient and block of ATP synthesis.
ATP synthase D i rectly i n h ibit m itochondrial ATPsynthase, Oligomyc i n .

inhibitors causing an t proton gradient. No ATP is
produced because electron tra nsport stops .
U ncoupling agents t permeab i l ity of membrane, causing a proton 2 ,4-DNP, a s p i r i n (fevers often occur after aspirin
grad ient and t 02 consumption. ATP synthesis overdose) , thermoge n i n i n brown fat.
stops, but electron transport continues.
Produces heat.
Gluconeogenesis.
irreversible enzymes Pathway Produces Fresh Glucose .
Pyruvate carboxylase I n m itochond r i a . Pyruvate -+ oxaloacetate . Req u i res biot i n , ATP. Activated by acetyl-CoA.
PE P carboxykinase I n cytosol . Oxaloacetate Req uires GTP.

-+ phosphoenolpyruvate.
Fructose-1 ,6- In cytosol. Fructose- 1 ,6-bi sphosphate

bisphosphatase -+ fructose- 6-P.
G lucose-6- I n E R . Glucose-6-P -+ glucose.

phosphatase
Occurs primarily in l iver. En zymes also found in kidney, i ntestinal epithel i u m . Defic iency of the
key gluconeogenic en zymes causes hypoglycem i a . ( Muscle can not participate in gluconeogenesis
because it lacks glucose-6-phosphatase) .
Odd-cha i n fatty acids yield l propionyi-CoA duri n g metabol i s m , which c a n e nter the TCA cycle
(as succinyl-CoA) , undergo gluconeogenesis, and serve as a glucose sour c e . Even-cha i n fatty ac ids
can not produce new glucose, since they yield only acetyl-CoA equ ivalents.
B I O C H E M I STRY B I O C H E M I S T R Y - M E TA B O L I S M S E CT I O N I I l 03
HMP shunt (pentose Provides a source of NADPH from an abundantly ava i l able glucose-6-phosphate ( NADPH i s
phosphate pathway) requ ired for reductive reactions , e . g . , glutathione reduction i n side R B C s ) . Additional ly, t h i s
pathway yields ribose for nucleotide synthesis a n d glycolytic i ntermed i ates . 2 d istinct phases
(oxidative a n d nonoxidative ) , both of wh ich occur i n the cytopla s m . No ATP i s used or produced.
S i te s : lactating m a m mary glands, l iver, adrenal cortex (sites of fatty acid or steroi d synthesi s ) , RBCs.
REACTIONS K E Y ENZYMES PRODUCTS
Oxidative
\.
NADP' NADPH
(irreversible) C0 2
Glucose-6-P dehydrogenase
Glucose- 6 -P 2 NADPH
,
Ribu lose-5-P
,
Rate- li m iting step
Nonoxidative Phosphopentose isomerase,

transketolases R i bose-5-P
(reversible) Ribulose-5-P' G3 P
,
Req u i res B 1 F6 P
Respiratory burst I nvolves the activation of membrane-bound NADPI-I oxidase ( e . g . , i n neutroph i l s , monocytes) .
(oxidative burst) Plays an i mportant role in the i m mune response -+ rapid release of reactive oxygen i n termediates
( ROis) . Note that NADPH plays a role in the creation of ROis a n d in their neutra l i zation .
NADPH oxidase
0 (deficiency = chronic
::t o
0
granulomatous disease)
NADPH
@ S u peroxide dism utase
NADP'
0 2-
r Neutro p h i l

E)
!a
Myeloperoxidase
c e l l mem brane
a Glutath ione peroxidase
0 Glutath ione red uctase H 202 Hp

..__;r
(:) dehyd rogenase (G6PD)
Glucose - 6- p hosp hate
GSH GSSG

GSH/ Glutathione (reduced!
GSSG oxidized) NADP' NADPH
..__;r (from HMP shunt)
HOCI ' Bleach (hypochlorite)
G6P 6PG
02-

Superoxide anion
WBCs of patients with CGD can uti l i z e H202 generated by i nvad i n g orga n i s m s and convert i t to
ROi s . Patients a re at t risk for in fection by catalase-positive species (e.g., S. aureus, Asperg illus)
because they neutra l i ze their own I-I 202 , leaving WBCs without ROi s for fighting i n fections.
1 04 SECTION II B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M
Cilucose-6-phosphate NADPH is necessary to keep glutath ione X-l i nked recessive d isorder; most common
dehydrogenase reduced, which i n turn detoxifies free rad icals h u man enzyme deficiency; more prevalent
deficiency and peroxides. NADPH i n RBCs leads to among blacks. t malarial resistance.
hemolytic a n e m i a due to poor RBC defense Hei n z b o d ie s - oxi d i zed Hem oglobin
aga i nst oxid i z i n g agents (e.g., fava beans, precipitated with i n R B C s .
s u l fonamides, primaquine, antituberculosis Bite cells - result from the phagocytic removal
drugs) . I n fection can also precipitate hemolysis of Heinz bodies by splenic m acrophage s .
(free rad icals generated via i n fl a m m atory T h i n k , "Bite i nto s o m e Heinz ketchup."
response can d i ffuse i nto RBCs and cause
ox idative d a mage) .
NADP+ 2 GSH
G6P
(reduced)
Glucose-6-phosphate Glutathione Glutathione

dehydrogenase reductase peroxidase
NADPH GSSG
6PG
(oxidized)
Disorders of frudose metabolism

Essential fructosuria I nvolves a defect i n fructokinase. Autosomal recessive. A benign, asymptomatic condition, since
fructose i s not trapped i n cel l s .
Sympto m s : fructose appears in blood and u rine.
D i sorders of fructose metabolism cause m i lder symptoms than analogous d i sorders of ga l actose
metabol i s m .
Fructose intolerance Hereditary deficiency o f aldolase B . Autosomal recessive. Fructose-1 -phosphate accumulates,
causing a i n ava i l able phosph ate, wh ich results i n i n h ibition of glycogenolys is and
gluconeogenesis.
Symptoms : hypoglycemia, jaundice, c i rrhosis, vom iti ng.
Treatment: intake of both fructose and sucrose (glucose + fructose) .
Fructose metabolism (liver)
0 E)
<
Dihydroxyacetone-P ........_
-....._
r\
Fructokinase Aldolase B
Fructose ---:::o-oo:::-
:- -+
Fructose-1-P -< .\fl-ase G lyceraldehyde-3-P - G lycolysis
E)
-----
\{\ose

ATP Glyceraldehyde
ADP
ATP
NADH
0 Deficiency essential fructosuria

=
E) Deficiency fructose intolerance

=
NAD'
Glycerol
E) Fructose bypasses rate-limiting step
of glycolysis (PFKJ via this pathway
B I O C H E M I ST R Y B I O C H E M I S T R Y - M E TA B O L I S M SECTION I I 1 05
Disorders of galadose metabolism

Galactokinase Hered itary deficiency of galactokinase. Galactitol accumulates i f galactose i s present in d iet.
deficiency Relatively m i ld condition . Autosomal recessive.
Sympto m s : galactose appears i n blood and ur ine, i n fantile cataracts. May i n itially present as fa i l ure
to track objects or to develop a social smile.
Classic galactosemia Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Dam age i s caused by
accumulation of tox ic substances ( includ in g galactitol , which accumulates in the lens of the eye) .
Sympto m s : fa i l ur e to thrive, jaundice, hepatomegaly, i n fantile cataracts, mental retardation .
Treatment: exclude galactose and lactose (galactose + glucose) fro m d iet.
G a l actose metabo l i s m Fructose is to Aldolase B a s Gal actose is to

UridylTransferase ( FAB GUT) .
Galactokinase U ridyl transferase The m ore serious defects lead to P04 depletion .
Galactose ----- Galactose - 1 - P ------- Glucose- 1 - P
n (\
1
A
ADP U DP-Giu U D P-Gal
u
Aldose
reductase G lycolysis/
4-epimerase gl uconeogenesis
Galactitol
Sorbitol An altern ative method of trapping glucose in the cell i s to convert it to its alcohol counterpart,
called sorbitol , v i a aldose reductase. Some ti ssues then convert sorbitol to fructose using sorbitol
dehydrogenase ; t i ssues with an insufficient a mount of t h i s enzyme a re at risk for i ntracellular
sorbitol accumulation, causing osmotic dam age ( e . g . , cataracts, ret i n opathy, and peripheral
neuropathy seen with chro n ic hyperglycemia in d i abete s ) .
H igh blood levels of galactose a l s o result i n conversion t o osmotically active alcohol for m s v i a
aldose reductase.
Liver, lens, ovaries, and seminal vesicles have both enzymes.
Aldose red uctase Sorbitol dehydrogenase

G l u cose Sorbitol Fructose
NADPH
Schwann cells, retina, and kidneys have only aldose reductase .
Aldose red uctase

G l u cose Sorbitol
NADPH
Lactase deficiency Age-dependent a n d /or hered itary lactose i ntolerance (African Americans, Asians) due to loss of
brush-border enzyme. May also follow gastroenteritis.
Symptom s : bloating, cramps, osmotic diarrhea.
Treatment: avoid d a i ry products or add lactase p i l l s to d iet.
1 06 SECTI O N I I B I O C H E M I ST R Y B I O C H E M I S T R Y - M E TA B O L I S M
Amino acids Only L-form amino acids are found i n prote i n s .
Essential Glucoge n i c : M e t , Val , H i s . All essential a m i n o acids need to be suppl ied i n

Glucoge n i c /ketoge n i c : l i e , Phe, Thr, Trp. t h e diet.
Ketoge n i c : Leu, Lys .
Acidic Asp a n d Glu (negatively charged at body p H ) .
Basic Arg, Lys , a n d H i s . Arg and His are req u i red duri n g periods of
Arg i s most basic. growth . Arg and Lys are t in h istones, which
His has n o charge at body pH. bind negatively charged DNA.
Urea cycle A m i n o acid catabol ism results i n the formation O rd i n a rily, Ca reless C rappers Are Al so
of common metabol ites (e.g., pyruvate, acetyl Frivolous About Urination .
C oA) , which serve as metabol ic fuels. Excess
nitrogen ( N H4 + ) generated by th is process is
t
converted to urea and excreted by the kidneys.
C02 + N H /
- 8{
2 ATP
Aspartate
la. (donates NH/1
Citrulline
Rate- limiting
2 AD P + p I
-1.
0

Carbamoyl
phosphate
%'l<>o> A M P + PP;
Mitochondria
'(0
Cytoplasm
Ornithine Arg i n i nosuccinate
(liver)
To kidney +-- U rea
U rea Arg i n i n e
N H / -----+- N H 2
I
C02 -----+- C = 0
I
Aspa rtate -----+- N H 2
Transport of ammonium by alanine and glutamate
)( ) c : r ,G : :: ) (
Muscle Liver
A m ino acids
1'"'' ""''""""
Ala n i n e
..
-----__--
-
A 1 an in e cyc le
....
Ala n i ne
''""'""""
Glutamate ( N H 3 l Cori cycle !v Glutamate ( N H 3 l
!
a- Ketoacids Pyruvate Pyr ate
! t
B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M SECTION I I 1 07
Hyperammonemia C a n be acqu i red ( e . g . , l iver d i sease) or hereditary A m m o n i a i ntoxicati o n -tremor ( asteri x i s ) ,

(e.g., urea cycle enzyme deficiencies) . slurr i n g of speech, somnolence, vom iting,
Results in excess N H4 +, which depletes cerebral edema, blurring of v i s i o n .
a-ketoglutarate, leading to i n h ibition of TCA
cycle.
Treatment: l i m it prote i n i n d iet. Benzoate or
phenylbutyrate (both of wh ich b i nd amino
acid and lead to excretion) may be given to !
a m m o n i a levels. Lactulose to acidify the GI
tract and trap N H 4 + for excretion .
Ornithine M o s t c o m m o n u r e a cycle d isorder. X-l i n kecl recessive ( v s . o t h e r u r e a cycle e n z y m e deficiencies,

transcarbamoylase which a re autosomal recessive) . Interferes with the body's :1bi l ity to el i m i n ate a m m o n i a . Often
deficiency evident in the first few clays of l i fe, but may present with late onset. Excess carbamoyl phosphate is
converted to orotic acid (part of the pyr i m i d i n e synthesis pathway) .
Findings: t orotic acid in blood and urine, ! B U N , symptoms of hypera m m onem i a .
Amino acid derivatives

Thyroxine Melanin
Phenyla l a n i ne
BH4 t
BH4 Vitamin 86 t
Vitamin c SAM
-- Tyrosine - Dopa -- Dopamine -- NE -- Epi
Y. Niacm -- NAD+/NADP+

Tryptop h a n
Serotonin -- Melato n i n
H istamine
B
H i sti d i n e
Porphyrin -- Heme
B
G lycine
Creatine
A rg i n i n e -- U rea
N itric oxide
GABA
G l utamate
G l u tathione
1 08 SECTION I I B I O C H E M I ST R Y B I O C H E M I S T R Y - M E TA B O L I S M
1
Catecholamine synthesis/tyrosine catabolism
Pheny l a l a n i n e
)( )
NADP THB Phenylalanine
Dihydropteridine reductase
DHB hydroxylase
1
NADPH
Tyrosine
NADP ?f THB \ Tyrosine
E nzyme legen d :
Dihydropteridine reductase / \.. v Hydroxylase adds OH
NADPH
DHB hydroxylase
Decarboxylase removes COOH
D i hydroxypheny l a l a n i ne,
SAM adds CH3
861
aka "dopa"
1
e carbidopa
Vitamin Dopa decarboxylase
B reakdown prod ucts v i a MAO a n d COMT:
Dopam i n e HVA
Dopa m i ne
Norepinephrine VMA
::r
Epinephrine Metanephrine
Vitam in C Dopamine -hydroxylase
N"' Mn
cortisol Phenylethanolamine
N-methyltransferase
Epinephrine
Phenylketonuria Due to phenylalanine hydroxylase or Autosomal recessive. I ncidence "" 1 :10,000.

tetrahydrobiopterin cofactor (malignant Screened for 2-3 days a fter birth (normal at
phenylketonuria) . Tyrosine becomes essentia l . b i rth because of maternal en zyme duri n g fetal
t phenylalanine l e a d s t o excess phenylketones l i fe) .
m unne. Phenylketone s - phenylacetate, phenyl l actate,
Findings : mental reta rdation, growth and phenyl pyruvate.
retardation, seizures, fa i r sk i n , eczema, musty D isorder of aromatic a m i n o acid metabol ism
body odor. --+ musty body odor.
Treatment: phenylalanine (conta ined in
aspartame [e.g., NutraSweet] ) and t tyrosine
i n d iet.
Maternal PKU - lack of proper d ietary therapy

duri n g pregnancy. Findings in in fant:
m icrocephaly, mental retardation, growth
retardation, congenital heart defects.
Alkaptonuria Congenital deficiency of homogentisic acid oxidase i n the degradative pathway of tyrosi ne to
(ochronosis) fumarate . Autosomal recessive. Ben ign d isease.
Findings: clark connective tissue, brown pigmented sclera , urin e turns black on prolonged exposure
to a i r. M ay h ave deb i l itating arthralgias ( homogentisic acid toxi c to cartil age) .
Albinism Congenital deficiency of either of the following: Lack o f mel a n i n results i n a n t risk of sk i n
Tyrosi nase ( inabil ity to synthesize mel a n i n cancer.
from tyrosine) - autosomal recessive Variable i n heritance clue to locus heterogeneity
Defective tyrosine transporters ( amounts of (vs . ocular albinism -X-l i nked recessive) .
tyrosine and thus melanin)
C a n result from a lack of m i gration of neural
crest cel l s .
B I O C H E M I S T RY B I O C H E M I S T R Y - M E TA B O L I S M S E CTI O N I I 1 09
Homocystinuria 3 forms (all autosomal recessive ) : All for m s result i n excess homocyste i n e .
Cystath ion i n e synthase deficiency Cyste i n e b e c o m e s essentia l .
(treatment: ! Met and t Cys, and t B12 and F i n d ings : t t homocyste i ne i n uri n e , mental
fol ate i n d iet) retardation , osteoporosi s , tall stature, kyphosis,
! a ffi n ity of cystath ionine synthase for lens subluxation (downward a n d inward ) , and
pyridoxal phosphate (treatment: t t vitam i n atherosclerosis (stroke and M I ) .
B 6 i n d iet)
Homocysteine methyltransferase (req u i res
B d deficiency
Homocysteine Cystathionine
methyltransferase . synthase
Methioni ne Homocysteme .......-;:; Cystath ionine --- Cysteine
B12 / B6
Serine
Cystinuria Hered itary defect of renal tubular amino acid Autosomal recessive. C o m mon ( 1 :7000).
transporter for cysteine, ornithine, lysine, and Treatment: goo d hyd ration a n d u r i n a ry
arg i n ine i n the PCT of the kidneys. alkal i n i zation.
Excess cystine i n the u ri n e can lead to Cystine i s made of 2 cyste i n e s connected by a
precipitation of hexagonal crysta l s and renal d i sulfide bond.
staghorn calcul i .
Maple syrup urine Blocked degradation of branched amino Autosomal recessive.

disease acids ( lie , Le u , Val) due to ! a-ketoacid Urine smells l i ke maple syrup.
dehydrogenase ( B 1 ) . Causes t a-ketoacids in I Love Vermont maple syrup from maple trees
the blood, especially Leu. (with branches) .
Causes severe CNS defects, mental retardation,
and death .
Hartnup disease An autosomal-recessive d isorder characterized by defective neutral a m i no acid transporter on renal
and i ntesti n a l epithel i a l cells.
Causes tryptophan excretion in urine and ! absorption from the gut. Leads to pellagra.
1 10 SECTION I I B I O C H E M I ST RY B I O C H E M I ST R Y - M E TA B O L I S M

Glycogen regulation by insulin and glucagon/epinephrine
Glucagon Epinephrine
(liver) (liver and muscle)
Ca 2 + I calmod u l i n i n m u scle Adenylyl

activates phosphorylase kinase cyclase
so that glycogenolysis
is coordinated with
cAMP
muscle activity
1 I
P,
Glycoge n Protei n kinase A Glycogen

Glycogenolysis
phosphorylase kinase phosphorylase kinase
(inactive) (active)
l
Glycogen
phosphorylase
Protein phosphatase (active)
Receptor tyrosi n e
-------'
k i n a s e d i merizes
l
Insulin
Glycogen Branches have a ( 1 ,6) bond s ; l i n kages have a ( 1 ,4) bonds.
Skeletal muscle Glycogen u ndergoes glycogenolysis -+ glucose- 1 -phosphate -+ glucose- 6-phosphate, wh ich i s
rapidly metabol ized dur i n g exerc ise.
Hepatocytes Glycogen i s stored and undergoes glycogenolysis to m a i nta i n blood sugar at appropriate levels.
Glucose- 6 - p hosphate
Jt 0 U D P - g lucose p yrophosphorylase
f) G lycogen synthase
Glucose-1-phosphate
oJ E) Bra n c h i n g enzym e
0 Glycogen phosphorylase
aJ
U DP-glucose
0 Debranching enzym e
o --
Storage form Limit dextrin
of g lycogen
Note : A small amount of glycogen i s degraded i n lysosomes by a- 1 ,4-glucosidase.

B I O C H E M I ST R Y B I O C H E M I S T RY - M E TA B O L I S M SECTION I I 1 1 1
Glycogenolysis/glycogen synthesis
G LYCOG EN Lysosomal degradation
-------------
Branching enzyme
\
G lycogen synthase
J
Limit dextri n
(4 g l ucose residues i n
branched configu ration)
Debra n c h i n g enzyme (type Ill)
t
G LUCOSE ----- G l u cose-6-phosphate --:::===;::==:::;:=
: - G l u cose + P ;
G l u cokinase G l ucose-6-
phosphatase (type I)
Glycogen storage 12 types, all resulting in abnormal glycogen Very Poor C arbohydrate Metabol i sm .
diseases metabo l i s m and a n accumulation of glycogen
with i n cell s .
DISEASE F I N D I NGS DEFICI ENT ENZYME COMMENTS
Von Gierke's disease S evere fasting hypoglycem i a , Glucose-6-phosphatase Autosomal recessive.

(type I) t t glycogen i n l iver, t blood
lactate, hepatomegaly
Pompe's disease Cardiomegaly and syste m i c Lysosomal a-1 ,4-glucosidase Autosomal recessive .
(type I I ) fi n d i n gs lead i n g t o early death (acid maltase) Pompe's trashes the Pump
( h e a rt, l iver, and muscl e ) .
Cori's disease M i lder form of type I with Debranch i n g enzyme Autosoma 1 recessive.
(type I l l ) normal blood lactate levels ( a-1 ,6-glucosidase) Gluconeogenesis i s i ntact.
McArdle's disease t glycogen i n muscle, but Skeletal muscle glycogen Autosomal recessive .
(type V) cannot break it clown, lead i n g phosphorylase McArd le's = Mu scle.
t o p a i n fu l muscle cramps,
myoglobi nuri a with strenuous
exercise
1 12 SECTION II B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M
Lysosomal storage Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation
diseases of abnormal metabolic products.
ACCUMU LATED
DISEASE FINDINGS DEFICIENT ENZYME SU BSTRATE I N H ERITANCE
Sphi ngol i p idoses
Fabry's disease Peripheral neuropathy of hands/feet, a-galactosidase A C e ra m i de XR

angiokeratomas, card iovascular/renal trihexoside
d isease
Gaucher's disease Most common . Glucocerebrosidase Glucocerebroside AR

, H epatosplenomegaly, aseptic necrosis
of femur, bone crises, Gaucher's
cells rJ (macrophages that look l i ke
crumpled ti ssue paper)
Niemann-Pick disease Progressive neurodegeneration, Sph i ngomyelinase S ph i n gomyel i n AR

hepatosplenomegaly, cherry-red spot
on macula, foa m cells rn
lay-Sachs d isease Progressive neurodegenera tion, Hexosa m i n idase A G M 2 gangl ioside AR

developmental delay, cherry-red spot
on macula, lysosomes with onion
ski n , no hepatosplenomegaly (vs .
Niemann-Pick)
Krabbe's disease Per ipheral neuropathy, developmental Galactocerebrosidase Galactocerebroside AR

delay, optic atrophy, globoid cells
Metachromatic C entral and peripheral demyel in ation Arylsulfatase A C erebroside sulfate AR

leukodystrophy with ataxi a , dementia
M ucopolysacc h a r i doses
H urler's syndrome Developmental delay, gargoyl ism, a-L-iduron idase Heparan sulfate, AR
a i rway obstruction, corneal cloud ing, dermatan sulfate
hepatosplenomegaly
Hunter's syndrome M il d Hurler's + aggressive behavior, no lduronate sulfatase Heparan sulfate, XR

corneal cloud i n g dermatan sulfate
t
GM2
No man picks (Niemann-Pick) h i s nose with
Tay-Sachs
his sphinger ( s phing om ye l i nase) .
t
C e ra m i d e tri h exos i d e Tay-SaX l acks heXosa m i n idase.
S u l fatides GM3

Hunters see clearly (no corneal cloud i n g) and
Metach ro m atic Fa bry's
leu kodystrophy / a i m for the X (X-l i nked recessive ) .
t i ncidence of Tay-Sachs, Nieman n-Pick, and
t
G l u cocerebros i d e
G a l a ctoce rebroside
G auc h er , s some forms of Gaucher's d i sease i n Ashkenazi
')(
'
Krab be's '\..... .
....---\--- S p h i n g o m ye l i n Jews.
Ce r a m l d e N ie m a n n -Pick
B I O C H E M I STRY B I O C H E M I S T RY - M E TA B O L I S M S E CT I O N I I 1 13
Fatty acid metabolism Fatty acid degradation occurs where its products Acyi-CoA dehydrogenase deficiency:
will be consumed-in the m itochondrion . t dicarboxyl ic acids, ! glucose and ketones.
Carnitine deficiency: i nabil ity to transport " SYtrate" SYnthesi s.
=
LCFAs i nto the m itochondria, resulting CARn itine CARnage of fatty acids.
=
in toxic accumulation. Causes weakness,

hypotonia, and hypoketotic hypoglycem ia.
Syn t h esis Degradation
Fatty acid synthesis

(palmitate, a 16C FA)
l
}-
Ma lonyi-CoA
Acetyi-CoA
C02 (biotin)
I
Fatty acid + CoA
Fatty acid CoA

synthetase
!1-0--
Acyi-CoA
lATP citrate
lyase M alonyi-CoA
Citrate Carnitine
shuttle s h uttle
M itochondria l
matrix
1
Citrate
I
Acyi-CoA
!
13-oxidation
(breakdown to
/"-.
acetyi-CoA groups)
Ketone TCA
bodies cycle
Ketone bodies In the liver, fatty acids and amino acids Breath smel ls l i ke acetone (fru ity odor) .
are metabol ized to acetoacetate and Urine test for ketones does not detect
-hydroxybutyrate (to be used in muscle -hydroxybutyrate (favored by h i gh redox
and bra i n ) . state) .
I n prolonged starvation a n d diabetic
ketoacidosis, oxaloacetate is depleted for
gluconeogenesis. In alcohol ism, excess ADH
shunts oxaloacetate to malate. Both processes
stall the TCA cycle, which shunts glucose and
F FA toward the production of ketone bodies.
Made from HMG-CoA. Metabol ized by the
brai n to 2 molecules of acetyl-CoA. Excreted
1 1 1 unne.
1 14 SECTION I I B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M
Metabolic fuel use

Exercise
1 00% 1 g protein or carbohydrate = 4 kcal .
1 g fat = 9 kca l .
(!)

:::>
0
(/)
>.
e>
(!)
c
w
M i n utes -- Hours ---

D u ration of exercise
Fasting a n d starvation Priorities are to supply sufficient glucose to the brain and RBCs and to preserve protein.
F e d state (afte r a Glycolysis and aerobic respiration . Insulin stimulates storage of l ipids, proteins,
meal) glycogen.
Fasting (between Hepatic glycogenolysis (major) ; hepatic Glucagon, adrenaline stimulate use of fuel
meals) gluconeogenesis, adipose release of FFA reserves.
(m inor) .
Sta rvation days 1 -3 Blood glucose level maintained by: Glycogen reserves depleted after clay 1 .
Hepatic glycogenolysis RBCs lack m itochondria and s o cannot use
Adipose release of FFA ketones.
Muscle and l iver, which shift fuel use from
glucose to F FA
Hepatic gluconeogenesis from peripheral
tissue lactate and alanine, and from

ad ipose tissue glycerol and propionyl
CoA (from odd-cha in FFA- the only
triacylglycerol components that contribute
to gluconeogenesis)
Starvat i o n after day 3 Ad ipose stores (ketone bodies become the main Amount of adipose stores determines survival
source of energy for the bra in and heart) . After time.
these are depleted, vital protein degradation
accelerates, lead ing to organ fa ilure and death.
Cholesterol synthesis Rate-l im iting step is catalyzed by HMG- Statins (e.g., lovastatin) inhibit HMG-CoA
CoA reductase, which converts HMG-CoA reductase.
to mevalonate. % of plasma cholesterol is
esterified by lecithi n-cholesterol acyl transferase
( LCAT) .
, B I O C H E M I ST RY B I O C H E M I S T R Y - M E TA B O L I S M S E CT I O N I I 1 15
Dietary fat+
Lipid transport, key
LPL ,
_
cholesterol
enzymes
-- Chylomicrons Chylomicron
""\FFA remnants
L::
IS
\ Ill
Y
Peripheral
l
t1ssues
(with LDL
receptors)
F FA
- LP)L L
I
VLDL I D L --- LDL
-----I
I H
Pancreatic l ipase - degradation of d ietary TG i n small intestine.

Lipoprotein l ipase (LPL) - degradation of TG circulating i n chylomicrons and VLDLs.
Hepatic TG l ipase ( H L) - degradation of TG remaining i n IDL.
Hormone-sensitive l ipase - degradation of TG stored i n adipocytes.
CE TP Tran sfe r of
cholesterol este rs
to V L D L , I D L , L D L
Lecithin-cholesterol acyl transferase ( LCAT) -catalyzes esterification of cholesterol .

Cholesterol ester transfer protein (CETP) -mediates transfer of cholesterol esters to other
l ipoprotein particles.
Major apolipoproteins
Chyl o m i cron
Apo l i poprotei n Function Chyl o m icron re m n a n t VLDL IDL LDL HDL
E Mediates remnant uptake X X X X X

A-1 Activates LCAT X
C-1 1 Lipoprotein l ipase cofactor X X X

B-48 Med iates chylomicron X X
secretion
B-1 00 Binds LDL receptor X X X
l l6 SECTION I I B I O C H E M I STRY B I O C H E M I S T R Y - M E TA B O L I S M
Lipoprotein fundions Lipoproteins are composed of varying

proportions of cholesterol , triglycericl e s (TGs) ,
and phosphol ipids. LDL and H DL carry most
cholesterol .
LDL transports cholesterol from l iver to tissues. LDL is Lousy.
HDL transports cholesterol from periphery to HDL is Healthy.
l iver.
Chylomicron Del ivers d ietary TGs to peripheral tissue. Del ivers cholesterol to l iver in the form of chylomicron
remnants, which are mostly depleted of their triacylglycerols. Secreted by intestinal epithel ial
cel ls.
VLDL Delivers hepatic TGs to peripheral tissue. Secreted by liver.
IDL Formed in the degradation ofVLDL. Del ivers triglycerides and cholesterol to l iver.
LDL Del ivers hepatic cholesterol to peripheral tissues. Formed by hepatic l ipase modification of iDL in
the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.
HDL Mediates reverse cholesterol transport from periphery to l iver. Acts as a repository for apoC and
apoE (wh ich are needed for chylom icron and VLDL metabol ism). Secreted from both l iver and
i ntestine.
Familial dyslipidemias
TYPE I NCREASED B L O O D LEVEL PATHOPHYSIOLOGY
1-hyper Chylomicrons, TG, cholesterol Autosomal recessive. Lipoprotein l ipase

chylomicronemia deficiency or altered apol ipoprotein C-I I .
Causes pancreatitis, hepatosplenomegaly,
and eruptive/pruritic xanthomas (no t risk for
atherosclerosis) .
lla-familial hyper LDL, cholesterol Autosomal dominant. Absent or LDL receptors.
cholesterolemia Causes accelerated atherosclerosis, tendon
(Achilles) xanthomas, and corneal arcus.
IV-hyper VLDL, TG Autosomal domi nant. Hepatic overproduction of
triglyceridemia VLDL. Causes pancreatitis.
Abetalipoproteinemia Autosomal recessive mutation i n m icrosomal triglyceride transfer protein ( MTP) gene B-48 -+
and B-100 chylomicron and VLDL synthesis and secretion. Symptoms appear i n the fi rst few
-+
months of l i fe. I ntestinal biopsy shows l ipid accumulation within enterocytes clue to inabil ity to
export absorbed l ipid as chylomicrons.
Findings : failur e to thrive, steatorrhea, acanthocytosis, ataxia, night blindness.
Microbiology
"Support bacteria. They're the only culture some people have."

-Anonymous
"What lies behind us and what lies ahead ofus are tiny matters
compared to what lies within us."
- Ol iver Wendell Holmes
This high-yield material covers the basic concepts of microbiology.

The emphasis in previous examinations has been approximately 40%
bacteriology (20% basic, 20% quasi-clinical), 25% immunology, 25%
virology (10% basic, 15% quasi-clinical), 5% parasitology, and 5%
mycology.
Microbiology questions on the Step l exam often require two (or more)
steps: Given a certain clinical presentation, you will first need to identify
the most likely causative organism, and you will then need to provide
an answer regarding some feature of that organism. For example, a
description of a child with fever and a petechial rash will be followed
by a question that reads, "From what site does the responsible organism
usually enter the blood?"
This section therefore presents organisms m two major ways: in

individual microbial "profiles" and in the context of the systems
they infect and the clinical presentations they produce. You should
become familiar with both formats. When reviewing the systems
approach, remind yourself of the features of each microbe by returning
to the individual profiles. Also be sure to memorize the laboratory
characteristics that allow you to identify microbes.
Additional tables that organize infectious diseases and syndromes

according to the most commonly affected hosts and the most
likely microbes are available on the First Aid team blog at www.
firstaiclteam.com.
11 8 SE CTION I I MI CRO B I O L O G Y MICROBIOLOGY-BASIC BACTERIOLOGY
MICROBIOLOGY-BASIC BACTERIOLOGY
Bacterial structures
STRUCTURE FUNCTION CHEM ICAL COMPOSITION
Pepti doglyc a n Gives rigid support, protects against osmotic Sugar backbone with peptide side chains cross
pressure. linked by transpeptidase.
Cell wall/cell Major surface antigen. Peptidoglycan for support. Lipoteichoic acid
m e m brane (gra m induces T F and IL- l .
positives)
Oute r m e m b ra n e (gram Site of endotoxin ( l ipopolysaccharide [LPS ] ) ; Lipid A induces T N F and IL-l;
n egatives) major surface antigen. 0 polysaccharide is the antigen.
Plasma m e m b ra n e Site of oxidative and transport enzymes. Lipoprotein bilayer.
Ribosome Protein synthesis. 50S and 30S subunits.
Periplasm Space between the cytoplasmic membrane and Contains many hydrolytic enzymes, including
outer membrane in gram-negative bacteria. -lactamases.
Capsule Protects against phagocytosis. Polysaccharide (except Bacillus anthracis, which
contains D-glutamate) .
Pilus/fi m b ria Mediate adherence of bacteria to cell surface ; Glycoprotein.
sex pilus forms attachment between 2 bacteria
during conjugation .
Flagellum Motility. Protein.
Spo re Resistant to dehydration, heat, and chemicals. Keratin-like coat; dipicolinic acid ;
peptidoglycan.
Pla s m i d Contains a variety of genes for antibiotic DNA.
resistance, enzymes, and toxins.
Glycocalyx Mediates adherence to surfaces, especially Polysaccharide.
foreign surfaces (e.g., indwelling catheters).
Cell walls Unique to Common to both

Unique to
gram-negative
gram-positive
organisms
1------ Pilus------;
Lipoteichoic
acid (combination
of lipids and
teichoic acids)
Peri plasm
Gram-positive Gram-negative
(Adapted, with permission, from Levinson W, Jawetz E. Medical Microbiology and Immunology: Examination ond Boord Review. 9th ed. New York: McGraw-Hill,
2006: 7.)
MI CRO B I O L O G Y MICROBIOLOGY-BASIC BACTERIOLOGY SECT I O N I I 11 9
Baderial taxonomy
MORPHOLOGY Gram-positive exa mples G ra m-negative examples
Ci rcular (coccus) Staphylococcus Neisseria
Streptococcus
Rod (bacillus) Clostridium Enteric s :
Corynebacterium E. coli
Bacillus Shigella
Listeria Salmonella
Mycobacterium (acid fast) Yersinia
Gardnerella ( Gram variable) Klebsiella
Proteus
Enterobacter
Serratia
Vibrio
Campylobacter
Helicobacter
Pseudomonas
Bacteroides
Respiratory:
Haemophilus (pleomorphic)
Legionella (silver)
Bordetella
Zoonotic:
Francisella
Brucella
Pasteurella
Bartonella
Bra nch i n g fila m entous Actinomyces

Nocardia (weakly acid fast)
Ple o m o rphic Rickettsiae (Giemsa)
Chlamydiae (Giemsa)
Spi ral Spirochete s :
Leptospira
Borrelia ( Giemsa)
Treponema
N o cell wall Mycoplasma (does not Gram stain)
Baderia with unusual cell membranes/walls

Mycoplasma Contain sterols and have no cell wall.
Mycobacteria Contain mycol ic acid. H igh lipid conteht.
12 Q SE CTION I I MI CRO B I O L O G Y MICROBIOLOGY-BASIC BACTERIOLOGY
Gram stain limitations These bugs do not Gram stain wel l : These Rascals May Microscopically Lack Color.
Treponema (too thin to be visualized) . Treponemes - dark-fielcl m icroscopy and
Rickettsia (intracel lular parasite). fluorescent antibody staining.
Mycobacteria (h igh l ipid content in cell wall

detected by carbolfuchsin in acid-fast stain).
Mycoplasma (no cell wall) .
Legionella pnewnophila (primarily Legionella -silver sta in.
intracellular) .
Chlamydia (intracellular parasite ; lacks
muramic acid in cell wall) .
Stains
Giemsa Chlamydia, Borrelia, Rickettsiae, Certai n Bugs Really Try my Patience.
Trypanosomes, Plasmodium .
PAS (periodic Stains glycogen, mucopolysaccharicles; used PASs the sugar.
acid-Schiff) to d iagnose Wh ipple's disease (Tropheryma
whipplei) .
Ziehi-Neelsen (carbol Acid-fast organisms (Nocardia, Mycobacterium) .
fuchsin)
India i nk Cryptococcus neoformans (mucicarmine can
also be used to stain thick polysaccharide
capsule reel ) .
Silver stain Fungi (e.g., Pneunwcystis) , Legionella,
Helicobacter pylori.
Special culture requirements

BUG MEDIA USED FOR ISOLATION
H. influenzae Chocolate agar with factors V (NAD+) and X ( hematin)
N. gonorrhoeae, Thayer-Martin (or VPN) media-Vancomycin (inhibits gram-positive organisms) , Polymyxin
N. meningitidis (inhibits gram-negative organ isms except Neisseria) , and Nystati n (inh ibits fungi ) ; " to connect to
Neisseria, please use your VPN client"
B. pertussis Borclet-Gengou (potato) agar (Bordet for Bordetella)
C. diphtheriae Tellurite plate, Loffler's media
M. tuberculosis Lowenstein-Jensen agar
M. pneumoniae Eaton's agar
Lactose-f e r m enti ng Pink colon ies on MacConkey's agar (fermentation produces acid, turning colony pink) ; E. coli is
enterics al s o grown o n eosin-methylene blue (EMB) agar as colonies with green metallic sheen
Legion ella Charcoal yeast extract agar buffered with cysteine and iron
Fungi Sabouraud 's agar. " Sab 's a fun guy! "
M I C R O B I O LO G Y MICROBIOLOGY-BASIC BACTERIOLOGY SEC T I O N I I 121
Obligate aerobes Use an 02 -dependent system to generate ATP. Nagging Pests Must Breathe.
Examples include Nocardia, Pseudomonas P. aeruginosa is a n aerobe seen i n burn wounds,
aeruginosa, Mycobacterium tuberculosis, and compl ications of di abetes, nosocom ial
Bacillus. pneumon ia, and pneumon ias i n cystic fibrosis
Reactivation of M. tuberculosis (e.g., after patients.
i m mune compromise or TNF-a inhibitor use)
has a predilection for the apices of the lung,
which have the highest Po 2 .
Obligate anaerobes Examples include Clostridium, Bacteroides, Anaerobes Can't Breathe Ai r.

and Actinomyces. They lack catalase and/or Anaerobes are normal flora in GI tract,
superoxide dismutase and are thus susceptible pathogenic elsewhere. Amin02 glycosides are
to oxidative damage. Generally foul smell ing ineffective against anaerobes because these
(short-chain fatty acids), are difficult to antibiotics require 02 to enter into bacterial
culture, and produce gas in tissue (C02 and cel l .
H z) .
Intracellular bugs
Obligate i ntracellular Rickettsia, Chlamydia. Can't make own ATP. Stay inside (cells) when i t is Real ly C old.
Facultative Salmonella, Neisseria, Brucella, Mycobacterium, Some Nasty Bugs May Live FacultativeLY
intracellular Listeria, Francisella, Legionella, Yersinia pestis.
Encapsulated baderia Positive quellung reaction - if encapsulated Quellung capsular "swellung."

=
bug is present, capsule swells when specific S HiNE S KiS.

anticapsular antisera are added. Are opson ized, and then cleared by spleen.
Examples are Streptococcus pneumoniae, Asplenics have decreased opsonizing abil ity
Haemophilus infiuenzae type B, Neisseria and are at risk for severe infections. Give
meningitidis, Escherichia coli, Salmonella, S. pneumoniae, H. infiuenzae, N. meningitidis
Klebsiella pneumoniae, and group B Strep. vaccmes.
Their capsules serve as an antiphagocytic
virulence factor. Capsule + protein conjugate
serve as an antigen in vaccines.
Catalase-positive Catalase degrades H 2 0 2 before it can be You need PLACESS for your cats .
organisms converted to microbicidal products by the
enzyme myeloperoxidase. People with chronic
granulomatous d isease (NADPH oxidase
deficiency) have recurrent infections with
these m icrobes because they degrade the
l i m ited H 2 0 2 .
Examples : Pseudomonas, Listeria, Aspergillus,
Candida, E. coli, S. aureus, Serratia.
1 22 SECTION I I MI CRO B I O L O G Y MICROBIOLOGY-BASIC BACTERIOLOGY
Vaccines For vaccines containing polysaccharide Pneumovax (polysaccharide vaccine with no

capsule antigens, a protein is conjugated to conjugated protein) and Prevnar (conjugated
the polysaccharide antigen to promote T-cell vaccine)
activation and subsequent class switching. H. influenzae type B (conjugated vaccine)
A polysaccharide antigen alone cannot be Meningococcal vaccines (conjugated vaccines)
presented to T cells ; therefore, only IgM
antibodies would be produced.
Urease-positive bugs Cryptococcus, H. pylori, Proteus, Vreaplasma, C Huck Norris hates PUNKSS.
Nocardia, Klebsiella, S. epidermidis,
S. saprophyticus.
Pigment-producing Actinomyces israelii-yellow "sulfur" granules, Israel has yellow sand.

bacteria which are composed of filaments of bacteria.
S. aureus-yellow pigment. aureus (Latin) = gold.
Pseudomonas ae rug inosa -blue- green pigment. Aerugula is green.
Serratia marcescens-red pigment. Serratia marcescens-think red maraschino
cherries.
Bacterial virulence These promote evasion of host immune response.

factors
Protein A Binds Fe region of Ig. Prevents opson ization and phagocytosis. Expressed by S. au reus.
lgA protease Enzyme that cleaves IgA. Secreted by S. pnewnoniae, H. influenzae type B , and Neisseria (SHiN)
in order to colonize respiratory mucosa.
M protei n Helps prevent phagocytosis. Expressed by group A streptococci.
MI CRO B I OLO G Y MICROBIOLOGY-BASIC BACTERIOLOGY SECT I O N I I 1 23
Main features of exotoxins and endotoxins

PROPERTY Exotoxin E ndotoxin
SOURCE Certain species of some gram-positive and Outer cell membrane of most gram-negative
gram-negative bacteria bacteria
SECRETED FROM CELL Yes No
CHEMISTRY Polypeptide Lipopolysaccharide (structur a l part of bacteria;
released when lysed)
lOCATION OF GENES Plasmid or bacteriophage Bacterial chromosome
TOXICITY H igh (fatal dose on the order of l pg) Low (fatal dose on the order of hundreds of
m icrograms)
CliNICAl EFFECTS Various effects (see below) Fever, shock
MODE OF ACTION Various modes (see below) Induces TNF and I L- l
ANTIGENICITY I nduces high-titer antibod ies called antitoxins Poorly antigenic
VACCI N ES Toxoids used as vaccines No toxoids formed and no vaccine ava ilable
HEAT STABiliTY Destroyed rapidly at 60C (except Stable at l 00 C for l hour
staphylococcal enterotoxin)
TYPICAl DISEASES Tetanus, botulism, diphtheria Meni ngococce m i a ; sepsis by gram-negative rods
1 24 SECT I O N I I M I CRO B I O L O G Y MICROBIOLOGY-BASIC BACTERIOLOGY
Bugs with exotoxins

BACTERIA TOX I N MECHANISM MANI FESTATION
In h i b it protei n synthesis
Corynebacterium Diphtheria toxin3 Pharyngitis with pseudomembranes i n throat

diphtheriae Inactivate elongation factor and severe lymphadenopathy (bull neck)
Pseudomonas Exotoxin N (E F-2) Host cell death
aeruginosa
Shigella spp. Sh iga toxin ( ST) GI mucosal damage dysentery; ST also

-+
Inactivate 60S ribosome by enhances cytokine release, causing H U S

Enterohemorrhagic Shiga-like toxin removing aden ine from SLT enhances cytokine release, causing H US;
E. coli ( E HEC), (S LT) rRNA unl ike Shigella , EHEC does not i nvade host
including 0157:H7 cells
strai n
Increase fluid secreti o n
Enterotoxigenic Heat-labile Overactivates adenylate Watery diarrhea: labile in the Ai r (Adenylate

E . coli ( ETEC) toxin ( LT)a cyclase (t cAMP) - t C) cyclase), stable on the Ground (Guanylate
secretion in gut and H 2 0 cyclase) .
efflux
Heat-stable Overactivate guanylate
toxin ( ST) cyclase (t cGMP)
-+ ! resorption of NaCI
and H 2 0 in gut
Bacillus anthracis Edema factor M i m ics the adenylate Likely responsible for characteristic edematous
cyclase enzyme (t cAM P) borders of black eschar i n cutaneous anthrax
Vibrio cholerae Cholera toxin3 Overactivates adenylate Voluminous "rice-water" diarrhea
cyclase (t cAM P) by
permanently activating G5
-+ t cJ- secretion in gut
and H 2 0 efflux
In h i bit phagocytic a b ility
Bordetella pertussis Pertussis toxina Overactivates adenylate Whoopi ng cough: child coughs on expiration
cyclase (t cAM P) by and "whoops" on inspiration (toxin may
disabl ing Gi, impairing not actually be a cause of cough; can cause
phagocytosis to permit " 1 00-day cough " in adults)
survival of microbe
In h i bit release of n eurotra n s m itter
Clostridium tetani Tetanospasmin Muscle rigidity and " lock j aw"; toxi n prevents
release of inhibitory ( GABA and glycine)
Cleave SNARE neurotransm itters i n spinal cord
protein required for
Clostridium Botulinum toxin neurotransm itter release Flaccid paralysis, Aoppy baby; toxi n prevents
botulinum release of stimulatory (ACh) signals at
neuromuscular junctions -+Aaccid paralysis
3Toxin is an ADP ribosylating A-B toxin : B (binding) component binds to host cell surface receptor, enabling endocytosis; A
(active) component attaches ADP-ribosyl to disrupt host cell proteins.
M I C R O B I OLOGY M I C R O BIO L O G Y - B A SIC B A C TERIO L O G Y SECT I O N I I 1 25
Bugs with exotoxins (continued)

BACTERIA TOXI N M ECHANISM MANIFESTATION
Lyse cell m e m b r a n e s
Clostridium Alpha toxi n Phosphol ipase that degrades Degradation of phosphol ipid C -+ myonecrosis
perfringens tissue and cell membranes ( "gas gangrene") and hemolysis ( "double zone"
of hemolysis on blood agar)
Streptococcus Streptolysi n 0 Protein that degrades cell Lyses RB Cs; contributes to -hemolysis;
pyogenes membrane host antibodies against toxi n (ASO) used to
diagnose rheumatic fever (do not confuse
with i m mune complexes of poststreptococcal
glomerulonephritis)
Superantigen s causing s hock
Staphylococcus Toxic shock Bring MHC I I and TCR Toxic shock syndrom e : fever, rash , shock; other
aureus syndrome toxin in proxim ity to outside toxi n s cause scalded skin syndrome (exfoliative
(TSST-l) of antigen binding site toxin) and food poison ing (enterotoxin)
Streptococcus Exotoxin A to cause overwhelming Toxic shock syndrome : fever, rash , shock
pyogenes release of i FN-y and I L-Z
-+shock
Endotoxin A l ipopolysaccharide found in outer membrane ENDOTOXIN :

of gram-negative bacteria. Edema
Nitric oxide
Endotoxin
(especially lipid A) DIC /Death
I Outer membrane
I II
t
Activates complement
TN F-a
0-antigen
't 't eXtremely heat stable
C3a C5a Coagulation IL-l
.J, .J, cascade
Hypotension, Neutrophil .J, Neutrophi l chemotaxis
edema chemotaxis DIC
(Adapted, with permission, from Levinson W. Review of Medical Microbiology and Immunology, 1 2th ed. New York:
McGraw-Hill, 20 1 2: Fig. 7-4.)
Baderial growth curve

Lag phase Metabol ic activity without division.
Exponential/log phase Rapid cell d ivision. Penicillins and Stationary phase
cephalosporins act here as peptidoglycan is
being made.
Stationary phase Nutrient depletion slows growth . Spore

formation in some bacteria.
Exponential growth phase
Death Prolonged nutrient depletion and buildup of
waste products lead to death .
Time
1 26 SECTION I I MI CROB I O LOG Y MICROBIOLOGY-BASIC BACTERIOLOGY
Bacterial genetics
Transformation Abi l ity to take up naked DNA (i.e., from cell lysis) from environment (also known as
"competence" ) . A feature of many bacteria, especially S. pneumoniae, H. influenzae type B, and
Neisseria ( SHiN ) . Any DNA can be used. Adding deoxyribonuclease to environment will degrade
naked DNA in medium -+ no transformation seen.
Conjugation
F+ X F- P plasmid contains genes required for sex pilus and conjugati on. Bacteria without this plasmid a re
termed F-. Plasmid (dsDNA) is repl icated and transferred through pilus from P cell. No transfer
of chromosomal genes.
Hfr x F- P plasmid can become incorporated into bacterial chromosomal DNA, termed high-frequency
recombination ( H fr) cell. Repl ication of incorporated plasmid DNA may i nclude some flanking
chromosomal DNA. Transfer of plasm id and chromosomal genes.
Transposition Segment of DNA that can " jump" (excision and reintegration) from one location to another, can
transfer genes from plasmid to chromosome and vice versa. When excision occurs, may i nclude
some flanking chromosomal DNA, wh ich can be incorporated i nto a plasmid and transferred to
another bacterium.
Transduction
Gen e ralized A "packaging" event. Lytic phage infects bacterium, leading to cleavage of bacterial DNA. Parts
of bacterial chromosomal DNA may become packaged in viral capsid. Phage infects another
bacterium, transferring these genes.
Specialized An "excision" event. Lysogenic phage infects bacterium; viral DNA i ncorporates i nto bacterial
chromosome. When phage DNA is excised, flanking bacterial genes may be excised with it. DNA
is packaged i nto phage viral capsid and can infect another bacterium.
Lysogeny, specialized Genes for the following 5 bacterial toxins ABC DE

transduction encoded i n a lysogenic phage :
ShigA-l ike toxi n
Botulinum toxi n (certain strains)
Cholera toxin
D iphtheria toxi n
Erythrogenic toxin of Streptococcus
pyogenes
MI CRO B I O L O G Y MICRO BIO LO G Y - C LINIC A L B A CTERIO L O G Y SECT I O N I I 1 27
MICRO BIO L O G Y - C LINIC A L B A CTERIO L OGY
Gram-positive lab algorithm
I Nocardia !
S. pneumoniae
Capsu l e ( <) q u e l l u ng)
Optoc h i n sen sitive
Clostridium (anaerobe)
Corynebacterium Viridans streptococci
Listeria
(e.g., S. mutans)
Bacillus (aerobe) No capsu le
Mycobacterium (acid-fast) Optoch i n re si stant
Gro u p A
S.pyogenes
Catalase<) Catalase8 Bacitraci n sen sitive
(clu sters) (chains)
Complete
l3
Staphylococcus Streptococcus
1-; hemolysis Grou p B
0& (clear) (S. agalactiae)
'?.
oj..& Bacitracin resi stant

Grou p D
(Enterococcus)
Coagu lase8
Growth in bile and
Novobiocin sen sitive
S. epidermidis
y
-
6.5% NaCI
(E. faecalis)
Novobiocin resi stant
S. saprophyticus
Non ente rococcu s
Growth i n b i l e , not
Important pathogens are in bold type. 6.5% NaCI
Note: Enterococcus is either a- or y-hemolytic. (S. bovis)
Identification of gram-positive cocci

Staphylococci NOvobiocin -Saprophyticus is Resistant; On the office's staph retreat, there was
Epidermidis is Sen sitive. NO StRESs .
Streptococci Optoch in -Viridans is Resistant; Pnewnoniae is OVRPS (overpass) .
Sensitive.
Bacitracin -group B strep are Resistant; group B-BRAS.
A strep are Sensitive.
a-hemolytic baderia Form green ring around colon ies on blood agar. Include the following orga n i s m s :
Streptococcus pnewnoniae (catalase negative and optoch in sensitive)
Viridans streptococci (catalase negative and optoch i n resistant)

l 28 SECT I O N I I M I C R O B I O L O GY M I C R O B I O L O G Y - C LI N I C A L B A C TERIO L O G Y
P-hemolytic baderia Form clear area of hcmolysis on blood agar. Include the following organisms:
Staphylococcus aureus (catalase and coagulase positive)
Streptococcus {Jyogenes-group A strep (catalase negative and bacitracin sensitive)
Streptococcus agalactiae-group B strep (catalase negative and bacitracin resistant)
Listeria monocytogenes (tumbling motil ity, meningitis in newborns, unpasteurized m i lk)
Staphylococcus aureus Gram-positive cocci in clusters (J. Protein A TSST is a superantigen that binds to M HC II
fJ (virulence factor) binds Fc-lgG, inh ibiting and T-cell receptor, resulting i n polyclonal
complement fixation and phagocytosis. T-cell activation. Presents as fever, vom iti ng,
Causes: rash, desquamation, shock, end-organ failure.
Inflammatory disease-skin infections, S. aureus food poisoning is clue to ingestion of
organ abscesses, pneumonia preformed toxin.
Toxi n-mediated disease-toxic shock Causes acute bacterial endocard itis,
syndrome (TSST- 1 ) , scalded skin syndrome osteomyelitis.
(exfol iative toxin), rapid-onset food Staph make catalase because they have more
poisoning (enterotoxins) "staff." Bad staph (aureus) make coagulase and
M RSA (meth icill in-resistant S. aureus) toxins. Forms fibrin clot around self; can lead
infection-important cause of serious to abscess.
nosocom ial and community-acqu ired
infection s ; resistant to P-lactams because of
altered penicillin-bi nding protein
Staphylococcus Infects prosthetic devices and i ntravenous catheters by producing adherent biofilms. Component of
epidermidis normal skin flora; contaminates blood cultures.
Streptococcus Most common cause of: S. pnewn oniae MOPS are Most OPtoch in
pneumoniae Meningitis Sensitive.
Otitis media (in children) Pneumococcus i s associated with "rusty"
Pneumon ia sputum , sepsis in sickle cell anem ia and
I
Sinusitis splenectomy.
Lancet-shaped, gram-positive diplococci (J. No virulence without capsule.
Encapsulated. IgA protease.
I
, ,-. '
Viridans group Viriclans streptococci are a-hemolytic. They Sanguis blood . T here is lots of blood in
=
streptococci are normal flora of the oropharynx and cause the heart (endocarditis) . S. sanguis sticks to
dental caries (Streptococcus mutans) and damaged valves by making glycocalyx.
subacute bacterial endocard itis at damaged Viriclans group strep l ive in the mouth because
valves (S. sanguis) . Resistant to optoch in, they are not afraid of-the-chin (op-to-chin
differentiating them from S. pneumoniae, resistant) .
wh ich is a-hemolytic but is optoch in sensitive.
M I C R O B I O L O GY MIC R O BIO L O G Y - C LI N IC A L B A CTERIO L O G Y SECTION II 1 29
Streptococcus Causes : JN E S criteria to d i agnose rheumatic fever:

pyogenes (group A Pyogenic-pharyngitis, cellul itis, impetigo Joints - polyarthritis
streptococci) Toxigenic- scarlet fever, toxic shock-l ike - carditis
syndrome, necrotizing fasciitis Nodules (subcutaneous)
I mmunologi c - rheumatic fever, acute Erythema marginatum
glomerulonephritis Sydenham's chorea
Bacitracin sensitive. Antibodies to M protein Pharyngitis can result in rheumatic "phever"
enhance host defenses against S. pyogenes but and glomeru lonephritis.
can give rise to rheumatic fever. Impetigo more commonly precedes
ASO titer detects recent S. pyogenes infection. glomerulonephritis than pharyngitis.
Scarlet fever: scarlet rash sparing face,
strawberry (scarlet) tongue, scarlet throat
Streptococcus Bacitraci n res istant, -hemolytic, colon izes Group B for Babies !
agaladiae (group B vagina; causes pneumon ia, meningitis, and
streptococci) sepsis, mainly in babies.
Produces CAM P factor, which enlarges the
area of hemolysis formed by S. au reus. (Note :
CAM P stands for the authors of the test, not
cyclic AMP.) H ippurate test positive.
Screen pregnant women at 35-37 weeks.
Patients with positive culture receive
intrapartum penicillin prophylaxis.
Enterococci (group D Enterococci (Enterococcus faecalis and Enterococci , hardier than nonenterococcal
streptococci) E. faecium) are normal colon ic flora that group D, can grow in 6 . 5 % NaCl and bile (lab
are pen icillin G resistant and cause UTI, test) .
bil iary tract infections, and subacute Entero = intestine, faecalis = feces, strepto =
endocarditis. Lancefield group D includes the twisted (chains), coccus= berry.
enterococci and the nonenterococcal group
D streptococci . Lancefield grouping is based
on differences in the C carbohydrate on the
bacterial cell wal l . Variable hemolysis.
VRE (vancomycin-resistant enterococci) are an
important cause of nosocom ial infection .
Streptococcus bovis Colonizes the gut. Can cause bacteremia and Bovis in the blood = cancer in the colon .
(group D streptococci) subacute endocarditis in colon cancer patients.
1 30 SECT I O N I I MI CRO BIO L O G Y MICROBIOLOGY-CLINICAL BACTERIOLOGY
Corynebaderium Causes d iphtheria via exotoxin encoded by Coryne club shaped.

=
diphtheriae -prophage. Potent exotoxin inh ibits protein Black colon ies on cystine-tellur i te agar.
synthesis via ADP-ribosylation of EF-2 . ABCDEFG :
Symptoms include pseudomembranous ADP-ribosylation
pharyngitis (grayish-wh ite membrane) Beta-prophage
with lymphadenopathy, myocarditis, and Corynebacterium
arrhythmias. Diphtheria
Lab d iagnosis based on gram-positive rods with Elongation Factor 2
metachromatic (blue and reel) granules and Granules
Elek's test for toxin.
Toxoid vaccine prevents diphtheria.
Spores: bacterial Some bacteria can form spores at the end of the Spore-forming gram-positive bacteria found
stationary phase when nutrients are lim ited. in soi l : Bacillus anthracis, Clostridium
Spores are highly resistant to heat and perfringens, C. tetani.
chem icals. H ave cl ipicol inic acid in thei r core. Other spore formers include B. cereus, C.
Have no metabol ic activity. Must autoclave to botulinum, Coxiella burnetii.
kill spores (as is clone to surgical equipment)
by steaming at 1 2 lC for 1 5 m inutes.
Clostridia (with Gram-positive, spore-forming, obl igate anaerobic bacilli.

exotoxins)
C. tetani Produces tetanospasm in, an exotoxin causing Tetanus is tetanic paralysis (blocks glycine and
tetanus. Tetanus toxin (and botulinum toxin) GABA release [inh ibitory neurotransmitters] )
are proteases that cleave releasing proteins for from Renshaw cells in spinal cord . Causes
neurotransmitters. spastic paralysis, trismus (lockjaw) , and risus
sarclonicus.
C. botulinum Produces a preformed , heat-labile toxin that Botulinum is from bad bottles of food and honey
inh ibits ACh release at the neuromuscular (causes a flaccid paralysis) .
j unction, causing botulism. In adults, disease
is caused by ingestion of preformed toxin. In
babies, ingestion of spores in honey causes
disease (floppy baby syndrome) .
C. perfringens Produces a toxin ( " lecithinase," a Perfringens perforates a gangrenous leg.
phosphol ipase) that can cause myonecrosis
(gas gangrene) and hemolysis.
C. difficile Produces 2 toxins. Toxin A, enterotoxin, binds Diffzcile causes diarrhea . Treatment:
to the brush border of the gut. Toxin B, metron idazole or oral vancomycin.
cytotoxi n , destroys the cytoskeletal structure
of enterocytes, causing pseudomembranous
col itis. Often 2 to antibiotic use, especially
clinclamycin or ampicill i n. Diagnosed by
detection of one or both toxins in stool .
MI C R OB I OLO G Y MIC RO BIOLOGY- C LINICAL BACTERIO LOGY S ECTION I I 131
Anthrax Caused by Bacillus anthracis, a gram-positive, spore-form ing rod that produces anthrax tox i n . The
only bacterium with a polypeptide capsule (contains D-glutamate) .
Cutaneous anthrax Contact black eschar (pa inless ulcer) ; can
--+ Black skin lesions - black eschar (necrosis)
progress to bacteremia and death . surrounded by edematous ring. Caused by
lethal factor and edema factor.
Pulmonary anthrax Inhalation of spores - flu-like symptoms Woolsorters' disease - inhalation of spores from
that rapidly progress to fever, pul monary contami nated wool .
hemorrhage, med iastinitis, and shock.
Bacillus cereus Causes food poisoning. Spores survive cooking Reheated rice syndrome.
rice. Keeping rice warm results in germination
of spores and enterotoxin formation.
Emetic type usually seen with rice and pasta.
Nausea and vom iting with in l-5 hour s .
Caused b y cereulide, a preformed toxin.
Diarrheal type causes watery, nonbloody
diarrhea and GI pain in 8-1 8 hours.
Listeria Facultative intracellular m icrobe; acqu ired by ingestion of unpasteuri zed milk/cheese and deli
monocytogenes meats or by vaginal transm ission dur i n g birth. Form "acti n rockets" by wh ich they move from cell
to cel l . Characteristic tumbl ing motility.
Can cause amn ionitis, septicem ia, and spontaneous abortion in pregnant women ; granulomatosis
infantiseptica ; neonatal meningitis ; meningitis in immunocompro m i sed patients ; mild
gastroenteritis in healthy individuals. Treatment: gastroenteritis usually self-l i m ited ; ampicillin in
infants, immunocomprom ised patients, and the elderly in empirical treatment of meni ngitis.
Adinomyces vs. Both form long, branching filaments resembl ing fungi.
Nocardia Actinomyces Nocardia
Gram-positive anaerobe Gram-positive aerobe

Not acid fast Acid fast
Normal oral flora Found in soil
Causes oral /facial abscesses that drain th rough Causes pulmonary infections in
sinus tracts, forms yellow "sulfur granules" immunocompromised and cutaneous infections
after traum a in immunocompetent
Treat with penicillin Treat with sulfona m ides
1 32 SECTIO N I I M I C R O B I O LO G Y M I C R O B I O LO G Y - C LI N IC A L B A C TE R I O L O G Y
1o and 2 tuberculosis
r Infection with Mycobacterium tuberculosis PPD+ if current infection, past exposure, or
BCG vacci nated.
Nonimmune host Partially immune hypersensitized host
(usually child)
PPD- i f no infection or anergic (steroids,
(usually adult)
l l Reinfection
mal nutrition, immunocompromise) and in
sarcoidosis.
I Secondary tuberculosis j -.-----,
Fibrocaseous
cavitary lesion
(} (usually !:!.per
lobes) t]
J
Hilar nodes
Reactivation
Ghon focus Ghon
tuberculosis
(usually in mid complex
of the lungs
zone of lung)
Heals by fibrosis
t
Progressive
lung disease
Severe bacteremia
1
Preallergic lymphatic or
hematogenou dissemination
!
(HIV, malnutrition)
;
Immunity and
hypers nsitivity
Miliary
tuberculosis
Dormant tubercle bacilli
Tuberculin positive Death (rare) Death in several organs

Extrapulmonary tuberculosis Reactivation in --
CNS (parenchymal tuberculoma or meningitis) adult life caseating granuloma. With multinucleated Langhan's
Vertebral body (Pott's disease) 1+------' giant cell (arrow).li!l
Lymphadenitis Renal Gl
Mycobacteria Mycobacterium tuberculosis (TB , often resistant TB symptoms include fever, n ight sweats,
to multiple dru gs) . weight loss, and hemoptysis.
M. kansasii (pul monary TB-l ike symptoms) . Cord factor in virulent strains inhibits
M. avium-intracellulare (causes cl issem i nated, macrophage maturation and induces release of
non-TB d isease i n AIDS ; often resistant to TNF-a. Sulfatides (surface glycolipids) inh ibit
multiple drugs) . Prophylactic treatment with phagolysosomal fusion.
azithromycin.
All mycobacteria are acid-fast organ isms rJ.
M I CRO B I O L O GY MIC R O BIO LO G Y - C LINICAL BACT E RIO L O G Y SECT I O N I I 1 33
Leprosy (Hansen's Caused by Mycobacterium leprae, an acid-fast

disease) bacillus that l ikes cool temperatures (infects
skin and superficial nerves-"glove and
stocki ng" loss of sensation) and cannot be
grown i n vitro. Reservoir in United States:
armadillos.
Nasal
collapse Hansen's disease has 2 forms :
Lepromatous -presents diffusely over skin
Lum py
earlobe
rn and i s communicable; characterized by
low cell-mediated im munity with a humoral
"Leonine facies" of
Th 2 response.
lepromatous leprosy
Tu bercu loid -l i m ited to a few hypoesthetic,
hairless skin plaques; characterized by h igh

cell-mediated immunity with a largely Th 1 -
type i m mune response.
Multidrug therapy consisting of dapsone and
rifampin for 6 months for tuberculoid form
and dapsone, rifampin, and clofazim ine for
2-5 years for lepromatous form.
Gram-negative lab algorithm
I Vibrio cholerae I
Diplococci "Coccoid" rods
Neisseria meningitidis, Haemophilus influenzae
N. gonorrhoeae ( req u i res factors V and X)
Pasteurella-animal bites
Brucella-brucellosis
Bordetella pertussis
Maltose Maltose
Lactose Lactose
fermenter nonfermenter
fermenter nonfermenter
N.meningitidis N.gonorrhoeae
Fast Slow
fermenter fermenter
Klebsiella Citrobacter
E. coli Serratia
Enterobacter Othe rs
OxidaseG
Oxidase @
Shigella
Pseudomonas
Salmonella
H. pylori
Proteus
Important pathogens are in bold type.
1 34 SECTI O N II MI CRO BIO L O G Y MICROBIOLOGY-CLINICAL BACTERIOLOGY
Lactose-fermenting Grow pink colon ies on MacConkey's agar. Lactose is KEE .

enteric bacteria Examples i nclude Citrobacter, Klebsiella, Test with MacCon KEE'S agar.
E . coli, Enterobacter, and Serratia. E. coli EMB agar-l actose fe rmenters grow a s purple/black
produces -gal actosidase, which breaks down colon i e s . E . coli grows purple colonies with a green
lactose into glucose and galactose. sheen.
Penicillin and Gram-negative bacilli are resistant to penicillin G but may be susceptible to penicillin derivatives
gram-negative bugs such as ampicil l i n and amoxicillin. The gram-negative outer membrane layer inh ibits entry of
penicillin G and vancomycin.
Neisseria Gram-negative d iplococci . Both ferment MeninGococci ferment Maltose and Glucose .
glucose and produce IgA proteases. Gonococci ferment Glucose.
N. gonorrhoeae within polymorphonuclear
leukocytes rJ.
Gonococci Meningococci
No polysaccharide capsule Polysaccharide capsule
No maltose fermentation Maltose fermentation
No vaccine (clue to rapid antigenic variation of Vaccine (none for type B )
pilus proteins)
Sexually transm itted Respiratory and oral secretions
Causes gonorrhea, septic arthritis, neonatal Causes meningococcemi a and meningitis,
conjunctivitis, PID, and Fitz- Hugh-Curtis Waterhouse-Friclerichsen syndrome
syndrome
Rifampin, ciproAoxaci n , or ceftriaxone
prophylaxis in close contacts
Treatment: ceftriaxone + (azithromycin Treatment: ceftriaxone or penicillin G
or doxycycline) for possible chlamydia
co infection
Haemophilus HaEMOPhilus causes Epiglottitis ( "cherry When a ch ild has "Au," mom goes to five (V)
influenzae reel " in children) , Meningitis, Otitis media, and clime (X) store to buy some chocolate.
and Pneumonia. Small gram-negative Vaccine contains type B capsular polysaccharide
(coccobacillary) rod . Aerosol transmission. (polyribosyl ribitol phosphate) conjugated
Most invasive disease caused by capsular to d iphtheria toxoid or other protein. Given
type B. Nontypeable strains cause mucosal between 2 and 18 months of age.
infections (otitis media, conjunctivitis, Does not cause the Au (influenza virus does) .
bronch itis) . Produces IgA protease. Culture
on chocolate agar requires factors V (NAD+)
and X ( hematin) for growth ; can also be grown
with S. aureus, which provides factor V.
Treat meningitis with ceftriaxone. Rifampin
prophylaxis in close contacts.
M I C R OB I OLO G Y M I C R O B I O L O G Y - C LIN I CAL BACTERIO L O G Y SECT I O N I I 1 35
Legionella severe pneumon ia,

Legi o n n a i res' d isease = Think of a French legionnaire (soldier) with
pneumophila fever, GI and CNS symptoms. his silver helmet, sitting around a campfire
Po ntiac fever = mild Au-like syndrome. (charcoal) with hi s iron dagger- he is no sissy
Gram-negative rod. Gram stains poorly-use (cysteine).
silver stain. Grow on charcoal yeast extract Labs show hyponatremia.
culture with iron and cysteine. Detected
clinically by presence of antigen in urine.
Aerosol transm ission from environmental
water source habitat. o person-to-person
transmission. Treatment: macrol ide or
quinolone.
Pseudomonas PSE UDOmonas is associated with wound Aeruginosa - aerobic. Think water connection
aeruginosa and burn infections, Pneumonia (especially and blue-green pigment.
in cystic fibrosis), Sepsis (black lesions on Think Pseudomonas in burn victi ms.
ski n) , External otitis (swim mer's ear) , UTI , Chronic pneumonia in C F patients is associated
Drug use and Diabetic Osteomyelitis, and with biofi l m .
hot tub foll iculitis. Mal ignant otitis externa
in diabetics. Aerobic gram-negative rod.
Non-lactose fermenting, oxidase positive.
Produces pyocyanin (blue-green) pigment;
has a grape-like odor. Water source. Produces
endotoxin (fever, shock) and exotoxin A
(inactivates E F-2 ) .
Treatment: am inoglycoside plus extended
spectrum penicillin (e.g., piperacillin,
ticarcillin).
E. coli E. coli virulence factors : fimbriae- cystitis a n d pyelonephriti s ; K capsule-pneumonia, neonatal

meningiti s ; LPS endotoxin- septic shock .
STRAIN TOXI N AND M ECHANISM PRESENTATION
E IEC M icrobe i nvades intestinal mucosa and Invasive ; dysentery.

causes necrosis and inflam mation. No toxins
produced. Clin ical manifestations similar to
Shigella .
ETEC Labile toxi n /stable toxin. No inflammation or Traveler's diarrhea (watery) .
invasion .
EPEC No toxin produced. Adheres to apical surface, Diarrhea usually i n children (Ped iatrics) .
flattens villi, prevents absorption.
EH EC O l 57: H 7 is the most common serotype. Produces Dysentery (toxin alone causes necrosis and
Shiga-l ike toxin and Hemolytic-uremic inflam mation ) .
syndrome (triad of anem ia, th rombocytopenia, D o e s n o t ferment sorbitol (d istingu ishes it from
and acute renal failure) . other E. coli) .
Endothel ium swells and narrows lumen , leading
to mechanical hemolysis and reduced renal
blood flow; damaged endothelium consumes
platelets.
1 36 SECTI O N II MI CRO B I O L O G Y MIC R O BIO LOGY - C LINICAL BACTERIO LOGY
Klebsiella An i ntestinal flora that causes lobar pneumonia 4 A's :

in alcoholics and diabetics when aspirated . Aspiration pneumonia
Very mucoid colonies caused by abundant Abscess i n lungs and liver
polysaccharide capsule. Red "currant jelly" Alcohol ics
sputum. d i-A-betics
Also cause of nosocomial UTis.
Salmonella vs. Salmonella Shigella

Shigella H ave flagella (salmon swim) No flagel la
Can disseminate hematogenously Cell to cell transm ission ; no hematogenous
spread
H ave many animal reservoirs Only reservoirs are humans and primates
Pro duce hydrogen sulfide Does not produce hyd rogen sulfide
Antibiotics may prolong symptoms Antibiotics prolong excretion of organism in
feces
I nvades intestinal mucosa and causes a I nvades intestinal mucosa and causes PMN
monocytic response infiltration
Can cause bloody diarrhea Often causes bloody diarrhea
Does not ferment lactose Does not ferment lactose
Salmonella typhi Causes typhoid fever. Found only in humans. Characterized by rose spots on the abdomen, fever,
headache, and d iarrhea. Can remain in gallbladder and cause a carrier state.
Campylobader jejuni Major cause of bloody diarrhea, especially i n children. Fecal-oral transmission through foods
such as poultry, meat, unpasteurized milk. Comma or S-shaped, oxidase positive, grows at 42 C
( "Campylobacter l ikes the hot campfire" ) . Common antecedent to Guillain-Barre syndrome and
reactive arth ritis.
Vibrio cholerae Produces profuse rice-water diarrhea via toxin that permanently activates G 5 , t cAM P. Comma
shaped, oxidase positive, grows in alkaline media. Endemic to developing countries. Prompt oral
rehydration is necessary.
Yersinia enterocolitica Usually transmitted from pet feces (e.g., puppies), contaminated milk, or pork. Causes mesenteric
adenitis that can mimic Crohn's or append icitis.
M I C R O B I O L O GY M I C R O BIO LO G Y - C L I N IC A L B A CTERIO L O G Y SECTION II 1 37
Helicoboder pylori Causes gastritis and up to 90% of duodenal ulcers. Risk factor for peptic ulcer, gastric
adenocarcinoma, and lymphoma. Curved gram-negative rod. Urease positive (can use urea breath
test for d iagnosis) . Creates alkaline environment. Most common in itial treatment is triple therapy:
proton pump inh ibitor; clarithromycin; amoxicillin or metron idazole.
Spirochetes The spirochetes are spiral-shaped bacteria with BLT.

axial filaments and include Borrelia (big size), B i s Big.
Leptospira, and Treponema. Only Borrelia can
be visualized using anil ine dyes (Wright's or
Giemsa stain) in l ight m icroscopy. Treponema
is visualized by dark-field m icroscopy.
Leptospira interrogons Found in water contam inated with animal urine, causes leptospirosi s : flu-l ike symptoms, jaundice,
photophobia with conjunctivitis. Prevalent among surfers and i n tropics (i .e., Hawa i i ) .
Weil's disease (icterohemorrhagic leptospirosis) - severe form with jaundice and azotemia from
l iver and kidney dysfunction ; fever, hemorrhage, and anemia.
Lyme disease Caused by Borrelia burgdorferi, which is FAKE a Key Lyme pie:
transmitted by the tick Ixodes (also vector for Facial nerve palsy (typically bilateral)
Babesia ) . Natural reservoir is the mouse. Arthritis
M ice are i mportant to tick life cycle. Kardiac block
Common in northeastern Un ited States. Erythema m igrans
Treatment: doxycycline, ceftriaxone.
3 stages of Lyme d isease :
Stage ! - erythema chron icum migrans
(expanding "bull's eye" red rash with central

clearing) , flu-l ike symptoms.
Stage 2 - neurologic (facial nerve palsy) and
cardiac (AV nodal block) manifestations .

Stage 3 - musculoskeletal (chronic
monoarthritis and m igratory polyarthritis),

neurological (encephalopathy and
polyneuropathy) , and cutaneous
manifestations.
1 38 SECT I O N I I M I C RO B I OLO G Y MICROBIOLOGY-CLINICAL BACTERIOLOGY
Syphilis Caused by spirochete Treponema pallidum. Treatment: pen icillin G.

1 syphilis Localized d isease presenting with painless
chancre [l Screen with VORL and confirm
diagnosis with FTA-ABS.
r syphilis Dissemi nated disease with constitutional
.B
symptoms, maculopapular rash (palms and
soles), condylomata lata. Treponemes are
;
present in chancres of 1 o and condylomata lata
of zo syph ilis and may be directly visual ized
through clark-field m icroscopy (I).
* Screen with VORL and confirm diagnosis with
FTA-ABS.
Secondary syph ilis = Systemic.
3 syphilis Gummas (chronic granulomas), aortitis (vasa
vasorum destruction) , neurosyph ilis (tabes
dorsal is), Argyl l Robertson pupi l .
Signs : broad-based ataxia, positive Romberg,
Charcot joint, stroke without hypertension.
Test spinal fluid with VORL.
Congenital syphilis Saber shins, saddle nose, C VI I I deafness,
Hutchinson's teeth, mulberry molars.
Early prevention is key, as placental
transmission typically occurs after first
trimester.
Argyll Robertson pupil Argyll Robertson pupil constricts with "Prostitute's pupil " -accommodates but does not
accommodation but is not reactive to light. react.
Associated with 3 syph ilis.
V D R L false positives VORL detects nonspecific antibody that reacts VORL :

with beef card iol ipin. Used for diagnosis of Vi ru ses (mono, hepatitis)
syph ilis, but many false positives, including D rugs
viral infection (mononucleosis, hepatitis) , Rheumatic fever
some drugs, rheumatic fever, SLE , and Lupus and leprosy
leprosy.
Jarisch-Herxheimer Flu-l ike syndrome immediately after antibiotics are started- due to killed bacteria releasing
readion pyrogens .
M IC R O B I O LOGY MIC R O BIO L O G Y - C LINIC A L B A CT E R I O LO G Y SEC T I O N I I 1 39
Zoonotic baderia Zoonosis: Infectious d isease transmitted between animals and humans.
SPECIES DISEASE TRANSMISSION A N D SOURCE
Bartonella spp. Cat scratch disease Cat scratch

Borrelia burgdorferi Lyme d isease Ixodes ticks ( l ive on deer and m ice)
Borrelia recurrentis Recurrent fever Louse (recurrent because of variable surface
antigens)
Brucella spp. Brucellosis/undulant fever Unpasteurized dairy
Campylobacter Bloody d iarrhea Puppies, livestock (fecal-oral , ingestion of
u ndercooked meat)
Chlamydophila Psittacosis Parrots, other birds
psittaci
Coxiella burnetii Q fever Aerosols of cattle/sheep amniotic fluid

Ehrlichia chaffeensis Ehrlichiosis Lone Star tick
Francisella tularensis Tularemia Ticks, rabbits, deer fly
Leptospira spp. Leptospirosis Animal urine
Mycobacterium leprae Leprosy Armad illos and humans with lepromatous
leprosy
Pasteurella multocida Cellulitis, osteomyel itis Animal bite, cats, dogs
Rickettsia prowazekii Epidemic typhus Louse
Rickettsia rickettsii Rocky Mountain spotted fever Dermacentor tick bite
Rickettsia typhi Endemic typhus Fleas
Yersinia pestis Plague Fleas (rats and prairie clogs are reservoirs)
Gardnerella vagina/is A pleomorph ic, gram-variable rod that causes I don't have a clue why I smell fish i n the vagina
vaginosis presenting as a gray vaginal garden !
d ischarge with a fishy smel l ; nonpainful.
Associated with sexual activity, but not an
STD. Bacterial vaginosis is characterized by
overgrowth of certa in bacteria i n vagina. Clue
cells, or vaginal epithelial cells covered with
bacteria, are visible under the m icroscope
(arrow) f.J.
Treatment: metronidazole.
1 40 SEC T I O N I I M I C RO B I O LO G Y MIC R O BIO LO G Y - CLINIC AL B A C TERIOLO G Y
Rickettsial diseases Treatment for all : doxycycline.

and vedor-bome
illness
Rash Rocky Mountain spotted fever (tick) -Rickettsia Classic triad -headache, fever, rash (vasculitis).
rickettsii. Broadly d istributed in US (in spite "Rickettsi i on the wRists, Typhus on the
of name) . Rash typically starts at wrists and Trunk."
ankles and then spreads to trunk, palms, and Palm and sole rash is seen in Coxsackieviru s
soles. Rickettsiae are obligate intracellular A infection (hand, foot, and mouth disease) ,
organisms that need CoA and NAD +. Rocky Mountain spotted fever, and secondary
Typhu s : Syph il is (you drive CARS using your palms
Endemic (fleas) -R. typhi. and soles) .
Epidemic (human body
louse) -R. prowazekii. Rash starts centrally

and spreads out, sparing palms and soles.
No rash Ehrlichiosis (tick) -Ehrlichia. Monocytes with
morula (berry-l ike inclusions) in cytoplasm.
Anaplasmosis (tick) -Anaplasma. Granulocytes
with morula i n cytoplasm .
Q fever (tick feces and cattle placenta release Q fever is Queer because it has no rash or vector
spores that are inhaled as aerosols) - Coxiella and its causative organ ism can survive outside
bumetii. No arthropod vector. Presents as i n its endospore form. Not i n the Rickettsia
pneumoma. genus, but closely related.
M I C R O B I O LO G Y MIC R O BIO LO G Y - C LI NIC A L B A C T E RIO L O G Y SECTION II 141
Chlamydiae Chlamydiae cannot make their own ATP. They Chlamys = cloak (intracellular) .
are obl igate i ntracellular organisms that cause Chla mydophila psittaci-notable for an avian
mucosal infections. 2 forms: reservOir.
Elementary body (small , dense) Lab d iagnosi s: cytoplasmic inclusions seen on
i s " Enfectious" and Enters cell via Giemsa or fluorescent antibody-stained smear.
Endocytosis. The chlamydia] cell wal l is unusual in that it
Reticulate body Repl icates i n cell by fission ; lacks m uram ic acid.
form seen on tissue culture.
Chlamydia trachomatis causes reactive arthritis,
conjunctivitis, nongonococcal urethritis, and
PID.
C. pneumoniae and C. psittaci cause atypical
pneumonia; transm itted by aerosol .
Treatment: azithromycin (favored because one
time treatment) or doxycycline.
Attach ment and entry

of elementary body
Cell nucleus
Formation of
reticulate body
M u ltipl ication of
Elementary
Reorganization
bodies
of reticulate bod ies
into elementary bodies
Chlamydia trachomatis serotypes

Types A, B, and C Chronic infection, cause blindness clue to ABC = Africa/Bl indness/Ch ronic infection .
fol l icular conjunctivitis in Africa.
Types 0-K Urethritis/Fl O, ectopic pregnancy, neonatal D-K = everything else.
pneumonia (staccato cough) , or neonatal Neonatal d isease can be acqu i red during
conjunctivitis. passage through infected birth canal.
Types Ll , Ll, and L3 Lymphogranuloma venereum.
1 42 SECTI O N II MI C R O B I O L O G Y MIC RO BIOLO G Y - C LINIC A L B A C TE RIO LO G Y
Mycoplasma Classic cause of atypical "walking" pneumon ia N o cell wall . N o t seen o n Gram stain.
pneumoniae (insidious onset, headache, nonproductive Bacterial membrane contains sterols for stabil ity.
cough, diffuse interstitial infiltrate) . X-ray Mycoplasmal pneumonia is more common in
looks worse than patient. H igh titer of cold patients < 30 years of age.
agglutinins (IgM ) , wh ich can agglutinate or Frequent outbreaks i n mi l itary recruits and
lyse RBCs. Grown on Eaton's agar. pnsons.
Treatment: macrol ide or fluoroquinolone
(penicil l i n ineffective since Mycoplasma have
no cell wal l ) .
M I CRO B I O L O G Y MIC R O BIO L OGY- MYC O LOGY SECT I O N I I 14 3
MIC R O BIO L OGY- MYC O L OGY
Systemic mycoses All of the following can cause pneumonia and can d isseminate. All arc caused by d imorphic
fungi: cold (20C ) = mold; heat (37C) = yeast. The only exception is coccidioidomycosis, wh ich
is a spherule (not yeast) in tissue. Treatment: fluconazole or itraconazole for local infection ;
amphotericin B for systemic infection. Systemic mycoses can m im i c TB (granuloma formation),
except, unl ike TB, have no person-person transm ission .
DISEASE ENDEMIC lOCATION AND PATHOlOGIC FEATURES N OTES
Histoplasmosis M i ssissippi and Ohio River valleys. Causes H i sto h ides (with in macrophages). Bird or bat
pneumoma. droppings.
Macrophage filled with HistofJlasma (smal ler
than RBC) fJ.
States east of M ississippi R iver and Central Blasto buds (broadly) .

America. Causes inflammatory lung disease
and can d issem inate to skin and bone. Forms
granulomatous nodules.
Broad-base budd ing (same size as RBC) [J.
Coccidioidomycosis Southwestern United States, California. Causes C occidio crowds.

pneumon ia and meningitis; can disseminate San Joaqu in Valley or desert (desert bu mps)
to bone and skin. Case rate t after earthquakes "valley fever."
(spores in dust are thrown up in the air and
become spherules in lungs) .
Spherule fi lled with endospores (much larger
than RBC) [!1.
Paracoccidioidomycosis Latin America. "Capta in's wheel " appearance.

'I Budd ing yeast with "captain's wheel " formation Paracoccidio parasails with the captain's wheel
(much larger than RBC) [!]. all the way to Latin America .
\ 44 S E CTIO N II M I C R O B I O LOGY M I C R O B I O LO G Y - MY C O L O G Y
Cutaneous mycoses
Tinea versicolor Caused b y Malassezia fmfur. Degradation of lipids produces acids that damage melanocytes and
cause hypopigmented and/or hyperpigmented patches. Occurs i n hot, humid weather.
Treatment: topical m iconazole, selenium sulfide ( Selsun) . " Spaghetti and meatba l l " appearance on
KOH prep rJ.
Other ti neae Includes tinea ped i s (foot) , tinea cruris (groin ), tinea corpori s (ringworm, on body) , tinea capitis
(head, scalp), tinea unguium (onychomycosis, on fingernails).
Pruritic lesions with central clearing resembl ing a ring, caused by dermatophytes (Microspontm,
Trichophyton, and Epidermophyton) . See mold hyphae in KOH prep, not d i morphic.
M I C R O B I O LO G Y M I C R O B I O LO G Y- M Y C O LO G Y SECTI O N I I 1 45
Opportunistic fungal i nfections

Candido olbicons rJ alba= white.
Systemic or superficial fungal infection.
Oral and esophageal thrush in
i m munocomprom ised (neonates, steroids,
diabetes, A I D S ) , vulvovaginitis (diabetes, use
of antibiotics ) , diaper rash, endocarditis in IV
drug users, disseminated cand idiasis (to any
organ), chronic mucocutaneous candidiasis.
Treatment: topical azole for vaginal ; fluconazole
or caspofungin for oral/esophageal ; Candido olbicons. Dimorphic yeast Pseudohyphae and
budding yeasts at 2oc (left). EI Germ tubes at 3 rc
fluconazole, amphotericin B, or caspofungin (right).D
for systemic.
Aspergillus I nvasive aspergillosis, especially in
fumigotus [l] i m munocompromised and those with chronic
granulomatous disease.
Allergic bronchopulmonary aspergillosis
(ABPA) : with asthma or CF.
Aspergillomas in lung cavities, especially after
TB infection .
Some species of Aspergillus produce aflatoxins,
which are associated with HCC.
Think "A:.' for Acute Angles in Aspergillus. Not Aspergillus fumigatus. Septate hyphae that branch
at 45 angle (left).li!f Conidiophore with radiat1ng chains of
d imorphic. spores (right).D
Cryptococcus Cryptococcal meningitis, cryptococcosis.

neoformons Heavily encapsulated yeast. Not dimorph ic.
Found in soil, pigeon droppings. Acquired
through inhalation with hematogenous
d issemination to meninges. Culture on
Sabouraud's agar. Stains with India ink. Latex
agglutination test detects polysaccharide
capsular antigen and is more specific. " Soap
bubble" lesions in brain.
Cryptococcus neofonnons. 5- 1 0 m yeasts with wide
capsular halos and unequal budding 1n lnd1a mk sta1n D
Mucor [!] and Mucormycosis. Disease mostly in ketoacidotic

Rhizopus spp. diabetic and leukemic patients. Fungi
prol iferate in blood vessel walls when
there is excess ketone and glucose,
penetrate cribriform plate, and enter brain.
Rhi nocerebral, frontal lobe abscesses.
Headache, facial pain, black necrotic eschar
on face; may have cranial nerve involvement.
Mucor. Irregular, broad, nonseptate hyphae branch1ng at

wide angles (arrows). a
1 46 SECT I O N I I MI CRO B I O L O G Y MIC R O BIO LO G Y - MY C O L O G Y
Pneumocystis jirovecii Causes Pneumocystis pneumon ia (PCP) , a diffuse interstitial pneumonia. Yeast (originally
classified as protozoan) . Inhaled. Most infections are asymptomatic. Immunosuppression (e.g.,
AIDS) predisposes to d isease. Diffuse, bilateral CXR appearance. Diagnosed by lung biopsy or
l avage. D isc-shaped yeast forms on methenamine silver stain of lung tissue f:l
Treatment: TMP-SMX, pentamidine, dapsone. Start prophylaxis when CD4 drops < 200 cel ls/mm 3
in H IV patients.
Sporothrix schenckii Sporotrichosis. D imorphic, cigar-shaped bmlcling yeast that lives on vegetation rJ. When spores
are traumatically introduced into the skin, typically by a thorn ( "rose gardener's" disease), causes
local pustule or ulcer with nodules along draining lymphatics (ascending lymphangitis) . Little
systemic illness.
Treatment: itraconazole or potassium iodide.
" Plant a rose in the pot."
M I C R OB I O L O G Y MIC R O BI O L O G Y - P A R A S IT O L O G Y SECT I O N I I 1 47
MIC R O BIO L O G Y - PA R A SITO L O G Y
Protozoa-GI infections
ORGANISM D ISEASE TRANSMISSION D IAGNOSIS TREATMENT
Giardia Iamblia Giardiasis: bloating, flatulence, Cysts in water Trophozoites rn or Metronidazole

fou l-smel l ing, fatty diarrhea cysts (arrow) m in
(often seen in campers/hikers) - stool
think fat-r i ch Ghirardelli
chocolates for fatty stools of
Giardia
Entamoeba Amebiasi s : bloody diarrhea Cysts in water Serology and/or Metron idazole ;
histolytica (dysentery) , l iver abscess trophozoites (with iodoqui nol for
( "anchovy paste" exudate), RBCs in the asymptomatic cyst
RUQ pain ( h istology shows cytoplasm) or passers
flask-shaped ulcer if submucosal cysts (with multiple
abscess of colon ruptu res) nuclei) I!] i n stool
Cryptosporidium Severe diarrhea in AIDS Cysts in water Cysts on acid-fast Prevention ( by

Mild d isease (watery d iarrhea) in stain I] fi l tering city
nonimmunocomprom ised water suppl ies);
n itazoxanide in
i mmunocompetent
hosts
1 48 SECT I O N I I M I C R O B I O L O GY MIC R O BIO L O G Y - PA R A SITO L O G Y
Protozoa-eN S infedions
ORGANISM DISEASE TRANSMISSION DIAGNOSIS TREATMENT
Toxoplasma Brain abscess i n H I V (seen as Cysts in meat or Serology, biopsy rJ Sulfadiazine +
gondii ring-enhancing brain lesions cat feces; crosses pyrimetham ine
on CT/M R I ) ; congenital placenta (pregnant
toxoplasmosis = "classic triad " of women should
chorioretin itis, hydrocephalus, avoid cats)
and intracranial calci fications
Noeglerio fowleri Rapidly fatal meningoencephalitis Swimming in Amoebas i n spinal Amphotericin has
freshwater lakes fluid m been effective for a
(think Nalgene few survivors
bottle filled
with freshwater
containing
Naegleria) ; enters
via cribriform plate
Trypanosoma African sleeping sickness : Tsetse fly, a painful Blood smear n Surami n for blood
brucei enlarged lymph nodes, recurring bite borne d i sease or
T. gambiense fever (clue to antigenic variation) , melarsoprol for
T. rhodesiense somnolence, coma CNS penetration
( " it sure i s nice
to go to sleep";
melaton i n helps
with sleep)
M I C R O B I O LOGY MIC R O BIO L O G Y - PARA S IT O L O G Y SECT I O N I I 1 49
Protozoa-Hematologic infections
Plasmodium Malaria : fever, headache, anem ia, Mosqu ito Blood smear, Begin with
P. vivaxjovale splenomegaly (Anopheles) trophozoite ring chloroquine, which
P. falciparum P. vivax/ovale - 48-hr cycle (tertian ; form fJ, RBC blocks Plasmodium
P. ma/ariae includes fever on first day and schizont with heme polymerase ;
third clay, thus fevers are actually merozoites rn if resistant, use
48 hr apart) ; dormant form mefloquine
( hypnozoite) i n l iver I f l i fe-threatening,
P. falc iparum - severe ; irregular use intravenous
fever patterns; parasitized RBCs quinidine (test for
occlude capillaries i n brain G6PD deficiency)
(cerebral malaria) , kidneys, lungs Vivaxlovale - add
P. malariae-72-hr cycle (quartan) primaquine for
hypnozoite (test for
G6PD deficiency)
Babesia Babesiosis: fever and hemolytic Ixodes tick (same as Blood smear, ring Atovaquone
anem ia; predom inantly in Borrelia burgdorferi form m, "Maltese + azithromycin
northeastern Un ited States; of Lyme disease; cross" m; PCR
asplenia t risk of severe disease may often coinfect
humans)
1 50 SECTION II MI CROB I O L O G Y MICRO BIOLO G Y - PARASITOLO G Y
Protozoa-Others
V isceral i nfectio n s
Trypanosoma Chagas' d isease : d ilated Reduviid bug Blood smear fJ Nifu rtimox
cruzi cardiomyopathy, megacolon, ("kissing bug" ) , a
megaesophagus; predom inantly painless bite (much
in South America like a kiss)
Leishmania Visceral leishmaniasis Sandfly Macrophages Sodium

donovani (kala-azar) : spiking fevers, containing stibogluconate
hepatosplenomegaly, amastigotes rn
pancytopenia
STDs
Trichomonas Vaginiti s : foul-smell ing, greenish Sexual (cannot exist Trophozoites Metron idazole for
vagina/is d ischarge ; itching and bur n ing; outside human (motile) on wet patient and partner
do not confuse with Gardnerella because it cannot mount (prophylaxis)
vaginalis, a gram-variable form cysts)
bacterium that causes vaginosis
MI CRO B I O L O G Y MICROBIOLOGY-PARASITOLOGY SECT I O N I I 151
Nematodes (roundworms)
ORGANISM TRANSMISSION DISEASE TREATMENT
Intestinal
Enterobius Food contaminated with eggs Intestinal infection causing Bendazoles or pyrantel
vermicularis anal pruritus (diagnosed via pamoate (worms are bendy;
(pinworm) the Scotch Tape test) treat with mebendazole)
Ascaris lumbricoides Fecal-oral ; eggs visible in feces Intestinal infection Bendazoles or pyrantel
(giant roundworm) under microscope pamoate
Strongyloides Larvae in soil penetrate the Intestinal infection causing lvermectin or albendazole
stercora/is skin vom iting, diarrhea, anemia
Ancylostoma Larvae penetrate skin I ntestinal infection causing Bendazoles or pyrantel
duodenale, Necator anem ia by sucking blood pamoate
americanus from intestinal wal l s
(hookworms)
Tissue
Dracunculus In drinking water S k i n inflammation and Slow extraction of worm

medinensis ulceration
Onchocerca volvulus Female blackfly bite Hyperpi gmented skin and lvermectin ( ivermectin for river
river bl indness ( black flies, bl indness)
black skin nodules, " black
sight"; allergic reaction to
microfilaria possible
Loa loa Deer fly, horse fly, mango fly Swell ing in skin, worm in D iethylcarbamazine
conjunctiva
Wuchereria bancrofti Female mosquito Blocks lymphatic vessels : Diethylcarbamazine
elephantiasis ; takes 9 mo-l yr
after bite to become
symptom a tic
Toxocara canis Food contaminated with eggs Visceral larva m igrans Albendazole or mebendazole
Nematode routes of I ngested- Enterobius, Ascaris, Trichinella. You'll get sick if you EAT these !
infection Cutaneou s - Strongyloides, Ancylostoma, These get into your feet from the SANd .
Necator
1 52 SECT I O N I I M I C R O B I O LOGY M I C R O B I O LO G Y - PA R A S I T O L O G Y
Cestodes (tapeworms)
Taenia so/ium I ngestion of larvae encysted in Intestinal infection Praziquantel

unclercookecl pork
Ingestion of eggs Cysticercosis, Praziquantel ; -benclazoles for
neurocysticercosis neurocysticercosis
Diphyllobothrium Ingestion of larvae from raw Vitamin B 1 2 deficiency Praziquantel
Iatum freshwater fish (tapeworm competes for B 1 2
in intestine) anemia
--+
Echinococcus Ingestion of eggs from cl o g Cysts in liver, causing -benclazoles

granulosus feces anaphylaxis if antigens
released (surgeons preinject
with ethanol to kill cysts
before removal)
Trematodes (flukes)
Schistosoma Snails are host; cercariae Liver and spleen granulomas, Praziquantel
penetrate skin of humans fibrosis, and inflammation
Chron ic infection with
S. haematobium can lead to
squamous cell carcinoma of
the bladder
Clonorchis sinensis Unclercookecl fish Bil iary tract inflam mation Praziquantel
--+pigmented gallstones
Associated with
cholangiocarcinoma
Paragonimus Uncl e rcookecl crab meat Lung inflammation and z o Praziquantel
westermani bacterial infection, with
hemoptysis
Parasite hints FINDINGS ORGANISM
Brain cysts, seizures Taenia soliwn (cysticercosis)

Liver cysts Echinococcus granulosus
Vitamin B 1 2 deficiency Diphyllobothrium latum
Biliary tract d isease, cholangiocarcinoma Clonorchis sinensis
Hemoptysis Paragonimus westermani
Portal hypertension Schistosoma mansoni
Hematuria, bladder cancer Schistosoma haematobium
M icrocytic anemia Ancylostoma, Necator
Perianal pruritus Enterobius
M I C R O B I O LOGY MIC R O BIO L O G Y - VIRO L O G Y SECTION I I 1 53
MIC R O BIO L O G Y - VIRO L O G Y
Viral strudure-genera l Naked virus with Enveloped virus with Enveloped virus with
features icosahedral capsid icosahedral capsid helical capsid
Helical capsid with

n u cleic acid i n s i d e
Viral genetics
Recombination Exchange of genes between 2 chromosomes by crossing over with in regions of significant base
sequence homology.
Reassortment When viruses with segmented genomes (e.g., influenza virus) exchange segments. H igh-frequency
recombi nation. Cause of worldwide influenza pandemics.
Complementation When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein. The
nonmutated virus "complements" the mutated one by making a functional protein that serves
both viruses.
Phenotypic mixing Occurs with simultaneous infection of a cell with 2 viru ses. Genome of virus A can be partially
or completely coated (forming pseudovirion) with the surface proteins of virus B . Type B protein
coat determines the tropism (infectivity) of the hybrid virus. However, the progeny from th is
infection have a type A coat that is encoded by its type A genetic material .
Viral vaccines
Live attenuated I nduce humoral and cell-mediated immun ity N o booster needed for l ive attenuated vaccines.
vaccines but have reverted to virulence on rare Dangerous to give l ive vaccines to
occasion s. Killed/inactivated vaccines induce immunocomprom ised patients or their close
only humoral immunity but are stable. contacts.
Live attenuated small pox, yellow fever,
- "Live ! One n ight only! See small yellow
chickenpox (VZV) , Sabin's polio viru s , chickens get vaccinated with Sabin's and
M M R, Influenza (intranasal) . MMR ! It's incredible ! "
M M R = measles, mumps, rubella (l ive
attenuated vaccine that can be given to H I V
positive patients who do not show signs of
immunodeficiency) .
Killed Rabies, Influenza (injected), Salk Polio, and SalK = Killed .
HAV vaccines. RIP Always.
Recombinant H BV (antigen = recombinant H BsAg), H PV
(types 6, 1 1 , 1 6 , and 1 8 ) .
DNA viral genomes A l l D A viru ses except the Parvoviridae are All are dsDNA (like our cells) , except "part-of-a
dsDNA. virus" (parvovirus) is ssDNA.
All are l inear except papilloma-, polyoma-, and Parvus = small.
hepadnaviru ses (circular) .
1 54 SECT I O N I I MI CRO B I O L O G Y MICROBIOLOGY-VIROLOGY
RNA viral genomes All RNA viruses except Reoviridae are ssRNA. All are ssRNA (like our m RNA) , except
Positive-stranded RNA viru ses : I went to a "repeato-vi ru s" (reoviru s) is dsRNA.
retro (retrovi ru s) toga (togaviru s) party,
where I drank flavored (flaviviru s) Corona
( coronaviru s) and ate hippy ( hepeviru s)
California (calicivirus) pickles (picornaviru s) .
Naked viral genome Purified nucleic acids of most dsDNA (except poxviru ses and H BV) and (+) strand ssR A
infedivity ("" mRNA) viruses are infectious. Naked nucleic acids of ( ) strand ssRNA and dsRNA viruses are
-
not infectious. They require polymerases conta ined in the complete virion.
Virus ploidy All viruses are haploid (with I copy of DNA or RNA) except retroviru ses, which have 2 identical
ssRNA molecules ("" d iploid) .
Viral replication
DNA viruses All repl icate in the nucleus (except poxvi rus) .
RNA viruses All repl icate in the cytoplasm (except influenza virus and retroviruses) .
Viral envelopes Naked (nonenveloped) viruses include Give PAPP smears and CPR to a naked Heppy
Papillomavi rus, Adenoviru s, Picornavirus, ( hippy) .
Polyomaviru s, Calcivirus, Parvovirus, DNA = PAPP; RNA = CPR and hepeviru s .
Reovirus, and Hepeviru s.
Generally, enveloped viru ses acqu ire their
envelopes from plasma membrane when
they exit from cell. Exceptions include
herpesviruses, wh ich acquire envelopes from
nuclear membrane.
DNA virus Some general rules-all DNA vi ruses :

charaderistics
GENERAL RULE COMMENTS
Are H HAPPPPy viruses Hepadna, Herpes, Adeno, Pox, Parvo,

Papilloma, Polyoma.
Are double stranded Except parvo (single stranded).
Are l i near Except papilloma and polyoma (circular,
supercoiled) and hepadna (circular,
incomplete).
Are icosahedral Except pox (complex) .
Repl icate in the nucleus Except pox (carries own DNA-dependent RNA
polymerase) .
M I C R O B I O LOGY MIC R O BIO LOGY - VI R O LOGY SECT I O N I I 1 55
DNA viruses
V I RAL FAM I LY ENV ELOPE DNA STRUCTURE MEDICAL I MPORTANCE
Herpesviruses Yes D S and l i near HSV- 1 - oral (and some gen ital) lesions,
spontaneous temporal lobe encephalitis,
keratoconjunctivitis
HSV-2 - gen ital (and some oral) lesions
VZV ( H H V-3 ) - ch ickenpox, zoster (sh i ngles) ;
vaccine available
E BV ( I-J HV-4) - mononucleosis, Burkitt's
lymphoma, Hodgkin's lymphoma
CMV ( H H V-5 ) - infection in
immunosuppressed patients (AI DS retinitis) ,
especially transplant rec ipients ; congen ital
defects ( "sightomegaloviru s")
H H V- 6 - roseola (exanthem subitum)
H H V-7-less common cause of roseola
H H V- 8 - Kaposi 's sarcoma-associated
herpesvirus ( K S H V)
Hepadnavirus Yes DS and partial circular H BV:
Acute or chronic hepatitis
Vaccine ava ilable- conta ins H BV surface
antigen
Not a retrovirus but has reverse transcriptase
Adenovirus No DS and linear Febrile pharyngitis- sore throat; acute
hemorrhagic cystitis
Pneumonia
Conjunctivitis-"pink eye"
Parvovirus No S S and l i near (-) B19 viru s - aplastic crises in sickle cell d i sease,
(smallest D A viru s ) "slapped cheeks" rash in children - erythema
infectiosum (fifth d isease) , RBC destruction
in fetus leads to hydrops fetal is and death, pure
RBC aplasia and rheumatoid arthritis-li ke
symptoms in adults
Papillomavirus No D S and circular H PV-warts ( 1 , 2, 6, 1 1 ) , CIN, cervical cancer
( 1 6, 18) vaccine available
Polyomavirus No DS and circular JC virus- progressive multifocal
leukoencephalopathy (PML) in HI V
B K viru s - transplant patients, commonly targets
kidney
(JC : Junky C erebrum ; BK: Bad Kidney)
Poxvirus Yes DS and l i near Smallpox, although erad icated, could be used in
(largest DNA virus) germ warfare
Vacci n i a - cowpox ("milkmaid's bl isters")
Molluscum contagiosu m - Aesh-colored dome
lesions with central d imple
DS, double-stranded ; S S , single-stranded
1 56 SECT I O N I I M I C RO B I O LOGY MIC R O BIO L O G Y - VI R O L O G Y
Herpesviruses
V I RUS DISEASES ROUTE OF TRANSMISSION
H SV-1 Gingivostomatitis, keratoconjunctivitis, Respi ratory secretions, sal iva
temporal lobe encephalitis (most common
cause of sporadic encephalitis in the Un ited
States) , herpes labialis fJ. Latent in trigeminal
ganglia.
H SV-2 Herpes gen ital i s fl], neonatal herpes. Latent in Sexual contact, perinatal
sacral gangl ia.
vzv Varicella-zoster (chickenpox, sh ingles) ' Respiratory secretions
encephalitis, pneumonia. Latent in dorsal root
or trigem inal gangl ia.
E BV Infectious mononucleosis, Burkitt's/I-Ioclgkin's Respi ratory secretions, saliva
lymphoma, nasopharyngeal carcinoma. Latent
in B cel l s .
CMV Congenital infection, mononucleosis (negative Congenital, transfusion, sexual contact, sal iva ,
Monospot) , pneumonia, retinitis. Infected urine, transplant
cells have characteristic "owl 's eye" inclusions
[!]. Latent in mononuclear cells.
H HV-6 Roseola : high fevers for several clays that can Not determined
cause seizures, fol lowed by a diffuse macular
rash.
H HV-8 Kaposi 's sarcoma ( H IV patients ) . Sexual contact
Zoster. Hemorrhag1c vesicles and pustules i n dermatomal CMV. Renal tubular cells 1 n a neonate with congemtal CMV
distribution. infection Note the "owl's eye" 1 nclusions (arrows). li!J
M I C R O B I O LO G Y MIC R O BIO L O G Y - VI R O LO G Y SECTION I I l 57
HSV identification PCR i s test of choice. Tzanck heavens I do not have herpes.
Tzanck test- a smear of an opened skin vesicle
to detect multinucleated giant cells commonly
seen i n HSV- 1 , H SV-2 , and VZV.
Infected cells also have intranuclear Cowdry A
inclusions.
EBV A herpesviru s . Can cause mononucleosis. Most common during peak kissing years
Infects B cells. Characterized by fever, ( " kissing di sease " ) .
hepatosplenomegaly, pharyngitis, and
lymphadenopathy (especially posterior cervical
nodes) . Peak incidence 1 5-20 years of age.
Atypical lymphocytes seen on peripheral blood
smear r1] are not infected B cells but rather
reactive cytotoxic T cells.
Positive Monospot test-heterophile antibodies
detected by agglutination of sheep or horse
RBCs. Also associated with development of
Hodgkin's and endemic Burkitt 's lymphomas
as well as nasopharyngeal carcinoma.
Atypical lymphocytes. Seen with EBV infection. Note
"hugging" of RBCs (arrow). D
1 58 SE CT I O N II MIC R OBI O L O G Y MIC RO BIO LOGY - VI RO LOGY
RNA viruses
CAPSID
VIRAL FAMILY ENVELOPE RNA STRUCTURE SYMMETRY MEDICAL IMPORTANCE
Reoviruses No OS l inear Ieos a heel ra 1 Coltivirusa - Coloraclo tick fever

1 0- 1 2 segments (double) Rotavirus - # 1 cause of fatal diarrhea in children
Picornaviruses No SS EEl l inear Icosa heel ra 1 Poliovi ru s -polio-Salk/Sabin vaccines - I PV/OPV
Echovirus - aseptic meningitis
Rh inoviru s -"common col d "
Coxsackieviru s - aseptic meningitis; herpangina
(mouth bl isters, fever) ; hand, foot, and mouth
disease; myocard itis
HAY- acute viral hepatitis
PERCH
Hepevirus No S S EEl l i near Icosahedral H EY
Caliciviruses No SS EEl l inear Icosahedral Norovirus-viral gastroenteritis
Flaviviruses Yes S S EEl l i near Icosahedral I-ICY
Yellow fever"
Dengue
St. Louis encephalitis3
West Nile virus"
Togaviruses Yes SS EEl l i near Icosahedral Rubella
Eastern equine encephalitis3
Western equine encephal itis"
Retroviruses Yes SS EEl l inear Icosahedral Have reverse transcriptase
( HTLV), HTLV-T-cell leukemia
complex H IV-AIDS
and conical
( I-I IV )
Coronaviruses Yes SS E8 l i near Helical Coronaviru s - "common cold" and SARS
Orthomyxoviruses Yes SS 8 l inear Helical Influenza virus
8 segments
Paramyxoviruses Yes SS 8 l inear Hel ical PaRaMyxovirus :
Nonsegmented Parainfluenza -croup
RSV- bronch iolitis in babies; Rx-ribavirin
Measles, Mumps
Rhabdoviruses Yes SS 8 linear Helical Rabies
Filoviruses Yes SS 8 l i near Hel ical Ebola/Marburg hemorrhagic fever-often fatal !
Arenaviruses Yes SS 8 circular Hel ical LCMV-lymphocytic choriomen ingitis virus
2 segments Lassa fever encephalitis- spread by mice
Bunyaviruses Yes SS 8 circular Helical California encephal itis3
3 segments SanclAy/Rift Valley fevers"
Crimean-Congo hemorrhagic fever"
Hantaviru s -hemorrhagic fever, pneumonia
Delta virus Yes SS 8 circular Uncertain H OY i s a " defective" virus that requires H BV
co-infection
SS, single-stranded; OS, double-stranded; EE>, positive sense; 8, negative sense ; "= arbovirus, transmitted by arthropods (mosquitoes,
ticks).
(Adapted, with permission, from Levinson W , Jawetz E . Medical Microbiology a n d Immunology: Examination a n d Boord Review, 6th e d . N e w York: McGraw-Hill, 2000: 1 82 .)
I
M I C R O B I O LO G Y MIC R O BIO LO G Y -VI RO L O G Y SECTION I I 1 59
Negative-stranded Must transcribe negative strand to positive. Always Bring Polymerase Or Fail Replication .
viruses Virion brings its own RNA-dependent RNA
polymerase. They include Arenavi ru ses,
Bunyavi ru ses, Paramyxoviruses,
Orthomyxoviruses, Filoviru ses, and
Rhabdovi ruses.
Segmented viruses All are RNA viruses. They include BOAR

Bunyaviruses, Orthomyxoviruses (inAuenza
viru ses) , Arenaviruses, and Reovi ruses.
Picornavirus I ncludes Poliovirus, Echovirus, Rhinovirus, PicoRNAvi ru s = small RNA virus.

Coxsack ieviru s, HAY. RNA is translated into PERC H on a "peak" (pica) .
1 large polypeptide that is cleaved by proteases
i nto functional viral proteins. Can cause
aseptic (viral) meningitis (except rhinovirus
and HAY ) . All are enterovi ruses (fecal-oral
spread) except rh i novi rus.
Rhinovirus A picornavi rus . Nonenveloped RNA virus. Rhino has a runny nose.
Cause of common cold; > 1 0 0 serologic types.
Acid labile - destroyed by stomach acid;
therefore, does not infect the GI tract (unl ike
the other picornaviru ses) .
Yellow fever virus A flaviviru s (also an arbovirus) transm itted by Flavi = yellow, jaundice.
Aedes mosquitoes . Virus has a monkey or
human reservoir.
Symptom s : h igh fever, black vom itus, and
jaundice.
Rotavirus Rotavirus rJ, the most important global cause ROTAvi ru s = Right Out The Anus.
of infantile gastroenteritis, is a segmented CDC recom mends routine vaccination o f a ll
dsRNA viru s (a reovirus) . Major cause of acute infants.
diarrhea in the Un ited States dur i ng winter,
especially in day-care centers, ki ndergartens.
Villous destruction with atrophy leads to
! absor p tion of Na+ and loss of K+.
l 60 S E CT I O N I I M I C R O B I O LOGY M I C R O B I O LO G Y - V I R O L O G Y
Influenza viruses Orthomyxoviru ses. Enveloped, negative single Killed viral vaccine i s major mode of protection ;
stranded RNA viruses with 8-segment genome. reformulated vaccine offered each fall.
C ontain hemagglutinin (promotes viral Vaccine containing l ive, temperature-sensitive
entry) and neuramin idase (promotes progeny mutant that repl icates in the nose but not in
virion release) antigens. Patients at risk for the lung is also available. Used in children.
fatal bacterial superinfection. Rapid genetic
changes.
Genetic shift Causes pandemics. Reassortment of viral Sudden shi ft i s more deadly than gradual drift.
/antigenic shifts genome; segments undergo high-frequency
recombination, such as when human Au A
virus recombines with swine Au A viru s .
Genetic d rift Causes epidem ics. Minor (antigen ic drift)
changes based on random mutation.
Rubella virus A togavirus. Causes rubella, once known as German ( 3 -clay) measles. Fever, postauricular
adenopathy, lymphadenopathy, arthralgias, fine truncal rash that starts at head and moves clown.
Causes mild disease i n children but serious congenital d isease (a ToRC HeS infection ) .
Paramyxoviruses Paramyxoviruses cause d isease in children. They include those that cause parainfluenza (croup :
seal-l ike barking cough), mumps, and measles as well as RSV, which causes respiratory tract
infection (bronch iolitis, pneumonia) in infants. All conta i n surface F (fusion) protein, which
causes respi ratory epithel ial cells to fuse and form multinucleated cells. Pal ivizu m ab (monoclonal
antibody against F protein) prevents pneumon ia caused by RSV infection in premature infants.
M I C R O B I O LOGY M I C R O B I O LO G Y - V I R O L O G Y SECTIO N I I 161
Measles virus A paramyxovirus that causes measles. 3 C 's of measles :

Kopl ik spots lZ) (red spots with blue-white C ough
center on buccal mucosa) and descending C oryza
maculopapular rash 1IJ are characteristic. Conjunctivitis
SSPE (subacute sclerosing panencephal itis,
occurring years later) , encephalitis (l :2000),
and giant cell pneumonia (rarely, in
immunosuppressed) are possible sequelae.
Rash presents last and spreads from head
to toe. I ncludes hands and feet (vs. truncal
rash in rubella) . Do not confuse with roseola
(caused by H H V-6) .
Koplik spots. Note small white lesions with an erythema Rash of measles. Discrete erythematous rash becomes
tous halo that precede the measles rash by 1 -2 days. m confluent as it progresses downward. m
Mumps virus A paramyxovirus. Mumps makes your parotid glands and testes as
Symptom s : Parotitis rJ, Orch itis (inAammation big as POM-poms.
of testes), and aseptic Meningitis. Can cause
steril ity (especially after puberty) .
1 62 SECTI O N I I M I C R O B I O L O Ci Y MIC R O BIO L O G Y - VI R O LO G Y
Rabies virus Bullet-shaped viru s [J. Negri bodies are

characteristic cytoplasmic inclusions in
neurons infected by rabies viru s ; commonly
found i n Purkinje cel ls of cerebel lum II).
Rabies has long incubation period (weeks to
months) before symptom onset. Postexposure
treatment is wound cleansing and vaccination
rabies immune globulin.
Travel s to the CNS by migrating in a retrograde
fashion up nerve axons.
Progression of disease : fever, malaise
..... agitation, photophobia, hydrophobia
..... paralysis, coma ..... death .
More com monly from bat, raccoon, and skunk
bites than from dog bites in the United States.
Hepatitis viruses
V I RUS TRANSMISSION CARRIER INCUBATION HCC RISK N OTES
HAVa RNA Fecal-oral No Short (weeks) No Asymptomatic

. .
picornavnus (usually) , Acute,

Alone (no carriers)
DNA Parenteral, Yes Long (month s) Yes : integrates
hepaclnavirus sexual, into host
maternal genome, acts as
fetal oncogene
HCV RNA flaviviru s Primarily Yes Long Yes : from chronic Ch ron ic, C irrhosis,
blood, inflam mation C arcinoma , Carrier
IVDU, post
transfusion
H DV RNA delta virus Parenteral, Yes Superinfection- Yes Defective virus
sexual, short Dependent on H BV;
maternal- Co-infection superinfection ..... !
fetal long prognosis
RNA hepeviru s Fecal-oral, No Short No H igh mortal ity in
especially pregnant women ;
with Enteric, Expectant
waterborne mothers, Epidemic
epidemics
Signs and symptoms of all hepatitis viruses : episodes of fever, jaundice, elevated ALT and AST.
aHAV and HEY are fecal-ora l : The vowels hit your bowels. Naked viruses do not rely on an envelope so they are not destroyed
by the gut.
b in H BV, the virus uses its own DNA-dependent DNA polymerase to make full double-stranded DNA. The host RNA
polymerase transcribes m R A from viral DNA and then makes viral proteins from the m RNAs.
M I C R O B I O LO G Y MICROBIOLOGY-VIROLOGY SECT I O N I I 1 63
Hepatitis serologic markers

Anti-HAV (lgM) lgM antibody to HAV; best test to detect active hepatitis A.
Anti-HAV ( lgG) IgG antibody indicates prior HAV infection and/or prior vaccination ; protects against reinfection.
H BsAg Antigen found on surface of H BV; ind icates hepatitis B infection.
Anti-HBs Antibody to H B sAg; ind icates immunity to hepatitis B.
H BcAg Antigen associated with core of H BV.
Anti- H Bc Antibody to H B cAg; IgM = acute/recent infection ; IgG = prior exposure or chronic infection.
Positive during window period.
H BeAg A second, different antigenic determinant in the H BV core. H B eAg indicates active viral
replication and therefore h igh transm issibility.
Anti-HBe Antibody to e antigen ; indicates low transmissibility.
I mportant diagnostic tests
I ncubation Prod rom e , Convalescence

period acute disease Late
H BsAg Anti-HBs
(anti-HBc) (anti-H Bc)
Coat p rotei n
1
(H BsAg)
0 2 3 4 5 6 7 8
DNA polymerase
42
nm
HBV particles Anti - H Bc
j DNA polymerase
Vi rus particle
Anti- H Bs
In vi ral hepatitis, ALT > AST. Anti - H Be

In alcoh o l i c hepatitis, AST > ALT.
SECES : S E a re antigens, C E S
a r e antibodies; labeled o n f i g u re
in order of appearance. 0 2 3 4 5 6 7 8
Months after expos u re
HBsAg Anti-H Bs H BeAg Anti-HBe Anti-HBc

Acute H BV + + IgM
Window + lgM
Chronic H BV ( h igh i nfectivity) + + IgG
Chron ic H BV (low i nfectivity) + + IgG
Recovery + + IgG
I m munized +
l 64 SECTION I I M I C RO B I O LO G Y MICRO B I O L O G Y - VIRO L O G Y
H IV
Diploid genome (2 molecules o f RNA) .
The 3 structural genes (protein coded for) :
env (gp l 2 0 and gp4l ) :
Formed from cleavage o f gpl60 to form
envelope proteins.
gpl 2 0 - attachment to host CD4+ T cel l .
Lipid
mem brane gp4 l - fusion and entry.
gp41
gag (p24) - capsid protein.
pol- reverse transcriptase, aspartate protease,
i ntegrase.
Reverse transcriptase synthesizes dsDNA from
RNA; dsDNA i ntegrates into host genome.
Virus binds CCR5 (early) or CXC R4 (late)
co-receptor and CD4 on T cells; binds CCR 5
and CD4 on macrophages.
Homozygous CCR5 mutation = immunity.
Heterozygous C C R 5 mutation = slower course.
H IV diagnosis Presumptive d iagnosis made with ELISA ELI SA/Western blot tests look for antibodies
(sensitive, h igh false-positive rate and low to viral proteins; these tests often are falsely
threshold, rule out test) ; positive results are negative i n the fi rst l -2 months of H I V
then confirmed with Western blot assay infection a n d falsely positive i nitially in babies
(specific, h igh false-negative rate and high born to infected mothers (anti-gp l 20 crosses
threshold, rule in test) . placenta ) .
H IV PCR/viral load tests determine the amount
of viral RNA in the plasma. H igh viral load
associated with poor prognosis. Also use viral
load to mon itor effect of drug therapy.
AIDS d iagnosis ::; 200 CD4+ cells/mm 3
(normal : 500-1 5 0 0 cells/mm 3 ) . HIV
positive with AIDS-defining condition (e.g.,
Pneumocystis pneumonia, or PCP) or CD4/
C DS ratio < 1 . 5 .
M I C R O B I O LO G Y MIC R O BIO LO G Y - VI R O LO G Y SECTION I I 1 65
Time course of H IV
infection
Acute H I V syndrome Four stages of infection :
Wide dissemination of virus
Seeding of lymphoid organs Opportunistic 1 . Flu-l ike (acute)
diseases
-
2. Feel i ng fine (latent)
Constitutional 3. Falli ng count
1 200
symptoms 4. Final crisis
1 1 00
1 000 1 01
D ur ing latent phase, viru s repl icates in lymph
nodes.
900
Clinical latency
'E
E 800
]!
a; 700
S-
c 600
::J
0
" 500
+
'<!'
0 @QQJ
(.)
300
[gQQ]
1 00
---7r-----L_ ----L_ --
0 1 02
0 2 3 2 3 4 5 6 7 8 9 10 1 1
Months Years
Red line = CD4+ T-lymphocyte count (cells/mm 3 ) ; blue line = HIV R A

copies/mL plasma.
Blue boxes ind icate i mmunocompromise (< 400 CD4+ cell/mm 3 ) and when
AIDS-defining illnesses emerge (< 200 CD4+ cells/mm 3 ) .
1 66 SEC T I O N I I MI CROBI O L O G Y MICRO BIOLO G Y - VIROLO G Y
Common diseases of A s C D 4 count !, risk o f reactivation of past infections (e.g., T B , H SV, sh ingles), dissemination
H IV-positive adults of bacterial infections and fungal infections (e.g., coccidioidomycosis) , and non-Hodgkin's
lymphomas t.
CliNICAl PRESENTATION FINDINGS/LABS PATHOGEN
Systemic
Low-grad e fevers, cough, Oval yeast cells with in macrophages, CD4 Histoplasma capsulatum (causes only
hepatosplenomegaly, < 100 cells/m m 3 pulmonary symptoms i n immunocompetent
tongue ulce r hosts)
Dermatologic
Fluffy white cottage Pseudohyphae, commonly oral if CD4 < 400 C. albicans (causes thru sh)
cheese lesi o n s cells/mm 3 , esophageal if CD4 < 100 cells/mm 3
Superfi cial vascula r Biopsy reveals neutroph ilic inAammation Bartonella henselae (causes bacillary
proliferat i o n angiomatosis)
Gastrointestinal
Chronic, watery Acid-fast cysts seen i n stool especially when CD4 Cryptosporidiwn spp.
d i a rrhea < 200 cells/mm 3
Neurologic
Encephalopathy Due to reactivation of a latent virus; results in JC virus reactivation (cause of PML)
demyel i nation, CD4 < 200 cells/mm 3
Abscesses Many ring-enhancing lesions on imaging, CD4 Toxoplasma gondii
< 1 0 0 cells/mm 3
M e n i ngitis India ink stain reveals yeast with narrow-based Cryptococcus neoformans
budding and large capsule, CD4 < 50 cells/mm 3
Retinitis Cotton-wool spots on funduscopic exam and CMV
may also occur with esophagitis, CD4 < 50
cells/mm 3
Dementia Must differentiate from other causes Directly associated with H I V
Oncologic
Supe rfi cial n e oplasti c Biopsy reveals lymphocytic inAammation H H V-8 (causes Kaposi's sarcoma), do not
prolife rat i o n of confuse with bacillary angiomatosis caused by
vasculature B. henselae
Hairy leukoplak i a Often on lateral tongue EBV
No n - Hodgk i n 's Often on oropharynx (Waldeyer's ring) May be associated with EBV
lymp h o m a (la rge cell
type)
Squa m ous cell Often in anus (men who have sex with men) or H PV
c a rci n o m a cervix (females)
Pri m a ry CNS lymph o m a Focal or multiple, differentiate from Often associated with E BV
toxoplasmosis
Respiratory
Interstitial pneum o n i a Biopsy reveals cells with intranuclear (owl 's eye) CMV
i nclusion bodies
Invasive a spe rgillosis Pleuritic pa in, hemoptysis, infiltrates on imaging Aspergillus fumigatus
Pneum o n i a Especially with CD4 < 200 cells/mm 3 Pneumocystis jirovecii
Tuberculosis-like Especially with CD4 < 5 0 cells/mm 3 Mycobacterium avium-intracellulare
d isease
M I C R O B I OLO G Y MICRO BIO LO GY- SYSTE M S SE C T I O N I I 1 67
Prions Prion diseases are caused by the conversion of a normal cellular protein termed prion protein
( PrPc) to a -pleated form ( Prpsc) , which is transmissible. Prpsc resists degradation and facilitates
the conversion of still more Prpc to PrPsc. Accumulation of Prpsc results in spongiform
encephalopathy and dementia, ataxia, and death. It can be sporadic (Creutzfeldt-Jakob d isease
rapidly progressive dementia) , inherited (Gerstmann-Straussler-Scheinker syndrome) , or acqu i red
(kur u ) .
MICRO BIO LOGY- S YS TE M S
Normal flora: LOCATION M I CROORGANISM

dominant Skin Staphylococcus epidermidis
Nose S. epidermidis; colon ized by S. aureus
Oropharynx Viridans group streptococci
Dental plaque Streptococcus mutans
Colon Bacteroides fragilis > E . coli
Vagina Lactobacillus, colon ized by E. coli and group
B strep
Neonates del ivered by cesarean section have no Aora but are rapidly colonized after birth.
Bugs causing food S. aureus and B. cereus food poisoning starts quickly and ends quickly.
poisoning
MICROORGANISM SOURCE OF I N FECTION
Vibrio parahaemolyticus and V vulnificusa Conta m inated seafood

Bacillus cereus Reheated rice. " Food poison ing from reheated
rice? Be serious ! " (B. cereus )
S. aureus Meats, mayonnaise, custard ; preformed toxin
Clostridium {Jerfringens Reheated meat d i shes
C. botu linum Improperly canned foods (sign is bulging cans)
E. coli Ol 57: H 7 Undercooked meat
Salmonella Poultry, meat, and eggs
"V vulnificus can also cause wound infections from contact with contaminated water or shellfish.
Bugs that can mimic Yersinia enterocolitica is most common cause of mesenteric aden itis, a d i sease that m i m ics
appendicitis append icitis. Nontyphoidal Salmonella can also be a cause. Camplyobacter jejuni may also mimic
appendicitis.
1 68 SECT I O N I I MI C R O B I O L O G Y MIC R O BIO LO G Y - S Y S TE M S
Bugs causing diarrhea

Bloody diarrhea
Campylobacter Comma- or S-shaped organisms; growth a t 42 C
Salmonella Lactose negative ; flagellar motil ity; has animal reservoir, especially poultry and eggs
Shigella Lactose negative ; very low 1050; produces Shiga toxin (human reservoir only)
Entero h e morrhagic O l 5 7 : H 7; can cause H U S ; makes Shiga-l ike toxin
E. coli
Enteroinvasive E. coli Invades colonic mucosa

Yersinia enterocolitica Day-care outbreaks, pseucl o appenclicitis
Entamoeba histolytica Protozoan
Watery diarrhea
Ente rotoxigenic E. coli Traveler's d iarrhea; produces ST and LT toxins
Vibrio cholerae Comma-shaped organisms; rice-water diarrhea
C. difficile Can also cause bloody d iarrhea. Pseudomembranous colitis
C. perfringens Also causes gas gangrene
Protozoa Giardia, Cryptosporidium (in immunocomprom ised)
Viruses Rotavi ru s , norovirus
Common causes of pneumonia

NEONATES (< 4 WK) C H I LDREN (4 WK- 1 8 YR) ADULTS ( 1 8-40 YR) ADULTS (40-65 YR) ELDERLY
Group B streptococci Viruses ( RSV) Mycoplasma S. pnewnon iae S. pneumoniae

E. coli Mycoplasma C. pneumoniae H. influenzae Influenza virus
Chlamydia S. pneumoniae Anaerobes Anaerobes
trachomatis Viruses H. influenzae
(infants-3 yr) Mycoplasma Gram-negative rods
C. pneumoniae
(school-age children)
Streptococcus
pneumoniae
Runts May Cough
Chunky Sputum
Special groups
Nosocomial (hospital Staphylococcus, enteric gram-negative rods
acquired)
l m munocompromised Staphylococcus, enteric gram-negative rods, fu ngi, viruses, Pneumocystis jirovecii-with H I V

Aspiration Anaerobes
Alco h olic/ IV d rug user S. pneumoniae, Klebsiella, Staphylococcus
Cystic fibrosis Pseudomonas, S. aureus, S. pneumoniae
Postviral Staphylococcus, H. influenzae, S. pnewnoniae
Atypical Mycoplasma, Legionella, Chlamydia
M I C R O B I O LO G Y MIC R O BIO L O GY - S Y S TE M S SECTI O N I I 1 69
Common causes of meningitis

NEWBORN (0-6 MO) C H I LDREN (6 M0-6 YR) 6-60 YR 60 YR +
Group B streptococci Streptococcus pneumoniae S. pneumoniae S. pnewnoniae

E. coli Neisseria meningitidis N. meningitidis (# 1 i n teens) Gram-negative rods
Listeria Haemophilus influenzae type B Enteroviruses Listeria
Enteroviruses HSV
Give ceftriaxone and vancomycin empirically (add ampicillin if Listeria is suspected) .
Viral causes of meningitis - e nteroviruses (esp. coxsackievirus) , I-I SV-2 ( I-ISV-1 = encephalitis) , 1-I IV, West ile virus, VZV.
In 1-II V- Cryptococcus, CMV, toxoplasmosis (brain abscess) , JC viru s (PML) .
Note : I ncidence of H. influenzae meningitis has greatly with introduction o f the conj ugate H . influenzae vaccine i n last
10-1 5 years. Today, cases are usually seen in unimmunizecl children.
CSF findings in meningitis

OPEN I NG PRESSURE CELL TYPE PROTEIN SUGAR
Bacterial t PMNs
Fungai/TB t lymphocytes
Viral Normallt t lymphocytes Normallt Normal
Osteomyelitis CONDITION CAUSE
Assume if no other information is available S. a ureus

Sexually active Neisseria gonorrhoeae (rare), septic arthritis
more common
D iabetics and IV dru g users Pseudomonas aeruginosa, Serratia
Sickle cell Salmonella
Prosthetic replacement S. aureus and S. epidermidis
Vertebral d isease Mycobacterium tuberculosis (Pott's d i sease)
Cat and clog bites or scratches Pasteurella mu.ltocida
Most osteomyel itis occurs i n children .
Elevated CRP and ESR classic but nonspecific.
Urinary trad Cystitis presents with dysuria, frequency, urgency, suprapubic pain, and WBCs (but not WBC
infedions casts) in urine. Primarily caused by ascension of microbes from urethra to bladder. Males
infants with congenital defects, vesicoureteral reflux. Elderly- enlarged prostate. Ascension to
kidney results in pyelonephritis, which presents with fever, chills, Aank pain, CVA tenderness,
hematuria, and WBC casts.
Ten times more common in women (shorter urethras colon ized by fecal flora) . Other predisposing
factors include obstruction , kidney surgery, catheterization, GU malformation , diabetes, and
pregnancy.
Diagnostic markers : positive leukocyte esterase test = bacterial UTI ; positive n itrite test = gram
negative bacterial UTI .
1 70 SECT I O N I I M I CROB I OLO G Y MICROBIOLOGY-SYSTEMS
UTI bugs
SPECIES FEATURES COMMENTS
Escherichia coli Lead ing cause of UTI . Colon ies show green Diagnostic markers :
metallic sheen on E M B agar. (f) Leukocyte esterase bacterial.
=
Staphylococcus 2nd leading cause of community-acqu ired UTI (f) Nitrite test = gram negative.
saprophyticus in sexually active women. (f) Urease test urease-producing bugs (e.g.,
=
Proteus, Klebsiella) .
Klebsiella pneumoniae 3rd leading cause of UTI. Large mucoid capsule
8 Urease test E . coli, Enterococcus.
=
and viscous colonies.

Serratia marcescens Some strains produce a red pigment; often
nosocom ial and dru g resistant.
Enterobacter cloacae Often nosocom ial and drug resistant.
Proteus mirabilis Motil ity causes "swarming" on agar; produces
urease; associ ated with struvite stones.
Pseudomonas Blue-green pigment and fruity odor; usually
aeruginosa nosocom ial and drug resistant.
MI C R O B I O L O G Y MICRO BIO LO G Y - S Y S TE M S SECT I O N I I 171
ToRCHeS infections M icrobes that may pass from mother to fetus. Transm i ssion is transplacental i n most cases, or via
delivery (especially H SV-2 ) . Nonspecific signs common to many ToRCHeS infections i nclude
hepatosplenomegaly, jaundice, thrombocytopenia, and growth retardation.
Other i mportant infectious agents include Streptococcus agalactiae (group B streptococci ) , E . coli,
and Listeria monocytogenes -all causes of meningitis in neonates. Parvovirus B l 9 causes hydrops
fetal is.
AGENT MODE OF TRANSMISSION MATERNAL MAN I FESTATIONS NEONATAL MANIFESTIO N S
Toxoplasma gondii Cat feces or ingestion of Usually asymptomatic ; Classic triad : chorioretin itis,
u ndercooked meat lymphadenopathy (rarely) hydrocephalus, and
i ntracranial calcifications
Rubella Respiratory droplets Rash , lymphadenopathy, Classic triad : PDA (or
arthritis pulmonary artery hypoplasia),
cataracts, and deafness
"blueberry muffin" rash
CMV Sexual contact, organ Usually asymptomatic ; Hearing loss, seizures, petechial
transplants mononucleosis-like illness rash, "blueberry muffin" rash
H IV Sexual contact, needlestick Variable presentation depending Recurrent infections, chron ic
on CD4+ count diarrhea
Herpes simplex virus-2 Skin or mucous membrane Usually asymptomatic; herpetic Encephal itis, herpetic (vesicular)
contact (vesicular) lesions lesions
Syphilis Sexual contact Chancre ( 1 ) and disseminated Often results in stillbirth,
rash (2) are the two stages hydrops fetal is; if child
likely to result in fetal infection survives, presents with facial
abnormalities rJIJ (notched
teeth , saddle nose, short
maxilla) , saber shins, CN VIII
deafness
Congenital syphilis facies. Skin i s dry, wrinkled with Hutchinson's teeth. Note the centrally notched, widely
yellow-brown hue. Note the hemorrhagic rhinitis. D spaced central incisors. D
1 72 SECTI O N I I M I C RO B I O LO G Y M I C R O B I O LO G Y - S Y S TE M S
Red rashes of childhood

AGENT ASSOCIATED SYNDROME/DISEASE CLINICAL PRESENTATION
Rubella virus Rubella Rash begins at head and moves clown; fi ne

-+
truncal rash ; postauricular lymphadenopathy

Measles virus Measles A para myxoviru s ; beginning at head and moving
clown ; rash is preceded by cough , coryza,
conjunctivitis, and blue-white ( Kopl ik) spots on
buccal mucosa
vzv Chickenpox Vesicular rash begins on trunk; spreads to face
and extrem ities with lesions of different age
H HV-6 Roseola A macular rash over body appears after several
clays of high fever; can present with febrile
seizures; usually affects infants
Pa rvovirus B 1 9 Erythema infectiosum " Slapped cheek " rash on face r.:J (can cause
hydrops fetal i s i n pregnant women)
Streptococcus Scarlet fever Erythematous, sandpaper-l ike rash with fever
pyogenes and sore throat
Coxsackievirus type A Hand-foot-mouth disease Vesicular rash on palm s and soles [I) ; ulcers in
oral mucosa
M I C R O B I O LOGY M I C R O B I O L O G Y - S Y S TE M S SECTIO N I I 1 73
Sexually transmitted diseases

DISEASE CLINICAL FEATURES ORGANISM
Gonorrhea Urethritis, cervicitis, PID, prostatitis, Neisseria gonorrhoeae

epididym itis, arthritis, creamy purulent
discharge
1 syphilis Pa inless chancre Treponema pallidum
2 syp h i l i s Fever, lymphadenopathy, skin rashes,
condylomata l ata
3 syp h i l i s Gummas, tabes dorsalis, general paresis, aortitis,
Argyll Robertson pupil
Cha ncroid Painful genital ulcer, inguinal adenopathy I-Iaemophilus ducreyi (it's so painfu l, you "do
cry" )
Genital herpes Pa inful penile, vulvar, o r cervical vesicles and H SV-2 , less commonly H SV- 1
ulcers ; can cause systemic symptoms such as
fever, headache, myalgia
Chlamyd ia Urethritis, cervicitis, conjunctivitis, Reiter's Chlamydia trachomatis (0-K)
syndrome, PI D
Lymphogra n u loma Infection of lymphatics ; genital ulcers, C. trachomatis ( L l -L3)
venereum lymphadenopathy, rectal strictures
Trichomoniasis Vagin itis, strawberry-colored mucosa, motile in Trichomonas vaginalis
wet prep
AIDS Opportun istic infections, Kaposi 's sarcoma, HIV
lymphoma
Condylomata Gen ital warts, koi locytes H PV-6 and - 1 1
acum inata
Hepatitis B Jaundice H BV
Bacterial vaginosis Noninflammatory, malodorous discharge (fishy Gardnerella vaginalis
smell); positive whiff test, clue cells, not
exclusively an STD
Pelvic inflammatory Top bugs - Chlamydia trachomatis (subacute, Salpingitis is a risk factor for ectopic pregnancy,
disease often undiagnosed), Neisseria gonorrhoeae infertil ity, chron ic pelvic pain, and adhesions.
(acute ) . C. trachomatis -the most common
bacterial STD in the United States. Cervical
motion tenderness (chandelier sign),
purulent cervical discharge. PID may include
salpingitis, endometritis, hydrosalpinx,
and tuba-ovarian abscess. Can lead to Fitz
Hugh-Curtis syndrom e infection of the
-
l iver capsule and "violi n string" adhesions of

parietal peritoneum to l iver.
l 74 SECT I O N II MI C R OBI OLO G Y MIC RO BIO LO G Y - S Y S TE M S
Nosocomial infedions
PATHOGEN RISK FACTOR NOTES
CMV, RSV Newborn nursery

E. coli, Proteus mirabi/is Urinary catheterization The 2 most common causes of nosocomial
infections are E . coli (UTI) and S. a ureus
(wound infection) .
Pseudomonas Respiratory therapy equ ipment Presume Pseudomonas "airuginosa " when air or
aeruginosa burns are involved.
H BV Work in renal d ialysis unit
Candida albicans Hyperal imentation
Legionella Water aerosol s Legionella when water source is i nvolved.
Bugs affeding unimmunized children

CliNICAL PRESENTATION FINDINGS/LABS PATHOGEN
Dermatologic
Rash Beginning at h ead and moving cl o wn with Rubella virus
postauricular lymphadenopathy
Beginning at head and moving cl own ; rash Measles virus
preceded by cough, coryza, conjunctivitis, and
blue-white ( Kopl ik) spots on buccal mucosa
Neurologic
Meni ngitis M icrobe colonizes nasopharynx H. influenzae type B
Can also lead to myalgia and paralysis Poliovirus
Respiratory
Pha ryngitis Grayish oropharyngeal exudate Corynebacterium diphtheriae (elaborates toxin
( "pseucl o membranes" may obstruct airway) ; that causes necrosis i n pharynx, card iac, and
painfu l throat CNS tissue)
Epiglottitis Fever with dysphagia, drool ing, and difficulty H. influenzae type B (also capable of causing
breath ing clue to edematous "cherry reel " epiglottitis i n fully i m mu n ized children)
epiglottis
MI CRO B I O L O G Y MICROBIOLOGY-SYSTE MS SEC T I O N I I 1 75
Bug hints (if all else CHARACTERISTIC ORGANISM

fails) Pus, empyema, abscess S. aureus
Ped iatric infection Haemophilus influenzae (includ ing epiglottitis)
Pneumonia in cystic fibrosis, burn infection Pseudomonas aeruginosa
Branch ing rods in oral infection, sulfur granules Actinomyces israelii
Traumatic open wound Clostridium perfringens
Surgical wound S. a ureus
Dog or cat bite Pasteurella multocida
"Cur rant j elly" sputu m Klebsiella
Positive PAS stain Tropheryma wh ipplei (Wh ipple's disease)
Sepsis/meni ngitis i n newborn Group B strep
Health care provider H BV (from needle stick)
Fungal infection in diabetic or Mucor or Rhizofnts spp.
im munocomprom ised patient
Asplenic patient Encapsulated m i crobes, especially SHiN
(S. pnewnoniae, H. influenzae type B ,
N . meningitidis)
Chronic granulomatous disease Catalase-positive m icrobes, especially S. aureus
Neutropenic patients Candida a lbicans (system ic) , Aspergillus
Facial nerve palsy Borrelia burgdorferi ( Lyme d i sease)
17 6 SECTION II M I C RO B I O LOGY MIC R O BIO L O G Y - ANTIMIC R O BIA L S
MIC R O BIO L O G Y - ANTIMIC R O BIA L S
Antimicrobial therapy MECHANISM OF ACTION DRUGS
0 Block cell wall synthesis by inh ibition of Penicillin, methicillin, ampicillin, piperacillin,
peptidoglycan cross-l inking cephalosporins, aztreonam, i mipenem
f) Block peptidoglycan synthesis Bacitracin, vancomycin
E) Block nucleotide synthesis by inhibiting folic Sulfonamides, trimethopri m

acid synthesis (involved in methylation)
0 Block DNA topoisomerases Fluoroqui nolones
0 Block m RNA synthesis Rifampin
0 Damage DNA Metronidazole
0 Block protein synthesis at 50S ribosomal Chloramphenicol, macrol ides, cl indamycin,

subunit streptogramins (qui nupristin , dalfopristin),
l i nezol id
(l) Block protein synthesis at 30S ribosomal Ami noglycosides, tetracycl i nes
subunit
E) SMX, TMP
0 - lacta ms
f) Vancomycin
and bacitraci n
0 Tetracycli nes, 0 Macrolides, c h lora m p h e n icol,

a m i noglycosides clindamycin, linezolid, streptogra m i n s
Penicillin Pen icillin G (IV and I M form), pen icillin V (oral) . Prototype P-lactam antibiotics.
MECHANISM Bind penicill in-binding proteins (transpeptidases)
Block transpeptidase cross-l inking of peptidoglycan
Activate autolytic enzymes
CLINICAL USE Mostly used for gram-positive organisms (S. pneumoniae, S. pyogenes, Actinomyces) . Also used for
Neisseria meningitidis, Treponema pallidum, and syphilis. Bactericidal for gram-positive cocc i ,
gram-positive rods, gram-negative cocci, an d spirochetes. N ot pen icillinase resistant.
TOXICITY Hypersensitivity reactions, hemolytic anem ia.
RESISTANCE P-lactamases cleave P-lactam ring.
M I C R O B I O LOGY MIC R O BI O L O G Y -ANTI MI C R O BIA L S SECTION II 1 77
Oxacillin, nafcillin, dicloxacillin (penicillinase-resistant penicillins)

MECHANISM Same as pen icil l i n . Narrow spectrum; "Use naf (nafcillin) for staph."
pen icillinase resistant because bulky R group
blocks access of -lactamase to -lactam ring.
CliNICAL USE S. au reus (except MRSA; resistant because of
altered penicill in-binding protein target site) .
TOXICITY Hypersensitivity reactions, interstitial nephritis.
Ampicillin, amoxicillin (aminopenicillins)

MECHANISM Same as penicillin. Wider spectrum ; AMinoPenicillins are AMPed-up penicill in .
penicill inase sensitive. Also combine with
clavulanic acid to protect against -lactamase.
Am Oxicillin has greater Oral bioavai labil ity
than ampicillin.
CliNICAL USE Extended-spectrum penicillin Haemophilus
- Coverage : ampici l l i n /amoxicillin HELPSS kill
influenzae, E. coli, Listeria monocytogenes, enterococci .
Proteus mirabilis, Salmonella, Shigella,
enterococci.
TOXICITY Hypersensitivity reactions ; ampicillin rash ;
pseudomembranous colitis.
RESISTANCE -lactamases cleave -lactam ring.
Ticarcillin, piperacillin (antipseudomonals)

MECHANISM Same as penicillin. Extended spectrum.
CliNICAL USE Pseudomonas spp. and gram-negative rods; susceptible to penicil l i nase; use with clavulanic acid.
TOXICITY Hypersensitivity reactions.
-ladamase inhibitors Include Clavulanic Acid, Sulbactam , CAST.

Tazobacta m . Often added to penici llin
antibiotics to protect the antibiotic from
destruction by -lactamase (pen icill inase) .
l 78 SECTION II MI CROBI OLO G Y MICROBIOLOGY-ANTIMICROBIALS
Cephalosporins
MECHANISM -lactam drugs that inhibit cell wall synthesis Organisms typically not covered by
but are less susceptible to pen icill inases. cephalosporins are LAME : Listeria, Atypicals
Bactericidal . (Chlamydia, Mycoplasma) , M RSA, and
Enterococci. Exception : ceftarol ine covers
MRSA.
CliNICAl USE 1 st generation (cefazol in, cephalexin) -gram- 1 st generation - PEcK.
positive cocci, Proteus mirabilis, E. coli,
Klebsiella pnewnoniae. Cefazol in used prior to
surgery to prevent S. aureus wound infections.
2nd generation (cefoxitin, cefaclor, 2nd generation - HEN PEcKS.
cefuroxime) -gram-positive cocci ,
Haemophilus influenzae, Enterobacter
aerogenes, Neisseria spp., Proteus mirabilis,
E. coli, Klebsiella fJneumoniae, Serratia
marcescens.
3rd generation (ceftriaxone, cefotaxime, Ceftriaxone-meningitis and gonorrhea.
ceftazidime) - serious gram-negative infections Ceftazid i me-Pseudomonas.
resistant to other -lactams.
4th generation (cefepime) - t activity against
Pseudomonas and gram-positive organisms.
TOXICITY Hypersensitivity reactions, vitamin K deficiency.
Low cross-reactivity with pen icillins.
t nephrotoxicity of aminoglycosides.
Aztreonam
MECHANISM A monobactam resistant to -lactamases. Prevents peptidoglycan cross-l inking by binding to PBP3.
Synergistic with aminoglycosicles. No cross-allergenicity with penicillins.
CliNICAl USE Gram-negative rods only-No activity against gram-positives or anaerobes. For penicill in-allergic
patients and those with renal insufficiency who cannot tolerate aminoglycosicles.
TOXICITY Usually nontoxic ; occasional GI upset.
lmipenem/ cilastatin, meropenem

MECHANISM Im ipenem is a broad-spectrum, -lactamase With im ipenem, " the kill is lastin' with
resistant carbapenem . Always adm inistered cilastatin."
with cilastatin (inh ibitor of renal ewer carbapenems i nclude ertapenem and
cl e hyclropepticlase I) to ! inactivation of drug cloripenem.
in renal tubules.
CliNICAl USE Gram-positive cocci, gram-negative rods, and
anaerobes. Wiel e spectru m , but the sign ificant
side effects l i m it use to life-threatening
infections, or after other drugs have failed.
Meropenem, however, has a reduced risk of
seizures and is stable to dehyclropepticlase I.
TOXICITY GI d istress, ski n rash, and CNS toxicity
(seizures) at high plasma levels.
M I C R O B I O LO G Y MICRO BIOLO G Y - ANTI MICRO BIAL S SECTION I I 1 79
Vancomycin
MECHANISM Inhibits cell wall peptidoglycan formation by binding 0-ala 0-ala portion o f cell wall precursors.
Bactericidal .
CLIN ICAL USE Cram positive only- serious, amulticlru g-resistant organisms, including M RSA, enterococci, and
Clostridium diffi.cile (oral close for pseudomembranous colitis) .
TOXICITY Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing- red m a n syn d ro m e (can largely
prevent by pretreatment with antihistam ines and slow infusion rate ) . Well tolerated in genera l
does N OT have many problems.
RESISTANCE Occurs with amino acid change of D-ala D-ala to 0-ala 0-lac. " Pay back 2 D-alas (dollars) for
vandalizing (vancomycin) ."
Protein synthesis Specifically target smaller bacterial ribosome "Buy AT 3 0, CCEL (sell) at 50."
inhibitors (70S, made of 30S and 50S subun its), leaving
human ribosome ( 80S) unaffected.
3 05 i n h i b itors
A = Am inoglycosicl e s [bactericidal ]
T Tetracycl i nes [bacteriostatic]
=
5 05 i n h i b itors
C = Chloramphen icol, Clinclamycin [bacteriostatic]

E Erythromycin (macrol icl e s) [bacteriostatic]
=
L Li nezol icl [variable]

=
l i nezolid Ribosomal A&P site

(50S) ,-A---.,
Z.l
PA
mRNA
J
I n itiator tRNA
I n itiation
com plex
1 t-0--
. .
A m 1 n og lycos1de s ( 3 0S) a
formation
PA

Macrolides (erythromycin ) (505)
aAlso causes misreading of mRNA. Clindamycin (50S)
1 80 S E CTI O N I I M I C RO B I O LO G Y M I C R O B I O LO G Y - A N T I M I C R O B I A L S
Aminoglycosides Gentamicin, Neomycin, Am ikacin , "Mean" (arninoglyc oside) GNATS caNNOT

Tobramyci n, Streptomycin. kill anaerobes.
MECHANISM Bactericidal ; inhibit formation of in itiation A " i nitiates" the Alphabet.
complex and cause m isreading of m RNA. Also
block translocation. Require 02 for uptake ;
therefore ineffective against anaerobes.
CLINICAL USE Severe gram-negative rod infections. Synergistic
with P-lactam antibiotics.
Neomycin for bowel surgery.
TOXICITY Nephrotoxicity (especially when used with
cephalosporins ) , Neuromuscular blockade,
Ototoxicity (especially when used with loop
d iuretics) . Teratogen.
RESISTANCE Transferase enzymes that inactivate the drug by
acetylation , phosphorylation, or adenylation.
Tetracyclines Tetracycline, doxycycline, demeclocycl ine, Demeclocycl i ne-ADI-1 antagonist; acts as a

m i nocycl ine. Diuretic in SIAD H . Rarely used as antibiotic.
MECHANISM Bacteriostatic; bind to 30S and prevent
attachment of aminoacyl-tRNA; lim ited CNS
penetration. Doxycycline is fecally el iminated
and can be used i n patients with renal failure.
Do not take with milk, antacids, or iron
containing preparations because divalent
cations inhibit its absorption in the gut.
CLINICAL USE Borrelia burgdorferi, M. pnewnoniae. Drug's
abil ity to accumulate intracellularly makes
it very effective against Rickettsia and
Chlamydia .
TOXICITY Gl distress, discoloration of teeth and inh ibition
of bone growth in children, photosensitivity.
Contraindicated in pregnancy.
RESISTANCE ! uptake into cells or t efflux out of cell by
plasmid-encoded transport pumps.
Macrolides Azithromycin, clarithromycin, erythromycin.

MECHANISM I n h ibit protein synthesis by blocking translocation ( "macroslides" ) ; bind to the 23S rRNA of the
50S ribosomal subunit. Bacteriostatic.
CLINICAL USE Atypical pneumonias (Mycoplasma, Chlamydia, Legionella) , STDs (for Chla mydia), and gram
positive cocci (streptococcal infections in patients allergic to penici l l i n ) .
TOXICITY MACRO : Moti lity issues, Arrhythmia caused b y prolonged QT, acute Cholestatic hepatitis, Rash,
eOsinophil ia. I ncreases serum concentration of theophyll ines, oral anticoagulants.
RESISTANCE Methylation of 23S rRNA binding site.
M I C RO B I O LOGY M I C R O BIO L O G Y - A N T I MIC R O BIA L S SECTI O N I I 1 81
Chloramphenicol
MECHANISM Blocks peptidyltransferase a t 50S ribosomal subunit. Bacteriostatic.
CLINICAL USE Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) .
C onservative use owing to toxicities but often still used in developing countries because of low
cost.
TOXICITY Anemia (close dependent) , aplastic anem ia (close independent) , gray baby syndrome (in premature
infants because they lack liver UDP-glucuronyl transferase) .
RESISTANCE Plasmid-encoded acetyltransferase that inactivates drug.
Clindamycin
MECHANISM Blocks peptide transfer (transpeptidation) at 50S
ribosomal subunit. Bacteriostatic.
CLINICAL USE Anaerobic infections (e.g., Bacteroides fragilis, Treats anaerobes above the diaphragm vs.
Clostridium perfringens) in aspiration metronidazole (anaerobic infections below
pneumonia or lung abscesses. Also oral diaphragm) .
infections with mouth anaerobes.
TOXICITY Pseudomembranous colitis ( C . difficile
overgrowth) , fever, diarrhea.
Sulfonamides Sulfa methoxazole ( SMX), sulfisoxazole, sulfadiazine.

MECHANISM PABA anti metabol ites inhibit dihydropteroate synthase. Bacteriostatic.
CLINICAL USE Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI .
TOXICITY Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial
nephritis) , photosensitivity, kernicterus in infants, d isplace other drugs from album i n (e.g.,
warfarin) .
RESISTANCE Altered enzyme (bacterial d ihydropteroate synthase), uptake, or t PABA synthesis.
tI
PABA + Pteridine
. Su lfo n a m ides I
Dihydropteroate
synthase
Dihydropteroic acid
1
t
D i hyd rofolic acid
'----___--'
Dihydrofolate lir i m e th o p r i m ,
reductase pyrimet h a m i n e
Tetrahydrofolic acid (THF)
1
N 5 N 1 0 -methylene T H F
Pu rines
/ 1 Thymi d i n e Methionine

DNA, RNA DNA P rotein
(Adapted, with permission, from Katzung BG. Basic and Clinical Pharmacology, 7th ed. Stamford, Cf: Appleton & lange, 1 99 7 : 762.)
1 82 SECTION II MI C R OBI OLO G Y MICROBIOLOGY-ANTI MICROBIALS
Trimethoprim
MECHANISM Inh ibits bacterial dihydrofolate reductase.
Bacteriostatic.
CLI N I CAL USE Used i n combination with sulfonamides
(trimethoprim-sulfamethoxazole [TMP
SMX] ) , causing sequential block of folate
synthesis. Combination used for UTis,
Shigella, Salmonella, Pneumocystis jirovecii
pneumonia (treatment and prophylaxis).
TOXICITY Megaloblastic anem ia, leukopenia, Abbreviated TMP.
granulocytopenia. ( May alleviate with TMP: Treats Marrow Poorly.
supplemental fol inic acid [leucovorin rescue ] . )
Fluoroquinolones CiproAoxaci n , norAoxacin, levoAoxacin, oAoxacin, sparAoxaci n , moxiAoxacin, gatiAoxaci n,

enoxacin (Auoroquinolones), nalidixic acid (a quinolone).
MECHAN ISM Inhibit DNA gyrase (topoisomerase I I ) and
topoisomerase IV Bactericidal. Must not be
taken with antacids.
CLINICAL USE Gram-negative rods of urinary and GI tracts
(including Pseudomonas), Neisseria, some
gram-positive organisms.
TOXICITY GI upset, superinfections, skin rashes, Fluoroquinolones hurt attachments to your
headache, dizziness. Less common ly, can bones.
cause tendon itis, tendon rupture, leg cramps,
and myalgias. Contraind icated in pregnant
women and in children because animal
studies show damage to cartilage. Some may
cause prolonged QT i nterval. May cause
tendon rupture i n people > 60 years old and in
patients taking predn isone.
RESISTANCE Chromosome-encoded mutation i n DNA
gyrase, plasm id-mediated resistance, efflux
pumps.
Metronidazole
MECHAN ISM Forms free radical toxic metabol ites in the
bacterial cell that damage DNA. Bactericidal,
antiprotozoal.
CLIN ICAL U S E Treats Giardia, Entamoeba, Trichomonas, GET GAP on the Metro with metron idazole !
Gardnerella vagina/is, Anaerobes (Bacteroides, Treats anaerobic infection below the diaphragm
C. difficile) . Used with a proton pump inhibitor vs. clindamyci n (anaerobic infections above
and clarithromycin for " triple therapy" against diaphragm ) .
H. Pylori.
TOXICITY Disulfiram-like reaction with alcohol ; headache,
meta II ic taste.
M I CROBI O L O G Y MICROBIOLOGY-ANTI MICROBIALS SE CTI O N I I 1 83
Antimycobaderia l d rugs
BACTERIUM PROPHYLAXIS TREATMENT
M. tuberculosis I son iazid Rifampin , Ison iazid , Pyrazinamide,

Ethambutol ( R IPE for treatment)
M . avium-intracellulare Azithromycin Azithromycin, rifampin, ethambutol ,
streptomycin
M. leprae N/A Long-term treatment with dapsone and rifampin
for tuberculoid for m. Add clofazim ine for
lepromatous for m.
Isoniazid (I N H)
MECHAN ISM l synthesis of mycol ic acids . Bacterial catalase INH Injures Neurons and Hepatocytes.
peroxidase ( KatG) needed to convert INH to
active metabolite.
CLINICAL USE Mycobacterium tuberculosis. The only agent Different I H half-lives in fast vs. slow
used as solo prophylaxis against TB. acetyla tors.
TOXICITY Neurotoxicity, hepatotoxicity. Pyridoxine
(vitamin B 6 ) can prevent neurotoxicity, lupus.
Rifampin
MECHANISM Inh ibits DNA-dependent R A polymerase. Rifampin's 4 R's :
CLINICAL USE Mycobacterium tuberculosis; delays resistance RNA polymerase inh ibitor
to dapsone when used for leprosy. Used Revs up m icrosomal P-45 0
for meningococcal prophylaxis and Red /orange body Auids
chemoprophylaxis in contacts of children with Rapid resistance i f used alone
Haemophilus inf/.uenzae type B .
TOXICITY M inor hepatotoxicity a n d drug interactions
( t P-4 5 0 ) ; orange body Auids (nonhazardous
side effect) .
Pyrazinamide
MECHAN ISM Mechanism u ncertain. Thought to acid ify intracel lular environ ment via conversion to pyrazinoic
acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.
CLINICAL U S E Mycobacterium tuberculosis.
TOXICITY Hyperuricem ia, hepatotoxicity.
Ethambutol
MECHANISM l carbohyd rate polymerization of mycobacterium cell wall by blocking arabinosyltransferasc.
CLINICAL USE Mycobacterium tuberculosis.
TOXICITY Optic neuropathy (red-green color blindness ) .
1 84 SECTI O N I I M I C RO B I O LOGY MIC RO BIO LO G Y - ANTIMIC ROBIA L S
Antimicrobial CONDITION MEDICATION

prophylaxis Meningococcal infection Ciprofloxacin (drug of choice) , rifampin for
children
Gonorrhea Ceftriaxone
Syphilis Benzathine pen icillin G
H istory of recurrent UTis TMP-SMX
Endocarditis with surgical or dental procedures Pen icillins
Pregnant woman carrying group B strep Ampicillin
Prophylaxis of strep pharyngitis in child with Oral penicillin
prior rheumatic fever
Prevention of postsurgical infection clue to Cefazol i n
S. aureus
Prevention of gonococcal or chlamydia! Erythromycin ointment
conjunctivitis in newborn
H IV prophylaxis
CELL COUNT PROPHYLAXIS I N FECTION
CD4 < 200 cel ls/m m3 TMP-SMXa Pneumocystis pneumon ia
CD4 < 1 00 cel ls/m m3 TMP-SMXa Pnewnocystis pneumonia and toxoplasmosis
C D 4 < 50 cel l s/mm3 Azithromycin Mycobacterium aviwn complex
a Aerosolized pentam idine may be used if patient is unable to tolerate TMP-SMX, but this may not prevent toxoplasmosis
infection concurrently.
Treatment of highly MRSA-vancomycin.

resistant baderia VRE -linezol icl and streptogramins ( quinupristin/dalfopristin) .
Antifungal therapy Cell w a ll synthesis

Membrane function Caspofungin
Anidu lfu n gi n
/
E rgosterol
N ucleic acid
synthesis
synthesis
Fluconazole
5-Fiucytosine
ltraconazole
Lanosterol synthes is
Voriconazole
Naftifine
Terbi nafine
(Adapted, with permission, from Katzung BG, Trevor AJ . USMLE Rood Mop: Phormocology, l st e d . New York: McGraw-Hill, 2003 : 1 20.)
M I CRO B I O L O G Y MIC R O BIO LO G Y - ANTI MIC R O BIA L S SECT I O N I I 1 85
Amphotericin B
MECHANISM Binds ergosterol (unique to fungi) ; forms Amphotericin " tears" holes i n the fungal
membrane pores that allow leakage of membrane by forming pores.
electrolytes.
CLINICAL USE Serious, systemic mycoses. Cryptococcus
(amphotericin B with/without Aucytosine
for cryptococcal men ingitis) , Blastomyces,
Coccidioides, Histoplasma, Candida,
Mucor. l ntrathecally for fungal men ingitis.
Supplement K and Mg because of altered
renal tubule permeabil ity.
TOXICITY Fever/chills ( "shake and bake"), hypotension,
nephrotoxicity, arrhythm ias, anemia, IV
phlebitis ( "amphoterrible" ) . Hydration
reduces neph rotoxicity. Liposomal
amphotericin reduces toxicity.
Nystatin
MECHANISM Same as amphotericin B. Topical form because too toxic for systemic use.
CLINICAL USE " Swish and swallow" for oral candidiasis (thrush); topical for d i aper rash or vaginal candidiasis.
Azoles Fluconazole, ketoconazole, clotrimazole, m iconazole, itraconazole, voriconazole.

MECHANISM I n h ibit fungal sterol (ergosterol) synthesis, by inhibiting the P-45 0 enzyme that converts lanosterol
to ergosterol.
CLINICAL USE Local and less serious systemic mycoses. Fluconazole for chronic suppression of cryptococcal
meningitis in AIDS patients and candidal infections of all types. Itraconazole for Blastomyces,
Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections.
TOXICITY Testosterone synthesis inh ibition (gynecomastia, esp. with ketoconazole), l iver dysfunction (inhibits
cytochrome P-4 5 0 ) .
Flucytosine
MECHAN ISM Inh ibits DNA a n d RNA biosynthesis b y conversion t o 5-Auorouracil b y cytosine deaminase.
CLIN ICAL USE Used i n systemic fungal infections (esp. men ingitis caused by Cryptococcus) i n combination with
amphotericin B .
TOXICITY B one marrow suppression.
Caspofungin, micafungin
MECHANISM Inh ibits cell wall synthesis by inh ibiting synthesis of -glucan.
CLINICAL USE Invasive aspergillosis, Candida.
TOXICITY GI upset, Aushing (by histam ine release) .
1 86 SECTION II MI CROBI OLO G Y MICROBIOLOGY-ANTI MICROBIALS
Terbinafine
MECHANISM Inhibits the fungal enzyme squalene epoxidase.
CLINICAL USE Used to treat dermatophytoses (especially onychomycosis-fungal infection of finger or toe nails).
TOXICITY Abnormal LFTs, visual d isturbances.
Griseofulvin
MECHANISM Interferes with m icrotubule function ; disrupts m itosis. Deposits i n keratin-containing tissues (e.g.,
nail s ) .
CLINICAL USE Oral treatment of superficial infections; inhibits growth of derm atophytes (tinea, ri ngworm) .
TOXICITY Teratogenic, carcinogenic, confusion , headaches, t P-450 and warfarin metabol ism.
Antiprotoz:oan therapy Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei) , nifurtimox
(T cruzi), sodium stibogluconate (leishmaniasis) .
Chloroquine
MECHAN ISM Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia.
CLIN ICAL USE Treatment of plasmodial species other than P. falciparum (frequency of resistance i n P. falciparwn
is too high) . Resistance due to membrane pump that i ntracellular concentration of d rug. Treat
P. falciparwn with artemether/lumifantrine or atovaquone/proguan i l. For life-threatening malaria,
use quinidine i n U. S . (quinine elsewhere) or artisunate.
TOXICITY Retinopathy.
Antihelminthic therapy Mebendazole, pyrantel pamoate, ivermecti n, diethylcarbamazine, praziquantel ; i mmobil ize
helminths. Use praziquantel against flukes (trematodes) such as Schistosoma.
M I C R O B I O LOGY MIC R O BIO LOGY -ANTI MIC R O BIAL S SECTI O N I I 1 87
Antiviral therapy
-::l ati n g
!
Early p rotei n
Blocked by synthesis
neuraminidase
i n h ibitors
( i nfluenza)
Mammalian
cell !
N u cleic acid
I Blocked by purine
and pyri m id i n e
synthesis analogs, a n d
reverse transcriptase
Packaging Late p rotei n
i n h ibitors
--->.;"'-- and _ synthesis and
assembly processing
--r--; Blocked by
t
Blocked by f---
p rotease
i n h ibitors
rifampin
(vaccinia)
(Adapted, with permission, from Katzung BG, Trevor AJ. USMLE Road Map: Pharmacology, 1 st ed. New York: McGraw-Hill, 2003 : 1 20.)
Zanamivir, oseltamivir
MECHAN ISM Inhibit influenza neur a m i n idase, decreasing the release of progeny virus.
CLINICAL USE Treatment and prevention of both influenza A and B.
Ribavirin
MECHAN ISM Inhibits synthesis of guanine nucleotides by competitively i n h ibiting IMP dehydrogenase.
CLIN ICAL USE RSV, chronic hepatitis C.
TOXICITY Hemolytic anemia. Severe teratogen.
Acyclovir
MECHANISM Monophosphorylated by H SV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by
cellular enzymes. Preferentially inh ibits viral DNA polymerase by chain term ination .
CLINICAL USE H SV and VZV. Weak activity against EBV. No activity against CMV. Used for H SV
induced mucocutaneous and gen ital lesions as wel l as for encephalitis. Prophyl axis in
im munocompromised patients. No effect on latent forms of H SV and VZV. Valacyclovir, a
prodrug of acyclovir, has better oral bioavailability.
For herpes zoster, use a related agent, famciclovir.
TOXICITY Few serious adverse effects.
MECHANISM OF RESISTANCE Mutated viral thym idine kinase.
1 88 SECTI O N I I M I C R O B I O LO G Y MIC RO BIOLOG Y - A N TI MIC RO BIA L S
Cianciclovir
MECHANISM 5'-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by
cellular kinases. Preferentially inh ibits viral DNA polymerase.
CliNICAL USE CMV, especially in im munocomprom ised patients. Valganciclovir, a prodrug of ganciclovir, has
better oral bioava ilabil ity.
TOXICITY Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than
acyclovir.
MECHANISM OF RESISTANCE Mutated CMV DNA polymerase or lack of viral kinase.
Foscamet
MECHANISM Viral DNA polymerase inhibitor that binds to Foscarnet = pyrofosphate analog.
the pyrophosphate-binding site of the enzyme.
Does not require activation by viral kinase.
CLINICAL USE CMV retinitis in immunocomprom ised patients
when ganciclovir fa ils; acyclovir-resistant HSV.
TOXICITY ephrotoxicity.
MECHANISM OF RESISTANCE Mutated DNA polymerase.
Cidofovir
MECHANISM Preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase.
CLINICAL USE CMV retinitis in immunocomprom ised patients ; acyclovir-resistant H SV. Long half-life.
TOXICITY Nephrotoxicity (coadminister with probenecid and IV saline to reduce toxicity) .
M I C R O B I O LO G Y M I C R O B I O LO G Y- A N T I M I C R O B I A L S S ECTI O N I I 1 89
H IV therapy H ighly active antiretroviral therapy ( HAART) : in itiated when patients present with A I D S -defining
illness, low C D4 cell counts (< 500 cells/m m 3 ) , or h igh viral load. Regimen consists of 3 d ru gs to
prevent resistance :
[2 nucleoside reverse transcriptase inh ibitors ( N RTis)] +
[ l non-nucleoside reverse transcriptase inh ibitor ( N N RTI) OR l protease inh ibitor OR l
i ntegrase i nh ibitor]
DRUG M ECHANISM TOXICITY
Protease inhibitors
Lopinavir Assembly of virions depends on HIV-l protease Hyperglycemia, G I i ntolerance (nausea,
Atazanavir (pol gene), wh ich cleaves the polypeptide diarrhea) , l ipodystrophy.
Darunavi r products of HIV mR A into their functional Neph ropathy, hematuria (indinavir) .
Fosamprenavir parts. Thus, protease i nh ibitors prevent
Saquinavir maturation of new viruses.
R itonavi r Ritonavir can "boost" other drug concentrations
l n d inavir by inh ibiting cytochrome P-450.
All protease inh ibitors end in -navir.
Navir ( never) tease a protease.
N RTis
Tenofovir (TDF) Competitively inhibit nucleotide binding to Bone marrow suppression (can be reversed
Emtricitabine (FTC) reverse transcriptase and terminate the D A with G-CSF and erythropoieti n ) , peripheral
Abacav i r (ABC) chai n ( lack a 3' OH group) . Tenofovir is a neuropathy, lactic acidosis (nucleosides ) , rash
Lamivudine (3TC) nucleotide analog and does not have to be (non-nucleosides), anemia (ZDV ) .
Zidovudine (ZDV, activate d ; the others are nucleoside analogs
formerly AZT) and do need to be phosphorylated to be active.
Didanosine (ddl) ZDV is used for general prophylaxis and during
Stavud i n e (d4T) pregnancy to reduce risk of fetal transm ission .
Have you dined (vudine) with my nuclear
( nu cleo sides) fam i ly?
N N RTis
Nevirapine Bind to reverse transcriptase at site different S a m e as N RTJs.
Efavi renz from RTis. Do not require phosphorylation
Delavirdine to be active or compete with nucleotides.
lntegrase inhibitors
Ra ltegravi r Inh ibits HIV genome integration i nto host cell I-Iypercholesterolem ia.
chromosome by reversibly inhibiting HTV
integrase.
Interferons
MECHANISM Glycoproteins synthesized by virus-infected cells ; block repl ication of both RNA and DNA viruses.
CLINICAL USE I FN-a - chronic hepatitis B and C , Kaposi 's sarcoma. I FN- - M S . I FN-y- NADPH oxidase
deficiency.
TOXICITY Neutropenia, myopathy.
l 90 SECTION I I M I C RO B I O LO G Y MIC R O BIO L O G Y - ANTI MIC R O BIA L S
Antibiotics to avoid i n ANTIBIOTIC

--------------------------------------------
ADVERSE EFFECT
pregnancy Sulfonam ides Kern icterus
Am inoglycosides Ototoxicity
Fl uoroqui nolones Cartilage damage
Clarithromycin Embryotoxic
Tetracyclines D iscolored teeth, inhibition of bone growth
Ribavirin (antiviral ) Teratogenic
Griseofulvin (antifungal) Teratogenic
Chloramphenicol "Gray baby"
SAFe Children Take Really Good Care.
Immunology
"I hate to disappoint you, but my rubber lips are immune to your charms."
-Batman & Robin
"No State shall abridge the privileges or immunities of its citizens."

-The United States Constitution
The immunology content on USMLE exams has been expanded and

reclassified into a new category called the immune system. Mastery of
the basic principles and facts in this area will be useful. Cell surface
markers are important to know because they are clinically useful (e.g.,
in identifying specific types of immune deficiency or cancer) and are
functionally critical to the jobs immune cells carry out. By spending a
little extra effort here, it is possible to turn a traditionally difficult subject
into one that is high yield.
l 92 SECTION II IMMUNOLOGY IMMUNOLOGY-LYMPHOID STRUCTURES
IMMUNOLOGY-LYMPHOID STRUCTURES
Lymph node A zo lymphoid organ that has many afferents, l or more efferents. Encapsulated, with trabeculae.
Functions are nonspecific filtration by macrophages, storage and activation of B and T cells,
antibody production.
Follicle Site of B-cell localization and proliferation. Subcapsular Capillary Postcapillary
sinus supply (high endothelial}
In outer cortex. l o follicles are dense and venules
dormant. zo follicles have pale central
Afferent
germinal centers and are active. lymphatic
Medullary
Medulla Consists of medullary cords (closely sinus
packed lymphocytes and plasma cells) (macrophages)
and medullary sinuses. Medullary X.....;I!Sit--

... Trabecula
sinuses communicate with efferent
Medullary
lymphatics and contain reticular cells cords (plasma
cells)
and macrophages. Efferent ---..c.
lymphatic
Paracortex Houses T cells. Region of cortex between Paracortex
(T cells)
follicles and medulla. Contains high
endothelial venules through which T Artery Vein
and B cells enter from blood. In an

extreme cellular immune response, Paracortex enlarges in an extreme cellular immune
paracortex becomes greatly enlarged. response (i.e., viral).
Not well developed in patients with
DiGeorge syndrome.
Lymph drainage A RE A OF BODY 1 lYMPH NODE D R AINA GE SITE
Upper limb, lateral breast Axillary

Stomach Celiac
Duodenum, jejunum Superior mesenteric
Sigmoid colon Colic --+ inferior mesenteric
Rectum (lower portion) of anal canal (above Internal iliac
pectinate line)
Anal canal (below pectinate line) Superficial inguinal
Testes Superficial and deep plexuses --+ para-aortic
Scrotum Superficial inguinal
Thigh (superficial) Superficial inguinal
Lateral side of dorsum of foot Popliteal
Right lymphatic duct-drains right arm, right chest, and right half ofhead.
Thoracic duct-drains everything else.
IMMUNOLOGY IMMUNOLOGY-LYMPHOCYTES SECTION II 1 93
Sinusoids of spleen Long, vascular channels in red pulp with T cells are found in the periarterial lymphatic
fenestrated "barrel hoop" basement sheath (PALS) within the white pulp of the
membrane. Macrophages found nearby. spleen. B cells are found in follicles within the
Arterial supply white pulp of the spleen.
Macrophages in the spleen remove encapsulated
bacteria.
Splenic dysfunction: IgM -+ complement
activation C3b opsonization
-+
-+ t susceptibility to encapsulated organisms:

Germinal center
Streptococcus pneumoniae
(B cells)
PALS (T cells) Haemophilus influenzae type B
Neisseria meningitidis
't'-'t--- Marginal zone Salmonella

(APCs)
Klebsiella pneumoniae
Group B Streptococci (SHiN SKiS)
Postsplenectomy:
Central arteriole Howell-Jolly bodies (nuclear remnants)
Target cells
Thrombocytosis
Venous drainage
Section of white pulp
(Reproduced, with permission, from Junqueira LC, Carneiro J: Basic Histology: Text and Atlas, lith ed. New York: McGraw
Hill, 2005.)
Thymus Site of T-cell differentiation and maturation. T cells = Thymus.

Encapsulated. From epithelium of 3rd B cells = Bone marrow.
branchial pouches. Lymphocytes of
mesenchymal origin. Cortex is dense with
immature T cells; medulla is pale with mature
T cells and epithelial reticular cells containing
Hassall's corpuscles. Positive selection (MHC
restriction) occurs in the cortex and negative
selection (nonreactive to self) occurs in the
m eel ulla.
IMMUNOLOGY-LYMPHOCYTES
Innate vs. adaptive immunity
Innate Receptors that recognize pathogens are germline encoded. Response to pathogens is fast and
nonspecific. No memory. Consists of neutrophils, macrophages, dendritic cells, natural killer cells
(lymphoid origin), and complement.
Adaptive Receptors that recognize pathogens undergo V(D)J recombination during lymphocyte
development. Response is slow on first exposure, but memory response is faster and more robust.
Consists ofT cells, B cells, and circulating antibody.
l 94 SECTION II IMMUNOLOGY IMMUNOLOGY-LYMPHOCYTES
MHC I and I I MHC =major histocompatibility complex, encoded by human leukocyte antigen (l-ILA) genes;
present antigen fragments to T cells and bind T CR.
M HCI HLA-A, BLA-B, HLA-C. Peptide-binding
Binds TCR and CDS.
Expressed on all nucleated cells. Not expressed
on RBC.
Antigen is loaded in RER with mostly
intracellular peptides.
Mediates viral immunity.
Pairs with 2-microglobulin (aids in transport to
cell surface).
M HCII HLA-DR, HLA-DP, HLA-DQ.
Binds TCR and CD4.
Expressed only on antigen-presenting cells
(APCs).
Antigen is loaded following release of invariant
chain in an acidified endosome.
H L A subtypes associated with diseases
A3 Hemochromatosis.
827 Psoriasis, Ankylosing spondylitis, Inflammatory PAIR.
bowel disease, Reiter's syndrome.
DQ2/DQ8 Celiac disease.
DR2 Multiple sclerosis, hay fever, SLE,
Goodpasture's.
DR3 Diabetes mellitus type l, Graves' disease.
DR4 Rheumatoid arthritis, diabetes mellitus type l.
DRS Pernicious anemia B12 deficiency,
-+
Hashimoto's thyroiditis.
Natural killer cells Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.
Only lymphocyte member of innate immune system.
Activity enhanced by IL-2, IL-12, IFN-, and lFN-a.
Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence
of class I MI-IC on target cell surface.
IMMUNOLOGY IMMUNOLOGY-LYMPHOCYTES SECTION II 1 95
Major functions of B and T cells
B cell functions Make antibody-opsonize bacteria, neutralize viruses (IgC); activate complement (IgM, IgC);
sensitize mast cells (IgE).
Allergy (type I hypersensitivity): IgE.
Cytotoxic (type II) and immune complex (type III) hypersensitivity: IgC.
Hyperacute and llllmorally mediated acute and chronic organ rejection.
T cell functions CD4+ T cells help B cells make antibody and produce cytokines to activate other cells of immune
system.
CDS+ T cells kill virus-infected cells directly.
Delayed cell-mediated hypersensitivity (type IV).
Acute and chronic cellular organ rejection.
Differentiation of T cells
Bone marrow Thymus Lymph node
I
I
COStTcell Cytotoxic Tcell (kills virus-infected, neoplastic, and donor graft cells)
.I
CD4tCDSt
Tcell
T-cell precursor Th, cell
0: I
CD4+Tcell Helper Tcell

y T-cell receptor
(bindsMHCI
orMHCII ) Cortex Medulla
'l (positive (negative

CDS selection) selection)
'l CD4
Positive selection Thymic cortex. T cells expressing TCRs capable of binding surface self MHC molecules survive.
Negative selection Medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis.
l 96 SECTION II IMMUNOLOGY IMMUNOLOGY-LYMPHOCYTES
T and B cell adivation Antigen-presenting cells (APCs):

Dendritic cell (only APC that can activate naive T-cell)
Macrophage
B cell
Two signals are required for T cell activation and B cell activation and class switching.
Naive T cell activation l. Foreign body is phagocytosed by dendritic cell.
2. Foreign antigen is presented on MHC II and recognized by TCR on Th (helper) cell. Antigen is
presented on MHC I to Tc (cytotoxic) cells (signal!).
3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2).
4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus
infected cell.
B cell activation and l. Helper T cell activation as above.
class switching 2. B cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by
TCR on Th cell (signal 1).
3. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2).
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and
undergoes class switching, affinity 1:naturation, and antibody production.
Helper T cells
Secretes lF N- y Secretes IL-4, IL-5, IL-10, IL-13

Activates macrophages Recruits eosinophils for parasite defense and
promotes IgE production by B cells
Inhibited by IL-4 and IL-10 (from Th2 cell) Inhibited by IF N-y (from Th1 cell)
Macrophage-lymphocyte interaction-activated lymphocytes (release IFN-y) and macrophages
(release IL-l, TNF-a) stimulate one another.
Helper T cells have CD4, which binds to MHC I I on APCs.
IMMUNOLOGY IMMUNOLOGY-LYMPHOCYTES SECTION II 197
Cytotoxic T cells Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis.
Release cytotoxic granules containing preformed proteins (perforin-helps to deliver the content
of granules into target cell; granzyme-a serine protease, activates apoptosis inside target cell;
granulysin-antimicrobial, induces apoptosis).
Cytotoxic T cells have CDS, which binds to MHC I on virus-infected cells.
Regulatory T cells Help maintain specific immune tolerance by suppressing CD4 and CDS T-cell effector functions.
Express CD3, CD4, CD25 (a chain ofiL-2 receptor) cell surface markers.
Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF- .
Antibody structure and Variable part of L and H chains recognizes antigens. Fe portion of lgM and IgG fixes complement.
function Heavy chain contributes to Fe and Fab fractions. Light chain contributes only to Fab fraction.
Fab:
Antigen-binding fragment
Determines idiotype: unique antigen
binding pocket; only l antigenic specificity

expressed per B cell
Fab
Fe:
Constant
Carboxy terminal
Complement binding at C 2 (IgG + IgM
Complement
11
binding only)
Fe Macrophage ::::::: Carbohydrate side chains
binding
Determines isotype (IgM, IgD, etc.)
Antibody diversity is generated by:

Random "recombination" of VJ (light-chain)
(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. New York: McGraw-Hill, 2005: 528.)
or V (D)J (heavy-chain) genes
Opsonization Neutralization Complement Random combination of heavy chains with
activation light chains
Somatic hypermutation (following antigen
stimulation)
Addition of nucleotides to DNA during
recombination (see lst entry in this list) by

terminal deoxynucleotidyl transferase
Antibody promotes Antibody prevents Antibody activates

phagocytosis bacterial adherence complement, enhancing
opsonization and lysis
1 98 SECTION II I M MUNOLOGY IMMUNOLOGY-LYMPHOCYTES
Immunoglobulin Mature B lymphocytes express IgM and IgD on their surfaces. They may differentiate by isotype
isotypes switching (gene rearrangement; mediated by cytokines and CD40 ligand) into plasma cells that
secrete IgA, IgE, or IgG.
lg G Main antibody in zo (delayed) response to an antigen. Most abundant isotype. Fixes complement,
crosses the placenta (provides infants with passive immunity), opsonizes bacteria, neutralizes
bacterial toxins and viruses.
lgA Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement.
Monomer (in circulation) or dimer (when secreted). Crosses epithelial cells by transcytosis. Found
in secretions (tears, saliva, mucus) and early breast milk (known as colostrum). Picks up secretory
component from epithelial cells before secretion.
lgM Produced in the 1 o (immediate) response to an antigen. Fixes complement but does not cross the
placenta. Antigen receptor on the surface of B cells. Monomer on B cell or pentamer. Shape of
pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves.
lgD Unclear function. Found on the surface of many B cells and in serum.
l gE Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I)
hypersensitivity through release of inflammatory mediators such as histamine. Mediates immunity
to worms by activating eosinophils. Lowest concentration in serum.
Antigen type and memory
Thymus-independent Antigens lacking a peptide component; cannot be presented by MHC to T cells (e.g.,
antigens lipopolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular
antigen). Stimulate release of antibodies and do not result in immunologic memory.
Thymus-dependent Antigens containing a protein component (e.g., diphtheria vaccine). Class switching and
antigens immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40
ligand interaction).
I M MUNO LOGY IMMUNOLOGY-IMMUNE RESPONSES SECTION II 1 99
IMMUNOLOGY-IMMUNE RESPONSES
Complement
Overview System of interacting proteins that play a role in

innate immunity and inflammation. Membrane
attack complex (MAC) of complement defends
against gram-negative bacteria.
Activation Classic pathway-IgG or IgM mediated. GM makes classic cars.
Alternative pathway-microbe surface
molecules.
Lectin pathway-mannose or other sugars on
microbe surface.
Functions C3b-opsonization. C3b binds bacteria.
C3a, C5a-anaphylaxis.
C5a-neutrophil chemotaxis.
C5b-9-cytolysis by MAC.
Opsonins C3b and IgG are the two lo opsonins in
bacterial defense; C3b also helps clear
immune complexes.
Inhibitors Decay-accelerating factor (DAF) and Cl
esterase inhibitor help prevent complement
activation on self cells (e.g., RBC).
Alternative
Spontaneous and
C3

C3b
C3
microbial surfaces
C6-C9
CSb
t
MAC
LYSIS,
CYTOTOXICITY
C4a
C4 C4b
Classic
C1
Antigen-antibody
complexes
C2 C2a C3
C2b
2 00 SECTION II I M MUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES
Complement disorders
C1 esterase inhibitor -+ hereditary angioedema. ACE inhibitors are contraindicated.

deficiency
C3 deficiency -+severe, recurrent pyogenic sinus and respiratory tract infections; t susceptibility to type III
hypersensitivity reactions.
C5-C9 deficiencies -+ recurrent Neisseria bacteremia.
OAF (GPI anchored -+ complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH).
enzyme) deficiency
lmportant cytokines
SECRETED BY MACROPH A GES
IL-1 An endogenous pyrogen. Causes fever, "Hot T-Bone stEAk":

acute inflammation. Activates endothelium IL-l: fever (hot).
to express adhesion molecules; induces IL-2: stimulates T cells.
chemokine secretion to recruit leukocytes. IL-3: stimulates Bone marrow.
IL-4: stimulates IgE production.
IL-5: stimulates IgA production.
IL-6 An endogenous pyrogen. Also secreted by Th2
cells. Causes fever and stimulates production
of acute-phase proteins.
IL-8 Major chemotactic factor for neutrophils. "Clean up on aisle 8." Neutrophils are recruited
by IL-8 to clear infections.
IL-12 Induces differentiation of T cells into Th1 cells.
Activates NK cells. Also secreted by B cells.
TNF-a Mediates septic shock. Activates endothelium.
Causes leukocyte recruitment, vascular leak.
SECRETED BY ALL T CELLS
IL-2 Stimulates growth of helper, cytotoxic, and

regulatory T cells.
IL-3 Supports the growth and differentiation of bone

marrow stem cells. Functions like GM-CSF.
FROM Th1 CELLS
lnterferon-y Activates macrophages and Th1 cells.

Suppresses Th2 cells. Has antiviral and
antitumor properties.
FROM Th2 CELLS
IL-4 Induces differentiation into Th2 cells. Promotes

growth of B cells. Enhances class switching to
IgE and IgG.
IL-5 Promotes differentiation of B cells. Enhances
class switching to IgA. Stimulates the growth
and differentiation of eosinophils.
IL-10 Modulates inflammatory response. Inhibits TGF- has similar actions to IL-10, because it is
actions of activated T cells and Th1 . Also involved in inhibiting inflammation.
secreted by regulatory T cells.
IMMUNOLOGY IMMUNOlOGY-IMMUNE RESPONSES SECTION II 2Q 1
Interferon mechanism Interferons (a, , y) are proteins that place Interferes with viruses:
uninfected cells in an antiviral state. a- and -interferons inhibit viral protein
Interferons induce the production of a synthesis.

ribonuclease that inhibits viral protein y-interferons t MHC I and II expression and
synthesis by degrading viral mRNA (but not antigen presentation in all cells.
host mRNA). Activates K cells to kill virus-infected cells.
Cell surface proteins All cells except mature RBCs have MHC I.
T cells TCR (binds antigcn-MI-IC complex)
CD3 (associated with TCR for signal
transduction)
CD28 (binds B7 on APC)
Helper T cells CD4, CD40 ligand
Cytotoxic T cells CDS
B cells Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV ), CD40 You can drink Beer at the Bar when you're 21:
MHC II, B7 B cells, Epstein-Barr virus; CD-21.
Macrophages CD14, CD40
MHC II, B7
Fe and C3b receptors (enhanced phagocytosis)
NK cells CD16 (binds Fe of lgC), CD56 (unique marker
for NK)
Anergy Self-reactive T cells become nonreactive without costimulatory molecule.

B cells also become anergic, but tolerance is less complete than in T cells.
Effects of bacterial Superantigens (S. pyogenes and S. aureus)-cross-link the region of the T-cell receptor to the
toxins MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines.
Endotoxins/lipopolysaccharide (gram-negative bacteria)-directly stimulate macrophages by
binding to endotoxin receptor CD14; Th cells are not involved.
Antigen variation Classic examples: Some mechanisms for variation include DNA
Bacteria-Salmonella (2 flagellar variants), rearrangement and RNA segment reassortment
Borrelia (relapsing fever), Neisseria (e.g., influenza major shift).
gonorrhoeae (pilus protein).
Virus-influenza (major= shift, minor=
drift).
Parasites-trypanosomes (programmed
rearrangement).
202 SECTION II I M MUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES
Passive vs. adive immunity

Passive Active
MEANS OF ACQUISITION Receiving preformed antibodies Exposure to foreign antigens
ONSET Rapid Slow
DURATION Short span of antibodies (half-life= 3 weeks) Long-lasting protection (memory)
EXAMPLES IgA in breast milk, antitoxin, humanized Natural infection, vaccines, toxoid
monoclonal antibody
NOTES After exposure to Tetanus toxin, Botulinum Combined passive and active immunizations
toxin, HBV, or Rabies virus, patients are can be given in case of hepatitis B or rabies
given preformed antibodies (passive)-"To Be exposure.
Healed Rapidly"
Vaccination Vaccines are used to induce an active immune response (humoral and/or cellular) to specific
pathogens.
VA CCINE TYPE DES C RIPTION PROS/CONS EXAMPLES
Live attenuated Microorganism loses its pathogenicity but Pro: induces strong, Measles, mumps, polio
vaccine retains capacity for transient growth within often life-long (Sabin), rubella,
inoculated host. Mainly induces a cellular immunity. varicella, yellow fever.
response. Con: may revert to
virulent form.
Inactivated or killed Pathogen is inactivated by heat or chemicals; Pro: stable and safer Cholera, hepatitis A,
vaccine maintaining epitope structure on surface than live vaccines. polio (Salk), rabies.
antigens is important for immune response. Con: weaker immune
Humoral immunity induced. response; booster
shots usually
required.
IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES SECTION II 2 03
Hypersensitivity types
Type I Anaphylactic and atopic-free antigen cross First (type) and Fast (anaphylaxis). Types I, II,
links lgE on presensitized mast cells and and III are all antibody mediated.
Mast cell
or basophil basophils, triggering release of vasoactive Test: skin test for specific lgE.
J
._.,,
Fe receptor amines that act at postcapillary venules
(i.e.,
9 histamine). Reaction develops rapidly after
antigen exposure because of preformed
antibody.
Type II Cytotoxic (antibody mediated) -lgM, lgC bind Type II is cy-2-toxic.

to fixed antigen on "enemy" cell, leading to Antibody and complement lead to membrane
cellular destruction. attack complex (MAC).
3 mechanisms: Test: direct and indirect Coombs'.
Opsonization leading to phagocytosis or
complement activation
Complement-mediated lysis
Antibody-dependent cell-mediated
= complement cytotoxicity (ADCC), usually due to NK

cells
Type Ill Immune complex-antigen-antibody (lgC) In type III reaction, imagine an immune
complexes activate complement, which attracts complex as 3 things stuck together: antigen
neutrophils; neutrophils release lysosomal antibody-complement.
enzymes.
Serum sickness-an immune complex Most serum sickness is now caused by drugs
disease (type III) in which antibodies to the (not serum) acting as haptens. Fever, urticaria,
foreign proteins are produced (takes 5 days). arthralgias, proteinuria, lymphadenopathy
Immune complexes form and are deposited in 5-10 days after antigen exposure.
membranes, where they fix complement (leads
to tissue damage). More common than Arthus
reaction.
Arthus reaction-a local subacute antibody Antigen-antibody complexes cause the Arthus
mediated hypersensitivity (type III) reaction. reaction.
Intradermal injection of antigen induces Test: immunofluorescent staining.
antibodies, which form antigen-antibody
complexes in the skin. Characterized
by edema, necrosis, and activation of
complement.
Type IV Delayed (T-cell-mediated) type-sensitized 4th and last-delayed. Cell mediated; therefore,
Antigen
T lymphocytes encounter antigen and then it is not transferable by serum.
presenting cell release lymphokines (leads to macrophage 4 T's T lymphocytes, Transplant rejections,
=
activation; no antibody involved). TB skin tests, Touching (contact dermatitis).

Test: patch test, PPD.
ACID :
Th cells Anaphylactic and Atopic (type I)
Cytotoxic (antibody mediated) (type II)
Immune complex (type Ill)
Delayed (cell mediated) (type IV )
204 SECTION II IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES
Hypersensitivity disorders
REACTION EXA MPLES PRESENTATION
Type I Anaphylaxis (e.g., bee sting, some food/drug Immediate, anaphylactic, atopic
allergies)
Allergic and atopic disorders (e.g., rhinitis, hay
fever, eczema, hives, asthma)
Type II Autoimmune hemolytic anemia (AIHA) Disease tends to be specific to tissue or site
Pernicious anemia where antigen is found
Idiopathic thrombocytopenic purpura
Erythroblastosis fetalis
Acute hemolytic transfusion reactions
Rheumatic fever
Goodpasture's syndrome
Bullous pemphigoid
Pemphigus vulgaris
Type Ill SLE Can be associated with vasculitis and systemic
Polyarteritis nodosa manifestations
Poststreptococcal glomerulonephritis
Serum sickness
Arthus reaction (e.g., swelling and inflammation
following tetanus vaccine)
Type IV Multiple sclerosis Response is delayed and does not involve
Guillain-Barre syndrome antibodies (vs. types I, II, and III)
Graft-versus-host disease
PPD (test forM. tuberculosis)
Contact dermatitis (e.g., poison ivy, nickel
allergy)
Blood transfusion readions

TYPE PATH OGENESIS CLINICAL PRESENTATION
Allergic reaction Type I hypersensitivity reaction against plasma Urticaria, pruritus, wheezing, fever. Treat with
proteins in transfused blood. antihistamines.
Anaphylactic reaction Severe reaction. IgA-deficient individuals must Dyspnea, bronchospasm, hypotension, respiratory
receive blood products that lack IgA. arrest, shock.
Febrile nonhemolytic Type II hypersensitivity reaction. Host Fever, headaches, chills, flushing.
transfusion reaction antibodies against donor HLA antigens and
(FNHTR) leukocytes.
Acute hemolytic 1ype II hypersensitivity reaction. Intravascular Fever, hypotension, tachypnea, tachycardia, flank
transfusion reaction hemolysis (ABO blood group incompatibility) pain, hemoglobinemia (intravascular), jaundice
(HTR) or extravascular hemolysis (host antibody (extravascular hemolysis).
reaction against foreign antigen on donor
RBCs).
IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES SECTION II 205
Autoantibodies AUTOANTIBODY ASSOCIATED DISORDER
Antinuclear antibodies (ANA) SLE, nonspecific

Anti-dsDNA, anti-Smith SLE
Antihistone Drug-induced lupus
Rheumatoid factor, anti-CCP Rheumatoid arthritis
Anticentromere Scleroderma (CREST syndrome)
Anti-Scl-70 (anti-DNA topoisomerase I) Scleroderma (diffuse)
Antimitochondrial 1 biliary cirrhosis
lgA antiendomysial, lgA anti-tissue Celiac disease
transglutaminase
Anti-basement mem brane Goodpasture's syndrome
Anti-desmoglein Pemphigus vulgaris
Antimicrosomal, antithyroglobulin Hashimoto's thyroiditis
Anti-Jo-1, anti-SR P, anti-Mi-2 Polymyositis, dermatomyositis
Anti-SSA (anti-Ro) Sjogren's syndrome
Anti-SSB (anti-La) Sjogren's syndrome
Anti-Ul RNP (ribonucleoprotein) Mixed connective tissue disease
Anti-smooth muscle Autoimmune hepatitis
Anti-glutamate decarboxylase Type l diabetes mellitus
c-ANCA (PR3-ANCA) Granulomatosis with polyangiitis (Wegener's)
p-ANCA ( M PO-ANCA) Microscopic polyangiitis, Churg-Strauss syndrome
Infections in immunodeficiency
PATHOGEN NO T CELLS NO B CELLS NO G RANULOCYTE NO COMPLEMENT
Bacteria Sepsis Encapsulated: Staphylococcus, Neisseria (no

Streptococcus Burkholderia cepacia, membrane attack
pnewnoniae, Serratia, Nocardia complex)
Haemophilus
influenzae type B,
Neisseria
meningitidis,
Salmonella,
Klebsiella
pnewnoniae, group B
Strep (SHiN SKiS)
Virus CMV, EBV, VZV, Enteroviral N/A N/A
chronic infection encephalitis,
with respiratory/GI poliovirus
viruses (live vaccine
contraindicated)
Fungi/parasites Candida, PCP GI giardiasis (no IgA) Candida, Aspergillus N/A
ote: B-cell deficiencies tend to produce recurrent bacterial infections, whereas T-cell deficiencies produce more fungal and
viral infections.
20 6 SECTION II IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES
Immune deficiencies
DISEASE DEFEC T PRESENTATION FINDINGS
B-cell disorders
X-linked (Bruton's) X-linked recessive (t in Boys). Recurrent bacterial infections Normal pro-B, ! maturation,
agammaglobulinemia Defect in BTK, a tyrosine after 6 months (! maternal ! number of B cells,
kinase gene- no B cell IgG) as a result of ! immunoglobulins of all
maturation. opsonization defect. classes.
Selective lgA Unknown. Most common Majority asymptomatic. Can IgA < 7 mg/dL with normal
deficiency primary immunodeficiency. see sinopulmonary infections, IgG, IgM, and IgG vaccine
GI infections, autoimmune titers. False-positive -HCG
disease, Anaphylaxis to tests due to presence of
IgA-containing blood heterophile antibody.
products.
Common variable Defect in B-cell maturation; Can be acquired in 20s-30s; Normal number of B
immunodeficiency many causes. t risk of autoimmune disease, cells; ! plasma cells,
(CVID) lymphoma, sinopulmonary immunoglobulin.
infections.
T-cell disorders
Thymic aplasia 22qll deletion; failure Tetany (hypocalcemia), Thymus and parathyroids
(DiGeorge syndrome) to develop 3rd and 4th recurrent viral/fungal fail to develop- ! T cells,
pharyngeal pouches. infections (T-cell deficiency), ! PTH, ! Ca2+.
congenital heart and great Absent thymic shadow on
vessel defects. CX R.
IL-12 receptor ! Th1 response. Disseminated mycobacterial ! IF N-y.
deficiency infections.
Hyper-lgE syndrome T h1 cells fail to produce IF -y FATED: coarse Facies, cold t IgE.
(Job's syndrome) - inability of neutrophils (noninflamed) staphylococcal
to respond to chemotactic Abscesses, retained primary
stimuli. Teeth, t IgE, Dermatologic
problems (eczema).
Chronic T-cell dysfunction. Candida albicans infections of
mucocutaneous skin and mucous membranes.
candidiasis
IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES SECTION II 207
Immune deficiencies (continued)

DISEASE DEFECT PRESENTATION FINDINGS
B- and T-cell disorders

Severe combined Several types: defective IL-2 Failure to thrive, chronic ! T-cell recombinant excision
immunodeficiency receptor (most common, diarrhea, thrush. Recurrent circles (T RECs).
(SCID) X-linked), adenosine viral, bacterial, fungal, and Absence of thymic shadow,
deaminase deficiency. protozoal infections. Absence germinal centers (lymph node
of thymic shadow, germinal biopsy), and T cells (flow
centers (lymph node biopsy), cytometry).
and B cells (peripheral blood
smear).
Treatment: bone marrow
transplant (no allograft
rejection).
Ataxia-telangiectasia Defects in the ATM gene, Triad: cerebellar defects t AFP.
which codes for DNA repair (ataxia), spider angiomas
enzymes. (telangiectasia), IgA
deficiency.
Hyper-lgM syndrome Most commonly defective Severe pyogenic infections t IgM; ! ! IgG, IgA, IgE.
CD40L on helper T cells = early in life.
inability to class switch.
Wiskott-Aidrich X-linked; in WAS gene on Triad (TIE): t IgE, IgA; ! IgM.
syndrome X chromosome T cells
-+ Thrombocytopenic purpura, Thrombocytopenia.
unable to reorganize actin Infections, Eczema.
cytoskeleton.
Phagocyte dysfunction
Leukocyte adhesion Defect in LFA-1 integrin Recurrent bacterial infections, Neutrophilia.
deficiency (type 1) (CD18) protein on absent pus formation, delayed
phagocytes. separation of umbilical cord.
Chediak-Higashi Autosomal recessive; defect in Recurrent pyogenic infections Giant granules in neutrophils.
syndrome lysosomal trafficking regulator by staphylococci and
gene (LYST). Microtubule streptococci; partial albinism,
dysfunction in phagosome peripheral neuropathy.
lysosome fusion.
Chronic Lack of NADPH oxidase t susceptibility to catalase Abnormal dihydrorhodamine
granulomatous -+ ! reactive oxygen species positive organisms (DHR) flow cytometry test.
disease (e.g., superoxide) and (e.g., S. aureus, E. coli, Nitroblue tetrazolium dye
absent respiratory burst in Aspergillus). reduction test no longer
neutrophils. preferred.
20 8 SECTION II IMMUNOLOGY IMMUNOLOGY-IMMUNE RESPONSES
Grafts
Autograft From self.

Syngeneic graft From identical twin or clone.
Allograft From nonidentical individual of same species.
Xenograft From different species.
Transplant rejection
TYPE OF REJECTION ONSET AFTER TRANSPLANTATION PATHOGENESIS FEAT U RES
Hyperacute Within minutes Antibody mediated (type II) Occludes graft vessels, causing
because of the presence ischemia and necrosis.
of preformed anti-donor
antibodies in the transplant
recipient.
Acute Weeks later Cell-mediated due to CTLs Vasculitis of graft vessels with
reacting against foreign dense interstitial lymphocytic
MHCs. Reversible with infiltrate.
immunosuppressants (e.g.,
cyclosporine, muromonab
CD3).
Chronic Months to years Class 1 -M H C non-s e l f is Irreversible. rf'-cell and
perceived by CTLs as class antibody-mediated vascular
1-M H C s e lf presenting a non damage (obliterative vascular
self antigen. fibrosis); fibrosis of graft tissue
and blood vessels.
Graft-versus-host Varies Grafted immunocompetent Maculopapular rash, jaundice,
T cells proliferate hepatosplenomegaly, and
in the irradiated diarrhea. Usually in bone
immunocompromised marrow and liver transplant
disease host and reject cells (organs rich in lymphocytes).
with "foreign" proteins, Potentially beneficial in bone
resulting in severe organ marrow transplant.
dysfunction.
IMMUNOLOGY IMMUNOLOGY-IMMUNOSUP PRESSANTS SECTION II 209
IM MUNOLOGY-IM M UNOSUPPRESSANTS
Cyclosporine
MECHANISM Binds to cycloph il ins. Comp l ex blocks the d i fferentiation and activation of T ce ll s by i n h ibiting
ca l cineurin, thus preventing the production of i L-2 and its receptor.
CLINI C AL USE Suppresses organ rejection after transplantation ; selected autoimmune d isorders.
TOXICITY Nephrotoxicity, hypertension, hyperlipidemia, hyperg l ycemia, tremor, gingiva l hyperplasia,
h i rsutism .
Tacrolimus {FK-506)
MECHANISM Similar to cyclosporine; binds to FK-binding protein, inhibiting ca l cineur i n and secretion of I L-2
and other cytokines.
CLINICAL USE Potent immunosuppressive used in organ transplant recipients.
TOXICITY S i m ilar to cyclosporine except no gingival hyperp l asia and h i rsuti sm.
Sirolimus (rapamycin)
MECHANISM Inh ibits mTOR. Inh ibits T-ce ll prol iferation in response to I L-2 .
CLINI C AL USE I m munosuppression after kidney transplantation in combination with cyclosporine and
corticosteroids. Also used with drug-e l uting stents.
TOXICITY Hyperl ipidemia, thrombocytopenia, l eukopen ia.
Azathioprine
MECHANISM Antimetabol ite precursor of 6-mercaptopurine that i nterferes with the metabo l ism and synthesis of
nucleic acids. Toxic to prol iferating l ymphocytes.
CLINICAL USE Kidney transplantation, autoim mune disorders (inc l uding glomeru lonephritis and hemolytic
anemia) .
TOXICITY Bone marrow suppression. Active metabol ite mercaptopurine is metabol ized by xanth ine oxidase ;
thus, toxic effects may be increased by allopurinol.
Muromonab-CD3 {OKT3)
MECHANISM Monoclona l antibody that binds to CD3 (epsilon chain) on the surface of T ce l ls. Blocks cel l u l ar
i nteraction with C D 3 protein responsib l e for T-ce l l signa l transduction.
CLINICAL USE I mmunosuppression after kidney transpl antation .
TOXICITY Cytokine re l ease syndrome, hypersensitivity reaction.
210 SECTION II I M MUN O LOGY IMMUNOLOGY-IMMUNOSU P PRESSANTS
Recombinant cytokines
AG N
E T CLI NI C A L U S ES
________________________________ ---------------------------
and clinical uses Aldesleukin (interleukin-2 ) Renal cell carcinoma, metastatic melanoma
Epoetin alfa (erythropoietin) Anem ias (especially in renal fai lure)
Filgrastim (granulocyte colony-stimulating Recovery of bone marrow
factor)
Sargramostim (granulocyte-macrophage colony Recovery of bone marrow
stimulating factor)
a-interferon Hepatitis B and C, Kapos i 's sarcoma, leukemias,
mal ignant melanoma
-interferon Multiple sclerosis
y-interferon Chron ic granulomatous d isease
O prelvekin (interleu kin- l l ) Thrombocytopen ia
Throm bopoietin Thrombocytopenia
Therapeutic antibodies
A GENT TARGET CL I NI C AL USE
Muromonab-CD3 CD3 Prevent acute transplant rej ection

(OKT3)
Digoxin I m mune Fab Digoxin Antidote for d igoxi n i ntoxication
lnfliximab TNF-a Crohn's disease, rheumatoid arthritis, psoriatic
arthritis, ankylosing spondyl itis
Adalimumab TNF-a Crohn's d isease, rheumatoid arthritis, psoriatic
arthritis
Abciximab Glycoprotein Jib/Ilia Prevent card iac ischem ia in unstable angina and
i n patients treated with percutaneous coronary
intervention
Trastuzumab HER2 H E R2-overexpressing breast cancer
(Herceptin)
Rituximab CD20 B-cell non-Hodgkin's lymphoma
O malizumab IgE Add itional l ine of treatment for severe asthma
Pathology
"Digressions, objections, delight in mockery, carefree mistrust are signs of

health; everything unconditional belongs in pathology."
-Friedrich Nietzsche
The fundamental principles of pathology are key to understanding

diseases in all organ systems. Major topics such as inflammation and
neoplasia appear frequently in questions across different organ systems,
and such topics are definitely high yield. For example, the concepts of
cell injury and inflammation are key to understanding the inflammatory
response that follows myocardial infarction, a very common subject of
board questions. Similarly, a familiarity with the early cellular changes
that culminate in the development of neoplasias-for example,
esophageal or colon cancer- is critical. Finally, make sure you
recognize the major tumor-associated genes and are comfortable with
key cancer concepts such as tumor staging and metastasis.
212 SECTION II PATHOLOGY PATHOLOGY-INFLAMMATION
PATHOLOGY-INFLAMMATION
Apoptosis Programmed cell death; AT P required. Intrinsic or extrinsic pathway; both pathways activation
-+
of cytosolic caspases that mediate cellular breakdown. No significant inflammation.

Characterized by cell shrinkage, nuclear shrinkage (pyknosis) and basophilia, membrane blebbing,
nuclear fragmentation (karyorrhexis), and formation of apoptotic bodies, which are then
phagocytosed.

Intrinsic pathway Involved in tissue remodeling in embryogenesis. Intrinsic
Occurs when a growth factor is withdrawn
from a proliferating cell population (e.g., l Fas-
IL-2 after a completed immune reaction -+

\ gaod
CD95 .
apoptosis of proliferating effector cells). Also (Fas-R)
occurs after exposure to injurious stimuli (e.g.,
jl
radiation, toxins, hypoxia).
Changes in proportions of anti- and
pro-apoptotic factors lead to increased
mitochondria permeability and cytochrome c
release. Cytosolic caspases
)
aclivated
Extrinsic pathway 2 pathways:
Ligand receptor interactions (Fas ligand
binding to Fas [CD95]).

Immune cell (cytotoxic T-cell release of
! +
Cellular
perforin and granzyme B). breakdown
Necrosis Enzymatic degradation and protein denaturation of a cell resulting from exogenous injury.
Intracellular components extravasate. Inflammatory process (unlike apoptosis).
Types of necrosis:
Coagulative-heart, liver, kidney
Liquefactive-brain, bacterial abscess, pleural effusion
Caseous-TB, systemic fungi

Fatty-peripancreatic fat (saponification via lipase)
Fibrinoid-blood vessels
Gangrenous-dry (ischemic coagulative) or wet (with bacteria); common in limbs and in

Gl tract
PATHOLOGY PATHOLOGY-INFLAMMATION SECTION II 213
Cell injury REVERSIBLE WITH 0 IRREVERSIBLE
ATP synthesis Nuclear pyknosis, karyolysis, karyorrhexis

Cellular swelling (no AT P-+ impaired Na+fK+ Ca2+ influx-+ caspase activation
pump) Plasma membrane damage
Nuclear chromatin clumping Lysosomal rupture
glycogen Mitochondrial permeability
Fatty change
Ribosomal detachment ( protein synthesis)
Ischemia: susceptible Areas susceptible to hypoxia and ischemia/infarction:

areas
ORGAN LOCATION
Brain ACA/MCA/PCA boundary areasa,b

Heart Subendocardium (LV)
Kidney Straight segment of proximal tubule (medulla)
Thick ascending limb (medulla)
Liver Area around central vein (zone III)
Colon Splenic flexure,3 rectuma
3Watershed areas receive dual blood supply from most distal branches of 2 arteries, which protects
these areas from single-vessel focal blockage. However, these areas are susceptible to ischemia
from systemic hypoperfusion.
b Hypoxic ischemic encephalopathy (HIE) affects pyramidal cells of hippocampus and Purkinje
cells.
Infarcts: red vs. pale Red (hemorrhagic) infarcts occur in loose Red reperfusion.
=
tissues with collaterals, such as liver, lungs, or Reperfusion injury is clue to damage by free
intestine, or following reperfusion. radicals.
Pale infarcts occur in solid tissues with a single
blood supply, such as heart, kidney, and
spleen.
Heart Kidney
infarcts
Shock Hypovolemic/cardiogenic Septic
Low-output failure High-output failure

t T PR ! T PR
Low cardiac output Dilated arterioles, high venous return
Cold, clammy patient (vasoconstriction) Hot patient (vasodilation)
Atrophy Reduction in the size or number of cells. Causes include:

! hormones (uterus/vagina)
! innervation (motor neuron damage)
! blood flow
! nutrients
t pressure (nephrolithiasis)
Occlusion of secretory ducts (cystic fibrosis)
Inflammation Characterized by rubor (redness), dolor (pain), calor (heat), tumor (swelling), and
functio laesa (loss of function).
Vascular component t vascular permeability, vasodilation, endothelial injury.
Cellular component Neutrophils extravasate from circulation to injured tissue to participate in inflammation through
phagocytosis, degranulation, and inflammatory mediator release.
Acute Neutrophil, eosinophil, and antibody mediated. Acute inflammation is rapid onset (seconds to
minutes), lasts minutes to days. Outcomes include complete resolution, abscess formation, and
progression to chronic inflammation.
Chronic Mononuclear cell mediated: characterized by persistent destruction and repair. Associated with
blood vessel proliferation, fibrosis. Granuloma: nodular collections of epithelioid macrophages
and giant cells. Outcomes include scarring and amyloidosis.
Leukocyte Neutrophils exit from blood vessels at sites of tissue injury and inflammation in 4 steps:
extravasation
STEP VASCULATURE/STROMA LEUKOCYTE
0 Rolling E-selectin Sialyl-Lewisx

P-selectin
@ Tight binding ICAM-1 LFA-1 ("integrin")
E) Diapedesis-leukocyte travels between PECAM-1 PECAM-1

endothelial cells and exits blood vessel
0 Migration-leukocyte travels through Bacterial products: Various
interstitium to site of injury or infection C5a, IL-8, LTB4 and
guided by chemotactic signals Kallikrein ( C I LK)
0 Rolling -----. @Tight binding ----+ E) Diapedesis---+ 0 Migration ----+ Phagocytosis
Vessel
lumen
Endothelium
____.. ...._
____ __
Interstitium
Free radical injury Free radicals damage cells via membrane lipid peroxidation, protein modification, and DNA
breakage.
Initiated via radiation exposure, metabolism of drugs (phase 1), redox reaction, nitric oxide,
transition metals, leukocyte oxidative burst.
Free radicals can be eliminated by enzymes (catalase, superoxide dismutase, glutathione
peroxidase), spontaneous decay, antioxidants (vitamins A, C, E).
Pathologies include:
Retinopathy of prematurity
Bronchopulmonary dysplasia
Carbon tetrachloride, leading to liver necrosis (fatty change)
Acetaminophen overdose (fulminant hepatitis)

Iron overload (hemochromatosis)
Reperfusion after anoxia (e.g., superoxide), especially after thrombolytic therapy

Wound healing
PHASE MEDIATORS CHARACTERISTICS
Inflammatory Platelets, neutrophils, macrophages Clot formation, t vessel permeability and
(immediate) neutrophil migration into tissue; macrophages
clear debris 2 days later
Proliferative Fibroblasts, myofibroblasts, endothelial cells, Deposition of granulation tissue and collagen,
{2-3 days after keratinocytes, macrophages angiogenesis, epithelial cell proliferation,
wound) dissolution of clot, and wound contraction
(mediated by myofibroblasts)
Remodeling Fibroblasts 1ype III collagen replaced by type I collagen,
(1 week after wound) t tensile strength of tissue
Granulomatous Mycobacterium tuberculosis Th1 cells secrete y-interferon, activating

diseases Fungal infections (e.g., histoplasmosis), macrophages. TNF-a from macrophages
coccidioidomycosis) induce and maintain granuloma formation.
Treponema pallidum (syphilis) Anti-TNF drugs can, as a side effect, cause
M. leprae (leprosy) sequestering granulomas to breakdown,
Bartonella henselae (cat scratch disease) leading to disseminated disease.
Sarcoidosis
Crohn's disease
Granulomatosis with polyangiitis (Wegener's)
Churg-Strauss syndrome
Berylliosis, silicosis
Transudate vs. exudate Transudate Exudate
Hypocellular Cellular
Protein poor Protein rich
Specific gravity< 1 .01 2 Specific gravity> 1 .020
Due to: Due to:
t hydrostatic pressure Lymphatic obstruction
! oncotic pressure Inflammation
a+ retention
Erythrocyte Products of inflammation (e.g., fibrinogen) coat RBCs and cause aggregation. When aggregated,
sedimentation rate RBCs fall at a faster rate within the test tube.
t ESR ESR
Infections Sickle cell (altered shape)
Inflammation (e.g., temporal arteritis) Polycythemia (too many)
Cancer CHF (unknown)
Pregnancy
SLE
Iron poisoning One of the leading causes of fatality from toxicologic agents in children.
MECHANISM Cell death due to peroxidation of membrane lipids.
SYMPTOMS Acute-gastric bleeding.
Chronic-metabolic acidosis, scarring leading to GI obstruction.
Amyloidosis Abnormal aggregation of proteins or their

fragments into -pleated sheet structures,
leading to cell damage and apoptosis (J.
Affected tissue has waxy appearance.
Amyloidosis. Note the apple-green birefringence (Congo

red sta1n) of the amyloid deposits 1n the artery wall.
COMMON TYPES DESCRIPTION
AL (primary) Due to deposition of proteins from Ig Light chains. Can occur as a plasma cell disorder or
associated with multiple myeloma. Often multiple organ sytem impact, including renal (nephrotic
syndrome), cardiac (heart failure, arrhythmia), hematologic (easy bruising), hepatomegaly, and
neuropathy.
AA (secondary) Seen with chronic diseases like RA, IBD, spondyloarthropathy, chronic infections. Fibrils
composed of serum Amyloid A. Often multisystem like AL amyloidosis.
Dialysis-related Fibrils composed of rmicroglobulin in patients with ESRD and long-term dialysis. Often presents
as carpal tunnel syndrome and other joint issues.
Heritable Heterogeneous group of disorders. Example is ATTR neurologic/cardiac amyloidosis due to
transthyretin (TTR or prealbumin) gene mutation.
Age-related (senile) Due to deposition of normal (wild-type) TTR in myocardium and other sites. Slower progression of
systemic cardiac dysfunction vs. AL amyloidosis.
Organ-specific Amyloid deposition localized to a single organ. Most important form is amyloidosis in Alzheimer's
disease due to deposition of amyloid- protein cleaved from amyloid precursor protein (APP).
218 SECTION II PATHOLOGY PATHOLOGY-NEO PLASIA
PATHOLOGY-NEOPLASIA
Neoplastic progression Hallmarks of cancer-evasion of apoptosis, self-sufficiency in growth signals, insensitivity to
anti-growth signals, sustained angiogenesis, limitless replicative potential, tissue invasion, and
metastasis.
Normal cells with basal apical differentiation
i(OJ[QJ[Q)I$[Q)
membrane
Normal

Cells have increased in number-hyperplasia
fE][QJLQ)[Qj[)

Abnormal proliferation of cells with loss of size, shape, and

00 0
0
0
0 Q
orientation-dysplasia
Carcinoma in situ
Neoplastic cells have not invaded basement membrane
High nuclear/cytoplasmic ratio and clumped chromatin
Neoplastic cells encompass entire thickness
Carcinoma in situ/
preinvasive

Cells have invaded basement membrane using collagenases and
hydrolases (metalloproteinases)
Can metastasize if they reach a blood or lymphatic vessel
Invasive carcinoma
Metastasis-spread to distant organ

Must survive immune attack
"Seed and soil" theory of metastasis
Seed =tumor embolus
Soil =target organ---jiver, lungs, bone, brain, etc.
Blood or
lymphatic
vessel
PATHOLOGY PATHOLOGY-NEOPLASIA SECTION II 219
-plasia definitions
REVERSIBLE
Hyperplasia t in number of cells.
Metaplasia One adult cell type is replaced by another. Often zo to irritation and/or environmental exposure
(e.g., squamous metaplasia in trachea and branchi of smokers).
Dysplasia Abnormal growth with loss of cellular orientation, shape, and size in comparison to normal tissue
maturation; commonly preneoplastic.
IRREVERSIBLE
Anaplasia Abnormal cells lacking differentiation; resemble primitive cells of same tissue, often equated with
undifferentiated malignant neoplasms. Little or no resemblance to tissue of origin.
Neoplasia A clonal proliferation of cells that is uncontrolled and excessive. Neoplasia may be benign or
malignant.
Desmoplasia Fibrous tissue formation in response to neoplasm.
Tumor grade vs. stage
Grade Degree of cellular differentiation based on Stage usually has more prognostic value than
histologic appearance of individual tumor. grade.
Usually graded l-4; l = low grade, well
differentiated to 4=high grade, poorly
differentiated, anaplastic.
Stage Degree of localization/spread based on site and TNM staging system (Stage=Spread):
size of l o lesion, spread to regional lymph T =Tumor size
nodes, presence of metastases; spread of tumor N =Node involvement
in a specific patient. Based on clinical (c) or M =Metastases (important prognostic factor)
pathology (p) findings. Example: cT3NlMO
Tumor nomenclature
CELL TYPE BENIGN MALIGNANT"
Epithelium Adenoma, papilloma Adenocarcinoma, papillary carcinoma

Mesenchyme
Blood cells Leukemia, lymphoma

Blood vessels Hemangioma Angiosarcoma
Smooth muscle Leiomyoma Leiomyosarcoma
Striated muscle Rhabdomyoma Rhabdomyosarcoma
Connective tissue Fibroma Fibrosarcoma
Bone Osteoma Osteosarcoma
Fat Lipoma Liposarcoma
"The term carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin. Both terms imply malignancy.
2 20 SECTION II PATHOLOGY PATHOLOGY-NEOPLASIA
Tumor differences
Benign Usually well differentiated, slow growing, well demarcated, no metastasis.

Malignant May be poorly differentiated, erratic growth, locally invasive/diffuse, may metastasize.
Cachexia Weight loss, muscle atrophy, and fatigue that occur in chronic disease (e.g., cancer, AIDS, heart
failure, tuberculosis). Mediated by TNF-a (nicknamed cachectin), IFN-y, and IL-6.
Disease CONDITION NEOPLASM

conditions associated Down syndrome ALL ("we ALL fall Down"), AML
with neoplasms
Xeroderma pigmentosum, albinism Melanoma, basal cell carcinoma, and especially
squamous cell carcinomas of skin
Chronic atrophic gastritis, pernicious anemia, Gastric adenocarcinoma
postsurgical gastric remnants
Tuberous sclerosis (facial angiofibroma, Giant cell astrocytoma, renal angiomyolipoma,
seizures, mental retardation) and cardiac rhabdomyoma
Actinic keratosis Squamous cell carcinoma of skin
Barrett's esophagus (chronic GI reflux) Esophageal adenocarcinoma
Plummer-Vinson syndrome (l iron) Squamous cell carcinoma of esophagus
Cirrhosis (alcoholic, hepatitis B or C) Hepatocellular carcinoma
Ulcerative colitis Colonic adenocarcinoma
Paget's disease of bone zo osteosarcoma and fibrosarcoma
Immunodeficiency states Malignant lymphomas
AIDS Aggressive malignant lymphomas (non
I-Iodgkin's) and Kaposi's sarcoma
Autoimmune diseases (e.g., Hashimoto's Lymphoma
thyroiditis, myasthenia gravis)
Acanthosis nigricans (hyperpigmentation and Visceral malignancy (stomach, lung, uterus)
epidermal thickening)
Dysplastic nevus Malignant melanoma
Radiation exposure Leukemia, sarcoma, papillary thyroid cancer,
and breast cancer.
PATHOLOGY PATHOLOGY-NEOPLASIA SECTION II 22 1
Oncogenes Gain of function -+ t cancer risk. Need damage to only l allele.

GENE ASSOCIATED TUMOR GENE PRODUCT
obi CML Tyrosine kinase

c-myc Burkitt's lymphoma Transcription factor
bc/-2 Follicular and undifferentiated lymphomas Anti-apoptotic molecule
(inhibits apoptosis)
HER2/neu (c-erb82) Breast, ovarian, and gastric carcinomas Tyrosine kinase
ros Colon carcinoma GTPase
L-myc Lung tumor Transcription factor
N-myc Neuroblastoma Transcription factor
ret Multiple endocrine neoplasia (MEN) types 2A Tyrosine kinase
and 2B
c-kit Gastrointestinal stromal tumor (GIS T ) Cytokine receptor
Tumor suppressor Loss of function -+ t cancer risk; both alleles must be lost for expression of disease.
genes
GENE ASSOCIATED TUMOR GENE PRODUCT
Rb Retinoblastoma, osteosarcoma Inhibits E2F; blocks Gl -+ S phase

p5l Most human cancers, Li-Fraumeni syndrome Transcription factor for p2l, blocks Gl -+ S phase
BRCAI Breast and ovarian cancer DNA repair protein
BRCA2 Breast and ovarian cancer DNA repair protein
p16 Melanoma
BRAF Melanoma B-raf
APC Colorectal cancer (associated with FAP)
WTI Wilms' Tumor (nephroblastoma)
NFI NeuroFibromatosis type l RAS GT Pase activating protein (RAS-GAP)
NF2 NeuroFibromatosis type 2 Merlin (schwannomin) protein
DPC4 Pancreatic cancer DPC-Deleted in Pancreatic Cancer
DCC Colon cancer DCC-Deleted in Colon Cancer
222 SECTION II PATHOLOGY PATHOLOGY-NEOPLASIA
Tumor markers
PSA Prostate-specific antigen. Used to follow prostate Tumor markers should not be used as the 1o
carcinoma. Can also be elevated in BPH tool for cancer diagnosis. They may be used
and prostatitis. Questionable risk/benefit for to confirm diagnosis, to monitor for tumor
screening. recurrence, and to monitor response to
Prostatic acid Prostate carcinoma. therapy.
phosphatase
CEA CarcinoEmbryonic Antigen. Very nonspecific

but produced by- 70% of colorectal and
pancreatic cancers; also produced by gastric,
breast, and medullary thyroid carcinomas.
a-fetoprotein Normally made by fetus. Hepatocellular
carcinomas. Nonseminomatous germ cell
tumors (e.g., testis, ovary).
-hCG Hydatidiform moles and Choriocarcinomas hCG is commonly associated with pregnancy.
(Gestational trophoblastic disease).
CA-125 Ovarian cancer.
S-100 Melanoma, neural tumors, schwannomas.
Alkaline phosphatase Metastases to bone, liver, Paget's disease of
bone.
Bombesin Neuroblastoma, lung and gastric cancer.
T RAP Tartrate-Resistant Acid Phosphatase (TRAP). TRAP the hairy animal.
Hairy cell leukemia-a B-cell neoplasm.
CA-19-9 Pancreatic adenocarcinoma.
Calcitonin Medullary thyroid carcinoma.
Oncogenic microbes Microbe Associated cancer
HTLV-1 Adult T-cell leukemia/lymphoma

HBV, HCV Hepatocellular carcinoma
EBV Burkitt's lymphoma, Hodgkin's lymphoma,
nasopharyngeal carcinoma, CNS lymphoma
(in immunocompromised patients)
HPV Cervical carcinoma (16, 18), penile/anal
carcinoma, upper respiratory sec
H HV-8 ( Kaposi's sarcoma-associated Kaposi's sarcoma, body cavity Auicl B-cell
herpesvirus) lymphoma
H. pylori Gastric adenocarcinoma and lymphoma
Schistosoma haematobium Bladder cancer (squamous cell)
Liver fluke (Clonorchis sinensis) Cholangiocarcinoma
PATHOLOGY PATHOLOGY-NEOPLASIA SECTION II 223
Chemical carcinogens
TOXIN ORGAN IMPACT
Aflatoxins (Aspergillus) Liver Hepatocellular carcinoma

Vinyl chloride Liver Angiosarcoma
Carbon tetrachloride Liver Centrilobular necrosis, fatty change
Nitrosamines (smoked Stomach Gastric cancer
foods)
Cigarette smoke Larynx Squamous cell carcinoma

Lung Squamous cell and small cell carcinoma
Kidney Renal cell carcinoma
Bladder Transitional cell carcinoma
Pancreas Pancreatic adenocarcinoma
Asbestos Lung Bronchogenic carcinoma> mesothelioma
Arsenic Skin Squamous cell carcinoma
Liver Angiosarcoma
Naphthalene (aniline) Bladder Transitional cell carcinoma
dyes
Alkylating agents Blood Leukemia
Paraneoplastic syndromes
HORMONE/AGENT EFFECT NEOPLASM($)
ACTH or ACTH-Iike Cushing's syndrome Small cell lung carcinoma
peptide
ADH SIADI-I Small cell lung carcinoma and intracranial

neoplasms
PTHrP Hypercalcemia Squamous cell lung carcinoma, renal cell
carcinoma, breast cancer
1 ,25-(0H) 2 D3 Hypercalcemia Hodgkin's lymphoma, some non-Hodgkin's
(calcitriol) lymphomas
Erythropoietin Polycythemia Renal cell carcinoma, hemangioblastoma,
hepatocellular carcinoma, pheochromocytoma
Antibodies against Lambert-Eaton syndrome (muscle weakness) Small cell lung carcinoma
presynaptic Ca2+
channels at NMJ
Psammoma bodies Laminated, concentric, calcific spherules PSaMMoma:

seen 111: Papillary (thyroid)
Papillary adenocarcinoma of thyroid Serous (ovary)
Serous papillary cystadenocarcinoma of Meningioma
ovary Mesothelioma
Meningioma
Malignant mesothelioma
2 24 SECTION II PATHOLOGY PATHOLOGY-NEOPLASIA
Cancer epidemiology
MALE FEMALE NOTES
Incidence Prostate (32%) Breast (32%) Lung cancer incidence has dropped in men, but
Lung (16%) Lung (13%) has not changed significantly in women
Colon/rectum (12%) Colon/rectum (13%)
Mortality Lung (33%) Lung (23%) Cancer is the 2nd leading cause of death in the
Prostate (13%) Breast (18%) United States (heart disease is lst)
Common metastases
SITE OF METASTASIS l0TUMOR NOTES
Brain Lung> breast> genitourinary> osteosarcoma 50% of brain tumors are from metastases.
> melanoma> GI. Typically multiple well-circumscribed tumors at
gray/white matter junction.
Liver Colon>> stomach> pancreas. Liver and lung are the most common sites of
metastasis after the regional lymph nodes.
Bone Prostate, breast> lung> thyroid, testes. Bone metastasis>> primary bone tumors.
Whole-body bone scan shows tumor
predilection for axial skeleton.
Lung= lytic.
Prostate = blastic.
Breast= lytic and blastic.
Pharmacology
"Take me, I am the drug; take me, I am hallucinogenic."

- Salvador Dal i
"I was under medication when I made the decision not to bum the tapes."
-Richard Nixon
"I wondher why ye can always read a doctor's bill an' ye niver can read his
fntrscription."
- Finley Peter Dunne
"Once you get locked into a serious drug collection, the tendency is to
push it as far as you can."
-Hunter S. Thompson
Preparation for questions on pharmacology is straightforward. Memorizing

all the key drugs and their characteristics (e.g., mechanisms, clinical use,
and important side effects) is high yield. Focus on understanding the
prototype drugs in each class. Avoid memorizing obscure derivatives.
Learn the "classic" and distinguishing toxicities of the major drugs.
Specific drug dosages or trade names are generally not testable. Reviewing
associated biochemistry, physiology, and microbiology can be useful
while studying pharmacology. There is a strong emphasis on ANS, CNS,
antimicrobial, and cardiovascular agents as well as on NSAIDs. Much of
the material is clinically relevant. Newer drugs on the market are also fair
game.
226 SECTION II PHARMACOLOGY PHARMACOLOGY-PHARMACOKINETICS & PHARMACODYNAMICS
PHARMACOLOGY-PHARMACOKINETICS & PHARMACODYNAMICS
Enzyme kinetics
Michaelis-Menten [ S] = concentration of substrate; V= velocity. Kill is inversely related to the affinity of the
kinetics enzyme for its substrate.
vlllax is directly proportional to the enzyme
concentration.
Most enzymatic reactions follow a hyperbolic
curve (follow Michaelis-Menten kinetics);
however, enzymatic reactions that follow
cooperative kinetics (i.e., hemoglobin) have a
sigmoid curve.
lineweaver-Burk plot t y-intercept,! vlllax

The further to the right the x-intercept, the
1
greater the Kill and the lower the affinity.
\
1
[S]
Enzyme inhibition Competitive inhibitors cross each other

competitively, whereas noncompetitive
inhibitors do not.
1
TSi
COMPETITIVE NONCOMPETITIVE
INHIBITORS INHIBITORS
Resemble substrate Yes No

Overcome by t [S] Yes No
Bind active site Yes No
Effect on V Unchanged
max
Effect on K Unchanged
m
Pharmacodynamics ! potency ! efficacy
I
PHARMACOLOGY PHARMACOLOGY-PHARMACOKINETICS & PHARMACODYNAMICS SECTION II 227
Pharmacokinetics
Bioavailability (F) Fraction of administered drug that reaches systemic circulation unchanged. For an I V dose,
F 100%.
=
Orally: F typically <100% to incomplete absorption and first-pass metabolism.

Volume of distribution Theoretical fluid volume required to maintain the total absorbed drug amount at the plasma
(Vd) concentration. Vel of plasma protein-bound drugs can be altered by liver and kidney disease
(protein binding, t Vel).
amount of drug in the body
Vel=
plasma drug concentration
DISTRIBUTION DRUG TYPES
Low (4-8 L) Blood Large/charged molecules; plasma protein

bound
Medium ECF Small hydrophilic molecules
High All tissues Small lipophilic molecules, especially if bound
to tissue protein
Half-life (t112) The time required to change the amount of drug in the body by Y, during elimination (or constant
infusion). Property of first-order elimination. A drug infused at a constant rate takes 4-5 half-lives
to reach steady state.
#of half-lives l 2 3 4
% remaining 50% 25% 12.5% 6.25%
Clearance (CL) Relates the rate of elimination to the plasma concentration. Clearance may be impaired with
defects in cardiac, hepatic, or renal function.
rate of elimination of drug
CL = = V 1 x Ke (e 1.ImmatiOn
constant)
plasma drug concentration c
Dosage calculations Loading dose= c X Vel/F. In renal or liver disease, maintenance dose and
p
Maintenance close= c X CL/ F. loading dose is unchanged.
p
c =target plasma concentration. Time to steady state depends primarily on t 112
p
and is independent of closing frequency or size.
22 8 SECTION II PHARMACOLOGY PHARMACOLOGY-PHARMACOKINETICS & PHARMACODYNAMICS
Elimination of drugs
Zero-order elimination Rate of elimination is constant regardless of C Capacity-limited elimination.

P
(i.e., constant amount of drug eliminated per PEA. (A pea is round, shaped like the "0" in
unit time). C ! linearly with time. Examples "zero-order. )
r
"
of drugs- Phenytoin, Ethanol, and Aspirin (at

high or toxic concentrations).
First-order elimination Rate of elimination is directly proportional to F low-dependent elimination.
the drug concentration (i.e., constant fraction
of drug eliminated per unit time). cp!
exponentially with time.
Zero-order elimination First-order elimination
5 units/h
U
2.5 units/h
elimination rate
U
c
elimination
c
0 0 rate
U
.;::;
......--

c
u
c
Ql
Ql
u 2.5 ""''"" u 2.5 oottslh
u
c c
y
0 0
u
-i units/h
u u
ell
ell
E 2.5 E
(/) (/) 125
ell ell
0::: 0:::
Time (h) Time (h)
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Boord Review, 5th ed. Stamford, CT: Appleton &
Lange, 1998: 5.)
Urine pH and drug Ionized species are trapped in urine and cleared quickly. Neutral forms can be reabsorbed.
elimination
Weak acids Examples: phenobarbital, methotrexate, aspirin. Trapped in basic environments. Treat overdose
with bicarbonate.
RCOOH RCOO- + H+
(lipid soluble) (trapped)
Weak bases Example: amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride.
RNI-13+ RNI-I2 + I-I+
(trapped) (lipid soluble)
Drug metabolism
Phase I Reduction, oxidation, hydrolysis with Geriatric patients lose phase I first.
cytochrome P-450 usually yield slightly polar,
water-soluble metabolites (often still active).
Phase II Conjugation (Glucuronidation, Acetylation, Geriatric patients have GAS (phase II).
Sulfation) usually yields very polar, inactive Patients who are slow acetylators have greater side
metabolites (renally excreted). effects from certain drugs because of! rate of
metabolism.
PHARMACOLOGY PHARMACOLOGY-PHARMACOKINETICS & PHARMACODYNAMICS SECTIONII 2 29
Efficacy vs. potency
Efficacy Maximal effect a drug can produce. High-efficacy drug classes are analgesic (pain) medications,
antibiotics, antihistamines, and decongestants. Partial agonists have less efficacy than full
agonists.
Potency Amount of drug needed for a given effect. t potency, t affinity for receptor. Highly potent drug
classes include chemotherapeutic (cancer) drugs, antihypertensive (blood pressure) drugs, and
antilipicl (cholesterol) drugs.
Receptor binding
100 100 100 --------------------
Agonist
t5 alone t5
:;::
Q)
:;::
Q)
t5
:;::
Q) Q)
Q)
E E Q)
:J Agonist plus :J
E E
E :J
competitive "'
x E
"'
x
50
E
__
antagonist "'
x
E
0 0 E
c c 0
Q) Q) Agonist plus c
" "
Q) Q) noncompetitive Q)
"
antagonist
a. a. Q)
a.
0 --
0 -
0
0.1 1.0 10 100 1000 0.1 1.0 10 100 1000 0.1 1.0 10 100 1000
Agonist dose (log scale) Agonist dose (log scale) Agonist dose (log scale)
0 0
(Image A and B reproduced, with permission, from Trevor AJ et al. Katzung & Trevor's Pharmacology: Examination & Board Review, 8th ed. New York: McGraw-Hill, 2008: 14. Image C adapted, with
permission, from Katzung BG. Basic and Clinical Pharmacology, 7th ed. Stamford, CT: Appleton & Lange, 1997: 13.)
FIGURE EFFECT EXAMPLE
0 Competitive Shifts curve to right-+ ! potency, no change in Diazepam + Aumazenil on GABA receptor.
antagonist efficacy. Can be overcome by increasing the
concentration of agonist substrate.
0 Noncompetitive Shifts curve clown -+ ! efficacy. Cannot be NE + phenoxybenzamine on a-receptors.

antagonist overcome by increasing agonist substrate
concentration.
E) Partial agonist Acts at same site as full agonist, but with Morphine (full agonist) + buprenorphine
reduced maximal effect-+ ! efficacy. Potency (partial agonist) at opioid !J.-receptor.
is a different variable and can be t or!.
Therapeutic index Measurement of drug safety. TILE: Therapeutic Index= L D50 I E D50.
L Dso _ median lethal close Safer drugs have higher TI values. Examples
of drugs with low TI values include digoxin,
-
EDso median effective close

lithium, theophylline, and warfarin.
Therapeutic window Measure of clinical drug safety. Range of minimum effective close to minimum toxic close.
230 SECTION II PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS
PHARMACOLOGY-AUTONOMIC DRUGS
Central and peripheral nervous system
ACh
ACh N
Parasympathetic
- -,
.....- Cardiac and smooth muscle,
Medulla
gland cells, nerve terminals
---
@
Sympathetic
A h Sweat glands
---- ,
NE
a
Sympathetic
Cardiac and smooth muscle,
gland cells, nerve terminals
D
Sympathetic
Spinal

cord Renal vasculature,
smooth muscle
ACh
:-4 Somatic
w Skeletal muscle
Voluntary motor nerve
(Adapted, with permission, from Katzung BG. Basic and Clinical Pharmacology, lOth ed. New York: McGraw-Hill, 2007: 76.)
Note that the adrenal medulla and sweat glands are part of the sympathetic nervous system but are
innervated by cholinergic fibers.
Botulinum toxin prevents release of neurotransmitter at all cholinergic terminals.
ACh receptors Nicotinic ACh receptors are ligand-gated Na+JK+ channels; NN (found in autonomic ganglia) and
N M (found in neuromuscular junction) subtypes.
Muscarinic ACh receptors are G-protein-coupled receptors that act through 2nd messengers;
5 subtypes: M 1, M2 , M3, M4, and M5.
PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS SECTIONII 23 l
G-protein-linked lnd messengers

RECEPTOR G-PROTEIN CLASS MAJOR FUNCTIONS
Sympathetic
q t vascular smooth muscle contraction, t pupillary dilator muscle

contraction (mydriasis), t intestinal and bladder sphincter muscle
contraction
! sympathetic outAow, ! insulin release ! lipolysis, t platelet aggregation
s t heart rate, t contractility, t renin release, t lipolysis
s Vasodilation, bronchodilation, t heart rate, t contractility, t lipolysis,
t insulin release,! uterine tone (tocolysis), ciliary muscle relaxation,
t aqueous humor production
Parasympathetic
Ml q CNS, enteric nervous system
M2 ! heart rate and contractility of atria
M3 q t exocrine gland secretions (e.g., lacrimal, gastric acid), t gut peristalsis,

t bladder contraction, bronchoconstriction, t pupillary sphincter muscle
contraction (miosis), ciliary muscle contraction (accommodation)
s Relaxes renal vascular smooth muscle

Modulates transmitter release, especially in brain
Histamine
Hl q t nasal and bronchial mucus production, contraction of bronchioles,

pruritus, and pain
s t gastric acid secretion
Vasopressin
vl q t vascular smooth muscle contraction
V2 s t H20 permeability and reabsorption in the collecting tubules of the

kidney ( V2 is found in the 2 kidneys)
"Qiss (kiss) and qiq (kick) till you're siq (sick) of sqs (super qinky sex)."
Lipids
Gq HAVe 1 M&M.
Receptor Phospholipase C DAG Protein
+/
PI P
kinase C
2
IP3 t [Ca2+]in Smooth muscle contraction
Receptor ATP
G;/
Adenylyl cyclase t t [Ca2+]in (heart)
Receptor / cAMP------ Protein kinase A /

.......__
......_, Myosin light-chain
kinase (smooth
muscle)
MAD 2's.
I
232 SECTIONII PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS
Autonomic drugs
Vesamicol
Circles with rotating arrows represent transporters. (Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review,
5th ed. Stamford, CT: Appleton & Lange, 1998: 42.)
Noradrenergic nerve terminal
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford, CT: Appleton & Lange, 1998: 42.)
Release of NE from a sympathetic nerve ending is modulated by NE itself, acting on presynaptic

a2-autoreceptors, and by ACh, angiotensin II, and other substances.
PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS SECTIONII 233
Cholinomimetic agents
DRUG CLINICAL APPLICATIONS ACTION
Direct agonists
Bethanechol Postoperative ileus, neurogenic ileus, and Activates bowel and bladder smooth
urinary retention muscle; resistant to AChE. "Bethany, call
(bethanechol) me, maybe, if you want to
activate your bowels and bladder."
Carbachol Glaucoma, pupillary contraction, and relief of Carbon copy of acetylcholine.
intraocular pressure
Pilocarpine Potent stimulator of sweat, tears, and saliva Contracts ciliary muscle of eye (open-angle
Open-angle and closed-angle glaucoma glaucoma), pupillary sphincter (closed-angle
glaucoma); resistant to AChE. "You cry, drool,
and sweat on your 'pilow.' "
Methacholine Challenge test for diagnosis of asthma Stimulates muscarinic receptors in airway when
inhaled.
Indirect agonists (anticholinesterases)
Neostigmine Postoperative and neurogenic ileus and t endogenous ACh.
urinary retention, myasthenia gravis, Neo CNS =No CNS penetration.
reversal of neuromuscular junction blockade
(postoperative)
Pyridostigmine Myasthenia gravis (long acting); does not t endogenous ACh; t strength. Pyridostigmine
penetrate CNS gets rid of myasthenia gravis.
Edrophonium Diagnosis of myasthenia gravis (extremely short t endogenous ACh.
acting)
Physostigmine Anticholinergic toxicity (crosses blood-brain t endogenous ACh. Physostigmine " p hyxes"
barrier - CNS) atropine overdose.
Donepezil Alzheimer's disease t endogenous ACh.
Note: With all cholinomimetic agents, watch for exacerbation of COP D, asthma, and peptic ulcers
when giving to susceptible patients.
Cholinesterase Often clue to organophosphates, such as DU M BBELSS.

inhibitor poisoning parathion, that irreversibly inhibit AChE. Organophosphates are components of
Causes Diarrhea, Urination, Miosis, insecticides; poisoning usually seen in farmers.
Bronchospasm, Bradycardia, Excitation
of skeletal muscle and CNS, Lacrimation,
Sweating, and Salivation.
Antidote-atropine+ pralicloxime (regenerates
active AChE).
234 SECTION II PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS
Muscarinic antagonists
DRUGS ORGAN SYSTEMS APPLICATIONS
Atropine, homatropine, Eye Produce mydriasis and cycloplegia

tropicamide
Benztropine CNS Parkinson's disease- "Park my Benz"
Scopolamine CNS Motion sickness
lpratropium, tiotropium Respiratory COPD, asthma ("' pray I can breathe soon!")
Oxybutynin Genitourinary Reduce urgency in mild cystitis and reduce
bladder spasms
Glycopyrrolate Gastrointestinal, respiratory Parenteral: preoperative use to reduce airway
secretions
Oral: drooling, peptic ulcer
Atropine Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications.
ORGAN SYSTEM ACTION
Eye t pupil dilation, cycloplegia Blocks DU MBBeLSS. Skeletal muscle and

Airway secretions CNS excitation mediated by nicotinic
receptors. See previous page.
Stomach acid secretion
Gut motility
Bladder urgency in cystitis
TOXICITY t body temperature (due to sweating); Side effects:
rapid pulse; dry mouth; dry, flushed skin; Hot as a hare
cycloplegia; constipation; disorientation Dry as a bone
Can cause acute angle-closure glaucoma in Red as a beet
elderly (clue to mydriasis), urinary retention Blind as a bat
in men with prostatic hyperplasia, and Mad as a hatter
hyperthermia in infants Jimson weed (Datura) -+ gardener's pupil
(mydriasis due to plant alkaloids)
I
PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS SECTION II 23 5
Sympathomimetics
DRUG
1 Dl APPLICATIONS
Direct sympathomimetics
Epinephrine +++ +++ ++++ ++++ 0 Anaphylaxis, glaucoma (open angle), asthma,
hypotension
Norepinephrine ++++ ++++ ++ 0 0 Hypotension (but renal perfusion)
Isoproterenol 0 0 ++++ ++++ 0 Torsacle de pointes (tachycardia decreases QT
interval), braclyarrhythmias (but can worsen
/..' ischemia)
Dopamine +++ +++ +++ ++ +++ Shock (renal perfusion), heart failure; inotropic
(high (high (medium (medium (low and chronotropic
close) close) close) close) close)
Dobutamine + + +++ + + 0 Heart failure, cardiac stress testing; inotropic
and chronotropic
Phenylephrine +++ ++ 0 0 0 Hypotension (vasoconstrictor), ocular
procedures (mydriatic), rhinitis (decongestant)
Albuterol, salmeterol, 0 0 ++ ++++ 0 Metaproterenol and albuterol for acute asthma;
terbutaline salmeterol for long-term asthma or COPD
control; terbutaline to reduce premature
uterine contractions
Ritodrine 0 0 0 + +++ 0 Reduces premature uterine contractions
Indirect sympathomimetics
Amphetamine Indirect general agonist, releases stored Narcolepsy, obesity, attention deficit disorder
catecholamines
Ephedrine Indirect general agonist, releases stored Nasal decongestion, urinary incontinence,
catecholamines hypotension
Cocaine Indirect general agonist, reuptake inhibitor Causes vasoconstriction and local anesthesia;
never give -blockers if cocaine intoxication is
suspected (can lead to unopposed a1 activation
and extreme hypertension)
23 6 SECTION II PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS
Norepinephrine vs. Norepinephrine causes an increase in systolic and diastolic pressures as a result of a1-mediated
isoproterenol vasoconstriction t mean arterial pressure
-+ bradycardia. However, isoproterenol has little a
-+
effect but causes rmediated vasodilation, resulting in! mean arterial pressure and t heart rate
through 1 and reflex activity.
Norepinephrine (a>) Isoproterenol (> a)

I

::J
Pulse ! - 150
(/)
(/)

c.
100
"0

0
0 50
as Mean
Diastolic
f
Q) -- --- -- - -------- -- 100

Q)
I
- -- -- 50
'
(Reflex bradycardia)
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford, 0: Appleton & Lange, 1998: 72.)
Sympathoplegics
Clonidine, Centrally acting a ragonists,! central Application: hypertension, especially with renal
a-methyldopa sympathetic outflow disease (no decrease in blood flow to kidney)
PHARMACOLOGY PHARMACOLOGY-AUTONOMIC DRUGS SECTIONII 23 7
a-blockers
DRUG APPLICATIONS TOXICITY
Nonselective
Phenoxybenzamine Pheochromocytoma (use phenoxybenzamine Orthostatic hypotension, reAex tachycard ia
(irreversible) before removing tumor, since high levels of
released catecholamines w ill not be able to
overcome blockage)
Phentolamine Give to patients on MAO inhibitors who eat
(reversible) tyram ine-conta ining foods
selective (-osin ending)
Prazosin, terazosin, Hypertension, urinary retention in BPI-I 1st-close orthostatic hypotension, d izziness,
doxazosin, tamsulosin headache
Cl:z selective
Mirtazapine Depression Sedation, t serum cholesterol, t appetite
a-blockade of epinephrine vs. phenylephrine

Before a. blockade After a. blockade
Epi (large dose) Epi (large dose)
c.
"0

j -L _________
0
0
OJ
'-----
Net pressor effect
Phenylephrine

::J
(/)
(/)

c.
"0
0
0
OJ
'----- '------
Net pressor effect Suppression of pressor effect
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford, a: Appleton & Lange, 1998: 80.)
Shown above are the effects of an a-blocker (e.g., phentolamine) on blood pressure responses to epinephr ine and
phenylephrine. The epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the
a response) to a net decrease (the 2 response). The response to phenylephr ine is suppressed but not reversed because
phenylephr ine is a "pure" a-agonist w ithout action.
23 8 SECTION II PHARMACOLOGY PHARMACOLOGY-A U TONOMIC DRUGS
-blockers Acebutolol, betaxolol, esmolol, atenolol, metoprolol, propranolol, timolol, pindolol, labetalol.
APPLICATION EFFECTS
Angina pectoris heart rate and contractility, resulting in 02

consumption
Ml -blockers mortality
SVT (metoprolol, AV conduction velocity (class II
esmolol) antiarrhythmic)
Hypertension cardiac output, renin secretion (clue to
1-receptor blockade on JGA cells)
CHF Slows progression of chronic failure
Glaucoma (timolol) secretion of aqueous humor
TOXICITY Impotence, exacerbation of asthma,
cardiovascular adverse effects (bradycardia, AV
block, CHF), CNS adverse effects (seizures,
sedation, sleep alterations); use with caution in
diabetics
SELECTIVITY 1-selective antagonists ( 1 > 2)- Acebutolol A BEA M of 1-blockers. Advantageous in
(partial agonist), Betaxolol, Esmolol (short patients with comorbicl pulmonary disease.
acting), Atenolol, Metoprolol
Nonselective antagonists ( 1 )
= Please Try Not eing Picky.
Propranolol, Timolol, Naclolol, and Pinclolol
Nonselective (vasodilatory) a- and
-antagonists-carveclilol, labetalol
Partial -Agonists- Pindolol, Acebutolol PAPA.
PHARMACOLOGY PHARMACOLOGY-TOXICITIES AND SI DE EFFECTS SECTION II 239
PHARMACOLOGY-TOXICITIES AN D SI DE EFFECTS
Specific antidotes TOXIN ANTIDOTE/TREATMENT
Acetaminophen N-acetylcysteine (replenishes glutathione)

Salicylates NaHC03 (alkalinize urine), dialysis
Amphetamines (basic) N H4Cl (acidify urine)
Acetylcholinesterase inhibitors, Atropine, pralidoxime
organophosphates
Antimuscarinic, anticholinergic agents Physostigmine salicylate, control hyperthermia
-blockers Glucagon
Digitalis Normalize K+, Lidocaine, Anti-dig Fab
2
fragments, Mg + (KLA M)
Iron Deferoxamine, deferasirox
Lead CaEDTA, dimercaprol, succimer, penicillamine
Mercury, arsenic, gold Dimercaprol ( BAL), succimer
Copper, arsenic, gold Penicillamine
Cyanide Nitrite + thiosulfate, hydroxocobalamin
Methemoglobin Methylene blue, vitamin C
Carbon monoxide 10 0 % 0 2 , hyperbaric 02
Methanol, ethylene glycol (antifreeze) Fomepizole >ethanol, dialysis
Opioids Naloxone/naltrexone
Benzodiazepines Flumazenil
TCAs NaHC03 (plasma alkalinization)
Heparin Protamine
Warfarin Vitamin K, fresh frozen plasma
t PA, streptokinase, urokinase Aminocaproic acid
Theophylline -blocker
2 40 SECTION II PHARMACOLOGY PHARMACOLOGY-TOXICITIES AND SI DE EFFECTS
Drug readions
DRUG REACTION BY SYSTEM CAUSAl AGENTS
Cardiovascular
Coronary vasospasm Cocaine, sumatriptan, ergot alkaloids
2
Cutaneous flushing Vancomycin, Adenosine, Niacin, Ca + channel VANC
blockers
Dilated Doxorubicin (Adriamycin), daunorubicin
cardiomyopathy
Torsades de pointes Class III (sotalol) and class lA (quinidine)
antiarrhythmics
Hematologic
Agranulocytosis Clozapine, Carbamazepine, Colchicine, Agranulocytosis Could Certainly Cause Pretty
Propylthiouracil, Methimazole, Dapsone Major Damage
Aplastic anemia Chloramphenicol, benzene, NSAIDs,
propylthiouracil, methimazole
Direct Coombs Methyldopa, penicillin
positive hemolytic
anemia
Gray baby syndrome Chloramphenicol
Hemolysis in G6PD Isoniazid (IN H), Sulfonamides, Primaquine, Hemolysis IS PAIN
deficient patients Aspirin, Ibuprofen, Nitrofurantoin
Megaloblastic anemia Phenytoin, Methotrexate, Sulfa drugs Having a blast with P MS
Thrombotic OC Ps (e.g., estrogens)
complications
Respiratory
Cough ACE inhibitors Note: ARBs like losartan-no cough
Pulmonary fibrosis BLeomycin, Amiodarone, Busulfan It's hard to BLA B when you have pulmonary
fibrosis
Gl
Acute cholestatic Erythromycin

hepatitis, jaundice
Focal to massive Halothane, Amanita phalloides, Valproic acid, Liver "HAVAc"
hepatic necrosis Acetaminophen
Hepatitis IN H
Pseudomembranous Clindamycin, ampicillin
colitis
Reproductive/endocrine
Adrenocortical Glucocorticoid withdrawal (HPA suppression)
insufficiency
Gynecomastia Spironolactone, Digitalis, Cimetidine, chronic Some Drugs Create Awkward Knockers
Alcohol use, estrogens, Ketoconazole
Hot flashes Tamoxifen, clomiphene
Hyperglycemia Niacin, tacrolimus, protease inhibitors, HCTZ,
corticosteroids
Hypothyroidism Lithium, amiodarone, sulfonamides
PHARMACOLOGY PHARMACOLOGY-TOXICITIES AND S I DE EFFECTS SECTION II 24 1
Drug reactions (continued)

DRUG REACTION BY SYSTEM CAUSAL AGENTS
Musculoskeletal/connective tissue
Fat redistribution Glucocorticoids, protease inhibitors
Gingival hyperplasia Phenytoin, verapamil
Gout Furosemide, thiazides, niacin, cyclosporine
Myopathies Fibrates, Niacin, Colchicine, Fish N CHIPS Give you myopathies
Hyclroxychloroquine, Interferon-a,
Penicillamine, Statins, Glucocorticoids
Osteoporosis Corticosteroids, heparin
Photosensitivity Sulfonamides, Amiodarone, Tetracycline SAT for a photo
Rash (Stevens- Penicillin, Ethosuximide, Carbamazepine, Bad rash after a PEC SLAPP
Johnson syndrome) Sulfa drugs, Lamotrigine, Allopurinol,
Phenytoin, Phenobarbital
SLE-Iike syndrome Hydralazine, INH, Procainamicle, Phenytoin It's not HIPP to have lupus
Teeth (kids) Tetracyclines
Tendonitis, tendon Fluoroquinolones
rupture, and
cartilage damage
Renai/GU
Diabetes insipidus Lithium, demeclocycline
Fanconi's syndrome Expired tetracycline
Hemorrhagic cystitis Cyclophosphamide, ifosfamide (prevent by
coaclministering with mesna)
Interstitial nephritis Methicillin, NSAIDs, furosemide
SIADH Carbamazepine, cyclophosphamide
Neurologic
Cinchonism Quinidine, quinine
Parkinson-like Antipsychotics, reserpine, metoclopramicle
syndrome
Seizures Isoniazid, Bupropion, lmipenem/cilastatin, With seizures, I BITE My tongue
Tramadol, EnAurane, Metoclopramide
Tardive dyskinesia Antipsychotics
Multiorgan
Antimuscarinic Atropine, TCAs, H 1-blockers, neuroleptics
Disulfiram-like Metronidazole, certain cephalosporins,

reaction procarbazine, 1st-generation sulfonylureas
Nephrotoxicity/ Aminoglycosides, vancomycin, loop diuretics,
ototoxicity cisplatin
24 2 SECTION II PHARMACOLOGY PHARMACOLOGY-TOXICITIES AND S I DE EFFECTS
P-450 interactions Inducers (+) Inhibitors (-)

Modafinil Macrolides
Barbiturates Amiodarone
St. John's wort Grapefruit juice
Phenytoin Isoniazid
Rifampin Cimetidine
Griseofulvin Ritonavir
Carbamazepine Acute alcohol abuse
Chronic alcohol use Ciprofloxacin
Ketoconazole
Momma Barb Steals Phen-phen and Refuses
Sulfonamides
Greasy Carbs Chronically.
Gemfibrozil
Quinidine
MAGIC RACKS in GQ.
Sulfa drugs Probenecid, Furosemide, Acetazolamide, Popular FACTSSS

Celecoxib, Thiazides, Sulfonamide antibiotics,
Sulfasalazine, Sulfonylureas
Patients with sulfa allergies may develop fever,
urinary tract infection, pruritic rash, Stevens
Johnson syndrome, hemolytic anemia,
thrombocytopenia, agrnulocytosis, and
urticaria (hives). Symptoms range from mild to
life-threatening.
PHARMACOLOGY PHARMACOLOGY-MISCELLANEOUS SECTION II 24 3
PHARMACOLOGY-MISCEL LANEOUS
Drug name
ENDING CATEGORY EXAMPLE
Antimicrobial
-azole Antifungal Ketoconazole
-cillin Penicillin Methicillin
-cycline Antibiotic, protein synthesis inhibitor Tetracycline
-navir Protease inhibitor Saquinavir
CNS
-triptan 5-HT18110 agonists (migraine) Sumatriptan
-ane Inhalational general anesthetic Halothane
-caine Local anesthetic Lidocaine
-operidol Butyrophenone (neuroleptic) Haloperidol
-azine Phenothiazine (neuroleptic, antiemetic) Chlorpromazine
-barbital Barbiturate Phenobarbital
-zolam Benzocliazepine Alprazolam
-azepam Benzodiazepine Diazepam
-etine SSRI Fluoxetine
-ipramine TCA Imipramine
-triptyline T CA Amitriptyline
Autonomic
-olol -antagonist Propranolol
-terol r agonist Albuterol
-zosin a1-antagonist Prazosin
Cardiovascular
-oxin Cardiac glycoside (inotropic agent) Digoxin
-pril ACE inhibitor Captopril
-afil Erectile dysfunction Sildenafil
Other
-trapin Pituitary hormone Somatotropin
-tidine I-12 antagonist Cimetidine
2 44 SECTION II PHARMACOLOGY
NOTES
SECTION Ill
High-Yield
Organ Systems
"Symptoms, then, are in reality nothing but the cry from SHf{ering organs."
-Jean-Martin Charcot
"Man is an intelligence in servitude to his organs."

-Aldous Huxley
24 6 SECTION Ill HIGH-YIELD ORGAN SYSTEMS
APPROACHING THE ORGAN SYSTEMS
In this section, we have divided the High-Yield Facts into the major Organ
Systems. Within each Organ System are several subsections, including
Embryology, Anatomy, Physiology, Pathology, and Pharmacology. As
you progress through each Organ System, refer back to information in
the previous subsections to organize these basic science subsections into a
"vertical" framework for learning. Below is some general advice for studying
the organ systems by these subsections.
Embryology
For 2013, we have shifted Embryology into the Organ Systems section.
Relevant embryology is tied to each organ system subsection. Embryology
tends to correspond well with the relevant Anatomy, especially with regard
to congenital malformations.
Anatomy
Several topics fall under this heading, including gross anatomy, histology,
and neuroanatomy. Do not memorize all the small details; however, do not
ignore anatomy altogether. Review what you have already learned and what
you wish you had learned. Many questions require two steps. The first step
is to identify a structure on anatomic cross section, electron micrograph, or
photomicrograph. The second step may require an understanding of the
clinical significance of the structure.
Wl1en studying, stress clinically important material. For example, be

familiar with gross anatomy related to specific diseases (e.g., Pancoast
tumor, Horner's syndrome), traumatic injuries (e.g., fractures, sensory and
motor nerve deficits), procedures (e.g., lumbar puncture), and common
surgeries (e.g., cholecystectomy). There are also many questions on the
exam involving x-rays, CT scans, and neuro MRI scans. Many students
suggest browsing through a general radiology atlas, pathology atlas, and
histology atlas. Focus on learning basic anatomy at key levels in the body
(e.g., sagittal brain MRI; axial CT of the midthorax, abdomen, and pelvis).
Basic neuroanatomy (especially pathways, blood supply, and functional
anatomy) also has good yield. Use this as an opportunity to learn associated
neuropathology and neurophysiology.
Physiology
The portion of the examination dealing with physiology is broad and

concept oriented and thus does not lend itself as well to fact-based review.
Diagrams are often the best study aids, especially given the increasing
number of questions requiring the interpretation of diagrams. Learn to
apply basic physiologic relationships in a variety of ways (e.g., the Fick
equation, clearance equations). You are seldom asked to perform complex
HIGHYIELD ORGAN SYSTEMS SECTION Ill 2 47
calculations. Hormones are the focus of many questions, so learn their sites
of production and action as well as their regulatory mechanisms.
A large portion of the physiology tested on the USMLE Step 1 is now

clinically relevant and involves understanding physiologic changes
associated with pathologic processes (e.g., changes in pulmonary function
with COP D). Thus, it is worthwhile to review the physiologic changes that
are found with common pathologies of the major organ systems (e.g., heart,
lungs, kidneys, GI tract) and endocrine glands.
Pathology
Questions dealing with this discipline are difficult to prepare for because
of the sheer volume of material involved. Review the basic principles
and hallmark characteristics of the key diseases. Given the increasingly
clinical orientation of Step 1, it is no longer sufficient to know only the
"buzz word" associations of certain diseases (e.g., cafe-au-lait macules and
neurofibromatosis); you must also know the clinical descriptions of these
findings.
Given the clinical slant of the USMLE Step 1, it is also important to

review the classic presenting signs and symptoms of diseases as well as
their associated laboratory findings. Delve into the signs, symptoms, and
pathophysiology of major diseases that have a high prevalence in the United
States (e.g., alcoholism, diabetes, hypertension, heart failure, ischemic heart
disease, infectious disease). Be prepared to think one step beyond the simple
diagnosis to treatment or complications.
The examination includes a number of color photomicrographs and

photographs of gross specimens that are presented in the setting of a brief
clinical history. However, read the question and the choices carefully before
looking at the illustration, because the history will help you identify the
pathologic process. Flip through an illustrated pathology textbook, color
atlases, and appropriate Web sites in order to look at the pictures in the clays
before the exam. Pay attention to potential clues such as age, sex, ethnicity,
occupation, recent activities and exposures, and specialized lab tests.
Pharmacology
Preparation for questions on pharmacology is straightforward. Memorizing

all the key drugs and their characteristics (e.g., mechanisms, clinical
use, and important side effects) is high yield. Focus on understanding the
prototype drugs in each class. Avoid memorizing obscure derivatives. Learn
the "classic" and distinguishing toxicities of the major drugs. Do not bother
with drug dosages or trade names. Reviewing associated biochemistry,
physiology, and microbiology can be useful while studying pharmacology.
There is a strong emphasis on ANS, CNS, antimicrobial, and cardiovascular
agents as well as on NSAI Ds. Much of the material is clinically relevant.
ewer drugs on the market are also fair game.
24 8 SECTION Ill HICiHYIELD ORGAN SYSTEMS
NOTES
HIGH-YIELD SYSTEMS
Cardiovascular
"As for me, except for an occasional heart attack, I feel as young as I ever
did."
- Robert Bench ley
"Hearts will never be practical until they are made unbreakable."

-The Wi zard of Oz
"As the arteries grow hard, the heart grows soft."

- H . L. Mencken
"Nobody has ever measured, not even poets, how much the heart can
hold."
-Zelda Fitzgerald
"Only from the heart can you touch the sky."

- Ru m i
2 50 SECT I O N I l l CA R D I OVASC U L A R C A R D I OVAS C U L A R-EMBRYO LOGY
C A R D I OVASC U L A R -E M B R YOLOGY
Heart embryology EMBRYON I C STRUCTURE GIVES RISE TO
Truncus arteriosus (TA) Ascending aorta and pulmonary trunk

Bulbus cord is Smooth parts (outAow tract) of left and right
ventricles
Prim itive ventricle Trabecul ated left and right ventricles
Prim itive atria Trabecu Ia ted left and right atria
Left horn of sinus venosus ( SV) Coronary sinus
Right horn of SV Smooth part of right atrium
Right common cardinal vein and right anterior svc
cardinal vei n
Truncus arteriosus Neural crest migration truncal and bulbar ridges that spiral and fuse to form the
-+
aorticopul monary (AP) septu m ascending aorta and pulmonary trunk.

-+
Pathology- transposition of great vessels (failure to spiral), tetralogy of Fallot (skewed AP septum
development) , persistent TA (partial AP septum development) .
Interventricular septum development
Membranous
ventricular
septum
MuscuIar ----T->T""'+
ventricular
septum
0 Muscular ventricular septum forms. Opening is called interventricular foramen .

f) AP septum rotates and fuses with muscular ventricular septum to form membranous
interventricular septum, closing interventricular foramen .
E) Growth of endocardial cushions separates atria from ventricles and contributes to both atrial
separation and membranous portion of the interventricular septum .
Pathology- improper neural crest migration into theTA c a n result in transposition o f t h e great
arteries or a persistent TA. Membranous septal defect causes an i n itial left-to-right shunt, wh ich
later reverses to a right-to-left shunt clue to the onset of pul monary hypertension (Eisenmenger's
syndrome) .
CA R D I O VASC U L A R C A R D I OVAS C U L A R-EMBRYO LOGY SECT I O N I l l 25 1
Interatrial septum development

Foramen
secundum
Dorsal
endocardial Septum
primum
Foramen
secundum -l\==#i; septum
cushion primum
Foramen
primum
Foramen Degenerating 0
secundum septum primum
Septum Foramen Foramen 4#1::;:;::rr-- Valve of

primum ovale ovale (open) foramen
(closed) ovale
0 Foramen pri mum narrows as septum primum grows toward endocardial cushions.
E) Perforations in septum primum form foramen secundum (foramen primum d i sappears) .
) Foramen secundum maintains right-to-left shunt as septu m secundum begins to grow.
0 Septum secundum contains a permanent open ing (foramen ovale).
0 Foramen secundum enlarges and upper part of septum pri mum degenerates.
0 Remain ing portion of septu m primum forms valve of foramen ovale.
7. ( Not shown) S eptum secundum and septum primum fuse to form the atrial septum.
8 . ( Not shown) Foramen ovale usually closes soon after birth because of t LA pressure.
Pathology- patent foramen ovale, caused by fa ilure of the septu m primum and septum secundum
to fuse after bi rth.
Fetal erythropoiesis Fetal erythropoiesis occurs i n : Young Liver Synthesizes Blood.

Yolk sac ( 3- 1 0 wk) Fetal hemoglobin =a2rz.
Liver (6 wk-birth) Adult hemoglobin =a22.
Spleen ( 1 5-30 wk)
B one marrow (22 wk to adult)

Cellularity
(%)
.-.-.--.-.----
100
80
60
40
20
10 20 30 40
Fetal weeks Birth

2 52 SECT I O N I l l CAR D I OVASC U L A R C A R D I OVASC U L A R-E M B R YOLOGY
fetal circulation Blood in umbilical vei n has a P02 of"' 30 m m H g

a n d is"' 8 0 % saturated with 02 . Umbil ical
arteries have low 0 2 saturation.
3 important shunts :
0 Blood entering the fetus through the
umbilical vei n is concluctecl via the ductus
venosus into the IVC to bypass the hepatic
circulation
0 Ductus venosus 0 Most oxygenated blood reaching the
heart via the IVC is d iverted through the
foramen ovale and pumped out the aorta
to the head and body
Inferior vena cava E) Deoxygenated blood entering the RA from
the SVC enters the RV, is expelled into
the pulmonary artery, and then passes
through the ductus arteriosus i nto the
descending aorta.
At birth, infant takes a breath; ! resistance in
pul monary vasculature causes t left atrial
pressur e vs. right atrial pressur e ; foramen ovale
closes (now called fossa oval is); t i n 0 2 leacls to
! in prostaglandins, causing closure of ductus
arteriosus.
I ndomethaci n helps close PDA.
Prostaglandins E 1 and E 2 keep PDA open.
arteries
To placenta '--- From placenta
Fetal-postnatal derivatives
Umbilical vein Ligamentum teres hepatis Conta ined i n falciform l i gament.
Umb ilical arteries MediaL u mbilical ligaments
Ductus arteriosus Ligamentum arteriosum
Ductus venosus Ligamentum venosum
Foramen ovale Fossa ovalis
AllaNtois Urachus-mediaN umbilical l igament The urachus is the part of the allantoic duct
between the bladder and the umbilicus.
Urachal cyst or sinus is a remnant.
Notochord Nucleus pulposus of intervertebral elise
CA R D I O VASC U L A R C A R D I OVASC U L A R-ANATO M Y SECT I O N I l l 2 53
C A R D I OVAS C U L A R-ANATOMY
Coronary artery anatomy SA and AV nodes are usually suppl ied

Right coronary by RCA.
artery
Right-dominant circulation = 85%
Left circumflex coronary = PO arises from RCA.
artery (LCX)-supplies
lateral and posterior walls
Left-dom inant circulation = 8% = PO
of left ventricle
arises from LCX.
___ Left anterior descending
Codominant circulation = 7% = PO
artery (LAD)-supplies
anterior 2/3 of interventricular arises from both LCX and RCA.
septum, anterior papillary
muscle, and anterior surface C oronary artery occlusion most
of left ventricle commonly occurs in the LAD.
Left marginal artery C oronary arteries fill during diastole.
The most posterior part of the heart

i s the left atrium ; enlargement can
cause dysphagia (due to compression
of the esophagus) or hoarseness
Posterior descending/interventricular
(clue to compression of the left
artery (PD)-supplies posterior '13 of
interventricular septum and posterior recurrent laryngeal nerve, a branch
walls of ventricles of the vagus) . Transesophageal
echocardi ography is useful for
d i agnosing left atrial enlargement,
aortic d i ssection , and thoracic aortic
aneurysm.
C A R D I OVASC U L A R - P H YS I O LOGY
Cardiac output x
C O =stroke volume ( SV) heart rate (HR). D ur i n g the early stages o f exercise, C O i s
Fick principle : maintained b y t H R and t S V. During the late
stages of exercise, C O is mainta ined by t H R
rate of 02 consumption
CO = only ( SV plateaus) .
arterial 02 content - venous 02 content
(cardiac) (total peripheral)

If H R is too high, d i astol ic filling is i ncomplete
Mean arterial x and C O (e.g., ventricular tachycard ia) .
=
pressure ( MAP) output resistance
MAP =% d i astol ic pressure+ X systolic pressure.

Pulse pressure = systolic pressure - diastol ic pressure.
Pulse pressure stroke volume.
ex:
CO
SV = = E DV - ESV
HR
CARDIOVASCULAR CARD I OVASC U LAR- PHYS IOLOGY
Cardiac output S troke Volume affected by C ontractility, S V CAP.

variables Afterload, and P reload . f SV when f preload,
! afterload , or f contractil ity.
Contractility (and SV) f with : SV f i n anxiety, exercise, and pregnancy.
2
Catecholamines (f activity of Ca + pump in A failing heart has ! SV.
sarcoplasmic reticulum) Myocard ial 0 2 demand is f by:
2
f i ntracellular Ca + f afterload ( arterial pressure)
oc
! extracel lular Na+ U activity of Na+/Ca +

2 f contractil ity
exchanger) f heart rate
Digitalis (blocks Na+fK+ pump f heart size (f wall tension)
--+ f intracellular Na+ --+ ! Na+/Ca 2 +

exchanger activity --+ f intracel lular Ca 2 +)
Contractil ity (and SV) ! with:
-bl ockade ( ! cAMP)
1
Heart failur e (systol ic dysfunction)
Acidosis
Hypoxia /hypercapnea ( ! Po 7 / f Pco7)

2 -
Non-dihydropyridine Ca + han nel blockers
Preload and afterload Preload =ventricular EDV. Preload f with :

Afterload =mean arterial pressure (proportional Exercise (slightly) .
to peripheral resistance) . f blood volume (e.g., overtransfusion) .
VE nodilators (e.g., n itroglycerin) ! prE load. Excitement (f sympathetic activity) .
VAsodilators (e.g., hydrAla zine) ! Afterload

(a rterial) .
Starling curve Sympathetic Force of contraction is proportional to end

nerve impulses
d iastol ic length of cardiac muscle fiber
(preload) .
Q)
E
::J
f contractil ity with sympathetic stimulation,
0 catecholam ines, d igoxin.
>
Q)
.OS: ! contractil ity with loss of myocard ium ( M I ) ,
e
iii -blockers, calcium channel blockers.
0
0
0
Ventricular EDV (preload)
Ejection fraction (EF) SV E DV- E SV E F ! in systol ic heart fa i lure.

EF = =
E DV EDV
EF is an index of ventricular contractility.
EF is normally;?: 5 5 % .
CA R D I OVASC U L A R C A R D I OVASC U L A R - P H YS I O LOGY SECT ION I l l 2 55
Resistance. pressure. p = Q x R Pressure grad ient drives flow from h igh pressure
flow Similar to Ohm's law: V = IR to low pressure.
Resistance Resistance is d i rectly proportional to viscosity
= driving pressure (P) 811 (viscosity) x length
= and vessel length and inversely proportional to
flow (Q) 1t r the radius to the 4th power.
Total resistance of vessels in series Arterioles account for most of total peripheral
= Rl + R 2 + R3 . . . resistance regulate capillary flow.
--+
l /Total resistance of vessel s in parallel

= l / R 1 + l /R 2 + l /R3 . . .
Viscosity depends mostly on hematocrit.
Viscosity t i n :
Polycythemia
Hyperpro teinemic states (e.g., multiple
myeloma)
Hereditary spherocytosis
Viscosity ! i n anemia.
Cardiac and vascular

fundion curves
-- -------,
' @. - - ------------ (+) I notropy
E
::l
/ \\ co
" I
\
(/)
::l ----, I
0
0 ' I
c
Ql
> '../
I,
0 I '
I
0 I
0 I
I
I
I
I
I
I
I
I
,.."
..:---------
:.... -+==---'--------; 0 Right atrial pressure
or EDV
0 Operating point of heart ( cardiac output and venous return are equal)
f) ,J. TPR, e.g., exercise, AV shunt
E) i TPR, e.g., hemorrhage before compensation can occur
0 As in heart failure, narcotic overdose
0 X-intercept of venous return curve mean systemic filling pressure
=
256 SECT I O N I l l C A R D I O VASC U L A R C A R D I OVASC U L A R- P H YS I OLOGY
Cardiac cycle Phases-left ventricl e :

0 Isovolumetric contraction - period
I Contractility between mitral valve closure and aortic
I sv
valve open ing; period of h ighest 0 2
!EF
IESV
consumption
I Afterload
140
I Aortic pressure
} Systol ic ejection - period between aortic
j sv valve open ing and closing
120 !ESV E) Isovolumetric relaxation - period between
aortic valve closing and m itral valve
100 openmg
-en
0 Rapid filling- period just after mitral
I valve open ing
E 80
E. 0 Reduced filling- period just before m itral
(1) Stroke
valve closure

(1) 60
+---volume
(EDV-ESV)
Q: E)
Mitral Mitral
40 valve
valve
opens closes
20 (h0
ESV Volume EDV
Systole Sounds :
Cl S l - m itral and tricuspid valve closure. Loudest
c .!:
0 at m itral area.
u S2 - aortic and pulmonary valve closure.
(!)
"(j)
Loudest at left sternal border.
S 3 - i n early diastole dur i n g rapid ventricular
filling phase. Associated with t filling pressures
120 (e.g., m itral regur g i tation, C H F) and more
common in dilated ventricles (but normal i n
Oi 100
I children and pregnant women) .
E 80 S 4 ( "atrial kick " ) - i n late diastole. H igh
.s atrial pressure. Associated with ventricular
60
:::>
(/) pressure hypertrophy. Left atrium must push against
I
(/) 40 stiff LV wal l .

c...
20 Jugular venous pulse (JVP) :
Mitral valve opens
-- I a wave - atrial contraction .
0 ----
c wave - RV contraction (closed tricuspid valve
1 Heart
sounds
bulging i nto atrium) .
x descent-atrial relaxation and downward
displacement of closed tricuspi d valve during

ventricular contraction.
v wave - t right atrial pressure due to filling
against closed tricuspid valve .
y descent-blood fl o w from RA t o R V.
Jugular
venous
pulse
ECG p
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Time (sec)
CA R D I O VASC U L A R C A R D I OVASC U L A R - P H YS I O LOGY SECT I O N I l l 2 57
Splitting
Normal splitting Inspiration ..... drop i n i ntrathoracic pressure
Expiration I II
--+ t venous return to the RV ..... increased RV Sl AZ PZ
stroke volume --+ t RV ejection time --+ del ayed lnspi ration I I I
closure of pulmonic valve. ! pulmonary
i mpedance (t capacity of the pulmonary
circulation ) also occurs during inspiration,
wh ich contributes to delayed closure of
pulmonic valve.
Wide splitting Seen in conditions that delay RV emptying
Expiration I I I
(pulmonic stenosis, right bundle branch
Sl A Z PZ
block). Delay in RV emptying causes delayed Inspiration I I I
pulmonic sound (regardless of breath). An
exaggeration of normal spl itting.
Fixed splitting Seen in ASD. ASD --+ left-to-right shunt --+ t RA
Expiration I I I
and RV volumes --+ t flow through pulmon ic
Sl A Z PZ
valve such that, regardless of breath, pulmon ic I nspi ration I I I
closure i s greatly delayed.
Paradoxical splitti ng Seen in conditions that delay LV emptying
Expiration I I I
(aortic stenosis, left bundle branch block).
Sl P Z AZ
Normal order of valve closure is reversed so I nspiration I II
that PZ sound occur s before delayed AZ sound.
Therefore on inspiration, PZ closes later and
moves closer to AZ, thereby "paradoxical ly"
elim inating the spl it.
-
'
2 58 SECT I O N I l l CA R D I OVASC U L A R C A R D I OVASC U L A R- P H YS I OLOGY
Auscultation of the heart
Where to listen: APT M

Aortic area: Pulmonic area:
Systolic murmur Systolic ejection murmur
Aortic stenosis Pulmonic stenosis
Flow murmur (e.g., atrial septal defect',
patent ductus arteriosus')
Tricuspid area:
Diastolic murmur Pansystolic murmur
Aortic regurgitation Tricuspid regurgitation
Pulmonic regurgitation Ventricular septal defect
Systolic murmur Diastolic murmur

Hypertrophic Tricuspid stenosis
cardiomyopathy
@

Atrial septal defect'
M itral area:
Systolic murmur
Mitral regurgitation
Diastolic murmur
Mitral stenosis
'ASD commonly presents with a pulmonary flow murmur li flow through pulmonary valve) and a diastolic rumble (i flow across tricuspid); blood flow
across the actual ASD does not cause a murmur because there is no pressure gradient. The murmur later progresses to a louder diastolic murmur of
pulmonic regurgitation from dilatation of the pulmonary artery.
'The continuous, machine-like murmur of PDA is best appreciated in the left infraclavicular region.
BEDSIDE MANEUVER EFFECT
Inspiration t intensity of right heart sounds

Expiration t intensity of left heart sounds
Hand grip (t systemic vascular resistance) t intensity of MR, AR, VSD, MVP murmur s
intensity of A S , hypertroph ic cardiomyopathy murmur s
Valsalva ( venous return) intensity o f most murmur s
t intensity of MVP, hypertroph ic card iomyopathy murmurs
Rapid squatting ( t venous return, t preload , t afterload with intensity of MVP, hypertroph ic card iomyopathy murmurs
prolonged squatting)
Systolic heart sounds include aortic/pulmon ic stenosis, mitral/tricuspid regurgitation , ventricular septal defect.
Diastol ic heart sounds i nclude aortic/pul monic regurgitation, mitral/tricuspid stenosis.
CARDIOVASCULAR CARDIOVASCULAR-PHYSIOLOGY SECTION Ill 2 59
Heart murmurs
Systolic
Mitral/tricuspi d regurgitation Holosystol ic, high-pitched " blowi ng murmur."

(MR/TR) M itra l -loudest at apex and radiates toward axilla. Enhanced by maneuvers that
t TPR (e.g., squatting, hand grip) or LA return (e.g., expiration) . MR is often due
51 52
to ischemic heart disease, mitral valve prol apse, or LV d ilation.
Tricuspid- loudest at tricuspid area and radiates to right sternal border. E nhanced by
maneuvers that t RA return (e.g., inspiration) . TR can be caused by RV d ilation .
Rheumatic fever and infective endocard itis can cause either M R or TR.
Aortic stenosis (AS) Crescendo-decrescendo systol ic ejection murmur followi ng ejection cl ick (EC ; due
to abrupt halting of valve leaflets) . LV >> aortic pressure during systole. Radiates
51 EC 52
to carotids/heart base. "Pulsus parvus et tardus" - pulses are weak with a del ayed
11 peak. Can lead to Syncope, Angina, and Dyspnea on exertion ( SAD) . Often due to
age-related calcific aortic stenosis or bicuspid aortic valve.
VSD Holosystol ic, harsh-sounding murmur. Loudest at tricuspid area, accentuated with
hand grip maneuver due to i ncreased afterload.
51 52

Mitral valve prolapse (MV P) Late systol ic crescendo murmur with midsystolic cl ick (MC ; due to sudden tensing
52
of chordae tendineae) . Most frequent valvular lesion. Best heard over apex. Loudest
51 MC
at S2. Usually benign. Can predispose to infective endocarditis. Can be caused
I by myxomatous degeneration , rheumatic fever, or chordae rupture. Enhanced by
maneuvers that ! venous return (e.g., stand ing or Valsalva) .
Diastolic
Aortic regurgitation (AR) Immed iate high-pitched " blowing" d iastolic decrescendo murmur. Wide pulse
pressure when chroni c ; can present with bound ing pulses and head bobbing. Often
51 52
u
due to aortic root d ilation, bicuspid aortic valve, endocard itis, or rheumatic fever.
I t murmur during hand grip. Vasodilators ! i ntensity of mur mur.
Mitral stenosis (MS) Follows opening snap (OS ; due to abrupt halt i n leaflet motion in diastole , after
51 52 OS
rapid open ing due to fusion at leaflet tips). Delayed rumbling late d iastolic
murmur. LA >> LV pressure during diastole. Often occurs zo to rheumatic fever.
I I Chronic MS can result in LA dilation . Enhanced by maneuvers that t LA return
(e.g., expi ration ) .
Continuous
PDA Conti nuous mach i ne-l ike murmur. Loudest at S 2 . Often d u e t o congenital rubella
or prematurity. Best heard at left infraclavicular area.
51 52

2 60 SECT I O N I l l CA R D I OVASCU L A R C A R D I OVASC U L A R-P H YS I OLOGY
Ventricular adion Also occurs in bundle of H i s and Purkinje fibers.

potential
Phase 0 = rapid upstroke - voltage-gated Na+ channels open.
Phase 1 = initial repolarization -inactivation of voltage-gated Na+ channels. Voltage-gated K+
channels begin to open .
Phase 2 = plateau - C a 2 + influx th rough voltage-gated Ca 2 + channels balances K+ efflux. C a Z+
influx triggers Ca 2 + release from sarcoplasmic reticulum and myocyte contraction .
Phase3 = rapid repolarization - massive K+ efflux clue to open ing of voltage-gated slow K+
channels and closure of voltage-gated Ca 2 + channels.
Phase 4 = resting potential-h igh K+ permeabil ity through K+ channels.
I n contrast to skeletal muscle :
Cardiac muscle AP has a plateau , wh ich is
clue to Ca 2 + influx and K+ efflux; myocyte

contraction occurs clue to Ca 2 + -induced
Ca 2 + release from the sarcoplasmic
Effective refractory period (ERP)
reticulum.
Cardiac nodal cells spontaneously
-85 mV depolarize during d iastole resulting in

Na+ 3 Na+ automaticity clue to Ir channels ( " funny
current" channels responsible for a slow,
m i xed Na+fK+ i nward current) .
Cardiac myocytes are electrically coupled to
K+ K+ Ca2+ each other by gap j u nctions.

Channel currents Pump Exchanger
"Leak" currents
Pacemaker adion Occurs in the SA and AV nodes. Key differences from the ventricular action potential i nclude :
potential
Phase =upstroke - opening of voltage-gated Ca 2 + channels. Fast voltage-gated Na+ channels are
0
permanently inactivated because of the less negative resting voltage of these cells. Results in a slow
con duction velocity that is used by the AV node to prolong transmission from the atria to ventricles.
Phase 2 = plateau is absent.
Phase 3 = inactivation of the Ca 2 + channels and t activation of K+ channels -+ t K+ efflux.

Phase 4 = slow d iastolic depolarization - membrane potential spontaneously clepolarizes as Na+
conductance t (If different from INa in phase 0 of ventricular action potential ) . Accounts for
automaticity of SA and AV nodes. The slope of phase 4 in the SA node determ ines heart rate.
ACh/aclenosine l the rate of d iastol ic depolarization and l heart rate, wh ile catecholamines t
depolarization and t heart rate. Sympathetic stimulation t the chance that Ir channels are open
and thus t H R .
.l!l -20
-40

-60
-80
100 msec
CA R D I OVASC U L A R C A R D I OVASC U L A R - P H YS I OLOGY SECT I O N I l l 26 1
Eledrocardiogram P wave -atrial depolarization. Atrial Speed of conduction - Purkinje > atri a
repolarization is masked by QRS complex. > ventricles > AV node.
PR i nterval - conduction delay through AV Pacemakers - SA > AV > bundle of H i s /
node (normally < 200 msec) . Purkinje/ventricles.
QRS complex-ventricular depolarization Conduction pathway- SA node atria ..... AV
-+
(normally < 1 20 msec ) . node ..... common bundle bundle branches

-+
QT i nterva l - mechanical contraction o f the Purkinje fibers ..... ventricles.

--+
ventricles. SA node "pacemaker" i nherent dominance with

T wave -ventricular repolarization. T-wave slow phase of upstroke .
i nversion may ind icate recent MT. AV node - 100-msec delay- atrioventricular
ST segment- isoelectric, ventricles depolarized. delay; allows time for ventricular filling.
U wave - caused by hypokalemia, bradycardia.
QRS complex
R
1.0 lsoelectric
line
Superior vena cava
ST
> 0.5
segment
.s

Cii
'E
(]) p T
Sinoatrial node

-0.5
s QT
interval
Bundle of His
0 0.2 0.4 0.6

Right bundle branch Time (s)
Purkinje system
Left posterior fascicle
Torsades de pointes Ventricular tachycardia, characterized by shifting si nusoidal waveforms on ECG, can progress
to ventricular fibri llation . Anyth ing that prolongs the QT i nterval can predispose to torsades de
pointes. Treatment includes magnesium sulfate.
Congen ital long QT syndromes are most often due to defects in cardiac sodium or potassium
channels. Can present with severe congenital sensorineural deafness (Jervell and Lange-Nielsen
syndrome).
262 SECT I O N I l l CA R D I O VASC U L A R C A R D I OVAS C U L A R- P HYS I O LOGY
ECG tracings
Atrial fibrillation Chaotic and erratic basel ine (irregularly irregular) with no discrete P waves in between irregularly
spaced QRS complexes. Can result in atrial stasis and lead to stroke. Treatment includes rate
control , anticoagulation, and possible cardioversion.
Atrial flutter A rapid succession of identical, back-to-back atrial depolarization waves. The identical appearance
accounts for the "sawtooth " appearance of the flutter waves. Pharmacologic conversion to sinus
rhythm : class lA, IC, or III antiarrhythm ics. Rate control : -blocker or calcium channel blocker.
Ventricular fibrillation A completely erratic rhythm with no identifiable waves. Fatal arrhythm i a without im med iate
C PR and defibri llation .
AV block
1st degree The PR i nterval is prolonged (> 200 msec). Asymptomatic.
2nd degree
Mobitz type I Progressive lengthening of the PR interval until a beat is " dropped" (a P wave not fol lowed by a
(Wenckebach) QRS complex) . Usually asymptomatic.
Progressive increase i n P R length before dropped beat
;; \
CA R D I O VASC U L A R C A R D I OVASC U L A R - P H YS I OLOGY SECT I O N I l l 2 63
ECG tracings (continued)

Mobitz type I I Dropped beats that are not preceded by a change in the length of the PR interval (as i n type 1).
These abrupt, nonconducted P waves result in a pathologic condition. It is often found as 2 : 1
block, where there are 2 or more P waves to l QRS response . M ay progress to 3rd-degree block.
Often treated with pacemaker.
No QRS lnllowlog P wa,., oocmal PR '""""'''
1'---./\ ---
A
3rd degree The atria and ventricles beat independently of each other. Both P waves and QRS complexes are
(complete) present, although the P waves bear no relation to the QRS complexes. The atrial rate is faster than
the ventricular rate. Usually treated with pacemaker. Lyme d i sease can result in 3rd-degree heart
block.
P wave on ST-T comp x i
Atrial natriuretic ANP is released from atrial myocytes in response to t blood volume and atrial pressure. Causes
peptide generalized vascular relaxation and ! Na+ reabsorption at the medullary collecting tubule.
Constricts efferent renal arterioles and dilates afferent arterioles (cGMP mediated), promoting
d iuresis and contributing to the "escape from aldosterone" mechanism.
I
264 SECT I O N I l l C A R D I O VASC U L A R C A R D I OVASC U L A R - P H YS I O LOGY
Baroreceptors and chemoreceptors

Receptors:
Aortic arch transm its via vagus nerve to solitary nucleus of medulla (responds
only to t BP) .
Carotid sinus transm its via glossopharyngeal nerve to sol itary nucleus of
Carotid sinus Carotid body medulla (responds to and t in BP) .
(baroreceptor) chemoreceptor
Baroreceptors:
Hypotension - arterial pressure - stretch - afferent baroreceptor firing
-+ t efferent sympathetic firing and efferent parasympathetic sti mulation
-+ vasoconstriction, t HR, t contractility, t B P. I mportant in the response to
severe hemorrhage.
Carotid massage - t pressure on carotid artery -+ t stretch t afferent
-+
baroreceptor firing HR.

-+
Contributes to Cushing reaction (triad o f hypertension, bradycard ia,

and respiratory depression) t i ntracra n ial pressure constricts arterioles
-+ cerebral ischemia and reflex sympathetic increase i n perfusion pressur e
(hypertension) t stretch reflex baroreceptor i nduced-bradycardia.
-+ -+
Chemoreceptors:
Peripheral- carotid and aortic bodies are stimulated by Po2 (< 60 m m Hg),
t Pco2 , and pH of blood.
Central- are stimulated by changes i n pH and Pco2 of bra i n i nterstitial
fluid, which in turn are influenced by arterial C 02 . Do not d irectly respond
to Po 2 .
Circulation through organs

Lung Organ with largest blood flow ( 1 00% of cardiac output) .
Liver Largest share of systemic cardiac output.
Kidney H ighest blood flow per gram of tissue.
Heart Largest arteriovenous 02 difference because 02 extraction is- 8 0 % . Therefore t 02 demand is met
by t coronary blood flow, not by t extraction of 02 .
Normal pressures PCWP- pulmonary capillary wedge pressure

<12 PCWP
(in m m Hg) is a good approximation of left
atrial pressure. I n m itral stenosis, PCWP > LV
diastol ic pressure.
Measured with pulmonary artery catheter
( Swan-Ganz catheter) .
C A R D I O VASC U L A R C A R D I OVASC U L A R- P AT H OLOGY SECT I O N I l l 26 5
Autoregulation How blood flow to an organ remains constant over a wide range of perfusion pressures.
ORGAN FACTORS DETERMI N I N G AUTOREGU LATION
Heart Local metabol ites (vasodilatory)-C0 2 , Note : the pulmonary vasculature is u n ique in
adenosine, NO that hypoxia causes vasoconstriction so that
Brain Local metabolites (vasodilatory) -C02 (pH) only well-ventilated areas a re perfused. In
other organs, hypoxia causes vasodilation.
Kidneys Myogenic and tubuloglomerular feedback
Lungs Hypoxia causes vasoconstriction
Skeletal muscle Local metabol ites-lactate, adenosine, K+
Skin Sympathetic stimulation most important
mechan ism - temperature control
Capillary fluid Starl ing forces determine fluid movement through capillary membranes :
exchange P =capillary pressure - pushes fluid out of capillary
c
P =i nterstitial fluid pressur e - pushes fluid into capillary
i
1t =plasma colloid osmotic pressur e - pulls fluid into capi llary
c
Capillary 1t =i nterstitial fluid colloid osmotic pressur e - pulls fluid out of capillary
i
Thus, net filtration pressure=Pnet=[(Pc- P)- (7tc 7t)] -
.
Kr=filtration constant (capillary permeabi l ity) .

Jv=net fluid flow=(Kr)(Pnet).
Edema- excess fluid outflow into interstitium commonly caused by:
t capi llary pressure (t P ; heart failure)
c
plasma proteins (! 1t ; nephrotic syndrome, 1 iver fa ilure)
c
t capillary permeability (t Kr; toxins, infections, burns)
t i nterstiti al fluid colloid osmotic pressu re (t 1t ; lymphatic blockage)

i
C A R D I OVASC U L A R- PAT H OLOGY
Congenital heart disease

Right-to-left shunts Tetralogy of Fallot (most common cause of early The 5 T's:
(early cyanosis) cyanosis) Tetralogy
"blue babies" Transposition of great vessels Transposition
Persistent Truncus arteriosus -failure of truncus Truncus
arteriosus to divide into pulmonary trunk and Tricuspid
aorta ; most patients have accompanying VSD TAPVR
Tricuspid atresia- characterized by absence of
tricuspid valve and hypoplastic RV; requires
both ASD and VSD for viabil ity
Total anomalous pulmonary venous return
(TAPVR) - pul monary veins drain into right
heart circulation ( SVC , coronary sinus, etc . ) ;
associated with ASD a n d sometimes PDA to
allow for right-to-left shunting to maintain CO
Left-to-right shunts VSD (most common congenital cardiac Frequency: VSD > ASD > PDA
(late cyanosis) anomaly)
"blue kids" ASD (loud Sl ; wide, fixed spl it S2 )
PDA (close with i ndomethacin)
I
266 SECT I O N I l l CA R D I OVASC U L A R C A R D I OVASC U L A R - PAT H OLOGY
Eisenmenger's Uncorrected VSD, ASD, or PDA causes

syndrome compensatory pulmonary vascular
hypertrophy, wh ich results in progressive
pulmonary hypertension. As pulmonary
resistance t, the shunt reverses from left
to-right to right-to-left, which causes late
cyanosis, clubbing, and polycythem ia.
Tetralogy of Fallot Tetralogy of Fallot is caused by anterosuperior PROVe.

d isplacement of the infundibular septum. Older patients h istorically learned to squat to
0 Pul monary infundibular stenosis (most rel ieve cyanotic symptoms. S quatting reduced
important determi nant for prognosis) blood flow to the legs, t peripheral vascular
@RVH resistance ( P VR), and thus ! the cyanotic
Overriding aorta (overrides the VSD) right-to-left shunt across the VSD.
avso Preferred treatment is early, primary surgical
Early cyanosis ( " tet spells") caused by a right correction .
to-left shunt across the VSD. Isolated VSDs
usually flow left to right (acyanotic) . In
tetralogy, pulmonary stenosis forces right-to
left (cyanotic) flow and causes RVH (on x-ray,
boot-shaped heart) .
D-transposition of Aorta leaves R V (anterior) and pulmonary trunk

great vessels leaves LV (posterior) -+ separation of systemic
and pulmonary circulations. Not compatible
with l i fe unless a shunt is present to allow
ade quate mixing of blood (e.g., VSD, PDA, or
patent foramen ovale) .
Due to failure of the aorticopulmonary septu m Right
to spiral. ventricle
Left
Without surgical correction, most infants die ventricle
with i n the first few months of life. Ventricular
septum
Coarctation of the Can result in aortic regurgitation.

aorta
Infantile type-aortic stenosis proximal to Infantile : in close to the heart.
insertion of ductus arteriosus (preductal) . Check femoral pulses on physical exa m .
Associated with Turner syndrome.
Adult type- stenosis is d istal to ligamentum Adult: d istal t o ductus.
arteriosum (postductal) . Associated with Most commonly associated w ith bicuspid aortic
notching of the ribs (due to collateral valve .
circulation), hypertension in upper
extrem ities, weak pulses in lower extremities.
CA R D I O VASC U L A R C A R D I OVASC U L A R- P AT H O LOGY SECT I O N I l l 2 67
Patent dudus I n fetal period, shunt is right to left (normal) . Endomethacin ( indomethacin) ends patency of
arteriosus I n neonatal period, lung resistance and PDA ; PGE k EEps it open (may be necessary to
shunt becomes left to right with subse quent sustain l i fe in conditions such as transposition
RVI-1 and/or LVH and fa ilur e (abnormal) . of the great vessels) .
Aorta
Associated with a continuous, "machine-l ike" PDA is normal i n utero and normally closes only
Ductus murmur. Patency is maintained by PGE after bi rth.
arteriosus
(patent)
synthesis and low 0 2 tension .
Uncorrected PDA can eventually result in late
Pulmonary
artery
cyanosis in the lower extrem ities (differential
cyanosis) .
Congenital cardiac DISORDER DEFECT

defed associations 2 2q l l syndromes Truncus arteriosus, tetral ogy of Fallot
Down syndrome ASD, VSD, AV septal defect (endocardial
cushion defect)
C ongenital rubella Septal defects, PDA, pulmonary artery stenosis
Turner syndrome Coarctation of aorta (preductal)
Marfan's syndrome Aortic insufficiency and dissection (late
compl ication)
Infant of diabetic mother Transposition of great vessels
Hypertension Defined as BP 140/90 mm Hg.

RISK FACTORS t age, obesity, diabetes, smoking, genetics, black > white > Asian .
FEATURES 9 0 % o f hypertension is 1 (essential) and related to t C O or t T P R ; remaining 1 0 % mostly 2 to
renal d isease. Mal ignant hypertension is severe (> 1 80 1 1 2 0 m m Hg) and rapidly progressing.
PREDISPOSES TO Atherosclerosis, left ventricular hypertrophy, stroke, C H F, renal fa ilure, reti nopathy, and aortic
d issection.
Hyperlipidemia signs
Atheromas Pla ques i n blood vessel walls.
Xanthomas Pla ques or nodules composed of lipid-laden histiocytes i n the skin, especially the eyel ids
(xanthelasma) .
Tendinous xanthoma Lipid deposit in tendon, especially Achilles.
Corneal arcus Lipid deposit in cornea, nonspecific (arcus sen ilis) .
Arteriosclerosis
Monckeberg Calcification in the media of the arteries, especially rad ial or ulnar. Usually ben ign; "pipestem"
arteries. Does not obstruct blood flow; intima not involved.
Arteriolosclerosis Two types : hyaline (thickening of small arteries i n essential hypertension or d iabetes mell itus) and
hyperplastic ("onion skinning" in mal ignant hypertension ) .
Atherosclerosis Fibrous pla ques a n d atheromas form i n intima o f arteries.
268 SECT I O N I l l CAR D I O VASC U L A R C A R D I OVAS C U L A R- PAT H O LOGY
Atherosclerosis D isease of elastic arteries and large- and medium-sized muscular arteries.
RISK FACTORS Modifiable : smoking, hypertension,
hyperl ipidemia, diabetes. Non-modifiabl e :
age, gender (t i n m e n a n d postmenopausal
women), and positive family history.
PROGRESSION Inflammation i mportant in pathogenesis.
Endothelial cell dysfunction - macrophage
and LDL accumul ation - foam cell
formation -+ fatty streaks - smooth muscle I
cell migration ( involves PDGF and FGF ) ,
proliferation, and extracel lular matrix
deposition - fibrous pla que - complex
Atherosclerosis. Atherosclerotic plaque 1n the LAD
atheromas rJ. coronary a rtery. Note the cholesterol crysta ls (arrow) 13
COMPLICATIONS Aneurysms, ischem ia, infarcts, peripheral

vascular d isease, thrombus, embol i.
LOCATION Abdom inal aorta > coronary artery > popliteal
artery > carotid artery.
SYMPTOMS Angina, claudication, but can be asymptomatic.
Aortic aneurysms Local ized pathologic dilation of blood vessel.

Abdominal aortic Associated with atherosclerosis. Occurs more fre quently in hypertensive male smokers > 5 0 years of
aneurysm age.
Thoracic aortic Associated with hypertension, cystic medial necrosis (Marfan's syndrome) and h istorically
aneurysm 3 syph il is.
Aortic dissection Longitud inal i ntraluminal tear forming a false

lumen rJ. Associated with hypertension,
bicuspid aortic valve, cystic medial necrosis,
and inherited connective tissue disorders (e.g.,
Marfan's syndrome) . Presents with tearing
chest pain radiating to the back. CXR shows
mediastinal widening. The false lumen can
be l i m ited to the ascending aorta, propagate
from the ascending aorta, or propagate from
the descending aorta. Can result in pericard ia!
tamponade, aortic rupture, and death.
Aortic dissection (CT). Note 1ntra lummal tea r form 1ng
a "flap" that separates the true and false lum1na 1n the
descend1ng aorta (arrow). C
CA R D I O VASC U L A R C A R D I OVAS C U L A R - PAT H O LOGY SECT I O N I l l 269
Ischemic heart disease manifestations

Angina CAD narrowing > 7 5 % ; no myocyte necrosis :
Sta ble - mostly 2 to atherosclerosis; ST depression on ECG (retrosternal chest pain with
exertion)
Prinzmeta l 's va riant- occurs at rest 2 to coronary artery spas m ; ST elevation on ECG
U n stable/crescendo -thrombosis with incomplete coronary artery occlusion ; ST depression on
ECG (worsen ing chest pain at rest or with m i n i mal exertion)

Coronary steal Vasod ilator may aggravate ischemia by shunting blood from area of critical stenosis to an area of
syndrome higher perfusion.
Myocardial infarction Most often acute thrombosis clue to coronary artery atherosclerosis with complete occlusion of
coronary artery and myocyte necrosis ; ECG in itially shows ST depression progressi ng to ST
elevation with continued ischemia and transmural necrosis.
Sudden cardiac death Death from cardiac causes with i n l hour of onset of symptoms, most commonly due to a lethal
arrhythmia (e.g., ventricular fibrillation ) . Associated w ith CAD (up to 70% of cases) .
Chronic ischemic Progressive onset of C H F over many years clue to chronic ischemic myocard i a l damage.
heart disease
270 SECT I O N I l l CAR D I OVASC U L A R C A R D I OVAS C U L A R-PAT H O LOGY
Evolution of M l Coronary artery occlusion : LAD > RCA > circumflex.

Symptoms : diaphoresis, nausea, vom iting, severe retrosternal pai n , pain i n left arm and/or jaw,
shortness of breath, fatigue.
TIME GROSS liGHT MICROSCOPE RISK
0-4 hr None one Arrhyth mia, C H F exacerbation,
cardiogen ic shock
4 - 1 2 hr Early coagulative necrosis, Arrhyth mia
edema, hemorrhage, wavy
fibers.
-
I nfarct
Dark mottl i n g ;
1 2-24 hr pale with Contraction bands from Arrhythmia
tetrazo l i u m reperfusion injury.
stain
Release of necrotic cell content
into blood.
Beginning of neutroph il
migration .
1 -3 days Extensive coagulative necrosis. Fibrinous pericarditis
Tissue surrounding infarct
shows acute inflammation .
Neutrophil m igration .
-
Hyperemia
3 - 1 4 days Macrophage infiltration Free wall rupture leading

followed by granulation tissue to tampon ade, papillary
Hyperemic bord e r ;
central yellow-brown
at the margins. muscle rupture, ventricular
softe n i ng - aneurysm , i nterventricular
maximally yellow
septal rupture due to
and soft by 10 d ays -
- macrophages that have
degraded i mportant structural
components
2 weeks to several Contracted scar complete. Dressler's syndrome

months
'. 1-M.-- Recanal ized

artery
G ray-white
CA R D I O VASC U L A R C A R D I OVASC U L A R - PAT H OLOGY SECT I O N I l l 27 1
Diagnosis of M l I n the first 6 hours, ECG is the gold standard.

Cardiac troponin I rises after 4 hours and is elevated for 7-1 0 days ; more specific than other protein
markers .
C K-MB is predom i nantly found in myocardium but can also be released from skeletal muscle.
Usefu l i n d iagnosing reinfarction following acute MI because levels return to normal after 48
hours.
ECG changes can include ST elevation (transmural infarct) , ST depression (subendocard ial
infarct) , and pathologic Q waves (transmural infarct) .
Types of infarcts Transmural i nfarcts Subendocardial i nfarcts

t necrosis Due to ischemic necrosis of < 5 0 % of ventricle
wall
Affects entire wal l Subendocard ium especially vulnerable to
ischem ia
ST elevation o n ECG, Q waves ST depression on ECG
ECG diagnosis of M l I N FARCT lOCATION lEADS WITH Q WAVES
Anterior wall ( LAD) V l -V4

Anteroseptal ( LAD) V l -V2
Anterolateral ( LCX) V4-V6
Lateral wall ( LCX) I , aVL
Inferior wall ( RCA) II, I I I , aVF
Ml complications Cardiac arrhythmia-important cause of death before reachi n g hospita l ; common i n fi rst few days
LV failure and pulmonary edema.
Cardiogenic shock (large infarct-high risk of mortal ity) .
Ventricular free wall rupture -+cardiac tamponade ; papillary muscle rupture severe mitral
-+
regurgitation ; and i nterventricular septum rupture - VSD.

Ventricular aneurysm formation - ! CO, risk of arrhythmia, embolus from mural thrombus ;
greatest risk approximately l week post-M I .
Postinfarction fibrinous pericarditis-friction rub ( l -3 days post-M I ) .
D ressler's syndrome - autoimmune phenomenon resulting i n fibrinous pericarditis (several weeks
post-M I ) .
272 SECT I O N I l l CAR D I OVASC U L A R C A R D IOVASC U l A R -PAT H O lOG Y
Cardiomyopathies
Dilated (congestive) Most common cardiomyopathy (90% of Systolic dysfu nction ensues.
cardiomyopathy cases ) . Often id iopathic (up to 5 0 % of Eccentric hypertrophy (sarcomeres added in
cases may be famil ial). Other etiologies series) .
include chron ic Alcohol abuse, wet Beriberi , ABCCCD.
Coxsackie B virus myocard itis, chron ic
Cocaine use, Chagas' d isease, Doxorubicin
toxicity, hemochromatosis, and peripartum
cardiomyopathy.
Findings : S 3, d i lated heart on ultrasound,
balloon appearance on chest x-ray.
Treatment: Na+ restriction, ACE inh ibitors,
d iuretics, d igoxin, heart transplant.
Hypertrophic Hypertrophied i nterventricular septum is " too Diastol ic dysfunction ensues.
cardiomyopathy close" to m itral valve leaflet, leading to outflow Asymmetric concentric hypertrophy (sarcomeres
tract obstruction r.J. 60-70 % of cases are added i n parallel ) .
fam i l ial, autosomal dom inant (commonly a Proxim ity o f hypertrophied interventricular
-myosin heavy chain mutation). Associated septum to m itral leaflet obstru cts outflow tract,
with Friedreich 's ataxia. Disoriented, tangled, resulting i n systolic murmur and syncopal
hypertrophied myocardial fibers. Cause of episodes.
sudden death in young athletes.
Findings: normal-sized heart, S4, apical
impulses, systolic murmur.
Treatment: -blocker or non-d ihydropyridine
calcium channel blocker (e.g., verapamil).
Restrictive/ Major causes include sarcoidosis, amyloidosis, Diastol ic dysfunction ensues.

obliterative postrad iation fibrosis, endocardial fibroelastosis
cardiomyopathy (th ick fibroelastic tissue in endocardium
of young children), Loftier's syndrome
(endomyocardial fibrosis with a prom inent
eosinoph ilic i n filtrate), and hemochromatosis
(dilated cardiomyopathy can also occur) .
CA R D I OVASCU L A R C A R D I OVASC U L A R - PAT H O LOGY SECT I O N I l l 273
CHF A clin ical syndrome that occurs in patients with an inherited or acqu ired abnormal ity of cardiac
structure or function, which is characterized by a constellation of clin ical symptoms (dyspnea,
fatigue) and signs (edema, rales) .
Right heart fa ilure most often results from left heart fa ilure. I solated right heart failure is usually
clue to cor pulmonale.
AC E inh ibitors, -blockers (except in acute decompensated I-I F ) , angiotensin receptor antagon ists,
and spironolactone reduce mortal ity. Thiazide or loop d iuretics are used mainly for symptomatic
rel ief. Hydralazine with nitrate therapy improves both symptoms and mortal ity i n select patients.
ABNORMALITY CAUSE
Cardiac dilation Greater ventricular end-diastol ic volume.

Dyspnea on exertion Fa ilur e of cardiac output to t during exercise.
Left heart failure
Pulmonary edema, t pulmonary venous pressure pulmonary
--+
paroxysmal venous d istention and transudation of fluid.

nocturnal dyspnea Presence of hemosiderin-laden macrophages
( " heart fa ilure" cells) in the lungs. I
Pulmonary
edema r Pulmonary venous
congestiOn
! Cardiac
output
t venous return i n supine position exacerbates

1
Orthopnea
(shortness of breath pul monary vascular congestion .
1
\
t_______J
_ i Renin
! RV output angiotensin
when supine) aldosterone
Right heart failure

Peripheral i Syslemic venous
i
Ren l Na
Hepatomegaly t central venous pressure --+ t resistance to edema

._______J
-
!
pressure +--- and H20
reabsorption
(nutmeg liver) portal flow. Rarely, leads to "cardiac cirrhosis."

i Preload, i cardiac i LV +----- i Sympathetic
Perip heral edema t venous pressure --+ fluid transudation . output (compensation) contractility activity
Jugular venous t venous pressure.

distention
2 74 SECT I O N I l l C A R D I O VASC U L A R C A R D I OVAS C U L A R- PAT H O L O G Y
Baderial endocarditis Fever (most common symptom) , Roth 's spots M itral valve is most frequently involved .
(round white spots on retina surrounded by Tricuspid valve endocarditis is associated with
hemorrhage), Osler's nodes (tender raised I V drug abuse (don't tri drugs) . Associated
lesions on finger or toe pads), new murmur, with S. aureus, Pseudomonas, and Candida.
Janeway lesions (smal l , painless, erythematous Complications: chordae rupture,
lesions on palm or sole), anemia, spl inter glomerulonephritis, suppurative pericarditis,
hemorrhages rzJ on nail bed. Multiple blood embol i .
cultures necessary for diagnosis. Bacteria F ROM JANE:
Acute - S . aureus (h igh viru lence ) . Fever
Large vegetations on previously normal Roth 's spots
valves [I). Rapid onset. Osler's nodes
Subacute -viriclans streptococci (low Murmur
virulence ) . Smaller vegetations on Janeway lesions
congenitally abnormal or diseased valves. Anemia
Sequela of dental procedures. More Nail-bed hemorrhage
insidious onset. Embol i
Endocarditis may also be non bacterial zo to
mal ignancy, hypercoagulable state, or lupus
(marantic/th rombotic endocarditis) . S. hovis
is present in colon cancer, S. epidermidis on
prosthetic valves.
Rheumatic fever A consequence of pharyngeal infection with FEVERS S :

group A -hemolytic streptococci . Early deaths Fever
clue to myocard itis. Late sequelae i nclude Erythema marginatum
rheumatic heart d isease, wh ich affects heart Valvular damage (vegetation and fibrosis)
valves - m itral > aortic >> tricuspid (high ESR t
pressure valves affected most) . Early lesion Reel - hot joints (migratory polyarthritis)
is m itral valve regurgitation ; late lesion is Subcutaneous nodules
m itral stenosis. Associated with Aschoff bodies St. Vitus' dance ( Syclenham's chorea)
(granuloma with giant cells) r.J, Anitschkow's
cells (activated histiocytes), elevated ASO
titers.
Immune mediated (type I I hypersensitivity) ;
not a d i rect effect of bacteria. Antibodies to M
protein.
CARDIOVASC U LAR C A R D I OV ASCUL A R -PAT H OLOGY SECTION I l l 275
Acute pericarditis Commonly presents with sharp pain, aggravated by inspiration , and rel ieved by sitting up and
leaning forward . Presents with friction rub. ECG changes i nclude widespread ST-segment
elevation and/or PR depression.
Fibrinous - caused by Dressler's syndrome, uremia, rad iation. Presents with loud friction rub.
Serous - viral pericarditis (often resolves spontaneously) ; noninfectious inflammatory diseases
(e.g., rheumatoid arthritis, SLE ) .

Suppurative/purulent- usually caused b y bacterial infections (e.g., Pneumococcus,
Streptococcus) . Rare now with antibiotics.
Cardiac tamponade Compression of heart by fluid (e.g., blood, effusions) i n pericardium, leading to ! CO.
Equil ibration of diastol ic pressures in all 4 chambers.
Find ings : hypotension, t venous pressure (JVD), distant heart sounds, t H R , pulsus paradoxus.
Pulsus paradoxus - ! in ampl itude of systol ic blood pressure by lO m m H g during inspiration .

Seen in severe cardiac tamponade, asthma, obstructive sleep apnea, pericard itis, and croup.
Syphilitic heart 3 syph ilis d isrupts the vasa vasorum of the Can result i n aneurysm of the ascending aorta
disease aorta with consequent atrophy of the vessel or aortic a rch and aortic insufficiency.
wall and d ilation of the aorta and valve ring.
May see calcification of the aortic root and
ascending aortic arch. Leads to "tree bark"
appearance of the aorta.
Cardiac tumors Myxomas - m ost common 1 cardiac tumor

i n adults r.:J. 90% occur in the atria (mostly
left atriu m) . Myxomas are usually described
as a "ball valve" obstruction in the left atrium
(associated with multiple syncopal episodes ) .
Rh a b domyomas - most frequent 1 cardiac

tumor in children (associated with tuberous
sclerosis) .
Most common heart tumor is a metastasis (from

melanoma, lymphoma) .
Kussmaul's sign t in JVP on inspiration i nstead of a normal ! .

I nspiration --+ negative i ntrathoracic pressure not transmitted to heart --+ impaired filling of right
ventricle --+ blood backs up into venae cavae --+JVD. May be seen with constrictive pericarditis,
restrictive cardiomyopath ies, right atrial or ventricular tumors, or cardiac tamponade.
276 SECT I O N I l l CA R D I OVASC U L A R C A R D I OVAS C U L A R- PAT HO LOGY
Raynaud's blood flow to the skin due to arteriolar Affects small vessels.
phenomenon vasospasm in response to cold temperature
or emotional stress. Most often in the fingers
and toes rJ. Called Raynaud's disease when
primary (idiopath ic), Raynaud's syndrome
when secondary to a disease process such
as m ixed connective tissue d isease, SLE, or
C REST (lim ited form of systemic sclerosis)
syndrome.
Raynaud's phenomenon. Note t h e fi ngertip cyanosis

(arrow).
Vasculitis
EPIDEMIOLOGY/PRESENTATION PATHOLOGY/lABS
Large-vessel vasculitis
Temporal (giant cell) Generally elderly females. Most commonly affects branches of carotid
arteritis Unilateral headache (temporal artery) , jaw artery.
claud ication . Focal gran ulomatous inflammation .
May lead to irreversible bli ndness clue to t ESR.
ophthalmic artery occlusion . Treat with high-close corticosteroids.
Associated with polymyalgia rheumatica .
Takayasu's arteritis Asian females < 40 years of age. Granulomatous thicken ing of aortic arch ,
"Pulseless d isease" (weak upper extremity proximal great vessels.
pulses) , fever, n ight sweats, arthritis, myal gias, t ESR.
skin nodules, ocular disturbances. Treat with corticosteroids.
Medium-vessel vasculitis
Polyarteritis nodosa Young adults. Typically involves renal and visceral vessels, not
Hepatitis B seropositivity in 30 % of patients. pulmonary arteries.
Fever, weight loss, malaise, headache. Immune-complex mediated.
Gl : abdominal pai n , melena. Transmural inflam mation of the arterial wall
Hypertension, neurologic dysfunction, with fibrinoid necrosis.
cutaneous eruptions, renal damage. Lesions are of different ages.
Many aneurysms and constrictions on arteriogram.
Treat with corticosteroids, cyclophosphamide.
Kawasaki disease Asian children < 4 years of age. May develop coronary aneurysms MI, -+
Fever, cervical lymphaden itis, conjunctival ruptur e .

injection, changes in l ips/oral mucosa Treat with IV immunoglobul i n a n d aspi rin.
( "strawberry tongue" ) , hand-foot erythema,
and desquamating rash .
Buerger's disease Heavy smokers, males < 40 years of age. Segmental thrombosing vascul itis.
(thromboangiitis Interm ittent claud ication may lead to gangrene, Treat with smoking cessation.
obliterans) autoamputation of digits, superficial nodular
phlebitis.
Raynaucl's phenomenon is often present.
CARD IOVASC U LAR C A R D I OVASC U L A R - P AT H OLOGY SECTION I l l 277
Vasculitis (continued)
EPIDEMIOLOGY/PRESENTATION PATHOLOGY/LABS
Small-vessel vasculitis
Microscopic Necrotizing vasculitis commonly i nvolving No granulomas.

polyangiitis lung, kidneys, and skin with pauci-immune p-AN CA.
glomeru lonephritis and palpable purpur a . Treat with cyclophospham ide and
corticosteroids.
Wegener's Upper respiratory tract: perforation o f nasal Triad:
granulomatosis septum , chronic si nusitis, otitis media, Focal necrotizing vascul itis
(granulomatosis with mastoiditis. Necrotizing granulomas in the lung and
polyangiitis) Lower respi ratory tract: hemoptysis, cough, upper a i rway

dyspnea. Necrotizing glomeru lonephritis.
Renal : hematuria, reel cell casts. c-AN CA.

Chest x-ray: large nodular densities.
Treat with cyclophosphamide, corticosteroids.
Churg-Strauss Asthma, sinusitis, palpable purpura, peripheral Granulomatous, necrotizing vasculitis with
syndrome neuropathy (e.g., wrist/foot drop) . eosinoph ilia.
Can also i nvolve heart, GI, kidneys (pauci- p-ANCA, elevated IgE level .
immune glomerulonephritis) .
Henoch-Schonlein Most common childhood systemic vascul itis. Vasculitis secondary to I gA complex deposition.
purpura Often follows U RI . Associated with I gA nephropathy.
Classic triad :
Ski n : palpable purpura on buttocks/legs
Arthralgia
GI : abdominal pain, melena, multiple
lesions of same age

27 8 SECT ION I l l CARD IOVAS C U L AR C A R D I OVAS C U L A R-PAT H O LOGY
Vascular tumors
Strawberry Benign capillary hemangioma of infancy. Appears in first few weeks of l i fe ( 1 /200 bi rths) ; grows
hemangioma rapidly and regresses spontaneously at 5-8 years of age.
Cherry hemangioma Benign capillary hemangioma of the elderly. Does not regress. Frequency t with age.
Pyogenic granuloma Polypoid capillary hemangioma that can ulcerate and bleed. Associated with trauma and
pregnancy.
Cystic hygroma Cavernous lymphangioma of the neck. Associated with Turner syndrome.
Glomus tumor Benign, painfu l , red-blue tumor under fingernails. Arises from modified smooth muscle cells of
glomus body.
Bacillary angiomatosis Ben ign capillary skin papules found in AIDS patients. Caused by Bartonella henselae infections.
Frequently m istaken for Kapos i 's sarcoma.
Angiosarcoma Rare blood vessel mal ignancy typically occurring in the head, neck, and breast areas. Associated
with patients receiving radiation therapy, especially for breast cancer and Hodgki n's lymphoma.
Very aggressive and difficult to resect clue to delay i n d iagnosis.
Lymphangiosarcoma Lymphatic mal ignancy associated with persistent lymphedema (e.g., post-radical mastectomy) .
Kaposi's sarcoma Endothelial mal ignancy most commonly of the ski n , but also mouth, GI tract, and resp iratory tract.
Associated with H H V-8 and HIV. Frequently m istaken for bacillary angiomatosis.
Sturge-Weber disease Congen ital vascular disorder that affects Affects small vessels.
capillary-sized blood vessels. Manifests with
port-wine stain (nevus A ammeus) on face,
ipsilateral leptomeningeal angiomatosis
(intracerebral AVM ) , seizu res, and early-onset
glaucoma.
CAR D I O VASC U LAR C A R D I OVA S C U LAR- P H A R M A C O LOGY SE C T I O N I l l 2 79
C A R D I OVAS C U L A R- P H A R M A COLOGY
Antihypertensive therapy
Essential hypertension Diuretics, ACE inh ibitors, angiotensin I I See the Ren a l chapter for more deta ils about
receptor blockers (ARBs) , calcium channel diuretics and ACE inh ibitors/ARBs.
blockers.
CHF Diuretics, AC E inh ibitors/ARBs, -blockers -blockers must be used cautiously in
(compensated C H F ) , K+ -sparing d iuretics. decompensated C H F, and are contraindicated
in cardiogen ic shock.
Diabetes mellitus AC E inhibitors/ARBs, calcium channel AC E i n h ibitors are protective aga inst diabetic
blockers, d iuretics, -blockers, a-blockers. nephropathy. See the Pharmacology chapter
for more details about a-blockers.
Calcium channel Nifedipine, verapamil, diltiazem, amlodipine.

blockers
MECHAN ISM Block voltage-dependent L-type calcium chan nel s of card iac and smooth muscle and thereby
reduce muscle contractil ity.
Vascular smooth muscle -amlodipine = nifed ipine > d iltiazem > verapamil.
Heart-verapamil > diltiazem > amlodipine = nifedipine (verapam il = ventricle) .
CliNICAL USE Hypertension, angina, arrhythm ias (not nifed ipine) , Prinzmeta l 's angina, Raynaud's.
TOXICITY Cardiac depression, AV block, peripheral edema, flush ing, d i zziness, and constipation.
Hydralazine
MECHAN ISM t cGMP -+ smooth muscle relaxation. Vasodilates arterioles > veins; afterload reduction .
CliNICAL USE Severe hypertension, C H F. First-l ine therapy for hypertension in pregnancy, with methyldopa.
Frequently coadmin istered with a -blocker to prevent reflex tachycardia.
TOXICITY Compensatory tachycardia (contra ind icated in angina/CAD ) , fluid retention, nausea, headache,
angina. Lupus-like syndrome.
Malignant Commonly used d rugs include n itroprusside, n icard ipine, clevidipine, labetalol , and fenoldopam.
hypertension treatment
Nitroprusside Short acting; t cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide) .
Fenoldopam Dopamine D 1 receptor agon ist- coronary, peripheral, renal, and splanchnic vasodilation. BP and
t natriuresis.
280 SECT I O N I l l CAR D I OVASC U L A R C A R D I OVASC U L A R- P H A R M A COLOGY
Nitroglycerin, isosorbide dinitrate

MECHANISM Vasodilate by releasing n itric oxide in smooth muscle, causing t i n cGM P and smooth muscle
rel axation . Dilate veins >> arteries. ! preload.
CLIN ICAL USE Angina, pulmon ary edema.
TOXICITY Reflex tachycardia, hypotension , Hushing, headache, " Monday disease" i n industrial exposur e :
development o f tolerance for the vasod ilating action during the work week a n d loss o f tolerance
over the weekend results in tachycardia, dizziness, and headache upon reexposure .
Antianginal therapy Goal- reduction o f myocard ial 02 consumption (MV0 2 ) b y decreasing 1 or more of the
determinants of MV0 2 : end-diastol ic volume, blood pressure, heart rate, contractility, ej ection
time.
COMPONENT N ITRATES (AFFECT PRELOAD) -BLOCKERS (AFFECT AFTERLOAD) N ITRATES + -BLOCKERS
End-diastolic volume No effect or !

Blood pressure
Contractility t (reflex response) Little/no effect

Heart rate t (reflex response)
Ejection time Little/no effect
MV02 !!
Calcium channel blockers - n ifedipine is similar to nitrates in effect; verapamil is similar to -blockers i n effect.
Pindolol and acebutolol - partial -agonists contraindicated in angina.
CARD I O VASC U LAR C A R D I OV ASC U L A R - P H A R M A C O LOGY SECT I O N I l l 28 1
Lipid-lowering agents
EFFECT ON lDl EFFECT ON HDl EFFECT ON
DRUG "BAD CHOlESTEROL" "GOOD CHOlESTEROl' TRIGlYCERIDE$ MECHANISMS O F ACTION SIDE EFFECTS/PROBlEMS
HMG -CoA reductase u I n h ibit conversion Hepatotoxicity

inhibitors (lovastatin, of H MG-CoA (t LFTs),
pravastatin, to mevalonate, a rhabdomyolysis
simvastatin, cholesterol precursor
atorvastatin,
rosuvastatin)
Niacin (vitamin 83) tt I n h ibits l ipolysi s Reel , flushed face,
in ad ipose tissue ; which is by aspirin
reduces hepatic or long-term use
VLDL secretion i nto Hyperglycemia
circulation (acanthosis
n i gricans)
Hyperuricemia
(exacerbates gout)
Bile acid resins u Slightly t Slightly t Prevent i ntestinal Patients hate it- tastes
(cholestyramine, reabsorption of bile bad and causes
colestipol, acids; l iver must use GI discomfort,
colesevelam) cholesterol to make absorption of fat-
more soluble vitam ins
Cholesterol gal l stones
Cholesterol absorption Prevent cholesterol Rare t LFTs, diarrhea
blockers (ezetimibe) reabsorption at small
i ntesti n e brush border
Fibrates (gemfibrozil, u Upregulate LPL Myositis,
clofibrate, t TG clearance
--+ hepatotoxicity
bezafibrate, (t LFTs), cholesterol
fenofibrate) gallstones
Gut
Hepatocytes
B lood Endothelial
cells
Ezetl mlbe
-
1 HMG
l
Ac-CoA
f oA
HMG-CoA
:J
reductase
bitors

I
/Li)L\
}
@ \
- Gemfibrozil
e I
T"'
]'"'
-
-r Nla::..
@
,------2-.,
/}'

L[ ""'

Reslns
._/
rr- Lipid
oxidation
(Adapted, with permission, from Katzung B G , Trevor AJ. USMLE Rood Map: Pharmacology, I st e d . N e w York: McGraw-Hill, 2003 : 56.)
28 2 SECTI O N I l l CAR D I OVASC U LAR C A R D I OVASC U L A R - P H A R M A COLOGY
Cardiac glycosides D igoxin-7 5 % bioavailabil ity, 20-40% protein bound, t 1 12 = 40 hours , u rinary excretion .
MECHAN ISM D i rect inh ibition of Na+fK+ ATPase leads to indirect inhibition of Na+fCa 2 + exchanger/antiport.
t [Ca 2 +] i positive inotropy. Stimulates vagus nerve ! H R .
-+ -+
CLIN ICAL USE C H F ( t contractil ity) ; atrial fibrillation ( ! conduction a t AV node a n d depression of SA node) .
TOXICITY Chol i nergi c - nausea, vom iting, diarrhea, blurry yel low vision (th ink Van Gogh) .
E C G - t PR, ! QT, ST scooping, T-wave inversion, arrhythm ia, AV block.
Can lead to hyperkalem ia, a poor prognostic indicator.
Factors predisposing to toxicity- renal fai l ur e ( ! excretion), hypokalemia (permissive for digoxin
binding at K+ -binding site on Na+fK+ ATPase), quinidine ( ! digoxin clearance ; d isplaces d igoxin
from tissue-binding sites) .
ANTIDOTE Slowly normalize K+, l i docaine, cardiac pacer, anti-digoxin Fab fragments, Mg 2 +.
CAR D I O VASC U LAR C A R D I OVAS C U L A R- P H A R M A COLOGY SECT I O N I l l 283
Antiarrhythmics Local anesthetics. Slow or block ( ! ) conduction (especially in depolarized cells). ! slope of phase 0
Na+ channel blockers depolarization and t threshold for firing in abnormal pacemaker cells. Are state dependent
(class I) (selectively depress tissue that is frequently depolarized [e.g., tachycardia] ) .
Hyperkalemia causes t toxicity for all class I d rugs.
Class lA Qu i n idine, Procainam ide, Disopyramide. "The Queen Proclai ms D iso's pyramid ."
t AP duration, t effective refractory period
( ERP) , t QT interval. Affect both atrial and
ventricular arrhythmias, especially reentrant
and ectopic supraventricular and ventricular
tachycard ia.
Toxicity: quinidine (ci nchon ism- headache,
tinn itus) ; procainam ide (reversible SLE-l ike
syndrome) ; d isopyram ide (heart failur e ) ;
thrombocytopen i a ; torsades d e pointes d u e to
t QT interval.
Class IB Lidocaine, Mexiletine, Tocainide. 'T clBuy Lidy's Mexican Tacos."
! AP duration . Preferentially affect ischem ic or Phenytoin can also fal l into the I B category.
depolarized Purkinje and ventricular tissue. IB is B est post- M I .
Usefu l i n acute ventricular arrhythmias
(especially post-MI) and in digital is-induced
arrhythmias.
Toxicity: local anesthetic. C S stimulation /
depression, cardiovascular depression .
Class IC Flecai nide, propafenone. IC is C ontra ind icated in structural heart d isease
No effect on AP duration. Useful in ventricular and post-M I .
tachycardias that progress to VF and in
intractable SVT. Usually used only as last
resort i n refractory tachyarrhythm ias. For
patients without structural abnormalities.
Toxicity: proarrhythm ic, especially post-MI
(contraind icated) . Significantly prolongs
refractory period in AV node.
All class I drugs
O mV
Phase 0
I Na
Phase 3 ( I K)
Phase 4
-85 mV
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Stamford, G: Appleton & Lange, 1 99 8 : 1 1 8.)
284 SECT I O N I l l CARD I O VASC U LAR C A R D I OVAS C U LA R -PH A R M A COLO G Y
Antiarrhythmics Metoprolol , propranolol , esmolol , atenolol , timolol.

-blockers (class I I)
MECHANISM Decreases SA and AV nodal activity by ! cAM P, ! Ca 2 + currents. Suppress abnormal pacemakers by
! slope of phase 4.
AV node particularly sensitive - t PR interval . Esmolol very short acting.
CliN ICAl USE Ventricular tachycard ia, SVT, slowing ventricular rate during atrial fibrillation and atrial flutter.
TOXICITY I mpotence, exacerbation of asthma, cardiovascular effects (bradycard ia, AV block, C H F) , CNS
effects (sedation, sleep alterations) . May mask the signs of hypoglycem i a .
Metoprolol c a n cause dysl ipidemia. Treat overdose with glucagon . Propranolol c a n exacerbate
vasospasm i n Prinzmetal 's angina.
Antiarrhythmics Am iodarone, Ibutil ide, Dofetil ide, Sotalol . "AIDS."

K+ channel blockers
(class I l l)
MECHANISM t AP duration, t ERP. Used when other
antiarrhyth m ics fai l . t QT interval.
TOXICITY Sotalol - torsades de pointes, excessive block; Remember to check PFTs, LFTs, and TFTs
ibutilide - torsades; am iodarone -pulmonary when using am iodarone.
fibrosis, hepatotoxicity, hypothyroidism/
hyperthyroidism (am iodarone is 40% iodine by
weight) , corneal deposits, skin deposits (blue/
gray) resulting in photodermatitis, neurologic
effects, constipation, cardiovascular effects
(bradycard ia, heart block, C H F ) .
Amiodarone h a s class I , I I , I I I , a n d IV effects
because it alters the lipid membrane.
C lass I l l act ion
(Adapted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Boord Review, 5th ed. Stamford, a: Appleton & Lange, 1 99 8 : 1 20.)
Antiarrhythmics Verapam i l , diltiazem.

Cal+ channel blockers
(class IV)
MECHANISM ! conduction velocity, t ERP, t PR interval. Used in prevention of nodal arrhythmias (e.g., SVT) .
TOXICITY Constipation , flushing, edema, CV effects ( C H F, AV block, sinus node depression ) .
Other antiarrhythmics
Adenosine t K + out o f cells --+ hyperpolarizing t h e cell + !
lea D r u g o f choice in d iagnosing/abol ishing
supraventricular tachycard ia. Very short acting ( 1 5 sec) . Toxicity includes flushing, hypotension,
chest pai n . Effects blocked by theophylline and caffeine.
Effective in torsades de pointes and digoxin toxicity.
HIGH-YIELD SYSTEMS
Endocrine
"We have leamed that there is an endocrinology of elation and despair, a

chemistry of mystical insight, and, in relation to the autonomic nervous
system, a meteorology and even ... an astro-physics of changing moods."
-Aldous (Leonard) Huxley
"Chocolate causes certain endocrine glands to secrete hormones that affect

your feelings and behavior by making you happy."
- Elaine Sherman, Book of Divine Indulgences
286 SECTION Ill ENDOCRINE ENDOCRINE-EMBRYOLOGY
ENDOCRINE-EMBRYOLOGY
Thyroid development Thyroid diverticulum arises from floor of Foramen cecum

primitive pharynx, descends into neck.
Connected to tongue by thyroglossal duct,
which normally disappears but may persist as
pyramidal lobe of thyroid. Foramen cecum
Persistent
thyroglossal
duct
_m'
:
1
is normal remnant of thyroglossal duct. Most

Thyroid
common ectopic thyroid tissue site is the gland
tongue.
Thyroglossal duct cyst presents as an anterior Trachea
midline neck mass that moves with swallowing
(vs. persistent cervical sinus leading to
branchial cleft cyst in lateral neck).
Thymus
Fetal adrenal gland Consists of an outer adult zone and inner active fetal zone. Adult zone is dormant during early
fetal life but begins to secrete cortisol late in gestation. Cortisol secretion is controlled by ACTH
and CRH from fetal pituitary and placenta. Cortisol is responsible for fetal lung maturation and
surfactant production.
ENDOCRINE-ANATOMY
Adrenal cortex and medulla

'"-A-- Cortex (from mesoderm) GFR corresponds w ith Salt ( a+), Sugar
Medulla (from neural crest) (glucocorticoids), and Sex (androgens).
"The deeper you go, the sweeter it gets."
Primary
Pheochromocytoma-most common tumor of
regulatory control Anatomy Secretory products the adrenal medulla in adults.
Capsule Neuroblastoma-most common tumor of the
adrenal medulla in children.
Renin-angiotensin --+Zona --+ Aldosterone
Glomerulosa
Pheochromocytoma causes episodic
ACTH, hypothalamic --+Zona --+ Cortisol,
hypertension; neuroblastoma does not.
CRH Fasciculata sex hormones
ACTH, hypothalamic --+Zona --+ Sex hormones

CRH Reticularis (e.g., androgens)
Preganglionic --+Medulla --+ Catecholamines

sympathetic fibers (Epi, NE)
Adrenal gland Left adrenal left adrenal vein

--+ left renal
--+ Same as left and right gonadal vein.
drainage vein-+ IVC.
Right adrenal right adrenal vein IVC.
__. __.
ENDOCRINE ENDOCR INE - ANATOMY SECTION Ill 287
Pituitary gland
Posterior pituitary Secretes vasopressin (ADH) and oxytocin, made
(neurohypophysis) in the hypothalamus and shipped to posterior
pituitary via neurophysins (carr.ier proteins).
Derived from neuroectoderm.
Anterior pituitary Secretes FSH, LH, ACTH, T SH, prolactin, Acidophils- GH, prolactin.
(adenohypophysis) GH, melanotropin (MSH). Derived from oral B-FLAT : Basophils-FSH, LH, ACTH, TSH.
ectoderm (Rathke's pouch). FLAT PiG : F SH, LH, ACTH, T SH, Prolactin,
a subunit-hormone subunit common to GH.
TSH, LH, FSH, and hCG.
subun it-determines hormone specificity.
Endocrine pancreas Islets of Langerhans are collections of a, ' and Insulin ( cells) inside.
cell types 8 endocrine cells. Islets arise from pancreatic
buds. a =glucagon (peripheral); = insulin
(central); 8 =somatostatin (interspersed).
288 SECTION Ill ENDOCRINE ENDOCR INE-ANATO M Y
Insulin
SOURCE Released from cells of pancreas. Insulin moves glucose Into cells.
Proinsulin
Glucose is major regulator of insulin release. Insulin does not cross the placenta.
ATP generated by glucose metabolism closes BRICK L (insulin-independent glucose uptake):
K+ channels and depolarizes cell membrane
Brain, RBCs, Intestine, Cornea, Kidney, Liver
opens voltage-gated Ca 2+ channels. Ca 2+
-+
influx stimulates insulin secretion. GLUT-1 (insulin independent) : RBCs, brain.

GLUT-2 (bidirectional) : islet cells, liver, kidney,
small intestine.
GLUT:.4 (insulin dependent): adipose tissue,
P-chain
skeletal muscle.
FUNCTION Anabolic effects of insulin :
t glucose transport in skeletal muscle and
adipose
t glycogen synthesis and storage
t triglyceride synthesis and storage
t Na+ retention (kidneys)
t protein synthesis (muscles)
t cellular uptake of K+ and amino acids
! glucagon release
REGULATION Hyperglycemia, GH, and z -antagonists

..... t insulin.
Hypoglycemia, somatostatin, and a2-agonists
-+ ! insulin.
) Insulin
ATP-sensitive
Voltage-gated
K' channels close
Ca1' channels
O
d'
open
ATP Tyrosine
D epolarization
phosphorylation
f) I 0 .
t ATP/ADP ratio t Intracellular r!
'ycol
: ysis
Ca1+ Phosphoinositide- 3 RAS/MAP
GLUT-1 O lui 0 kinase pathway kinase

Insulin
\....._ pathway
J
Glucose GLUT-4
"\
l
Glucose Glucose -::::::=-

Glycogen,
lipid, protein
synthesis
Vesicles Cell growth,

Blood containing DNA
Insulin secretion-pancreatic cells vessel GLUT-4 synthesis
Glucose uptake
Insulin-dependent Resting skeletal muscle and adipose tissue depend on insulin fort glucose uptake (GLUT-4).
organs Brain and R BCs take up glucose independent of insulin levels (GLUT-1). Brain depends on
glucose for metabolism under normal circumstances and uses ketone bodies in starvation. RBCs
always depend on glucose because they have no mitochondria for aerobic metabolism.
ENDOCRINE ENDOCR INE-PHYSIOLOGY SECTION Ill 289
Glucagon
SOURCE Made by a cells of pancreas.
FUNCTION Catabolic effects of glucagon :
Glycogenolysis, gluconeogenesis
Lipolysis and ketone production
REGULATION Secreted in response to hypoglycemia. Inhibited by insulin, hyperglycemia, and somatostatin.
ENDOCRINE-PHYSIOLOGY
Hypothalamic-pituitary TRH----(!)---+ TSH, prolactin.

hormone regulation
Dopamine -0--+ prolactin.
CRH----(!)---+ ACTH, melanocyte-stimulating hormone, -endorphin.
GHRH ----(!)---+ G H.
Somatostatin -0--+ GH, TSH.
GnRH----(!)---+ FSH, LH.
Prolactin -0--+ GnRH.
290 SECTION Ill ENDOCRINE ENDOCRINE-PHYSIOLOGY
Prolactin
SOURCE Secreted mainly by anterior pituitary.

FUNCTION Stimulates milk production in breast; inhibits
ovulation in females and spermatogenesis
in males by inhibiting CnRH synthesis and
release.
REGULATION Prolactin secretion from anterior pituitary Dopamine agonists (bromocriptine) inhibit
is tonically inhibited by dopamine from prolactin secretion and can be used in
hypothalamus. Prolactin in turn inhibits treatment of prolactinoma.
its own secretion by increasing dopamine Dopamine antagonists (most antipsychotics)
synthesis and secretion from hypothalamus. and estrogens (OCPs, pregnancy) stimulate
TRH t prolactin secretion. prolactin secretion.
Anterior pituitary
o/ Spermatogenesis
'-----Prolactin------. GnRH
I 8 Ovulation
.8
Milk production
Growth hormone (somatotropin)
SOURCE Secreted mainly by anterior pituitary.

FUNCTION Stimulates linear growth and muscle mass
through ICF-1/somatomedin secretion.
t insulin resistance (diabetogenic).
REGULATION Released in pulses in response to CHRI-1. Excess secretion of CI-1 (e.g., pituitary adenoma)
Secretion t during exercise and sleep. may cause acromegaly (adults) or gigantism
Secretion inhibited by glucose and (children).
somatostatin.
ENDOCRINE EN DOCRINE- PHY SIO LOGY SECTION Ill 29 1
Adrenal steroids
ACTH Ketoconazole
/ 8
Chot"""'
Desmolase
Pregnenolone
3 - hydroxysteroid l 17u-hydroxylase
3 -hydroxysteroid
1
17-hydroxypregnenolone Dehydroepiandrosterone (DHEA)
13 -hydroxysteroid
dehydrogenase dehydrogenase dehydrogenase
Aromatase
Progesterone 17-hydroxyprogesterone Androstenedione Estrone
17u-hydroxylase
21-hydroxylase ) 21-hydroxylase
Aromatase
11-deoxycorticosterone 11-deoxycortisol Testosterone Estradiol
11 -hydroxylase 11 -hydroxylase Sa-reductase

Corticosterone Cortisol DHT
I Aldosterone
t
'<l
synthase
Aldosterone
Angiotensin ll
Glomerulosa Fasciculata
Mineralocorticoids Glucocorticoids
Congenital bilateral adrenal hyperplasiasa

SEX
DEFICIENCY MINERALOCORTICOIDS CORTISOL HORMONES PRESENTATION
17a-hydroxylase Hypertension, hypokalemia.

deficiency XY: ! DHT pseudohermaphroditism
-+
(variable, ambiguous genitalia; unclescenclecl

testes).
XX: externally phenotypic female with normal
internal sex organs, lacks zo sex characteristics.
) 21-hydroxylase Most common form.

deficiency Hypotension, hyperkalemia, t renin activity,
volume depletion.
Masculinization, leading to
pseudohermaphroditism in females.
11 p-hydroxylase ! aldosterone Hypertension (11-cleoxycorticosterone is a
deficiency t 11-cleoxycorticosterone mineralocorticoid and secreted in excess).
Masculinization.
aAil congenital adrenal enzyme deficiencies are characterized by an enlargement of both adrenal glands clue tot ACTH
stimulation because of ! cortisol.
Cortisol
SOURCE Adrenal zona fasciculata. Bound to corticosteroid-binding globulin (CBG).

FUNCTION Maintains Blood pressure (upregulates Cortisol is BBIIG
a1-receptors on arterioles -+ t sensitivity toNE
and epinephrine)
! Bone formation
An ti-ln A ammatory/1mmunosuppressive :
Inhibits production of leukotrienes and
prostaglandins
Inhibits leukocyte adhesion- neutrophilia
Blocks histamine release from mast cells
Reduces eosinophils
Blocks IL-2 production
t Insulin resistance (diabetogenic)

t Gluconeogenesis, lipolysis, proteolysis
Inhibits fibroblasts (causes striae)
REGULATION CRH (hypothalamus) stimulates ACTH release Chronic stress induces prolonged secretion.
(pituitary), causing cortisol production in
adrenal zona fasciculata. Excess cortisol
! CRH, ACTH, and cortisol secretion.
ENDOCRINE ENDOCRINE-PHYSIOLOGY SECTION Ill 293
PTH
SOURCE Chief cells of parathyroid.
FUNCTION t bone resorption of calcium and phosphate PTH t serum Ca 2 +, ! serum (P0 43-), t urine
t kidney reabsorption of calcium in distal (P0 43- ).
convoluted tubule t production of M-CSF and RAN K-L in
! reabsorption of phosphate in proximal osteoblasts, stimulating osteoclasts.
convoluted tubule PTH = Phosphate Trashing Hormone.
t l,2 5 - (0H) 2 03 (calcitriol) production by
stimulating kidney !a-hydroxylase
REGULATION serum Ca 2 + .... t PTH secretion.
! serum Mg 2 + .... t PTH secretion.
2
! ! serum Mg + .... ! PTH secretion.
Common causes of ! Mg 2 + include diarrhea,
aminoglycosides, diuretics, and alcohol abuse.
Low ionized calcium
Four
parathyroid-+------
glands
8 8
Feedback Feedback
inhibition PTH (1-84) inhibition
of PTH released into of PTH
synthesis circulation secretion
v A Renal
lobe lac ooll'
Low serum I Conversion
-
phosphorus 25-(0H) 03 -. 1,25-(0H)2 03
Stimulates reabsorption
of calcium Stimulates calcium release
Inhibits phosphate from bone mineral compartment
reabsorption Stimulates osteoblastic cells
Stimulates production of Stimulates bone resorption via
1,25-(0H)2 03 indirect effect on osteoclasis
Enhances bone matrix
degradation

j
Increases intestinal ------ Increases serum calcium Releases phosphate Increases intestinal
phosphate reabsorption
calcium absorption from matrix
Calcium Phosphate
homeostasis homeostasis
(Adapted, with permission, from Chandrasoma Pet al. Concise Pathology, 3rd ed. Stamford, CT: Appleton & Lange, 1998.)
Vitamin D (cholecalciferol)
SOURCE 03 from sun exposure in skin. 02 ingested from Vitamin 0 deficiency causes rickets in kids and
plants. Both converted to 2 5-0H in liver and osteomalacia in adults.
to 1,2 5 - (0H)2 (active form) in kidney. 24, 2 5 - (0H)2 03 is an inactive form of vitamin
2
FUNCTION t absorption of dietary Ca + and P0 43- D.
PTH leads to t Ca + reabsorption and ! P0 4 -
2 2 3
t bone resorption of Ca + and P0 43-
2 reabsorption in the kidney, whereas 1,2 5- (0H)2
REGULATION t PTH, ! [Ca +], ! P0 43- causet 1,2 5- (0H)2 2
leads tot absorption of both Ca + and P0 43-
production.
in the gut.
1,2 5 - (0H)2 feedback inhibits its own
production.
Calcitonin
SOURCE Parafollicular cells (C cells) of thyroid. Calcitonin opposes actions of PTH. Not
FUNCTION ! bone resorption of calcium. important in normal calcium homeostasis.
2 Calcitonin tones clown calcium levels.
REGUlATION t serum Ca + causes calcitonin secretion.
Signaling pathways of endocrine hormones

cAMP F SH, LH, ACTH, T SH, CRH, hCG, AOH (V2 FLAT ChAM P
receptor), MSH, PTH, calcitonin, GHRH,
glucagon
cGMP ANP, NO (EORF) Think vasodilators
IP3 GnRH, GHRH, Oxytocin, AOH (V1 receptor), GGOAT
TRI-I, histamine (H1), angiotensin II, gastrin
Steroid receptor Vitamin 0, Estrogen, Testosterone, T3 /T4 VETTT CA P
Cortisol, A ldosterone, Progesterone
Intrinsic tyrosine Insulin, IGF-1, FGF, POGF, EGF MAP kinase pathway
kinase Think growth factors
Receptor-associated Prolactin, lmmunomodulators (e.g., cytokines JA K/ STAT pathway
tyrosine kinase IL-2, IL-6, IL-8, I F N), GH Think acidophiles and cytokines
PIG
ENDOCRINE END OCRIN E - PHY SIOLOGY SECTION Ill 29 5
Signaling pathway of Steroid hormones are lipophilic and therefore

steroid hormones must circulate bound to specific binding
Cytoplasm / Nucleus
globulins, which t their solubility.
In men, t sex hormone-binding globulin
( SHBG) lowers free testosterone
--+gynecomastia. mRNA
)
In women, ! SH BG raises free testosterone receptor to expose DNA t
binding domain mRNA
--+hirsutism ; SHBG levels t during pregnancy. t +
Binding to receptor
Protein
t
located in nucleus or
in cytoplasm
Response
Hormone
Signaling mechanism
Thyroid hormones Iodine-containing hormones that control the body's metabolic rate.
(Tl/T4)
SOURCE Follicles of thyroid. Most T3 formed in target T3 functions -4 B's :

tissues. Brain maturation
FUNCTION Bone growth (synergism with GH) Bone growth
CNS maturation Beta-adrenergic effects
t 1 receptors in heart= t CO, HR, SV, Basal metabolic rate t
contractility Thyroxine-binding globulin (T BG) binds most
t basal metabolic rate via t a+J K+-ATPase T 3/T4 in blood ; only free hormone is active.
activity= t 02 consumption, RR, body ! TBG in hepatic failure ; t TBG in pregnancy
temperature or OCP use (estrogen t TBG).
t glycogenolysis, gluconeogenesis, Iipolysis T4 is major thyroid product; converted to T 3 in
peripheral tissue by 5'-deiodinase.
REGULATION TRH (hypothalamus) stimulates TSH
T 3 binds receptors with greater affinity than T4.
(pituitary), which stimulates follicular cells.
Peroxidase is enzyme responsible for oxidation
Negative feedback by free T3 to anterior
and organification of iodide as well as coupling
pituitary ! sensitivity to TRH. Thyroid
of MIT and orr.
stimulating immunoglobulins (TSis), like
Propylthiouracil inhibits both peroxidase
TSH, stimulates follicular cells (Graves'
and 5'-deiodinase. Methimazole inhibits
disease).
peroxidase only.
Wolff-Chaikoff effect- excess iodine
temporarily inhibits thyroid peroxidase
--+! iodine organification--+! T 3/T4
production.
Blood Follicular cell Lumen
Anions

(perchlorat
8 Thyroglobulin TG } MIT
pertechnetate) 8
1---+---,.,. Oxidation --..... 1 2 DIT ....___
Antithyroid drugs
(propylthiouracil, methimazole)
296 SECTION Ill ENDOCRINE ENDOCRINE-PATHO LOGY
ENDOCRINE-PATHOLOGY
Cushing's syndrome t cortisol due to a variety of causes.

Exogenous (iatrogenic) steroids-#] cause ; ACTH.
Endogenous causes :
Cushing's disease (70%) -due to ACTH secretion from pituitary adenoma; t ACTH
Ectopic ACTH (15%) -from nonpituitary tissue making ACTH (e.g., small cell lung cancer,
bronchial carcinoids); t ACTH

Adrenal (15%) -adenoma fit carcinoma, nodular adrenal hyperplasia; ACTH
Findings : hypertension, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia
(insulin resistance), skin changes (thinning, striae), osteoporosis, amenorrhea, and immune
suppression [).
Effed of dexamethasone suppression test on cortisol

CORTISOL LEVEL CORTISOL LEVEL
WITH LOW-DOSE "DEX" WITH HIGH-DOSE "DEX"
Normal Suppressed Suppressed

ACTH-pituitary tumor Remains elevated Suppressed
Ectopic ACTH-producing tumor Remains elevated Remains elevated
Cortisol-producing tumor Remains elevated Remains elevated
Adrenocortical adenoma. This can also present as

primary aldosteronism (Conn's syndrome).D striae.
Hyperaldosteronism
Primary Caused by adrenal hyperplasia or an Treatment: surgery to remove the tumor and/
aldosterone-secreting adrena 1 adenoma or spironolactone, a K+-sparing diuretic that
(Conn's syndrome), resulting in hypertension, works by acting as an aldosterone antagonist.
hypokalemia, metabolic alkalosis, and low
plasma renin. May be bilateral or unilateral.
Secondary Renal perception of low intravascular volume Treatment: spironolactone.
results in an overactive renin-angiotensin
system. Due to renal artery stenosis, chronic
renal failure, CHF, cirrhosis, or nephrotic
syndrome. Associated with high plasma renin.
ENDOCRINE ENDOCRINE-PATHOLOGY SECTION Ill 297
Addison's disease Chronic l0 adrenal insufficiency due to adrenal atrophy or destruction by disease (e.g.,
autoimmune, TB, metastasis). Deficiency of aldosterone and cortisol , causing hypotension
(hyponatremic volume contraction), hyperkalemia, acidosis, and skin hyperpigmentation
(due to MSH , a by-product oft ACTH production from P OMC). Characterized by A drenal
Atrophy and A bsence of hormone production ; involves A ll 3 cortical divisions (spares medulla).
Distinguish from zo adrenal insufficiency ( pituitary ACTH production), which has no skin
hyperpigmentation and no hyperkalemia.
Waterhouse- Acute lo adrenal insufficiency due to adrenal hemorrhage associated with Neisseria meningitidis
Friderichsen syndrome septicemia, DIC, and endotoxic shock.
Pheochromocytoma Most common tumor of the adrenal medulla in Rule of lO's:

adults. Derived from chromaffin cells (arise 10% malignant
from neural crest) r.J. 10% bilateral
Most tumors secrete epinephrine, NE, 10% extra-adrenal
and dopamine, which can cause episodic 10% calcify
hypertension. Urinary V MA (a breakdown 10% kids
product of norepinephrine and epinephrine) Symptoms occur in "spells" -relapse and remit.
and plasma catecholamines are elevated.
Associated with neurofibromatosis type l,
MEN types 2A and 2 B.
Treatment: tumor surgically removed only
after effective a- and -blockade is achieved.
Irreversible a-antagonists (phenoxybenzamine)
must be given first to avoid a hypertensive
crisis. -blockers are then given to slow the
heart rate.
Episodic hyperadrenergic symptoms (5 P s) :
'
Pressure (elevated blood pressure)

Pain (headache)
Perspiration
Palpitations (tachycardia)
Pallor
Phenylalanine - Tyrosine - L-dopa -Dopamine -Norepinephrine -Epinephrine
1
HVA
1
Normetanephrine,
1
Metanephrine,
VMA VMA
Neuroblastoma The most common tumor of the adrenal medulla in children. Can occur anywhere along the
sympathetic chain. Homovanillic acid (HVA), a breakdown product of dopamine, elevated in
urine. Less likely to develop hypertension. Overexpression of N-myc oncogene associated with
rapid tumor progression.
298 SECTION Ill ENDOCRINE ENDOCRINE-PATHOLOGY
Hypothyroidism vs. hyperthyroidism

Hypothyroidism Hyperthyroidism
SIGNS/SYMPTOMS Cold intolerance U heat production) Heat intolerance (t heat production)
Weight gain, ! appetite Weight loss, t appetite
Hypoactivity, lethargy, fatigue, weakness Hyperactivity
Constipation Diarrhea
! reflexes t reflexes
Myxedema (facial/periorbital) Pretibial myxedema (Craves' disease)
Dry, cool skin ; coarse, brittle hair Warm, moist skin ; fine hair
Bradycardia, dyspnea on exertion Chest pain, palpitations, arrhythmias,
t -adrenergic receptors
lAB FINDINGS t TSH (sensitive test for l o hypothyroidism) ! TSH (if 1)
! free T4 t free or total T4
t free or total T 3
Hypothyroidism
Hashimoto's Most common cause of hypothyroidism; an May be hyperthyroid early in course
thyroiditis autoimmune disorder (thyroid peroxidase, (thyrotoxicosis during follicular rupture).
antithyroglobulin antibodies). Associated with
HLA-DR 5. t risk of non-Hodgkin's lymphoma.
Histology: Hiirthle cells, lymphocytic infiltrate
with germinal centers.
Findings: moderately enlarged, nontender
thyroid.
Cretinism Due to severe fetal hypothyroidism. Endemic 5 P 's
cretinism occurs wherever endemic goiter is
prevalent (lack of dietary iodine); sporadic
cretinism is caused by defect in T4 formation
or developmental failure in thyroid formation.
Findings : Pot-bellied, Pale, Puffy-faced child
with Protruding umbilicus and Protuberant
tongue.
Subacute thyroiditis Self-limited hypothyroidism often following a May be hyperthyroid early in course.
(de Quervain's) flu-like illness.
Histology: granulomatous inflammation.
Findings : t E SR, jaw pain, early inflammation,
very tender thyroid.
Riedel's thyroiditis Thyroid replaced by fibrous tissue Considered a manifestation of IgC 4 -related
(hypothyroid). systemic disease.
Findings : fixed, hard (rock-like), and painless
goiter.
Other causes Congenital hypothyroidism, iodine deficiency,
goitrogens, Wolff-Chaikoff effect, painless
thyroiditis.
Hyperthyroidism
Toxic multinodular Focal patches of hyperfunctioning follicular cells working independently ofT SH due to mutation
goiter in T SH receptor [J. t release ofT3 and T4. Hot nodules are rarely malignant.
Jod-Basedow phenomenon -thyrotoxicosis if a patient w ith iodine deficiency goiter is made iodine
replete.
Graves' disease An autoimmune hyperthyroidism with thyroid-stimulating i mmunoglobulins. Ophthalmopathy
(proptosis, EOM swelling)[], pretibial myxedema, t in connective t issue deposition, diffuse
goiter. Often presents during stress (e.g., childbirth).
Thyroid storm Stress-induced catecholam ine surge leading to death by arrhythmia. Seen as a serious complication
of Graves' and other hyperthyroid disorders. May see t ALP due to t bone turnover.
Multinodular goiter. Note follicles distended with colloid Graves' disease (exophthalmos). Patient with bilateral
and lined by flattened epithelium with areas of fibrosis and proptosis and eyelid retraction. Visible sclera causes
hemorrhage.li!J appearance of a "stare".li!J
Thyroid cancer Papillary carcinoma- most common, excellent

prognosis, empty-appearing nuclei (Orphan
Annie's eyes) [J, psammoma bodies, nuclear
grooves. t risk with childhood irradiation.
Follicular carcinoma-good prognosis, uniform
follicles.
Medullary carcinoma-from parafollicular
"C cells"; produces calcitonin, sheets of cells
in amyloid stroma. Associated with MEN types
ZA and ZB.
Undifferentiated/anaplastic-older patients; very
Thyroid papillary carcinoma. Note classic nuclear
poor prognosis.
chromatin clearing ("Orphan Annie's eyes," arrows).li!J
Lymphoma-associated with Hashimoto's
thyroiditis.
Hyperparathyroidism
Primary Usually an adenoma. Hypercalcemia, Osteitis fibrosa cystic a- cystic bone spaces
hypercalciuria (renal stones), filled with brown fibrous tissue (bone pain).
hypophosphatemia, t PTH, t alkaline "Stones, bones, and groans."
phosphatase, t cAMP in urine. Often
asymptomatic, or may present with weakness
and constipation ("groans").
Secondary zo hyperplasia due to gut Ca2+ absorption Renal osteodystrophy-bone lesions due to zo
and t phosphate, most often in chronic or 3 hyperparathyroidism due in turn to renal
renal disease (causes hypovitaminosis D disease.
-+ Ca2+ absorption). Hypocalcemia,
hyperphosphatemia in chronic renal failure
(hypophospatemia with most other causes),
t alkaline phosphatase, t PTH.
Tertiary Refractory (autonomous) hyperparathyroidism
resulting from chronic renal disease. t t PTH,
t Ca2+
Hypoparathyroidism Due to accidental surgical excision (thyroid Pseudohypoparathyroidism (Albright's

surgery), autoimmune destruction, or hereditary osteodystrophy) -autosomal
DiGeorge syndrome. Findings : hypocalcemia, dominant kidney unresponsiveness to PTH.
tetany. Hypocalcemia, shortened 4th/ 5th digits, short
Chvostek 's sign-tapping of facial nerve stature.
-+ contraction of facial muscles.
Trousseau's sign- occlusion of brachial artery
with BP cuff-+ carpal spasm.
PTH and calcium pathologies
100
1o hyperparathyroidism
2 hyperparathyroidism
(hyperplasia, adenoma,
(chronic renal failure)
carcinoma)
Normal
3
{n
.,!; 10
:I:
I
ll.
Hypoparathyroidism PTH-independent
(surgical removal, hypercalcemia
autoimmune (excess calcium
destruction) ingestion, cancer)
4 6 8 10 12 14
Calcium (mg/dl)
ENDOCRINE ENDOCRINE-PATHOLOGY SECTION Ill 30 1
Pituitary adenoma Most commonly prolactinoma. Findings : amenorrhea, galactorrhea, low libido, infertility
U GnRH). Can impinge on optic chiasm bitemporal hemianopia. Treatment: dopamine
__.
agonists (bromocriptine or cabergoline) cause shrinkage of prolactinomas.
Acromegaly Excess GH in adults. Typically caused by pituitary adenoma.

FINDINGS Large tongue with deep furrows, deep t GH in children __. gigantism (t linear bone
voice, large hands and feet, coarse facial growth).
features, impaired glucose tolerance (insulin
resistance).
DIAGNOSIS t serum IGF-1; failure to suppress serum GH
following oral glucose tolerance test; pituitary
mass seen on brain MRI.
TREATMENT Pituitary adenoma resection followed by
somatostatin analog if not cured.
Diabetes insipidus Characterized by intense thirst and polyuria together with an inability to concentrate urine owing
to lack of A DH (central DI-pituitary tumor, trauma, surgery, histiocytosis X) or to a lack of renal
response to A DH (nephrogenic 01-hereditary or zo to hypercalcemia, lithium, demeclocycline
[ADH antagonist]).
FINDINGS Urine specific gravity< 1.006 ; serum osmolality > 290 mOsm/L.
DIAGNOSIS Water deprivation test-urine osmolality doesn't t. Response to desmopressin distinguishes central
DI from nephrogenic DI.
TREATMENT Adequate fluid intake. For central DI-intranasal desmopressin (ADH analog). For nephrogenic
DI-hydrochlorothiazide, indomethacin, or amiloricle.
SIADH Syndrome of inappropriate antidiuretic Causes include:

hormone secretion: Ectopic A DH (small cell lung cancer)
Excessive water retention CNS disorders/head trauma
Hyponatremia with continued urinary Na+ Pulmonary disease
excretion Drugs (e.g., cyclophosphamide)
Urine osmolarity >serum osmolarity

Treatment: fluid restriction, IV saline,
Body responds with ! aldosterone
conivaptan , tolvaptan , clemeclocycline.
(hyponatremia) to maintain near-normal
volume status. Very low serum sodium levels
can lead to seizures (correct slowly).
Hypopituitarism Undersecretion of pituitary hormones clue to :

Nonsecreting pituitary adenoma, craniopharyngioma
Sheehan's syndrome (ischemic infarct of pituitary following postpartum bleeding; usually
presents with failure to lactate)

Empty sella syndrome (atrophy or compression of pituitary, often idiopathic, common in obese
women)
Brain injury, hemorrhage
Radiation
Treatment: substitution therapy (corticosteroids, thyroxine, sex steroids, human growth hormone).
Diabetes mellitus
ACUTE MANIFESTATIONS Polydipsia, polyuria, polyphagia, weight loss,

Insulin deficiency (and glucagon excess) DKA (type 1), hyperosmolar coma (type 2),
I
unopposed secretion of GH and epinephrine
Decreased glucose Increased protein

1
Increased
(exacerbating hyperglycemia).
uptake catabolism lipolysis
1
Hyperglycemia, Increased plasma
1
Increased plasma FFAs,
/
glycosuria, _ amino acids, ketogenesis, ketonuria,
osmotic diuresis, nitrogen loss in ketonemia
''"'"''' dplotloo " '' " '
Dehydration,
acidosis
1
Coma,
death
CHRONIC MANIFESTATIONS Nonenzymatic glycosylation :

Small vessel disease (diffuse thickening
of basement membrane) .... retinop athy

(hemorrhage, exudates, microaneurysms,
vessel proliferation) r.;;], glaucoma,
nephropathy (nodular sclerosis, progressive
proteinur ia, chronic renal failure,
arteriosclerosis leading to hypertension,
Kimmelstiel-Wilson nodules)
Large vessel atherosclerosis, CA D,
peripheral vascular occlusive disease, and

Diabetic retinopathy. Note microhemorrhages and vessel
gangrene .... limb loss, cerebrovascular proliferation.C
disease
Osmotic damage (sorbitol accumulation in
organs with aldose reductase) :
Neuropathy (motor, sensory, and autonomic
degeneration)
Cataracts
TESTS Fasting serum glucose, oral glucose tolerance test, HbAlc (reflects average blood glucose over prior
3 months).
Type 1 vs. type 2 diabetes mellitus

Variable Type 1 Type 2
1 DEFECT Autoimmune destruction of cells t resistance to insulin, progressive pancreatic
-cell failure
INSULIN NECESSARY IN Always Sometimes
TREATMENT
AGE (EXCEPTIONS COMMONLY < 30 > 40

OCCUR)
ASSOCIATION WITH OBESITY No Yes

GENETIC PREDISPOSITION Relatively weak ( 50% concordance in identical Relatively strong (90% concordance in identical
twins), polygenic twins), polygenic
ASSOCIATION WITH HLA Yes (HLA-DR 3 and 4) No
SYSTEM
GLUCOSE INTOLERANCE Severe Mild to moderate

INSULIN SENSITIVITY High Low
KETOACIDOSIS Common Rare
-CELL NUMBERS IN THE Variable (with amyloid deposits)
ISLETS
SERUM INSULIN LEVEL Variable

CLASSIC SYMPTOMS OF Common Sometimes
POLYURIA, POLYDIPSIA,
POLYPHAGIA, WEIGHT LOSS
HISTOLOGY Islet leukocytic infiltrate Islet amyloid (AIAPP) deposit
Diabetic ketoacidosis One of the most important complications of diabetes (usually type l). Usually clue to t insulin
requirements from t stress (e.g., infection). Excess fat breakdown and t ketogenesis from t free
fatty acids, which are then made into ketone bodies (-hyclroxybutyrate >acetoacetate).
SIGNS/SYMPTOMS Kussmaul respirations (rapid/deep breathing), nausea/vomiting, abdominal pain, psychosis/
delirium, dehydration. Fruity breath odor (clue to exhaled acetone).
LABS Hyperglycemia, t H+, ! HC03- (anion gap metabolic acidosis), t blood ketone levels, leukocytosis.
Hyperkalemia, but depleted intracellular K+ clue to transcellular shift from ! insulin.
COMPLICATIONS Life-threatening mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart
failure.
TREATMENT IV fluids, IV insulin, and K+ (to replete intracellular stores); glucose if necessary to prevent
hypoglycemia.
Carcinoid syndrome Rare syndrome caused by carcinoid tumors Rule of l /3 s :

(neuroendocrine cells), especially metastatic l / 3 metastasize
small bowel tumors, which secrete high levels l / 3 present with 2nd malignancy
of serotonin (5-HT). Not seen if tumor is l / 3 multiple
limited to GI tract (5-HT undergoes first-pass Most common tumor of appendix.
metabolism in liver). Results in recurrent
diarrhea, cutaneous flushing, asthmatic
wheezing, and right-sided valvular disease.
t 5-HIAA in urine, niacin deficiency.
Treatment: somatostatin analog (e.g.,
octreotide).
Zollinger-EIIison Gastrin-secreting tumor of pancreas or duodenum. Stomach shows rugal thickening with acid
syndrome hypersecretion. Causes recurrent ulcers. May be associated with MEN type 1.
Multiple endocrine neoplasias (M E N)

SUBTYPE CHARACTERISTICS COMMENTS
MEN 1 (Wermer's Parathyroid tumors MEN l 3 P s (from cephalad to caudad :

= '
syndrome) Pituitary tumors (prolactin or GH) Pituitary, Parathyroid, and Pancreas;

Pancreatic endocrine tumors-Zollinger- remember by drawing a diamond).
Ellison syndrome, insulinomas, V IPomas, MEN 2A 2 P s ( Parathyroids and
= '
glucagonomas (rare) Pheochromocytoma; remember by drawing a

Commonly presents with kidney stones and square).
stomach ulcers M E N 2B 1 P ( Pheochromocytoma;
=
MEN 2A (Sipple's Medullary thyroid carcinoma (secretes remember by drawing a triangle).

syndrome) calcitonin) All MEN syndromes have autosomal-dominant
Pheochromocytoma inheritance.
Parathyroid tumors Associated with ret gene mutation in MEN
types 2A and 2 B .
MEN 2B Medullary thyroid carcinoma (secretes
calcitonin)
Pheochromocytoma
Oral/intestinal ganglioneuromatosis (associated
with marfanoid habitus)
MEN 1 MEN 2A MEN 28

"Diamond" "Square" "Triangle"
Parathyroid Parathyroid Oral
Pituitary
Parathyroid Parathyroid
Pheo Pheo Pheo Pheo

Pancreas (adrenals) (adrenals) (adrenals) (adrenals)
EN DOCRINE ENDOCRINE-PHA R M ACOLOGY SECTION Ill 305
ENDOCRINE-PHA R M ACOLOGY
Diabetes drugs Treatment strategy for type l DM -low-sugar diet, insulin replacement.
Treatment strategy for type 2 DM-dietary modification and exercise for weight loss; oral
hypoglycemics and insulin replacement.
DRUG CLASSES ACTION CLINICAL USE TOXICITIES
Insulin : Bind insulin receptor (tyrosine Type l DM, type 2 DM, Hypoglycemia, very rarely
Lispro (rapid-acting) kinase activity). gestational diabetes, life hypersensitivity reactions.
Aspart (rapid-acting) Liver: t glucose stored as glycogen. threatening hyperkalemia,
Glulisine (rapid-acting) Muscle : t glycogen and protein and stress-induced
Regular (short-acting) synthesis, K+ uptake. hyperglycemia.
NPH (intermediate) Fat: aids TG storage.
Glargine (long-acting)
Detemir (long-acting)
Biguanides : Exact mechanism is unknown. Oral. First-line therapy in GI upset; most serious
M etformin gluconeogenesis, t glycolysis, type 2 DM. adverse effect is
t peripheral glucose uptake Can be used in patients lactic acidosis (thus
(insulin sensitivity). without islet function. contraindicated in renal
failure).
Sulfonylurea s : Close K+ channel in -cell Stimulate release of First generation : disulfiram
First generation : membrane, so cell depolarizes endogenous insulin in type like effects.
Tol butamide -+ triggering of insulin release via 2 DM. Require some islet Second generation :
Chlorpropamide t Ca 2+ influx. function, so useless in type hypoglycemia.
Second generation: l DM.
G lyburide
Glimepiride
G l ipizide
G litazones/ t insulin sensitivity in peripheral Used as monotherapy in type Weight gain, edema.
thiazolidinediones : tissue. Binds to PPAR-y nuclear 2 DM or combined with Hepatotoxicity, heart failure.
Piogl itazone transcription regulator." above agents.
Rosiglitazone
a-glucosidase Inhibit intestinal brush-border Used as monotherapy in type GI disturbances.
inhibitors : a-glucosidases. 2 DM or in combination
Acarbose Delayed sugar hydrolysis with above agents.
M igl itol and glucose absorption
-+ postprandial hyperglycemia.
Amylin analogs: glucagon. Type l and type 2 DM. Hypoglycemia,
Pra m lintide nausea, diarrhea.
GLP-1 analogs : t insulin, glucagon release. Type 2 DM. Nausea, vomiting;
Exenatide pancreatitis.
Liraglutide
DPP-4 inhibitors : t insulin, glucagon release. Type 2 DM. Mild urinary or respiratory
Linagliptin infections.
Saxagliptin
Sitagliptin
"Genes activated by PPAR-y regulate fatty acid storage and glucose metabolism. Activation of PPAR-y t insulin sensitivity and
levels of adiponectin.
30 6 SECTION Il l ENDOCRINE ENDOC R I NE- P H A R M ACO LOG Y
Propylthiouracil. methimazole
MECHANISM Block peroxidase, thereby inhibiting organification of iodide and coupling of thyroid hormone
synthesis. Propylthiouracil also blocks 5 '-deiodinase, which peripheral conversion of T4 to T 3 .
CLINICAL USE Hyperthyroidism.
TOXICITY Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil). Methimazole is
a possible teratogen.
Levothyroxine. triiodothyronine
MECHANISM Thyroxine replacement.

CLINICAL USE Hypothyroidism, myxedema.
TOXICITY Tachycardia, heat intolerance, tremors, arrhythmias.
Hypothalamic/pituitary d rugs
DRUG CLINICAL USE
GH GH deficiency, Turner syndrome.

Somatostatin Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices.
(octreotide)
Oxytocin Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.
ADH (desmopressin) Pituitary (central, not nephrogenic) DI.
Demeclocycline
MECHANISM ADH antagonist (member of the tetracycline family).
CLINICAL USE SIADH.
TOXICITY Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.
Glucocorticoids Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone.

MECHANISM the production of leukotrienes and prostaglandins by inhibiting phospholipase A 2 and expression
of COX-2.
CliNICAl USE Addison's disease, inflammation, immune suppression, asthma.
TOXICITY Iatrogenic Cushing's syndrome -buffalo hump, moon facies, truncal obesity, muscle wasting, thin
skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic).
Adrenal insufficiency when drug stopped abruptly after chronic use.
HIGH-YIELD SYSTEMS
Gastrointestinal
"A good set of bowels is worth more to a man than any quantity of brains."
-Josh Billings
"Man should strive to have his intestines relaxed all the days of his life."
-Moses Maimonides
"The colon is the playing field for all human emotions."

-Cyrus Kapadia, MD
308 SECTION I l l G A ST R O I N T E S T I N A L GASTROINTESTINAL-EMBRYOLOGY
GASTROINTESTINAL-EMBRYOLOGY
Gl embryology Foregut-pharynx to duodenum. Gastroschisis-extrusion of abdominal contents

Midgut-duodenum to transverse colon. through abdominal folds; not covered by
Hindgut-distal transverse colon to rectum. peritoneum .
Developmental defects of anterior abdominal Omphalocele-persistence o f herniation of
wall clue to failure of: abdominal contents into umbilical cord,
Rostral fold closure: sternal defects covered by peritoneum rn.
Lateral fold closure: omphalocele,
gastroschisis
Caudal fold closure: bladder exstrophy
Duodenal atresia-failure to recanalize

(trisomy 2 1 ).
Jejunal,ileal,colonic atresia-due to vascular
accident (apple peel atresia).
Midgut development:
6th week-midgut herniates through
umbilical ring
lOth week-returns to abdominal cavity+
rotates around SMA Omphalocele. Note protruding intestine covered in

Pathology-malrotation of midgut, peritoneum.!!
omphalocele,intestinal atresia or stenosis,

volvulus.
Tracheoesophageal Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common ( 8 5 %).
anomalies Results in drooling,choking,and vomiting with first feeding. TEF allows air to enter stomach
(visible on CXR). Cyanosis is secondary to laryngospasm (to avoid reflux-related aspiration).
Clinical test: failure to pass NG tube into stomach.
In H-type it is a fistula alone. In pure atresia (isolated) EA the CXR shows gasless abdomen.
Tracheoesophageal
fistula
Esophageal
atresia
Normal anatomy Pure EA Pure TEF EA with distal TEF

{atresia or stenosis) {H-type) {most common)
Congenital pyloric Hypertrophy of the pylorus causes obstruction. Palpable "olive" mass in epigastric region and
stenosis nonbilious projectile vomiting at"" 2 weeks of age. Treatment is surgical incision. Occurs in 1/600
live births,more often in firstborn males.
G A ST R O I N T E S T I N A L GASTROINTESTINAL-ANATOMY S E CT I O N I l l 30 9
Pancreas and spleen Pancreas-derived from foregut. Ventral pancreatic buds contribute to the pancreatic head and
embryology main pancreatic duct. The uncinate process is formed by the ventral bud alone. The dorsal
pancreatic bud becomes everything else (body,tail,isthmus,and accessory pancreatic duct).
Annula r pancreas-ventral pancreatic bud abnormally encircles 2nd part of duodenum; forms a
ring of pancreatic tissue that may cause duodenal narrowing.
Pancreas divisum-ventral and dorsal parts fail to fuse at 8 weeks.
Spleen-arises in mesentery of stomach (hence is mesodermal) but is supplied by foregut (celiac
artery).
Pancreatic
duct
._.,____c..-,_ Dorsal
pancreatic
bud
Main
Ventral pancreatic
pancreatic bud uct
Uncinate process
GASTROINTESTINAL-ANATOMY
Retroperitoneal Retroperitoneal structures include GI structures SAD PUCKER:

strudures that lack a mesentery and non-GI structures. Suprarenal (adrenal) gland [not shown)
Injuries to retroperitoneal structures can cause Aorta and IVC
blood or gas accumulation in retroperitoneal Duodenum (2nd and 3rd parts)
space. Pancreas (except tail)
Ureters [not shown)
Right Left Colon (descending and ascending)
Kidneys
Esophagus (lower 213) [not shown)
Rectum (lower 213) [not shown)
Descending
colon
Transversalis fascia IVC Aorta

31Q S E CTI O N I l l G A S T R O I N T E ST I N A L GASTROINTESTINAL-ANATOMY
Important Gl ligaments
Falciform
ligament
Proper hepatic artery
Portal triad Gastric
mon bile duct vessels
Portal vein
Liver
Omental foramen
(epiploic foramen
of Winslow)
Greater
sac r------
-,Visceral
peritoneum
...,_-
__ Splenorenal
Right kidney ligament
Left kidney
LIGAMENT CONNECTS STRUCTURES CONTAINED NOTES
Falciform Liver to anterior abdominal Ligamentum teres hepatis Derivative of ventral mesentery
wall (derivative of fetal umbilical
vein)
Hepatoduodenal Liver to duodenum Portal triad: hepatic artery, Pringle maneuver-ligament
portal vein,common bile may be compressed between
duct thumb and index finger
placed in omental foramen to
control bleeding
Connects greater and lesser
sacs
Gastrohepatic (not Liver to lesser curvature of Gastric arteries Separates greater and lesser sacs
shown) stomach on the right
May be cut during surgery to
access lesser sac
Gastrocolic (not Greater curvature and Gastroepiploic arteries Part of greater omentum
shown) transverse colon
Gastrosplenic Greater curvature and spleen Short gastrics,left Separates greater and lesser sacs
gastroepiploic vessels on the left
Splenorenal Spleen to posterior abdominal Splenic artery and vein,tail of
wall pancreas
G A ST R O I NT E ST I N A L GASTROINTESTINAL-ANATOMY S E CT I O N I ll 31 1
Digestive trad anatomy

Mesentery (binding Layers of gut wall (inside to outside-MSMS):
of digestive tract to
Mucosa-epithelium (absorption), lamina
abdominal wall)
propria (support), muscularis mucosa
Mesothelium
(protective coating;
(motility)
reduction of friction) Submucosa-includes Submucosal nerve
plexus (Meissner's)
Serosa (support)
Muscularis externa-includes Myenteric
Muscularis mucosae
(mucosal motility) nerve plexus (Auerbach's)
Serosa (when intraperitoneal)/adventitia
Outer longitudinal
(when retroperitoneal)
Submucosal plexus
(control of secretory
muscle layer Ulcers can extend into submucosa,inner or outer
(motility)
activity) muscular layer. Erosions are in the mucosa
only.
Inner circular muscle
layer (motility) Frequencies of basal electric rhythm (slow
waves):
Stomach- 3 waves/min
Gland in submucosal
layer (secretion) Duodenum- 1 2 waves/min
Ileum-8-9 waves/min
Digestive trad ORGAN HISTOlOGY
histology Esophagus Nonkeratinized stratified squamous epithelium.

Stomach Gastric glands.
Duodenum Villi and microvilli t absorptive surface.
Brunner's glands (submucosa) and crypts of
Lieberki.ihn.
Jejunum Plicae circulares and crypts of Lieberki.ihn.
lieum Peyer's patches (lamina propria,submucosa),
plicae circulares (proximal ileum),and crypts
of Lieberki.ihn .
Largest number of goblet cells in the small
intestine.
Colon Colon has crypts but no villi,numerous goblet
cells.
312 S E CT I O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-ANATOMY
Abdominal aorta and branches
Left inferior phrenic artery

Arteries supplying GI structures branch
anteriorly. Arteries supplying non-GI
Left middle suprarenal artery structures branch laterally.
Left renal artery (L 1)
Superior mesenteric artery (SMA) syndrome
occurs when the transverse portion (third
segment) of the duodenum is entrapped
Right renal artery between SMA and aorta,causing intestinal
Right testicular (ovarian) obstruction.
artery
Inferior mesenteric artery (L3)
Bifurcation of abdominal aorta (L4)
Left common iliac artery
Median sacral artery
Cil blood supply and innervation

EMBRYONIC PARASYMPATHETIC VERTEBRAL
GUT REGION ARTERY INNERVATION LEVEL STRUCTURES SUPPliED
Foregut Celiac Vagus Tl2/Ll Stomach to proximal duodenum; liver,

gallbladder,pancreas,spleen (mesoderm)
Midgut SMA Vagus Ll Distal duodenum to proximal 213 of transverse
colon
Hindgut IMA Pelvic L3 Distal 113 of transverse colon to upper portion of
rectum; splenic flexure is a watershed region
G A S T R O I N T E ST I N A L GASTROINTESTINAL-ANATOMY SECTION I l l 313
Celiac trunk Branches of celiac trunk: common hepatic, Short gastrics have poor anastomoses if splenic
splenic,left gastric. These constitute the main artery is blocked.
blood supply of the stomach. Strong anastomoses exist between:
Left and right gastroepiploics
Left and right gastrics
Esophageal branch of
left gastric artery Left gastric artery
Right gastric artery
Hepatic artery --
proper
Common
hepatic artery - ----'
Gastroduodenal __._.
artery
Collateral circulation If branches off of the abdominal aorta are blocked,these arterial anastomoses (origin) compensate:
Superior epigastric (internal thoracic/mammary) H inferior epigastric (external iliac)
Superior pancreaticoduodenal (celiac trunk) H inferior pancreaticoduodenal (SMA)
Middle colic (SMA) H left colic (IMA)
Superior rectal (IMA) H middle and inferior rectal (internal iliac)

3l4 SECTI O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-ANATOMY
Portosystemic
anastomoses
0 Esophageal varices
) Caput medusae
) Rectal varices
0 TIPS
Colon
Epigastric veins
SITE OF ANASTOMOSIS CLINICAl SIGN PORTAl H SYSTEMIC
0 Esophagus Esophageal varices Left gastric H esophageal
f) Umbilicus Caput medusae Paraumbilical H superficial

and inferior epigastric below
the umbilicus,and superior
epigastric and lateral thoracic
above the umbilicus.
E) Rectum Internal hemorrhoids Superior rectal H middle and
inferior rectal
Varices of gut, butt, and caput (medusae) are commonly seen with portal hypertension.
Treatment with a transjugular intrahepatic portosystemic shunt (TIPS) 0 between the portal vein
and hepatic vein percutaneously relieves portal hypertension by shunting blood to the systemic
circulation.
G A ST R O I N T E S T I N A L GASTROINTESTINAL-ANATOMY SECTION Ill 315
Pedinate (dentate) line Formed where endoderm (hindgut) meets ectoderm.

Internal Above pectinate line - inte rn al
hemorrhoids, Internal hemorrhoids receive visceral
adenocarcinoma. Arterial supply from superior innervation and are therefore not painful.
rectal artery (branch of IMA). Venous drainage Lymphatic drainage to deep nodes.
is to superior rectal vein inferior mesenteric
-+
vein -+ portal system.

Below pectinate line - external hemorrhoids, External hemorrhoids receive somatic
squamous cell carcinoma. Arterial supply innervation (inferior rectal branch of pudendal
from inferior rectal artery (branch of internal nerve) and are therefore painful.
pudendal artery). Venous drainage to inferior Lymphatic drainage to superficial inguinal nodes.
rectal vein internal pudendal vein internal
-+ -+
iliac vein IVC.

-+
External Pectinate
hemorrhoid line
Liver anatomy Apical surface of hepatocytes faces bile canaliculi. Zone I: periportal zone:
Basolateral surface faces sinusoids. Affected lst by viral hepatitis
Zone II: intermediate zone.

Sinusoids draining
to central vein---,..._ Zone III : pericentral vein (centrilobular)
zone :
Affected lst by ischemia
Space of Disse
Contains P-45 0 system
(lymphatic drainage)
------ Most sensitive to toxic injury
Central ;
i ',,, Site of alcoholic hepatitis
(to hepatic \
veins and l
systemic ,'
circulation) ,/
,/
---
Portal
triad Bile flow
Zone I Zone II Zone Ill

3l6 SECTION I l l G A ST R O I N T E S T I N A L GASTROINTESTINAL-ANATOMY
Biliary strudures
Right hepatic duct --"""7"-:....-.:r---- Left hepatic duct
Cystic duct Common hepatic duct
Gallbladder
Pancreas
Main pancreatic duct
Gallstones that reach the common channel at ampulla of Vater can block both the bile and
pancreatic ducts.
Tumors that arise in the head of the pancreas (near the duodenum) can cause obstruction of the
common bile duct.
Femoral region
ORGANIZATION Lateral to medial: Nerve-Artery-Vein-Empty You go from lateral to medial to find your
space-Lymphatics. NAVEL.
Femoral triangle Contains femoral vein,artery,nerve. Venous near the penis.
Femoral sheath Fascial tube 3-4 em below inguinal ligament.
Contains femoral vein,artery,and canal (deep
inguinal lymph nodes) but not femoral nerve.
Inguinal
ligament
Sartorius
muscle
Femoral
sheath
Adductor longus
muscle
G A ST R O I N T E ST I N A L G ASTROINTESTINAL -ANATO M Y S E CT I O N I l l 317
Inguinal canal
Internal inguinal ring: Abdominal wall:
site of protrusion of site of protrusion of
indirect hernia direct hernia
Parietal peritoneum
Extraperitoneal tissue
Transversalis fascia
Deep inguinal ring

Transversus abdominis muscle ----
Aponeurosis of external Spermatic cord

oblique muscle --"""""
External spermatic fascia
Inguinal ligament (external oblique)
,...__
_ __ Cremasteric muscle and fascia
(internal oblique)
'---- Internal spermatic fascia
(transversalis fascia)
3l8 S E CT I O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-ANATOMY
Hernias A protrusion of peritoneum through an opening,usually a site of weakness.

Diaphragmatic hernia Abdominal structures enter the thorax; may Sliding h iatal hernia is most common. GE
occur in infants as a result of defective junction is displaced f; "hourglass stomach."
development of pleuroperitonea] membrane. Paraesophageal hernia - GE junction is normal.
Most commonly a hiatal hernia, in which Fundus protrudes into the thorax.
stomach herniates upward through the
esophageal hiatus of the diaphragm.
Indirect inguinal Goes through the internal (deep) inguinal ring, An indirect inguinal hernia follows the path of
hernia external (superficial) inguinal ring,and into descent of the testes. Covered by all 3 layers of
the scrotum. Enters internal inguinal ring spermatic fascia.
lateral to inferior epigastric artery. Occurs in
infants owing to failure of processus vaginalis
to close (can form hydrocele). Much more
common in males.
Direct inguinal hernia Protrudes through the inguinal (1-Iesselbach's) MDs don' t Lie:
triangle. Bulges directly through abdominal Medial to inferior epigastric artery = Direct
wall medial to inferior epigastric artery. Goes hernia.
through the external (superficial) inguinal Lateral to inferior epigastric artery = Indirect
ring only. Covered by external spermatic hernia.
fascia. Usually in older men.
Femoral hernia Protrudes below inguinal ligament through Leading cause of bowel incarceration.
femoral canal below and lateral to pubic
tubercle. More common in women.
Inguinal
(Poupart's) Inferior 1-Iesselbach's triangle:
ligament --+---\ epigastric vessels
Inferior epigastric vessels
Direct inguinal hernia Lateral border of rectus abdominis
Indirect
(through Hesselbach's
inguinal hernia
triangle) Inguinal ligament
G A S T R O I N T E ST I N A L GASTROINTESTINAL-PHYSIOLOGY S E CTI O N I l l 3l9
GASTROINTESTINAL-PHYSIOLOGY
G l hormones
HORMONE SOURCE ACTION REGULATION NOTES
Gastrin G cells (antrum of gastric H+ secretion by stomach t t in Zollinger-EIIison

stomach) growth of gastric mucosa distention/ syndrome.
gastric motility alkalinization, t by chronic PPI use.
amino acids, Phenylalanine and
peptides, vagal tryptophan are potent
stimulation stimulators.
by stomach
pH < 1 . 5
Cholecystokinin I cells pancreatic secretion by fatty acids, CCK acts on neural
(duodenum, gallbladder contraction amino acids muscarinic pathways
jejunum) gastric emptying to cause pancreatic
sphincter of Oddi secretion.
relaxation
Secretin S cells pancreatic HC0 3- by acid, fatty t HC0 3 - neutralizes
(duodenum) secretion acids in lumen gastric acid in duodenum,
gastric acid secretion of duodenum allowing pancreatic
bile secretion enzymes to function.
Somatostatin 0 cells gastric acid and by acid Inhibitory hormone.
(pancreatic islets, pepsinogen secretion by vagal Antigrowth hormone
GI mucosa) pancreatic and small stimulation effects (inhibits digestion
intestine fluid secretion and absorption of
gallbladder contraction substances needed for
insulin and glucagon growth).
release
Glucose-dependent K cells Exocrine: by fatty acids, Also known as gastric
insulinotropic (duodenum, ! gastric H+ secretion amino acids, inhibitory peptide (GIP).
peptide jejunum) Endocrine : oral glucose An oral glucose load is used
t insulin release more rapidly than the
equivalent given by IV
clue to GIP secretion.
Vasoactive intestinal Parasympathetic intestinal water and by distention VIPoma-non-a, non-
polypeptide (VIP) ganglia in electrolyte secretion and vagal islet cell pancreatic
sphincters, relaxation of intestinal stimulation tumor that secretes VIP.
gallbladder, smooth muscle and by adrenergic Copious Watery Diarrhea,
small intestine sphincters input Hypokalemia, and
Achlorhydria (WDHA
syndrome).
Nitric oxide smooth muscle Loss of NO secretion is
relaxation, including implicated in t lower
lower esophageal esophageal tone of
sphincter achalasia.
Motilin Small intestine Produces migrating motor t in fasting state Motilin receptor agonists
complexes (MMCs) (such as erythromycin)
are used to stimulate
intestinal peristalsis.
3 20 S E CTIO N Ill G A ST R O I N T E S T I N A L GASTROINTESTINAL-PHYSIOLOGY
G l secretory products
PRODUCT SOURCE ACTION REGULATION NOTES
Intrinsic factor Parietal cells Vitamin B 1 z -binding Autoimmune destruction

(stomach) protein (required for B 1 2 of parietal cells chronic
-+
uptake in terminal ileum) gastritis and pernicious

anemia.
Gastric acid Parietal cells stomach pH by histamine, Gastrinoma: gastrin-
(stomach) ACh,gastrin secreting tumor that
by somatostatin, causes continuous high
GIP, levels of acid secretion
prostaglandin, and ulcers.
secretin
Pepsin Chief cells Protein digestion by vagal Inactive pepsinogen -+
(stomach) stimulation, pepsin by H+.

local acid
HCOl- Mucosal cells Neutralizes acid by pancreatic HC0 3 - is trapped in
(stomach, and biliary mucus that covers the
duodenum, secretion with gastric epithelium .
salivary glands, secretin
pancreas) and
Brunner's glands
(duodenum)
Saliva Secretion from parotid,submandibular,and sublingual glands is stimulated by sympathetic and

parasympathetic activity. Amylase digests starch, HC0 3 - neutralizes bacterial acids, mucins
lubricate food. Normally hypotonic because of absorption but more isotonic with higher flow rates
(less time for absorption).
G A S T R O I N T E ST I N A L GASTROINTESTINAL-PHYSIOLOGY S E C T I O N I ll 32 1
Locations of Cil secretory cells
Atropine blocks vagal
(::'
stimulation of parietal
cells. Vagal stimulation
Vagus nerve------<!l:> of G cells is unaffected,
Atropine
Fundus as a different transmitter
IGRPI""'"' ooiACh
Body
HC
Intrinsic-
factor
@
ffl
t:f Parietal
cells
Pyloric ----...._
sphincter """
Pepsinogen Histamine
CCK
<:7
J
Antrum ......._ Chief
Somato
J
cells
statm
I cells t
y
Mucus

\ GRP ECLcells
S cells (it' ' +
Secretin Duodenum Mucous G cells..._

{
__ Gastrin
to circulation)
cells
-
GIP
K cells
Gastrin t acid secretion primarily through its effects on ECL cells (leading to histamine release)
rather than through its direct effect on parietal cells.
Gastric parietal cell
Atropine

M3 receptor
\G/"""'''
CCK
q
'
IP/Ca2
H+
Gastric parietal cell

Gastric lumen
Proton pump inhibitors
Brunner's glands Located in duodenal submucosa. Secrete alkaline mucus. Hypertrophy seen in peptic ulcer disease.
322 SECTI O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PHYSIOLOGY
Pancreatic secretions Isotonic fluid; low flow - high Cl-,high flow - high HC0 3 -.
ENZYME ROLE NOTES
a-amylase Starch digestion Secreted in active form

Lipase, Fat digestion
phospholipase A,
colipase
Proteases Protein digestion Includes trypsin,chymotrypsin,elastase,

carboxypeptidases
Secreted as proenzymes also known as
zymogens
Trypsinogen Converted to active enzyme trypsin -+ Converted to trypsin by enterokinase/
activation of other proenzymes and creation of enteropeptidase,an enzyme secreted from
more trypsinogen (positive feedback loop) duodenal mucosa
Carbohydrate digestion
Salivary amylase Starts digestion,hydrolyzes a- 1,4 linkages to yield disaccharides (maltose and a-limit dextrins).
Pancreatic amylase Highest concentration in duodenal lumen,hydrolyzes starch to oligosaccharides and disaccharides.
Oligosaccharide At brush border of intestine,the rate-limiting step in carbohydrate digestion,produce
hydrolases monosaccharides from oligo- and disaccharides.
Carbohydrate Only monosaccharides (glucose,galactose,fructose) are absorbed by enterocytes. Glucose and

absorption galactose are taken up by SGLTl (Na+ dependent). Fructose is taken up by facilitated diffusion by
GLUT-5. All are transported to blood by GLUT-2 .
0-xylose absorption test: distinguishes GI mucosal damage from other causes of malabsorption.
Vitamin/mineral absorption
Iron
2
Absorbed as Fe + in duodenum.
Folate Absorbed in jejunum.
Absorbed in terminal ileum along with bile acids,requires intrins ic factor.
G A ST R O I NT E ST I N A L GAST ROINTESTINAL - P HYSIOLOGY S E CT I O N I ll 323
Peyer's patches Unencapsulated lymphoid tissue rJ found in Think of IgA,the Intra-gut Antibody. And
lamina propria and submucosa of ileum. always say "secretory lgA."
Contain specialized M cells that take up
antigen.
B cells stimulated in germinal centers of Peyer's
patches differentiate into IgA-secreting plasma
cells, which ultimately reside in lamina
propria. IgA receives protective secretory
component and is then transported across the
epithelium to the gut to deal with intraluminal
antigen.
Bile Composed of bile salts (bile acids conjugated to glycine or taurine,making them water soluble),
phospholipids,cholesterol,bilirubin,water,and ions. Cholesterol 7a-hydroxylase catalyzes
rate-limiting step.
Functions:
Digestion and absorption of lipids and fat-soluble vitamins
Cholesterol excretion (body's only means of eliminating cholesterol)
Antimicrobial activity (via membrane disruption)
Bilirubin Product of heme metabolism. Bilirubin is removed from blood by liver, conjugated with
glucuronate,and excreted in bile.
Direct biliru bin-conjugated with glucuronic acid; water soluble.
Indirect bilirubin-unconjugated; water insoluble.
Excreted in urine as
urobilin, which gives +--- Kidney
characteristic color of
urine
20%
Macro phages Bloodstream Liver Gut
1 Albumin I
"'----,

Unconjugated : Unconjugated bilirubin- : Conjugated :
RBCs - Heme ---+ Urobilinogen
bilirubin albumin complex : _U_D_P---- bilirubin
1 :
--j--
I
Indirect bilirubin
glucuronosyl-
transferase
: G ut .
Direct bilirubin
b actena
l 80%
(water insoluble) (water soluble)

Excreted in feces as
stercobilin, which gives
characteristic color of stool
324 SECTION I l l GASTRO I NTESTINAL GASTROINTESTINAL-PATHOLOGY
GASTROINTESTINAL-PATHOLOGY
Salivary gland tumors Generally benign and occur in parotid gland:

Pleomorphic adenoma (benign mixed tumor) is the most common salivary gland tumor.
Presents as a painless,mobile mass. It is composed of cartilage and epithelium and recurs

frequently.
Warthin's tumor (papillary cystadenoma lymphomatosum) is a benign cystic tumor with
germinal centers.
Mucoepidermoid carcinoma is the most common malignant tumor and has mucinous and
squamous components. It presents as a painful mass because of common involvement of the

facial nerve.
Achalasia Failure of relaxation of lower esophageal A-chalasia= absence of relaxation.

sphincter (LES) due to loss of myenteric " Bircl's beak" on barium swallow fJ.
(Auerbach's) plexus. High LES opening 2 achalasia may arise from Chagas' disease.
pressure and uncoordinated peristalsis Scleroderma (CREST syndrome) is associated
--+progressive dysphagia to solids and liquids with esophageal clysmotility involving low
(vs. obstruction-solids only). Barium swallow pressure proxi mal to LES.
shows dilated esophagus with an area of
distal stenosis. Associated with an t risk of
esophageal squamous cell carcinoma.
Esophageal pathologies
Gastroesophageal Commonly presents as heartburn and regurgitation upon lying clown. May also present with
reflux disease (GERD) nocturnal cough and dyspnea,adult-onset asthma. Decrease in LES tone.
Esophageal varices Painless bleeding of dilated submucosal veins in lower 1/3 of esophagus secondary to portal
hypertension.
Esophagitis Associated with reflux, infection (Candida: white pseudomembrane; HSV-1 : punched-out ulcers;
CMV: linear ulcers),or chemical ingestion.
Mallory-Weiss Mucosal lacerations at the gastroesophageal junction due to severe vom iting. Leads to
syndrome hematemesis. Usually found in alcoholics and bulim ics.
BoerHaave Syndrome Transmural esophageal rupture due to violent retching. "Been-Heaving Syndrome."
Esophageal strictures Associated with lye ingestion and acid reflux.
Plummer-Vinson Triac! of:
syndrome Dysphagia (due to esophageal webs)
Glossitis
Iron deficiency anemia

G A ST R O I NT E ST I N A L GASTROINTESTINAL-PATHOLOGY S E CT I O N I ll 32 5
Barrett's esophagus Glandular metaplasia-replacement of nonkeratinized (stratified) squamous epithelium with

intestinal (nonciliated columnar) epithelium in the distal esophagus rJ. Due to chronic acid
reflux (GERD). Associated with esophagitis,esophageal ulcers,and increased risk of esophageal
adenocarcinoma.
Squamocolumnar
(epithelial) junction
(SCJ or Z line)
Lower
Barrett's esophagus. Characterized by metaplastic

columnar epithelium with goblet cells (arrow)..!
Esophageal cancer Can be squamous cell carcinoma or adenocarcinoma. Typically presents with progressive dysphagia
(first solids,then liquids) and weight loss; poor prognosis. Risk factors include:
Achalasia AABCDEFFGH.
Alcohol-squamous Worldwide, squamous cell is more common.
Barrett's esophagus-adena In the United States,adenocarcinoma is more
Cigarettes-both common.
Diverticula (e.g., Zenker's)-squamous Squamous cell- upper 2A
Esophageal web-squamous Adenocarcinoma-lower 1A
Familial
Fat (obesity)-adeno
GERD-adeno
Hot liquids-squamous
326 SECTION I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PATHOLOGY
Malabsorption Can cause diarrhea,steatorrhea,weight These Will Cause Devastating Absorption

syndromes loss,weakness,and vitamin and mineral Problems.
deficiencies.
Tropical sprue Unknown cause,but responds to antibiotics.
Similar to celiac sprue,can affect entire small
bowel.
Whipple's disease Infection with Tropheryma whipplei (gram Foam y Whipped cream in a CAN .
positive); PAS-positive foamy macrophages
in intestinal lamina propria,mesenteric
nodes. Cardiac symptoms,Arthralgias,and
Neurologic symptoms are common. Most often
occurs in older men.
Celiac sprue Autoantibodies to gluten (gliadin) in wheat
and other grains. Primarily affects distal
duodenum or proximal jejunum. Histology
shows loss of villi.
Disaccharidase Most common is lactase deficiency-+ milk Lactose tolerance test: positive for lactase
deficiency intolerance. Normal-appearing villi. Osmotic deficiency if:
diarrhea. Since lactase is located at tips of Administration of lactose produces symptoms,
intestinal villi,self-limited lactase deficiency and

can occur following injury (e.g.,viral Glucose rises < 20 mg/dL
diarrhea).
Abetalipoproteinemia synthesis of apolipoprotein B-+ inability
to generate chylomicrons secretion of
-+
cholesterol, VLDL into bloodstream fat -+
accumulation in enterocytes. Presents in early

childhood with malabsorption and neurologic
manifestations.
Pancreatic Due to cystic fibrosis,obstructing cancer,and t neutral fat in stool
insufficiency chronic pancreatitis. Causes malabsorption
of fat and fat-soluble vitamins (vitamins A, D,
E,K).
Celiac sprue Autoimmune-mediated intolerance of gliadin

(wheat) leading to steatorrhea. Associated
with HLA-DQZ,HLA-DQ8,and people of
northern European descent. Findings include
anti-endomysia!,anti-tissue transglutaminase,
and anti-gliadin antibodies; blunting of villi;
and lymphocytes in the lamina propria fZl
mucosal absorption that primarily
affects jejunum. Serum levels of tissue
transglutaminase antibodies are used for
screening. Associated with dermatitis
herpetiformis. Moderately t risk of malignancy
Celiac sprue. Blunting of villi (single arrow) and crypt
hyperplasia (double arrows).
(e.g.,T-cell lymphoma).
G A ST R O I NT E ST I N A L GASTROINTESTINAL-PATHOLOGY S E CT I O N I l l 327
Gastritis
Acute gastritis Disruption of mucosal barrier-+ inflammation. Burned by the Curling iron.
(erosive) Can be caused by stress,NSAIDs ( l PGE1 Always Cushion the brain.
-+ l gastric mucosa protection),alcohol, Especially common among alcoholics and
uremia, burns (Curling's ulcer-l plasma patients taking daily NSAIDs (e.g.,patients
volume -+ sloughing of gastric mucosa), with rheumatoid arthritis).
and brain injury (Cushing's ulcer- t vagal
stimulation - tACh-+ t H+ production).
Chronic gastritis
(nonerosive)
Type A (fu ndus/body) Autoimmune disorder characterized by Think ABBA:

Autoantibodies to parietal cells,pernicious Pernicious Anemia affects gastric Body.
Anemia,and Achlorhydria. Associated with H. pylori Bacterium affects Antrum.
other autoimmune disorders.
Type B (antrum) Most common type. Caused by H. pylori
infection. t risk of MALT lymphoma.
Mimetrier's disease Gastric hypertrophy with protein loss,parietal cell atrophy,and t mucous cells. Precancerous.
Rugae of stomach are so hypertrophied that they look like brain gyri.
Stomach cancer Almost always adenocarcinoma. Early aggressive Vi rchow's node-involvement of left
local spread and node/liver metastases. Often supraclavicular node by metastasis from
presents with acanthosis nigricans. stomach.
Intestinal -associated with H. pylori Kru kenberg's tumor-bilateral metastases to
infection, dietary nitrosamines (smoked ovaries. Abundant mucus, signet ring cells.
foods),achlorhydria,chronic gastritis,type A Sister Mary Joseph's nodule-subcutaneous
blood. Commonly on lesser curvature; looks periumbilical metastasis.
like ulcer with raised margins.
Diffuse-not associated with H. pylori;
signet ring cells rn; stomach wall grossly

thickened and leathery (linitis plastica).
Peptic ulcer disease

Gastric ulcer Duodenal ulcer
Pa in Can be Greater with meals-weight loss Decreases with meals-weight gain

H. pylori i nfection In 70 % In almost 1 0 0 %
Causes l mucosal protection against gastric acid; l mucosal protection or t gastric acid secretion
NSAID use also implicated (e.g.,Zollinger-Ellison syndrome)
Risk of carci noma Increased Generally benign
Other Often occurs in older patients Hypertrophy of Brunner's glands
328 S E CTI O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PATHOLOGY
Ulcer complications
Hemorrhage Gastric,duodenal (posterior > anterior). Ruptured gastric ulcer on the lesser curvature
of the stomach - bleeding from left gastric
artery.
An ulcer on the posterior wall of the duodenum
- bleeding from gastroduodenal artery.
Perforation Duodenal (anterior > posterior).
Inflammatory bowel disease

Crohn's disease Ulcerative colitis
POSSIBLE ETIOLOGY Disordered response to intestinal bacteria. Autoimmune.

lOCATION Any portion of the GI tract,usually the terminal Colitis = colon inflammation. Continuous
ileum and colon. Skip lesions,rectal sparing. colonic lesions,always with rectal involvement.
GROSS MORPHOLOGY Transmural inflammation. Cobblestone Mucosal and submucosal inflammation only.
mucosa, creeping fat, bowel wall thickening Friable mucosal pseudopolyps with freely
("string sign" on barium swallow x-ray r.J) , hanging mesentery II). Loss of haustra - "lead
linear ulcers, fissures,fistulas. pipe" appearance on imaging.
MICROSCOPIC MORPHOLOGY Noncaseating granulomas and lymphoid Crypt abscesses and ulcers,bleeding,no
aggregates (Th 1 mediated). granulomas (Th 2 mediated).
COMPLICATIONS Strictures, fistulas,perianal disease, Malnutrition,sclerosing cholangitis,toxic
malabsorption,nutritional depletion, megacolon, colorectal carcinoma (worse with
colorectal cancer. right-sided colitis or pancolitis).
INTESTINAl MANIFESTATION Diarrhea that may or may not be bloody. Bloody diarrhea.
EXTRAINTESTINAl Migratory polyarthritis,erythema nodosum, Pyoderma gangrenosum, 1 sclerosing
MANIFESTATIONS ankylosing spondylitis,uveitis,kidney stones. cholangitis,ankylosing spondylitis,uveitis.
TREATMENT Corticosteroids,azathioprine,methotrexate, ASA preparations (sulfasalazine),
infliximab, adalimumab. 6-mercaptopurine,infliximab,colectomy.
For Crohn's, think of a fat granny and an old
crone skipping down a cobblestone road away
from the wreck (rectal sparing).
G A ST R O I NT E ST I N A L GASTROINTESTINAL-PATHOLOGY S E CT I O N I ll 32 9
Irritable bowel Recurrent abdominal pain associated with ;:::: 2 of the following:
syndrome Pain improves with defecation
Change in stool frequency
Change in appearance of stool
No structural abnormalities. Most common in miclclle-agecl women. Chronic symptoms. May

present with diarrhea,constipation,or alternating symptoms. Pathophysiology is multifaceted.
Treat symptoms.
Appendicitis Acute inflammation of the appendix clue to obstruction by fecalith (in adults) or lymphoid
hyperplasia (in children).
Initial diffuse periumbilical pain migrates to McBurney's point ( 1/3 the distance from anterior
superior iliac spine to umbilicus). Nausea,fever; may perforate -. peritonitis.
Differential: diverticulitis (elderly),ectopic pregnancy (use -hCG to rule out).
Treatment: appendectomy.
Diverticular disease
Diverticulum Blind pouch protruding from the alimentary "True" d iverticu l u m - all 3 gut wall layers
tract that communicates with the lumen of outpouch (e.g.,Meckel 's).
the gut. Most diverticula (esophagus,stomach, " Fa lse" d iverticu l u m or pseudodive rticu l u m
duodenum, colon) are acquired and are only mucosa and submucosa outpouch.
termed "false" in that they lack or have an Occur especially where vasa recta perforate
attenuated muscularis externa. Most often in muscularis externa.
sigmoid colon.
Diverticulosis Many false diverticula. Common (in 50% of Often asymptomatic or associated with vague
people > 60 years). Caused by t intraluminal discomfort. A common cause of hematochezia.
pressure and focal weakness in colonic wall. Complications include diverticulitis,fistulas.
Associated with low-fiber diets. Most often in
sigmoid colon.
Diverticulitis Inflammation of diverticula classically causing Stool occult blood is common +1-
LLQ pain,fever,leukocytosis. May perforate hematochezia. May also cause colovesical
-+ peritonitis,abscess formation,or bowel fistula (fistula with bladder) pneumaturia.
-+
stenosis. Give antibiotics. Sometimes called "left-sided appendicitis" clue

to overlapping clinical presentation.
Zenker's diverticulum False diverticulum. Herniation of mucosal tissue at Killian's triangle between the thyropharyngeal
and cricopharyngeal parts of the inferior pharyngeal constrictor. Presenting symptoms: halitosis
(clue to trapped food particles),dysphagia,obstruction.
330 S E CTI O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PATHOLOGY
Meckel's diverticulum True diverticulum. Persistence of the vitelline The five 2's :
duct. May contain ectopic acid-secreting 2 inches long.
gastric mucosa and/or pancreatic tissue. Most 2 feet from the ileocecal valve.
common congenital anomaly of the GI tract. 2 % of population.
Can cause melena,RLQ pain,intussusception, Commonly presents in first 2 years of life.
volvulus,or obstruction near the terminal May have 2 types of epithelia (gastric/
ileum. Contrast with omphalomesenteric cyst pancreatic).
= cystic dilation of vitelline duct.
Diagnosis: pertechnetate study for ectopic
uptake.
Intussusception and volvulus

Intussusception "Telescoping" of l bowel segment into distal segment,commonly at ileocecal junction; can
cause "currant jelly" stools and compromise blood supply. Unusual in adults (associated with
intraluminal mass or tumor). Majority of cases occur in children (usually idiopathic; may be viral
[adenovirus] ). Abdominal emergency in early childhood.
Volvulus Twisting of portion of bowel around its mesentery; can lead to obstruction and infarction. May
occur at cecum and sigmoid colon,where there is redundant mesentery. Usually in elderly.
Hirschsprung's disease Congenital megacolon characterized by lack Think of Hirschsprung's as a giant spring that
of ganglion cells/enteric nervous plexuses has sprung in the colon. Risk t with Down
(Auerbach's and Meissner's plexuses) in syndrome.
segment on intestinal biopsy. Due to failure of Diagnosed by rectal suction biopsy.
neural crest cell migration. Treatment: resection.
Presents as chronic constipation early in life.
Dilated portion of the colon proximal to the
aganglionic segment,resulting in a "transition
zone." Involves rectum. Usually failure to pass
mecontum.
GASTRO I NTESTINAL GASTROINTESTINAL-PATHOLOGY SECTION I l l 33 1
Other intestinal disorders

Duodenal atresia Causes early bilious vomiting with proximal stomach distention ("double bubble" on X-ray)
because of failure of recanalization of small bowel. Associated with Down syndrome.
Meconium ileus In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.
Necrotizing Necrosis of intestinal mucosa and possible perforation. Colon is usually involved, but can involve
enterocolitis entire GI tract. In neonates, more common in preemies U immunity).
Ischemic colitis Reduction in intestinal blood flow causes ischemia (pain out of proportion with physical findings).
Pain after eating - weight loss. Commonly occurs at splenic flexure and distal colon. Typically
affects elderly.
Adhesion Fibrous band of scar tissue; commonly forms after surgery; most common cause of small bowel
obstruction. Can have well-demarcated necrotic zones.
Angiodysplasia Tortuous dilation of vessels - hematochezia. Most often found in cecum, terminal ileum, and
ascending colon. More common in older patients. Confirmed by angiography.
Colonic polyps Masses protruding into gut lumen - sawtooth appearance. 9 0 % are non-neoplastic. Often
rectosigmoid. Can be tubular r.J or villous [I).
Tubular adenoma. Smaller, more rounded, and more Villous adenoma. Note long, finger-like projections.
likely to be benign.
Adenomatous Adenomatous polyps are precancerous. Malignant risk is associated with t size, villous histology,
t epithelial dysplasia. Precursor to colorectal cancer (CRC). The more villous the polyp, the more
likely it is to be malignant (villous villainous).
=
Polyp symptoms-often asymptomatic, lower GI bleed, partial obstruction, secretory diarrhea.

Hyperplastic Most common non-neoplastic polyp in colon (> 5 0 % found in rectosigmoid colon).
Juvenile Mostly sporadic lesions in children < 5 years of age. 8 0 % in rectum. If single, no malignant
potential.
Juvenile polyposis syndrome-multiple juvenile polyps in GI tract, t risk of adenocarcinoma.
Peutz-Jeghers Single polyps are not malignant.
Peutz-)eghers syndrome-autosomal-dominant syndrome featuring multiple nonmalignant
hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia.
Associated with t risk of CRC and other visceral malignancies.
332 SECTION I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PATHOLOGY
Colorectal cancer
EPIDEMIOLOGY 3rd most common cancer; 3rd most deadly in United States. Most patients are > 5 0 years of age.
2 5 % have a family history.
GENETICS Fa m i l i a l adenomatous polyposis (FAP) -autosomal-dominant mutation of APC gene on
chromosome 5q. 2-hit hypothesis. 1 0 0 % progress to CRC. Thousands of polyps; pancolonic;
always involves rectum.
Gardner's synd rome - FAP + osseous and soft tissue tumors,congenital hypertrophy of retinal
pigment epithelium.
Tu rcot's syndrome - FAP + malignant CNS tumor. Turcot = Turban.
H ered itary non polyposis colo recta l cancer ( H N PCC/Lynch synd rome) -autosomal-dominant
mutation of DNA mismatch repair genes. 80% progress to CRC. Proximal colon is always

involved.
ADDITIONAL RISK FACTORS IBD, tobacco use,large villous adenomas,juvenile polyposis syndrome, Peutz-Jeghers syndrome.
PRESENTATION Rectosigmoid > ascending > descending.
Ascending-exophytic mass,iron deficiency
anemia,weight loss.
Descending-infiltrating mass,partial
obstruction,colicky pain,hematochezia.
Rarely presents as Streptococcus bovis
bacteremia.
DIAGNOSIS Iron deficiency anemia in males (especially
> 5 0 years of age) and postmenopausal females
ra1ses suspiCIOn.
Screen patients > 50 years of age with
colonoscopy or stool occult blood test.
"Apple core" lesion seen on barium enema
x-ray r.J.
CEA tumor marker: good for monitoring
recurrence, not useful for screening.
Molecular There are 2 molecular pathways that lead to Order of gene events-AK-53.
pathogenesis of CRC CRC :
Microsatellite instability pathway ( 1 5 %):
DNA mismatch repair gene mutations

sporadic and HNPCC syndrome.
_.
Mutations accumulate,but no defined

morphologic correlates.
APC/-catenin (chromosomal instability)
pathway (85%):
Loss of A PC gene K-RAS mutation Loss of p53
Normal colon I ----. 1 Colon at risk I ----. 1

'- -
Adenoma
--____
_ _,l ----. 1 Carcinoma
Decreased intercellular Unregulated Increased tumorigenesis

adhesion and increased intracellular signal
proliferation transduction
GASTR O I N T E STI NAL GASTROINTESTINAL-PATHOLOGY SECTION I l l 3 33
Carcinoid tumor Tumor of neuroendocrine cells. Constitute 5 0 % of small bowel tumors. Most common sites are
the appendix, ileum,and rectum . Most common malignancy in the small intestine. "Dense
core bodies" seen on EM. Often produce 5 -HT,which can lead to carcinoid syndrome. Classic
symptoms: wheezing,right-sided heart murmurs, diarrhea, flushing. If tumor is confined to GI
system,no carcinoid syndrome is observed,since liver metabolizes 5 -HT. If tumor or metastases
(usually to liver) exist outside GI system,carcinoid syndrome is observed. Thus,tumor location
determines whether the syndrome appears. Treatment: resection,octreotide,somatostatin.
Cirrhosis and portal hypertension

Effects of Effects of Cirrhosis-diffuse fibrosis and nodular
portal hypertension liver cell failure
regeneration destroys normal architecture of
liver rJ (]] ; t risk for hepatocellular carcinoma.
Esophageal varices Coma
Scleral icterus
j Hematem sis
!
Peptic ----1-
ulcer
Fetor hepaticus (breath
smells musty)
Etiologies-alcohol (60-70 % ) , viral hepatitis,
biliary disease,hemochromatosis.
Portosystemic shunts partially alleviate portal
Spider nevi
Gynecomastia hypertension:
Melena _j Jaundice Esophageal varices
Splenomegaly .-f--.,L-J- Testicular atrophy
Caput medusae
Caput medusae,
ascites Liver "flap" asterixis
=
Portal hypertensive (coarse hand tremor)

gastropathy Bleeding tendency
( l clotting factors,
Hemorrhoids t prothrombin time)
Anemia
Ankle edema
Cirrhosis, microscopic. Typical regenerative nodules and

bridging fibrosis. D
334 SECTION I l l G A ST R O I N T E ST I N A L GA STROINTESTINAL-PATHOLOGY
Serum markers of SERUM MARKER MAJ OR DIAGNOSTIC USE
liver and pancreas Aminotransferases (AST and ALT) (often called Viral hepatitis (ALT > AST)
pathology "l iver enzymes") Alcoholic hepatitis (AST > ALT)
A l ka l i n e phosphatase (ALP) Obstructive I iver disease (hepatocellular
carcinoma),bone disease,bile duct disease
y-gl utamyl transpeptidase (GGT) t in various liver and biliary diseases like ALP,
but not in bone disease.
Amylase Acute pancreatitis,mumps
Lipase Acute pancreatitis
Ceru loplasmin ! in Wilson's disease
Reye's syndrome Rare,often fatal childhood hepatoencephalopathy. Findings: mitochondrial abnormalities,fatty

liver (microvesicular fatty change),hypoglycemia,vomiting,hepatomegaly,coma. Associated with
viral infection (especially VZV and influenza B) that has been treated with aspirin. Mechanism:
aspirin metabolites ! -oxidation by reversible inhibition of mitochondrial enzyme. Avoid aspirin
in children, except in those with Kawasaki's disease.
Alcoholic liver disease

Hepatic steatosis Short-term change with moderate alcohol
intake.
Macrovesicular fatty change that may be
reversible with alcohol cessation [:J.
Macrovesicular steatosis. Hepatocytes filled with fat

droplets. li!l
Alcoholic hepatitis Requires sustained,long-term consumption. Make a toAST with alcohol:

Swollen and necrotic hepatocytes with AST > ALT (ratio usually > 1. 5 ).
neutrophilic infiltration. Mallory bodies
(intracytoplasmic eosinophilic inclusions) are
present.
Alcoholic cirrhosis Final and irreversible form. Micronoclular,
irregularly shrunken liver with "hobnail"
appearance. Sclerosis around central vein
(zone III) . Has manifestations of chronic liver
disease (e.g., jaundice,hypoalbuminemia) .
GASTROI NTESTINAL GASTROINTESTINAL-PATHOLOGY SECTION I l l 335
Hepatocellular Most common 1 malignant tumor of the Commonly spread by hematogenous

carcinoma/hepatoma liver in adults. t incidence is associated dissemination.
with hepatitis B and C,Wilson's disease, t a-fetoprotein.
hemochromatosis, <:xrantitrypsin deficiency, May lead to Budd-Chiari syndrome.
alcoholic cirrhosis,and carcinogens (e.g.,
aflatoxin from Aspergillus) . Findings: jaundice,
tender hepatomegaly,ascites,polycythemia,
and hypoglycemia.
Other liver tumors

Cavernous Common,benign liver tumor; typically occurs at age 30-50 years. Biopsy contraindicated because
hemangioma of risk of hemorrhage.
Hepatic adenoma Benign liver tumor,often related to oral contraceptive or steroid use; can regress spontaneously.
Angiosarcoma Malignant tumor of endothelial origin; associated with exposure to arsenic,polyvinyl chloride.
Nutmeg liver Due to backup of blood into liver. Commonly caused by right-sided heart failure and Budd-Chiari
syndrome. The liver appears mottled like a nutmeg. If the condition persists,centrilobular
congestion and necrosis can result in cardiac cirrhosis.
Budd-Chiari syndrome Occlusion of IVC or hepatic veins with centrilobular congestion and necrosis, leading to
congestive liver disease (hepatomegaly,ascites,abdominal pain,and eventual liver failure). May
develop varices and have visible abdominal and back veins. Absence of JVD. Associated with
hypercoagulable state,polycythemia vera,pregnancy,and hepatocellular carcinoma.
a.1 -antitrypsin Misfolded gene product protein aggregates in hepatocellular ER cirrhosis with PAS-positive
--+
deficiency globules in liver. In lungs,lack of functioning enzyme ! elastic tissue

--+ panacinar emphysema.
--+
Codominant trait.
Jaundice Yellow skin and/or sclerae resulting from elevated bilirubin. Caused by:
Direct hepatocellular injury
Obstruction to bile flow
Hemolysis
JAUNDICE TYPE HYPERBILIRUBINEMIA URINE BILIRUBIN URINE UROBILINOGEN
Hepatocellular Direct/indirect Normal/!

Obstructive Direct
Hemolytic Indirect Absent (acholuria)
Physiologic At birth,immature UDP-glucuronyl transferase unconjugated hyperbilirubinemia

--+ --+ jaundice/
neonatal jaundice kernicterus.
Treatment: phototherapy (converts UCB to water-soluble form).
336 S E CTIO N Ill G A ST R O I N T E STI N A L GASTROINTESTINAL-PATHOLOGY
Hereditary hyperbilirubinemias
Gilbert's syndrome Mildly ! UDP-glucuronyl transferase or ! No clinical consequences.
bilirubin uptake. Asymptomatic. Elevated
unconjugated bilirubin without overt
hemolysis. Bilirubin increases with fasting and
stress.
Crigler-Najjar Absent UDP-glucuronyl transferase. Presents Type II is less severe and responds to
syndrome, type I early in life; patients die within a few years. phenobarbital, which t liver enzyme synthesis.
Findings: jaundice, kernicterus (bilirubin
deposition in brain) , t unconjugated bilirubin.
Treatment: plasmapheresis and phototherapy.
Dubin-Johnson Conjugated hyperbilirubinemia due to defective Rotor's synd rome is similar but even milder and
syndrome liver excretion. Grossly black liver. Benign. does not cause black liver.
0 Gilbert's = problem with bilirubin uptake

-+ unconjugated bilirubinemia
E) Crigler-Najjar = problem with bilirubin
conjugation -+ unconjugated bilirubinemia
@ Dubin-Johnson = problem with excretion
of conjugated bilirubin -+ conjugated
bilirubinemia
Bilirubin formed in other parts of the Hemoglobin Kupffer cell

mononuclear phagocyte system
(Adapted, with permission, from Junqueira LC, Carneiro J. Basic Histology. l l th ed. New York: McGraw-Hill, 2005: 335.)
GASTRO I N T E STI NAL GASTRO INT ESTINAL-PATHOLO GY S E C TI O N I l l 337
Wilson's disease Inadequate hepatic copper excretion and failure Treat with penicillamine. Autosomal-recessive
(hepatolenticular of copper to enter circulation as ceruloplasmin. inheritance (chromosome 1 3). Copper is
degeneration) Leads to copper accumulation, especially in normally excreted into bile by hepatocyte
liver,brain,cornea,kidneys,and joints. copper transporting ATPase (ATP7B gene).
Characterized by: "Copper is Rella BAD."
Ceruloplasmin !, Cirrhosis,Corneal deposits
(Kayser-Fleischer rings) rJ, Copper
accumulation,Carcinoma (hepatocellular)
Hemolytic anemia
Basal ganglia degeneration (parkinsonian
symptoms)
Asterixis
Dementia, Dyskinesia,Dysarthria
Kayser-Fleischer ring. Note golden brown corneal ring

(arrows).
Hemochromatosis Hemosiderosis is the deposition of hemosiderin Hemochromatosis Can Cause Deposits.

(iron); hemochromatosis is the disease caused Total body iron may reach 50 g,enough to set
by this iron deposition. Classic triad of off metal detectors at airports.
micronodular Cirrhosis, Diabetes mellitus, Primary hemochromatosis clue to C282Y or
and skin pigmentation ..... " bronze" diabetes. H63D mutation on HFE gene. Associated with
Results in CHF,testicular atrophy in males, HLA-A3.
and t risk of hepatocellular carcinoma. Treatment of hereditary hemochromatosis:
Disease may be l o (autosomal recessive) repeated phlebotomy,cleferasirox,
or zo to chronic transfusion therapy (e.g., deferoxamine.
-thalassemia major). t ferritin, t iron, ! TIBC
t transferrin saturation.
.....
338 S E CT I O N I l l G A S T R O I N T E ST I N A L GAST ROINTESTINAL-PATHOLOGY
Biliary trad disease

Secondary biliary cirrhosis Primary biliary cirrhosis Primary sclerosing cholangitis
PATHOPHYSIOLOGY/ Extrahepatic biliary Autoimmune reaction Unknown cause of concentric

PATHOLOGY obstruction (gallstone, biliary -+lymphocytic infiltrate "onion skin" bile duct fibrosis
stricture, chronic pancreatitis, + granulomas. -+ alternating strictures and
carcinoma of the pancreatic dilation with " beading" of
head) -+ t pressure in intra- and extrahepatic bile
intrahepatic ducts injury/
-+ ducts on E RCP.
fibrosis and bile stasis.
PRESENTATION Pruritus, jaundice, dark Same. Same.
urine, light stools,
hepatosplenomegaly.
LABS t conjugated bilirubin, Same. Same.
t cholesterol, t alkaline
phosphatase.
ADDITIONAL INFORMATION Complicated by ascending t serum mitochondrial Hypergammaglobulinemia
cholangitis. antibodies, including IgM. (IgM). Associated with
Associated with other ulcerative colitis. Can lead to
autoimmune conditions (e.g., z o biliary cirrhosis.
CREST, rheumatoid arthritis,
celiac disease).
G A S T R O I N T E ST I N A L GASTROINTESTINAL-PATHOLOGY S E C TI O N I l l 339
Gallstones t cholesterol and/or bilirubin, ! bile salts,and Risk factors (4 F's):

(cholelithiasis) gallbladder stasis all cause stones [J. l . Female
2 types of stones: 2 . Fat
Cholesterol stones (radiolucent with 1 0-2 0% 3. Fertile (pregnant)
opaque due to calcifications)-80% of 4. Forty
stones. Associated with obesity,Crohn's Charcot's triad of cholangitis:
disease,cystic fibrosis,advanced age, Jaundice
clofibrate, estrogens,multiparity, rapid Fever
weight loss,and Native American origin. RUQ pain
Pigment stones (radiopaque) -seen in Positive Murphy's sign-inspiratory arrest on

patients with chronic hemolysis,alcoholic deep RUQ palpation clue to pain.
cirrhosis,advanced age,and biliary
infection. Black-hemolysis; brown
infection.
Most often causes cholecystitis; also ascending
cholangitis,acute pancreatitis,bile stasis.
Can also lead to biliary col ic-nemohormonal
activation (e.g.,by CCK after a fatty meal)
triggers contraction of the gallbladder,forcing
a stone into the cystic duct. May present
without pain (e.g.,in diabetics).
Can cause fistula between gallbladder and small
intestine,leading to air in the biliary tree. If
gallstone obstructs ileocecal valve (gallstone
ileus),air can be seen in biliary tree on
tmagmg.
Diagnose with ultrasound,raclionuclicle biliary
scan (HIDA). Treat with cholecystectomy.
Cholecystitis Inflammation of gallbladder. Usually from gallstones; rarely ischemia or infectious (CMV).
t alkaline phosphatase if bile duct becomes involved (e.g.,ascending cholangitis).
Acute pancreatitis Autodigestion of pancreas by pancreatic enzymes. GET SMASH ED.

Causes: idiopathic,Gallstones,Ethanol,
Trauma,Steroids,Mumps,Autoimmune
disease,Scorpion sting, Hypercalcemia/
Hypertriglycericlemia (> 1 0 00),ERCP,Drugs
(e.g.,sulfa drugs).
Clinical presentation: epigastric abdominal pain
radiating to back,anorexia,nausea.
Labs: elevated amylase,lipase (higher specificity) .
Can lead to DIC,ARDS,diffuse fat necrosis,
2
hypocalcemia (Ca + collects in pancreatic
calcium soap deposits), pseudocyst formation,
hemorrhage,infection,ancl multiorgan failure. Acute pancreatitis. With peri-pancreatic edema
Complication: pancreatic pseudocyst (lined by (arrows). Ill
granulation tissue,not epithelium; can rupture

and hemorrhage).
3 40 SECTI O N I l l G A ST R O I N T E ST I N A L GASTROINTESTINAL-PHARMA COLOGY
Chronic pancreatitis Chronic inflammation,atrophy,calcification of the pancreas. Major causes are alcohol abuse and
idiopathic.
Can lead to pancreatic insufficiency-+ steatorrhea,fat-soluble vitamin deficiency,diabetes mellitus,
and t risk of pancreatic adenocarcinoma.
Amylase and lipase are less elevated (compared to levels in acute pancreatitis).
Pancreatic Prognosis averages 6 months or less; very aggressive tumor arising from pancreatic ducts; usually
adenocarcinoma already metastasized at presentation; tumors more common in pancreatic head (-+ obstructive
jaundice). Associated with CA-1 9-9 tumor marker (also CEA,less specific).
Risk factors:
Tobacco use (but not EtOH)
Chronic pancreatitis (especially > ZO years)
Age > 5 0 years
Jewish and African-American males
Often presents with:

Abdominal pain radiating to back
Weight loss (clue to malabsorption and anorexia)
Migratory thrombophlebitis-redness and tenderness on palpation of extremities (Trousseau's
syndrome)
Obstructive jaundice with palpable,nontender gallbladder (Courvoisier's sign)
Treatment: Whipple procedure,chemotherapy,radiation therapy.
GASTROINTESTINAL-PHARMA COLOGY
Cil therapy Somatostatin

(octreotide) Fundus Antrum
Enteric
ST2 i G (CCK-B)
- ,......_
I /
/
Antacids Stomach lumen
(Adapted, with permission, from Katzung BG, Trevor AJ . USMLE Road Mop: Pharmacology, I st ed. New York: McGraw-Hill, 2003 : 1 59.)
G A S T R O I N T E ST I N A L GASTRO INTEST INAL-PHARMA COLOGY SECTION I l l 34 1
H2 blockers Cimetidine,ranitidine,famotidine,nizatidine. Take H z blockers before you dine. Think " table
for 2" to remember H2 .
MECHANISM Reversible block of histamine Hrreceptors -+ H+ secretion by parietal cells.
CLINICAL USE Peptic ulcer,gastritis,mild esophageal reflux.
TOXICITY Cimetidine is a potent inhibitor of cytochrome P-45 0 (multiple drug interactions); it also has
antiandrogenic effects (prolactin release,gynecomastia,impotence, libido in males); can
cross blood-brain barrier (confusion,dizziness,headaches) and placenta. Both cimetidine and
ranitidine renal excretion of creatinine. Other H z blockers are relatively free of these effects.
Proton pump inhibitors Omeprazole,lansoprazole,esomeprazole,pantoprazole,dexlansoprazole.

MECHANISM Irreversibly inhibit H+fK+ ATPase in stomach parietal cells.
CLINICAL USE Peptic ulcer,gastritis, esophageal reflux,Zollinger-Ellison syndrome.
TOXICITY Increased risk of C. difficile infection,pneumonia. Hip fractures, serum MgZ+ with long-term use.
Bismuth, sucralfate
MECHANISM Bind to ulcer base,providing physical protection and allowing HC0 3 - secretion to reestablish pH
gradient in the mucous layer.
CliNICAl USE t ulcer healing, traveler's diarrhea.
Misoprostol
MECHANISM A PGE 1 analog. t production and secretion of gastric mucous barrier, acid production.
CLINICAL USE Prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used
to induce labor (ripens cervix).
TOXICITY Diarrhea. Contraindicated in women of childbearing potential (abortifacient).
Odreotide
MECHANISM Long-acting somatostatin analog.
CliNICAl USE Acute variceal bleeds,acromegaly,VIPoma,and carcinoid tumors.
TOXICITY Nausea,cramps,steatorrhea.
Antacid use Can affect absorption,bioavailability,or urinary excretion of other drugs by altering gastric and
urinary pH or by delaying gastric emptying.
All can cause hypokalemia.
Overuse can also cause the following problems.
Aluminum hydroxide Constipation and hypophosphatemia; proximal Aluminimum amount of feces.
muscle weakness, osteodystrophy,seizures
Magnesium hydroxide Diarrhea,hyporeflexia,hypotension,cardiac Mg = Must go to the bathroom.
arrest
Calcium carbonate Hypercalcemia,rebound acid t Can chelate and effectiveness of other drugs
(e.g.,tetracycline).
3 42 SECTION I l l G A ST R O I N T E S T I N A L GASTROINTESTINAL-PHARMACOLOGY
Osmotic laxatives Magnesium hydroxide,magnesium citrate,polyethylene glycol,lactulose.

MECHANISM Provide osmotic load to draw water out.
Lactulose also treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid
and acetic acid) that promote nitrogen excretion as NH4 +.
CLINICAL USE Constipation.
TOXICITY Diarrhea,dehydration; may be abused by bulimics.
lnfliximab
MECHANISM Monoclonal antibody to TNF-a.
CLINICAL USE Crohn's disease,ulcerative col itis,rheumatoid arthritis.
TOXICITY Infection (including reactivation of latent TB),fever,hypotension.
Sulfasalazine
MECHANISM A combination of sulfapyridine (antibacterial) and 5 -aminosalicylic acid (anti-inflammatory).
Activated by colonic bacteria.
CLINICAL USE Ulcerative colitis,Crohn's disease.
TOXICITY Malaise,nausea,sulfonamide toxicity,reversible oligospermia.
Ondansetron
MECHANISM 5 - H T 3 antagonist. Powerful central-acting At a party but feeling queasy? Keep on dancing
antiemetic. with ondansetron !
CLINICAL USE Control vomiting postoperatively and in patients
undergoing cancer chemotherapy.
TOXICITY Headache,constipation.
Metoclopramide
MECHANISM D2 receptor antagonist. t resting tone,contractility, LES tone, motility. Does not influence colon
transport time.
CLINICAL USE Diabetic and post-surgery gastroparesis,antiemetic.
TOXICITY t parkinsonian effects. Restlessness,drowsiness,fatigue,depression,nausea,diarrhea. Drug
interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel
obstruction or Parkinson's disease.
HIGH-YIELD SYSTEMS
Hematology
and Oncology
"Of all that is written, I love only what a person has written with his own
blood."
-Friedrich ietzsche
"I used to get stressed out, but my cancer has put everything into
perspective."
- Delta Goodrem
"The best blood will at some time get into a fool or a mosquito."
-Austin O'Mal ley
Study tip: When reviewing oncologic drugs, focus on mechanisms and

side effects, rather than details of clinical uses, which may be lower
yield.
344 SECTION Ill HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y-A N AT O M Y
H E M ATO LO G Y A N D O N C O L O G Y-A N ATO M Y
Erythrocyte Carries 0 2 to tissues and C0 2 to lungs. Eryth= red ; cyte= cel l .

Anucleate and biconcave r.J, with large surface Erythrocytosis= polycythemia= t hematocrit.
area-to-volume ratio for rapid gas exchange. Anisocytosis= varying sizes.
Life span of 1 20 clays. Source of energy is Poiki locytosis= varying shapes.
glucose (90% used in glycolysis, 1 0% used in
H M P shunt) . Membrane contains chloricle Reticulocyte immature erythrocyte, marker of
=
HC03- anti porter, which allows RBCs to erythroid prol iferation.

sequester HC03- and transport C0 2 from the
periphery to the lungs for elimination.
Platelet (thrombocyte) I nvolved in 1 o hemostasis. Small cytoplasmic Thrombocytopenia or platelet dysfunction

fragment derived from megakaryocytes r.J. results in petechiae.
Life span of 8-10 clays. When activated by vWF receptor: Gplb.
endothel ial injury, aggregates with other Fibrinogen receptor: Gpllb/Illa.
platelets and interacts with fibrin to form
platelet plug. Contains dense granules (ADP,
calcium) and a granules (vWF, fibrinogen) .
Approximately YJ of platelet pool is stored in
the spleen.
Leukocyte Divided into granulocytes (neutroph il, Leuk= white ; cyte= cell .
eosinoph il, basophil) and mononuclear cells
(monocytes, lymphocytes) . Responsible for
defense against infections. ormally 4000-
1 0,000 cells/mm3.
Blood cell WBC differential from highest to lowest Neutroph i ls Like Making Everything Better.
differentiation (per USMLE ) :
Neutroph ils ( 54-62%)
Lymphocytes (2 5-33%)
Monocytes (3-7%)
Eosinophi ls (l-3%)
Basophils (0-0.7 5%)
HEMATOLOGY AND ONCOLOGY H E M ATOLO G Y A N D O N C OLO G Y - A N AT O M Y SECTION Ill 34 5
Neutrophil Acute inflammatory response cell. Increased in Hypersegmented polys ( 5 or more lobes) are
bacterial infections. Phagocytic. Multilobed seen in vita m i n B 1z! folate deficiency.
nucleus rJ. Small, more numerous specific t band cells (immature neutrophils) reflect states
granules contain alkal ine phosphatase, of increased myeloid prol iferation ( bacterial
collagenase, lysozyme, and lactoferrin. infections , C M L) .
Larger, less numerous azuroph ilic granules
( lysosomes) contain acid phosphatase,
peroxidase, and -glucuronidase.
Monocyte Differentiates into macrophages in tissues. Mono= one (nucleus) ; cyte= cel l .
Large, kidney-shaped nucleus rJ. Exten sive Monocyte : in the blood.
" frosted glass" cytoplasm .
Macrophage Phagocytoses bacteria, cell debris, and Macro= large ; phage= eater.
senescent RBCs and scavenges damaged Macrophage : in the tissue.
cells and tissues rJ. Long life in tissues.
Macrophages differentiate from circulating
blood monocytes . Activated by y-interferon.
Can function as antigen-presenting cell via
MHC II. CDl4 is a cell surface marker for
macrophages.
Eosinophil Defends against helminthic infections (major Eosin= a dye ; philic= loving.
basic protein). Bilobate nucleus rJ. Packed Causes of eosinoph i l i a= NAACP:
with large eosinoph ilic granules of uniform Neoplastic
size . H ighly phagocytic for antigen-antibody Asthma
complexes. Al lergic processes
Produces histam inase and arylsulfatase Collagen vascular d iseases
( helps l i m it reaction following mast cell Parasites (i nvasive)
degranulation) .
Basophil Med iates allergic reaction. Densely Basoph ilic - sta ining readily with basic stains.
basoph ilic granules rJ containing heparin
(anticoagulant) , h istamine (vasod ilator ) , and
leukotrienes (LTD4 ) .
34 6 SECTION Ill HEMATOLOGY AN D ON COLOGY H E M AT O L O G Y A N D O N C O L O G Y-A N ATO M Y
Mast cell Med iates allergic reaction i n local tissues. Mast I nvolved i n type I hypersensitivity reactions.
cells resemble basoph ils structurally and Cromolyn sodium prevents mast cell
functionally but are not the same cell type f'J. degranulation (used for asthma prophylaxis) .
Can bind the Fe portion of lgE to membrane.
IgE cross-l i nks upon antigen binding, causing
degranulation , which releases h istamine,
heparin, and eosinoph il chemotactic factors.
Dendritic cells H ighly phagocytic antigen-presenting cells (APCs) . Function as l ink between innate and adaptive
immune system. Express MHC class Il and Fe receptor on surface. Called Langerhans cells in
the skin.
Lymphocyte Mediates adaptive immunity. Divided into B cells and T cells. Round, densely staining nucleus
with small amount of pale cytoplasm f'J.
B lymphocyte Part of humoral immune response. Arises B = Bone marrow.

from stem cells in bone marrow. Matures
in marrow. M igrates to peripheral lymphoid
tissue (foil icles of lymph nodes, white pulp
of spleen, unencapsulated lymphoid tissue).
When antigen is encountered, B cel ls
differentiate into plasma cells that produce
antibodies, and memory cells. Can function as
an APC via M HC I I .
Plasma cell Produces large amounts o f antibody specific to Multiple myeloma is a plasma cell cancer.
a particular antigen. Off-center nucleus, clock-
face chromatin d istribution, abundant RER,
and well-developed Golgi apparatus f'J.
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y-P H Y SIO L O G Y SECTION Ill 3 47
T lymphocyte Mediates cel lular i m mune response. Origi nates T is for Thym us.
from stem cel l s in the bone marrow, but CD is for Cluster of Differentiation .
matures in the thymus. T cells differentiate MHC x C D= 8 (e.g., M H C 2 x CD4= 8 , and
CD8 into cytotoxic T cells (express CD8, recognize MHC l x CD8 = 8 ) .
MHC 1), helper T cells (express CD4,
recogn ize M H C I I ) , and regulatory T cel ls.
CD28 (costimulatory signal) necessary for
T-cell activation. The majority of circulating
lymphocytes are T cells ( 8 0 % ) .
H E M AT O L O G Y A N D O N C O LO G Y-P H Y SIO L O G Y
Blood groups
A A antigen on RBC surface and anti-B antibody Incompatible blood transfusions c a n cause
in plasma . i mmunologic response, hemolysis, renal
B B antigen on RBC surface a n d anti-A antibody failure, shock, and death .
in plasma . Note : anti-A and anti-B antibod ies - lgM (do
not cross placenta ) ; anti-Rh - lgC (cross
AB A a n d B antigens on RBC surface; no antibodies
placenta) .
in plasma ; "un iversal recipient" of RBCs,
"un iversal donor" of plasma.
0 Neither A nor B antigen on RBC surface; both
antibod ies in plasma ; "un iversal donor" of
RBCs, "un iversal recipient" of plasma.
Rh Rh antigen on RBC surface. Rh- mothers Treatment: Rho ( D ) immune globulin for mother
exposed to fetal Rh+ blood (often during at fi rst del ivery to prevent i n itial sensitization of
del ivery) may make anti-Rh lgC. In Rh- mother to Rh antigen .
subsequent pregnancies, anti-Rh lgC crosses
the placenta, causing hemolytic disease of the
newborn (erythroblastosis fetal i s) in the next
fetus that is Rh+.
348 SECTION Ill HEMATOLOGY AND ONCOLOGY H E M AT O L O G Y A N D O N C O L O G Y-P H Y SIO L O G Y
Coagulation, complement, and kinin pathways

Collagen, basement
membrane,
1
activated platelets
___ HMWK
Kinin cascade
'/11 , , i vasodilation
Intrinsic _
y .(----
coagulation XII - Xlla,
,
/ Bradykinin <:------ 1> i permeability
pathway
XI-
t Xla
'
- -... i pa1n
c t
I: 1

Prekallikrein
Thromboplastin IX -
- --
Extrinsic
coagulation VII
(=tissue factor)
VIla
. llla ; --,.. '
pathway
, Plasminogen
; y
X Xa ,
Kallikrein C3
1 -------1
L--- _ _
l va v i
l t c-----

lla Plasmin

= require Ca2', phospholipid
(prothrombin) (thrombin)
C3a
t Complement
c:::
::> 0
Fibrin cascade
Fibrinogen
monomers
(aggregation) I

*' t
Ca2 Xllla +---- XIII
Fibrin mesh acts to

stabilize platelet plug
_,. Fibrin degradation
products
'
Note: Kallikrein activates bradykinin; ACE inactivates bradykinin.
Hemophilia A: deficiency of factor VI I I .

Hemophilia B: deficiency o f factor IX.
Coagulation cascade components
(
Procoagulation Warfarin inhibits epoxide reductase. Neonates
lack enteric bacteria, which produce vitamin
epoxide (acts as precursors of II, VII, IX, X, C, 5
reductase cofactor) +
K.
Oxidized reduced
vitamin K ----- vitamin K Vitamin K deficiency: ! synthesis of factors I I ,
mature II, VII, IX, X, C, 5 V I I , IX, X , protein C , protein S .
vWF carries/protects V I I I .
Anticoagulation Antithrombin inh ibits activated forms of factors
I I , V I I , IX, X, XI, X I I .
thrombomodulin Protein Heparin activates antithrombi n .
(endothelial cells) S
Factor V Leiden mutation produces a factor V
Protein C activated protein C ---- cleaves and inactivates Va, VIlla
resistant to inh ibition by activated protein C .
tPA is used clin ically a s a th rombolytic.
tPA
Plasminogen - plasmin - cleavage of fibrin mesh
I
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N CO L O G Y -PH YS I O LO G Y SECTION Ill 349
Platelet plug formation
0
INJURY ADHESION ACTIVATION AGGREGATION
vWF binds to exposed Platelets bind vWF via Gplb ADP binding to receptor Fibrinogen bind s Gpllb/llla receptors a n d links p latelets
collagen upon receptor at the site of injury induces Gpllb/llla
Balance between
endothelial damage only (specific) expression at p latelet
Pro-aggregation factors: Anti-aggregation factors:
su rface
TXA (released PGI and NO (relea sed
LJ
2 2
Platelets release ADP a n d by platelets) by endothelial cells)
Ca 2+ (necessary for .J. blood flow i blood flow
coagu lation cascade) i p latelet a g g regation J, platelet a g g regation
ADP helps p latelets a d h ere Temporary plug stops bleeding

to endothelium
Thrombogenesis
Formation of i nsoluble fibrin mesh.
Aspirin i n hibits cyclooxygenase (TXA2
Irreversibly blocked by synthesis).
clopidogrel and
ticlopidine
Ticlopidine and clopidogrel inh ibit ADP
inducecl expression of Gpiib/IIIa.
Abciximab inh ibits Gpiib/IIIa d i rectly.
Platelet phospholipid
Vascular endothelial cells
{CJ
/ \
------._-- /------
Inside (vWF)
endothelial thromboplastin
collagen cells tPA, PGI2
Erythrocyte Acute-phase reactants i n plasma (e.g., fibrinogen) can cause RBC aggregation, thereby t RBC
sedimentation rate sedimentation rate (RBC aggregates have a h igher density than plasma).
t ESR -+ infections, autoimmune diseases (e.g. , SLE , rheumatoid arthritis, temporal arteritis),
malignant neoplasms, GI disease (ulcerative col itis), pregnancy.
! ESR -+ polycythemia, sickle cell anem ia, congestive heart failure, m icrocytosis,
hypofibrinogenemia.
3 50 SECTION Ill HEMATOLOGY AN D ONCOLOGY H E M AT O L O G Y A N D O N C O LO G Y - PAT H O L O G Y
H E M ATO L O G Y A N D O N C O LO G Y - PAT H O L O G Y
Pathologic RBC forms

TYPE ASSOCIATED PATHOLOGY N OTES
Acanthocyte (spur Liver disease, Acantha= spiny.

cell) abetal ipoproteinemia (states of
cholesterol dysregul ation ) .
Basophilic stippling Thalassemias, Anem ia o f chronic Baste the ox TAiL.

disease, Lead poison ing.
Bite cell G6PD deficiency.
Elliptocyte He red ita ry ell iptocytosis.
Macro-ovalocyte Megaloblastic anemia (also

hypersegmented PMNs) , marrow
fai lure.
Ringed sideroblasts S ideroblastic anem ia. Excess iron

in mitochondria= pathologic.
Schistocyte, helmet DIC , TTP/H U S , traumatic

cell hemolysis (i.e., metal heart valve
prosthesis) .
HEMATOLOGY AND ONCOLOGY H E M ATO LO G Y A N D O N CO LO G Y -PAT H O L O G Y SECTION Ill 35 1
Pathologic RBC forms (continued)

TYPE EXAMPLE ASSOCIATED PATHOLOGY N OTES
Sickle cell Cl Sickle cell anem ia.
Spherocyte 0 Hereditary spherocytosis,

autoimmune hemolysis.
Teardrop cell Bone marrow infiltration (e.g., RBC "sheds a tear" because it's
myelofibrosis) . been forced out of its home in the
bone marrow.
Target cell HbC disease, Asplen ia, Liver "HALT," said the hunter to his
d isease, Thalassemia. target.
Other RBC pathologies

TYPE PROCESS ASSOCIATED PAT H O LOGY
Heinz bodies Oxidation of iron from ferrous to Seen in G6PD deficiency; Heinz
ferric form leads to denatured body-l ike inclusions seen in
hemoglobin precipitation and a-thalassemia.
damage to RBC membrane
-+formation of bite cells.
Howell-Jolly bodies Basoph i l ic nuclear remnants found Seen in patients with functional
in RBCs. hyposplenia or asplenia, or
Howell-Jol ly bod ies are normally after mothball ingestion
removed from RBCs by splenic (naphthalene) .
macrophages.
3 52 SECTION Ill HEMATOLOGY AND ONCOLOGY H E MATOLO G Y AN D ONC OLO G Y-PAT H OLO G Y
Anemias
ANEMIAS
MCV (< 80 fL) MCV (80-100 fL) MCV (> 100)

(Microcytic) (Normocytic) (Macrocytic)
NON
NONHEMOLYTIC HEMOLYTIC MEGALOBLASTIC
MEGALOBLASTIC
INTRINSIC
ABC membrane defect:

hereditary spherocytosis
ABC enzyme deficiency:

Orotic aciduria Reticulocytosis
G6PD,PK
HbC
Sickle cell anemia
Paroxysmal nocturnal
hemoglobinuria
"ACD may first present as a normocytic anemia and then progress to a microcytic anemia.
Microcytic, hypochromic (MCV < 80 fL) anemia

DESCRIPTION F I N D I NGS
Iron deficiency l iron due to chronic bleeding (GI loss, l i ron, t TIBC, l ferritin.
menorrhagia), mal nutri bon /absorption M icrocytosis and hypochrom ia rJ. May
disorders or t demand (e.g., pregnancy) manifest as Plummer-Vinson syndrome (triad
--+l final step in heme synthesis. of i ron deficiency anemia, esophageal webs,
and atrophic glossitis) .
a-thalassemia Defect: a-globin gene mutations l a-globin

--+ 4 gene deletion: No a-globi n . Excess y-globi n
synthesis. forms y4 ( H b Barts) . I ncompatible with l i fe
cis deletion prevalent in Asian populations; trans (causes hydrops fetal is) .
deletion prevalent in African populations. 3 gene deletion: HbH d isease. Very l ittle
a-globin. Excess P-globin forms P4 ( H b H ) .
1-2 gene deletion : n o clinically significant anemia.
I
HEMATOLOGY AND ONCOLOGY H E MATOLO G Y AND ONCOLO G Y-PAT H OLO G Y SECTION Ill 3 53
Microcytic, hypochromic (MCV < 80 fL) anemia (continued)

DESCRIPTION FINDINGS
P-thalassemia Point mutations in spl ice sites and promoter P-thalassemia minor ( heterozygote):
sequences -+ -globin synthesis. chain is underproduced
Prevalent in Mediterranean populations. Usually asymptomatic
Diagnosis con firmed by t HbA2 (> 3. 5%) on
electrophoresis
P-thalassemia major ( homozygote):
chai n is absent-+ severe anemia rn
requ iring blood transfusion (2

hemochromatosis)
M arrow expansion ( "crew cut" on skull x-ray)
-+ skeletal deform ities. "Chipmunk" facies

Major-+ t HbF (a2y2).
HbS/P-thalassemia heterozygote: mild to
moderate sickle cell d isease depending on
IS-thalassemia major. Note anisocytosis, poikilocytosis, amount of -globi n production.
microcytosis, hypochromia, target cells, and schistocytes.li!l
Lead poisoning Lead inhibits ferrochelatase and ALA LEAD:

dehydratase -+ heme synthesis. Lead Li nes on gingivae ( B ur ton's l ines) and on
Also inhibits rRNA degradation, causing RBCs metaphyses of long bones on x-ray.
to retai n aggregrates of rRNA (basophi l ic Encephalopathy and Erythrocyte basoph i l ic
stippling) . stippling.
High risk i n houses with chipped paint. Abdom inal col ic and sideroblastic Anemia.
Drops-wrist and foot drop. Dimercaprol and
EDTA are 1st l i ne of treatment.
Succi mer used for chelation for k ids ( It "sucks" to
be a kid who eats lead) .
Sideroblastic anemia Defect in heme synthesis. Ringed sideroblasts (with i ron-laden
Hereditary: X-l inked defect in 8-ALA synthase mitochondria) .
gene. t i ron, normal T I B C , t ferritin .
Reversible etiologies: alcohol , lead, and Treatment: pyridoxine ( B 6 , cofactor for 8-ALA
isoniazid. synthase) .
3 54 SECTION Ill HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y-PAT H O L O G Y
Macrocytic
(MCV > 100 fL) anemia
D ESCRIPT I O N F I N D I NGS
Megaloblastic anemia Impaired DNA synthesis ..... maturation of nucleus delayed relative to maturation of cytoplasm .
Ineffective erythropoiesis ..... pancytopenia.
Folate deficiency Etiologies: malnutrition (e.g., alcoholics) , Hypersegmented neutroph ils, glossitis, ! folate,
malabsorption, antifolates (e.g., methotrexate, t homocysteine but normal methylmalonic
trimethoprim, phenytoin), t requ irement (e.g., acid.
hemolytic anemia, pregnancy) .
812deficiency Etiologies: insufficient intake (e.g., strict Hypersegmented neutroph i ls, glossitis, ! B 1 2 ,
(cobalamin) vegans) , malabsorption (e.g., Crohn's disease), t homocysteine, t methyl malonic acid.
pernicious anemia, Diphyllobothrium latum Neurologic symptoms: subacute combined
(fish tapeworm), proton pump inh ibitors. degeneration (due to i nvolvement of B 1 2 in
fatty acid pathways and myelin synthesis):
Peripheral neuropathy with sensorimotor
dysfunction
Posterior columns (vibration/proprioception)
Lateral corticospinal (spasticity)
Dementia
Orotic aciduria Genetic mutation in enzyme that synthesizes Hypersegmented neutroph ils, glossitis, orotic
uridine from orotic acid. Presents in children as acid in urine.
megaloblastic anem ia that cannot be cured by Treatment: uridine monophosphate to bypass
folate or B 1 2 . mutated enzyme.
Nonmegaloblastic Macrocytic anemia in wh ich DNA synthesis is Macrocytosis and bone marrow suppression can
macrocytic anemias unimpaired. occur in the absence of folate /B 12 deficiency.
Causes: Liver d isease ; alcohol ism ;
reticulocytosis t MCV; drugs ( 5 -FU, AZT,
.....
hydroxyurea) .
Normocytic, Normocytic, normochromic anemias are classified as non hemolytic or hemolytic. The hemolytic
normochromic anemia anemias are further classified accord ing to the cause of the hemolysis (intrinsic vs. extrinsic to the
RBC) and by the location of the hemolysis (intravascular vs. extravascular) .
Intravascular Findings: ! haptoglobin, t LDH, hemoglobin in urine (e.g., paroxysmal nocturnal hemoglobinur ia,
hemolysis mechanical destruction [aortic stenosis, prosthetic valve ] ) .
Extravascular Findings: macrophage i n spleen clears RBC . t L D H plus t U C B , which causes jaundice (e.g.,
hemolysis hered itary spherocytosis) .
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N CO L O G Y - PAT H O L O G Y SECTION Ill 35 5
Nonhemolytic, normocytic anemia

DESCRIPTION F I N D I NGS
Anemia of chronic Inflammation t hepciclin (released by l iver,

..... i ron, TIB C , t ferritin.
disease (ACD) binds ferroportin on intestinal mucosal Can become m icrocytic, hypochrom ic
cells and macrophages thus inhibiting
i ron transport) release of iron from
.....
m acrophages.
Aplastic anemia Caused by failure or destruction of myeloid Pancytopenia characterized by severe anemia,
stem cells clue to: leukopenia, and thrombocytopenia. Normal
Radiation and drugs (benzene, cell morphology, but hypocellular bone
chloramphenicol, alkylating agents, marrow with fatty i n filtration (dry bone
anti metabol ites) marrow tap ) .
Viral agents (parvovirus B l 9, EBV, HIV, Symptoms: fatigue, malaise, pallor, purpura,
HCV) mucosal bleeding, petechiae, infection .
Fanconi 's anemia ( DNA repair defect) Treatment: withdrawal of offending agent,
Idiopath ic (immune mediated, 1 stem cell i mmunosuppressive regimens (antithymocyte
defect) ; may follow acute hepatitis globu l i n , cyclosporine), allogeneic bone
m arrow transplantation, RBC and platelet
transfusion, G - C S F, or GM-C S F.
Chronic kidney erythropoietin ..... hematopoiesis.
disease
3 56 SECTION Ill HEMATOLOGY AND ONCOLOGY H E M ATOLO G Y AN D ONCOLO G Y-PAT H OL O G Y
Intrinsic hemolytic E = extravascular; I = intravascular.

normocytic anemia
D ESCRIPT I O N FINDINGS
Hereditary Defect i n proteins interacting with RBC Splenomegaly, aplastic crisis ( Parvovirus B l9
spherocytosis (E) membrane skeleton and plasma membrane infection) .
(e.g., ankyrin, band 3, protein 4.2, spectrin ) . Labs: positive osmotic fragility test. Normal
Less membrane causes small a n d round RBCs to ! MCV with abundance of cells; masks
with no central pallor (t MCHC, t red cell m icrocytia.
d istribution width) premature removal of
-+ Treatment: splenectomy.
RBCs by spleen.
G6PD deficiency (1/E) X-l inked. Defect in G6PD ! glutathione
-+ t -+ Back pain, hemoglobinuria a few days later.
RBC susceptibil ity to oxidant stress. Hemolytic Labs: blood smear shows RBCs with Heinz
anemia following oxidant stress (e.g., sulfa bodies and bite cells.
drugs, infections, fava beans) . RBCs primarily
destroyed extravascula rly.
Pyruvate kinase Autosomal recessive. Defect in pyruvate kinase Hemolytic anemia in a newborn.
deficiency (E) - ! ATP - rigid RBCs.
HbC defect (E) Glutamic acid-to-lysine mutation at residue 6 in Patients with HbSC (l of each mutant gene)
-globin . have m ilder disease than have HbSS patients.
Paroxysmal nocturnal t complement-mediated R B C lysis (impaired PNH triad: hemolytic anemia, pancytopenia,
hemoglobinuria (I) synthesis of GPI anchor or decay-accelerating and venous thrombosis.
factor that protect RBC membrane from Labs: C D 5 5/59 8 RBCs on flow cytometry.
complement) . Acqui red mutation in a Treatment: eculizumab.
hematopoietic stem cel l .
Sickle cell anemia (E) HbS point mutation causes a single amino Sickled cells are crescent-shaped RBCs rJ.
acid replacement in chain (substitution of "Crew cut" on skul l x-ray due to marrow
glutamic acid with val i ne) at position 6. expansion from t erythropoiesis (also i n
Pathogenesis: low 02 or dehydration precipitates thalassemias) .
sickling (deoxygenated HbS polymerizes) , Complications in homozygotes (sickle cell
which results in anemia and vasa-occlusive disease):
d isease. Aplastic crisis (cl u e to parvoviru s B l9)
Newborns are initially asymptomatic because of Autosplenectomy ( H owell-Jolly bodies)

t HbF and ! HbS . t risk of infection with encapsulated
-+
Heterozygotes (sickle cell trait) have resistance organisms; functional splenic dysfunction
to malaria. occurs in early childhood
8% of African Americans carry the HbS trait. Splenic sequestration crisis
Salmonella osteomyelitis
Painful crisis (vasa-occlusive): dactylitis
(painful hand swelling), acute chest

syndrome, avascular necrosis
Renal papillary necrosis (clue to low 0 in
2
papilla) and microhematuria (medullary
infarcts)
Treatment: hydroxyurea (t HbF) and bone
marrow transplantation.
HEMATOLOGY AND ONCOLOGY H EMAT OLO G Y AN D ONCOLO G Y-PAT H OLO G Y SECTION Ill 3 57
Extrinsic hemolytic normocytic anemia

DESCRIPT ION FI NDINGS
Autoimmune Warm agglutinin ( IgG) - chronic anemia seen Autoimmune hemolytic anem ias are usually
hemolytic anemia in SLE, CLL, or with certain drugs (e.g., C oombs' positive.
a-methyldopa) ( "warm weather is GGGreat" ) . Direct C oombs' test- anti-Ig antibody added to
Cold agglutinin ( IgM ) -acute anemia triggered patient's serum . RBCs agglutinate i f RBCs are
by col d ; seen in CLL, Mycoplasma pneumonia coated with Ig.
infections, or infectious mononucleosis ( "cold Indirect C oombs' test- normal RBCs added to
ice cream-yuMMM " ) . patient's serum agglutinate if serum has anti
Many warm and cold AIHA are idiopath ic in RBC surface I g.
etiology.
Microangiopathic Pathogenesis: RBCs are damaged when passing Schistocytes (helmet cells) are seen on blood
anemia through obstructed or narrowed vessel lumina. smear clue to mechanical destruction of RBCs.
Seen in DIC , TTP-HUS, SLE, and malignant
hypertension.
Macroangiopathic Prosthetic heart valves and aortic stenosis may Schistocytes on peripheral blood smear.
anemia also cause hemolytic anemia zo to mechanical
destruction.
Infections t destruction of RBCs (e.g., malaria, Babesia).
Lab values in anemia

Iron Chronic Hemo- Pregnancy/
deficiency disease chromatosis OCP use
Serum iron ! W) t ( 1 0)
Transferrin or TIBC !a t W) b
(indirectly measures
transferrin)
Ferritin t (P)
%transferrin saturation tt
(serum iron/TIBC)
Transferrin- transports iron in blood.

Ferriti n - 1 iron storage protei n of body.
a Evolutionary reasoning- pathogens use circulating iron to thrive. The body has adapted a system i n which iron is stored
within the cells of the body and prevents pathogens from acquiring circulating iron .
bTransferrin production is t in pregnancy and by oral contraceptives.
3 58 SECTION Ill HEMATOLOGY AN D ON COLOGY H E M ATO L O G Y A N D O N C O L O G Y-PAT H O L O G Y
Heme synthesis, The porphyrias are hered itary or acqu ired conditions of defective heme synthesis that lead to the
porphyrias, and lead accumulation of heme precursors . Lead inh ibits specific enzymes needed in heme synthesis,
poisoning leading to a similar condition.
CON DITION AF FECTED ENZYME ACCUMULATED SUBSTRATE PRESENTI NG SYMPTOMS
Lead poisoning Ferrochelatase and Protoporphyrin, 8-ALA M icrocytic anem ia, GI and kidney disease.
ALA dehydratase (blood) Ch ildren - exposure to lead paint -+ mental
deterioration .
Adults- environmental exposure (battery/
ammunition/radiator factory) -+ headache,
memory loss, demyel ination .
Acute intermittent Porphobil inogen Porphobili nogen, Symptoms (5 P's) :
porphyria deaminase 8-ALA, uroporphyrin Painful abdomen
(urine) Port wine-colored urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs
Treatment: glucose and heme, which inh ibit

ALA synthase.
Porphyria cutanea Uroporphyrinogen Uroporphyrin (tea Bl istering cutaneous photosensitivity. Most
tarda decarboxylase colored urine) common porphyria.
Location Intermediates Enzymes Diseases
Glycine + succinyi-CoA
8-aminolevulinic acid
Mitochondria
8s synthase: rate-limiting step
Sideroblastic anemia (X-Iinked)
1
_______________ Ji:.?.rnln_ole_yl,!li[l[g jifiQ
_______________
----------------------- -
1 _.,.-----------1 8-aminolevulinic acid
-+-
Porphobilinogen --1
. dehydratase
. I
Lead poisoning
--
..._
,. -
--
Porphobilinogen
deaminase Acute intermittent porphyria
Cytoplasm Hydroxymethylbilane
t
Uroporph rinogen Ill
I
t
,.
Coproporphyrinogen Ill
I Uroporphyrinogen
decarboxylase I Porphyria cutanea tarda
--------------------- {
------------------------------------------------------------
i
Mitochondria
Protoporphyrin
fe2 ,.----1 Ferrochelatase Lead poisoning
Heme ?-------------
.L heme i ALA synthase activity

i heme .L ALA synthase activity
HEMATOLOGY AND ONCOLOGY H E M AT O L O G Y AND ONCO L O G Y-PAT H O L O G Y SECTION Ill 3 59
Coagulation disorders P T-tests function of common and extri nsic pathway (factors I , I I , V, V I I , and X ) . Defect -+ t PT.
PTT- tests function of common and intrinsic pathway (all factors except VII and X I I I ) . Defect
- t PTT.
DISORDER PT PTT MECHAN I SM AND COMMENTS
Hemophilia A or B I ntrinsic pathway coagulation defect.

A: deficiency of factor VIII -+ t PTT .
B: deficiency of factor IX - t PTT.
Macrohemorrhage in hemophil ia-hemarthroses (bleed ing into joints) , easy

bru ising, t PTT.
Vitamin K deficiency General coagulation defect.
synthesis of factors II, VI I , IX, X, protein C, protein S .
Platelet disorders Defects in platelet plug formation - t bleed ing time (BT) .
Platelet abnormal ities -+ m icrohemorrhage : mucous membrane bleed ing, epistaxis, petech iae,
purpura, t bleeding time, possible platelet count ( PC ) .
D I SORDER PC BT M ECHANISM AND COMMENTS
Bernard-Soulier Defect in platelet plug formation .

syndrome Gpib -+ defect in platelet-to-vWF adhesion.
Glanzmann's Defect in platelet plug formation.
thrombasthenia Gpiib/IIIa -+ defect in platelet-to-platelet aggregation.
Labs : blood smear shows no platelet clumping.
Idiopathic Defect: anti-Gpi ib/I IIa antibodies -+ splenic macrophage consumption of
thrombocytopenic platelet/antibody complex.
purpura (ITP) platelet survival.
Labs : t megakaryocytes.
Thrombotic Deficiency of ADAMT S l3 (vWF metalloprotease) -+ degradation of vWF
thrombocytopenic multimers.
purpura (TTP) Pathogenesis: t large vWF multimers - t platelet aggregation and thrombosis.
platelet survival.
Labs : sch istocytes, t LDH.
Symptoms: pentad of neurologic and renal symptoms, fever, thrombocytopenia,
and microangiopathic hemolytic anem ia.
360 SECTION Ill HEMATOLOGY AN D ON COLOGY H E M ATO L O G Y A N D O N C O L O G Y-PAT H O L O G Y
Mixed platelet and coagulation disorders

D I SORDER PC BT PT PTT MEC H A N I SM A N D COMMENTS
von Willebrand's - or t Intrinsic pathway coagulation defect: ! vWF

disease -+ normal or t PTT (depends on severity;
vWF acts to carry/protect factor V I I I ) .
Defect i n platelet plug formation : ! vWF
- defect i n platelet-to-vWF adhesion.
Mild but most common i n herited bleeding
disorder. Autosomal dom inant. D iagnosed
i n most cases by ri stocetin cofactor assay.
Treatment: DDAVP (desmopressi n) , which
releases vWF stored in endothel ium.
DIC Widespread activation of clotti ng leads to a
deficiency i n clotting factors, which creates a
bleeding state.
Causes : Sepsis (gram-negative), Trauma,
Obstetric compl ications, acute Pancreatitis,
Mal ignancy, Nephroti c syndrome,
Transfusion ( STOP Making New Th rombi) .
Labs : schistocytes, t fibrin split products
(D-dimers) , ! fibrinogen, ! factors V and
VIII.
Hereditary thrombosis syndromes leading t o hypercoagulability

D I SEASE DESCRIPTIO N
Factor V Leiden Production of mutant factor V that is resistant to degradation by activated protein C. Most com mon
cause of inherited hypercoagulabil ity in whites .
Prothrombin gene Mutation in 3' untranslated region -+ t production of prothrombi n -+ t plasma levels and venous
mutation clots.
Antithrombin I nherited deficiency of antithrombin; t in P TT is blunted after heparin administration .
deficiency
Protein C or S ! ability to inactivate factors V and VIII. t risk of thrombotic ski n necrosis with hemorrhage
deficiency following administration of warfarin.
Blood transfusion therapy

COMPONENT DOSAGE E F FECT CliN ICAL USE
Packed RBCs t Hb and 02 carrying capacity Acute blood loss, severe anemia
Platelets t platelet count (t - 5,000/mm3 /unit) Stop significant bleeding (thrombocytopenia,
qual itative platelet defects)
Fresh frozen plasma t coagulation factor levels DIC , cirrhosis, warfarin overdose
Cryoprecipitate Contains fibrinogen, factor V I I I , factor X I I I , Treat coagulation factor deficiencies i nvolving
vWF, a n d fibronectin fibrinogen and factor V I I I
Blood transfusion risks include infection trans m ission (low) , transfusion reactions, i ron overload, hypocalcemia (citrate is a
calcium chelator) , and hyperkalemia ( RBCs may lyse in old blood un its) .
HEMATOLOGY AND ONCOLOGY H E M ATOLO G Y AN D ONCOLO G Y-PAT H OL O G Y SECTION Ill 3 61
Leukemia vs. lymphoma

Leukemia Lymphoid or myeloid neoplasms with widespread involvement of bone marrow. Tumor cells are
usually found in peripheral blood.
Lymphoma D iscrete tumor masses arising from lymph nodes. Presentations often blur definitions.
Leukemoid readion Acute inflammatory response to infection. t WBC count with t neutroph ils and neutroph il
precursors such as band cells ( left sh ift) ; t leukocyte alkaline phosphatase. C ontrast with CML
(also t WBC count with left shift, but leukocyte alkaline phosphatase) .
Hodgkin's vs. Hodgkin's Non-Hodgkin's

non-Hodgkin's Localized, single group of nodes ; extra nodal Multiple, peripheral nodes; extranodal
lymphoma rare ; contiguous spread (stage is strongest i nvolvement common ; noncontiguous spread
predictor of prognosis)
Characterized by Reed-Sternberg cells Maj ority i nvolve B cells (except those of
lymphoblastic T-cell origin)
B imodal d istribution-young adulthood and Peak i ncidence for certa in subtypes at 20-40
> 55 years; more common in men except for years of age
nodular sclerosing type
50% of cases associated with E BV May be associated with H I V and
. .
1mmu nosuppress10n
Constitutional (" B " ) signs/symptoms-low Fewer constitutional signs/symptoms
grade fever, night sweats, weight loss
Reed-Sternberg cells Distinctive tumor giant cell seen in Hodgkin's

disease ; binucleate or bilobed with the 2
halves as m irror images ( "owl 's eyes" r.J). RS
cells are C D30 + and CD1 5 + B-cell origin.
Necessary but not sufficient for a diagnosis of
Hodgkin's disease. Better prognosis with strong
stromal or lymphocytic reaction against RS
cells. Nodular sclerosing form most common
(affects women and men equally) with best
prognosis. Lymphocyte m ixed or depleted
forms have poor prognosis.
3 62 SECTION Ill HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y - PAT H O L O G Y
Non-Hodgkin's lymphoma
TYPE OCCURS I N GENETICS COMMENTS
Neoplasms o f mature B cells

Burkitt's lymphoma Adolescents or young t(8 ;14) -translocation " Starry sky" appearance [J, sheets of
adults of c-myc ( 8 ) and lymphocytes with interspersed macrophages.
heavy-chain Ig (14) Associated with E BV.
Jaw lesion II] in endemic form i n Africa ; pelvis
or abdomen in sporad ic form.
Diffuse large B-cell Usually older adults, Most common adult N I-I L.
lymphoma but 20% in children M a y b e mature T cell in origin (20% ) .
Mantle cell lymphoma Older males t(1 1 ;14) -translocation Poor prognosis, C D 5 +.
of cyclin Dl (11) and
heavy-chain lg (14)
Follicular lymphoma Adults t ( l 4 ;18) -translocation Difficult to cure ; indolent cour s e ;
of heavy-chain Ig (14) bcl-2 i n h ibits apoptosis.
and bcl-2 (18)
Neoplasms of mature T cells
Adult T-cell lymphoma Adults Caused by 1-IT LV-1 Adults present with cutaneous lesions; especially
affects populations in Japan, West Africa, and
the Carib bean.
Aggressive .
Mycosis fungoides/ Adults Adults present with cutaneous patches/nodules.
Sezary syndrome CD4+, indolent course.
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y AN D ONC O L O G Y - PAT H O LO G Y S ECTION Ill 363
Multiple myeloma Monoclonal plasma cell ( " fried egg" T h i n k C RAB :

appearance) cancer that arises in the marrow HyperCalcemia
and produces large amounts of IgG ( 5 5 %) or Renal insufficiency
IgA (2 5 % ) . Most common 1 a tumor arising Anemia
within bone i n the elderly (> 40-50 years of Bone lytic lesions/Back pain
age ) . Multiple Myelom a : Monoclonal M protein
Associated with : spike
t susceptibil ity to infection
Primary amyloidosis (AL)

M spike -!\
Punched-out lytic bone lesions on x-ray [J
M spike on protein electrophoresis
I g light chains in urine (Bence Jones
protein)
Rouleaux formation ( RBCs stacked l ike
poker ch ips in blood smear)

Numerous plasma cells with "clock face"
chromatin and intracytoplasmic inclusions
containing immunoglobul i n rn.
Distinguish from Waldenstrom's Multiple myeloma smear. "Clock face" chromatin (black
macroglobuli nemia - M spike IgM=
arrow) and whitish intracytoplasmic inclusions containing
immunoglobulin (red arrow). D
( hyperviscosity symptoms) ; no lytic bone
-+
lesions.
MGUS Monoclonal gammopathy of undeterm ined significance (MGUS) is a monoclonal expansion of

plasma cells with M spike. Asymptomatic precursor to multiple myeloma. Patients with MGUS
develop multiple myeloma at a rate of 1-Z% per year.
3 64 SECTION Ill HEMATOLOGY AN D ON COLOGY H E M ATO L O G Y A N D O N C O L O G Y-PAT H O L O G Y
Leukemias Unregulated growth of leukocytes i n bone marrow - t o r number o f circulating leukocytes i n

blood a n d marrow failure - anemia ( RBCs), infections ( ! mature W B C s ) , a n d hemorrhage
(! platelets) ; leukemic cell infiltrates in l iver, spleen, and lymph nodes a re possible.
TYPE PERIPHERAL B L O O D SMEAR COMMENTS
Lymphoid neoplasms
Acute lymphoblastic Age : < 15 years. T-cell ALL can present as
leukemia/ lymphoma mediastinal mass ( leukem ic infiltration of the
(ALL) thymus) .
Peripheral blood and bone marrow h ave t t t
lymphoblasts r:J.
TdT+ (marker of pre-T and pre-B cells),
CALLA+.
Most responsive to therapy.
May spread to CNS and testes.
t( l 2 ; 2 l ) - better prognosis.
Small lymphocytic Age : > 60 years. Often asymptomatic ;

lymphoma (SLL)/ smudge cells in peripheral blood smear II);
chronic lymphocytic autoim mune hemolytic anemia.
leukemia (CLL) SLL same as CLL except CLL has t peripheral
blood lymphocytosis or bone marrow
i nvolvement.
Hairy cell leukemia Age : Adults. Mature B -ee!! tumor in the

elderly. Cells have filamentous, h air-l ike
projections .
Stains TRAP (tartrate-resistant acid
phosphatase) positive.
Treatment: cladribine, an adenosine analog.
HEMATOLOGY AND ONCOLOGY H E M ATOLO G Y AN D ONCOLO G Y-P AT H OL O G Y SECTION Ill 365
Leukemias (continued)
TYPE PERIPHERAL BLOOD SMEAR COMMENTS
Myeloid neoplasms
Acute myelogenous Age : median onset 65 years. Auer rods [!];
leukemia (AM L) t t t circulating myeloblasts on peripheral
smear; adults. t( l 5 ; 1 7 ) -+ M3 AML subtype
responds to all-trans retinoic acid (vitamin A) ,
inducing d i fferentiation of myeloblasts; DIC is
a common presentation in M3 A M L .
Chronic myelogenous Age : h i ghest incidence at 3 0 - 6 0 years. Defined

leukemia (CML) by the Ph iladelphi a chromosome (t[9;ZZ ] ,
bcr-abl); myeloid stem cell prol iferation ;
presents with t neutroph ils, metamyelocytes,
basophils (]; splenomegaly; may accelerate
and transform to A M L or ALL ( " blast crisis" ) .
Very low leukocyte alkaline phosphatase a s a
result of i mmature granulocytes (vs. leukemoid
reaction - mature cells) .
Responds to imati n ib (a small-molecule
inhibitor of the bcr-abl tyrosine kinase) .
Auer bodies (rods) Peroxidase-positive cytoplasmic inclusions in granulocytes and myeloblasts. Commonly seen in
acute promyelocytic leukemia ( M 3 ) . Treatment of AML M3 can release Auer rods -+ DIC .
Chromosomal translocations
TRANSLOCATION ASSOCIATED D I SORDER
t(9;22) (Philadelphia CML (bcr-abl hybrid) Philadelphia C reaML cheese.

chromosome)
t( 8 ; 14) Burkitt's lymphoma ( c-myc activation)
t( l l ; l4) Mantle cell lymphoma (cycl in 0 1 activation)
t( l4; 1 8 ) Foll icular lymphomas (bcl-2 activation)
t( l 5 ; 17) M3 type of AML (responsive to all-trans retinoic
acid)
366 SECTION Ill HEM ATOLOGY AND ONCOLOGY H E M AT O L O G Y A N D O N C O L O G Y - PAT H O L O G Y
Langerhans cell Prol iferative d isorders of dendritic ( Langerhans)

histiocytosis cells from monocyte lineage. Presents in
a child as lytic bone lesions and skin rash.
Cells are functionally immature and do not
efficiently stimulate T lymphocytes via antigen
presentation. Cells express S-100 (neural crest
origin) and C D l a . Birbeck granules ( " tennis
rackets" on EM) are characteristic f.J.
Chronic myeloproliferative disorders

RBCS WBCS PLATELETS PHI LADELPH IA C H ROMOSOME JAK2 MUTATI O N S
Polycythemia vera Negative Positive

Essential Negative Positive ( 3 0-5 0 % )
thrombocytosis
Myelofibrosis Variable Variable egative Positive ( 3 0 -5 0 % )
CML Positive Negative
The myelofibroproliferative disorders represent an often-overlapping spectrum , but the classic
findings are described below. JAK2 is involved in hematopoietic growth factor signal ing.
Mutations are impl icated in myeloprol iferative disorders other than C M L .
Polycythemia vera Abnormal clone of hematopoietic stem cells with constitutively active JAK2 receptors, prol iferate
without EPO stimulation. Often presents as intense itching after hot shower.
Essential Similar to polycythemia vera, but specific for megakaryocytes.
thrombocytosis
Myelofibrosis Fibrotic obl iteration of bone marrow. Teardrop cel l . "Bone marrow is crying because it's fibrosed."
CML bcr-abl transformation leads to t cell division and i n h ibition of apoptosis.
Polycythemia
PLASMA VOLU M E RBC MASS 02 SATURATION ASSOCIATED D ISEASES
Relative
Appropriate absolute Lung disease, congenital heart disease, h i gh
altitude.
Inappropriate absolute Renal cell carcinoma, Wilms' tumor, cyst,
hepatocellular carcinoma, hydronephrosi s.
Due to ectopic erythropoietin .
Polycythemia vera tt
HEMATOLOGY AND ONCOLO GY H E M AT O L O G Y A N D O N C O LO G Y-P H A R M A C O LO G Y SECTION Ill 3 67
H E M AT O L O G Y A N D O N C O L O G Y-P H A R M A C O LO G Y
Heparin
MECHAN ISM Cofactor for the activation of antithrombin, ! thrombin, and ! factor Xa. Short half-l i fe .
CliNICAl USE Immediate anticoagulation for pulmonary embol ism, acute coronary syndrome, M I , DVT. Used
during pregnancy (does not cross placenta ) . Follow PTT.
TOXICITY Bleeding, thrombocytopenia ( H IT), osteoporosis, drug-dru g i nteractions. For rapid reversal
(antidote), use protamine sulfate (positively charged molecule that binds negatively charged
hepari n ) .
NOTES Low-molecular-weight heparins (e.g., enoxaparin, dalteparin) a c t more on factor X a , h ave better
bioavailabil ity and 2-4 times longer half-l ife. Can be adm i n i stered subcutaneously and without
laboratory mon itoring. Not easily reversible.
Heparin-induced thrombocytopenia ( H IT) - development of IgC antibodies against heparin

bound to platelet factor 4 ( PF4 ) . Antibody-heparin-PF4 complex activates platelets -+ thrombosis
and thrombocytopenia.
Lepirudin, bivalirudin Derivatives of hirudin, the anticoagulant used by leeches ; i n h ibit thrombin. Used as an alternative
to heparin for anticoagulating patients with H IT.
Warfarin (Coumadin)
MECHAN ISM Interferes with normal synthesis and The EX-PresidenT went to war (farin) .
y-carboxylation of vitamin K-dependent
clotting factors I I , V I I , IX, and X and proteins
C and S . Metabol ized by the cytochrome
P-450 pathway. In laboratory assay, has effect
on EXtrinsic pathway and t PT. Long half-
life.
CliNICAl USE Chronic anticoagulation (after STE M I , venous
thromboembolism prophylaxis, and prevention
of stroke i n atrial fibrillation ) . Not used in
pregnant women (because warfarin, unl ike
heparin, can cross the placenta ) . Follow PT/
I N R values.
TOXICITY Bleeding, teratogenic, skin/tissue necrosis, drug For reversal of warfarin overdose, give vitamin
drug interactions. K. For rapid reversal of severe warfarin
overdose, give fresh frozen plasma.
368 SECTI O N Ill HEMATOLOGY AND ONC OLOGY H E M AT O L O G Y A N D O N C O L O G Y-P H A R M A C O L O G Y
Heparin vs. warfarin

Heparin Warfarin
STRUCTURE Large anionic, acidic polymer Small l ipid-soluble molecule
ROUTE O F ADMIN ISTRAT I O N Parenteral (IV, S C ) Oral
S ITE O F ACTION Blood Liver
ONSET OF ACTION Rapid (seconds) Slow, l i m ited by half-l ives of normal clotting
factors
MECHAN I SM OF ACTION Activates antithrombin, which the action of Impairs the synthesis of vita m i n K-clepenclent
I la (thrombin) and factor Xa clotti ng factors II, VII, IX, and X (vita m i n K
antagon ist)
DURATIO N O F ACTI O N Acute ( hours) Chronic (clays)
I N H IBITS COAGULATION Yes No
I N VITRO
TREATMENT O F ACUTE Protamine sulfate IV vita m i n K and fresh frozen plasma

OVERDOSE
MONITO R I N G PTT (intrinsic pathway) PT/INR (extrinsic pathway)

CROSSES PLACENTA No Yes (teratogenic)
Thrombolytics Alteplase (tPA) , reteplase (rPA) , tenecteplase (TN K-tPA) .

MECHANISM Directly or indirectly a iel conversion of plasm inogen to plasm i n , which cleaves thrombin and fibrin
clots. t PT, t PTT, no change in platelet count.
CLINICAL USE Early Ml, early ischemic stroke, direct thrombolysis of severe pul monary embol ism.
TOXICITY Bleeding. Contra ind icated in patients with active bleeding, h istory of i ntracranial bleeding, recent
s urgery, known bleeding diatheses, or severe hypertension . Treat toxicity with a minocaproic acid,
an inhibitor of fibrinolysis.
Aspirin (ASA)
MECHAN ISM Irreversibly inh ibits cyclooxygenase (both COX-I and C OX-2) enzyme by covalent acetylation.
Platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced :
t bleeding time, TXA 2 and prostaglandins. No effect on PT or PTT
CLI N ICAL USE Antipyretic, analgesic, anti-inflammatory, antiplatelet ( aggregation ) .
TOXICITY Gastric ulceration, tinnitus (CN V I I I ) . Chronic use can lead to acute renal failure, i nterstitial
nephritis, and upper GI bleeding. Reye's syndrome in children with viral infection . Overdose
causes respiratory alkalosis and metabol ic acidosis.
ADP receptor inhibitors Clopiclogrel, ticlopicline, prasugrel , ticagrelor.

MECHANISM Inhibit platelet aggregation by irreversibly blocking ADP receptors. I n h ibit fibrinogen binding by
preventing glycoprotein l ib/lila from binding to fibrinogen .
CLIN ICAL USE Acute coronary syndrome; coronary stenting. incidence or recurrence of thrombotic stroke.
TOXICITY Neutropen ia (ticlopid ine) .
HEMATO LOGY AND ONC O LOGY H E M ATO L O G Y A N D O N C O L O G Y-P H A RMA C O LO G Y SECTION Ill 3 69
Cilostazol, dipyridamole
MECHANISM Phosphodiesterase I I I inh ibitor; t cAM P in platelets, thus i n h ibiting platelet aggregation ;
vasodilators.
CliN ICAL USE I nterm ittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with
aspirin), angina prophylaxis.
TOXICITY Nausea, headache, facial flushing, hypotension, abdom inal pain.
GP l i b/ l i la inhibitors Abciximab, eptifibatide, tirofiban.

MECHANISM Bind to the glycoprotein receptor lib/Ilia on activated platelets, preventing aggregation . Abciximab
is made from monoclonal antibody Fab fragments .
CliN ICAL USE Acute coronary syndromes, percutaneous transluminal coronary angioplasty.
TOXICITY Bleeding, thrombocytopenia.
Cancer drugs-cell cycle
G2
Synthesis
.
G,
. '

.
of components Go

'\\
needed for Synthesis
mitosis of components Resting ;
needed for
DNA synthesis
s
DNA
Anti metabolites
(Adapted, with permission, from Katzung BG, Trevor AJ. USMLE Road Map: Pharmacology, I st ed. New York:
McGraw-Hill, 200 3 : 1 33.)
3 70 SECTION Ill HE MATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O LO G Y-P H A R M A C O L O G Y
Antineoplastics
Nucleotide synthesis ...- DNA ---- RNA ---- Protei n --- Ce llular d i v i s i o n
---
J _ T
Vinca alkaloids:
Methotrexate, 5-FU: Alkylating agents, cisplatin :
i n h i b i t m i c rotu b u le formation
J.. t h y m i d i n e synthesis cross-link DNA
6 - M P:
Paclitaxel:
J.. p u r i n e synthesis Dactinomycin, doxoru bicin :
i n h i bits m i c rotu b u le d i sassem bly
DNA i ntercalators
Etoposide:
i n h i b i ts topoisomerase I I
H EMATO LOGY AND ONCO LOGY H E M AT O L O G Y A N D O N C O LO G Y - P H A R M A C O L O G Y SECTION Ill 37 1
Anti metabolites
DRUG MECHANISMa C L I N I CAL U S E TOXICITY
Methotrexate ( MTX) Fol ic acid analog that inh ibits Cancers : leukem ias, Myelosuppression, which is
cl ihyclrofolate reductase lymphomas, choriocarcinoma, reversible with leucovorin
.... ! clTM P .... ! DNA and sarcomas. (fol inic acid) "rescue."
! protein synthesis. Non-neoplastic: abortion, Macrovesicular fatty change in
ectopic pregnancy, l iver.
rheumatoid arthritis, psoriasis. Mucositis.
Teratogenic.
5-fluorouracil (5-FU) Pyrimidine analog bioactivatecl Colon cancer, basal cell Myelosuppression, which is not
to S F-clUMP, which carcinoma (topica l ) . reversible w ith leucovorin.
covalently complexes folic Overdose : "rescue" with
acid. thymidine.
This complex i n h ibits Photosensitivity.
thymicl y late synthase
.... ! clT M P .... ! DNA and
! protein synthesis.
Cytarabine Pyrimidine analog .... inh ibition Leukemias, lymphomas. Leukopenia,
(arabinofuranosyl of D A polymerase. thrombocytopenia,
cytidine) megaloblastic anemia.
Azathioprine Purine (thiol) analogs Leukem ias. B one marrow, GI, l iver.
6-mercaptopurine .... ! de novo purine synthesis. Metabol i zed by xanthine
(6-MP) Activated by HGPRT. oxidase ; thus t toxicity with
6-thioguanine (6-TG) allopurinol.
3Al l are S-phase specific.
5 - FU
Thymidylate
1
synthase
d U M P --------- dTMP
{ \
372 SECTION Ill HE MATOLOGY AN D ONCOLOGY H E M ATO L O G Y AND O NC O L O G Y-P H A R M A C O LO G Y
Antitumor antibiotics
DRUG MECHANISM CLIN ICAL USE TOXICITY
Dactinomycin I ntercalates in DNA. Wilms' tumor, Ewing's Myelosuppression .

(actinomycin D) sarcoma, rhabdomyosarcoma.
Used for childhood tumors
("children act out " ) .
Doxorubicin Generate free radicals. Solid tumors, leukemias, Ca rdiotoxicity (dilated
(Adriamycin), Noncovalently intercalate lymphomas. cardi omyopathy) ,
daunorubicin in DNA breaks in DNA
-+ myelosuppression, alopecia.
-+ repl ication. Toxic to tissues following
extravasation.
Dexrazoxane (iron chelating
agent) , used to prevent
cardiotoxicity.
Bleomycin I nduces free rad ical formation, Testicular cancer, Hodgkin's Pul monary fibrosis, skin
which causes breaks in DNA lymphoma. changes. Minimal
strands. myelosuppression.
Alkylating agents
DRUG MECHANISM CLIN ICAL U S E TOXICITY
Cyclophosphamide, Covalently X-l ink ( interstrand) Solid tumors, leukemia, Myelosuppression ;

ifosfamide DNA at guanine N-7. Requ ire lymphomas, and some bra in hemorrhagic cystitis, partially
bioactivation by l iver. cancers. prevented with mesna (thiol
group of mesna binds toxic
metabolite) .
Nitrosoureas Requ ire bioactivation. Brain tumors (includ ing CNS toxicity (dizziness,
(carmustine, Cross blood-brain barrier gl ioblastoma multiforme ) . ataxia) .
lomustine, semustine, -+ CNS.
streptozocin)
Busulfan Alkylates DNA. CML. Also used to ablate Pulmonary fibrosis,
patient's bone marrow before hyperpigmentation .
bone marrow transplantation .
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y - P H A R M A C O L O G Y SECTION Ill 373
Microtubule inhibitors
DRUG M ECHANISM CLIN ICAL USE TOXI C ITY
Vincristine, vinblastine Alkaloids that bind to Solid tumors, leukemias, and Vincristine-neurotoxicity
tubulin i n M phase and lymphomas. (areflexia, peripheral neuritis) ,
block polymerization of paralytic ileus.
m icrotubules so that m itotic Vinblastine blasts bone
spindle cannot form. marrow (suppression) .
"M icrotubules are the vines
of your cells."
Paclitaxel, other taxols Hyperstabil ize polymerized Ovarian and breast carcinomas. Myelosuppression and
m icrotubules i n M phase so hypersensitivity.
that m itotic spindle cannot
break clown (anaphase cannot
occur) .
"It is taxing to stay
polymerized ."
Cisplatin, carboplatin
MECHANISM Cross-l ink DNA.
CLIN ICAL USE Testicular, bladder, ovary, and lung carcinomas.
TOXICITY Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxic ity with amifostine (free rad ical
scavenger) and chloride diuresis.
Etoposide, teniposide
MECHANISM I n h ibit topoisomerase I I -+ t DNA degradation .
CLINICAL USE Solid tumors, leukemias, lymphomas.
TOXICITY Myelosuppression , GI irritation, alopecia.
Hydroxyurea
MECHAN I S M Inh ibits ribonucleotide reductase -+ ! DNA Synthesis ( S-phase specific) .
CLIN ICAL U S E Melanoma, C M L , sickle cell d isease (t HbF).
TOXICITY B one marrow suppression, GI upset.
Prednisone, prednisolone
MECHANISM May trigger apoptosis. May even work on nondividing cells.
CLIN ICAL USE Most commonly used glucocorticoid in cancer chemotherapy. Used in CLL, non-Hoclgkin's
lymphomas (part of combination chemotherapy regimen) . Also used as an immunosuppressant
(e.g., autoimmune cl iseases) .
TOXICITY Cushing-l ike symptoms; immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic
ulcers, hyperglycemia, psychosis.
3 74 SECTION Ill HEMATOLOGY AN D ON COLOGY H E M AT O l O G Y A N D O N C O l O G Y - P H A R M A C O l O G Y
Tamoxifen, raloxifene
MECHANISM SERMs-receptor antagonists i n breast and agonists i n bone. Block the binding of estrogen to
estrogen receptor-positive cells.
CLINICAL USE Breast cancer treatment and prevention . Also useful to prevent osteoporosis.
TOXICITY Tamoxifen-partial agon ist in endometrium, wh ich t the risk of endometrial cancer; " hot flashes."
Raloxifene-no t in endometrial carcinoma because it is an endometrial antagon ist.
Trastuzumab (Herceptin)
MECHANISM Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase. Helps kill breast cancer cells that
overexpress H E R-2 , possibly through antibody-dependent cytotoxicity.
CLIN ICAL USE H E R-2-positive breast cancer.
TOXICITY Cardiotoxicity.
lmatinib (Gieevec)
M ECHAN ISM Ph iladelph ia chromosome bcr-abl tyrosine kinase inh ibitor.
CLINICAL USE C M L , CI stromal tumors.
TOXICITY Fluid retention .
Rituximab
MECHANISM Monoclonal antibody against CD20, which is found on most B -cell neoplasms.
CLIN ICAL USE Non-Hodgkin's lymphoma, rheumatoid arthritis (with methotrexate) .
Vemurafenib
MECHANISM Small molecule inh ibitor of forms of the B-Raf kinase with the V600E mutation.
CLIN ICAL USE Metastatic melanoma.
Bevacizumab
MECHANISM Monoclonal antibody aga inst VECF. Inh ibits angiogenesis.
C L I N I CAL USE Solid tumors.
HEMATOLOGY AND ONCOLOGY H E M ATO L O G Y A N D O N C O L O G Y - P H A R M A C O L O G Y SECTION Ill 375
Common
chemotoxicities
Cisplati n /Carboplatin --+ acoustic nerve damage
(and neph rotoxicity)
Vincristine peripheral neuropathy

--+
Bleomycin , Busulfan pulmonary fibrosis

--+
Doxorubicin cardiotoxicity
--+
Trastuzumab cardiotoxicity
--+
Cisplatin /Carboplatin - nephrotoxic (and

acoustic nerve damage)
CYclophospham i de - hemorrhagic cystitis
5-FU --+ myelosuppression

6-MP --+ myelosuppression
Methotrexate --+ myelosuppression

376 SECTION Ill HEMATOLOGY AN D ONCOLOGY
N OT E S
HIGH-YIELD SYSTEMS
Musculoskeletal, Skin,
and Connective Tissue
"Rigid, the skeleton of habit alone upholds the human frame."

-Virgi n ia Woolf
"Beauty may be skin deep, but ugly goes clear to the bone."
-Redel Foxx
"The function of muscle is to pull and not to push, except in the case of
the genitals and the tongue."
-Leonardo da Vinci
3 78 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECT IVE T ISSUE A N ATO M Y A N D PHYSIOLOG Y
M U SC U LOSK ELE TAL, SKIN , A N D CON N E C TIV E TISSU E - AN ATOM Y A N D PHYSIOLOG Y
Epidermis layers From surface to base :

Stratum Corneum ( keratin)
Stratum Lucidum
Stratum Granulosum
Stratum Spinosum (spines=
desmosomes)
Stratum Basale (stem cell site)
Californians Like Girls i n String Bikinis.
Epidermis layers. A , Stratum corneum; B , stratum

lucidum; C, stratum granulosum; D, stratum spinosum;
E, stratum basa le.(i!J
Epidermal appendages
Sebaceous gland Holocrine secretion of sebum. Associated with hair foll icle.
Eccrine gland Secretes sweat. Found throughout the body ( "Eccrine glands are Everywhere") .
Apocrine gland Secretes milky viscous fluid. Found in the axillae, gen italia, and areolae. Does not become
functional until puberty. Malodorous because of bacterial action .
Epithelial cell junctions
Apical
i--- Tight junction (zonula occludens)-prevents paracellular

movement of solutes; composed of claudins and occludins.
E-cadherin
}- Adherens junction (zonula adherens)-below tight junction,

forms "belt" connecting actin cytoskeletons of adjacent cells
with CADherins (Ca''-dependent adhesion proteins) Loss o f
l E-cadherin promotes metastasis.
Keratin
J"--- Desmosome (macula adherens)-structural support via keratin
Desmoplakin _____/' 1 interactions. Autoantibodies - pemphigus vulgaris.
Connexon
with central
--{ lr Gap junction-channel proteins called connexons permit
electrical and chemical communication between cells.
channel
Cell membrane
Basolateral
iii
'iiiiiii;;iiiiiiiiiiliS:i

ii -il.ii.-
-- Basement membrane
lntegrins-membrane proteins that Hemidesmosome-connects keratin in basal cells to

maintain integrity o f basement membrane underlying basement membrane. Autoantibodies - bullous
by binding to laminin in BM. pemphigoid. (Hemidesmosomes are down "bullow").
MUSCULOSKELETAL, SKIN, AND CONNECTI VE TISSUE ANATOMY A N D PHYSIOLOG Y SECTION Ill 3 79
Unhappy triad/ Common i njury in contact sports: lateral force Positive anterior drawer sign ACL tear =
knee injury appl ied to a planted leg. Triad includes tear Abnormal passive abduction MCL tear =
of the AC L , MCL, and meniscus (classically

Femur -1 -
medial, but lateral more common ) . Often
requ ires surgical AC L reconstru ction.
Lateral condyle Medial condyle
"Anterior" and "posterior" in ACL and PCL refer ACL --- PCL ---
to sites of tibial attachment. LCL-

Lateral meniscus _/'
MCL
Medial meniscus
Fibula --
-
,
-- Tibia
Clinically important Pudendal nerve block (to rel ieve pa in of del ivery)-ischial spine.
landmarks Appendix-213 of the way from the umbil icus to the anterior superior i l iac spine
( McBur ney's point) .
Lumbar puncture-il iac crest.
Rotator cuff Shoulder muscles that form the rotator cuff: SitS (small t is for teres minor).
muscles Supraspinatus-abducts arm in itially (before
deltoid) ; most common rotator cuff injur y.
Infraspinatus-lateral ly rotates arm ; pitch ing
Biceps tendon
Ill Jury.
Teres m i nor-adducts and laterally rotates Teres minor Subscapularis

arm.
Subscapularis-medially rotates and adducts
Posterior --- Anterior
arm .
I n nervated by C 5 -C6.
Wrist bones Scaphoid , Lu nate, Triquetrum ,

Pisiform , Hamate, Capitate, Trapezoid ,
Trapezium rn. ( So Long To Pinky, Here
C omes T he Thumb) . Capitate
Scaphoid is most commonly fractured carpal
and is prone to avascular necrosis owing to
retrograde blood supply.
Dislocation of lunate may cause acute carpal
tunnel syndrome.
Carpal tunnel syndrome: entrapment of

median nerve i n carpal tunnel ; nerve
compression .... paresthesia, pa in, and
numbness i n distribution of median nerve.
3 80 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECTIVE T ISSUE A N ATO M Y A N D PHYSIOlOG Y
Upper extremity innervation

Upper trunk:
Lesioned by trauma
r---C7 root:
Compressed by
Axillary nerve:
cervical disk les1on
Lesioned by fracture of surgical
neck; dislocation of
the humerus; intramuscular
injections---- Lower trunk of
brachial plexus:
Compressed by cervical rib
Radial nerve in
1 or by Pancoast tumor of lung;
leads to Klumpke's palsy
i
Radial nerve:
Compressed in axilla by
incorrect use of a crutch
Radial nerve
(deep branch):
Stretched by subluxation
of radius
Anterior interosseous nerve:

Compressed in deep forearm
of median nerve:
Lesioned by
superficial
Median nerve:
Compressed in carpal tunnel syndrome
laceration
and by dislocated lunale
Ulnar nerve:
Lesioned by trauma to heel of the hand;
fracture of hook of hamate
A. Upper limb nerve routes and common lesions B. Dermatomes of the upper limb/hand
Cutaneous branches
of median nerve to fingers
Branches of deep
ulnar nerve to
the interossei and
adductor pollicis
Recurrent branch
of median nerve
to thenar muscles
Abductor pollicis Abductor digiti

brevis muscle (in minimi muscle
thenar eminence) (in hypothenar
eminence)
Trapezium
Hook of hamate
Palmar cutaneous
branch of the Ulnar nerve in
median nerve
Flexor retinaculum
Ulnar nerve
Scaphoid
Cutaneous branch
of ulnar nerve to
dorsum of hand
Palm of hand Dorsum of hand
Median nerve in
D. Cutaneous innervation of the hand

carpal tunnel
(9tendons in tunnel Flexor carpi
not shown) ulnaris

Ulna
C. Innervation of the hand

(Adapted, with permission, from White JS. USMLE Road Map: Gross Anatomy, 2nd ed. New York: McGraw-Hill, 2005: 145-147.)
MUSCULOSKELETAL, SKIN, AND CONNECT IVE T ISSUE ANATOM Y AND PHYSIOLOGY SECTION Ill 3 81
Brachial plexus lesions

ca T1
}
C5 C6 C7 Randy
Long Roots Travi s
thoracic Drinks
Cold
Beer
0"Waiter's tip" (Erb's palsy)

E) claw hand (Kiumpke's palsy)
UpperO Middle Lower E) } Trunks
@wrist drop
()Winged scapula
0 Deltoid paralysis
} Divisions
@"Saturday night palsy" (wrist drop)

QDifficulty flexing elbow, variable Lateral Posterior E) Medial } Cords
sensory loss
}
0 Decreased thumb function,
"Pope's blessing"
0@
Axillary Radial
(=)Intrinsic muscles of hand, claw (Extensors)
hand
Branches
(=)
Musculocutaneous Median Ulnar
(Flexors)
Clavicle fracture is relatively common-brachial plexus is protected from i n j ur y by subclavius muscle.

') () ) SECTION Il l MUSCULOSKELETAL, SKI N , A N D CO N N ECTIVE T ISSUE A N ATOM Y A N D P HYS IOlOGY
Upper extremity nerves

NERVE TYPICAL INJURY MOTOR DEFICIT SENSORY DEFICIT SIGN
Axillary (CS, C6) Fractured surgical Deltoid-arm Over deltoid muscle Atroph ied deltoid
neck of humeru s , abduction at shoulder
dislocation of
humeral head
Radial (CS-Tl) Fracture at m idshaft "BEST extensors" Posterior arm and Wrist d rop
of humeru s ; Brachioradial is, dorsal hand and
" Saturday n ight Extensors of thumb
palsy" (extended wrist and fingers,
compression of axilla Supinator, Triceps
by back of chair or
crutches)
Median (CS-CB, Tl) Fracture of Opposition of thumb Dorsal and palmar "Ape hand"; " Pope's
supracondylar Lateral fi nger flexion aspects of lateral blessing" ( hand)
humerus (proximal Wrist flexion 3 1/z fingers, thenar
lesion) em mence
Ulnar (CB, Tl) Fracture of medial Medial fi nger flexion Medial 1 1/z fingers, Radial deviation of
epicondyle of Wrist flexion hypothenar wrist upon wrist
humeru s , " funny emmence flexion
bone" (proximal
lesion)
Musculocutaneous Upper trunk Biceps, brach ialis, Lateral forearm
(CS-C7) compression coracobrachialis
Flexion of arm at
elbow
ote : Always consider the lesion location ; generally, muscles innervated by nerve branches distal to the lesion will be affected.
Note that this table is h ighly simpl ified. Distal median and ulnar lesions d iscussed later.
Erb-Duchenne Traction or tear of the upper trunk of the "Waiter's tip" owing to appearance of arm.
palsy ("walter's tip") brach ial plexus (C5 and C6 roots); seen in
infants following trauma dur i n g del ivery.
Findings : l i mb hangs by side (paralysis of
abductors), medially rotated (paralysis of lateral
rotators), forearm is pronated (loss of biceps) .
Klumpke's palsy An embryologic or childbirth defect affecting inferior trunk of brach ial plexus ( C 8 , Tl ) ; a cervical
and thoracic outlet rib can compress subclavian artery and inferior trunk, resulting in thoracic outlet syndrom e :
syndrome Atrophy o f t h e thenar a n d hypothenar eminences
Atrophy of the interosseous muscles

Sensory deficits on the medial side of the forearm and hand
D isappearance of the rad ial pulse upon movi ng the head toward the ipsilateral side
MUSCULOSKELE TAL, SKI N, AND CONNECTIVE TISSUE ANATOM Y AND PHY SIOLOGY SECTION Ill 383
Distortions of the hand "Clawing" is easily conceptualized as loss of the lumbricals, which flex the MCP joints and extend
both the DIP and PI P joints.
Ulnar claw Can be caused by long-standing injur y to ulnar nerve at hook of hamate (e.g., by fal l i n g onto
outstretched hand) . D istal ulnar nerve lesion -+ loss of medial lumbrical fu nction -+ inability to
extend 4th and 5th digits ( "clawing") when tryi ng to open the hand.
Median claw Can be caused by carpal tunnel syndrome or dislocated lunate. Distal median nerve lesion (after
branch conta i n i n g C 5-C7 branches off to feed forearm flexors) -+ loss of lateral l umbrical
function ; 2nd and 3rd digits are clawed upon attempted Finger extension.
"Pope's blessing" Proximal median nerve lesion causes loss of lateral Finger flexion and thumb opposition . When
asked to make fist, 2nd and 3rd digits remain extended and thumb remains unopposed, which
looks l ike the hand of benediction or "Pope's blessing."
"Ape hand" Proximal median nerve lesion- loss of opponens poll icis muscle function -+ unopposable thumb
(i nabil ity to abduct thumb) , hence "ape hand."
Klumpke's total claw Lesion of lower trunk ( C 8 , Tl) of brach ial plexus-+ loss of function of all lumbricals; forearm
Finger flexors (fed by part of median nerve with C 5 -C7) and Finger extensors (fed by radial nerve)
are unopposed -+ clawing of all d i gits.
Distal ulnar claw Median claw Klumpke's total claw hand

Claw hand of 4th and 5th digits Claw hand of 2nd and 3rd digits Lower trunk (C8, Tl) lesion
when straightening fingers when straightening fingers
Long thoracic nerve Serratus anterior-anchors scapula to thoracic

(C5-C7) cage . Used for abduction above hor i zontal
position . Can be injured in mastectomy
-+ winged scapula and ipsilateral lymphedema.
Winged
right
scapula
Hand muscles Thenar (median) -Opponen s pollicis, Abductor Both groups perform the same functions :
Thenar pollicis brevis, Flexor pollicis brevis. Oppose, Abduct, a n d Flex (OAF) .
Hypothenar (ulnar) -Opponens digiti m i n i m i ,
Abductor d igiti m i n imi, Flexor d i giti min i m i .
Dorsal interosseous muscles-abduct t h e fingers. DAB = Dorsals ABduct.
Palmar i nterosseous muscles-adduct the PAD= Palmars ADduct.
Fingers.
Hypothenar Lumbrical muscles-flex at the MCP joint,
eminence extend PI P and DIP joints.
3 84 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECT IVE TISSUE ANATOM Y AND PHYSI OLOGY
Lower extremity nerves

NERVE CAUSE OF INJURY MOTOR DEFICIT SENSORY DEFICIT
Obturator (L2-L4) Anterior hip dislocation Thigh adduction Medial thigh

Femoral (L2-L4) Pelvic fracture Thigh flexion and leg extension Anterior thigh and medial leg
Common peroneal Trauma or compression of Foot eversion and dorsiflexion; Anterolateral l e g and dorsal
(L4-S2) lateral aspect of leg or fibula toe extension; foot drop, foot aspect of foot
neck fracture slap, steppage gait
Tibial (L4-S3) Knee trauma Foot inversion and Sole of foot
plantarflexion; toe flexion
Superior gluteal Posterior hip dislocation or Th igh abduction (positive
(L4-S1) polio Trendelenbur g sign
contralateral hip drops when
standing on leg ipsilateral to
site of lesion)
Inferior gluteal Posterior hip dislocation Can' t j ump, climb stairs, or rise
(LS-52) from seated position; can't
push inferiorly (downward)
PED= Peroneal Everts and Dorsifl.exes; if inj ured, foot dropPED.
T IP= Tibial Inverts and Plantarfl.exes; if inj ured, can't stand on T I Ptoes.
Sciatic nerve ( L4-S3)-posterior thigh, splits into common peroneal and tibial nerve .
MUSCULOSKELE TAL, SKIN, AND CONNE CTIVE T ISSUE ANATOM Y AND PHYSIOLOGY SECTION Ill 385
Muscle condudion to contradion
A.
Ryanodine receptor
Dihydropyridine receptor
T-tubule membrane
e'ta2 +
:::tU

: } sarcoplasmic
reticulum
B.
Plasma membrane
Sarcomere
A band
.____ _ _ _ _
_,ll I band
u
H band
(Reproduced, with permission, from USMLE-Rx.com.)
Muscle contraction
l. Action potential depolarization opens presynaptic voltage-gated Ca 2 + channels, i nducing neur otransm itter release.
2. Postsynaptic l igand binding leads to muscle cell depolarization i n the motor end plate .
3. Depolarization travels along muscle cell a n d clown the T tubule.
4. Depolarization of the voltage-sensitive dihydropyridine receptor, mechanically coupled to the ryanodine receptor on the
sarcoplasmic reticulum, i nduces a conformational change causing Ca 2 + release from sarcoplasmic reticulum.
5. Released Ca 2 + binds to troponin C, causing a conformational change that moves tropomyosin out of the myosin-binding
groove on actin filaments.
6. Myosin releases bound ADP and is d isplaced on the actin filament (power stroke ) . C ontraction results i n shortening of H
and I bands and between Z l i nes (H IZ shrinkage), but the A band remains the same length (A band is Always the same
length ) .
Types of muscle fibers

Type 1 muscle Slow twitch; red fibers resulting from Think "1 slow red ox. "
t m itochondria and myoglobin concentration
(t oxidative phosphorylation) sustained
-+
contraction.
Type 2 muscle Fast twitch; white fibers resulting from
l m itochondria and myoglobin concentration
(t anaerobic glycolysis); weight training results
in hypertrophy of fast-twitch muscle fibers.
386 SECTION Ill MUSCULOSKELE TAL, SKI N, AND CONNECT I VE TISSUE ANATOM Y AND PHYSI OLOGY
Skeletal and cardiac muscle contraction
2+
Ca binds to troponin c.
causing conformational
change. This displaces
tropomyosin and P1 is released, changing myosin head
/f)
:''"' """'""'
act;n/myos;n cycling.
Cross-bridged state
Actin ;< opomyos1n
0
Cocked state - Power-stroke state
ATP hydroly;< =

myosin he
Released state
Bone formation
Endochondral Bones of axial and append icular skeleton, and base of the skull. Cartilaginous model of bone is
ossification fi rst made by chondrocytes. Osteoclasts and osteoblasts later replace with woven bone and then
remodel to lamellar bone. In adults, woven bone occur s after fractures and i n Paget's disease.
Membranous Bones of calvarium and facial bones. Woven bone formed d i rectly without cartilage. Later
ossification remodeled to lamellar bone.
Cell biology of bone
Osteoblasts Build bone by secreting col lagen and catalyzing m i nerali zation . Differentiate from mesenchymal
stem cells in periosteum.
Osteoclasts Multinucleated cells that di ssolve bone by secreting acid and collagenases. D i fferentiate from
monocytes/macrophages.
Parathyroid hormone At low, interm ittent levels, exerts anabol ic effects (building bone) on osteoblasts and osteoclasts
(indirect) . Chronic high PTH levels (primary hyperparathyroidism) cause catabol ic effects
(osteitis fibrosa cystica) .
Estrogen Estrogen inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing
osteoclasts. Under estrogen deficiency (surgical or postmenopausal ) , excess remodel i n g cycles and
bone resorption lead to osteoporosis.
MUSC ULOSKELETAL, SKIN, AND CONN E CTIVE TISSUE PAT H OLOG Y SECTION Il l 5 () I
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE-PATHOLOGY
Achondroplasia Fa ilure of longitud inal bone growth (endochondral ossi fication)-+ short l i mbs. Membranous
ossification is not affected-+ large head relative to l imbs. Con stitutive activation of fibroblast
growth factor receptor ( FGFR3) actually inh ibits chondrocyte prol i feration . > 85% of mutations
occur sporadically and are associated with advanced paternal age, but the condition also
demonstrates autosomal-dom inant inheritance. Common cause of dwarfism. Normal l i fe span
and fertil ity.
Osteoporosis Trabecular (spongy) bone loses mass and intercon nections despite normal bone m ineralization and
lab values (serum Ca 2 + and P0 43-) .
Can lead to vertebral crush fractures-acute back pain, loss of height, kyphosis.
Type I Postmenopausal: t bone resorption due to Femoral neck fracture, d istal radius (Colles' )
! estrogen levels. fractures.
Type II Senile osteoporosi s : affects men and women > Prophylaxis: regular weight-bearing exercise
70 years of age. and adequate calcium and vita m i n 0 intake
throughout adulthood.
Treatment: estrogen ( SERMs) and/or calcitonin;
bisphosphonates or pulsatile PTH for severe
cases. Glucocorticoids are contraindicated.
Mild compression fracture Normal vertebrae
Osteopetrosis Failur e of normal bone resorption due to defective osteoclasts -+ thickened, dense bones that are
(marble bone disease) prone to fracture. Bone fills marrow space, causing pancytopen ia, extramedullary hematopoiesis.
Mutations (e.g., carbonic anhydrase II) impair abil ity of osteoclast to generate acidic environment
necessary for bone resorption. X-rays show bone-in-bone appearance. Can result i n cranial nerve
impingement and palsies as a result of narrowed foramina. Bone m arrow transplant is potentially
curative as osteoclasts are derived from monocytes.
Osteomalacia/rickets Vita m i n 0 deficiency. Osteomalacia in adults; rickets i n ch ildren. Due to defective m ineralization/
calcification of osteoid -+ soft bones that bow out. ! vita m i n 0- ! serum calciu m- t PTH
secretion - ! serum phosphate. Hyperactivity of osteoblasts -+ t alkaline phosphatase (osteoblasts
require alkal ine environment) .
Paget's disease of bone Common, localized disorder of bone Hat size can be t; hearing loss is common due
(osteitis deformans) remodel ing caused by t in both osteoblastic to auditory foramen narrowing.
and osteoclastic activity. Seru m calcium,
phosphorus, and PTH levels are normal.
t ALP. Mosaic ( "woven") bone pattern; long
bone chalk-stick fractures. t blood flow from
t arteriovenous shunts may cause high-output
heart failure. t risk of osteogenic sarcoma.
388 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECT I VE T ISSUE PATHOLOGY
Lab values in bone disorders

SERUM Ca2 PHOSPHATE ALP PTH COMMENTS
Osteoporosis bone mass

Osteopetrosis t Thickened, dense bones
Osteomalacia/rickets t Soft bones
Osteitis fibrosa cystica "Brown tumors" of hyperparathyroidism
Paget's disease Abnormal bone architectur e
Polyostotic fibrous Bone i s replaced b y fibroblasts, collagen, and irregular bony trabeculae. McCune-Albright syndrome
dysplasia is a form of polyostotic fibrous dysplasia characterized by multiple unilateral bone lesions
associated with endocrine abnormalities (precocious puberty) and cafe-au-lait spots.
MUSCULOSKELETAL, SKI N, AND CONNECTIVE TISSUE PATHOLOGY SECTION Ill 389
Primary bone tumors

TUMOR TYPE EPIDEMIOLOGY/LOCATION CHARACTERISTICS
Benign tumors
Giant cell tumor 20-40 years of age. Locally aggressive benign tumor often around
(osteoclastoma) Epiphyseal end of long bones. the d i stal femur, proximal tibial region (knee) .
" Double bubble" or "soap bubble" appearance
on x-ray.
Spindle-shaped cells with multinucleated giant
cells.
Osteochondroma Most common benign tumor. Males < 25 years Matur e bone with cartilaginous cap. Commonly
(exostosis) of age. originates from long metaphysis. Mal ignant
transformation to chondrosarcoma is rare.
Malignant tumors
Osteosarcoma 2nd most common l o malignant bone tumor Cadman's triangle (from elevation of
(osteogenic sarcoma) (after multiple myeloma) . periosteum) or sunburst pattern on x-ray.
Male > female, 1 0-20 years of age 00). Aggressive. Treat with surgical en bloc resection
Predisposing factors: Paget's disease of (with l i mb salvage) and chemotherapy.
bone, bone infarcts, radiation, familial
retinoblastoma.
Metaphysis of long bones, often around d istal
femur, proximal tibial region (knee) .
Ewing's sarcoma Boys < 1 5 years of age. Anaplastic small blue cell mal ignant tumor.
Commonly appears in diaphysis of long bones, Extremely aggressive with early metastases, but
pelvis, scapula, and ribs. responsive to chemotherapy.
"Onion skin" appearance in bone ( "goi ng out for
Ewings and onion rings" ) .
Associated with t(ll;22) translocation.
ll + 22 33 ( Patrick Ewing's jersey number) .
=
Chondrosarcoma Men 30-60 years of age. Usually located in Mal ignant cartilaginous tumor.
pelvis, spine, scapula, humerus, tibia, or May be of l o origin or from osteochondroma.
femur. Expansile gl isten ing mass within the medullary
cavity.
Giant cell tumor

(soap bubble)
[J
Benign
Mongooot
--.......,_ Osteosarcoma
--=--=----
(Godman's triangle)
L_________________________
Epiphysis Metaphysis Diaphysis Metaphysis Epiphysis
I
390 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECTIVE T ISSUE PATHOLOGY
Osteoarthritis and rheumatoid arthritis

Osteoarthritis Rheumatoid arthritis
ETIOLOGY Mechan ical-j oint wear and tear destroys Autoimmune-inflammatory destruction of
articular cartilage synovial joints. 1ype I I I hypersensitivity.
JOINT FINDINGS Subchondral cysts, sclerosis [J, osteophytes Pannus formation in joi nts (MCP, PI P),
(bone spurs), eburnation (pol ished, ivory subcutaneous rheumatoid nodules (fibrinoid
l ike appearance of bone), Heberden's nodes necrosis), ulnar deviation of fingers,
( D I P), and Bouchard's nodes ( PI P) . No MCP subluxation (I), Baker's cyst ( i n popl iteal fossa) .
i nvolvement. No DIP i nvolvement.
PREDISPOSING FACTORS Age, obesity, joint deform ity Females > males. 80% have positive rheumatoid
factor (anti-IgG antibody); anti-cycl ic
citrul l inated peptide antibody is more specific.
Strong association with H LA-D R4.
CLASSIC PRESENTATION Pai n i n weight-bearing joints after use (e.g., at Morning stiffness lasting > 30 m inutes
the end of the day), improving with rest. Knee and i mproving with use, symmetric joint
cartilage loss begins medially (" bowlegged " ) . involvement, systemic symptoms (fever,
Noninflammatory. N o systemic symptoms. fatigue, pleuritis, pericard itis) .
TREATMENT NSAIDs, i ntra-articular glucocorticoids NSAI Ds, glucocorticoids, d isease-modifying
agents (methotrexate, sulfasalazine, TNF-a
inh ibitors)
Normal Osteoarthritis Normal R heumatoid
arthritis
-----Thickened capsule
y::;:, '.
/ Slight synovial
Joint capsule
and synovial '\
/ hypertrophy Joint capsule
and synovial '\ l
lining lining ,. ; ,
-Osteophyte --- Increased
Synovial _/ Synovial _/
cavity """ Ulcerated cartilage cavity /
synovial fluid
------Pannus
Cartilage / \

Sclerotic bone
Joint space narrowing

Cartilage .../ formation
Subchondral bone cyst
Osteoarthritis. X-rays of the knee show joint space

narrowing and sclerosis (arrows).(!! digits with ulnar deviation.
MUSCULOSKELE TAL, SKIN, AND CONNECTIVE TISSUE PATHOLOGY SECTION Ill 391
Sjogren's syndrome Lymphocytic i n filtration of exocrine glands, Predom i nantly affects females between 40 and
especially lacrimal and salivary. 60 years of age.
Classic triad: Associated with rheumatoid arth ritis.
Xerophthalmia ( cl ry eyes, conjunctivitis,
"sand in my eyes")
Xerostomia (dry mouth, dysphagia)
Arthritis
Parotid enlargement, t risk of B-cell

lymphoma, dental caries. Autoantibod ies to
ribonucleoprotein antigens: SS-A ( Ro), S S-B
(La) .
Gout
FINDINGS Precipitation of monosodium urate crystals i nto
joints rJ clue to hyperuricem ia, which can
be caused by Lesch-Nyhan syndrome, PRPP
excess, excretion of uric acid (e.g., thiazide
diuretics), t cell turnover, or von Gierke's
d isease. 90% clue to unclerexcretion; 1 0 % cl u e
to overproduction . Crystals are needle shaped
and negatively birefringent= yellow crystals
under parallel l ight. More common in men.
SYMPTOMS Asymmetric joint distribution . Joint is swollen,
reel, and painful [l]. Classic manifestation is
painful MTP joint of the big toe (podagra).
Tophus formation (often on external ear,
olecranon bursa, or Ach illes tendon) . Acute
attack tends to occur after a large meal or
alcohol consumption (alcohol metabol ites
compete for same excretion sites in kidney as
uric acid, causing uric acid secretion and
subsequent buildup in blood).
TREATMENT Acute: NSAIDs (e.g., i ndomethacin),
glucocorticoicls.
Chronic: xanth ine oxidase inhibitors (e.g.,
allopur i nol, febuxostat) .
Gout. Left b i g toe (podagra) is swollen and red. D
Pseudogout Caused by deposition of calcium pyrophosphate crystals with i n the joint space. Forms basoph il ic,
rhomboid crystals that are weakly positively birefringent. Usually affects large joi nts (classically the
knee) . > 50 years old; both sexes affected equal ly. Treatment i ncludes NSAIDs for sudden, severe
attacks; steroids; and colch icine.
Gout-crystals are yellow when parallel (II) to the light.
Pseucl o gout-crystals are blue when parallel (II) to the l ight.
392 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE PATHOLOGY
lnfedious arthritis S. aureus, Streptococcus, and Neisseria gonorrhoeae are common causes. Gonococcal arthritis is an
ST D that presents as a m igratory arthritis with an asymmetric pattern. Affected joint is swollen,
reel, and painful. ST D = Synovitis (e.g., knee), Tenosynovitis (e.g., hand), and Dermatitis (e.g.,
pustules) .
Osteonecrosis Infarction of bone and marrow. Pa in associated with activity. Caused by trauma, high-close
(avascular necrosis) corticosteroids, alcohol ism, sickle cell. Most common site is femoral head.
Seronegative Arthritis without rheumatoid factor (no anti-IgG PAIR

spondyloarthropathies antibody) . Strong association with H LA-B27
(gene that codes for l-ILA MHC class I ) .
Occur s more often in males.
Psoriatic arthritis Joint pain and stiffness associated with psoriasis.
Asymmetric and patchy involvement.
Dactyl itis ( "sausage fingers" ) , "pencil-in-cup"
deformity on x-ray. Seen in fewer than 1/3 of
patients with psoriasis.
Ankylosing spondylitis Chronic inAammatory disease of spine and Bamboo spine (vertebral fusion) .
sacroil iac joints-+ ankylosis (stiff spine
clue to fusion of joints), uveitis, and aortic
regurgitation.
Inflammatory bowel Crohn's d isease and ulcerative colitis are often accompanied by anklyosing spondyl itis or peripheral
disease arthritis.
Reactive arthritis Cl assic triad: "Can't see, can't pee, can't climb a tree."
(Reiter's syndrome) Conjunctivitis and anterior uveitis Post-GI or chlamydia infections.
Urethritis
Arthritis
MUSCULOSKELETAL , SKIN, AND CONNECTIVE T ISSUE PATHOLOGY SECTION Ill 393
Systemic lupus 90% are female and between ages 14 and 45. I'M DAMN SHARP:
erythematosus Most common and severe in black females. Immunoglobu l i ns (anti-clsD A, anti-Sm,
Presentation can i nclude fever, fatigue, weight antiphosphol ipicl)
loss, Libman-Sacks endocarditis (verrucous, Malar rash fJ
wart-l ike, sterile vegetations on both sides Discoid rash
of valve), hilar adenopathy, and Raynaucl's Antinuclear a ntibody
phenomenon . Mucositis (oropharyngeal ulcers)
Nephritis is common cause of death in SLE. Neurologic d isorders
Diffuse prol iferative glomerulonephritis (if Serositis (pleur itis, pericarditis)
nephritic); membranous glomerulonephritis (if Hematologic d isorders
nephrotic) . Arth ritis
False positives on syphilis tests ( R PR/VDRL) Renal d isorders
clue to antiphosphol ipicl antibod ies, which Photosen sitivity
cross-react with card iol ipin used in tests. Lab
tests detect presence of:
Antinuclear antibodies (A A) -sensitive,
(primary screeni ng) but not specific for SLE
Antibodies to clouble-stranclecl DNA (anti
clsDNA) -very specific, poor prognosis

Anti-Sm ith antibodies (anti-Sm)-very
specific, but not prognostic

Anti histone a ntibod ies-more sensitive for
dru g-induced lupus
Sarcoidosis Characterized by i mmune-med iated, widespread

noncaseating granulomas r.J and elevated
serum ACE levels. Common in black females.
Often asymptomatic except for enlarged lymph
node. I ncidental findings on CXR of bilateral
hilar adenopathy or reticular opacities.
Associated with restrictive lung d isease
(i nterstitial fibrosis), erythema noclosum,
Bel l 's palsy, epithel ial granulomas containing
m icroscopic Schaumann and asteroid bodies,
uveitis, and hypercalcemia (cl u e to elevated
l a-hyclroxylase-mecl iatecl vitamin D activation
i n epithel ioid macrophages ) .
Treatment: steroids.
Polymyalgia rheumatica
SYMPTOMS Pai n and stiffness in shoulders and hips, often with fever, malaise, and weight loss. Does not cause
muscular weakness. More common in women > 5 0 years of age; associated with temporal (giant
cell) arteritis.
FINDINGS f ESR, normal CK.
TREATMENT Rapid response to low-close corticosteroids.
394 SECTION Ill MUSCULOSKELETAL, SK IN, AND CONNECTIVE T ISSUE PATHOLOGY
Fibromyalgia Most commonly seen in women 20-5 0 years of age. Chronic, widespread musculoskeletal pain
associated with stiffness, paresthesia, poor sleep, and fatigue.
Polymyositis/ dermatomyositis
SYMPTOMS Polymyositis-progressive symmetric proximal
muscle weakness, characterized by endomysia!
inflammation with CDS+ T cells. Most often
i nvolves shoulders .
Dermatomyositis-similar to polymyositis,
but also i nvolves malar rash (similar to SLE) ,
Gottron's papules rJ, hel iotrope rash (1],
"shawl and face" rash , "mechan ic's hands."
t risk of occult malignancy. Perimysial
inflammation a nd atrophy with CD4+ T cells.
FINDINGS t CK, positive ANA, positive anti-Jo-1

antibodies.
TREATMENT Steroids.
Neuromuscular jundion diseases

Myasthenia gravis Lambert-Eaton myasthenic syndrome
FREQUENCY Most common NMJ disorder Uncommon
PATHOPHYSIOLOGY Autoantibodies to postsynaptic ACh receptor Autoantibodies to presynaptic Ca 2 + channel
-+ ! ACh release
CLINICAL Ptosis, diplopia, weakness Proximal muscle weakness
Worsens with muscle use Improves with muscle use
ASSOCIATED WITH Thymoma, thym ic hyperplasia Small cell lung cancer
AChE INHIBITOR Reversal of symptoms No effect
A DMINISTRATION
Myositis ossificans Metaplasia of skeletal muscle to bone following

muscular trauma fJ. Most often seen in upper
or lower extremity. May present as suspicious
"mass" at site of known trauma or as incidental
findi ng on radiography.
Myositis ossificans. Heterotopic ossification of elbow after

injury.D
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE PATHOLOGY SECTION Ill 39 5
Scleroderma (systemic Excessive fibrosis and collagen deposition

sclerosis) throughout the body. Commonly sclerosis
of ski n , man ifesting as puffy and taut skin
with absence of wrinkles. Also sclerosis of
renal, pulmonary (most likely cause of death) ,
cardiovascular, and GI systems. 75% female. 2
major types:
Diffuse scleroderma widespread skin-
i nvolvement, rapid progression, early

visceral i nvolvement. Associated with anti
Scl-70 antibody (anti-DNA topoisomerase I Scleroderma. Note "tightening" of skin with ulceration
antibody) . (arrows).
C REST syndrome- Calcinosis, Raynaud's

phenomenon , Esophageal dysmotility,
Sclerodactyly, and Telangiectasia. Lim ited
ski n i nvolvement, often confined to fingers
and face. More ben ign clinical course.
Associated with antiCentromere antibody
( C for CREST) .
Dermatologic macroscopic terms (morphology)

LESION CHARACTERISTICS EXAMPLES
Macule Flat lesion with well-ci rcumscribed change in Freckle, labial macule
skin color < 5 m m
Patch M acule > 5 mm Large birthmark (congen ital nevus) [J
Papule Elevated solid skin lesion < 5 mm Mole (nevus) f], acne
Plaque Papule > 5 m m Psoriasis [!]
Vesicle Small fluid-conta ining blister < 5 m m Chickenpox (varicella), shingles (zoster) I]
Bulla Large fluid-conta ining blister > 5 mm Bullous pemph igoid I]
Pustule Vesicle containing pus Pustular psoriasis[!)
Wheal Transient smooth papule or plaque Hives (ur ticaria) C1
Scale Flaking off of stratum corneum Eczema, psoriasis, sec D
Crust Dry exudate I mpetigo 0
/ll!J Courtesy of Dr. Richard P. Usatine and the Color Atlas of Family Medicine (www.usatinemedia.com).
39 6 SECTION Ill MUSCULOSKELE TAL, SKIN, AND CONNECTIVE T ISSUE PATHOLOGY
Dermatologic microscopic terms

LESION CHARACTERISTICS EXA MPLES
Hyperkeratosis t thickness of stratum corneum Psoriasis

Parakeratosis Hyperkeratosis with retention of nuclei i n Psoriasis
stratum corneum
Acantholysis Separation of epidermal cells Pemph igus vulgaris
Acanthosis Epidermal hyperplasia (t spinosum) Acanthosis nigricans
Dermatitis I n fl ammation of the skin Atopic dermatitis
Pigmented skin disorders

Albinism Normal melanocyte number with ! melanin production clue to ! tyrosinase activity [J. Can also be
caused by fai lure of neural crest cell migration during development.
Melasma (chloasma) Hyperpigmentation associated with pregnancy ( "mask of pregnancy") or OCP use (IJ.
Vitiligo I rregular areas of complete depigmentation I]. Caused by a ! i n melanocytes.
'
MUSCULOSKELETAL, SKIN, AND CONNECTIVE T ISSUE PATHOLOG Y SECTION Ill 3 97
Common skin disorders

Verrucae Warts ; caused by HPV. Soft, tan-colored, caul iflower-l ike papules r.J. Epidermal hyperplasia,
hyperkeratosis, koi locytosis. Condyloma acuminatum on genitals Q.
Melanocytic nevus Com mon mole . Benign, but melanoma can arise i n congen ital or atypical moles. I ntradermal nevi
are papular [!1. Junctional nevi are flat macules rn.
Urticaria Hives. Prur itic wheals that form after mast cell degranulation (].
Ephelis Freckle. ormal number of melanocytes, t melanin pigment ll
Atopic dermatitis Prur itic eruption, commonly on skin flexures. Often associ ated with other atopic diseases (asthma,
(eczema) al lergic rh i n itis) . Usually starts on the face in infancy [!I and often appears i n the antecubital
fossae Cl thereafter.
Allergic contact Type IV hypersensitivity reaction that follows exposure to allergen. Lesions occur at site of contact
dermatitis (e.g., n ickel 0, poison ivy, neomycin 0) .
Psoriasis Papules and plaques with silvery scaling, especially on knees and elbows. Acanthosis with
parakeratotic scaling (nuclei still in stratum corneum ) . t stratum spinosum , stratum
granulosum. Auspitz sign 1!J - pinpoint bleeding spots from exposur e of dermal papillae when
scales are scraped off. Can be associated with nail pitting and psoriatic arthritis [!.
Seborrheic keratosis Flat, greasy, pigmented squamous epithel ial prol iferation with keratin-filled cysts (horn cysts) [i!J.
Looks "stuck on" m. Lesions occur on head, trunk, and extrem ities. Common benign neoplasm
of older persons.
Leser-Trelat sign - sudden appearance of multiple seborrheic keratoses, indicating an underlying
mal i gnancy (e.g., GI, lymphoid) .
3 Cj (3 SECTION Il l MUSCU LO S KE LETA L , S KIN, AND C ONNECTIVE TISSUE PAT H O LOG Y
Blistering skin disorders
Pemphigus vulgaris Potentially fatal autoimmune skin disorder

with IgG antibody against desmoglein 3 ( l
and/or 3 ) , a part of the desmosomes (needed
for cell adhesion ) . Immunofluorescence
reveals antibodies around epidermal cells in
a reticular or netl ike pattern. Acantholysis
i ntraepidermal bullae causing flaccid blister
fJ i nvolving the skin and oral mucosa . Positive
Nikolsky's sign (separation of epiderm is upon
manual stroking of skin).
Pemphigus vulgaris. Note multiple crusty and weepy

erythematous erosions where blisters have broken. li!l
Bullous pemphigoid Autoimmune disorder with IgG antibody

aga inst hem idesmosomes (epidermal basement
membrane ; antibodies are " bullow" the
epidermis); shows l i near immunofluorescence.
Eosinoph ils with in tense blisters [l]. Siinilar
to but less severe than pemph igus vulgaris
affects skin but spares oral mucosa . Negative
Nikolsky's sign.
Dermatitis Pruritic papules, vesicles, and bullae [).

herpetiformis Deposits of IgA at the tips of dermal papillae.
Associated with celiac disease.
Dermatitis herpetiformis. Vesicles and bullae are often

found on elbows. D
MUSCULOSKELE TAL, SKI N, AND CONNECTIVE TISSUE PATHOLOG Y SECTION Ill 399
Blistering skin disorders (continued)

Erythema multiforme Associated with infections (e.g., Mycoplasma
pneumoniae, HSV), drugs (e.g., sulfa
drugs, -lactams, phenytoin), cancers, and
autoimmu n e disease. Presents with multiple
types of lesions- macules, papules, vesicles,
and target lesions ( look l ike targets with
multiple rings and a dusky center showing
epithelial disruption) [!].
Erythema multiforme. Note target lesions in patient with

erythema multiforme secondary to H SV. !il!J
Stevens-Johnson Characterized by fever, bulla formation and

syndrome necrosis, slough ing of skin, and a h igh
mortality rate . Typically 2 mucus membranes
are i nvolved (] and ski n lesions may be appear
l ike targets as seen in erythema multiforme.
Usually associated with adverse drug reaction.
A more severe form of Stevens-Johnson
syndrome with > 30% of the body surface area
i nvolved is toxic epidermal necrolysis () [!1.
Toxic epidermal necrolysis. Large bullae led to skin

sloughing. !il!J
400 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE PATHOLOGY
Miscellaneous skin disorders

Acanthosis nigricans Epidermal hyperplasia causing symmetrical,
hyperpigmented, velvety thicken ing of skin,
especially on neck or in axilla [J. Associated
with hyperinsul inemia (e.g., diabetes, obesity,
Cushing's syndrome) and visceral mal ignancy.
Acanthosis nigricans. Note multiple skin tags on left lll1l.

and velvety appearance on right lll!J.
Actinic keratosis Premal ignant lesions caused by sun exposure.

Small, rough, erythematous or brown ish
papules or plaques (I). Risk of squamous
cell carcinoma is proportional to degree of
epithel ial dyspl asia.
Actinic keratosis. Biopsy-proven AK in case of suspeded

early skin cancer (left). lll!l Multiple AKs on hands and
forearms (right) . {ll!J
Erythema nodosum Inflammatory lesions of subcutaneous

fat, usually on anterior shins. Associated
with sarcoidosis, coccidioidomycosis,
h istoplasmosis, TB, streptococcal infections,
leprosy, and Crohn's disease 0.
Erythema nodosum Lesions on leg in patient with

streptococcal infedion (left) lll!l and patient with leprosy and
erythema nodosum leprosum (right). lll!l
M USCULOSKELETAL , SKIN, AND CONNECTIVE TISSUE PATHOLOGY SECTION Ill 40 1
Miscellaneous skin disorders (continued)

Lichen Planus Pruritic, Purple, Polygonal Planar Papules
and Plaques are the 6 P's of l ichen planus.
(!] Sawtooth infiltrate of lymphocytes at
dermal-epidermal junction . Associated with
hepatitis C .
Lichen planus. Appearance o n light skin (left) 1ll!l and dark

skin (right). 1ll!l
Pityriasis rosea "Herald patch " fol lowed clays later by

"Christmas tree" d istribution 1]. Multiple
plaques with collarette scale. Self-resolving in
6-8 weeks.
Pityriasis rosea. Herald patch (left, arrow) !il!l and

Christmas tree distribution (right). !il!l
Sunburn UV irradiation causes DNA mutations,

inducing apoptosis of keratinocytes. UVA is
dominant i n tanning and photoaging, UVB
i n sunburn . Can lead to impetigo I] and ski n
cancers ( basal cell carcinoma, squamous cell
carcinoma, and melanoma).
402 SECTION I l l MUSCULOSKELETAL, SKI N , AND CO N N ECTIVE TISSUE PATHOLOG Y
lnfedious skin disorders
Impetigo Very superficial skin infection. Usually from S. aureus o r S. pyogenes. H ighly contagious. Honey
colored crusting a.
Bullous impetigo [I) has bullae and is usually caused by S. aureus.
Cellulitis Acute, painfu l , spreading infection of derm is and subcutaneous tissues. Usually from S. pyogenes or
S. aureus. Often starts with a break in skin from trauma or another infection fit.
Necrotizing fasciitis Deeper tissue inj ury, usually from anaerobic bacteria or S. pyogenes. Results in crepitus from
methane and C02 production. "Flesh-eating bacteria." Causes bullae and a purple color to the
skin [!].
Staphylococcal Exotoxin destroys keratinocyte attachments in the stratum granulosum only (vs. toxic epidermal
scalded skin necrolysis, which destroys the epidermal-dermal junction ) . Characterized by fever and
syndrome (SSSS) generalized erythematous rash with sloughing of the upper layers of the epidermis that heals
completely. Seen in newborns and children I].
Hairy leukoplakia Wh ite, painless plaques on the tongue that can not be scraped off. EBV mediated . Occurs in
I-I IV-positive patients ().
M U S CULO SKE LETA L, SKIN, AND CONNECTIVE TIS SUE PATHO LOGY S E CT I O N I l l 403
Skin cancer
Basal cell carcinoma Most common ski n cancer. Found in sun-exposed areas of body. Locally i nvasive, but al most never
metastasizes. Pink, pearly nodules, commonly with telangiectasias, rolled borders, and central
crusting or ulceration rJ. BCCs also appear as non healing ulcers with infiltrating growth rn or as
a scal ing plaque (superficial BCC ) [3. Basal cell tumors have "palisadi ng" nuclei [!].
Basal cell carcinoma. Appearance includes rolled borders, : nonhealing ulcer, or

basaloid cells in dermis with peripheral "palisading:'
Squamous cell Second most common skin cancer. Associated with excessive exposure to sunl ight,
carcinoma immunosuppression , and occasionally arsen ic exposure. Commonly appears on face (],
lower lip ll ears, and hands. Locally i nvasive, but may spread to lymph nodes and will rarely
metastasize. Ulcerative red lesions with frequent scale. Associated with chronic d rain ing si nuses.
H istopathology: keratin "pearls" [3.
Acti n i c keratosis, a scaly plaque, is a precursor to squamous cell carcinoma.
Keratoacanthoma is a variant that grows rapidly (4-6 weeks) and may regress spontaneously over
months Cl
Melanoma Common tumor with significant risk of metastasis. S - 1 0 0 tumot marker. Associated with sunlight
exposur e ; fa i r-skinned persons are at t risk. Depth of tumor correlates with risk of metastasis.
Look for the ABCDEs : Asymmetry, B order irregularity, C olor variation, D iameter > 6 m m , and
Evolution over time. At least 4 different types of melanoma 0 0 1!1 (). Often driven by activating
mutation i n B RAF kinase. Primary treatment is excision with appropriately wide margins.
Metastatic or unresectable melanoma i n patients with BRAF V60 0 E mutation may benefit from
vemurafen ib, a BRAF kinase inh ibitor.
Melanoma. M ultiple variants, incl uding superficial spreading melanoma

acrolentiginous melanoma
404 SECTION Ill MUSCULOSKELETAL, SKIN, AND CONNECTIVE T ISSUE PHAR M ACOLOGY
M U S C U LOS K EL E TAL, S K I N , AN D C O N N E C T I V E TI S S U E - PHAR M ACOLOGY
Arachidonic acid Lipoxygenase pathway yields Leukotrienes. L for Lipoxygenase and Leukotriene.
products LT B 4 is a neutrophil chemotactic agent. Neutrophils arrive " B4" others.
LTC 4 , 0 4 , and E4 function in
bronchoconstriction, vasoconstriction ,
contraction of smooth muscle, and t vascular
permeabil ity.
PGI 2 inhibits platelet aggregation and promotes Platelet-Gathering Inhibitor.
vasod ilation.
Membrane lipid (e.g . , phosphatidylinositol)
N SAI DS, aspirin,

acetaminophen,
Hydroperoxides Endoperoxides COX-2 inhibitors
(HPET Es) (PGG2, PGH2)
t
1 / ( j omboxane

Leu ko enes Prostacycli
(LT B4) (LTC4 . LT D4)
- =! (PG I 2) A(TX 2)
J
Prostaglandins
.)
(PGE2, PGF2a)
+
It Bronchial tone I t Platelet aggregation t Uterine tone t Platelet aggregation
----
t Vascular tone t Vascular tone t Vascular tone

t Bronchial tone t Bronchial tone t Bronchial tone
t Uterine tone
.
{Ada pted, with permission, from Katzung BG, Trevor AJ. Pharmacology: Examination & Board Review, 5th ed. Sta mford,
CT: Appleton & Lange, 1 998: 1 5 0 )
Aspirin
MECHANISM Irreversibly inh ibits cyclooxygenase (both COX- I and C OX-2 ) by acetylation, which synthesis of
both thromboxane A 2 (TXA 2 ) and prostaglandins. t bleed ing time. No effect on PT, PTT. A type
of NSAID.
CLINICAL USE Low close (< 300 mg/clay) : platelet aggregation. Intermediate close ( 3 0 0 -240 0 mg/clay) : antipyretic
and analgesic. H igh close (2400-4000 mg/clay) : anti-inflammatory.
TOXICITY Gastric ulceration, tinn itus (CN V I I I ) . Chron ic use can lead to acute renal fa i lure, interstitial
nephritis, and upper GI bleeding. Risk of Reye's syndrome i n children treated with aspirin for
viral infection . Also stimulates respiratory centers, causing hyperventilation and respiratory
alkalosis.
M USCULOSKELETAL, SKI N, AND CONNECTIVE TISS U E PHA R M ACOLO G Y SECT ION Ill 40 5
NSAI Ds I buprofen, naproxen, indomethacin, ketorolac, diclofenac.

MECHANISM Reversibly inhibit cyclooxygenase (both COX- 1 and C OX-2 ) . Block prostaglandin (PC) synthesis.
CLINICAL USE Antipyretic, analgesic, anti-inflam matory. Indomethacin is used to close a PDA.
TOXICITY I nterstitial neph ritis, gastric ulcer ( PGs protect gastric mucosa ) , renal ischemia ( PGs vasodilate
afferent arteriole) .
COX-2 inhibitors (celecoxib)

MECHANISM Reversibly inhibit specifically the cyclooxygenase (COX) isoform 2 , which is found in inflammatory
cells and vascular endothelium and med iates inflammation and pain; spares COX- 1 , which helps
mainta i n the gastric mucosa. Thus, should not have the corrosive effects of other NSAIDs on the
GI l i n ing. Spares platelet function as TXA 2 production is dependent on COX- I .
CLINICAL USE Rheumatoid arthritis and osteoarthritis; patients with gastritis o r u lcers.
TOXICITY t risk of thrombosis. Sulfa allergy.
Acetaminophen
MECHANISM Reversibly inh ibits cyclooxygenase, mostly in C N S . Inactivated peripherally.
CLINICAL USE Antipyretic, a nalgesic, but not anti-inflammatory. Used i nstead of aspirin to avoid Reye's syndrome
i n children with viral infection .
TOXICITY Overdose produces hepatic necrosis; acetami nophen metabol ite depletes glutathione and forms
toxic tissue adducts i n l iver. N-acetylcysteine is antidote - regenerates glutath ione.
Bisphosphonates Alendronate, other -d ronates.

MECHANISM Pyrophosphate analogs; bind hydroxyapatite in bone, inh ibiti ng osteoclast activity.
CLINICAL USE Osteoporosis, hypercalcemia, Paget's d isease of bone.
TOXICITY C orrosive esophagitis, osteonecrosis of the jaw.
4 () b S E CT I O N I l l M USCULOSK E L E TAL, S K I N, AND C ONN E C T I V E T I SSUE PHAR M ACOLOG Y
Ciout drugs
Chronic gout drugs
Allopurinol I n h ibits xanthine oxidase, conversion of Diet --- Purines -- Nucleic acids
xanth ine to uric acid. Also used in lymphoma l
and leukemia to prevent tumor lysis
>
Hypoxanthine
associated urate nephropathy. t concentrations
of azathioprine and 6-MP (both normally l Xanthine
oxidase
metabolized by xanth ine oxidase) .
Xanthine Allopurinol
Do not give sal icylates; all but the highest
closes depress uric acid clearance. Even h igh
l Xanthine
oxidase
closes ( 5 -6 g/clay) have only m inor uricosuric Plasma --- Urate crystals --- Gout
activity. uric acid deposited
in j oints
Febuxostat Inh ibits xanthine oxidase.
Probenecid Inh ibits reabsorption of uric acid in PCT (also
Tubular
inh ibits secretion of penicillin) . T reabsorption
Probenecid and
Colchicine Binds and stabil izes tubulin to inhibit
polymerization, impa iring leukocyte +-\--- --=,.------
high-dose salicylates
Tubular
T secretion
chemotaxis and degranulation . Diuretics and
GI side effects, especially if given orally. low-dose salicylates
Urine
Acute gout drugs
NSAI Ds Naproxen , indomethacin.

Cilucocorticoids Oral or i ntraarticular.
TN F-a inhibitors All TNF-a inhibitors predispose to infection including reactivation of latent TB since TNF
blockade prevents activation of macrophages and destruction of phagocytosed m icrobes.
DRUG MECHANISM CLINICAL USE
Etanercept Fusion protein (receptor for TNF-a + IgG 1 Fe) , Rheumatoid arthritis, psoriasis, ankylosing
produced b y recombinant DNA. spondyl itis
Etanercept is a TNF decoy receptor.
lnfliximab, Anti-TNF-a monoclonal antibody Crohn's disease, rheumatoid arthritis, ankylosing
adalimumab spondyl itis, psoriasis
HIGH-YIELD SYSTEMS
Neurology
"Estimated amount of glucose used by an adult human brain each day,

expressed in M6Ms: 250."
- Harper's Index
"He has two neurons held together by a spirochete."

-Anonymous
"I never came upon any of my discoveries through the process of rational
thinking."
-Albert E instein
"I like nonsense; i t wakes u p the brain cells."

- Dr. Seuss
408 SECTI O N Ill N E U R O LO G Y NEUROLOGY-EMBRYOLOGY
NEUROLOGY-EMBRYOLOGY
Neural development Notochord i nduces overlying ectoderm to differentiate into neuroectoderm and form the neural
Neural plate plate.
- Day 18 Neural plate gives rise to the neural tube and neural crest cells.
Notochord
Notochord becomes nucleus pulposus of the intervertebral el ise in adults.
.
Neural crest
J
Alar plate (dorsal) : sensory . .
Same onentat10n as spmal cord .
B asa I p I ate ( ventra I) : motor
Neural
crest
cells
Day 21
Regional specification of developing brain
Three primary Five secondary Adult derivatives of:

vesicles vesicles Walls Cavities
Cerebral Lateral
Wal l Cavity Telencephalon hemispheres ventricles
. _.,.---
.,. - Forebrain
(prosencephalon)
/ Thalamus Third
ventricle
Midbrain Mesencephalon M i dbrain Aqueduct

(mesencephalon)
Pons Upper part of

fou rth ventricle
==== Metencephalon
H i ndbrain Cerebe l l u m
(rhombencephalon)

Myelencephalon
Medulla Lower part of
fou rth ventricle
Spinal cord
N E U R O LOGY NEUROLOGY-EMBRYOLOGY S E C T I O N Ill 409
Neural tube defects Neuropores fail to fuse (4th week) -+ persistent connection between amniotic cavity and spinal
canal. Associated with low fol ic acid intake before conception and during pregnancy. Elevated
a-fetoprotei n (AFP) in amn iotic fluid and maternal serum . t acetylchol inesterase (AC h E ) in
amniotic fluid is a helpful confirmatory test (fetal ACh E in C S F transudates across defect into the
amn iotic fluid) .
Spina bifida occulta Failure of bony spinal canal to close, but no structural herniation. Usually seen at lower vertebral
levels . Dura is intact. Associated with tuft of hair or ski n d imple at level of bony defect.
Meningocele Meni nges (but not the spinal cord) herniate through spinal canal defect.
Meningomyelocele Meninges and spinal cord herniate through spinal canal defect.
S u barachnoid
Normal Spina bifida occults Meningocele Meningomyelocele
Forebrain anomalies
Anencepha l y Malformation of anterior neural tube resulting in no forebrai n , open calvarium ( " frog-l ike
appearance" ) . Clinical findings : t AFP; polyhydramn ios (no swallowing center in bra i n ) .
Associated with maternal diabetes (type 1). Maternal folate supplementation l risk.
Holoprosencephaly Fa ilure of left and right hemispheres to separate ; usually occurs during weeks 5-6. C omplex
multifactorial etiology that may be related to mutations in sonic hedgehog signaling pathway.
Moderate form has cleft l ip/palate, most severe form results in cyclopia.
Posterior fossa malformations

Chiari II (Arnold-Chiari Significant cerebellar tonsillar and verm ian herniation through foramen m agnum with aqueductal
ma l formation) stenosis and hydrocephalus. Often presents with thoraco-lumbar myelomen ingocele and paralysis
below the defect.
Dandy-Walker Agenesis of cerebellar vermis with cystic enlargement of 4th ventricle (fills the enlarged posterior
fossa) . Associated with hydrocephalus and spina bifida.
4l 0 S E CT I O N Ill N E U R O LOGY NEUROLOGY-EMBRYOLOGY
Syringomyelia Cystic enlargement of central canal of spinal Syrinx= tube, as i n syringe.

cord . Crossing fibers of spinothalamic tract are Associated with Chiari I malformation
typically damaged first. Results in a "cape (> 3-5 mm cerebellar tonsillar ectopia).
l i ke," bilateral loss of pain and temperature Most common at C8-T l .
sensation in upper extrem ities (fine touch
sensation is preserved) .
Ch iari I
malformation
Tongue development l st branch ial arch forms anterior 213 (thus Taste - C N VII, IX, X (solitary nucleus ) .
sensation via CN V3, taste via CN VI I ) . Pai n - C N V3, IX, X.
3rd a n d 4th arches form posterior 113 (thus Motor- C N XII.
sensation and taste mainly via CN IX, extreme
Anterior tongue
posterior via CN X).
Motor i nnervation is via C XII.
Muscles of the tongue are derived from occipital
myotomes.
Arch 1
Arches 3, 4
Posterior tongue
NEUROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY S E C T I O N Ill 41 1
NEUROLOGY-ANATOMY AND PHYSIOLOGY
CNS/PNS origins Neuroectoderm - CNS neurons; ependymal cells (inner l i n i n g of ventricles, make C S F ) ;
ol igodend rogl i a ; astrocytes.
Neural crest- PNS neurons, Schwann cells.
Mesoderm - M icrogl ia (l ike Macrophages, originate from Mesoderm) .
Neurons Signal-transm itting cells of the nervous system. Permanent cells - do not d ivide in adulthood (and,
as a general rule, have no progenitor stem cell population) .
Signal-relaying cells with dendrites (receive input) , cell bodies, and axons (send output) . Cell bodies
and dendrites can be sta ined via the Nissl substance (sta i ns RER) . RER is not present in the axon .
If an axon is injured, it undergoes Wallerian degeneration-degeneration d i stal to the injur y and
axonal retraction proximally; allows for potential regeneration of axon (if i n PNS ) .
Astrocytes Physical support, repair, K+ metabol ism, removal o f excess neurotransm itter, maintenance o f blood
brain barrier. Reactive gliosis in response to inj ury. Astrocyte marker- GFAP.
Microglia CNS phagocytes. Mesodermal origin . Not H I V-infected m icrogl ia fuse to form
readily d iscern ible in Nissl stains . Have small multinucleated giant cells in the C N S .
irregular nuclei and relatively l ittle cytoplasm.
Scavenger cells of the CNS. Respond to tissue
damage by differentiating into large phagocytic
cells.
Myelin t conduction velocity of signals transm itted Wraps and insulates axons: t space constant and
clown axons. Results in saltatory conduction t conduction velocity.
of action potential between nodes of Ranvier,
where there are high concentrations of Na+
channels. CNS - ol igoclendrocytes; PNS
Schwann cells.
4l 2 S E C T I O N Ill N E U ROLOGY NEUROLOGY-ANATOMY A ND PHYSIOLOGY
Oligodendroglia Each ol igodendrocyte myel inates multiple CNS These cells are destroyed in multiple sclerosis.
axons (up to 5 0 each ) . In Nissl stains, they Look l ike fried eggs on 1-I&E stain ing.
appear as small nuclei with clark chromatin
and l ittle cytoplasm. Predominant type of glial
cell i n white matter.
Schwann cells Each Schwann cell myel inates only l PNS axon . T hese cells are destroyed i n Guillai n-Barre
Node of Ranvier
Also promote axonal regeneration. Derived syndrome.
from neural crest. Acoustic neuroma-type of schwannoma.
t conduction velocity via saltatory conduction Typically located i n internal acoustic meatus
between nodes of Ranvier, where there are (CN VII I ) .
high concentrations of Na+ chan nels.
Sensory corpuscles
RECEPTOR TYPE DESCRIPTION LOCATION SENSES
Free nerve endings C - slow, unmyel inated fibers All sk in, epiderm is, some Pai n and temperature
A8 -fast, myelinated fibers viscera
Meissner's corpuscles Large, myel i nated fibers; adapt Glabrous (hairless) skin Dynamic, fine/l ight touch ;
quickly position sense
Pacinian corpuscles Large, myel i nated fibers Deep skin layers, l igaments, Vibration, pressure
and joints
Merkel's discs Large, myelinated fibers; adapt Hair fol l icles Pressure, deep static touch
slowly (e.g., shapes, edges) , position
sense
Peripheral nerve Endoneurium - invests single nerve fiber layers Endo = in ner.
(inflammatory infiltrate in Guillain-Barre) . Peri = around.
Ner e tru n k Perineurium ( Permeability barrier) -surrounds Epi = outer.
Epineurium a fascicle of nerve fibers. Must be rejoined in
Peri neurium
m icrosurgery for l imb reattachment.
Endone u r i u m Epi neurium-dense connective tissue that
N erve fibers surrounds entire nerve (fascicles and blood
vessel s ) .
N E U ROLOGY NEUROLOGY-A NATOMY A ND PHYSIOLOGY S E C T I O N Ill 41 3
Neurotransmitters
TYPE CHANGE IN DISEASE LOCATIONS OF SYNTHESIS
NE t in anxiety; ! in depression Locus ceruleus (pons)

Dopamine t in schizophren i a ; ! in Parkinson's ; ! in Ventral tegmentum and SNc ( m idbra in)
depression
5-HT ! i n anxiety; ! i n depression Raphe nucleus (pons)
ACh ! i n Alzhei mer's ; ! in Huntington's ; t in REM Basal nucleus of Meynert
sleep
GABA ! in anx iety; ! i n Huntington's Nucleus accumbens
aLocus ceruleus- stress and panic. Nucleus accumbens and septal nucleus-reward center, pleasure, addiction, fear.
Blood-brain barrier Prevents circulating blood substances from Other notable barriers i nclude :
reach ing the C SF/CNS. Formed by 3 Blood-testis barrier
structures: Maternal-fetal blood barrier of placenta
Capillary Tight junctions between nonfenestrated Infarction and/or neoplasm destroys endothel ial
lumen
capillary endothel ial cel ls cell tight j unctions vasogenic edema.
-+
Basement
membrane Basement membrane Hypothalamic i nputs and outputs permeate the
Astrocyte foot processes BBB.
Glucose and amino acids cross slowly by carrier Helps prevent bacterial infection from spreading
med iated transport mechanism. i nto the CNS. Also restricts dru g del ivery to
Nonpolar/l ipid-soluble substances cross rapidly bra i n .
via diffusion.
A few specialized brain regions with fenestrated
capillaries and no blood-brain barrier al low
molecules in the blood to affect brain
function (e.g., area postrema-vomiting
after chemo, OVLT- osmotic sensing) or
neurosecretory products to enter circul ation
(e.g., neurohypophysis -AD!-! release) .
1\1 4 SECTION Ill NEUROLOGY NEUHOLOGY -ANATOMY AND PHYSIOLOGY
Hypothalamus The hypothalamus wears TAN HATS -Thirst and water balance, Adenohypophysis control
(regulates a nterior pituitary) , Neurohypophysis releases hormones produced in the hypothalamus,
Hunger, Autonomic regulation, Temperature regulation, Sexual urges. I nputs: OVLT (senses
change i n osmolarity) , area postrema (responds to emetics) -areas not protected by B B B .
Supraoptic nucleus makes AD H .
Paraventricular nucleus makes oxytocin.
ADH and oxytocin: made by hypothalamus but stored and released by posterior pitu itary.
Lateral area Hunger. Destruction --+ anorexia, failure to If you zap your lateral nucleus, you shrink
thrive (infants) . Inh ibited by leptin. laterally.
Ventromedial a rea Satiety. Destruction (e.g., craniopharyngioma) If you zap your ventromedial nucleus, you grow
--+hyperphagia. Stimulated by leptin. ventrally and medially.
Anterior Cooling, parasympathetic. Anterior nucleus = cool off (cool ing,
hypothalamus pArasympathetic) . A/C =anterior cooling.
Posterior Heating, sympathetic. Posterior nucleus= get fi red up ( heating,
hypothalamus sympathetic) . If you zap your posterior
hypothalamus, you become a poikilotherm
(cold-blooded, l ike a snake) .
Suprachiasmatic C ircadian rhythm . You need sleep to be charismatic (chiasmatic) .
nucleus
Posterior pituitary Receives hypothalamic axonal projections Oxytocin: oxys = quick; tocos = birth.
(neurohypophysis) from supraoptic (ADH) and paraventricular Adenohypophysis = Anterior pituitary.
(oxytocin) nuclei.
I
N E U R O L O GY NEUROLOGY-A NATOMY A ND PHYSIOLOGY S E C T I O N Ill 41 5
Thalamus Major relay for all ascend ing sensory information except olfaction .
NUCLEUS INPUT INFO DESTINATION MNEMONIC
VPL Spinothalamic and Pa in and temperatur e ; l o somatosensory cortex.

dorsal columns/medial pressure, touch, vibration,
lemniscus. and proprioception .
VPM Trigem inal and gustatory Face sensation and taste. l o somatosensory cortex. Makeup goes on the face
pathway. (VPM) .
LGN CN I I . Vision . Calcarine sulcus. Lateral = Light.
MGN Superior ol ive and inferior Heari ng. Aud itory cortex of Medial = Music.
colliculus of tectum . temporal lobe.
VL Basal gangl ia. Motor. Motor cortex.
Limbic system Collection of neural structures involved in The famous 5 F's .

emotion , long-term memory, olfaction,
behavior modulation, and autonomic nervous
system function .
Structures include h ippocampus, amygdala,
fornix, mammillary bodies, and cingul ate
gyrus. Responsible for Feeding, Fleeing,
Fighting, Feeling, and Sex.
Cerebellum Modulates movement; aids in coord ination and balance.

I nput:
Contralateral cortex via middle cerebellar peduncle.
Ipsilateral proprioceptive information via inferior cerebel lar peduncle from the spinal cord
(i nput nerves= cl i mbing and mossy fibers ) .

Output:
Sends information to contralateral cortex to modulate movement. Output nerves= Purkinje
fibers send information to deep nuclei of cerebel lum, which i n turn sends information to the
contralateral cortex via the superior cerebel lar peduncle.
Deep nuclei (lateral--+ medial)- Dentate, Embol iform , Globose, Fastigial ( " Don't Eat Greasy
Foods" ) .
Lateral -voluntary movement of extrem ities ; when injured, propensity to fall toward injured
(ipsil ateral) side.
Medial - balance, truncal coordi nation.
41 6 S E C T I O N Ill N E U R O LO G Y NEUROLOGY-A NATOMY A ND PHYSIOLOGY
Basal ganglia Important in voluntary movements and making postural

adjustments.
Receives cortical input, provides negative feedback to cortex to
modulate movement.
Striatum = putamen (motor) + caudate (cogn itive ) . 01-Receptor = DIRect
Lentiform = putamen + globus pall idus. pathway.
Indirect = Inh ibitory.
I n put from SNc
Stimulatory
I n h ibitory
SNc Substantia nigra pars compacta

GPe Globus pal lidus externus
Globus pal lidus internus
D i rect lndire t
Subthalamic nucleus
Motor cortex pathway pathway Dopam ine D1 receptor
facilitates inhibits Dopam ine D2 receptor
movement
I
I
I
Putamen
Thalamus
Pedunculo
pontine
nucleus
Spinal
cord
Excitatory pathway-cortical inputs stimulate the striatum , stimulating the release of GABA, which
disinhibits the thalamus via the GPi/SNr (t motion ) .
Inh ibitory pathway- cortical inputs stimulate the striatum, which disinhibits STN v i a GPe, and
STN stimulates GPi/SNr to inh ibit the thalamus U motion ) .
Dopamine binds to D 1 , stimulating the excitatory pathway, a n d to D2 , i n h ibiting the i nh ibitory
pathway --+ t motion.
Parkinson's disease Degenerative d isorder of CNS associated with Your body becomes a TRAP = Tremor (at
Lewy bodies (composed of a-synuclein rest- e.g., pill-rolling tremor) , cogwheel
intracellular inclusion) and loss of Rigidity, Ak inesia (or bradyk inesia) , and
dopa m inergic neurons (i.e., depigmentation) of Postural in stabil ity.
the substantia n igra pars compacta.
N E U RO LO G Y NEUROLOGY-A NATOMY A ND PHY S IOLOGY S E CTI O N Ill 417
Huntington's disease Autosomal-dominant trinucleotide repeat Expansion of CAG repeats (anticipation ) .

disorder. Characterized by chorea, aggression, Caudate loses ACh and GABA.
depression, and dementia (sometimes in itially
m istaken for substance abuse) . Neuronal death
via M DA-R binding and glutamate toxicity.
Atrophy of striatal nuclei (main inh ibitors of
movement) can be seen on imagi ng.
Movement disorders
DISORDER PRESENTATION CHARACTERISTIC lESION NOTES
Hemiballismus Sudden, wild flailing of l arm Contralateral subthalamic "Half-of-body ballistic."

+1- ipsilateral leg nucleus (e.g., lacunar stroke) C ontralateral lesion.
Chorea Sudden, jerky, purposeless Basal gangl ia (e.g., Chorea = danci ng.
movements Huntington's)
Athetosis Slow, writh ing movements ; Basal gangl ia (e.g., Writh ing, snake-l ike
especially seen in fingers Huntington's) movement.
Myoclonus Sudden , brief, uncontrolled Jerks; h iccups; common in
muscle contraction metabol ic abnormal ities such
as renal and l iver fa ilure.
Dystonia Susta ined, involu ntary muscle Writer's cramp ; blepharospasm
contractions (susta ined eyel id twitch) .
Essential tremor Action tremor; exacerbated by Genetic pred isposition .
(postural tremor) hold ing posture /l imb position Patients often self-med icated
with EtOH, which ! tremor
amplitude. Treatment:
-blockers, prim idone.
Resting tremor Uncontrol led movement of Parkinson's d isease Occurs at rest; "pill-rolling
distal appendages (most tremor" of Parkinson's disease.
noticeable i n hands) ; tremor
alleviated by intentional
movement
Intention tremor Slow, zigzag motion when Cerebellar dysfunction
pointing/extending toward a
target
41 8 S ECTI O N Ill N E U ROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY
Cerebral cortex fundions
P remolar area (part of Principal motor area

extrapyramidal circuit)
Principal sensory areas
.r-___c____:,__
::: __ Central sulcus
Frontal eye
fields
Motor speech
(Broca's area;
domi nant
hemisphere) -+-----
P rincipal
visual
cortex
Associative auditory
cortex (Wernicke's area;
dominant hem isphere)
Homunculus Topographical representation of sensory and

motor areas in the cerebral cortex. Used to
localize lesion (e.g., in blood supply) leading to
specific defects.
For example, lower extrem ity deficit in sensation
or movement may ind icate i nvolvement of the
anterior cerebral artery.
Medial Lateral
NEUROLOGY NEUROLOGY-ANATOMY AND PHY)IOLOGY S ECTION Ill 4 l C)
Common brain lesions

AREA OF LESION CONSEQUENCE NOTES
Amygdala (bilateral) KIGver-Bucy syndrome ( hyperorality, Associated with HSV- 1 .

hypersexual ity, disinhibited behavior)
Frontal lobe Disinhibition and deficits in concentration,
orientation, and judgment; may have
reemergence of primitive reflexes
Right parietal lobe Spatial neglect syndrome (agnosia of the
contralateral side of the world)
Reticular activating Reduced levels of arousal and wakefulness (e.g.,
system (midbrain) coma)
Mammillary bodies Wernicke-Korsakoff syndrome : confusion, Associated with thiamine ( B 1 ) deficiency and
(bilateral) ophthalmoplegia, ataxia; memory loss excessive EtOH use ; can be precipitated by
(anterograde and retrograde amnesia) , giving glucose without B 1 to a B 1 -deficient
confabulation, personality changes patient.
Basal ganglia May result in tremor at rest, chorea, or athetosis Parkinson's d isease.
Cerebellar hemisphere I ntention tremor, l i mb ataxia, and loss of Cerebellar hem ispheres are laterally located
balance ; damage to the cerebel lum results in affect lateral l imbs.
ipsil ateral deficits ; fall toward side of lesion
Cerebellar vermis Truncal ataxia, dysarthria Vermis is centrally located-affects central body.
Subthalamic nucleus Contralateral hemiball i sm us
Hippocampus Anterograde amnesia - inabil ity to make new
memones
Paramedian pontine Eyes look away from side of lesion
reticular formation
(PPRF)
Frontal eye fields Eyes look toward lesion
Central pontine Acute paralysis, dysarthria, dysphagia,

myelinolysis d iplopia, and loss of consciousness. Can
cause " locked-in syndrome." Massive axonal
demyel ination in pontine wh ite matter tracts.
Commonly iatrogenic, caused by overly rapid
correction of Na+ levels (hyponatrem ia) . Arrow
in axial T2-weighted M RI with FLAIR shows
abnormal increased signal in central pons f'J.
420 SECTI O N Ill N E U R O LO G Y NEUROLOGY-ANATOMY A ND PHYSIOLOGY
Aphasia Aphasia = higher-order i nabil ity to speak (language deficit) . Dysarth ria = motor inabil ity to speak
(movement deficit) .
Broca's Non fluent aphasia with intact comprehension . Broca's Broken Boca (boca= mouth in
Broca's area-inferior frontal gyrus of frontal Spanish) .
lobe.
Wernicke's Fluent aphasia with impaired comprehension . Wernicke's is Wordy but makes no sense.
Wern icke's area -superior temporal gyrus of Wern icke's = "W hat?"
temporal lobe.
Global Nonfluent aphasia with impaired
comprehension. Both Broca's and Wernicke's
areas affected.
Conduction Poor repetition but fluent speech, intact Can't repeat phrases such as, "No ifs, ands, or
comprehension . Can be caused by damage to buts."
arcuate fasciculus.
Cerebral arteries-cortical distribution
Anterior cerebral artery (supplies anteromedial surface)

D Middle cerebral artery (supplies lateral surface)
Posterior cerebral artery (supplies posterior and inferior surfaces)
Watershed zones Between anterior cerebral/m iddle cerebral, posterior cerebral/m iddle cerebral arteries. Damage in
severe hypotension upper leg/upper arm weakness, defects i n higher-order visual processing.
--+
N E UROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY S E C T I O N Ill 42 1
Regulation of cerebral Brain perfusion rel ies on tight autoregulation. Therapeutic hyperventilation ( Pco2) helps
perfusion Cerebral perfusion is primarily driven by ICP in cases of acute cerebral edema (stroke,
Pco2 (Po2 also modulates perfusion in severe trauma) via decreasing cerebral perfusion.
hypoxia) .
Cerebral Cerebral
blood blood
flow flow
Cerebral p e rfusion -----

pressure Pco2 u ntil
oc
C 02
Pco2 > 90 m m H g
normal Po2
Normal
Hypoxemia increases
cerebral perfusion pressu re
only when Po2 < 50 m m H g
Normal
normal Pco2
Arterial gas Arterial gas

50 100 150 pressure (mmHg) 40 80 120 pressure ( m m H g )
422 S ECTI O N Ill N E U R O LO G Y NEUROLOGY-ANATOMY AND PHYSIOLOGY
Effects of strokes
ARTERY AREA OF LESION SYMPTOMS NOTES
Anterior circulation
MCA Motor cortex- upper l i mb and face. Contralateral paralysis- upper
limb and face.
Sensory cortex-upper l imb and face. Contralateral loss of sensation
upper limb and face.
Temporal lobe (Wernicke's area) ; Aphasia if i n dom inant (usually
frontal lobe (Broca's area) . left) hemisphere. Hemineglect
if lesion affects nonclominant
(usually right) side.
ACA M"tor cortex-lower l imb. Contralateral paralysis-lower
limb.
Sensory cortex-lower l imb. Contralateral loss of sensation
lower l imb.
Lateral Striatum , i nternal capsule. Contralateral hemiparesis/ Common location of lacunar
striate hemiplegia. infarcts, zo to unmanaged
artery hypertension.
Posterior circulation
ASA Lateral corticospinal tract. Contral ateral hemiparesis- lower Stroke commonly bilateral.
l imbs. Medial medullary syndrome
Medial lemniscus. ! contralateral proprioception. caused by infarct of
Caudal medulla-hypoglossal nerve. Ipsilateral hypoglossal dysfunction paramedian branches of ASA
(tongue deviates ipsilaterally) . and vertebral arteries.
PICA Lateral medulla-vestibular nuclei, Vomiting, vertigo, nystagmus; Lateral medullary
lateral spinothalamic tract, spinal ! pai n and temperature (Wallenberg's) syndrome.
trigem inal nucleus, nucleus sensation to limbs/face; dysphagia, Nucleus ambiguus effects are
ambiguus, sympathetic fibers, hoarseness, ! gag reflex; specific to PICA lesions.
inferior cerebellar peduncle. ipsilateral Horner's "Don't pick a ( PICA) horse
syndrome ; ataxia, dysmetria. ( hoarseness) that can't eat
(dysphagia) ."
AICA Lateral pons- cranial nerve nuclei; Vom iting, vertigo, nystagmus. Lateral pontine syndrome.
vestibular nuclei , facial nucleus, Paralysis of face, ! lacrimation, Facial nucleus effects are
spinal trigeminal nucleus, cochlear sal ivation, ! taste from anterior specific to AICA lesions.
nuclei, sympathetic fibers. lfl of tongue, ! corneal reflex. "Facial droop means A ICA's
Face - ! pa in and temperature pooped."
sensation. Ipsilateral ! hearing.
Ipsilateral Horner's syndrome.
M iddle and inferior cerebellar Ataxia, dysmetria.
peduncles.
PCA Occipital cortex, visual cortex. Contralateral hemianopia with
macular sparing.
Communicating arteries
AComm Common site of saccular ( berry) Visual field defects. Lesions are typically
aneurysm impingement on
-+ aneurysms, not strokes.
cranial nerves.
PComm Common site of saccular ( berry) CN III palsy- eye is " clown Lesions are typically
aneu rysm . and out" with ptosis and pupil aneurysms, not strokes.
dilation .
N E UROLOGY NEUROLOGY-ANATOMY A ND PHYSIOLOGY S E C T I O N Ill 4 23
Aneurysms I n general, an abnormal dilation of artery due to weakening of vessel wall.

Berry aneurysm Occurs at the bifurcations i n the circle of Willis
rz). Most common site is bifurcation of the
anterior communicating artery. Rupture (most
common complication) leads to subarachnoid
hemorrhage ( "worst headache of I ife") or
hemorrhagic stroke. Can also cause bitemporal
hemianopia via compression of optic chiasm.
Associated with ADPKD, Ehlers-Danlos
syndrome, and Marfan's syndrome. Other risk
factors : advanced age, hypertension, smoking,
race ( h igher risk i n blacks) .
Berry aneurysm (arrow). D
Charcot-Bouchard Associated with chron ic hypertension ; affects
microaneurysm small vessels (e.g., i n basal ganglia, thalamus) .
4 24 SECTI O N I l l N E U ROLOGY NEUROLOGY-ANATOMY A ND PHYSIOLOGY
Intracranial hemorrhage
Epidural hematoma Rupture of middle meningeal artery (branch
of maxillary artery) , often zo to fracture
of temporal bone. Lucid interval. Rapid
expansion under systemic arterial pressure
--+transtentorial herniation, CN III palsy.
CT shows biconvex ( lentiform), hyperdense
blood collection rJ not crossing suture l ines.
Can cross falx, tentorium .
Epidural hematoma. 1-fracture; 2-epidural hematoma;

3-temporalis muscle, 4 Sylvian fissure; 5-frontal sinus.
Subdural hematoma Rupture o f bridging veins. Slow venous bleed ing

(less pressure = hematoma develops over time) .
Seen in elderly individuals, alcohol ics, blunt
trauma, shaken baby (predisposing factors :
bra i n atrophy, shak ing, wh iplash).
C rescent-shaped hemorrhage that crosses suture
l ines IIJ. M idline shift. Cannot cross falx,
tentorium.
Subarachnoid Rupture of an aneurysm (such as a berry

hemorrhage [saccular] aneurysm, as seen in Marfan's,
Ehlers-Danlos, ADPKD) or an AVM. Rapid
time course. Patients complain of "worst
headache of my life (WHOML) ." Bloody or
yellow (xanthochromic) spinal tap. 2-3 days
afterward, risk of vasospasm due to blood
breakdown (not visible on CT, treat with
n imodipine) and rebleed (visible on
CT).
lntraparenchymal Most commonly caused by systemic

(hypertensive) hypertension[!]. Also seen with amyloid
hemorrhage angiopathy, vascul itis, and neoplasm.
Typically occurs in basal ganglia and internal
capsule (Charcot-Bouchard aneurysm of
lenticulostriate vessels), but can be lobar.
N E U R O LO G Y NEUROLOGY-ANATOMY AND PHYSIOLOGY SECTION Ill 425
Ischemic brain Irreversible damage begins after 5 minutes of hypoxia. Most vul nerabl e - h ippocampus, neocortex,
disease/stroke cerebellum, watershed areas . Irreversible neuronal injury-red neurons ( 1 2-48 hour s ) , necrosis+
neutroph ils (24-72 hours), macrophages ( 3 -5 clays), reactive gl iosis + vascular prol i feration ( l -2
weeks) , gl ial scar (> 2 weeks) .
Stroke i maging: bright on diffusion-weighted M R I in 3-30 m inutes and remains bright for 1 0 clays,
clark on noncontrast CT in 24 hours. Bright areas on noncontrast CT indicate hemorrhage (tPA
con traincl ica ted) .
Atherosclerosis Thrombi lead to ischemic stroke with subsequent necrosis. Form cystic cavity with reactive gliosis.
Hemorrhagic stroke I ntracerebral bleeding, often clue to hypertension, anticoagulation, and cancer (abnormal vessels
can bleed) . May be 2 to ischemic stroke followed by reperfusion (t vessel fragil ity) .
Ischemic stroke Atherosclerotic emboli block large vessels ; etiologies i nclude atrial fibrillation, carotid dissection,
patent foramen ovale, endocarditis. Lacunar strokes block small vessels, may be 2 to
hypertension. Treatment: tPA within 4. 5 hours (so long as patient presents with in 3 hours of onset
and there is no major risk of hemorrhage) .
Transient ischemic Brief, reversible episode of focal neurologic dysfu nction typically lasting < l hour without acute
attack (TIA) infarction (8 M R I ) ; deficits clue to focal ischem ia.
Dural venous sinuses Large venous channels that run through the dur a . Drain blood from cerebral veins and receive C S F
from arach noid granulations. Empty into internal jugular vei n .
Superior sagittal sinus -- -+l

(main location of CSF return
via arachnoid granulations)
Superior ophthalmic vein
Internal jugular vein

42 6 S E CTI O N I l l N E U RO L O G Y NEUROLOGY-ANATOMY AND PHYSIOLOGY
Ventricular system Lateral ventricle --+ 3rd ventricle via right and
Posterior left i ntraventricular foram ina of Monro.
3rd ventricle --+ 4th ventricle via cerebral
aqueduct (of Sylvius) .
Foramen J 4th ventricle--+ subarachnoid space via :
of Monro (J I. Foramina of Luschka = Lateral.
Third Foramen of Magendie = Medial.
ventricle
Foramen of Luschka _/
Foramen of Magendie
C SF is made by ependymal cell s of choroid plexus ; it is reabsorbed by arachnoid granulations and
then drains into dural venous sinuses.
Hydrocephalus
Communicating (nonobstructive)
Communicating CSF absorption by arachnoid granulations,
hydrocephalus wh ich can lead to t i ntracran ial pressure,
papilledema, and hern iation (e.g., arachnoid
scarring post-meni ngitis) .
Normal pressure Results in t subarachnoid space volume but
hydrocephalus no increase in CSF pressure. Expansion of
ventricles d istorts the fibers of the corona
rad iata and leads to the clinical triad of
urinary incontinence, ataxia, and cognitive
dysfunction (sometimes reversible) [J.
"Wet, wobbly, and wacky."
Normal pressure hydrocephalus. Lateral ventricle
enlargement in absence of, or out of proportion to, sulcal
enlargement (marker for brain atrophy).!!!
Hydrocephalus ex Appearance of t C S F i n atrophy (e.g., Apparent increase i n C S F observed on imaging is

vacuo Alzheimer's d isease, advanced HIV, Pick 's actually result of decreased neural tissue clue to
d isease) . I ntracran ial pressure is normal; neuronal atrophy.
triad is not seen.
Noncommuncating (obstructive)
Noncomm u nicating Caused by a structural blockage of CSF
hydrocephalus circulation within the ventricular system
(e.g., stenosis of the aqueduct of Sylvius) .
NEUROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY S E C T I O N Ill 4 27
Spinal nerves There are 31 spinal nerves in tota l : 8 cervical, 31, just l ike 31 Aavors of Baskin-Robbins ice
12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal . cream!
Nerves C 1 -C7 exit above the corresponding Vertebral disc hern iation: nucleus pulposus (soft
vertebra . All other nerves exit below (e.g., C3 central d isc) hern iates through anulus fibrosus
exits above the 3rd cervical vertebra ; L2 exits (outer ring); usually occurs posterolaterally at
below the 2nd lumbar vertebra) . L4-L5 or L 5 -S l .
Spinal cord-lower In adults, spinal cord extends to lower border of Goal o f lumbar puncture i s to obtai n sample of
extent L l -L2 vertebrae . Subarachnoid space (which C S F without damaging spinal cord . To keep
contains the C SF) extends to lower border the cord alive, keep the spinal needle between
of S2 vertebra . Lumbar puncture is usually L3 and L5.
performed between L3-L4 or L4-L 5 ( level of
cauda equina) .
Spinal cord and associated tracts

Dorsal columns Legs are Lateral in Lateral corticospi nal,
(pressure, vibration,
touch, proprioception)
spinothalamic tracts.
Dorsal column is organ ized as you are, with
Fascic u l u s Fascicu l u s hands at sides. Arms outside, legs inside.
cuneatus g racil i s
(upper body, (lower body,
extre m ities) extre m ities)
Lateral spi nothalamic
Posterior spinal
tract (pai n , temperature
arteries
Posterior horn
Intermediate horn
sympathetics
(T 1- L2/L3) Lateral
corticospinal tract
(volu ntary motor)
Anterior
Anterior spinal a rtery Anterior horn spinothalamic tract
(crude touch, pressu re)
428 SECTI O N Ill N E U R O LO G Y NEUROLOGY-ANATOMY AND PHYSIOLOGY
Spinal trad anatomy Remember, ascend ing tracts synapse and then cross.
and fundions
3RD-ORDER
TRACT AND FUNCTION 1ST-ORDER NEURON SYNAPSE 1 2ND -ORDER NEURON SYNAPSE 2 NEURON
Dorsal column Sensory nerve ending Ipsilateral Decussa tes VPL Sensory
Medial lemniscal -+ cell body in dorsal root nucleus in medulla (thalamus) cortex
pathway ganglion -+enters spinal cuneatus -+ ascends
Ascend ing pressure, cord, ascends ipsilaterally in or gracilis contra laterally
vibration, fine touch, dorsal column (medulla) i n medial
and proprioception lemn iscus
Spinothalamic tract Sensory nerve ending (A8 Ipsilateral gray Decussates at VPL Sen sory
Lateral : pain, and C fibers) (cell body matter (spinal a nterior wh ite (thalamus) cortex
temperature in dorsal root ganglion) -+ cord) com m 1ssu re
Anterior: crude touch, enters spinal cord -+ ascends
pressure contralaterally
Lateral corticospinal U M N : cell body in ] 0 Cell body of L M N : leaves NMJ
tract motor cortex -+ descends anterior horn spinal cord
Descend ing voluntary ipsilaterally (through (spinal cord)
movement of internal capsule) until
contralateral l i mbs decussating at caudal
medulla (pyramidal
decussation) -+ descends
contralaterally
Motor neuron signs

SIGN UMN lESION lMN lESION COMMENTS
Weakness + + Lower M N = everyth ing lowered ( less muscle
Atrophy + mass, ! muscle tone, ! reflexes, downgoing
toes ) .
Fasciculations +
Upper M N = everyth ing u p (tone, DTRs, toes) .
Reflexes
Fasciculation = muscle twitch ing.
Tone
Positive Babinski is normal i n infants.
Babinski +
Spastic paralysis +
Flaccid paralysis +
Clasp knife spasticity +
N E U R O LOGY NEUROLOGY-ANATOMY AND PHYS I OLOGY SECTION Ill 429
Spinal cord lesions

DISEASE CHARACTERISTICS
Pol iomyel itis and Werdn ig-Hoffman disease LMN lesions only, clue to destruction of anterior
horns; flaccid paralysis.
Multiple sclerosis Mostly white matter of cervical region ; random and

asymmetric lesions, cl u e to demyeli nation ; scanning
speech, intention tremor, nystagmus.
Amyotroph ic lateral sclerosis (ALS) Combined UMN and LMN deficits with no sensory,
cognitive, or oculomotor deficits ; both UMN and
LMN signs.
Can be caused by defect in superoxide d ismutase l .
Commonly presents a s fasciculations w ith eventual
atrophy; progressive and fatal .
Riluzole treatment modestly t survival by
! presynaptic glutamate release.
Commonly known as Lou Gehrig's disease. Stephen
Hawking is a wel l-known patient who h ighlights
the lack of cogn itive deficit.
Posterior spinal arteries Complete occlusion of anterior Spares dorsal columns and Lissauer's tract; upper
be spinal artery thoracic ASA territory is a watershed area, as artery
of Adamkiewicz suppl ies ASA below -'T8.
0
I
Anterior spinal artery
Tabes dorsalis Caused by 3 syphilis. Results from degeneration

(demyel ination) of d01sal columns and roots
-+impaired sensation and proprioception and
progressive sensory ataxia (i nabil ity to sense or feel
the legs ) .
Associated w i t h Charcot's joi nts, shooting p a i n , Argyll
Robertson pupils (small bilateral pupils that further
constrict to acco m modation but not to light) .
Exam will demonstrate absence of DTRs and positive
Romberg.
Syringomyel ia Syrinx expands and damages anterior white
commissure of spinothalamic tract (2nd-order
neurons) bilateral loss of pain and temperature
-+
sensation (usually C 8 -T l ) ; seen with Chiari I

malformation ; can expand and affect other tracts.
Vitamin B12 or vitamin E deficiency Subacute combined degeneration- demyel ination
of dorsal columns, lateral corticospinal tracts, and
spinocerebellar tracts ; ataxic gait, paresthesia,
impa ired position and vibra tion sense.
430 S E CT I O N I l l N E U R O LO G Y NEUROLOGY-ANATOMY AN D PH YSIOLOGY
Poliomyelitis Caused by pol iovirus (fecal-oral transmission) . Repl icates in the oropharynx and small i ntestine
before spreading via the bloodstream to the CNS. Infection causes destruction of cells in anterior
horn of spi nal cord (LMN death ) .
SYMPTOMS LMN lesion signs-weakness, hypotonia, flaccid paralysis, atrophy, fasciculations, hyporeflexia, a n d
muscle atrophy. Signs o f infection-malaise, headache, fever, nausea, etc.
FINDINGS CSF with t WBCs with sl ight elevation of protein (with no change i n CSF glucose ) . Virus
recovered from stool or throat.
Werdnig-Hoffman Congenital degeneration of anterior horns of spinal cord - LMN lesion. " Floppy baby" with
disease marked hypotonia and tongue fasciculations. Infantile type has median age of death of 7 months.
Autosomal-recessive inheritance.
Friedreich's ataxia Autosomal-recessive trinucleotide repeat Friedreich is Fratastic (frataxin) : he's your
d isorder (GAA) in gene that encodes frataxin. favorite frat brother, always stumbl ing,
Leads to i mpairment in mitochondrial staggering, and falling.
functioning. Staggering gait, frequent falling,
nystagmus, dysarthria, pes cavus, hammer toes,
hypertroph ic cardiomyopathy (cause of death) .
Presents in childhood with kyphoscol iosis.
Brown- Sequard Hemisection of spinal cord . Findings :

syndrome Ipsilateral U M N signs below the level of the
lesion (clue to corticospinal tract damage)

Ipsilateral loss of tactile, vibration,
proprioception sense below the level of the

lesion (clue to dorsal column damage)
Contralateral pain and temperature
Lesion loss below the level of the lesion (due to

spinothalamic tract damage)
Ipsilateral loss of all sensation at the level of
the lesion Impaired pai n

Ipsilateral LMN signs (e.g., flaccid paralysis) and temperature Impaired
sensation proprioceptio n ,
at the level of the lesion vibrati o n , 2-point
If lesion occurs above T l , patient may present discri m i nation ,
and joint and
with Horner's syndrome due to damage of
position sensation
sympathetic ganglion.
N E U ROLOGY NEUROlOGY-ANATOMY AND PHYSIOlOGY SECTION I l l 43 1
Horner's syndrome Sympathectomy of face: PAM is horny ( Horner's ) .

Ptosis (sl ight drooping of eyel id: superior Ptosis, anhidrosis, and miosis (rhym ing) .
tarsal muscle)
Anhidrosis (absence of sweating) and
flushing (rubor) of affected side of face

M iosis (pupil constriction)
Associated with lesion of spinal cord above

Tl (e.g., Pancoast tumor, Brown-Sequard
syndrome [cord hemisection] , late-stage
syringomyel ia).
Long c i l iary nerve
To sweat g lands
of forehead
To smooth m u scle of eyelid

=;:3--'--< To p u p i l lary d i l ator
I nternal carotid artery -....:.r.h;==:,
:, _,..------< To sweat g lands of face
External carotid artery
Third n e u ron
Fi rst neuron
Superior cervical ganglion
Synapse is
in lateral horn
Spinal cord
The 3-neuron oculosympathetic pathway projects from the hypothalamus to the i ntermediolateral
colum n of the spinal cord , then to the superior cervical (sympathetic) ganglion, and finally
to the pupil, the smooth muscle of the eyel ids, and the sweat glands of the forehead and face.
I nterruption of any of these pathways results in Horner's syndrome.
Landmark dermatomes C 2 - posterior half of a skull "cap." Diaphragm and gal lbladder pain referred to the
C 3 - h igh turtleneck shirt. right shoulder via the phrenic nerve.
C4- low-collar shirt.
T4 -at the n ipple. T4 at the teat pore.
T7-at the xiphoid process.
T l O -at the umbil icus (important for early Tl O at the belly butten .
appendicitis pain referral ) .
L l -at t h e inguinal l igament. Ll is IL ( Inguinal Ligament) .
L4 - i ncludes the kneecaps. Down on ALL 4's (L4) .
S2, S3, S4- erection and sensation of penile and " S2 , 3, 4 keep the penis off the floor."
anal zones.
432 S E C T I O N Ill N E U ROLOGY N E U ROLOGY-ANATOMY AND P HYS I OLOGY
Clinical reflexes Biceps = C5 nerve root. Reflexes count up i n order:

Triceps = C 7 nerve root. Sl, 2
Patella = 14 nerve root. 13, 4
Achilles = Sl nerve root. C5, 6
Babinski - clorsiflexion of the big toe and C 7, 8
fanning of other toes; sign of UMN lesion, but
normal reflex in l st year of life.
Primitive reflexes CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult.
Normally disappear within l st year of life. These "primitive" reflexes are inh ibited by a mature/
developing frontal lobe. They may reemerge in adults following frontal lobe lesions loss of -+
inhibition of these reflexes.

Moro reflex "Hang on for life" reflex-abcluct/extencl l imbs when startled, and then draw together
Rooting reflex Movement of head toward one side if cheek or mouth is stroked (n ipple seeking)
Sucking reflex Sucking response when roof of mouth is touched
Palmar reflex Curling of fingers if palm is stroked
Plantar reflex Dorsiflexion of large toe and fanning of other toes with plantar stimulation
Babinski sign- presence of this reflex in an adult, wh ich may signify a UMN lesion
Galant reflex Stroking along one side of the spine while newborn is in ventral suspension (face clown) causes
lateral flexion of lower body toward stimulated side
Brain stem-ventral
Optic chiasm
view
Infundibulum
Ante rior perforated
substance
Tuber cinereum
Mammil lary body
CN XI
CN XII
C N s that lie medially a t bra in ste m : III, V I , XII. 3 (x 2 ) = 6(x2) = 1 2 ( Motor = Medial) .
NEUROLOGY N E UROLOGY-ANATOMY AND P H Y SIOLOGY S E C T I O N Ill 433
Brain stem-dorsal view (cerebellum removed)
S uperior cerebellar
pedu ncles
Middle cerebellar
pedu ncles
Pineal gland- melaton in secretion , circad ian You r eyes are above your ears, and t h e superior
rhythms. col l iculus (visual) is above the inferior
Superior coll icul i - conjugate vertical gaze colliculus (aud itory) .
center.
Inferior collicu l i - aud itory.
Pa rinaud syndrome - paralysis of conjugate
vertical gaze due to lesion in superior colliculi
(e.g., pinealoma ) .
434 SECTION I l l N E U R O L O GY NEUROLOGY-ANATOMY AND PHYSIOLOGY
Cranial nerves
NERVE CN FUNCTION TYPE MNEMONIC
Olfactory Smell (only CN without thalamic relay to cortex) Sensory Some
Optic II Sight Sensory Say
Oculomotor III Eye movement ( S R , IR, MR, IO) , pupillary constriction Motor Marry
(sph incter pupillae : Edinger-Westphal nucleus, muscarinic
receptors) , accommodation, eyelid open ing (levator palpebrae)
Trochlear IV Eye movement (SO) Motor Money
Trigeminal v Mastication , facial sensation (ophthalmic, maxillary, mand ibular Both But
d ivisions), somatosensation from anterior 213 of tongue
Abducens VI Eye movement (LR) Motor My
Facial VII Facial movement, taste from anterior 213 of tongue, lacrimation, Both Brother
sal ivation (submandibular and subl ingual glands) , eyelid closing
(orbicularis ocul i), stapedius muscle in ear (note : nerve courses
through the parotid gland, but does not innervate it)
Vestibulocochlear VIII Hearing, balance Sensory Says
Glossopharyngeal IX Taste and somatosensation from posterior 1 13 of tongue, swallowing, Both B ig
sal ivation (parotid gland) , mon itoring carotid body and sinus
chemo- and baroreceptors, and stylopharyngeus (elevates pharynx,
larynx)
Vagus X Taste from epiglottic region, swallowing, palate elevation, midline Both Bra ins
uvula, talking, coughing, thoracoabdominal viscera, mon itoring
aortic arch chemo- and baroreceptors
Accessory XI Head turning, shoulder shrugging ( S C M , trapezius) Motor Matter
Hypoglossal XII Tongue movement Motor Most
Cranial nerve nuclei Located in tegmentum portion of brain stem Lateral nuclei = sensory (aLar plate ) .
( between dorsal and ventral portions) : - Sulcus l i m itans-
M idbra i n - nuclei of C III, IV Medial nuclei = Motor ( basal plate ) .
Pons - nuclei of CN V, VI, VII, VIII
Medulla- nuclei o f CN IX, X, XII
Spinal cord - nucleus of CN XI
Cranial nerve reflexes

REFLEX AFFERENT EFFERENT
Corneal V1 ophthalmic (nasocil iary branch) VII (temporal branch : orbicularis oculi)
Lacrimation V1 ( loss of reflex does not preclude emotional VII
tears)
Jaw jerk V 3 (sensory-muscle spindle from masseter) V 3 (motor- masseter)
Pupillary II III
Gag IX X
N E U ROLOGY NEU ROLOGY-ANATOMY A ND PHYSIOLOGY S E CTI O N I l l 43 5
Vagal nuclei
Nucleus Solitarius Visceral Sensory information (e.g., taste, V I I , IX, X.
baroreceptors, gut d istention ) .
Nucleus aM biguus Motor innervation o f pharynx, larynx, and IX, X.
upper esophagus (e.g., swal lowing, palate
elevation ) .
Dorsal motor nucleus Sends autonom ic (parasympathetic) fibers to X.
heart, lungs, and upper GI.
Cranial nerve and Cribriform plate ( C N 1). D ivisions of C N V exit owing to Standing Room
vessel pathways M iddle cranial fossa (CN I I-VI ) - through On ly.
sphenoid bone :
Optic canal ( C N I I , ophthalmic artery,
central retinal vein)

Superior orbital fissure (CN I I I , IV, V , VI,
1
ophthalmic vei n , sympathetic fibers)
Foramen Rotundum (C V2)
Foramen Ovale ( C N V )
3
Foramen spinosum (m iddle meningeal
artery)
Posterior cranial fossa ( C VII-XI I ) - through
temporal or occipital bone :
I nternal aud itory meatus (CN VII, VIII)
Jugular foramen (CN IX, X, XI, jugular
vein)
Hypoglossal canal (CN XII)
Foramen magnum (spinal roots of CN XI,
bra i n stem, vertebral arteries)

43 6 SECTION I l l N E U RO LOGY NEUROLOGY-ANATOMY AND PHYS I OLOGY
Cavernous sinus A collection of venous sinuses on either side of The nerves that control extraocular muscles
the pituitary. Blood from eye and superficial (plus V 1 and V 2 ) pass through the cavernous
cortex ..... cavernous sinus ..... internal jugular sinus.
vem . Cavernous sinus syndrome (e.g., cl u e to mass
C N I I I , IV, V 1 , V 2 , a n d VI a n d postgangl ionic effect, fistula, thrombosis) - ophthal moplegia
sympathetic fibers en route to the orbit all and corneal and maxillary sensation with
pass through the cavernous sinus. Cavernous normal vision.
portion of i nternal carotid artery is also here.
,.------ Anterior cerebral artery
----- I nternal carotid artery
---- Anterior clinoid p rocess
r---- S u barachnoid
space
Optic
chiasm
Ocu lomotor ( I l l ) n e rve
Trochlear ( IV ) nerve
Hypophysis
Ophthalmic (V , ) n e rve
Abducens (VI) nerve
Common cranial nerve lesions

CN V motor lesion Jaw deviates toward side of lesion clue to unopposed force from the opposite pterygoid muscle.
CN X lesion Uvula deviates away from side of lesion. Weak side collapses and uvula points away.
CN XI lesion Weakness tur n i n g head to contralateral side of lesion ( S C M ) . Shoulder droop on side of lesion
(trapezius) .
The left SCM contracts to help turn the head to the right.
CN XII lesion (LMN) Tongue deviates toward side of lesion ( " l ick your wounds") due to weakened tongue muscles on the
affected side.
Hearing loss
RINNE TEST WEBER TEST
Conductive Abnormal ( bone > air) Local izes to affected ear

Sensorineural Normal (air > bone) Local izes to unaffected ear
Noise-i nduced Damage to stereocilliated cells in organ of Corti; loss of high-frequency hearing l st; sudden
extremely loud noises can produce hearing loss due to tympanic membrane ruptur e .
N E U ROLOGY N EUROLOGY-A NATOMY A ND PHYSIOLOGY SECTION Ill 43 7
Facial lesions
UMN lesion Lesion of motor cortex or connection between
cortex and facial nucleus. Contralateral
paralysis of lower face; forehead spared clue to
bilateral U M N i nnervation .
LMN lesion Ipsilateral paralysis of upper and lower face.
Facial nerve palsy C omplete destruction of the facial nucleus itself
or its branchial efferent fibers (facial nerve
proper) . -- LMN
lesion
Peripheral ipsilateral facial paralysis with
inabil ity to close eye on involved side.
Can occur id iopath ically; gradual recovery in
most cases.
Seen as a compl ication in AIDS, Lyme d isease, lesion =
Facial nerve
herpes si mplex and ( less common) herpes palsy)
zoster, sarcoidosis, tumors, and diabetes.
Called Bell's palsy when id iopathic.
Mastication muscles 3 muscles close jaw: Masseter, teMporalis, M's Munch.

Med ial pterygoid. l opens : lateral pterygoid. Lateral Lowers (when speaking of pterygoids
All are innervated by the trigeminal nerve with respect to jaw motion) .
(VJ "It takes more muscle to keep your mouth shut."
Eye and retina
}
Ora serrata
Central
Ciliary m u scle
ciliary body
C i l iary p rocess
CN I I (optio) { .-.-- Schlemm's canal

m:l";;.-- Lens
Capsule of lens
Iris
- Cornea
Pupil
chamber
Posterior chamber
} Anterior segment
(Reproduced, with permission, from Mescher A L . Junqueira's Basic Histology: Text & Atlas, 1 2th e d . N e w York: McG rawHill, 2 0 1 0 : Fig. 23 1 .)
43 8 SECTION I l l N E U ROLOGY NEUROLOGY-ANATOMY AN D PHYSIOLOGY
Common eye conditions

Refractive errors Impaired vision that improves with glasses.
Hyperopia : eye too short for refractive power of cornea and lens -+ l ight focused behind retina.
Myopia : eye too long for refractive power of cornea and lens -+ l ight focused i n front of retina.
Astigmatism: abnormal curvature of cornea resulting i n different refractive power at different axes.
Accommodation : focusing on near objects -+ cil iary muscles tighten - zonular fibers relax -+ lens
becomes more convex. Occurs with convergence and m iosis.
Presbyopia: change i n focusing abil ity during accommodation clue to sclerosis and decreased
elasticity.
Uveitis Inflam mation of uveal coat (consists of iris, ciliary body, and choroid) . Often associated with
systemic inflam matory d isorders (e.g., sarcoid, rheumatoid arthritis, j uvenile idiopathic arthritis,
TB, H LA-B27-associatecl conditions ) .
Retinitis Retinal edema a n d necrosis leading to scar. Often viral (CMV, HSV, HZV) . Associated with
. .
ImmunosuppressiOn.
Central retinal artery Acute, painless monocular vision loss. Retina wh iten ing with cherry-red spot.
occlusion
Aqueous humor pathway
Canal of Schlemm
(collects aqueous humor from
trabecular meshwork)
Trabecular meshwork
(col lects aqueous humor
that flows through
anterior chamber)
C i l iary epithe l i u m ()
(produces aqueous h u mor)
Cil iary muscle ( M )
(Adapted, with permission, from Riordan-Eva P, Whitcher J P. Vaughan & Asbury's General Ophthalmology, 1 7th ed. N e w York: McGraw-Hill, 2008.)
N E U ROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY SECTION I l l 439
Glaucoma Optic neuropathy, usually with t intraocular pressure (lOP).

Open/wide angle Characterized by peripheral then central vision loss usually with t lOP; optic disc atrophy with
cupping; associated with t age, African-American race, fam i ly history, t lOP. Pa inless, more
common i n U . S .
Primary cause unclear. Secondary causes include uveitis, trauma, corticosteroids, and
vasoprol iferative retinopathy that can block or ! outflow at the trabecular meshwork.
Closed/narrow angle Enlargement or forward movement of lens against central iris leads to obstruction of normal
aqueous flow through pupil fluid builds up behind iris, pushing peripheral iris against cornea
-+
and impeding flow through the trabecular meshwork .

Chron i c closure : Often asymptomatic with damage to optic nerve and peripheral vision.
Acute closure : True ophthalmic emergency. t IOP pushes iris forward angle closes abruptly. -+
Very painful, sudden vision loss, halos around l i ghts, rock-hard eye, frontal headache. Do not give
epinephrine because of its mydriatic effect.
Catarad Pa inless, often bilateral, opacification of lens ! i n vision. R isk factors : age, smoking, EtO H ,
-+
excessive sunlight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency,

d iabetes (sorbitol) , trauma, infection.
Papilledema Optic d isc swell ing (usually bilateral) due to t i ntracranial pressure (e.g., 2 to mass effect) .
Enlarged blind spot and elevated optic el ise with blurred margins seen on fundoscopic exam .
Extraocular muscles Superior rectus m. (CN I l l ) C N VI i nnervates the Lateral Rectus.

Superior oblique m.
and nerves (CN IV) C N IV i n nervates the Superior Obl ique.
C N III innervates the Rest.
The "chemical formula" LR6 S0 4 R 3 .
The superior obl ique abducts, i ntorts, and
Late ral depresses wh ile adductecl .
rectus m . rectus m .
(CN V I ) (CN Ill)
I nferior
rectus m.
(CN I l l )
Inferior oblique m.
(CN Ill)
(Reproduced, with permission, from Morton D et a l. The Big Picture: Cross

Anatomy. New York: McGraw-Hill, 2 0 1 1 : Fig. 1 8-3(.)
CN I I I damage - eye looks clown and out; ptosis,

pupillary d ilation, loss of accommodation.
C N IV damage- eye moves upward, particularly
with contralateral gaze and ipsilateral head tilt
(problems going down sta irs) .
C N VI damage - medially directed eye that
cannot abduct.
440 SECTI O N I l l N E U ROLOGY N E U ROLOGY-ANATOMY AND P HYSIOLOGY
Testing extraocular To test the function of each muscle, have the IOU: to test In ferior Oblique,
muscles patient look in the following directions (e.g., have patient look Up.
to test SO, have patient depress eye from Obliques move the eye i n the Opposite
adducted position) : direction.
SA 10
LA -------?t---+ M A
(temporal} (nasal)
lA so
Pupillary control Miosis (constriction, parasympathetic) :

l st neuron : Edinger-Westphal nucleus to cil iary ganglion via CN I I I
2 n d neuron : short ciliary nerves to pupillary sphincter muscles
Mydriasis (dilation , sympathetic)

l st neuron : hypothalamus to cil iospi nal center of Budge ( C 8-T2)
2nd neuron : exit at T l to superior cervical ganglion (travels along cervical sympathetic chain
near lung apex, subclavian vessels)
3rd neuron : plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary
nerve to pupillary dilator muscles
Pupillary light reflex Light i n either retina sends a signal via CN I I to pretectal nuclei (clashed l ines) i n m idbrain that
activate bilateral Edinger-Westphal nucle i ; pupils contract bilaterally (consensual reflex) .
Result: illumi nation of l eye results in bilateral pupillary constriction .
Marcus Gunn pupil -afferent pupill ary defect (e.g., due to optic nerve damage or retinal
detachment) . ! bilateral pupillary constriction when l ight is shone in affected eye relative to
unaffected eye . Tested with the "swinging flashlight test."
Light
v
Edinger-Westphal nucleus
Late ral geniculate nucleus
(Adapted, with permission, from Simon RP e t a l . Clinical Neurology, 7 t h e d . New York: McG raw-Hill, 2009 : Fig. 4 1 2.)
N E U ROLOGY N E UROLOGY-ANATOMY AN D PHYS I OLOGY SECTION I l l 44 1
Cranial nerve Ill CN I I I has both motor (central) and parasympathetic (peripheral) components.
Motor output to ocular muscles -affected primarily by vascular d i sease (e.g., d iabetes: glucose
- sorbitol) clue to diffusion of oxygen and nutrients to the interior fibers from comprom ised
vasculature that resides on outside of nerve. Signs: ptosis, " clown and out" gaze.
Parasympathetic output- fibers on the periphery are 1 st affected by compression (e.g., posterior
communicating artery aneurysm, uncal herniation ) . Signs : d i m i n ished or absent pupillary l ight
CN Ill
reflex, " blown pupil."
Retinal detachment Separation of neurosensory layer of retina (photoreceptor layer with rods and cones) from
outermost pigmented epithel ium (normally shields excess l i ght, supports retina) - degeneration
of photoreceptors - vision loss. May be zo to retinal breaks, d iabetic traction, inflammatory
effusions.
Breaks more common in patients with high myopia and are often preceded by posterior vitreous
detachment (flashes and floaters) and eventual monocular loss of vision l ike a "curta i n drawn
clown." Surgical emergency.
Age-related macular Degeneration of macula (central area of retina) . Causes distortion (metamorphopsia) and eventual
degeneration loss of central vision (scotomas) .
Dry (nonexuclative, > 80%) - deposition of yellowish extracellular material beneath retinal
pigment epithelium ( " drusen") with gradual in vision. Prevent progression with multivitamin
and antioxidant supplements.
Wet (exudative, 1 0-1 5%) -rapid loss of vision clue to bleed ing secondary to choroidal
neovascularization. Treat with anti-vascular endothelial growth factor injections (anti-VEGF) or

laser.
Visual field defects 1. Right anopia Defect i n visual field of
2. B itemporal hemianopia L eye R eye
3. Left homonymous hemianopia

4. Left upper quadran tic anopia (right temporal 7 Macula
/
Lt.
Optic
At.
lesion, MCA) Optic

nerve
-1 3 Optic tract
I /
5. Left lower quadran tic anopia (right parietal /
chiasm
2 4
lesion, MCA)
Lateral
g enicu late
/
/ eyer s
cop
.
body 5 -
6. Left hemianopia with macular sparing (temporal
Dorsal optic lobe)
( PCA infarct) , macula - bilateral projection rad iation
(parietal
to occiput lobe)
-
3 (6 if
7. C entral scotoma (macular degeneration)
/a
Visual PCA infarct)
Cal rine cortex
fissure
Meyer's loop - i n ferior retina; loops around

inferior horn of lateral ventricle.
Note: When an i m a ge h its 1 visu a l cortex, it is upside
Dorsal optic radiation - superior retina; takes down a n d left-right reversed.
shortest path via internal capsule.
44 2 SECTI O N I l l N E U ROLOGY NEUROLOGY-ANATOMY AND PHYSIOLOGY
Internuclear Medial longitudinal fasciculus (MLF) : pair of MLF i n M S .

ophthalmoplegia tracts that allows for crosstalk between CN When looking left, the left nucleus of C N VI
(MLF syndrome) VI and CN I I I nuclei. Coordinates both eyes fires, which contracts the left lateral rectus and .
to move in same horizontal direction. H ighly stimulates the contralateral (right) nucleus of
myelinated (must commun icate quickly so eyes CN I I I via the right MLF to contract the right
move at same time) . Lesions seen in patients medial rectus.
with demyeli nation (e.g., multiple sclerosis) .
Lesion in MLF INO : lack of communication
=
such that when CN VI nucleus activates

ipsilateral lateral rectus, contralateral CN I I I
nucleus does n o t stimulate medial rectus to
fi re. Abducting eye gets nystagmus (CN VI
overfires to stimulate C I I I ) . Convergence
normal.
Medial Right
rectus INO
subnucleus
of C N 1 1 1 ---.s.
- -'-..
Impaired adduction Nystagm u s
N E U ROLOGY N E U ROLOGY- PAT H OLOGY SECTION Ill 443
N E U ROLOGY-PATH OLOGY
Dementia A ! in cognitive abil ity, memory, or function with intact consciousness.

DISEASE DESCRIPTION HISTOLOGIC/GROSS FINDINGS
Alzheimer's disease Most common cause in elderly. Down Widespread cortical atrophy
syndrome patients have an t risk of developing ! ACh
Alzheimer's . Senile plaques ri]: extracellular -amyloid core ;
Fam i l ial form ( 10 % ) associated with the may cause amyloid angiopathy -+ intracranial
following altered proteins (respective hemorrhage ; A (amyloid-) synthesized by
chromosomes in parentheses) : cleaving amyloid precursor protein
Early onset: APP (2 1 ) , presen ilin-1 ( 14), Neurofibrillary tangles : intracel lular,
presenilin-2 ( 1 ) abnormally phosphorylated tau protein =
Late onset: ApoE4 ( 19) insoluble cytoskeletal elements ; tangles

ApoE2 ( 19 ) is protective . correlate with degree of dementia
Pick's d isease Dementia, aphasia, parkinsonian aspects ; Pick bodies: spherical tau protein aggregates
(frontotem poral change in personality. Frontotemporal atrophy
dementia) Spares parietal lobe and posterior 2/3 of superior
temporal gyrus.
Lewy body dementia Parkinson ism with dementia and hallucinations. a-synuclein defect
Creutzfeldt-Jakob Rapidly progressive (weeks to months) dementia Spongiform cortex
disease (CJD) with myoclonus ( "startle myoclonus" ) . Prions ( Prpc -+ Prpsc sheet [ -pleated sheet
resistant to pro teases] )
Other causes Multi-infarct (2nd most common cause of
dementia in elderly) ; syph ilis; H I V; vitamins
B1, B3, or B12 deficiency; Wilson's disease ; and
NPH.
444 S E CT I O N I l l N E U ROLOGY NEUROLOGY-PATHOLOGY
Multiple sclerosis Autoimmune inflammation and demyelination Charcot's classic triad of M S is a SIN :
of CNS ( brain and spinal cord ) . Patients Scanning speech
can present with optic neuritis (sudden loss Intention tremor (also Incontinence and
of vision ) , MLF syndrome (internuclear Internuclear ophthalmoplegia)

ophthal moplegia) , hemiparesis, hemisensory Nystagmus
symptoms, or bladder/bowel incontinence.
Relapsing a nd rem itting course. Most often
affects women in their 20s and 30s; more
common in whites.
FINDINGS t protein ( IgG) i n C S F. Ol igoclonal bands
are d iagnostic. MRI is gold standard.
Periventricular plaques fJ (areas of
ol igodendrocyte loss and reactive gl iosis) with
destruction of axons.
TREATMENT -interferon, immunosuppression, natal izumab.
Symptomatic treatment for neurogenic bladder
Multiple sclerosis. T2-weighted MRI shows typical
(catheterization, muscari nic antagon ists),
plaques (a rrows) . D
spasticity ( baclofen, GABA receptor agon ist) ,
pain (opioicls) .
Acute inflammatory Most common variant of Guilla in-Barre Associated with infections (Campylobacter
demyelinating syndrome. Autoimmune condition that jejuni and CMV) autoimmune attack of
-+
polyradiculopathy destroys Schwann cells -+ inflammation peripheral myel i n clue to molecular m i m icry,
and demyel ination of peripheral nerves and i noculations, and stress, but no defin itive link
motor fibers. Results in symmetric ascending to pathogens.
muscle weakness/paralysis beginning in lower Respiratory support is critical until recovery.
extremities. Facial paralysis in 50% of cases. Add itional treatment: plasmapheresis, IV
Autonomic function may be severely affected i mmune globulins.
(e.g., cardiac i rregularities, hypertension, or
hypotension) . Almost all patients survive ; the
majority recover completely after weeks to
months.
Findi ngs : t CSF protein with normal cell count
(albuminocytologic dissociation ) . t protein
-+ papilledema.
N E U ROLOGY NEURO LOGY- PATHO LOGY SECTIO N I l l 44 5
Other demyelinating and dysmyelinating diseases

Progressive multifocal Demyel i nation of CNS due to destruction of ol igodendrocytes. Associated with JC viru s. Seen in
leukoencephalopathy 2-4% of AIDS patients (reactivation of latent viral infection ) . Rapidly progressive, usually fatal .
(PML)
Acute disseminated Multifocal perivenular inflammation a n d demyel i nation after infection (commonly measles o r
(postinfectious) VZV) o r certa i n vaccinations (e.g., rabies, smallpox) .
encephalomyelitis
Metachromatic Autosomal-recessive lysosomal storage d isease, most commonly due to arylsulfatase A deficiency.
leukodystrophy Bu ildup of sulfatides leads to impa ired production of myel in sheath .
Charcot- Marie-Tooth Also known as hereditary motor and sensory neuropathy ( H M S N ) . Group of progressive hered itary
disease nerve d isorders related to the defective production of proteins involved i n the structure and
function of peripheral nerves or the myel in sheath .
Krabbe's disease Autosomal-recessive lysosomal storage disease due to deficiency of galactocerebrosidase. B u ildup of
galactocerebroside destroys myelin sheath .
Seizures Characterized by synchron ized, h igh-frequency neuronal firing. Variety of forms.

Partial (focal) seizures Affect 1 area of the brain. Most commonly Epi lepsy- a d isorder of recurrent seizures
originate i n medial temporal lobe. Often (febrile seizures are not epilepsy) .
preceded by seizu re aur a ; can secondarily Status epi lepticus - continuous seizure for > 30
generalize. Types: m i n or recurrent seizures without regaining
Simple partia l (consciousness intact) consciousness between seizures for > 30 min.
motor, sensory, autonomic, psychic Medical emergency.
Complex partial (impaired consciousness) Causes of seizures by age :
Chi ldren - genetic, infection (febrile),
trauma, congenital, metabolic

Adults - tu mors, trauma, stroke, infection
Elderly- stroke, tumor, trauma, metabol ic,
infection
Generalized seizures Diffuse. Types:
Absence (petit mal) - 3 Hz, no postictal
confusion, blank stare

Myoclonic- qu ick, repetitive jerks
Ton ic-clonic (grand mal) -alternating
stiffening and movement

Tonic- stiffen i ng
Atonic- " drop" seizures (falls to floor) ;
commonly m istaken for fainting

446 SECTION I l l N E U ROLOGY N EUROLOGY-PATHOLOGY
Differentiating Pai n due to irritation of structures such as the dura, cranial nerves, or extracranial structures .
headaches
CLASSIFICATION LOCALIZATION DURATION DESCRIPTION TREATMENT
Clustera Unilateral 1 5 min-3 hr; Repetitive brief headaches. Excruciating Inhaled oxygen ,
repetitive periorbital pain with lacrimation and sumatriptan
rhinorrhea. May induce Horner's
syndrome.
More common in males.
Tension Bilateral > 30 min Steady pain. No photophobia or
(typically 4-6 phonophobia. No aura.
hr) ; constant
Migraine Unilateral 4-72 hr Pulsating pain with nausea, photophobia, Abortive therapies
or phonophobia. May have "aura." Due (e.g., triptans)
to irritation of CN V, meninges, or blood and prophylactic
vessels (release of substance P, CGRP, (propranolol ,
vasoactive peptides) . topiramate)
Other causes of headache include subarachnoid hemorrhage ( "worst headache of life " ) , meni ngitis, hydrocephalus, neoplasia,
and arteritis.
a cluster headaches can be differentiated from trigem inal neuralgia (TN) based on duration . TN produces repetitive shooting
pain in the d istribution of CN V that lasts (typically) for < 1 mi nute. The pain from cluster headaches lasts considerably
longer (> 1 5 m inutes) .
Vertigo Sensation of spinning wh ile actually stationary. Subtype of "dizziness," but d istinct from
" 1 ightheadedness."
Peripheral vertigo More common. Inner ear etiology (e.g., semicircular canal debris, vestibular nerve infection,
Meniere's disease) . Positional testing - delayed horizontal nystagmus .
Central vertigo Brain stem or cerebellar lesion (e.g., stroke affecting vestibular nuclei or posterior fossa tumor) .
Findings: directional change of nystagmus, skew deviation, d iplopia, dysmetria. Positional testing
- immediate nystagmus in any direction ; may change directions.
Neurocutaneous disorders
Sturge-Weber Congenital disorder with port-wine stains (aka nevus flammeus), typically i n V 1 ophthalmic
syndrome d istribution ; ipsilateral leptomeningeal angiomas, pheochromocytomas.
Can cause glaucoma, seizures, hemiparesis, and mental retardation. Occurs sporadically.
Tuberous sclerosis HAMARTOMAS : Hamartomas in CNS and skin ; Adenoma sebaceum (cutaneous angiofibromas) ;
Mitral regurgitation ; Ash-leaf spots ; cardiac Rhabdomyoma ; (Tuberous sclerosis) ; autosomal
dOm i nant; Mental retardation ; renal Angiomyol ipoma ; Seizur es.
Neurofi bromatosis Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), neurofibromas i n ski n , optic
type I (von gl iomas, pheochromocytomas. Autosomal dom inant, 1 0 0 % penetrant, variable expression.
Reck\inghausen's Mutated NFl gene on chromosome 17.
disease)
von Hippel-Lindau Cavernous hemangiomas in skin, mucosa, organs ; bil ateral renal cell carcinoma,
disease hemangioblastoma in retina, brain stem, cerebellum; pheochromocytomas. Autosomal dominant;
mutated tumor suppressor VHL gene on chromosome 3 .
N E U ROLOGY NEUROLOGY-PATHOLOGY S E C T I O N Ill 44 7
Adult primary brain tumors

Glioblastoma Most common 1 brai n tumor. Mal ignant with
multiforme (grade IV < 1 -year life expectancy. Found in cerebral
astrocytoma) hemispheres. Can cross corpus callosum
( " butterfly glioma" ) rJ. Stain astrocytes for
CFAP.
" Pseudopal isadi ng" pleomorph ic tumor
cells-border central areas of necrosis and
hemorrhage.
Glioblastoma multiforme. T2-weighted M R I shows a

lobulated mass near the corpus callosum that enhances with
contrast and crosses the midline in an adult with positional
h eadaches. 1i!1
Meningioma 2nd most common 1 o brain tumor. Most often Spindle cells concentrically arranged in
occurs in convexities of hemispheres (near a whorled patte rn ; psammoma bodies
surfaces of brain) and parasagittal region . Arise (laminated calcifications) .
from arachnoid cells, are extra-axial (external
to brain parenchyma) , and may have a dural
attachment ( " tail " ) . Typically benign and
resectable. Often asymptomatic ; may present
with seizures or focal signs.
Schwannoma 3rcl most common 1 brain tumor. Schwann Bilateral acoustic schwannoma found in
cell origi n ; often localized to C VIII neurofibromatosis type 2 .
- acoustic schwannoma (aka acoustic
neuroma) . Resectable or treated with
stereotactic radiosurgery. Usually found at
cerebellopontine angle ; S-100 positive.
Oligodendroglioma Relatively rare, slow growing. Most often in
frontal lobes. Chicken-wire capillary pattern.
Oligoclendrocytes = "fried egg" cells-round
nuclei with clear cytoplasm 1]). Often calcified
i n ol igodendroglioma.
Oligodendroglioma. Infiltrating tumor cells with

perinuclear halos and prominent delicate vasculature. li!l
Pituitary adenoma Most commonly prolactinoma. Bitemporal

hem ianopia (clue to pressure on optic chiasm)
and hyper- or hypopituitarism are sequelae.
448 SECT I O N I l l N E U ROLOGY N EUROLOGY-PAT H OLOGY
Childhood primary brain tumors

Pilocytic (low-grade) Usually well circumscribed. In children, Rosenthal fibers - eosinoph i l ic, corkscrew fibers.
astrocytoma most often found in posterior fossa (e.g., Cystic + solid (gross ) .
cerebellum) . May be supratentorial . GFAP
positive. Benign ; good prognosis.
Medulloblastoma H ighly mal ignant cerebellar tumor. A form Homer-Wright rosettes. S o l i d ( gross), s m a l l blue
of primitive neuroectodermal tumor. Can cells ( h istology) . Radiosensitive.
compress 4th ventricle, causing hydrocephalus.
Can send "drop metastases" to spinal cord.
Ependymoma Ependymal cell tumors most commonly found Characteristic perivascular pseudorosettes. Rod
i n 4th ventricle. Can cause hydrocephalus. shaped blepharoplasts ( basal cil iary bodies)
Poor prognosis. found near nucleus.
Hemangioblastoma Most often cerebellar; associated with von Foamy cells and high vascularity are
H ippel-Li ndau syndrome when found with characteristic.
retinal angiomas. Can produce EPO -+ 2
polycythemia.
Cra n iopharyngioma Benign childhood tumor, confused with Derived from rem nants of Rathke's pouch .
pituitary adenoma (can also cause bitemporal Calcification is common (tooth enamel-like) .
hemianopia) . Most common childhood
supratentorial tumor.
Herniation syndromes 0 C ingulate (subfalcine) herniation Can compress anterior cerebral artery.
under falx cerebri
Lateral 0 Downward transtentorial (central)

ventricles
hern iation
Supratentorial
mass
6) Uncal herniation Uncus = medial temporal lobe.
Uncus
Tentorium 0 Cerebellar tonsillar herniation into the Coma and death result when these herniations
cerebelli
foramen magnum compress the brain stem.
N E U ROLOGY N E U ROLOGY- PHA RMACOLOGY SECTI O N I l l 44 9
NE U ROLOGY- PHA RMACOLOGY
Glaucoma drugs l intraocular pressure via l amount of aqueous humor ( i n h ibit synthesis/secretion or increase
drainage ) .
DRUG MECHANISM SIDE EFFECTS
a-agonists
Epinephrine l aqueous humor synthesis via vasoconstriction Mydriasis; do not use i n closed-angle glaucoma
Brimonidine () l aqueous humor synthesis Blurry vision, ocular hyperem ia, foreign body
sensation , ocular allergic reactions, ocular
pruritus
-blockers
Timolol, betaxolol, l aqueous humor synthesis No pupillary or vision changes
carteolol
D i uretics
Acetazolamide l aqueous humor synthesis via inh ibition of No pupillary or vision changes
carbonic anhydrase
Cholinomimetics
Direct (pilocarpine, t outflow of aqueous humor via contraction M iosis and cyclospasm (contraction of cili ary
carbachol) of cil iary muscle and open ing of trabecular muscle)
Indirect meshwork
(physostigmine, Use pilocarpine in emergencies-very effective
echothiophate) at opening meshwork into canal of Schlemm
Prostaglandin
Latanoprost (PG F2a) t outflow of aqueous humor Darkens color of iris ( brow n ing)
Opioid analgesics Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan, d iphenoxylate.
MECHANISM Act as agonists at opioid receptors (mu = morph ine, delta = en kephalin, kappa = dynorph in)
to modulate synaptic transmission- open K+ channels, close C a 2 + channels l synaptic
--+
transmission. I n h ibit release of ACh, NE, 5-HT, glutamate, substance P.

CliNICAL USE Pain, cough suppression (dextromethorphan), diarrhea ( lopera m ide and d iphenoxylate ) , acute
pulmonary edema, maintenance programs for add icts (methadone ) .
TOXICITY Addiction , respi ratory depression , constipation , m iosis (pinpoint pupils), add itive CNS depression
with other drugs. Tolerance does not develop to miosis and constipation . Toxicity treated with
naloxone or naltrexone (opioid receptor antagon ist) .
Butorphanol
MECHANISM Mu-opioid receptor partial agon ist and kappa-opioid receptor agon ist; produces analgesia.
CliNICAL USE Severe pain (migraine, labor, etc . ) . Causes less respiratory depression than full opioid agon ists.
TOXICITY Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for
opioid receptors ) . Overdose not easily reversed with naloxone.
4 50 SEC T IO N I l l N E U R O LO G Y NEUROLOGY- PHARMACOLOGY
Tramadol
MECHANISM Very weak opioid agonist; also inh ibits seroton in and NE reuptake (works on mu ltiple
neurotransm itters-" tram it all " in with tramadol) .
CliNICAL USE Chron ic pa i n .
TOXICITY Similar t o opioids. Decreases seizur e threshold.
N E U R O LO G Y NEUROLOGY- PHARMACO LOGY SECTION Ill 45 1
Epilepsy drugs
PARTIAL (FOCAL) GENERALIZED
STATUS
SIMPLE COMPLEX TONIC-CLONIC ABSENCE EPILEPTICUS MECHANISM NOTES
Phenytoin ./ ./ lst l ine l st l ine for t Na+ channel Fosphenytoin for

prophylaxis in activation parenteral use
Carbamazepine l st line l st l i ne l st l ine t Na+ channel lst line for
inactivation trigeminal
neuralgia
Lamotrigine ./ ./ Blocks voltage-
gated Na+
channels
Gabapentin ./ ./ Designed as GABA Also used for
analog, but peripheral
primarily i n h ibits neuropathy,
h igh-voltage- postherpetic
activated C a 2 + neuralgia,
channels m tgrame
prophylaxis,
bipolar d isorder
Topiramate ./ ./ ./ Blocks a+ Also used for
channels, mtgrame
t GABA action prevention
Phenobarbital ./ ./ ./ t GABA A action l st l i ne i n children
Valproic acid ./ ./ lst l ine ./ t Na+ channel Also used for
inactivation, myoclon ic
t GABA setzures
concentration
Ethosuximide l st l ine Blocks thalamic
T-type C a 2 +
channels
Benzodiazepines l st l ine for t GABA A action Also used for
(diazepam or acute seizures of
lorazepam) eclampsia ( l st
l ine is MgS0 4 )
Tiagabine ./ ./ Inh ibits GABA
reuptake
Vigabatrin ./ ./ Irreversibly
inh ibits GABA
transaminase
..... t GABA
Levetiracetam ./ ./ Unknow n ; may
modulate GABA
and glutamate
release
4 52 SECTION I l l N E U R O LOGY NEURO LOGY- PHARM ACO LOGY
Epilepsy drug toxicities

Benzodiazepines Sedation, tolerance, dependence. Stevens-Johnson syndrome -prodrome of
Carbamazepine Diplopia, ataxia, blood dyscrasias malaise and fever followed by rapid onset of
(agranulocytosis, aplastic anem ia) , l iver erythematous/purpuric macules (oral, ocular,
toxicity, teratogenesis, i nduction of cytochrome gen ital ) . Skin lesions progress to epidermal
P-450, SIADH , Stevens-Johnson syndrome. necrosis and sloughing.
Ethosuximide GI d istress, fati gue, headache, urticaria, EFGH - Ethosuxim ide, Fatigue, GI , Headache.
Stevens-Johnson syndrome.
Phenobarbital Sedation, tolerance, dependence, i nduction of
cytochrome P-450.
Phenytoin Nystagmus, d iplopia, ataxia, sedation , gingival
hyperplasia, h i rsutism, megaloblastic anem ia,
teratogenesis (fetal hydantoin syndrome) , SLE
l ike syndrome, i nduction of cytochrome P-450,
lymphadenopathy, Stevens-Johnson syndrome,
osteopenia.
Valproic acid GI d istress, rare but fatal hepatotoxicity
(measure 1FT's), neural tube defects in
fetus (spina bifida), tremor, weight ga in.
Contraindicated i n pregnancy.
Lamotrigine Stevens-Johnson syndrome.
Gabapentin Sedation, ataxi a .
Topiramate Sedation , mental dulling, kidney stones, weight
loss.
Phenytoin
MECHANISM Use-dependent blockade of Na+ channels; inh ibition of glutamate release from excitatory
presynaptic neuron.
CLINICAL USE Ton ic-clon ic seizures. Also a class I B antiarrhythm ic .
TOXICITY Nystagmus, ataxia, d iplopia, sedation, SLE-l ike syndrome, i nduction o f cytochrome P-4 5 0 . Chronic
use produces gingival hyperplasia in children, peripheral neuropathy, h i rsutism, megaloblastic
anem ia U folate absorption) . Teratogen ic (fetal hydantoin syndrome) .
Barbiturates Phenobarbital, pentobarbital, thiopental , secobarbital.

MECHANISM Facil itate GABA A action by t duration of CJ- chan nel open ing, thus ! neuron firing (barbidurates
t duration) . Contraindicated in porphyria.
CLINICAL USE Sedative for anxiety, seizures, insomnia, i nduction of anesthesia (th iopental ) .
TOXICITY Respiratory and card iovascular depression (can b e fatal ) ; CNS depression (can b e exacerbated by
EtOH use) ; dependence; drug interactions (i nduces P-4 5 0 ) .
Overdose treatment is supportive (assist respiration a n d mainta i n BP) .
N E U R O LOGY NE UROLOGY- PHARMACOLOGY S E C TI O N I l l 4 53
Benzodiazepines Diazepam, lorazepam, triazolam, temazepam , oxazepam , m idazolam, chlord iazepoxide,

alprazolam.
MECHANISM Facilitate GABA A action by t frequency of Frenzodiazepines t frequency.
Cl- chan nel opening. ! REM sleep. Most Benzos, barbs, and EtOH all bind the
have long half-l ives and active metabol ites GABA A receptor, which is a l igand-gated
(exception s : triazolam, oxazepam, and chloride channel .
m idazolam are short acting ..... higher addictive
potential ) .
CLINICAL USE Anxiety, spasticity, status epilepticus (lorazepam
and d iazepam) , detoxification (especially
alcohol withd rawal-DTs), n ight terrors,
sleepwalking, general anesthetic (amnesia,
muscle relaxation ) , hypnotic (insomn ia) .
TOXICITY Dependence, add itive CNS depression effects
with alcohol . Less risk of respiratory depression
and coma than with barbiturates.
Treat overdose with flumazenil (competitive
antagonist at GABA benzodiazepine receptor) .
Nonbenzodiazepine Zolpidem (Ambien) , zaleplon, eszopiclone.

hypnotics
MECHANISM Act via the B Z l subtype of the GABA receptor. Effects reversed by flumazen i l .
CLINICAL USE Insomnia.
TOXICITY Ataxia, headaches, confusion. Short duration because of rapid metabol ism by l iver enzymes. Unlike
older sedative-hypnotics, cause only modest day-after psychomotor depression and few am nestic
effects. Lower dependence risk than benzodiazepines.
Anesthetics-general CNS drugs must be l ipid soluble (cross the blood-brain barrier) or be actively transported.
principles Drugs with ! solubility in blood = rapid induction and recovery times.
Drugs with t solubi l ity i n l ipids = t potency = _l

_
MAC
MAC = m i n imal alveolar concentration at which 5 0 % of the population is anesthetized. Varies
with age .
Examples: N 2 0 has ! blood and l ipid solubility, and thus fast induction and low potency.
Halothane, in contrast, has t lipid and blood solubi lity, and thus h i gh potency and slow induction.
Inhaled anesthetics Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, n itrous oxide.

MECHANISM Mechanism unknown .
EFFECTS Myocard ial depression, respiratory depression , nausea /emesis, t cerebral blood flow ( ! cerebral
metabol ic demand) .
TOXICITY Hepatotoxicity (halothane), neph rotoxicity (methoxyflurane), proconvu lsant ( enflurane) , mal ignant
hyperthermia (all but nitrous oxide; rare, life-threatening, inherited susceptibility) , expansion of
trapped gas in a body cavity (n itrous oxide ) .
4 54 SEC T IO N I l l N E U R O LO G Y NEU ROLOGY- PHARMACOLOGY
Intravenous anesthetics
Barbiturates Th iopental-h igh potency, high l ipid solubility, B . B. Ki ng on OPIOIDS PROPOses
rapid entry into brain. Used for induction FOOLishly.
of anesthesia and short surgical procedures.
Effect term inated by rapid redi stribution into
tissue (i.e., skeletal muscle) and fat. ! cerebral
blood Aow.
Benzodiazepines Midazolam most com mon dru g used for
endoscopy; used adjunctively with gaseous
anesthetics and narcotics. May cause severe
postoperative respiratory depression, ! BP (treat
overdose with Aumazen il), and amnesia.
Arylcyclohexyla mines PCP analogs that act as dissociative anesthetics.
(Ketamine) Block M DA receptors. Cardiovascular
stimulants. Cause disorientation ,
hallucination , and bad dreams. t cerebral
blood Aow.
Opioids Morphine, fentanyl used with other CNS
depressants during general anesthesia.
Propofol Used for sedation in ICU, rapid anesthesia Not recommended for home use by pop stars.
induction, and short procedures. Less
postoperative nausea than thiopental.
Potentiates GABA A '
Local anesthetics Esters -procaine, cocai ne, tetracaine.

Amides -l ldocalne, meplvacalne, buplvacalne (amldes have 2 I's in name) .
MECHANISM Block a+ channels by binding to specific receptors on inner portion of channel. Preferentially
bind to activated Na+ channels, so most effective i n rapidly firing neurons. 3 amine local
anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
PRINCIPLE Can be given with vasoconstrictors (usually epi nephrine) to enhance local action - ! bleedi ng,
t anesthesia by ! systemic concentration.
In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane
effectively need more anesthetic.
--+
Order of nerve blockade: small-diameter fibers > large diameter. Myel inated fibers > un myel inated
fibers. Overall, size factor predominates over myel ination such that small myel inated fibers
> small unmyel inated fibers > large myel inated fibers > large unmyel inated fibers.
Order of loss : ( l ) pain, (2) temperature, ( 3 ) touch, (4) pressure.
CliNICAL USE M inor surgical procedures, spinal anesthesia. If allergic to esters, give am ides.
TOXICITY CNS excitation, severe card iovascular toxicity (bupivacaine), hypertension, hypotension, and
arrhythm ias (cocaine) .
N E U R O LO G Y NEUROLOGY- PHARMACOLOGY SECTION I l l 455
Neuromuscular Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs . autonomic)
blocking drugs nicotinic receptor.
Depo l arizing Succinylcholine- strong ACh receptor agonist; produces sustained depolarization and prevents
muscle contraction .
Reversal of blockade:
Phase I (prolonged depolari zation) -no antidote. Block potentiated by chol inesterase inh ibitors.
Phase I I (repolarized but blocked; ACh receptors are ava ilable, but desensitized) -antidote
consists of chol inesterase inhibitors (e.g., neostigm ine) .

Complications include hypercalcemia, hyperkalemia, and malignant hyperthermia.
Nondepo l arizing Tubocurarine, atracurium, mivacurium, pancuron ium, vecuronium, rocuronium. C ompetitive
antagonists - compete with ACh for receptors.
Reversal of blockade-neostigmine, ecl r ophon ium, and other cholinesterase inh ibitors.
Dantrolene
MECHANISM Prevents the release of Ca 2 + from the sarcoplasmic reticulum of skeletal muscle.
CLINICAL USE Used in the treatment of mal ignant hyperthermia, a rare but l i fe-threatening side effect of
inhalation anesthetics (except N 2 0) and succinylchol ine. Also used to treat neuroleptic mal ignant
syndrome (a toxicity of antipsychotic drugs).
Parkinson's disease Parkinsonism is clue to loss of cloparninergic neurons and excess chol inergic activity.
drugs
STRATEGY AGENTS
Dopamine agonists Bromocriptine (ergot) , pram ipexole, ropinirole BALSA :

(non-ergot) ; non-ergots are preferred Bromocriptine
t dopamine Amantadine (may t dopamine release) ; also Am antad ine
used as an antiviral against influenza A and Levocl o pa (with carbiclopa)
rubella; toxicity = ataxia Selegiline (and COMT inh ibitors)
L-clopa/carbidopa (converted to dopamine in Antimuscarin ics
CNS) For essential or fam i l ial tremors, use a -blocker
(e.g., propranolol ) .
Prevent dopamine Selegiline (selective MAO type B inh ibitor) ;
breakdown entacapone, tolcapone (COMT inh ibitors
prevent L-clopa clegraclation , thereby increasing
dopamine availabil ity)
Curb excess chol inergic Benztropine (Antimuscarinic ; improves Park your Mercedes-Benz.
activity tremor and rigidity but has l ittle effect on
bradykinesia)
456 SECTI O N I l l N E UROLOGY NEUROLOGY- PHARMACOLOGY
Ldopa (levodopa)/ carbidopa

MECHANISM t level of dopamine in brain. Unl ike dopamine, L-clopa can cross blood-brai n barrier and is
converted by dopa decarboxylase in the CNS to dopamine. Carbiclopa, a peripheral decarboxylase
inhibitor, is given with L-clopa to t the bioavailabil ity of L-clopa i n the bra i n and to l i m it peripheral
s i cl e effects.
CliNICAL USE Parkinson's disease.
TOXICITY Arrhythmias from increased peripheral formation of catecholamines. Long-term use can lead
to dyskinesia following administration, akinesia between clo ses.
Selegiline
MECHANISM Selectively inh ibits MAO-B, which preferentially metabol izes dopamine over N E and 5-HT,
thereby increasing the availability of dopamine.
CLINICAL USE Adjunctive agent to L-clopa in treatment of Parkinson's disease.
TOXICITY May enhance adverse effects of L-cl o pa .
Alzheimer's drugs
Memantine
MECHANISM N M DA receptor antagon ist; helps prevent excitotoxicity (mediated by Ca 2 +) .
TOXICITY Dizziness, confusion, hallucinations.
Donepezil, galantam ine, rivastigmine
MECHANISM Acetylchol inesterase inh ibitors.
TOXICITY Nausea, dizziness, insomnia.
Huntington's drugs Neurotransmitter changes in Huntington's d isease : GABA, ACh, t dopamine.

Treatments :
Tetrabenazine and reserpine - inhibit VMAT; l i m it dopamine vesicle packaging and release.
H aloperidol - dopa m i ne receptor antagonist.
Sumatriptan
MECHANISM 5-HT J B/ID agonist. Inh ibits trigem inal nerve A SUMo wrestler TRIPs ANd falls on your
activation ; prevents vasoactive peptide release ; head.
i nduces vasoconstriction. Half-life < 2 hours.
C liNICAL USE Acute m igraine, cluster headache attacks.
TOXICITY Coronary vasospasm (contraindicated in
patients with CAD or Prinzmetal's angina),
mild tingling.
Psychiatry
"A Freudian slip is when you say one thing but mean your mother."
-Anonymous
"Men will always be mad, and those who think they can cure them are the
maddest of all."
-Voltaire
"Anyone who goes to a psychiatrist ought to have his head examined."

- Samuel Goldwyn
4 58 SECTION Ill PSYCHI ATRY PSYCHIATRY-PSYCHOLOGY
PSYCHIATRY-PSYCHOLOGY
Classical conditioning Learning in which a natural response Pavlov's classical experiments with dogs
(salivation) is elicited by a conditioned, ringing the bell provoked salivation.
or learned, stimulus (bell) that previously
was presented in conjunction with an
u nconditioned stimulus (food) .
Operant conditioning Learning in which a particular action is elicited because it produces a reward .
Positive reinforcement Desired reward produces action (mouse presses button to get food) .
Negative Target behavior (response) is fol lowed by removal of aversive stimulus (mouse presses button to turn
rei nforcement off continuous loud noise) .
Punish ment Repeated application of aversive stimulus extinguishes u nwanted behavior.
Extinction Discontinuation of reinforcement (positive or negative) eventually eliminates behavior.
Transference and countertransference

Transference Patient projects feelings about formative or other important persons onto physician (e.g.,
psychiatrist is seen as parent) .
Cou ntertransference Doctor projects feelings about formative or other important persons onto patient.
Ego defenses Unconscious mental processes used to resolve conflict and prevent undesirable feelings (e.g.,
anxiety, depression) .
IMMATURE DEFENSES DESCRIPTION EXAMPLE
Acting out Unacceptable feelings and thoughts are Ta ntmm s.

expressed through actions.
Dissociation Temporary, drastic change in personality, Extreme forms can result in dissociative identity
memory, consciousness, or motor behavior to disorder (multiple personality disorder) .
avoid emotional stress.
Denial Avoidance of awareness of some painful reality. A common reaction in newly diagnosed AIDS
and cancer patients .
Displacement Process whereby avoided ideas and feelings are Mother yells at her child, because her husband
transferred to some neutral person or object yelled at her.
(vs. projection) .
Fixation Partially remaining a t a more childish level of Men fixating on sports games.
development (vs. regression) .
Identification Modeling behavior after another person who Abused child identifies himself/herself with an
is more powerful (though not necessarily abuser.
admired ) .
Isolation (of affect) Separation o f feelings from ideas a n d events. Describing murder in graphic detail with no
emotiona 1 response.
Projection An unacceptable internal impulse is attributed A man who wants another woman thinks his
to an external source (vs. displacement) . wife is cheating on him .
PSYCHIATRY PSYCHIATRY-PATHOLOGY SECTION Ill 4 59
Ego defenses (continued)

IMMATURE DEFENSES DESCRIPTION EXAMPLE
Rational ization Proclaiming logical reasons for actions actually After getting fi red, claimin g that the job was not
performed for other reasons, usually to avoid important anyway.
self-blame.
Reaction formation Process whereby a warded-off idea or feeling A patient with libidinous thoughts enters a
is replaced by an (unconsciously derived) monastery.
emphasis on its opposite (vs. sublimation).
Regression Turning back the maturational clock and going Seen in children u nder stress such as ill ness,
back to earlier modes of dealing with the world punishment, or birth of a new sibling (e.g.,
(vs. fixation). bed wetting in a previously toilet-trained ch ilcl
when hospitalized).
Repression I nvoluntary withholding of an idea or feeling Not remembering a conflictual or traumatic
from conscious awareness (vs. suppression). experience; pressing bad thoughts into the
u nconSCIOUS.
Splitting Belief that people are either all good or all A patient says that all the nurses are cold and
bad at different times clue to intolerance of insensitive but that the doctors are warm and
a mbiguity. Seen in borderline personality friendly.
disorder.
MATURE DEFENSES
Altru ism Guilty feelings alleviated by unsolicited Mafia boss makes large donation to charity.
generosity toward others.
Humor Appreciating the amusing nature of an anxiety Nervous medical student jokes about the boards.
provoking or adverse situation.
Sublimation Process whereby one replaces an unacceptable Teenager's aggression toward his father is
wish with a course of action that is similar to redirected to perform well in sports.
the wish but does not conflict with one's value
system (vs. reaction formation).
Suppression Voluntary withholding of an idea or feeling Choosing not to think about the U S M LE until
from conscious awareness (vs. repression). the week of the exam.
Mature adults wear a SASH: Sublimation, Altruism, Suppression, Hu mor.
PSYCHIATRY-PATHOLOGY
Infant deprivation Long-term deprivation of affection results in: The 4 W 's: Weak, Wordless, Wanting (socially),
effects ! muscle tone Wary.
Poor language skills Deprivation for> 6 months can lead to
Poor socialization skil ls irreversible changes.
Lack of basic trust Severe deprivation can result in infant death.
Anaclitic depression (infant withdrawn/
u nresponsive)
Weight loss
Physical illness
460 SECTION Ill PSYCHIATRY PSYCHIATRY-PATHOLOGY
Child abuse
Physical abuse Sexual abuse
EVIDENCE Healed fractures on x-ray, burns (e.g., cigarette, Genital, anal, or oral trauma; STis ; U Tis
scalding), subdural hematomas, multiple
bruises, retinal hemorrhage or detachment
ABUSER Usually male caregiver Known to victim, usually male
EPIDEMIOLOGY -3000 deaths/yr in U. S ., 80% < 3 yr of age Peak incidence 9-12 years of age
Child negled Failure to provide a child with adequate food, shelter, supervision, education, and/or affection .
Most common form o f child maltreatment. Evidence: poor hygiene, malnutrition, withdrawal,
impaired social/emotional development, failure to thrive.
As with child abuse, child neglect must be reported to local child protective services.
Childhood and early-onset disorders

Attention-deficit Onset before age 7. Limited attention span and poor impulse control. Characterized by
hyperactivity hyperactivity, impulsivity, and inattention in multiple settings (school, home, places of worship,
disorder (ADHD) etc.). Normal intelligence, but commonly coexists with difficulties in school . Continues into
adulthood in as many as 50% of individuals. Associated with !frontal lobe volumes. Treatment:
methylphenidate, amphetamines, atomoxetine, behavioral interventions (reinforcement, reward).
Conduct d isorder Repetitive and pervasive behavior violating the ba sic rights of others (e.g., physical aggression,
destruction of property, theft). After 18 years of age, many of these patients will meet criteria for
diagnosis of antisocial persona lity disorder.
Oppositional defiant Enduring pattern of hostile, defiant behavior toward authority figures in the absence of serious
d i sorder violations of social norms.
Tou rette's syndrome Onset before age 18. Characterized by sudden, rapid, recurrent, nonrhythmic, stereotyped motor
and vocal tics that persist for> 1 year. Lifetime prevalence of 0.1-1.0% in the general population.
Coprolalia (involuntary obscene speech) found in only 10-20% of patients. Associated with
OCD. Treatment: antipsychotics and behavioral therapy.
Separation anxiety Common onset at 7-9 years of age. Overwhelming fear of separation from home or loss of
d i sorder attachment figure. May lead to factitious physical complaints to avoid going to or staying at
school. Treatment: SSRis and relaxation techniques/behavioral interventions.
PSYCHIATRY PSYCHIATRY-PATHOLOGY SECTION Ill 46 l
Pervasive Characterized by difficulties with language and fa ilure to acqu i re or early loss of social sk ills.
developmental
disorders
Autistic d i sorder Severe language i mpairment and poor social i nteractions. Greater focus on objects than on
people. Characterized by repetitive behavior and usually below-normal i ntel l i gence. Rarely
accompanied by unusual abil ities (savants). More common in boys. Treatment: behavioral and
supportive therapy to improve communication and social skills. Medication when appropriate
(i.e., disruptive/harmful behavior).
Asperger's d isorder M ilder form of autism. Characterized by all-absorbing interests, repetitive behavior, and problems
with social relationships. Children are of normal i ntel l igence and lack verbal or cognitive deficits.
No language impairment.
Rett's disorder X-linkecl disorder seen al most exclusively in girls (affected males die in utero or shortly after birth).
Symptoms usually become apparent around ages l-4, includ ing regression characterized by loss
of development, loss of verbal abilities, mental retardation, ataxia, and stereotyped hand-wringing.
Childhood Common age of onset is 3-4 years. Marked regression in multiple areas of function ing after at least
disintegrative 2 years of apparently normal development. Significant loss of expressive or receptive language
disorder skills, social skills or adaptive behavior, bowel or bladder control, play, or motor skills. More
common in boys.
Neurotransmitter DISORDER NEUROTRANSMITIER CHANGES
changes with disease Anxiety t NE, ! GABA, ! serotonin ( 5 -HT)

Depression !NE, ! serotonin ( 5 -HT) , ! dopa m i ne
Alzheimer's dementia !ACh
Huntington's disease !GABA, !ACh, t dopa m i ne
Schizophrenia t dopamine
Parkinson's disease ! dopa m ine, t seroton i n ( 5 -HT), t ACh
Understanding these changes can help guide pharmacologic treatment choice.
Orientation Patient's abil ity to know who he or she is, where Order of loss: 1st-time ; 2nd - place ; last
he or she is, and the elate and time. person.
Common causes of loss of orientation: Often abbreviated i n the medical chart as "alert
alcohol, drugs, Au icl/electrolyte imbalance, and oriented x 3" (AOx3).
head trauma, hypoglycemia, nutritional
deficiencies.
Amnesias
Retrograde a m ne sia Inabil ity to remember things that occurred before a CNS insult.
Anterograd e amnesia Inabil ity to remember things that occurred after a CNS insult (no new memory).
Korsakoff's a mnesia Classic anterograde amnesia caused by thiamine deficiency and the associated destruction
of mamm illary bodies. May also include some retrograde am nesia. Seen i n alcohol ics, and
associated with confabulations.
Dissociative a m n e s i a Inability to recall i mportant personal information, usually subsequent to severe trauma or stress.
46 2 SECTION Ill PSYCHI ATRY PSYCHIATRY-PATHOLOGY
Cognitive disorder Sign ificant change i n cognition (memory, attention, language, judgment) from previous level of
functioning. Associated with abnormal ities in CNS, a general medical condition, med ications, or
substance use. I ncludes del irium and dementia.
Delirium "Waxing and wan ing" level of consciousness Delirium= changes i n sensorium.
with acute onset; rapid ! in attention span and Check for drugs with antichol inergic effects.
level of arousal. Characterized by disorganized Often reversible.
thinking, hallucinations (often visual),
illusions, misperceptions, disturbance in sleep
wake cycle, cognitive dysfunction.
Usually secondary to other illness (e.g., CNS
disease, infection, trauma, substance abuse/
withdrawal).
Most common presentation of altered mental
status in i npatient setting. Abnormal EEG.
Treatment:
Identify and address underlying cause . T-A-DA approach (Tolerate, Anticipate, Don't
Optimize bra in condition (02, hydration, Agitate) helpful for management.
pain, etc .)
Antipsychotics (mainly haloperidol).
Dementia Gradual ! in intellectual abil ity or "cogn ition" "Dememtia" is characterized by memory loss.
without affecting level of consciousness. Usually irreversible.
Characterized by memory deficits, aphasia, I n elderly patients, depression may present l ike
apraxia, agnosia, loss of abstract thought, dementia (pseuclodementia).
behavioral/personality changes, impaired
judgment. A patient with dementia can
develop del irium (e.g., an Alzheimer's patient
who develops pneumonia is at increased risk
for delirium).
Caused by Alzheimer's disease, cerebral
vascular infarcts, H I V, Pick 's disease, chron ic
substance abuse (cl u e to neurotoxicity of
drugs), Creutzfelclt-Jakob disease, NPH, and
many other disorders.
t incidence with age. EEG usually normal.
Psychotic disorder A distorted perception of real ity (psychosis) characterized by delusions, hallucinations, and/or
disorganized thinking. Psychosis can occur in patients with medical illness, psychiatric i llness, or
both.
PSYCHIATRY PSYCHIATRY-PATHOLOGY SECTION Ill 463
Signs of psychosis
Hallucinations Perceptions in the absence of external stimuli (e.g., seeing a l ight that is not actually present).
Delusions False beliefs about oneself or others that persist despite the facts (e.g., th inking the CIA is spying on
you).
Disorganized speech Words and ideas are strung together based on sounds, puns, or "loose associations."
Hallucination types
Visual More commonly a feature of medical illness (e.g., drug i ntoxication) than psych iatric ill ness.
Auditory More commonly a feature of psych iatric illness (e.g., schi zophren ia) than medical i l l ness.
Olfactory Often occur as an aura of psychomotor epilepsy and i n bra i n tumors.
Gustatory Rare.
Tactile Common in alcohol withdrawal (e.g., formication-the sensation of bugs crawl ing on one's skin).
Also seen in cocaine abusers ("cocaine crawl ies").
HypnaGOgic Occurs wh ile GOing to sleep.
Hypno POM Pic Occurs wh ile waking from sleep ("POMPous upon awakening").
Schizophrenia Chronic mental disorder with periods of 5 subtypes:

psychosis, disturbed behavior and thought, Paranoid (delusions)
and decl ine in function ing that lasts> 6 Disorganized (with regard to speech,
months. Associated with t dopaminergic behavior, and affect)

activity, ! dendritic branching. Catatonic (automatisms)
Undifferentiated (elements of all types)

D iagnosis requi res 2 or more of the following
Residual
(first 4 i n this l ist are "positive symptoms"):
Delusions Genetics and environment contribute to the
H allucinations-often auditory etiology of schizophrenia.
D isorgan ized speech (loose associations) Frequent cannabis use is associated with
D isorgan ized or catatonic behavior psychosis/schizophren ia i n teens.
"Negative symptoms"-flat affect, social Lifetime prevalence-1 . 5 % (males= females,
withdrawal, lack of motivation, lack of blacks= whites). Presents earl ier i n men (late
speech or thought teens to early 20s vs . late 20s to early 30s in
B rief psychotic d isorder-< l month, usually women). Patients are at t risk for suicide.
stress related.
Schizophre n iform d isorder -l-6 months.
Schizoaffective d isorder-at least 2 weeks of

stable mood with psychotic symptoms, plus
a major depressive, man ic, or m ixed (both)
episode. 2 subtypes : bipolar or depressive.
Delusional disorder Fixed, persistent, non bizarre bel ief system lasting> l month. Function ing otherwise not impaired.
Example: a woman who genu inely believes she is married to a celebrity when, in fact, she is not.
Shared psychotic d isorder (folie a deux) -development of delusions i n a person in a close
relationship with someone with delusional disorder. Often resolves upon separation .
46 4 SECTION Ill PSYCHIATRY PSYCHIATRY-PATHOLOGY
Dissociative disorders
Dissociative identity Formerly known as multiple personal ity disorder. Presence of 2 or more d istinct identities or
d i sorder personal ity states. More common in women. Associated with h istory of sexual abuse.
Depersona l i zation Persistent feel ings of detachment or estrangement from one's own body, a social situation, or the
d i sorder environment.
Dissociative fugue Abrupt change in geographic location with inabil ity to recall the past, confusion about personal
identity, or assumption of a new identity. Associated with traumatic circumstances (e.g., natural
disasters, wartime, trauma). Leads to significant distress or impairment. Not the result of
substance abuse or general medical condition.
Mood disorder Characterized by an abnormal range of moods or internal emotional states and loss of control over
them. Severity of moods causes distress and impa irment in social and occupational functioning.
Includes major depressive disorder, bipolar disorder, dysthymic disorder, and cyclothymic
disorder. Psychotic features (delusions or hallucinations) may be present.
Manic episode D istinct period of abnormally and persistently elevated, expansive, or irritable mood and
abnormally and persistently increased activity or energy lasting at least l week. Often disturbing
to patient.
Diagnosis requ ires hospitalization or at least 3 of the following (manics DIG FAST ):
Distractibility Fl i ght of ideas - racing thoughts
Irresponsibi lity-seeks pleasure without t in goal-directed Activity/psychomotor
regard to consequences (hedon istic) Agitation

Grandiosity- inflated self-esteem ! need for Sleep
Talkativeness or pressured speech
Hypomanic episode Like manic episode except mood disturbance is not severe enough to cause marked impai rment in
social and/or occupational functioning or to necessitate hospital ization . No psychotic features.
Bipolar disorder Defined by the presence of at least 1 manic (bipolar I ) or hypomanic (bipolar II) episode.
Depressive symptoms always occur eventually. Patient's mood and function ing usually return
to normal between episodes. Use of antidepressants can lead to t mania. High su icide risk.
Treatment: mood stabili zers (e.g., l ith ium, valproic acid, carbamazepine), atypical antipsychotics.
Cyclothym ic d i sorder - dysthymia and hypomania; m ilder form of bipolar d isorder lasting a t least
2 years.
PSYCHIATRY PSYCHIATRY-PATHOLOGY SECTION Ill 46 5
Major depressive Self-l im ited d isorder, with major depressive

disorder episodes usually lasting 6-12 months.
Episodes characterized by at least 5 of the
following 9 symptoms for 2 or more weeks
(symptoms must include patient-reported
depressed mood or anhedonia and occur more
frequently as the d isorder progresses):
Characterized by:
Sleep disturbance SIG E C AP S. Com monly used mnemonic
Loss of Interest (anhedon ia) for depression screen ing. Historically used
Gu i lt or feelings of worth less ness by physicians in prescription writing. SIG is
Loss of Energy short for signatura (Lati n for "directions").
Loss of Concentration Depressed patients were d i rected to take
Appetite/weight changes Energy C APSules .
Psychomotor retardation or agitation Lifetime prevalence of major depressive episode :
Su icidal ideations 5-12% m ale, 10-25% female.
Depressed mood
Dysthymi a -milder form of depression lasting

at least 2 years.
Seasonal affective d isorder- symptoms

associated with winter season ; improves
in response to ful l-spectrum bright-l ight
exposure.
Atypical depression Differs from classical forms of depression. Characterized by mood reactivity (being able to
experience improved mood in response to positive events), "reversed" vegetative symptoms
(hypersomnia and weight ga in), leaden paralysis (heavy feeling i n arms and legs), and
long-standing i nterpersonal rejection sensitivity. Most common subtype of depression .
Treatment: MAO inhibitors, SSRis.
Postpartum mood disturbances

Maternal 50-85% i ncidence rate. Characterized by depressed affect, tearfu lness, and fatigue starting 2-3
(postpartum) "blues" clays after del ivery. Usually resolves within 10-14 clays. Treatment: supportive . Fol low-up to
assess for possible postpartum depression .
Postpartum 10-15% i ncidence rate. Characterized by depressed affect, anxiety, and poor concentration starting
depression with i n 4 weeks after del ivery. Lasts 2 weeks to a year or more. Treatment: antidepressants,
psychotherapy.
Postpartum psychosis 0.1-0.2% i ncidence rate. Characterized by delusions, hallucinations, confusion, unusual
behavior, and possible homicidal/su icidal ideations or attempts. Usually lasts days to 4-6 weeks.
Treatment: antipsychotics, antidepressants, possible inpatient hospital ization .
466 SECTION Ill PSYCHIATRY PSYCHIATRY-PATHOLOGY
Eledroconvulsive Treatment option for major depressive disorder refractory to other treatment and for pregnant
therapy women with major depressive disorder. Also considered when immediate response is necessary
(acute suicidality), in depression with psychotic features, and for catatonia. Produces a painless
seizure in a n anesthetized patient. Major adverse effects are disorientation and temporary
anterograde/retrograde am nesia usually fully resolving in 6 months.
Risk fadors for suicide Sex (male), Age (teenager or elderly), SAD PERSONS are more likely to complete
completion Depression, Previous attempt, Ethanol or suicide.
dru g use, loss of Rational thinking, Sickness
(medical illness, 3 or more prescription
medications), Organized plan, No spouse
(divorced, widowed, or single, especially if
childless), Social support lacking.
Women try more often ; men succeed more
often.
Anxiety disorder Inappropriate experience of fear/worry and its physical manifestations (anxiety) when the source
of the fear/worry is either not real or insufficient to account for the severity of the symptoms.
Symptoms interfere with daily functioning. Lifetime prevalence of 30% in women and 19% in
men. Includes panic disorder, phobias, OCD, PTSD, and generalized anxiety disorder.
Panic disorder Defined by the presence of recurrent periods PANICS.

of intense fear and discomfort peaking in Described in context of occurrence (e.g., panic
10 minutes with at least 4 of the following: disorder with agoraphobia).
Palpitations, Paresthesias, Abdominal distress, Associated with persistent fear of having another
Nausea, Intense fear of dying or losing attack.
control, light-headed ness, Chest pain, Chills, Symptoms are the systemic m anifestations of
Choking, disConnectedness, Sweating, fear.
Shaking, Shortness of breath. Strong
genetic component. Treatment: cognitive
behavioral therapy (CBT), SSRis, venlafaxine,
benzodiazepines (risk of tolerance, physical
dependence).
Specific phobia Fear that is excessive or unreasonable and interferes with normal function. Cued by presence or
anticipation of a specific object or situation. Person recognizes fear is excessive. Can treat with
systematic desensitization.
Social phobia (social anxiety disorder) - exaggerated fear of embarrassment in social situations
(e.g., public speaking, using public restrooms). Treatment: SSRis.
Obsessive-compulsive Recurring intrusive thoughts, feelings, or sensations (obsessions) that cause severe distress ;
disorder relieved in part by the performance of repetitive actions (compulsions). Ego dystonic: behavior
inconsistent with one's own beliefs and attitudes (vs. obsessive-compulsive personality disorder).
Associated with Tourette's disorder. Treatment: SSRis, clomipramine.
Post-trau matic stress Persistent reexperiencing of a previous traumatic event (e. g., war, rape, robbery, serious accident,
disorder fire) . May i nvolve n i ghtmares or flashbacks, i ntense fear, helplessness, or horror. Leads to
avoidance of sti muli associated with the trauma and persistently t arousal . Disturbance lasts>
I month, with onset of symptoms beginning anytime after event, and causes significant distress
and/or impaired functioning. Treatment: psychotherapy, SSRis.
Acute stress d i sorder - lasts between 2 days and I month.
Generalized anxiety Pattern of u ncontrollable anxiety for at least 6 months that is u nrelated to a specific person,
disorder situation, or event. Associated with sleep disturbance, fatigue, GI disturbance, and difficulty
concentrating. Treatment: SSRis, SNRis.
Adj u stment d isorder emotional symptoms (anxiety, depression) causing impairment following
-
an identifiable psychosocial stressor (e.g., divorce, illness) and lasting< 6 months(> 6 months i n
presence of chron ic stressor) .
Malingering Patient consciously fakes or claims to have a d isorder i n order to attai n a specific zo gain (e.g.,
avoiding work, obtaining dru gs) . Poor compl iance with treatment or follow-up of di agnostic tests.
C omplai nts cease after gain (vs . factitious di sorder) .
Factitious disorder Patient consciously creates physical and/or psychological symptoms in order to assume "sick role"
and to get medical attention (1 gain) .
Munchausen's Chronic factitious disorder with predomi nantly physical signs and symptoms. Characterized by a
synd rome h istory of multiple hospital admissions and willi ngness to receive i nvasive procedures.
Munchausen's When i l l ness i n a child or elderly patient is caused by the caregiver. Motivation is to assume a sick
syndrome by proxy role by proxy. Form of child/elder abuse.
Somatoform disorders Category of di sorders characterized by physical symptoms with no identifiable physical cause. Both
illness production and motivation are unconscious drives. Symptoms not i ntentionally produced
or feigned. More common in women.
Somatization d i sorder Variety of complaints in multiple organ systems (at least 4 pain, 2 GI, l sexual, l pseudoneurologic)
over a period of years, developing before age 30 years
Conversion Sudden loss of sensory or motor function (e.g., paralysis, blindness, mutism), often following
an acute stressor; patient is aware of but sometimes indifferent toward symptoms ("'a belle
indifference" ) ; more common in females, adolescents, and young adults
Hypochondriasis Preoccupation with and fear of having a serious illness despite medical evaluation and reassur ance
Body dysmorphic Preoccupation with m inor or imagined defect in appearance, leading to significant emotional
disorder d istress or impaired functioning; patients often repeatedly seek cosmetic surgery
Pa in disorder Prolonged pain with no physical findi ngs ; pain is the predom inant focus of clin ical presentation
and psychological factors play an important role i n severity, exacerbation, or maintenance of the
pam
46 8 SECTION Ill PSYCHIATRY PSYCHIATRY-PATHOLOGY
Personality
Personality trait An enduring, repetitive pattern of perceiving, relating to, and thinking about the environment and
oneself.
Personality d i sorder I nflexible, maladaptive, and rigidly pervasive pattern of behavior causing subjective d istress and/
or impaired functioni ng; person is usually not aware of problem. Usually presents by early
adulthood.
Cluster A personality Odd or eccentric ; inability to develop "Weird" (Accusatory, Aloof, Awkward).
disorders mean ingful social relationsh ips. No psychosis;
genetic association with sch izophren ia.
Paranoid Pervasive distrust and suspiciousness; projection
is the major defense mechanism.
Schizoid Voluntary social withdrawal, lim ited emotional Schizoid= distant.
expression, content with social isolation (vs.
avoidant).
Schizotypal Eccentric appearance, odd beliefs or magical Schizotypal = magical thinking.
thinking, i nterpersonal awkwardness.
Cluster B personality Dramatic, emotional, or erratic; genetic "Wild" (Bad to the Bone).
disorders association with mood disorders and substance
abuse.
Antisocial Disregard for and violation of rights of others, Antisocial =sociopath .
criminal ity; males> females; conduct disorder
if< 18 years.
Borderline Unstable mood and interpersonal relationsh ips,
impulsiveness, self-mutilation, boredom, sense
of empti ness ; females> males; spl itting is a
major defense mechanism.
Histrionic Excessive emotional ity and excitabil ity,
attention seeking, sexually provocative, overly
concerned with appearance.
Narcissistic Grandiosity, sense of entitlement; lacks empathy
and requi res excessive adm iration ; often
demands the "best" and reacts to criticism
with rage.
Cluster C personality Anxious or fearfu l ; genetic association with "Worried" (Cowardly, Compulsive, Clingy).
disorders anxiety disorders.
Avoidant Hypersensitive to rejection, socially inh ibited,
tim id, feelings of inadequacy, desires
relationships with others (vs. schizoid).
Obsessive-compulsive Preoccupation with order, perfectionism, and
control ; ego-syntonic: behavior consistent with
one's own beliefs and attitudes (vs. OCD).
Dependent Submissive and clinging, excessive need to be
taken care of, low self-confidence.
Keeping ..schizo-.. Schizoid < Schizotypal < Schizophrenic < Schizoaffective

straight (schizoid+ (greater odd (sch izophren ic psychotic symptoms
odd thinking) thinking than + bipolar or depressive mood
schizotypal) disorder)
Schizophrenia time course:
< l mo - brief psychotic disorder, usually stress related
l-6 mo - schizophren iform disorder
> 6 rna- schizophrenia
Eating disorders
Anorexia nervosa Excessive dieting +1- purging; intense fear of ga ining weight, body i m age distortion, and
t exercise, leading to body weight< 85% of ideal body weight. Associated with ! bone density.
Severe weight loss, metatarsal stress fractures, amenorrhea, anem ia, and electrolyte d isturbances.
Seen primarily in adolescent girls. Commonly coexists w ith depression.
Bulimia nervosa B inge eating +1- purging; often followed by self-induced vom iting or use of laxatives, d iuretics, or
emetics. Body weight often maintained within normal range. Associated with parotitis, enamel
erosion, electrolyte disturbances, alkalosis, dorsal hand calluses from i nduced vom iting (Russell 's
sign). Seen predom inantly in adolescent girls.
Gender identity Strong, persistent cross-gender identification. Characterized by persistent discomfort with one's sex,
disorder causing significant distress and/or impaired function ing.
Transsexual ism - desire to l ive as the opposite sex, often through surgery or hormone treatment.
Transvestism - paraph ilia ; wearing clothes (e.g., vest) of the opposite sex (cross-dressing).
47 0 SECTION Ill PSYCHI ATRY PSYCHIATRY-PATHOLOGY
Substance dependence Maladaptive pattern of substance use defined as 3 or more of the following signs in l year:
Tolerance- need more to ach ieve same effect
Withdrawal
Substance taken i n larger amounts, or over longer time, than desired
Persistent desire or unsuccessful attempts to cut clown
Significant energy spent obtain ing, usi ng, or recovering from substance
I mportant social, occupational, or recreational activities reduced because of substance use
Continued use in spite of knowing the problems that it causes
Substance abuse Maladaptive pattern leading to clin ically significant impairment or d istress.
Recurrent use resulting in failure to fulfill major obl igations at work, school, or home
Recurrent use i n physically hazardous situations
Recurrent substance-related legal problems
Continued use in spite of persistent problems caused by use
Stages of change in l . Precontemplation - not yet acknowledging that there is a problem

overcoming substance 2. Contemplation - acknowledging that there is a problem, but not yet ready or willing to make a
addidion change
3. Preparation/determination - getting ready to change behavior
4. Action/willpower - changing behaviors
5. M a i ntenance - maintain ing the behavior change
6. Relapse - returning to old behaviors and abandon ing new changes
Psychoadive drug intoxication and withdrawal

DRUG IN TOXICATION WITH DRAWAL
Depressants
onspecific: mood elevation, anxiety, Nonspecific: anxiety, tremor, seizures,
. .
sedation, behavioral disinh ibition, respiratory ll1SOlll11 1a.
depression .
Alcohol Emotional lability, slurred speech, ataxia, Mild alcohol withdrawal: symptoms similar to
coma, blackouts. Serum y-glutamyltransferase other depressants. Severe alcohol withdrawal
(GGT) - sensitive indicator of alcohol use. can cause autonomic hyperactivity and DTs.
Lab AST value is twice ALT value. Treatment for DTs: benzocl iazepines.
Opioids (e.g., Euphoria, respiratory and CNS depression, Sweating, d ilated pupils, piloerection ("cold
morphine, heroin, gag reflex, pupillary constriction (pinpoint turkey"), fever, rh inorrhea, yawning, nausea,
methadone) pupils), seizures (overdose). Treatment: stomach cramps, diarrhea ("flu-l ike" symptoms).
naloxone, naltrexone. Treatment: long-term support, methadone,
buprenorph ine.
Barbitu rates Low safety margin, marked respiratory Delirium, l i fe-threatening cardiovascular
depression . Treatment: symptom management collapse.
(assist respiration, t BP).
Benzodiazepines Greater safety margin . Ataxia, minor Sleep disturbance, depression, rebound anxiety,
respiratory depression. Treatment: flumazen il seizure (severe).
(competitive benzocl iazepine antagonist).
PSYCHIATRY PSYCHIATRY-PATHOLOGY SECTION I l l 47 1
Psychoactive d ru g intoxication and withdrawal (continued)

DRUG IN TOXICATION WI TH DRAWAl
Sti mulants
Nonspecific: mood elevation, psychomotor Nonspecific: post-use "crash," includ ing
agitation, insomn ia, cardiac arrhythmias, depression, lethargy, weight gain, headache.
tachycardia, anxiety.
Amphetamines Euphoria, grandiosity, pupillary dilation, Anhedon ia, increased appetite,
prolonged wakefulness and attention, hypersomnolence, existential crisis.
hypertension, tachycardia, anorexia, paranoia,
fever. Severe: cardiac arrest, seizure.
Cocaine Impaired judgment, pupil lary dilation, 1-Iypersomnolence, malaise, severe
hallucinations (including tactile), paranoid psychological craving, clepression/su iciclal ity.
ideations, angina, sudden cardiac death.
Treatment: benzocl iazepines.
Caffeine Restlessness, t diuresis, muscle twitching. Lack of concentration, headache.
Nicotine Restlessness. I rritability, anxiety, craving. Treatment:
n icotine patch, gum, or lozenges; bupropion/
varen icl ine.
Hallucinogens
PCP Belligerence, impulsiveness, fever, psychomotor Depression, anxiety, i rritabil ity, restlessness,
agitation, analgesia, vertical and horizontal anergia, d isturbances of thought and sleep.
nystagmus, tachycarcl ia, hom iciclal ity,
psychosis, del irium, seizures. Treatment:
benzocliazepines, rapid-acting antipsychotic.
LSD Perceptual d istortion (visual, auditory),
depersonalization, anxiety, paranoia,
psychosis, possible Aashbacks.
Marijuana Euphoria, anxiety, paranoid delusions, I rritabil ity, depression, insomn ia, nausea,
(ca nnabinoid) perception of slowed time, impaired anorexia. Most symptoms peak in 48 hours and
judgment, social withdrawal, t appetite, last for 5-7 days. Generally detectable in urine
dry mouth, conjunctival injection, for 4-10 clays.
hallucinations. Prescription form is clronabinol
(tetrahydrocannabinol isomer): used as
antiemetic (chemotherapy) and appetite
stimulant (in AIDS).
Heroin addiction Users at t risk for hepatitis, abscesses, overdose, hemorrhoids, AIDS, and right-sided endocarditis.
Look for track marks (needle sticks in veins).
Methadone - long-acting oral opiate ; used for heroin detoxi fication or long-term mai ntenance.
agoni st; long acting with fewer withdrawal symptoms than
N a loxon e + b u prenorphine - Partial
methadone. Naloxone is not active when taken orally, so withdrawal symptoms occur only if
i njected (lower abuse potential).
I
47 2 SECTION I l l PSYCHI ATRY PSYCHIATRY-PHAR MACOLOGY
Alcoholism Physiologic tolerance and dependence with symptoms of withdrawal (tremor, tachycard ia,
hypertension, malaise, nausea, DTs) when intake is interrupted.
Complication s : alcohol ic cirrhosis, hepatitis, pancreatitis, peripheral neuropathy, testicular atrophy.
Treatment: disulfiram (to condition the patient to abstai n from alcohol use), supportive care.
Alcoholics Anonymous and other peer support groups are helpful i n sustaining abstinence.
Wernicke- Korsakoff Caused by th iamine deficiency. Triad of confusion, ophthal moplegia, and ataxia (Wernicke's
syn d rome encephalopathy) . May progress to irreversible memory loss, confabulation, personal ity change
( Korsakoff's psychosis) . Associated with periventricular hemorrhage/necrosis of mamm illary
bodies. Treatment: IV vitamin B1 (thiamine).
Mallory-Weiss Longitudinal lacerations at the gastroesophageal junction caused by excessive vom iting. Often
synd rome presents with hematemesis. Associated with pain (vs. esophageal varices).
Delirium tremens (DTs) Life-threatening alcohol withdrawal syndrome that peaks 2-5 clays after last drink.
Symptoms in order of appearance : autonom ic system hyperactivity (tachycardia, tremors, anx iety,
seizures), psychotic symptoms (halluci nations, delusions), confusion .
Treatment: benzodiazepines.
PSYCHIATRY-PHAR MACOLOGY
Treatment for selected PSYCHIATRIC CONDI TION

-------
PREFERRED DRUGS
psychiatric conditions Alcohol withdrawal Benzocliazepines

Anxiety SSRis, SNRis, buspirone
ADHD Methylphen idate, ampheta m i nes
Bipolar d isorder "Mood stabilizers" (e.g., l ithium, valproic acid,
carbamazepine), atypical antipsychotics
Bulimia SSRis
Depression SSRis, SNRis, TCAs, buspi rone, m irtazapine
(especially with insomnia)
Obsessive-compulsive d isorder SSRis, clomipra m i ne
Panic disorder SSRis, venlafaxine, benzodiazepines
PTSD SSRis
Sch izophrenia Antipsychotics
Social phobias SSRis
Tourette's syndrome Antipsychotics (e.g., haloperidol, rispericlone)
CNS stimulants Methylphenidate, dextroamphetamine, methamphetamine.

MECHANISM t catecholamines at the synaptic cleft, especially NE and dopamine.
CliNICAL USE ADHD, narcolepsy, appetite control.
PSYCHIATRY PSYCHIATRY-PHAR MACOLOGY SECTION I l l 4 73
Antipsychotics Haloperidol, trifluoperazine, fluphenazine, thioriclazine, chlorpromazine (haloperidol + "-azines").

(neuroleptics)
MECHANISM All typical antipsychotics block dopamine D 2 High potency: Trifluoperazine, Fluphenazine,
receptors ( t [cAMP]). Haloperidol (Try to Fly H igh) -neurologic
C LINICAL USE Schizophren ia (primarily positive symptoms), side effects (extrapyram idal symptoms).
psychosis, acute man ia, Tourette's syndrome. Low potency: Chlorpromazine, Thioridazine
TOXICITY H ighly lipid soluble and stored in body fat; thus, (Cheating Thieves are low) -non-neurologic
very slow to be removed from body. side effects (antichol inergic, antihistami ne,
Extrapyram idal system (EPS) side effects (e.g., and a 1 -blockacle effects).
clyski nesias). Chlorpromazine- C orneal deposits ;
Endocrine side effects (e.g., dopamine receptor Th ioriclazine - reT inal deposits ; halopericl o l
antagonism .... hyperprolactinem ia .... N M S, tard ive dyskinesia.
galactorrhea). Evolution of EPS side effects :
Side effects arising from blocking muscarinic 4 hr acute dystonia (muscle spasm, stiffness,
(dry mouth, constipation), a 1 (hypotension), oculogyric crisis)
and h ista m i ne (sedation) receptors. 4 clay akath isia (restlessness)
OTHER TOXICITIES N e u roleptic m a l ignant syndrome ( N M S ) 4 wk bradykinesia (parki nsonism)
rigid ity, myoglobinuria, autonomic instability, 4 mo tard ive dyskinesia
hyperpyrexia. Treatment: clantrolene, 02 For N M S, think FEVER:

agonists (e.g., bromocriptine). Fever
Ta rdive dysk i nesiastereotypic oral
-
Encephalopathy
facial movements as a result of long-term Vitals unstable
antipsychotic use. Often irreversible. Elevated enzymes
Rigidity of muscles
Atypical antipsychotics Olanzapine, clozapine, quetiapine ris per icl o ne,

, It's atypical for old closets to quietly risper from
aripiprazole, ziprasicl o ne. A to Z .
MECHANISM Not completely u nderstood. Varied effects on
5-HT 2 , dopami ne, and a- and H 1 -receptors.
C LINICAL USE Sch izophrenia- both positive and negative
symptoms. Also used for bipolar disorder,
OCD, anxiety disorder, depression, man ia,
Tourette's syndrome.
TOXICITY Fewer extrapyram idal and antichol inergic Must watch clozapine clozely !
side effects than trad itional antipsychotics.
Olanzapine/clozapine may cause significant
weight gai n . Clozapine may cause
agranulocytosis (requ ires weekly WBC
mon itoring) and seizu re. Ziprasiclone may
prolong the QT i nterval.
47 4 SECTION I l l P SYCHI ATRY PSYCHIATRY-PHAR MACOLOGY
Lithium
MECHANISM Not establ ished ; possibly related to inh ibition of LMNOP:
phosphoinositol cascade. Lith ium side effects
C LINICAl USE Mood stabil izer for bipolar disorder; blocks Movement (tremor)
rel apse and acute manic events . Also SIAD H . Neph rogenic diabetes i nsipidus
HypOthyroid ism
TOXICITY Tremor, sedation, edema, heart block,
Pregnancy problems
hypothyroidism, polyuria (ADH antagon ist
causing nephrogenic diabetes insipidus),
teratogenesis. Fetal cardiac defects include
Ebstein anomaly and malformation of the
great vessels. Narrow therapeutic window
requires close monitoring of serum levels.
Almost exclusively excreted by the kidneys ;
most is reabsorbed at the proximal convoluted
tubules fol lowing Na+ reabsorption.
Buspirone
MECHANISM Stimulates 5-HT 1 A receptors. I 'm always anxious if the bus will be on ti me, so
C LINICAl USE General ized anxiety disorder. Does not cause I take buspirone.
sedation, addiction, or tolerance. Takes 1-2
weeks to take effect. Does not interact with
alcohol (vs. barbiturates, benzodiazepines).
Antidepressants
Norad renergic Serotonergic
neuron n e u ron
receptor receptor
Postsynaptic
neuron
(Adapted, with permission, from Katzung B G , Trevor A J . USMLE Road Map: Pharmacology, 2nd ed. N e w York: McGraw-Hill, 2006: Fig. 5-7.)
PSYCHIATRY PSYCHIATRY-PHAR MACOLOGY SECTION Il l 47 5
SSRis Fluoxetine, paroxetine, sertraline, citalopram. Flashbacks paralyze senior citizens .

MECHANISM Serotonin-specific reuptake inh ibitors. It normally takes 4-8 weeks for antidepressants
C LINICAL USE Depression, general ized anxiety disorder, panic to have an effect.
disorder, O C D, bulim ia, social phobias,
PTSD.
TOXICITY Fewer than TCAs . CI distress, sexual
dysfunction (anorgasm ia and ! l ibido) .
Serotonin syndrome with any drug that t
seroton i n (e.g., MAO inhibitors, SNRis,
TCAs) - hypertherm ia, confusion, myoclonus,
cardiovascular collapse, Hushing, di arrhea,
seizures. Treatment: cyproheptadine (5 -HT 2
receptor antagon ist) .
SNRis Venlafaxine, cluloxetine.

MECHANISM I n h ibit seroton i n and NE reuptake.
C LINICAL USE Depression. Venlafaxine is also used in general ized anxiety and panic d isorders ; cluloxetine is also
ind icated for diabetic peripheral neuropathy. Duloxetine has greater effect on N E .
TOXICI TY t B P most common ; also stimulant effects, sedation, nausea.
Tricyclic Am itriptyl i ne, nortriptyl ine, im ipramine, desipramine, clomipra m ine, cloxepin, amoxapine (all
antidepressants TCAs end i n -iptyl ine or -ipramine except cloxepin and amoxapine ) .
MECHANISM Block reuptake o f NE a n d seroton in.
C LINICAL USE Major depression, becl wetting (im ipramine), OCD (clomipram ine), fibromyalgia.
TOXICITY Sedation, a 1 -blocki ng effects including postural hypotension, and atropi ne-like (antichol inergic)
side effects (tachycardia, urinary retention, dry mouth ) . 3 TCAs (am itriptyl ine) have more
antichol i nergic effects than 2 TCAs (nortriptyl ine) have. Desipramine is less sedating and has
higher seizure threshold.
Tri-C 's : C onvulsions, Coma, Carcliotoxicity (arrhythm ias); also respiratory depression,
hyperpyrexia. Confusion and hallucinations in elderly clue to anticholinergic side effects (use
nortriptyl ine) . Treatment: NaHC03 for card iovascular toxicity.
Monoamine oxidase Tranylcyprom ine, Phenel zine, Isocarboxazicl, Selegi line (selective MAO-B inh ibitor) .
(MAO) inhibitors (MAO Takes Pride In Shanghai) .
MECHANISM Nonselective MAO inh ibition t levels of amine neurotransm itters (NE, seroton in, dopamine) .
C LINICAL USE Atypical depression, anxiety, hypochondriasis.
TOXICITY Hypertensive crisis (most notably with ingestion of tyram i ne, which is found i n many foods such
as wine and cheese); CNS stimulation . Contraind icated with SSRis, TCAs, St. John's Wort,
meperidine, and clextromethorphan (to prevent seroton i n syndrome) .
47 6 SECTION Ill PSYCHI ATRY PSYCHIATRY-PHAR MACOLOGY
Atypical antidepressants
B upropion Also used for smoking cessation . t N E and
dopa m i ne via unknown mechanism. Toxicity:
stimulant effects (tachycardia, insomnia),
headache, seizure in bulimic patients. No
sexual side effects.
M i rtazapine a2-antagon ist ( t release of N E and seroton in)
and potent 5-HT2 and 5-HT 3 receptor
antagonist. Toxicity: sedation (wh ich may be
desirable in depressed patients with insom nia),
t appetite, weight ga in (wh ich may be
desirable i n elderly or anorexic patients), dry
mouth .
Maprotiline Blocks N E reuptake. Toxicity: sedation,
orthostatic hypotension.
Trazodone Primarily inh ibits seroton in reuptake. Used Called trazobone due to male-specific side
primarily for insomn ia, as high doses are effects.
needed for antidepressant effects. Toxicity:
sedation, nausea, priapism, postural
hypotension.
HIGH-YIELD SYSTEMS
Renal
"But I know all about love already. I know precious little still about
kidneys."
-Aldous Huxley, Antic Hay
"This too shall pass. Just like a kidney stone."

-Hunter Madsen
"I drink too much. The last time I gave a urine sample it had an olive
in it."
-Rodney Dangerfield
47 8 SECTION Ill RENAL RENAL-EMBRYOLOGY
RENAL-EMBRYOLOGY
Kidney embryology Pronephros-week 4; then degenerates

Mesonephros-functions as interim kidney for lst trimester; later contributes to male genital system
Metanephros-permanent; first appears in 5th week of gestation; nephrogenesis continues through
32-36 weeks of gestation
Ureteric bud-derived from caudal end of mesonephros; gives rise to ureter, pelvises, calyces,
and collecting ducts; fully canalized by lOth week

Metanephric mesenchyme-ureteric bud interacts with this tissue; interaction induces
differentiation and formation of glomerulus through to distal convoluted tubule

Aberrant interaction between these 2 tissues may result in several congenital malformations of
the kidney
Ureteropelvic junction-last to canalize ..... most common site of obstruction (hydronephrosis) in
fetus.
} Degenerated pronephros
Mesonephros
Mesonephric --1
duct

} "'""''"'"
r Urogenital sinus
Potter's syndrome Oligohydramnios ..... compression of fetus Babies who can't "Pee" in utero develop Potter's.
--+limb deformities, facial deformities, and Causes include ARPKD, posterior urethral
pulmonary hypoplasia (cause of death). valves, bilateral renal agenesis.
Horseshoe kidney Inferior poles of both kidneys fuse. As they

ascend from pelvis during fetal development, Renal artery
horseshoe kidneys get trapped under inferior

Horseshoe
mesenteric artery and remain low in the kidney
abdomen. Kidney functions normally.
Associated with Turner syndrome.
Multicystic dysplastic Due to abnormal interaction between ureteric bud and metanephric mesenchyme. This leads to
kidney a nonfunctional kidney consisting of cysts and connective tissue. If unilateral (most common),
generally asymptomatic with compensatory hypertrophy of contralateral kidney. Often diagnosed
prenatally via ultrasound.
RENAL RENAL-ANATOM Y SECTION Ill 4 79
RENAL-ANATOM Y
Kidney anatomy and glomerular structure
Cortex Interlobar
Arcuate
artery
Renal --=-=--"""'"....
" .
pelvis
Renal
vein Normal glomerulus. Showing (A) macula densa and
distal convoluted tubule, (B) afferent arteriole, (C) efferent
arteriole, and (D) Bowman's capsule.
Ureter
The left kidney is taken during living donor

transplantation because it has a longer renal vein.
Parietal layer of
Efferent arteriole Bowman's capsule
Macula densa
Distal renal
tubule
Ureters: course Ureters pass under uterine artery and under Ureter
ductus deferens (retroperitoneal).
Vas
"Water (ureters) under the bridge (uterine Uterine deferens
artery (in male)
artery, vas deferens)." (in female)
Internal urethral orifice --1

480 SECTION Ill RENAL RENAL-PHYSIOLOGY
RENAL-PHYSIOLOGY
Fluid compartments
HIKIN': High K INtracellular.
60-40-20 rule (% of body weight):
40% nonwater 1/4 plasma 60% total body water
<
volume
v
mass
Total 40% ICF
body 113 extracellular
20% ECF
fluid
K
weight
(kg) 60% total body
water (L)
I 3/4 interstitial
volume
Plasma volume measured by radiolabeled
albumin.
2/3 intracellular Extracellular volume measured by inulin.
fluid Osmolarity=290 mOsm/L.
Glomerular filtration Responsible for filtration of plasma according to The charge barrier is lost in nephrotic
barrier size and net charge. syndrome, resulting in albuminuria,
Composed of: hypoproteinemia, generalized edema, and
Fenestrated capillary endothelium (size hyper! ipidem ia.
barrier)
Fused basement membrane with heparan
sulfate (negative charge barrier)

Epithelial layer consisting of podocyte foot
processes
Renal clearance ex= UXV/Px= volume of plasma from which the Be familiar with calculations.
substance is completely cleared per unit time. C, =clearance of X. Units are mL/min.
C, < GF R: net tubular reabsorption of X. U,= urine concentration of X.
Cx > GF R: net tubular secretion of X. P,= plasma concentration of X.
C,= GF R: no net secretion or reabsorption. V= urine flow rate.
Glomerular filtration Inulin clearance can be used to calculate GF R Normal GF R"" 100 mL/min.
rate (GFR) because it is freely filtered and is neither Creatinine clearance is an approximate measure
reabsorbed nor secreted. of GF R. Slightly overestimates GFR because
GF R = uinulin X V/Pinulin = cinulin creatinine is moderately secreted by the renal
= Kr [ ( P cc- Pss)- (nee -rrss)]. tubules.
(GC=glomerular capillary; BS= Bowman's Incremental reductions in GF R define the stages
space.) rr85 normally equals zero. of chronic kidney disease.
Effective renal plasma ERPF can be estimated using PAH clearance because it is both filtered and actively secreted in the
flow proximal tubule. All PAH entering the kidney is excreted.
ERPF = UPAH X V/PPAH = CPAI-1'
RBF = RPF/(1 - Hct).
ERPF underestimates true RPF by 10%.
RENAL RENAL-PHYSIOLOGY SECTION Ill 48 1
Filtration Filtration fraction (FF)=GFR/RPF. GF R can be estimated with creatinine

Normal FF = 20%. clearance.
[
Filtered load=GF R x plasma concentration. RPF is best estimated with PAH clearance.
Prostaglandins
NSAIDs
dilate afferent arteriole
(I RPF, I GFR, so
FF remains constant)
convoluted
tubule
Efferent arteriole
ACE inhibitor
[ Angiotensin II
t: e;nt,
preferentially
I GFR, so FF
increases)
Changes in glomerular dynamics

Effect RPF GFR FF (GFR/RPF)
Afferent arteriole constriction NC
Efferent arteriole constriction !
t plasma protein concentration NC
! plasma protein concentration NC
Constriction of ureter NC
Calculation of Filtered load= GF R X Px.

reabsorption and Excretion rate= V xUX .
secretion rate Reabsorption= filtered - excreted.
Secretion= excreted - filtered.
Glucose clearance Glucose at a normal plasma level is completely Glucosuria is an important clinical clue to
reabsorbed in proximal tubule by a+fglucose diabetes mellitus.
cotransport. Normal pregnancy reduces reabsorption
At plasma glucose of -160 mg/dL, glucosuria of glucose and amino acids in the
begins (threshold). At 350 mg/dL, all proximal tubule, leading to glucosuria and
transporters are fully saturated (Tm). aminoaciduria.
Amino acid clearance Sodium-dependent transporters in proximal tubule reabsorb amino acids.
Hartnup's disease-deficiency of neutral amino acid (tryptophan) transporter; results in pellagra.
RENAL RENAL-PHYSIOLOGY SECTION Ill 483
Nephron physiology
Interstitium
blood
Lumen Interstitium
urine blood
I I
Thiazide diuretics
-c-
Early distal convoluted tubule-actively

reabsorbs Na+, CJ-. Makes urine hrpotonic.
Early proximal tubule-contains brush PT H-i Ca2+J Na+ exchange Ca +
border. Reabsorbs all of the glucose and reabsorption.
amino acids and most of the bicarbonate, 5-10% Na+ reabsorbed.
sodium, chloride, phosphate, and water.
Isotonic absorption. Generates and secretes
ammonia, which acts as a buffer for secreted
H+.
PT H-inhibits Na+fphosphate cotransport
phosphate excretion.
AT 11-stimulates Na+J H+ exchange
i Na+, H20, and HC03- reabsorption
(permitting contraction alkalosis).
65-80% Na+ reabsorbed.
/
T hin descending loop of Henle-passively
reabsorbs water via medullary hypertonicity
(impermeable to sodium). Concentrating Loop of Henle
segment. Makes urine hypertonic. IAmiloride, triamterenel

--- Na+-.&-+
Lumen Interstitium
urine blood
Na+,.L-..-
1 Loop diuretics I K+ -t-----:--t+
---2CI- __,;z-
loiffu-;J ;,;nth;
electrochemical 1
:
l i:_ --- _j

Collecting tubules-reabsorb Na+ in exchange for

T hick ascending loop of Henle-actively reabsorbs Na+, K+, secreting K+ and H+ (regulated by aldosterone).
and Cl-. Indirectly induces the paracellular reabsorption of Aldosterone-acts on mineralocorticoid receptor
Mg2+ and Ca2+ through (+) lumen potential generated by K+ -+ insertion of Na+ channel on luminal side.
backleak. Impermeable to H20. Makes urine less concentrated
ADH-acts at V2 receptor- insertion of
as it ascends.
aquaporin H20 channels on luminal side.
Relative concentrations TF/P > 1 when: PAH

Solute is reabsorbed 3.0
along proximal tubule less quickly than water
DSecretion
2.0 D Reabsorption
1
Urea
TF/P = 1 when: 1.4
Solute and water TF
are reabsorbed at p 1.2
same rate 1.0 - ______ -_IS_+- Na+
Osmolarity
0.8
TF/P < 1 when:

Solute is
1 0.6
0.4
0.2
-----P;
reabsorbed TF [Tubular fluid]

0 I
more quickly p [Plasmal
25 50 75 100
than water
Percent distance along proximal tubule
Neither secreted nor reabsorbed; concentration increases as water is reabsorbed.

(Adapted, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. New York: McGraw-Hill, 2005.)
Tubular inulin t in concentration (but not amount) along the proximal tubule as a result of water
reabsorption.
Cl- reabsorption occurs at a slower rate than a+ in the proximal 1/3 of the proximal tubule and
then matches the rate of a+ reabsorption more distally. Thus, its relative concentration t before it
plateaus.
RENAL RENAL-PHYSIOLOGY SECTION Ill 485
Renin-angiotensin-aldosterone system
l BP (JG cells)
l Na delivery Acts at AT, receptors on
Vasoconstriction ------+ iBP
n ,I
------+
(MD cells)
vascular smooth muscle
isympathetic tone
(,-receptors)
l
r' t Constncts efferent
artenole of glomerulus
------+ iFF to preserve renal function (GFR )
1n low-volume states (i.e., when R BF l)
Renin
A E-----j Bradykin1n
vr Aldosterone ------+ iNa channel and Na/K
------+ Creates

(adrenal gland) pump msertion in pnnc1pal favorable Na
Angiotensmogen ------+ Angiotensin 1 ------+ Angiotensin 1 1 cells; enhances K and H+ gradient for

excretion (upregulates Na and H,O
P
principal cell K channels and reabsorption
intercalated cell H+ channels)
6--+ ADH ------+ iH,O channel insertion ------+ H,O
(posterior
in principal cells reabsorption
pituitary)
iProximal tubule Na/H+ activity ------+

Na+, HCO -, and H,O reabsorption

(can perm1t contract1on alkalosis)
Stimulates hypothalamus------+ Thirst
AT II Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor
effects. Helps maintain blood volume and blood pressure.
ANP Released from atria in response to t volume; may act as a "check" on renin-angiotensin-aldosterone
system; relaxes vascular smooth muscle via cGMP, causing t GF R, ! renin.
ADH Primarily regulates osmolarity but also responds to low blood volume, which takes precedence over
osmolarity.
Aldosterone Primarily regulates blood volume; in low-volume states, both ADI--1 and aldosterone act to protect
blood volume.
Juxtaglomerular Consists of JG cells (modified smooth muscle of JGA defends glomerular filtration rate via renin
apparatus afferent arteriole) and the macula densa (NaCl angiotensin-aldosterone system.
sensor, part of the distal convoluted tubule). JG -blockers can decrease BP by inhibiting
cells secrete renin in response to ! renal blood receptors of the JGA, causing ! renin release.
pressure, ! NaCl delivery to distal tubule, and Juxta= close by.
t sympathetic tone (1).
4 86 SECTION Ill RENAL RENAL-PHYSIOLOGY
Kidney endocrine fundions

Erythropoietin Released by interstitial cells in the peritubular
capillary bed in response to hypoxia.
1,15-(0Hh vitamin D Proximal tubule cells convert 25-0H vitamin D 25-0H vitamin D 1 ,25-(0H)2 vitamin D
to 1,25- (0H)z vitamin D (active form). 1 a-hydroxylase
I
PTH
Renin Secreted by JG cells in response to ! renal

arterial pressure and t renal sympathetic
discharge (1 effect).
Prostaglandins Paracrine secretion vasodilates the afferent NSAIDs can cause acute renal failure
arterioles to t GF R. by inhibiting the renal production of
prostaglandins, which keep the afferent
arterioles vasodilated to maintain GF R.
Hormones ading on kidney

Atrial natriuretic peptide (ANP)
secreted in response to i atrial pressure.
Causes iGFR and iNa+ filtration with
no compensatory Na reabsorption
in distal nephron.
Net effect: Na+ loss and volume loss.
(response to
.!. blood volume)
Angiotensinogen
ATI
t ACE (lung)
Angiotensin II (AT !I)

synthesized in response to Aldosterone
.!. BP. Causes efferent arteriole secreted in response to
constriction iGFR and iFF .!. blood volume (via AT II) and
Parathyroid hormone (PTH) but with compensatory Na+ iplasma [K+]; causes iNa+
Secreted in response to reabsorption in proximal and 1Im::::===' reabsorption, iK+ secretion,
41 iH+ secretion.
.!. plasma [Ca2+], iplasma [P043-], distal nephron.
or .!. plasma 1 ,25-(0H) 2 vitamin D. Net effect: preservation of renal
Causes i[Ca2+] reabsorption (DCT), function in low-volume state
.!. P043- reabsorption (PC T), (iFF) with simultaneous Na+ ADH (vasopressin)
i1 ,25-(0H) 2 vitamin D production. reabsorption (both proximal ..Aim-:::::=="
: secreted in response to
Additional effect: iCa2+ and P043- and distal) to .!. additional iplasma osmolarity and
absorption from gut. volume loss. .J. blood volume. Binds to
receptors on principal cells,
causing inumber of water
channels and i H20
reabsorption.
RENAL RENAL-PHYSIOLOGY SECTION Ill 4 87
Potassium shifts SHIFTS K+ OUT OF CELL (CAUSING HYPERKALEMIA) SHIFTS K+ INTO CELL (CAUSING HYPOKALEMIA)
Digitalis
HyperOsmolarity Hypo-osmolarity
Insulin deficiency Insulin (t a+JK+ AT Pase)
Lysis of cells
Acidosis Alkalosis
-adrenergic antagonist -adrenergic agonist (t Na+JK+ AT Pase)
Patient with hyperkalemia? DO Insulin LA Insulin shifts K+ into cells
work.
Eledrolyte disturbances
Electrolyte Low serum concentration High serum concentration
Na+ Nausea and malaise, stupor, coma Irritability, stupor, coma
U waves on ECG, Battened T waves, Wiele Q RS and peaked T waves on ECG,
arrhythmias, muscle weakness arrhythmias, muscle weakness
Ca2+ Tetany, seizures Stones (renal), bones (pain), groans (abdominal
pain), psychiatric overtones (anxiety, altered
mental status), but not necessarily calciuria
Mg2+ Tetany, arrhythmias 4 DT Rs, lethargy, bradycardia, hypotension,
cardiac arrest, hypocalcemia
Bone loss, osteomalacia Renal stones, metastatic calcifications,
hypocalcemia
Acid-base physiology
pH Pco COMPENSATORY RESPONSE
Metabolic acidosis Hyperventilation (immediate)
Metabolic alkalosis t Hypoventilation (immediate)
Respiratory acidosis t renal [HC0 3 ] reabsorption (delayed)
-
Respiratory alkalosis 4 renal [HC0 3 -] reabsorption (delayed)

Key: t = 1 disturbance; 4 t =compensatory response.
Henclerson-Hasselbalch equation: pH= 6.1 +log 62

The predicted respiratory compensation for a simple metabolic acidosis can be calculated using
Winter's formula. If the measured Pco2 differs significantly from the predicted Pco2, then a
mixed acid-base disorder is likely present:
Pco2 = 1.5 (HC0 3 ) + 8 +1- 2
-
Acidosis/alkalosis
Check arterial pH
pH< 7.4 pH> 7.4

Acidemia Alkalemia
Pco2 > 40 mmHg

Pco2< 40 mmHg

Pco2< 40 mmHg Pco2> 40 mmHg

R espiratory

Metabolic acidosis

Respiratory alkalosis Metabolic alkalosis with
acidosis with compensation -Hyperventilation compensation (hypoventilation)
L.
(hyperventilation) (e.g., early high -Loop diuretics

altitude exposure) -Vomiting
Hypovent1lat1on -Salicylates (early} -Antacid use
-Airway obstruction -Hyperaldosteronism
Check anion gap
-Acute lung disease
Anion gap= Na - (CI- + HC03-)
-Chronic lung disease

-Opioids, sedatives
-Weakening of
respiratory
muscles tanion gap Normal anion gap (8-12 mEq/L)
MUDPILES: HARD-ASS:
Methanol (formic acid} Hyperalimentation
Uremia Addison's disease
Diabetic ketoacidosis Renal tubular acidosis
Propylene glycol Diarrhea
Iron tablets or INH Acetazolamide
Lactic acidosis Spironolactone
Ethylene glycol (oxalic acid} Saline infusion
Salicylates (late)
Renal tubular acidosis (RTA)

Type 1 ("distal") Defect in collecting tubule's ability to excrete H+ Untreated patients have urine pH >5.5.
Associated with hypokalemia. t risk for calcium phosphate kidney stones as a result oft urine pH
and bone resorption.
Type 2 ("proximal") Defect in proximal tubule HC0 3 - reabsorption. May be seen with Fanconi's syndrome. Untreated
patients typically have urine pH < 5.5. Associated with hypokalemia.t risk for hypophosphatemic
rickets.
Type 4 Hypoaldosteronism or lack of collecting tubule response to aldosterone. The resulting
("hyperkalemic") hyperkalemia impairs ammoniagenesis in the proximal tubule, leading to buffering capacity
and urine pH.
RENAL RENAL-PATHOLOGY SECTION Ill 4 89
RENAL-PATHOLOGY
Casts in urine Presence of casts indicates that hematuria/pyuria is of renal (vs. bladder) origin.
RBC casts Glomerulonephritis, ischemia, or malignant Bladder cancer, kidney stones hematuria, no
-+
hypertension. casts.
WBC casts Tubulointerstitial inflammation, acute Acute cystitis pyuria, no casts.
-+
pyelonephritis, transplant rejection.

Fatty casts ("oval fat Nephrotic syndrome.
bodies")
Granular ("muddy Acute tubular necrosis.
brown") casts
Waxy casts Advanced renal disease/chronic renal failure.
Hyaline casts Nonspecific, can be a normal finding.
Nomenclature of glomerular disorders

TYPE CHARACTERISTICS EXAMPLE
Focal < 50% of glomeruli are involved Focal segmental glomerulosclerosis

Diffuse >50% of glomeruli are involved Diffuse proliferative glomerulonephritis
Proliferative Hypercellular glomeruli Mesangial proliferative
Membranous T hickening of glomerular basement membrane Membranous nephropathy
1 glomerular disease Involves only glomeruli, thus a primary disease Minimal change disease
of the kidney
2 glomerular disease Involves glomeruli and other organs, thus a SLE, diabetic nephropathy
disease of another organ system, or a systemic
disease that has impact on the kidney
Glomerular diseases
Nephritic syndrome Nephrotic syndrome
Acute poststreptococcal Focal segmental glomerulosclerosis

Diffuse proliferative
glomerulonephritis
glomerulonephritis Membranous nephropathy
Rapidly progressive glomerulonephritis
Minimal change disease
Membranoproliferative
Berger's lgA glomerulonephropathy glomerulonephritis Amyloidosis
Alport syndrome
Diabetic glomerulonephropathy
490 SECTION Ill RENAL RENAL-PATHOLOGY
Nephrotic syndrome NephrOtic syndrome presents with massive prOteinuria (> 3.5g/day, frothy urine), hyperlipidemia,
fatty casts, edema. Associated with thromboembolism (hypercoagulable state due to AT I I I loss in
urine) and t risk of infection (loss of immunoglobulins).
Focal segmental 1M-segmental sclerosis and hyalinosis r.J.
glomerulosclerosis EM-effacement of foot process similar to
minimal change disease.
Most common cause of nephrotic syndrome in
adults.
Associated with HIV infection, heroin abuse,
massive obesity, interferon treatment, and
chronic kidney disease due to congenital
absence or surgical removal.
Membranous 1M-diffuse capillary and GBM thickening (1].

nephropathy
EM-"spike and dome" appearance with
subepithelial deposits.
IF-granular. SLE's nephrotic presentation.
Second most common cause of primary
nephrotic syndrome in adults. Can be
idiopathic or caused by drugs, infections, SLE,
solid tumors.
Minimal change LM-normal glomeruli.

disease (lipoid EM-foot process effacement-
nephrosis) Selective loss of albumin, not globulins, caused
by GBM polyanion loss.
May be triggered by a recent infection or an
immune stimulus. Most common in children.
Responds to corticosteroids.
Minimal change disease (lipoid nephrosis). Note

effacement of foot processes on EM (red arrow).
Amyloidosis LM-Congo red stain shows apple-green Associated with chronic conditions
birefringence under polarized light. (e.g., multiple myeloma, TB, RA).
Nephrotic syndrome (continued)

Membrana Type !-subendothelial IC deposits with
proliferative granular IF; "tram-track" appearance clue
glomerulonephritis to GBM splitting caused by mesangial
(MPGN) ingrowth [!].
Type 11-intramembranous IC deposits; "dense
deposits."
Can also present as nephritic syndrome. Type I
is associated with HBV, HCV.
Type II is associated with C3 nephritic factor.
Diabetic glomerulo Nonenzymatic glycosylation ( EG) of GBM -+
nephropathy t permeability, thickening.

NEG of efferent arterioles-+ t GF R -+
mesangial expansion.
LM-mesangial expansion, GBM thickening,
eosinophilic nodular glomerulosclerosis
(Kimmelstiel-Wilson lesion) 1].
49 2 SECTION Ill RENAL RENAL-PATHOLOGY
Nephritic syndrome Nephritic syndrome=an Inflammatory process. When it involves glomeruli, it leads to hematuria
and RBC casts in urine. Associated with azotemia, oliguria, hypertension (clue to salt retention),
and proteinuria (< 3.5 g/clay).
Acute LM-glomeruli enlarged and hypercellular, Most frequently seen in children. Peripheral and
poststreptococcal neutrophils, "lumpy-bumpy" appearance. periorbital edema, dark urine, and hypertension.
glomerulonephritis EM-subepithelial immune complex (IC) Resolves spontaneously.
humps.
IF-granular appearance clue to IgG, IgM, and
C3 deposition along GBM ancl mesangium.
Rapidly progressive LM and IF-crescent-moon shape [;J. Crescents Poor prognosis. Rapidly deteriorating renal
(crescentic) consist of fibrin and plasma proteins (e.g., C3b) function (days to weeks).
glomerulonephritis with glomerular parietal cells, monocytes, and
(RPGN) macrophages.
Several disease processes may result in this
pattern, including:
Goodpasture's syndrome-type II Hematuria/hemoptysis.
hypersensitivity; antibodies to GBM and
alveolar basement membrane -+ linear IF
Granulomatosis with polyangiitis c-AN CA.
(Wegener's)
Microscopic polyangiitis p-AN CA.
Diffuse proliferative Due to SLE or MPGN. Most common cause of death in SLE. SLE and
glomerulonephritis LM-"wire looping" of capillaries. MPGN can present as nephrotic syndrome and
(DPGN) EM-subendothelial and sometimes nephritic syndrome concurrently.
intramembranous IgG-basecl ICs often with
C3 deposition.
IF-granular.
Berger's disease {lgA Related to Henoch-Schi:inlein purpura. Often presents/flares with a U R I or acute
nephropathy) LM-mesangial proliferation. gastroenteritis.
EM-mesangial IC deposits.
IF-IgA-basecl IC deposits in mesangium.
Alport syndrome Mutation in type IV collagen -+ split basement Glomerulonephritis, deafness, and, less
membrane. X-linkecl. commonly, eye problems.
LM=light microscopy; EM=electron microscopy; IF= immunofluorescence.
RENAL RENAL-PATHOLOGY SECTION Ill 493
Kidney stones Can lead to severe complications, such as hydronephrosis and pyelonephritis. Treat and prevent by
encouraging Auid intake.
CONTENT FREQUENCY PRECIPITATES AT X-RAY NOTES
Calcium 80% t pH (calcium Radiopaque Calcium oxalate, calcium phosphate, or both.

phosphate) Conditions that cause hypercalcemia (cancer,
! pH (calcium t PT H) can hypercalciuria and stones.
-+
oxalate) Oxalate crystals can result from ethylene glycol

(antifreeze) or vitamin C abuse. Treatments for
recurrent stones include thiazides and citrate.
Most common kidney stone presentation:
calcium oxalate stone in a patient with
hypercalciuria and normocalcemia.
Ammonium 15% t pH Radiopaque Caused by infection with urease-positive bugs
magnesium (Proteus mirabilis, Staphylococcus, Klebsiella)
phosphate that hydrolyze urea to ammonia urine
-+
("struvite") alkalinization. Can form staghorn calculi [J

that can be a nidus for UTis.
Uric acid 5% ! pH RadiolUcent Visible on CT and ultrasound but not x-ray.

Strong association with hyperuricemia
(e.g., gout). Often seen in diseases with
t cell turnover, such as leukemia. Treat with
alkalinization of urine.
Cystine l% ! pH Radiopaque Most often zo to cystinuria. Hexagonal crystals.
Treat with alkalinization of urine.
Hydronephrosis Back-up of urine into the kidney. Can be caused by urinary tract obstruction or vesicoureteral
reAux. Causes dilation of renal pelvis and calyces proximal to obstruction. May result in
parenchymal thinning in chronic, severe cases.
Renal cell carcinoma Originates from proximal tubule cells Most common renal malignancy.
-+ polygonal clear cells rJ filled with Associated with gene deletion on chromosome
accumulated lipids and carbohydrates. 3 (deletion may be sporadic or inherited as von
Most common in men 50-70 years of age. t Hippel-Lindau syndrome).
incidence with smoking and obesity. Manifests Associated with paraneoplastic syndromes
clinically with hematuria, palpable mass rn (ectopic EPO, ACTI-1, PTHrP).
, 2 polycythemia, flank pain, fever, and " Silent" cancer because in retroperitoneum,
weight loss. Invades renal vein then IVC and commonly presents as a metastatic neoplasm.
spreads hematogenously; metastasizes to lung Treatment: resection if localized disease.
and bone. Resistant to conventional chemotherapy and
radiation therapy.
Wilms' tumor Most common renal malignancy of early Deletion of tumor suppressor gene WTl on
(nephroblastoma) childhood (ages 2-4). Contains embryonic chromosome ll. May be part of Beckwith
glomerular structures. Presents with huge, Wiedemann syndrome or WAGR complex:
palpable flank mass and/or hematuria. Wilms' tumor, Aniridia, Genitourinary
malformation, and mental Retardation.
Transitional cell Most common tumor of urinary tract system

carcinoma (can occur in renal calyces, renal pelvis,
ureters, and bladder) rJ. Painless hematuria
(no casts) suggests bladder cancer.
Associated with problems in your Pee SAC:
Phenacetin, Smoking, Aniline dyes, and
Cyclophosphamide.
Transitional cell carcinoma. Papillary growth lined

by transitional epithelium with mild nuclear atypia and
pleomorphism.
Pyelonephritis
Acute Affects cortex with relative sparing of glomeruli/
vessels fJ. Presents with fever, costovertebral
angle tenderness, nausea, and vomiting.
White cell casts in urine are classic.
Acute pyelonephritis. Neutrophilic infiltration into renal

interstitium.
Chronic The result of recurrent episodes of acute

pyelonephritis. Typically requires
predisposition to infection such as
vesicoureteral reflux or chronically obstructing
kidney stones.
Coarse, asymmetric corticomedullary scarring,
blunted calyx II). Tubules can contain
eosinophilic casts (thyroidization of kidney).
Chronic pyelonephritis. Lymphocytic invasion with

fibrosis.
Drug-induced Acute interstitial renal inflammation. Pyuria Associated with fever, rash, hematuria, and
interstitial nephritis (classically eosinophils) and azotemia costovertebral angle tenderness, but can be
(tubulointerstitial occurring after administration of drugs that act asymptomatic.
nephritis) as haptens, inducing hypersensitivity. Nephritis
typically occurs l-2 weeks after certain
drugs (e.g., diuretics, penicillin derivatives,
sulfonamides, rifampin), but can occur months
after starting NSAIDs.
Diffuse cortical Acute generalized cortical infarction of both Associated with obstetric catastrophes (e.g.,
necrosis kidneys. Likely due to a combination of abruptio placentae) and septic shock.
vasospasm and DIC.
49 6 SECTION Ill RENAL RENAL-PATHOLOGY
Acute tubular necrosis Most common cause of intrinsic renal failure. Associated with renal ischemia (e.g., shock,
Self-reversible in some cases, but can be fatal if sepsis), crush injury (myoglobinuria), drugs,
left untreated. Death most often occurs during toxins.
initial oliguric phase. Key finding: granular ("muddy brown") casts.
3 stages:
1. Inciting event
2. Maintenance phase-oliguric; lasts 1-3
weeks; risk of hyperkalemia
3. Recovery phase-polyuric; BUN and
serum creatinine fall; risk of hypokalemia
Renal papillary Sloughing of renal papillae ...... gross hematuria and proteinuria. May be triggered by a recent
necrosis infection or immune stimulus. Associated with:
Diabetes mellitus
Acute pyelonephritis
Chronic phenacetin use (acetaminophen is phenacetin derivative)
Sickle cell anemia and trait
Acute renal failure In normal nephron, BUN is reabsorbed (for countercurrent multiplication), but creatinine is not.
(acute kidney injury) Acute renal failure is defined as an abrupt decline in renal function with t creatinine and t BUN
over a period of several clays.
Prerenal azotemia As a result of RBF (e.g., hypotension) ...... GF R. Na+fH20 and urea retained by kidney in an
attempt to conserve volume, so BUN/creatinine ratio t.
Intrinsic renal failure Generally clue to acute tubular necrosis or ischemia/toxins; less commonly clue to acute
glomerulonephritis (e.g., RPGN). Patchy necrosis leads to debris obstructing tubule and fluid
backflow across necrotic tubule ...... GF R. Urine has epithelial/granular casts. BUN reabsorption
is impaired ...... BUN/creatinine ratio.
Postrenal azotemia Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies). Develops only with
bilateral obstruction.
Variable Prerenal Intrinsic Renal Postrenal

Urine osmolality >500 < 350 < 350
(mOsm/kg)
Urine Na (mEq/L) < 20 >40 >40
FeN a < 1% >2% >2%
Serum BUN/Cr >20 < 15 > 15
RENAL RENAL-PATHOLOGY SECTION Ill 497
Consequences of renal Inability to make urine and excrete nitrogenous 2 forms of renal failure-acute (e.g., AT N) and
failure wastes. chronic (e.g., hypertension and diabetes).
Consequences:
Na+JH 0 retention (CHF, pulmonary
2
edema, hypertension)
Hyperkalemia
Metabolic acidosis
Uremia-clinical syndrome marked by
t BUN and t creatinine

Nausea and anorexia
Pericarditis
Asterixis
Encephalopathy
Platelet dysfunction
Anemia (failure of erythropoietin
production)
Renal osteodystrophy (see below)
Dyslipidemia (especially t triglycerides)
Growth retardation and developmental delay
(in children)
Renal osteodystrophy Failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemia 2 --+
hyperparathyroidism. Hyperphosphatemia also independently serum Ca2+ by causing

tissue calcifications, whereas 1,25-(0H)z vitamin D intestinal Ca2+ absorption. Causes
--+
subperiosteal thinning of bones.

Renal cysts
ADPKD Formerly adult polycystic kidney disease.
Multiple, large, bilateral cysts fJ that
ultimately destroy the kidney parenchyma.
Presents with flank pain, hematuria,
hypertension, urinary infection, progressive
renal failure.
Autosomal-Dominant mutation in PKDl or
PKD2 . Death from complications of chronic
kidney disease or hypertension (caused by
t renin production). Associated with berry
aneurysms, mitral valve prolapse, benign
hepatic cysts.
ARPKD Formerly infantile polycystic kidney disease. Infantile presentation in parenchyma. Autosomal
Recessive. Associated with congenital hepatic fibrosis. Significant renal failure in utero can lead to
Potter's syndrome. Concerns beyond neonatal period include hypertension, portal hypertension,
and progressive renal insufficiency.
Medullary cystic Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability
disease to concentrate urine. Medullary cysts usually not visualized; shrunken kidneys on ultrasound.
Poor prognosis.
RENAL RENAL-PHARM ACOLOGY SECTION Ill 499
RENAL-PHARM ACOLOGY
Diuretics: site of adion
Acetazolam ide
D i stal convoluted
tubule
ca 2 +
(+ PTH )
Th iazides
Potassi u m-spa r i n g
d i u retics
Cortex NaCI
(+aldoste ron e)
Outer med u l l a
M a n n itol
ADH
t antagon i sts
C o l l ecti n g
d uct
(
I n n e r med u l l a
(Adapted, with permission, from Katzung BG. Basic and Clinical Pharmacology, 7th ed. Stamford, G: Appleton & Lange, 1 997: 243.)
500 SECTION Ill R ENAL RENAL-PHARM ACOLOGY
Mannitol
MECHANISM Osmotic diuretic, t tubular fluid osmolarity,
producing t urine flow, * intracranial/
intraocular pressure.
CliNICAl USE Drug overdose, elevated intracranial/intraocular
pressure.
TOXICITY Pulmonary edema, dehydration.
Contraindicated in anuria, CHF.
Acetazolamide
MECHANISM Carbonic anhydrase inhibitor. Causes self
limited NaHC0 3 diuresis and reduction in
total-body HC0 3 - stores.
CliNICA l USE Glaucoma, urinary alkalinization, metabolic
alkalosis, altitude sickness, pseudotumor
cerebri.
TOXICITY Hyperchloremic metabolic acidosis, "ACID"azolamide causes ACIDosis.
paresthesias, NH 3 toxicity, sulfa allergy.
Loop diuretics
Furosemide
MECHANISM Sulfonamide loop diuretic. Inhibits cotransport
system (Na+, K+, 2 CJ-) of thick ascending
limb of loop of Henle. Abolishes hypertonicity
of medulla, preventing concentration of urine.
Stimulates PGE release (vasodilatory effect
on afferent arteriole); inhibited by NSAIDs.
t Ca2 + excretion. Loops Lose calcium.
CliNICAl USE Edematous states (CHF, cirrhosis, nephrotic
syndrome, pulmonary edema), hypertension,
hypercalcemia.
TOXICITY Ototoxicity, Hypokalemia, Dehydration, Allergy OH DANG!
(sulfa), Nephritis (interstitial), Gout.
Ethacrynic acid
MECHANISM Phenoxyacetic acid derivative (not a
sulfonamide). Essentially same action as
furosemide.
CliNICAl USE Diuresis in patients allergic to sulfa drugs.
TOXICITY Similar to furosemide; can cause
hyperuricemia; never use to treat gout.
RENAL RENAL - PHARM ACOLOGY SECTION Ill 50 1
Hydrochlorothiazide
MECHANISM Thiazide diuretic. Inhibits aCl reabsorption in
early distal tubule, reducing diluting capacity
of the nephron. ! Ca2+ excretion.
CLINICAL USE Hypertension, CHF, idiopathic hypercalciuria,
nephrogenic diabetes insipidus.
TOXICITY Hypokalemic metabolic alkalosis, HyperGLUC.
hyponatremia, hyperGlycemia,
hyperLipidemia, hyperUricemia, and
hyperCalcemia. Sulfa allergy.
K+sparing diuretics Spironolactone and eplerenone; Triamterene, T he K+ STAys.

and Amiloride.
MECHANISM Spironolactone and eplerenone are competitive
aldosterone receptor antagonists in the cortical
collecting tubule. Triamterene and amiloride
act at the same part of the tubule by blocking
Na+ channels in the CCT.
CLINICAL USE Hyperaldosteronism, K+ depletion, CHF.
TOXICITY Hyperkalemia (can lead to arrhythmias),
endocrine effects with spironolactone (e.g.,
gynecomastia, antiandrogen effects).
Diuretics: electrolyte changes

Urine NaCI t (all diuretics). Serum NaCl may ! as a result.
Urine K+ t (all except K+ -sparing diuretics). Serum K+ may ! as a result.
Blood pH ! (acidemia) : carbonic anhydrase inhibitors- ! HC0 3 - reabsorption. K+ sparing-aldosterone
blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering
all cells (via H+fK+ exchanger) in exchange for J-I+ exiting cells.
t (alkalemia) : loop diuretics and thiazides cause alkalemia through several mechanisms:
Volume contraction -+ t AT II .... t Na+fJ-I+ exchange in proximal tubule .... t HC0 3 -
reabsorption ("contraction alkalosis")
K+ loss leads to K+ exiting all cells (via J-I+fK+ exchanger) in exchange for f-I+ entering cells
In low K+ state, f-I+ (rather than K+) is exchanged for Na+ in cortical collecting tubule, leading
to alkalosis and "paradoxical aciduria"

Urine Cal+ t with loop diuretics: ! paracellular Ca2+ reabsorption hypocalcemia.
-+
! with thiazides : Enhanced paracellular Ca2+ reabsorption in proximal tubule and loop of Henle.
502 SECTION Ill RENAL RENAL-PHARM ACOLOGY
ACE inhibitors Captopril, enalapril, lisinopril.

MECHANISM Inhibit angiotensin-converting enzyme (ACE) Angiotensin II receptor blockers (-sartans) have
-+ angiotensin II GF R by preventing
- effects similar to ACE inhibitors but do not
constriction of efferent arterioles. Levels t bradykinin -+ no cough or angioedema.
of renin t as a result of loss of feedback
inhibition. Inhibition of ACE also prevents
inactivation of bradykinin, a potent vasodilator.
CLINICAL USE Hypertension, CHF, proteinuria, diabetic renal
disease. Prevent unfavorable heart remodeling
as a result of chronic hypertension.
TOXICITY Cough, Angioedema, Teratogen (fetal renal Captopril's CATCHH.
malformations), Creatinine increase U GF R),
Hyperkalemia, and Hypotension. Avoid in
bilateral renal artery stenosis, because ACE
inhibitors will further GF R -+ renal failure.
HIGH-YIELD SYSTEMS
Reproductive
"Artificial insemination is when the fanner does it to the cow instead of the
bull."
- Student essay
"Whoever called it necking was a poor fudge of anatomy."

- Groucho Marx
"See, the problem is that God gives men a brain and a penis, and only
enough blood to run one at a time."
- Robin Williams
504 SECTION Ill REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY
REPRODUCTIVE-EMBRYOLOGY
Important genes of embryogenesis
Sonic hedgehog gene Produced at base of l i mbs in zone of polarizing activity. I nvolved in patterning along anterior-
posterior axis. I nvolved in CNS development; mutation can cause holoprosencephaly.
Wnt-7 gene Produced at apical ectodermal ridge (th ickened ectoderm at distal end of each developing l i m b ) .
Necessary for proper organization along dorsal-ventral axis.
FGF gene Produced at apical ectodermal ridge. Stimulates m itosis of underlying mesoder m , providing for
lengthening of l i mbs.
Homeobox (Hox) I nvolved in segmental organization of embryo in a craniocaudal d i rection. Hox mutation s
genes -+ appendages in wrong locations.
Early fetal development
DAYO Fertilization by sperm forming zygote, initiating

embryogenesis.
Day 3
WITHIN WEEK 1 hCG secretion begins after implantation of .--"'

blastocyst.
@ Morula
t', DayS
V Blastocyst
WITHIN WEEK 2 Bilaminar disc (epibl ast, hypoblast) . 2 weeks= L Endometrium
2 layers . }_
- Day6
Implantation
WITHIN WEEK 3 Trilaminar disc. 3 weeks = 3 layers. Uterine-
wall
Gastrulation .
Prim itive streak, notochord, mesoderm and its
organization, and neural plate begin to form.
WEEKS 3-8 (EMBRYONIC Neural tube formed by neuroectoderm and
PERIOD) closes by week 4.
Organogenesis.
Extremely susceptible to teratogens.
WEEK4 Heart begins to beat.
Upper and lower l i mb buds begin to form.
4 weeks= 4 limbs .
WEEK 8 (START OF Fetal movement, fetus looks l ike a baby.
FETAL PERIOD)
WEEK 10 Genitalia have male /female characteristics.
Gastrulation Process that forms the trilaminar embryon ic elise. Establ ishes the ectoderm, mesoderm, and
endoderm germ layers. Starts with the epiblast invagi nating to form the primitive streak.
REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY I SECTION Ill 50 5
Embryologic derivatives
Ectoderm
Surface ectoderm Adenohypophysis (from Rathke's pouch) ; lens Craniopharyngioma- benign Rathke's pouch
of eye ; epithel ial l i n i ngs of oral cavity, sensory tumor with cholesterol crystal s, calcifications.
organs of ear, and olfactory epithel ium;
epiderm is; anal canal below the pectinate line;
parotid , sweat, and mammary glands.
Neuroectoderm B ra i n (neurohypophysis, CNS neurons, Neuroectoderm -think C N S .
ol igoclenclrocytes, astrocytes, ependymal cells,
pineal gland), retina and optic nerve, spinal
cord .
Neural crest PNS (dorsal root gangl ia, cranial nerves, celiac Neural crest- think P N S a n d non-neural
gangl ion, Schwann cells, ANS ) , melanocytes, structures nearby.
chromaffin cells of adrenal medulla,
parafoll icular (C) cells of thyroid, Schwann
cells, pia and arachnoid, bones of the skull,
oclontoblasts, aorticopulmonary septum.
Mesoderm Muscle, bone, connective tissue, serous Mesodermal defects= VACT ERL :
l i n i ngs of body cavities (e .g., peritoneum), Vertebral defects
spleen (derived from foregut mesentery) , Anal atresia
cardiovascular structures, lymphatics, blood, Cardiac defects
wall of gut tube, wall of bladder, urethra, Tracheo-Esophageal fistula
vagina, kidneys, adrenal cortex, derm is, testes, Renal defects
ovanes. Limb defects (bone and muscle)
Notochord induces ectoderm to form
neuroectoderm (neural plate) . Its only
postnatal derivative is the nucleus pulposus of
the intervertebral el ise.
Endoderm Gut tube epithel ium (includ ing anal canal
above the pectinate l ine) and luminal
epithelial derivatives (e.g., lungs, l iver,
gal lbladder, pancreas, eustach ian tube,
thymus, parathyroid, thyroid foll icular cells) .
Types of errors in organ morphogenesis
Agenesis Absent organ clue to absent primordial tissue.

Aplasia Absent organ despite present primordial tissue.
Deformation Extrinsic disruption ; occurs after the embryon ic period.
Hypoplasia Incomplete organ development; primordial tissue present.
Malformation Intrinsic disruption ; occurs during the embryonic period (weeks 3-8).
506 SECTION Ill REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY
Teratogens Most susceptible in 3rd-8th weeks (embryon ic period - organogenesis) of pregnancy. B efore week
3 : all-or-none effects. After week 8: growth and function affected.
TERATOGEN EFFECTS ON FETUS NOTES
Medications
ACE inhibitors Renal damage

Alkylating agents Absence of digits, multiple anomalies
Aminoglycosides CN VIII toxicity A mean guy hit the baby in the ear.
Carbamazepine Neural tube defects, craniofacial defects,
fingernail hypoplasia, developmental delay,
I UGR
Diethylstilbestrol (DES) Vaginal clear cell adenocarcinoma, congen ital
Mi.illerian anomalies
Folate antagonists Neural tube defects
Lithium Ebstein's anomaly (atrial ized right ventricle)
Phenytoin Fetal hydantoin syndrome: m icrocephaly,
dysmorphic craniofacial features, hypoplastic
nails and distal phalanges, cardiac defects,
I UGR, mental retardation
Tetracyclines Discolored teeth
Thalidomide Limb defects ( "fl ipper" l i mbs) Limb defects with " tha-l i mb-domide."
Valproate Inh ibition of maternal fol ate absorption
-+ neural tube defects
Warfarin Bone deformities, fetal hemorrhage, abortion , Do not wage warfare on the baby; keep it heppy
ophthalmologic abnormal ities with hepari n (does not cross placenta) .
Substance abuse
Alcohol Leading cause of birth defects and mental

retardation ; fetal alcohol syndrome
Cocaine Abnormal fetal development and fetal
addiction ; placental abruption
Smoking Preterm labor, placental problems, IUGR,
(nicotine, CO) ADI-ID
Other
Iodide (lack or excess) Congenital goiter or hypothyroidism (cretinism)

Maternal diabetes Caudal regression syndrome (anal atresia to
sirenomel ia), congenital heart defects, neural
tube defects
Vitamin A (excess) Extremely h i gh risk for spontaneous abortions
and bi rth defects (cleft palate, cardiac
abnormalities)
X-rays M icrocephaly, mental retardation
Fetal infections and certain antibiotics can also cause congenital malformations (see the Microbiology chapter) .
,,
REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY SECTION Ill 5 07
Fetal alcohol syndrome Lead ing cause of congenital malformations in the United States. Newborns of mothers who
consumed significant amounts of alcohol during pregnancy have an t incidence of congenital
abnormal ities, includ ing mental retardation , pre- and postnatal developmental retardation ,
microcephaly, holoprosencephaly, facial abnormal ities, l i mb dislocation , and heart and lung
fistulas.
Twinning Dizygotic twins arise from 2 eggs that are separately fertilized by 2 different sperm (always 2
zygotes) , and will have 2 separate amn iotic sacs and 2 separate placentas (chorions) . Monozygotic
twins arise from 1 fertil i zed egg (1 egg+ 1 sperm) that splits i nto 2 zygotes i n early pregnancy.
The degree of separation between monozygotic twins depends on when the fertilized egg splits
i nto 2 zygotes. The timing of this separation determines the number of chorions and the number
of a m n ions.
Monozygotic (20%) Dizygotic (80%)
rn w
j
Fused
2-cell stage placenta
/
2-cell stage 2-cell stage
I I
Clea age Dichorionic
0-4 days or diamniotic
(-25%)
\ Separate
placenta
j
Morula Morula
I
4-8 days Cleavage
-
(-75%)
Blastocyst Blastocyst Blastocyst
l ! !
Monochorionic
8-12 days Cleavage
monoamniotic
(<1%)
0
'- Amniotic
cavity
Chorionic
cavity Formed Formed Formed
embryonic embryonic embryonic
disc disc disc
j
Cleavage Monochorionic
> 13 days monoamniotic
conjoined twins
Amnion
(inner)
Chorion J!j!l\\
(outer)
No twinning if Dichorionic
no cleavage diamniotic
(Adapted, with permission, from Cunningham FG et al. Williams Obstetrics, 23rd ed. New York: McGraw-Hill, 2009: Fig. 39-2.)
508 SECTION Ill REPRODUCT IVE REPRODUCT I VE-EMBRYO LOGY
Placental development 1 site of nutrient and gas exchange between mother and fetus.
Fetal component
Cytotrophoblast I nner layer of chorionic villi. Cytotrophoblast makes Cells.
Syncytiotrophoblast Outer layer of chorionic villi; secretes hCG
(structurally similar to LH; stimulates corpus
luteum to secrete progesterone during fi rst
trimester) .
Maternal component
Decidua basalis Derived from the endometrium. Maternal
blood in lacunae.
Umbilical cord Umbilical arteries (2) - return deoxygenated Single umbil ical artery is associated with
blood from fetal internal il iac arteries to congenital and chromosomal anom alies.
placenta. Umbilical arteries and veins are derived from
Umbilical vei n ( 1 ) - suppl ies oxygenated blood allantois.
from placenta to fetus; drains via ductus
venosus i nto IVC .
Umbilical
arteries
Umbilical
vein
Urachal duct 3rd week-yolk sac forms allantois, which extends into urogenital sinus. Allantois becomes urachus,
a duct between bladder and yolk sac.
Failure of urachus to obl iterate :
Patent urachus- urine d ischarge from umbil icus.
Vesicourachal diverticulum- outpouchi ng of bladder.
Vitelline duct 7th week- obl iteration of vitelline duct (omphalo-mesenteric duct) , which connects yolk sac to
m idgut lumen.
Failure of vitelline duct to close:
Vitelline fistula ..... meconium discharge from umbilicus.
Meckel's diverticulum- partial closur e , with patent portion attached to ileum. May h ave ectopic
gastric mucosa ..... melena, periumbil ical pain, and ulcer.

REPRODUCT IVE REPRODUCTIVE-EMBRYOLOGY SECTION Ill 509
Aortic arch derivatives Develop into the arterial system.

1st Part of maxillary artery (branch of external lst arch is maximal.
carotid) .
2nd Stapedial artery and hyoid artery. Second =Staped ial.
3rd Common Carotid artery and proximal part of C is 3rd letter of alphabet.
internal Carotid artery.
4th On left, aortic arch ; on right, proximal part of 4th arch (4 l i m bs) =systemic.
right subclavian artery.
6th Proximal part of pul monary arteries and (on left 6th arch =pulmonary and the pulmonary-to
only) ductus arteriosus. systemic shunt (ductus arteriosus) .
Right recurrent
laryngeal nerve
loops around here
Branchial apparatus Also called pharyngeal apparatus. Composed of CAP covers outside from inside :
branch ial clefts, arches, and pouches. Clefts = ectoderm
Branch ial clefts - derived from ectoderm. Also Arches = mesoderm
called branch ial grooves. Pouches = endoderm
}
Branch ial arches- derived from mesoderm
Primitive pharynx
(muscles, arteries) and neural crest (bones,
cartilage) .
Branchial pouches - derived from endoderm. 1st
2 nd
Pharyngeal
3rd arches
4th
Primitive
esophagus
Branchial cleft lst cleft develops i nto external aud itory meatus.
derivatives Znd through 4th clefts form temporary cervical sinuses, which are obl iterated by prol iferation of Znd
arch mesenchyme.
Persistent cervical sinus -+ branch ial cleft cyst with i n lateral neck.
510 SECTION Ill REPRODUCTIVE REPRODUCTIV E-EMBRYOLOGY
Branchial arch derivatives

ARCH CARTI LAGE MUSCLES NERVES ABNORMALITIES/COMMENTS
1st arch Meckel's cartilage : Muscles of Mastication CN V2 and V3 Treacher Collins

Mandible, Malleus, (temporalis, Masseter, chew syndrome: 1 s t-arch
incus, spheno lateral and Medial neural crest fails to
Mandibular l i gament pterygoids), Mylohyoid , m igrate mandibular
--+
anterior belly of digastric, hypoplasia, facial

tensor tympani, tensor vel i abnormal ities
palatini
2nd arch Reichert's cartilage : Muscles of facial expression , CN VII (facial
Stapes, Styloid Stapedius, Stylohyoid, expression)
process, lesser horn posterior belly of digastric smile
of hyoid, Stylohyoid
l igament
3rd arch Cartilage : greater horn Stylopharyngeus (think CN IX (stylo Congenital pharyngo
of hyoid of stylo phary n geu s pharyngeus) cutaneous fistula:
innervated by swallow stylishly persistence of cleft
glossopharyngeal nerve) and pouch - fistula
between tonsillar area,
cleft i n lateral neck
4th-6th arches Cartilages: thyroid, 4th arch : most pharyngeal 4th arch : C N Arches 3 and 4 form
cricoid, arytenoids, constrictors; cricothyroid, X (superior posterior YJ of tongue;
corniculate, cuneiform levator vel i palatini laryngeal branch) arch 5 makes no
6th arch : all intrinsic simply swallow major developmental
muscles of larynx except 6th arch : C N contributions
cricothyroid X (recurrent
laryngeal branch)
speak
aThese are the only CNs with both motor and sensory components (except V2, wh ich is sensory only) .
When at the restaurant of the golden arches, children tend to first chew ( 1 ) , then smile ( 2 ) , then swallow styl ish ly (3) or
simply swallow (4) , and then speak ( 6 ) .
'
REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY SECTION Ill 51 1
Branchial pouch derivatives
1st pouch Develops into m iddle ear l st pouch contributes to Ear, tonsils, bottom-to-top:
cavity, eustach ian tube, endoderm-] ined structures of l (ear),
mastoid a ir cells. ear. 2 (tonsils),
2nd pouch Develops into epithelial l in ing 3 dorsal (bottom for in ferior
of palatine tonsil . parathyroids) ,
3 ventral (to= thymus ) ,
3rd pouch Dorsal wings - develops into 3rd pouch contributes to 3
4 (top= superior
inferior parathyroids. structures (thymus, left and
parathyroids) .
Ventral w ings- develops into right inferior parathyroids) .
thymus. 3rd-pouch structures end up
below 4th-pouch structures.
4th pouch Dorsal wings - develops into

superior parathyro ids.
DiGeorge syndrome Aberrant development of 3rd and 4th pouches -+ T-cell deficiency (thy m ic aplasia) and
hypocalcemia (fa ilure of parathyroid development) .
MEN2A Mutation of germ l ine RET (neural crest cells) :
Ad renal medulla (pheoch romocytom a ) .
Parathyroid (tumor) : 3rd /4th pharyngeal pouch .
Parafol l icular cells (medullary thyroid cancer) : derived from neural crest cells; associated with
the 4th / 5 th pha ryngeal pouches.
Cleft lip and cleft Cleft lip - fa ilure of fusion of the maxil lary Roof of Nasal
mouth cavity
palate and medial nasal processes (formation of l a
palate ) .
Cleft palate-fa ilure o f fusion o f the lateral Palatine shelves

(2 palate)
palatine processes, the nasal septum, and/or
the median palatine process (formation of zo
palate) . Uvula
Cleft palate (partial)
Cleft 1 ip and cleft palate have two distinct
Cleft lip
etiologies, but often occur together.
5l 2 SECTION Ill REPRODUCT IVE REPRODUCTIVE-EMBRYOLOGY
Genital embryology
Female Default development. Mesonephric duct Gubernaculum
degenerates and paramesonephric duct

develops.
Male SRY gene on Y chromosome- produces testis
determin ing factor (testes development) .
Sertoli cells secrete Mullerian inh ibitory
factor ( M I F) that suppresses development of
paramesonephric ducts. Paramesonephric duct -
Leydig cells secrete androgens that stimulate
the development of mesonephric ducts.
Mesonephric duct
Paramesonephric Develops into female internal structures
(Mullerian) duct fallopian tubes, uterus, and upper portion
of vagina (lower portion from urogen ital
sinus ) . Mullerian duct abnormal ities result in
anatom ical defects that may present as primary
Urogenital sinus
amenorrhea in females with fully developed
secondary sexual characteristics (indicator of
functional ovaries) .
Mesonephric Develops into male internal structures
(Wolffian) duct (except prostate) - Sem inal vesicles,
Epid idym is, Ejaculatory duct, and Ductus
deferens ( SEED) .
Bicornuate uterus Results from incomplete fusion of the paramesonephr ic ducts. Can lead to urinary tract
abnormal ities and m iscarriages.
REPRODUCTIVE REPRODUCTIVE-EMBRYOLOGY SECTION Ill 5l3
SRYgene
0 No Sertol i cells or lack of Mi.illerian inh ibitory

factor: develop both male and female internal
gen ital ia and male external gen italia
e 5u-reductase deficiency: male internal
gen italia, a mbiguous external gen italia until
puberty
Degeneration of
paramesonephric (Mullerian)
duct (female internal
genitalia) DHT

Genital tubercle, Male external genitalia,
urogenital sinus prostate
Male/female genital homologues
Male
Urethral
closure
Scrotum
Dihydrotestosterone Estrogen
Glans penis -------Genital tubercle -------- Glans clitoris

Corpus cavernosum
--- bulbs
and spongiosum -- Genital tubercle -- Vestibular
---
Bulbourethral glands ------- Greater vestibular glands

Urogenital sinus ------
(of Cowper) (of Bartholin)
Urethral and paraurethral
Prostate gland ---- Urogenital sinus -----
glands (of Skene)
Ventral shaft of penis
------ Urogenital folds ------- Labia minora
(penile urethra)
Scrotum ------ Labioscrotal swelling -------- Labia majora
(Adapted, with permission, from Strong Bet al. Human Sexuality: Diversity in Cantempor01y Amenca, 5th ed. New York: McGraw-Hill, 2005: Fig. 3.1)
Congenital penile abnormalities
Hypospadias Abnormal open ing of pen ile urethra on inferior Hypospadias is more common than epispad ias.
(ventral) side of penis due to fa ilur e of urethral Fix hypospad ias to prevent UTis.
folds to close. Hypo is below.
Epispadias Abnormal open ing of pen ile urethra on superior Exstrophy of the bladder is associated with
(dorsal ) side of penis clue to faulty position ing Epispadias.
of gen ital tubercle. When you have Epispad ias, you hit your Eye
when you pEE.
514 SECTION Ill REPRODUCTIVE R EPRODUCTIVE - ANATOMY
Descent of testes and ovaries

MALE REMNANT FEMALE REMNANT
Gubernaculum (band Anchors testes within scrotum . Ovarian ligament+ round 1 igament of uterus.
of fibrous tissue)
Processus vaginalis Forms tun ica vaginalis. Obl iterated.
(evagination of
peritoneum)
R EPRODUCTIV E-ANATOMY
Cionadal drainage
Venous drainage Left ovary/testis left gonadal vein .... left renal
--+ Just as the left adrenal vein drains to the left
vei n IVC.
--+ renal vei n before the IVC.
Right ovary/testis .... right gonadal vein - IVC. Because the left spermatic vei n enters the
Lymphatic drainage Ovaries/testes .... para-aortic lymph nodes. left renal vei n at a 90 angle, flow is less
Di stal 113 of vagina/vulva /scrotum .... superficial continuous on the left than on the right.
inguinal nodes. --+ left venous pressure > right venous pressure
Proximal 2/3 of vagina/uterus --+obturator, .... varicocele more common on the left.
external i l iac and hypogastric nodes.
REPRODUCTIVE REPRODUCT I V E - ANATOM Y SECTION Ill 515
Female reprodudive anatomy
Mesosalpinx
Mesovarium
(of broad ligament)
(of broad ligament)
Fallopian tube Ligament

of the ovary
Suspensory
ligament -----l:+-'..:-.
Round l1gament
of the uterus
Labia minora
Fornix
ligament
Posterior view Sagittal view
liGAMENT CONNECTS STRUCTURES CONTAINED NOTES
Suspensory ligament Ova ries to lateral Ova rian vessels Ureter at risk of injur y dur i n g ligation of ovarian
of the ovaries pelvic wall vessels in oophorectomy.
Suspensory l i gament suspends ovary to pelvic
wall .
Cardinal ligament (not Cervix to side wall of Uterine vessels Ureter at risk o f injur y during l i gation o f uterine
labeled) pelvis vessels in hysterectomy.
Round ligament of the Uterine fundus to labia Artery of Sampson Derivative of gubernaculum . Travel s through
uterus maJora round ingu inal canal .
Broad ligament Uterus, fallopian tubes, Ovaries, fallopian Mesosalpinx, mesometrium, and mesovarium
and ovaries to pelvic tubes, and round are the components of the broad l igament.
side wall ligaments of uterus
Ligament of the ovary Medial pole of ovary to one Ligament of the ovary Latches ovary to Lateral
lateral uterus uterus; is a derivative of the gubernaculum.
Female reprodudive TISSUE H I STOLOGY

epithelial histology Vagina Stratified squamous epithel ium, nonkeratinized
Ectocervix Stratified squamous epithel ium
Endocervix Si mple colu mnar epithel ium
Uterus Simple colu mnar epithel ium, pseudostratified
tubular glands
Fallopian tube Simple columnar epithel ium , cil iated
Ovary Si mple cuboidal epithel ium
51 6 SECTION Ill REPRODUCTIVE REPRODUCTIVE-ANATOMY
Male reprodudive anatomy

Bladder
y
Seminal vesicle Head of epididymis
\
----
Roto ""''
Symphysis pubis -...._
Prostate
Inguinal canal
\ Vas deferens
;;:, !
Ejaculatory duct
Cowper's Tooio giooo

(bulbourethral) gland
Tail of epididymis
Pathway of sperm during ejaculation

SEVENUP:
Seminiferous tubules
Epididymis
Vas deferens
Ejaculatory ducts
(Nothing)
Urethra
Penis
Autonomic innervation Erection- Parasympathetic nervous system Point and Shoot.

of the male sexual (pelvic nerve):
Sildenafil and vardenafil inhibit cGMP
response NO --+ t cGMP --+ smooth muscle
breakdown.
relaxation --+vasodilation proerectile.
--+
NE --+ t [Ca2 +Ln smooth muscle

--+
contraction --+ vasoconstriction

--+ antierectile.
Emission-Sympathetic nervous system
(hypogastric nerve).
Ejaculation-visceral and somatic nerves
(pudendal nerve).
REPRODUCTIVE REPRODUCTIVE-ANATOMY SECTION Ill 517
Seminiferous tubules
CELL FUNCTION LOCATION/NOTES
Spermatogonia Maintain germ pool and produce ]0 Line seminiferous tubules r.:J
(germ cells) spermatocytes
Sertoli cells Secrete inhibin -+ inhibit FSH Line seminiferous tubules

(non-germ cells) Secrete androgen-binding protein (ABP) Sertoli cells Support Sperm Synthesis
- maintain local levels of testosterone
Tight junctions between adjacent Sertoli cells
form blood-testis barrier -+ isolate gametes
from autoimmune attack
Support and nourish developing spermatozoa
Regulate spermatogenesis
Produce anti-mi.illerian hormone
Temperature sensitive; sperm production and t temperature seen in varicocele,
inhibin with t temperature cryptorchidism
Leydig cells Secrete testosterone; testosterone production Interstitium

(endocrine cells) unaffected by temperature
---"--- Lumen of
seminiferous
tubule
.;r--=::..__---::,....;---;--7'-
----- Secondary
spermatocyte
.:. ---'-;--;.--+--- Primary

.;.>,,.------'.-
spermatocyte
518 SECTION Ill REPRODUCT IVE R EPRODUCTIV E-PHYSIOLOGY
REPRODUCTIV E-PHYSIOLOGY
Spermatogenesis Spermatogenesis begins at puberty with "Conium" is going to be a sperm; "Zoon" is

spermatogonia. Full development takes 2 "Zooming" to egg.
months. Occurs in seminiferous tubules.
Produces spermatids that undergo
spermiogenesis (loss of cytoplasmic contents,
gain of acrosomal cap) to form mature
spermatozoon.
Spermiogenesis
Spermatogonium 1' spermatocyte 2' spermatocyte Spermatid ------- Mature spermatozoon

Diploid Diploid Haploid Haploid Haploid
(2N, 2C) (2N, 4C) (lN. 2C) (lN, lC) (N)
Sperm
Acrosome
'\
Head 1

Nucleus____,...
Blood-testis
barrier
Middle
piece
Note: Impaired tail mobility can lead to

infertility (seen in ciliary
dyskinesia/Kartagener's syndrome).
Replication
(interphase) Meiosis I
REPRODUCTIVE R EPRODUCTIV E-PHYSIOLOGY SECTION Ill 519
Regulation of spermatogenesis
-------- --
H yp othalamus
_ _ _ _ _ __
I
@ stimulates synthesis
of testosterone in
Leydig cells
Sertoli cells
Leydig
-- - ---- - ------ -LI __
Inhibi n
_ _ _ __J
cells
\\\------,
Testosterone
Blood
vessel
Androgens Testosterone, di hydrotestosterone (DHT), androstenedione.

SOURCE DHT and testosterone (testis), AnDrostenedione Potency: DHT > testosterone >
(ADrenal) androstened ione.
FUNCTION Testosterone : Testosterone is converted to DHT by the enzyme
Differentiation of epididym is, vas deferens, 5 a-reductase, which is inh ibited by fin asteride.
sem inal vesicles (internal genitalia, except Testosterone and androstenedione are converted
prostate) to estrogen in adipose tissue and Leyd ig cells
Growth spurt by the enzyme aromatase. Aromatase is the
Penis key enzyme in the conversion of androgens to
Sem inal vesicles estrogen.
Sperm Exogenous testosterone i n hibition of
-+
Muscle
hypothalam ic-pitu itary-gonadal axis * -+
RBCs intratesticular testosterone * testicular size

-+
Deepeni ng of voice -+azoosperm ia.

Closing of epiphyseal plates (via estrogen
converted from testosterone)

Libido
DHT:
Early - d ifferentiation of penis, scrotu m ,
prostate
Late - prostate growth, balding, sebaceous
gland activity
520 SECTION Ill REPRODUCTIVE REPRODUCTIVE-PHYSIOLOGY
Estrogen
SOURCE Ovary ( 1 7-estradiol ) , placenta (estriol ) , adipose Potency: estradiol > estrone > estriol
tissue (estrone via aromatization)
FUNCTION Development of genitalia and breast, female fat Pregnancy:
distribution 5 0-fold t in estradiol and estrone
Growth of foll icle, endometrial prol iferation, 1 000-fold t in estriol ( indicator of fetal wel l
t myometrial excitability being)

Upregulation of estrogen, LH, and progesterone Estrogen receptors expressed in the cytoplasm ;
receptors ; feedback inh ibition of FSH and translocate to the nucleus when bound by
L H , then LH surge ; stimulation of prolactin l i gand
secretion (but blocks its action at breast)
t transport proteins , S H B G ; t H D L ; ! LDL
+ Pulsatile GnRH +
FSH LH

I I
Aro rri'atase
Des olase
,
;;
Estrog
Estrog 0. ndrostenedione Androstenedio 0c holesterol
Granulosa cell Theca cell
Progesterone
SOURCE Corpus luteum, placenta, adrenal cortex, testes Elevation of progesterone is indicative of
FUNCTION Stimulation of endometrial glandular secretions ovulation.
and spiral artery development Progesterone is pro-gestation .
Maintenance of pregnancy
! myometrial excitabil ity
Production of thick cervical mucus, which
inhibits sperm entry into the uterus
t body temperature
Inh ibition of gonadotropins (LH, FSH )
Uterine smooth muscle relaxation (preventing
contractions)
! estrogen receptor expressivity
<t
REPRODUCTIVE REPRODUCTIVE-PHYSIOLOGY SECTION Ill 52 1
Tanner stages of sexual I . Childhood

development
I I . Pubic hair appears (pubarche) ; breast bud forms (thelarche)
III. Pubic hair darkens and becomes curly; penis size /length t; breast enlarges
IV. Penis width t, darker scrotal skin, development of glans; raised a reolae
V. Adult; areolae are no longer raised
Menstrual cycle
Regressing corpus Fol licular phase can vary i n length. Luteal

luteum
Ovulation phase is usually a constant 14 clays. Ovulation
Maturing clay + 14 clays = menstruation .
graafian
Fol l icular growth is fastest during 2nd week of
follicle
pro! iferative phase.
l Estrogen sti mulates endometrial prol iferation.
Progesterone maintains endometrium to
support impl a n tation .
progesterone --+ fertil ity.
Ol igomenorrhea: > 3 5 -cl a y cycle.
v
Proliferative phase Secretory phase Polymenorrhea: < 2 1 -clay cycle.
(follicular) (luteal) Metrorrhagia: frequent but i rregular
menstruation .
Blood hormone levels Menometrorrhagia : heavy, i rregular
menstruation at irregular interval s .
t estrogen

LH surge

Ovulation
Progesterone (from corpus luteum)

0 7 14 21 28
Days Progesterone levels fall

Menstruation (via apoptosis of endometrial cells)
Ovulation t estrogen, t GnRH receptors on anterior Mittelschmerz- blood from ruptured fol l icle
pituitary. Estrogen surge then stimulates LH or fol l icular enlargement causes peritoneal
release, causing ovulation (rupture of fol l icle) . irritation that can m i m i c appendicitis.
t temperature (progesterone induced).
522 SECTION Ill REPRODUCTIVE REPRODUCTIVE-PHYSIOLOGY
Oogenesis l o oocytes begin meiosis I dur i n g fetal life and

complete meiosis I just prior to ovulation .
Meiosis I is arrested in prOphase I for years until
Ovulation (l o oocytes) .
Meiosis I I is arrested in metaphase II until An egg met a sperm .
fertilization (2 oocytes) .
If fertilization does not occur with i n l day, the
zo oocyte degenerates.
Oogonium 1' oocyte 2' oocyte Ovum
Diploid Diploid Haploid Haploid
(2N, 2C) (2N. 4C) (lN. 2CI (lN. lC)
Arrested in Arrested in
prophase I metaphase II
until ovulation until fertilization
Polar body
{can degenerate
or give rise to 2
polar bodies) Polar body
Replication Meiosis I Meiosis II

(interphase)
REPRODUCTIVE REPRODUCTIVE-PHYSIOLOGY SECTION Ill 523
Pregnancy Fertilization most commonly occur s i n upper end of fallopian tube (the ampul la) . Occurs with in l
Corpus clay of ovulation .
luteum Placenta
hCG / Prolactin
I mplantation within the wall of the uterus occurs 6 clays after fertil ization . Trophobl asts secrete
// / Progesterone hCG, which is detectable in blood l week after conception and on home test in urine 2 weeks
/i / Estriol after conception.
10 20 30 40
Weeks
Lactation After labor, the in progesterone cl isinhibits l actation. Suckl ing is requ i red to maintain milk
production, since t nerve stimulation t oxytocin and prolacti n .
Prolactin- induces a n d maintains lactation a n d reproductive function.
Oxytocin - appears to help with milk letdown and may be i nvolved with uterine contractions
(function not yet entirely known ) .
hCG
SOURCE Syncytiotrophoblast o f placenta.

FUNCTION Maintains the corpus luteum (and thus progesterone) for the lst trimester by acting l ike LH
(otherwise no luteal cell stimulation, and abortion resu lts ) . I n the 2nd and 3rd trimesters, the
placenta synthesizes its own estriol and progesterone and the corpus luteum degenerates.
Used to detect pregnancy because it appears early in the urine (see above) .
Elevated hCG i n pathologic states (e.g., hydatidiform moles, choriocarci noma) .
Menopause estrogen production clue to age-l inked decl ine Hormonal change s : estrogen, t t FSH, t LH
in number of ovarian foil icles. Average age at (no surge ) , t GnRH.
onset is 51 years (earlier i n smokers) . Menopause causes H HAVOC : H irsuti sm , Hot
Usually preceded by 4-5 years of abnormal flashes, Atrophy of the Vagina, Osteoporosis,
menstrual cycles. Source of estrogen (estrone) Coronary artery d isease.
after menopause becomes peripheral Menopause before age 40 can indicate
conversion of androgens. t androgens cause premature ovarian fa ilure.
h i rsutism .
t t F S H is the best test to confirm menopause
(loss of negative feedback for FSH clue to
! estrogen) .
5 24 SECTION Ill REPRODUCTIVE R EPRODUCTI V E-PATHOLOGY
REPRODUCT I V E - PATH OLOGY
Sex chromosome disorders
Klinefelter's syndrome Testicular atrophy, eunuchoid body shape, Dysgenesis of seminiferous tubules -+ i n h ibin
[male] (XXV), 1 : 850 tal l , long extremities, gynecom astia, female - t FSH.
hair distribution (J. May present with Abnormal Leydig c e l l function -+ testosterone
developmental delay. Presence of inactivated X -+ t LH -+ t estrogen.
chromosome ( Barr body) . Common cause of
hypogonadism seen in infertil ity work-up.
Turner syndrome Short stature (if left untreated, < 5 feet) , ovarian " Hugs and kisses" (XO) from Tina Turner.
[female] (XO) dysgenesis (streak ovary with infertil ity) , Menopause before menarche.
shield chest, bicuspid aortic valve, defects estrogen leads to t LH and F S H .
rn
in lymphatics -+ webbing of neck (cystic
hygroma) and lymphedema in feet and hands,
preductal coarctation of the aorta, horseshoe
kidney, dysgerminoma II]. Most common
cause of 1 amenorrhea. No Barr body.
Double V males [male] Phenotypically norm al, very tal l , severe acne,
(XVV), 1 : 1000 antisocial behavior (seen in 1 -2% of XYY
males) . Normal fertility. Small percentage
diagnosed with autism spectru m disorders.
Diagnosing disorders Testosterone LH Diagnosis

of sex hormones Defective androgen receptor
Testosterone-secreting tumor, exogenous

steroids
1 o hypogonadism
Hypogonadotropic hypogonadism
Pseudo Disagreement between the phenotypic (external gen ital ia) and gonadal (testes vs. ovaries) sex.
hermaphroditism
Female pseudo Ovaries present, but external gen ital ia are viril ized or ambiguous. Due to excessive and
hermaphrodite (XX) inappropriate exposure to androgenic steroids during early gestation (e.g., congenital ad renal
hyperplasia or exogenous adm inistration of androgens during pregnancy) .
Male pseudo Testes present, but external gen italia are female or ambiguous. Most common for m is androgen
hermaphrodite (XV) insensitivity syndrome (testicular fem inization) .
,
REPRODUCTIVE REPRODUCTIVE-PATHOLOGY SECTION Ill 52 5
True hermaph roditism Both ovary and testicular tissue present (ovotestis) ; ambiguous gen italia. Very rare.
(46,XX or 47,XXY)
Androgen insensitivity Defect in androgen receptor resulting in normal-appearing fem a l e ; female external genitalia
syndrome (46,XY) with rudi mentary vagina; uterus and fallopian tubes generally absent; presents with scant sexual
hair; develops testes (often found in labia maj ora ; surgically removed to prevent mal ignancy) .
t testosterone, estrogen, LH (vs. sex chromosome d isorders) .
Sa-reductase Autosomal recessive ; sex l i m ited to genetic males. Inabil ity to convert testosterone to DHT.
deficiency Ambiguous genitalia until puberty, when t testosterone causes mascu l i n ization /t growth of
external genitalia. Testosterone/estrogen levels are normal ; LH is normal or t. I nternal gen italia
are normal.
Kallmann syndrome Defective m igration of GnRH cells and formation of olfactory bul b ; ! synthesis of GnRH in
the hypothalamus; anosmia; lack of secondary sexual characteristics; ! GnRH , F S I-l , L H ,
testosterone, a n d sperm count.
Hydatidiform mole Cystic swel l ing of chorionic villi and prol iferation of chorionic epithelium (trophoblast) that
presents with abnormal vaginal bleeding. Most common precursor of choriocarcinoma. t
-hCG. " Honeycombed uterus" or "cluster of grapes" appearance fl), abnorm ally enlarged uterus.
Complete moles classically have "snowstorm" appearance with no fetus during l st sonogram IIl
Moles can lead to uterine rupture. Treatment: dilation and curettage and methotrexate . Monitor
-hCG .
Complete mole Partial mole

KARYOTYPE 46,XX; 46,XY 69,XXX; 69,XXY; 69,XYY
hCG tttt
UTERINE SIZE
CONVERT TO CHORIOCARCINOMA 2% Rare

FETAL PARTS No Yes (partial = fetal parts)
COMPONENTS 2 sperm + empty egg 2 sperm + l egg
RISK OF COMPLICATIONS 1 5-20 % malignant Low risk of malignancy
troph oblastic dis ease (< 5 % )
526 SECTION Ill REPRODUCTIVE R EPRODUCTIV E -PATHO LOGY
Pregnancy-induced Preeclampsia - hypertension , proteinur i a , and edema . Eclampsia - preeclampsia + seizures.

hypertension Preeclampsia occurs in 7% of pregn ant women from 20 weeks' gestation to 6 weeks postpartum
(preeclampsia (before 20 weeks suggests molar pregnancy) . t incidence in patients with preex isting
eclampsia) hypertension, diabetes, chron ic renal disease, and autoimmune d isorders. C aused by placental
ischemia clue to impaired vasodilation of spiral arteries, resulting i n t vascular tone. Can be
associated with HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) . Mortality
as a result of cerebral hemorrhage and ARD S .
CliNICAl FEATURES Headache, blurred vision, abdom inal pain, edema o f face a n d extrem ities, altered mentation ,
hyperreflexia; lab findings may include thrombocytopenia, hyperuricemia.
TREATMENT Del ivery of fetus as soon as viable. Otherwise bed rest, monitoring, and treatment of hypertension .
Treatment: IV magnesium sulfate to prevent and treat seizures of eclampsia.
Pregnancy complications
Abruptio placentae Premature detachment of placenta from

implantation site. May be associ ated with
DIC . t risk with smoking, hypertension,
coca me use.
Painful bleeding i n 3rd tri mester. Abrupt
detachment. Life threatening for both fetus
and mother.
(Reproduced, with permission, from Cunningham F G e t al. Williams Obstetrics,

23rd ed. New York: McGraw-Hill, 2010, Fig. 35-4.)
Placenta accreta Defective decidual layer allows placenta

to attach to myometrium . No separation
of placenta after birth. t risk with prior
C-section , inflammation, and placenta previa.
Massive bleed ing after del ivery.
Accreta = "encased in" = encased in
myometrium .
REPRODUCTIVE REPRODUCTIVE -PATHOLOGY SECTION Ill 52 7
Pregnancy complications (continued)

Placenta previa Attachment of placenta to lower uterine
segment. Lies near or extends over internal
cervical os. t risk with multiparity and prior
C -section .
Painless bleeding i n any trimester.
,.r
r
(Reproduced, with permission, from Cunningham FG et al. Williams Obstetrics,

23rd ed. New York: McGraw-Hill, 20 1 0, Fig. 35-1 1 .)
Retained placental May cause postpartum hemorrage, t risk of

tissue infection .
Ectopic pregnancy Most often in fal lopian tubes. Suspect with Pai n with or without bleed ing.
h istory of amenorrhea, lower-than-expected Risk factors :
t hCG based on dates, and sudden lower H istory of i n fertil ity
abdom inal pai n ; confirm with ultrasound. Salpingitis ( P I D )
Often clin ically mistaken for append icitis. Ruptured append ix
Endometrial biopsy shows decidualized Prior tubal surgery
endometrium but no chorionic villi (develop

only in intra-uterine pregnancy) .
Amniotic fluid abnormalities
Polyhydramnios > 1 . 5 -2 L of amn iotic fluid ; associated with esophageal/duodenal atresia, causing inabil ity to
swallow amn iotic fluid, and with anencephaly.
Oligohydramnios < 0 . 5 L of amniotic fluid; associated with placental insufficiency, bilateral renal agenesis, or
posterior urethral valves (in males) and resultant inabil ity to excrete urine. Can give rise to Potter's
syndrome.
528 SECTION Ill REPRODUCTIVE REPRODUCTIVE-PATHOLOGY
Cervical pathology
Dysplasia and Disordered epithelial growth ; begins at basal

carcinoma in situ layer of squamo-columnar junction and
extends outward . Classified as CIN l , CIN
2 , or C I N 3 (severe dysplasia or carcinoma
i n situ) , depending on extent of dysplasia.
Associated with H PV 1 6 (E6 gene product
inh ibits p 5 3 suppressor gene), and H PV 18 (E7
gene product inh ibits RB suppressor gene) .
Vaccine ava ilable. May progress slowly to
i nvasive carcinoma if left untreated.
Risk factors : multiple sexual partners (# l ) ,
Koilocytes in cervical condyloma. N ote the wrinkled,
smoking, early sexual intercourse, HIV "raisinoid" n uclei, some of which have clearing or a
i n fection . perinuclear halo.
Invasive carcinoma Often squamous cell carcinoma. Pap smear can

catch cervical dysplasia (koilocytes r.J) before
it progresses to invasive carcinoma. Lateral
invasion can block ureters, causing renal
fai lure.
Endometritis Inflammation of the endometrium associated with reta ined products of conception following
del ivery (vaginal!C-section)/m iscarriage/abortion or foreign body such as an I U D. Retained
material i n uterus promotes infection by bacterial flora from vagina or intestinal tract.
Treatment: gentamycin + clindamycin with or without ampicill i n .
Endometriosis Non-neoplastic endometrial glands/stroma Menorrhagia, dysmenorrhea, dyspareunia,

i n abnormal locations outside the uterus. infertil ity; uterus is normal sized.
Characterized by cyclic bleed ing (mens trual
type) from ectopic endometrial tissue,
resulting i n blood-fi lled "chocolate cysts." In
ovary or on peritoneum. Manifests clinically as
severe menstrual-related pa in. Often results in
painful intercourse and infertility. Can be due
to retrograde menstru a l flow.
Treatment: oral contraceptives, NSAIDs,
leuprol ide, danazol .
Adenomyosis endometrium within the
- Menorrhagia, dysmenorrhea, pelvic pain ; uterus
myometriu m . Treatment: hysterectomy. is enlarged.
REPRODUCTIVE REPRODUCTIVE-PATHO LOGY SECTION Ill 52 9
Endometria l proliferation
Endometrial Abnormal endometrial gland prol iferation usually caused by excess estrogen stimulation. t risk for
hyperplasia endometrial carcinoma. Clin ically manifests as postmenopausal vagi nal bleeding. Risk factors
i nclude anovulatory cycles, hormone replacement therapy, polycystic ovarian synd rome, and
granulosa cell tumor.
Endometrial Most common gynecologic malignancy. Peak occurrence at 5 5-65 yea rs of age. Clin ically presents
carcinoma with vaginal bleeding. Typically preceded by endometrial hyperplasia. Risk factors i nclude
prolonged use of estrogen without progestins, obesity, d iabetes, hypertension, null iparity, and late
menopause. t myometrial invasion ! prognosis.
_.
Myometria l tumors
Leiomyoma (fibroid) Most common of all tumors in females. Often presents with multiple tumors with wel l-demarcated
borders fJ. t incidence in blacks. Benign smooth muscle tumor; mal ignant transformation is rare.
Estrogen sensitive - tumor size t with pregnancy and ! with menopause. Peak occurrence at 20-
40 years of age. May be asymptomatic, cause abnormal uterine bleed ing, or result in m iscarriage.
Severe bleed ing may lead to iron deficiency anemia. Does not progress to leiomyosarcoma.
Whorled pattern of smooth muscle bundles.
Leiomyosarcoma Bulky, irregularly shaped tumor with areas of necrosis and hemorrhage, typically arising de novo
(not from leiomyoma) . t incidence in blacks. H i ghly aggressive tumor with tendency to recur.
May protrude from cervix and bleed. Most commonly seen i n m iddle-aged women.
Gynecologic tumor I ncidence - endometrial > ovarian > cervical (data perta i n to the Un ited State s ; cervical cancer is
epidemiology most common worldwide) .
Worst prognosis- ovarian > cervical > endometrial .
Premature ovarian Premature atresia of ovarian foll icles in women ! estrogen, t L H , FSI-I.
failure of reproductive age . Patients present with signs
of menopause after puberty but before age 40.
Most common causes Pregnancy, polycystic ovarian syndrome, obesity, H PO axis abnormal ities, premature ovarian
of anovulation failur e , hyperprolactinem ia, thyroid disorders, eating disorders, Cushi ng's syndrome, adrenal
insufficiency.
5 30 SECTION Ill REPRODUCTIVE R E P RODUCTIVE - PAT H OLOGY
Polycystic ovarian t LH production leads to anovulation and t L H , ! F S H , t testosterone, t estrogen (from

syndrome therefore no progesterone, hyperanclrogenism testosterone aromatization) .
due to deranged steroid synthesis by theca
cells. Enlarged, bilateral cystic ovaries
f.i] manifest clin ically with amenorrhea,
infertil ity, obesity, and h i rsutism . Associated
with insulin resistance. t risk of endometrial
cancer, secondary to t in estrogens from
the aromatization of testosterone in fat cells
without progesterone to oppose.
Treatment: weight reduction, low-dose
OCPs or medroxyprogesterone (l LH and
androgenesis), spironolactone (treats acne and
h i rsutism) , clom iphene (for women who want
to get pregnant) , metformin (for patients with
features of diabetes or metabol ic syndrome) .
Ovarian cysts
Follicular cyst Distention o f unruptured graafian follicle. May b e associated with hyperestrinism and endometrial
hyperplasia. Most common ovarian mass in young women.
Corpus luteum cyst Hemorrhage i nto persistent corpus luteum. Commonly regresses spontaneously.
Theca-lutein cyst Often bilateral/multiple. Due to gonadotropin stimulation . Associated with choriocarcinoma and
moles.
Hemorrhagic cyst Blood vessel rupture i n cyst wall. Cyst grows with t blood retention ; usually self-resolves.
Dermoid cyst Mature teratoma. Cystic growths filled with various types of tissue such as fat, hair, teeth, bits of
bone, and cartil age.
Endometrioid cyst Endometriosis with i n ovary with cyst formation. Varies with menstru al cycle. When filled with
clark, reddish-brown blood it is called a "chocol ate cyst."
..
REPRODUCTIVE R EPRODU C TIV E-PATHOLOGY SECTION Ill 53 1
Ovarian germ cell Most common in adolescents.

tumors
TYPE CHARACTERISTICS TUMO R MARKERS
Dysgerminoma Mal ignant, equivalent to male semi noma but hCG, LDH
rarer (l % of germ cell tumors in females
vs. 30% i n males) . Sheets of uniform cells.
Associated with Tur ner syndrome.
Choriocarcinoma Rare but malignant; can develop during or after hCG
pregnancy i n mother or baby. Mal ignancy of
trophoblastic tissue ; chorionic villi are not
present. t frequency of theca-lutein cysts.
Along with moles, comprise spectrum of
gestational trophoblastic neoplasia. Early
hematogenous spread to lungs.
Yolk sac (endodermal Aggressive mal ignancy in ovaries (testes in boys) AFP
sinus) tumor and sacrococcygeal area of young children .
Yel low, friable, solid masses. 50% have Schiller
D uval bodies (resemble glomeruli) .
Teratoma 90% of ovarian germ cell tumors. Contain cells
from 2 or 3 germ layers fJ rn.
Mature teratoma ( " dermoid cyst") -most
common ovarian germ cell tumor; mostly
benign.
I mmature teratoma-aggressively mal ignant.
Struma ovari i - contains functional thyroid
tissue. Can present as hyperthyroidism.
Teratoma of the ovary (gross). Note the teeth ( 1 ) and Teratoma, histology. Note the glial tissue ( 1 ), stratified
hair (2). squamous epithelium (2), and respiratory epithelium (3).
532 SECTION Ill REPRODUCT IVE REPRODUCTIVE-PATHOLOGY
Ovarian non-germ cell tumors
Serous cystadenoma 4 5 % of ovarian tumors. Frequently bil ateral, t CA- 1 2 5 is general ovarian cancer marker.
l i ned with fal lopian tube-l ike epithel ium. Good for mon itoring progression, not for
Benign. screen i n g.
Serous 4 5 % of ovarian tumors, mal ignant and Risk factors-BRCA-1 , BRCA-2 , H N P C C .
cystadenocarcinoma frequently bilateral. Psammoma bodies seen Significant genetic predisposition makes family
on h istology. h istory the most i mportant risk factor.
Mucinous Multilocular cyst l ined by mucus-secreting
cystadenoma epithel ium rn. Benign. I ntestine-l ike tissue.
Mucinous Mal ignant. Pseudomyxoma peritonei
cystadenocarcinoma i ntraperitoneal accumulation of mucinous
material from ovarian or appendiceal tumor.
Brenner tumor Benign and unilatera l . Looks l ike bladder. Solid
tumor that is pale yellow-tan in color and
appears encapsulated. "Coffee bean" nuclei on
H&E stain ing.
Fibromas Bundles of spindle-shaped fibroblasts. Meigs'
syndrome - triad of ovarian fibroma, ascites,
and hydrothorax. Pulling sensation in groin.
Granulosa cell tumor Secretes estrogen -+ precocious puberty
(kids) . Can cause endometrial hyperplasia or
carcinoma in adults. Call-Exner bodies - small
foll icles filled with eosinoph ilic secretions.
Abnormal uterine bleed ing.
Krukenberg tumor GI mal ignancy that metastasizes to ovaries,
causing a muci n-secreting signet cell
adenocarcinoma.
Vaginal tumors Squamous cell carcinoma (SCC) -usually 2 to cervical SCC ; l o vaginal carcinoma rare.
Clear cell adenocarcinoma- affects women who had exposure to DES in utero.
Sarcoma botryoides (rhabdomyosarcoma variant) -affects girls < 4 years of age ; spindle-shaped
tumor cells that are desm in positive.
REPRODUCTIVE REPRODUCTIVE-PATHOLOGY SECTION Ill 533
Breast pathology
Lobules Stroma
Nipple
Lactiferous
sinus
Major duct
Paget's disease, Intraductal papilloma, Fibrocystic cha nge, Tubular Lobular Fibroadenoma,
breast abscess breast abscess, ductal cancer carcinoma carcinoma, phyllodes tumor
mastitis sclerosing
ade nosis
Benign breast tumors

TYPE CHARACTERISTICS EPIDEMIOLOGY NOTES
Fibroadenoma Small, mobile, firm mass with Most common tumor in those t size and tenderness with
sharp edges. < 3 5 years of age. t estrogen (e.g., pregnancy,
menstruation ) . Not a
precursor to breast cancer.
Intraductal papilloma Small tumor that grows in S erous or bloody n ipple
lactiferous ducts. Typically di scharge. Slight ( 1 . 5 -2 x)
beneath areola. t i n risk for carcinoma.
Phyllodes tumor Large bulky mass of connective Most common in 6th decade. Some may become malignant.
tissue and cysts. "Leaf-like"
projections.
534 SECTION Ill REPRODUCTIVE R EPRODUCTIV E-PATHOLOGY
Malignant breast Com mon postmenopause. Usually arise from Risk factors : t estrogen exposure, t total number
tumors terminal duct lobular unit. Overexpression of menstrual cycles, older age at l st l ive birth,
of estrogen/progesterone receptors or c-erbB2 obesity (t estrogen exposure as adipose tissue
( H E R-2 , an EGF receptor) is common ; affects converts androstenedione to estrone) , BRCA J
therapy and prognosis. Axillary lymph node and BRCA2 gene mutations.
i nvolvement i ndicating metastasis is the single
most important prognostic factor. Most often
located in upper-outer quadrant of breast.
TYPE CHARACTERISTICS NOTES
Noninvasive
Ductal carcinoma in Fills ductal lumen. Arises from ductal Early malignancy without basement membrane
situ (DCIS) hyperplasia. penetration.
Comedocarcinoma Ductal, caseous necrosis [J. Subtype of DCIS.
Comedotarcinoma. Note central necrosis surrounded by

cancer cells. D
Invasive
Invasive ductal Firm, fibrous, "rock-hard " mass with sharp Worst and most i nvasive. Most common ( 76% of
margins and small, glandular, duct-l ike cel ls. all breast cancers ) .
Classic "stellate" morphology.
Invasive lobular Orderly row of cells ("'ndian file" ) . Often bil ateral w i t h multiple lesions in t h e same
location .
Medullary Fleshy, cellular, lymphocytic infiltrate. Good prognosis.
Inflammatory Dermal lymphatic invasion by breast 5 0 % survival at 5 years.
carcinoma. Peau d 'orange (breast skin
resembles orange peel ) ; neoplastic cel ls block
lymphatic d rainage.
Paget's disease Eczematous patches on n ipple. Paget cells = Suggests underlying D C I S . Also seen on vulva.
large cell s in epiderm is with clear halo.
REPRODUCTIVE REPRODUCTIVE-PATHOLOGY SECTION Ill 53 5
Common breast conditions
Fibrocystic disease Most common cause of "breast lumps" from age 25 to menopause. Presents with premenstru a l
breast p a i n a n d multiple lesions, often bil atera l . Fluctuation i n size of mass. Usually does not
ind icate t risk of carcinoma. H istologic types :
Fibrosis- hyperplasia o f breast stroma.
Cystic- fl u i d filled, blue dome. Ductal dilation .
Sclerosing adenosis- t acini and intralobular fibrosis. Associ ated with calcifications. Often

confused with cancer.

Epithelial hyperplasia- t in number of epithel ial cell l ayers in term inal duct lobule. t risk of
carcinoma with atypical cells. Occurs in women > 30 years of age.

Acute mastitis Breast abscess; during breast-feeding, t risk of bacterial infection through cracks i n the nippl e ; S.
aureus is the most common pathogen.
Fat necrosis A benign, usually pain less lump; forms as a result of injur y to breast tissue. Up to 50% of patients
may not report trauma.
Gynecomastia Occurs in males. Results from hyperestrogenism (cirrhosis, testicular tumor, puberty, old age),
Kli nefelter's syndrome, or drugs (estrogen, marijuana, heroin, psychoactive drugs, Spironolactone,
Digital is, Cimetidine, Alcohol , Ketoconazole) . ( " Some Drugs Create Awkward Knockers." )
Prostate pathology Prostatiti s - dysuria, frequency, urgency, low back pain. Acute : bacterial (e.g., E. coli); chron ic:
bacterial or abacterial (most common ) .
Benign prostatic Common in men > 5 0 years o f age. Hyperplasia

hyperplasia (BPH) (not hypertrophy) of the prostate gland.
Characterized by a nodular enlargement of the
periurethral ( lateral and middle) lobes, wh ich
compress the urethra i nto a vertical slit. Not
considered a premal ignant lesion .
Often presents with t frequency of urination ,
noctur i a , difficulty starting and stopping the
stream of urine, and dysuria. May lead to
distention and hypertrophy of the bladder,
hydronephrosis, and UTJs. t free prostate-
specific antigen (PSA) .
Treatment: a 1 -antagon ists (terazosi n ,
tamsulosi n ) , wh ich cause relaxation o f smooth
muscl e ; finasteride.
53 6 SECTION Ill REPRODUCTIVE REPRODUCTIVE-PATHOLOGY
Prostatic Common in men > 50 years of age. Arises most

adenocarcinoma often from the posterior lobe (peripheral zone)
of the prostate gland rJ and is most frequently
d iagnosed by t PSA and subsequent needle
core biopsies. Prostatic acid phosphatase ( PAP)
and P SA are useful tumor markers ( t total
PSA, with fraction of free PSA) . Osteoblastic
metastases in bone may develop in late stages,
as ind icated by lower back pain and an t in
serum alkaline phosphatase and PSA.
Prostatic adenocarcinoma. Note the small infiltrating

glands with prominent n ucleoli. li!l
Cryptorchidism Undescended testis (one or both); impaired spermatogenesis (since sperm develop best at
temperatures < 37C ) ; can have normal testosterone levels ( Leyd ig cells are unaffected by
temperatur e ) ; associated with t risk of germ cel l tumors. Prematurity t the risk of cryptorch idism .
inhibin, t FSH, and t L H ; testosterone in bilateral cryptorch idism, normal in unilatera l .
Varicocele Dilated veins in pampiniform plexus as a result of t venous pressure ; m o s t common cause of scrotal
enlargement in adult males; most often on the left side because of t resistance to flow from left
gonadal vei n drainage into the left renal vein ; can cause infertil ity because of t temperatur e ; " bag
of worms" appearance; diagnosed by ultrasound.
Treatment: varicocelectomy, embol ization by interventional radiologist.
Testicular germ cell -9 5 % of all testicular tumors. Most often mal ignant. Can present as a m i xed germ cell tumor.
tumors Differential diagnosis for testicular mass that does not transillumi nate : cancer.
Seminoma Mal ignant; painless, homogenous testicular enlargement; most common testicular tumor, mostly
affecting males age 1 5-35. Large cells in lobules with watery cytoplasm and a " fried egg"
appearance. t placental alkaline phosphatase ( PLAP) . Radiosensitive. Late metastasis, excellent
prognosis.
Yol k sac (endodermal Yellow, mucinous. Analogous to ovarian yolk sac tumor. Schiller-Duval bodies resemble primitive
sinus) tumor glomeru l i (t AFP) .
Choriocarcinoma Malignant, t hCG. Disordered syncytiotrophoblastic and cytotrophoblastic elements.
Hematogenous metastases to lungs. May produce gynecomastia as hCG is an L H analog.
Teratoma Unl ike in females, mature teratoma in adult males is more often mal ignant. Ben ign in children.
t hCG and/or AFP i n 5 0 % of cases.
Embryonal carcinoma Mal ignant; painfu l ; worse prognosis than seminoma. Often glandular/papillary morphology.
" Pure" embryonal carcinoma is rare ; most commonly mixed with other tumor types. M ay be
associated with t hCG and normal AFP levels when pure (t AFP when mixed) .
REPRODUC TIVE REPRODUCTIVE-PATHOLOGY SECTION Ill 53 7
Testicular non-germ 5 % of all testicular tumors. Mostly benign.

cell tumors
Leydig cell Contains Reinke crystals; usually androgen producing, gynecomastia in men , precocious puberty
i n boys. Golden brown color.
Sertoli cel l Ancl roblastoma from sex cord stroma.
Testicular lymphoma Most common testicular cancer in older men. Not a pri mary cancer, arises from lymphoma
metastases to testes. Aggressive.
Tunica vaginalis Lesions in the serous covering of testis present as testicular masses that can be transilluminatecl (vs.
lesions testicular tumors) .
Hydrocele- t fluid zo to incomplete fusion of processus vagi nalis
Spermatocele- d i lated epididymal duct
Penile pathology
Squamous cell More com mon i n Asia, Africa, and South America. Commonly associated with H PV, lack of
carcinoma (SCC) ci rcumCISIOn.
Peyronie's disease Bent penis clue to acqu ired fibrous tissue formation .
Priapism Painfu l sustained erection not associated with sexual stimul ation or desire. Associated with trauma,
sickle cell disease (sickled RBCs get trapped in vascular chan nel s), medications (anticoagulants,
PDE 5 inh ibitors, antidepressants, a-blockers, cocaine) .
53 8 SECTION Ill REPRODUCTIVE R EPRODUCTIVE-PHARMACOLOGY
REPRODUCTIVE-PHARMACOLOGY
Control of reproductive Hypothalamus
hormones
Hypothalamus
$ H
---0- GnRH antagonists
+--G)- GnRH agonists
-&-- GnR H a ntagonists
GnRH agonists
Anterior
---0- 0ral Pituitary
pituitary
contraceptives, gonadotrophs
danazol
Ovary Testis
Progesterone
(luteal phase)
------e-- Ketoconazole,
l --0- Ketoconazole,
spironolactone
j
'-7------.r' danazol
Testosterone
Testosterone
Sa- +-0--- Finasteride
reductase
A ndrostenedione
Dihydrotestostero ne
Flutamide,
cyproterone,
spironolactone
Estradiol Estrone -- Estriol

Fulvestrant
l
Androgen-receptor complex
m {/\\ rf\
J :.---=--cB- SEAMs
Estrogen
response
Androgen
response
element
l
, W W element
' Expression of appropriate

Expression in estrogen-responsive cells genes in androge n-responsive cells
Control of female hormones Control of androgen secretion

(Adapted, with permission, from Katzung BG. Basic & Clinical (Adapted, with permission, from Katzung BG. Basic & Clinical
Pharmacology, I Oth ed. New York: McGraw,Hill, 2006, Fig. 40-5.) Pharmacology, I Oth ed. New York: McGraw-Hill, 2006, Fig. 40-6.)

REPRODUCTIVE REPRODUCTIVE-PHARMACOLOGY SECTION Ill 53 9
Leuprolide
MECHANISM GnRH analog with agon ist properties Leuprol ide can be used i n lieu of G n R H .
when used i n pulsatile fashion ; antagon ist
properties when used in continuous fashion
(downregulates GnRH receptor in pituitary
F S H /L H ) .
....
CliNICAl USE Infertil ity (pulsatile) , prostate cancer

(continuous- use with flutamide), uterine
fibroids (continuous), precocious puberty
(continuous) .
TOXICITY Antiandrogen, nausea, vom iting.
Testosterone, methyltestosterone
MECHANISM Agon ist at androgen receptors.

CliNICAl USE Treats hypogonadism and promotes development of zo sex characteristics ; stimulation of anabol ism
to promote recovery after burn or injur y.
TOXICITY Causes masculinization in females; reduces intratesticular testosterone in males by inh ibiting
release of LH (via negative feedback) , leading to gonadal atrophy. Premature closure of epiphyseal
plates. t LDL, H DL .
Antiandrogens Testosterone ) a-reductase DHT (more potent) .

Finasteride A 5 a-reductase inh ibitor ( ! conversion of To prevent male-pattern hair loss, give a drug
testosterone to DHT). Useful in BPH . Also that will encourage female breast growth .
promotes hair growth - used to treat male
pattern baldness.
Flutamide A nonsteroidal competitive inh ibitor of
androgens at the testosterone receptor. Used in
prostate carcinoma.
Ketoconazole I n h ibits steroid synthesis (inhibits Ketoconazole and spironolactone are used in
1 7, 20-desmolase ) . the treatment of polycystic ovarian syndrome
Spironolactone I n h ibits steroid binding. to prevent h i rsutism. B oth h ave side effects of
gynecomastia and amenorrhea.
Estrogens (ethinyl estradiol, DES, mestranol)
MECHANISM Bind estrogen receptors.

CliNICAl USE Hypogonadism or ovarian failure, menstru al abnormal ities, H RT in postmenopausal women ; use
in men with androgen-dependent prostate cancer.
TOXICITY t risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of
vagina in females exposed to DES in utero, t risk of thrombi . Contraind ications - E R-positive
breast cancer, history of DVTs.
540 SECTION Ill REPRODUCTIVE REPRODUCTIVE-PHARMACOLOGY
Selective estrogen receptor modulators-SERMs
Clomiphene Partial agonist at estrogen receptors in hypothalamus. Prevents normal feedback inh ibition and
t release of LH and FSH from pituitary, which stimulates ovulation. Used to treat infertil ity and
polycystic ovarian syndrome. May cause hot flashes, ovarian enlargement, multiple simultaneous
pregnancies, and visual disturbances.
Tamoxifen Antagonist on breast tissue ; used to treat and prevent recurrence of E R-positive breast cancer.
Raloxifene Agon ist on bone ; reduces resorption of bone ; used to treat osteoporosis.
Hormone replacement Used for rel ief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and
therapy osteoporosis (t estrogen, osteoclast activity) .
Unopposed estrogen replacement therapy (ERT) t the risk of endometrial cancer, so progesterone
is added. Possible t CV risk.
Anastrozole/ Aromatase i n hibitors used in postmenopausal women with breast cancer.

exemestane
Progestins
MECHANISM Bind progesterone receptors, reduce growth and t vasculari zation of endometrium.
CLINICAL USE Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine
bleeding.
Mifepristone (RU-486)
MECHANISM Competitive inh ibitor of progestins at progesterone receptors.

CLINICAl USE Termination of pregnancy. Administered with m isoprostol ( PGE 1 ) .
TOXICITY Heavy bleed ing, G I effects (nausea, vom iting, anorexia) , abdom inal pa i n .
Oral contraception Estrogen a n d progestins inhibit LH/FSH a n d thus prevent estrogen surge. o estrogen surge -+ no
(synthetic progestins. LH surge -+ no ovulation.
estrogen) Progestins cause th ickening of the cervical mucus, thereby l i m iting access of sperm to uterus.
Progestins also inhibit endometrial prol iferation , thus making endometrium less suitable for the
implantation of an embryo.
Contra ind ications- smokers > 35 years of age (t risk of cardiovascular events ) , patients with h istory
of thromboembol ism and stroke or history of estrogen-dependent tumor.
Terbutaline T agonist that relaxes the uteru s ; reduces premature uterine contractions.
Tamsulosin a 1 -antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for a 1A,D
receptors (found on prostate) vs. vascular a 1 B receptors.
REPRODUCTIVE REPRODUCTIV E-PHARMACOLOGY SECTION Ill 54 1
Sildenafil, vardenafil
MECHANISM Inh ibit phosphodiesterase 5, causing t cGM P, Sildenafil and vardenafil fill the pen is.
smooth muscle relaxation in the corpus
cavernosu m , t blood flow, and penile erection .
CLINICAL USE Treatment of erectile dysfunction .
TOXICITY Headache, flushing, dyspepsia, impaired blue "Hot and sweaty," but then Headache,
green color vision. Risk of l i fe-threatening Heartburn , Hypotension .
hypotension i n patients taking nitrates.
Danazol
MECHANISM Synthetic androgen that acts as partial agon ist at androgen receptors.
CLINICAL USE Endometriosis and hereditary angioedema.
TOXICITY Weight gai n , edema, acne, hirsuti sm, masculinization, ! HDL levels, hepatotoxicity.
542 SECTION Ill REPRODUCTIVE
NOTES
HIGH-YIELD SYSTEMS
Respiratory
"There's so much pollution in the air now that if it weren't for our lungs,
there'd be no place to put it all."
-Robert Orben
"Mars is essentially in the same orbit. Somewhat the same distance from
the Sun, which is very important. We have seen pictures where there are
canals, we believe, and water. If there is water, that means there is oxygen.
If there is oxygen, that means we can breathe."
-Former Vice President Dan Quayle
"None of us is different either as barbarian or as Greek; for we all breathe

into the air with mouth and nostrils."
-Antiphon
544 SECTION Ill RESPIRATORY RESPIRATORY-ANATOMY
RESPIRATORY-ANATOMY
Respiratory tree
Conducting zone Large airways consist of nose, pharynx,
trachea, and bronchi. Small airways consist of
bronchioles and terminal bronchioles.
Warms, humidifies, and filters air but does not
participate in gas exchange -+ "anatomic dead
space."
Extending to end of bronchi:
Cartilage
Goblet cells
Extending to end of terminal bronchioles:

Pseudostratified ciliated columnar cells
Alveolar capillary beds
(beat mucus up and out of lungs) Alveoli

Smooth muscle of the airway walls (sparse
beyond this point)

Respiratory zone Lung parenchyma; consists of respiratory
bronchioles, alveolar ducts, and alveoli.
Participates in gas exchange.
Mostly cuboidal cells in respiratory bronchioles,
then simple squamous cells up to alveoli. No
cilia. Alveolar macrophages clear debris and
participate in immune response.
Pneumocytes
Type I cells 97% of alveolar surfaces. Line the alveoli. p 2 (surface tension)
CoIIapsmg pressure
.
= = .
Squamous; thin for optimal gas diffusion. rad1us
Type II cells Secrete pulmonary surfactant-+ ! alveolar Alveoli have t tendency to collapse on expiration
surface tension and prevention of alveolar as radius ! (law of Laplace).
collapse (atelectasis). Cuboidal and clustered. Pulmonary surfactant is a complex mix of
Also serve as precursors to type I cells and lecithins, the most important of which is
other type I I cells. Type II cells proliferate dipalmitoylphosphatidylcholine.
during lung damage. Surfactant synthesis begins around week 26 of
gestation, but mature levels are not achieved
Clara cells Nonciliated; columnar with secretory granules.
until around week 3 5.
Secrete component of surfactant; degrade
A lecithin-to-sphingomyelin ratio> 2.0 in
toxins; act as reserve cells.
amniotic fluid indicates fetal lung maturity.
RESPIRATORY RESPIRATORY-ANATOMY SECTION Ill 54 5
Lung relations Right lung has 3 lobes; Left has 2 Lobes and Instead of a middle lobe, the left lung has a
Lingula (homologue of right middle lobe). space occupied by the heart. T he relation
Right lung is more common site for inhaled of the pulmonary artery to the bronchus at
foreign body because the right main stem each lung hilus is described by RALS -Right
bronchus is wider and more vertical than Anterior; Left Superior.
the left.
Aspirate a peanut:
While upright-lower portion of right
inferior lobe.
While supine -superior portion of right
inferior lobe.
Trachea
Right Left R L L R
bro n c h u s bro n c h u s Anterior view Posterior view
Diaphragm strudures Structures perforating diaphragm: Number of letters T level:

=
AtT8: IVC T8: vena cava

At TIO: esophagus, vagus (2 trunks) TIO: esophagus
At Tl2: aorta (red), thoracic duct (white), Tl2: aortic hiatus
azygos vein (blue) ("At T-1-2 it's the red, I ( IVC) ate ( 8) ten (10) eggs (esophagus) at
white, and blue") (aorta) twelve (12).
Diaphragm is innervated by C3, 4, and 5
C3, 4, 5 keeps the diaphragm alive.
(phrenic nerve). Pain from the diaphragm
can be referred to the shoulder (C5) and the
trapezius ridge (C3, 4).
Central tendon
Inferior view
546 SECTION Ill RESPIRATORY RESPIRATORY-PHYSIOLOGY
Muscles of respiration Quiet breathing:

Inspiration -diaphragm
Expiration -passive
Exercise:
InSpiration -external intercostals, Scalene muscles, Sternocleidomastoids
Expiration -rectus abdominis, internal and external obliques, transversus abdominis, internal
intercostals
RESPIRATORY-PHYSIOLOGY
Lung volumes
Inspiratory reserve Air that can still be breathed in after normal Lung volumes (LITER):
volume (IRV) inspiration
:::111
Tidal volume (TV) Air that moves into lung with each quiet
inspiration, typically 500 mL IRV
Expiratory reserve Air that can still be breathed out after normal
IC VC T LC
volume (ERV) expiration
11
2.7
Residual volume (RV) Air in lung after maximal expiration; cannot be 2.2
measured on spirometry
Inspiratory capacity IRV+ TV
j
(I C)
RV
Functional residual RV+ ERV (volume in lungs after normal
capacity (FRC) expiration) L-------0
Vital capacity (VC) T V+ IRV+ ERV A capacity is a sum of 2 volumes.

Maximum volume of gas that can be expired
after a maximal inspiration
Total lung capacity TLC = IRV + T V + ERV + RV
(T LC) Volume of gas present in lungs after a maximal
inspiration
Determination of (Paco 2 - PECOz) Taco, Paco, PEco, Paco (refers to order of

V 0- V T x
_
physiologic dead space Paco2 variables in equation)
V 0 =physiologic dead space=anatomic dead
space of conducting airways plus functional
dead space in alveoli; apex of healthy lung is
largest contributor of functional dead space.
Volume of inspired air that does not take part
in gas exchange.
VT=tidal volume.
Paco 2 =arterial Pco 2 , PEco 2=expired air
Pco 2.
RESPIRATORY RESPIRATORY-PHYSIOLOGY SECTION Ill 54 7
Lung and chest wall Tendency for lungs to collapse inward and chest Chest wall
wall to spring outward.
At FRC, inward pull of lung is balanced by
outward pull of chest wall, and system pressure
is atmospheric.
Elastic properties of both chest wall and lungs
determine their combined volume.
At FRC, airway and alveolar pressures are 0,
and intrapleural pressure is negative (prevents
pneumothorax).
Compliance -change in lung volume for a o ---------L--
-20 -10 0 10 20 30 40
given change in pressure; ! in pulmonary
Transorgan static pressure (cmH20)
fibrosis, pneumonia, and pulmonary edema;
t in emphysema and normal aging.
Hemoglobin Hemoglobin is composed of 4 polypeptide Fetal hemoglobin (2 a and 2 y subunits)

subunits (2 a and 2 ) and exists in 2 forms: has lower affinity for 2,3-BPG than adult
T (taut) form has low affinity for 0 .
2 hemoglobin and thus has higher affinity for
R (relaxed) form has high affinity for 0
2 O z.
(300x). Hemoglobin exhibits positive Taut in Tissues.
cooperativity and negative allostery. Relaxed in Respiratory.
t CJ-, H+, C0 2 , 2,3-BPG, and temperature
favor taut form over relaxed form (shifts
dissociation curve to right, leading to t 0 2
unloading).
Hemoglobin Lead to tissue hypoxia from ! 0 2 saturation and ! 0 2 content.

modifications
Methemoglobin Oxidized form of hemoglobin (ferric, Fe3+) that Methemoglobinemia can be treated with
does not bind 0 2 as readily, but has t affinity methylene blue.
for cyanide. Nitrites cause poisoning by oxidizing Fe 2+ to
Iron in hemoglobin is normally in a reduced Fe3+
state (ferrous, Fe 2 +).
To treat cyanide poisoning, use nitrites to
oxidize hemoglobin to methemoglobin, which
binds cyanide, allowing cytochrome oxidase to
function. Use thiosulfate to bind this cyanide,
forming thiocyanate, which is renally excreted.
Carboxyhemoglobin Form of hemoglobin bound to CO in place CO has 20 0x greater affinity than 0 2 for
of 0 2 . Causes ! oxygen-binding capacity hemoglobin.
with a left shift in the oxygen-hemoglobin
dissociation curve. ! oxygen unloading
in tissues.
548 SECTION Ill RESPIRATORY RESPIRATORY-PHYSIOLOGY
Oxygen-hemoglobin dissociation curve

100 .-----.--.---,---, Sigmoidal shape clue to positive cooperativity
(i.e., tetrameric hemoglobin molecule can
bind 4 oxygen molecules and has higher
affinity for each subsequent oxygen molecule
bound). Myoglobin is monomeric and thus
c
0
does not show positive cooperativity; curve
-:::> 50 1-1----+1---1-+---+--+--1 lacks sigmoidal appearance.
iii When curve shifts to the right, ! affinity of
C/)
.0
I
hemoglobin for 0 2 (facilitates unloading of 0 2
to tissue).
Ant in all factors (except pH) causes a shift of
the curve to the right.
A ! in all factors (except pH) causes a shift of
25 50
the curve to the left.
Po2 (mmHg)
Fetal Hb has a higher affinity for oxygen than
20 adult Hb, so its dissociation curve is shifted
lblod left.
Right shift-C-BEAT:
:g 16 /
/
0
C0 2
I
0

-- B PG (2,3-BPG)
ON 12 Exercise
I
_l
50% CO Hb
g Acid/Altitude
.0 -
I
8
Temperature
.8
v
;/
""0
c
:::>
0
.0 4
j!
ON
0
0 20 40 60 80 100
Po2 (mmHg)
Pulmonary circulation Normally a low-resistance, high-compliance A consequence of pulmonary hypertension is cor

system. Po 2 and Pco 2 exert opposite effects pulmonale and subsequent right ventricular
on pulmonary and systemic circulation. A failure (jugular venous distention, edema,
! in PAo 2 causes a hypoxic vasoconstriction hepatomegaly).
that shifts blood away from poorly ventilated Diffusion: V as= AIT x Dk ( P1- P 2 ) where
g
regions of lung to well-ventilated regions of A=area, T=thickness, and Dk ( P1- P 2 )""
lung. difference in partial pressures:
Perfusion limited -02 (normal health), C0 2 , A ! in emphysema.
N 20. Gas equilibrates early along the length of T t in pulmonary fibrosis.
the capillary. Diffusion can be t only if blood

flow t.
Diffusion limited -0 2 (emphysema, fibrosis),
CO. Gas does not equilibrate by the time
blood reaches the end of the capillary.
Perfusion limited (e.g., C02. N20) Diffusion limited (e.g., CO) Oxygen
-- - -- - -- Normal
PA PA -- - --
Equilibration
Partial pressure
difference between ' ...... - Fibrosis
- --
- .
co
[l_
alveolar air and co
[l_
pulmonary capillary
blood
Length along pulmonary capillary Length along pulmonary capillary Length along pulmonary capillary
P a =partial pressure of gas in pulmonary capillary blood

PA =partial pressure of gas in alveolar air
Pulmonary Normal pulmonary artery pressure=10-14 mmHg; pulmonary hypertension 25 mmHg or> 35
hypertension mmHg during exercise. Results in arteriosclerosis, medial hypertrophy, and intimal fibrosis of
pulmonary arteries.
Primary-due to an inactivating mutation in the BMPR2 gene (normally functions to inhibit
vascular smooth muscle proliferation); poor prognosis.
Secondary-due to COPD (destruction of lung parenchyma); mitral stenosis (t resistance
-+ t pressure); recurrent thromboemboli (! cross-sectional area of pulmonary vascular bed);
autoimmune disease (e.g., systemic sclerosis; inflammation-+ intimal fibrosis-+ medial
hypertrophy); left-to-right shunt (t shear stress-+ endothelial injury); sleep apnea or living at high
altitude (hypoxic vasoconstriction).
Course: severe respiratory distress-+ cyanosis and RV H-+ death from decompensated cor
pulmonale.
P
Pulmonary vascular ppulm artery- p L atrium pulm artery= pressure in pulmonary artery
resistance PV R= PL atrium =pulmonary wedge pressure
Cardiac output
Remember: P =Q X R, so R= PIQ rt=the viscosity of blood; I=vessel length;

R= 8rtlI 1t1.4 r=vessel radius
5 50 SECTION Ill RESPIRATORY RESPIRATORY-PHYSIOLOGY
Oxygen content of 0 2 content= (0 2 binding capacity x% saturation)+ dissolved 0 2 .

blood Normally I gl-Ib can bind 1.34 m L 0 2; normal Hb amount in blood is 15 g/dL. Cyanosis results
when deoxygenated Hb> 5 g/dL.
07 binding capacity"" 20.1 mL 0 2 /dL.
0 2 content of arterial blood ! asl-Ib falls, but 0 2 saturation and arterial Po 2 do not.
Oxygen delivery to tissues=cardiac output xoxygen content of blood.
Paco 2
Alveolar gas equation P'A07-
- PI Oz-
_ -- PAo 2=alveolar Po 2 (mm Hg).
R Plo 2= Po 2 in inspired air (mmHg).
Can normally be approximated: Paco 2=arterial Pco 2 (mmHg).
PAo 2= 150- Paco 2I 0. 8 R =respiratory quotient= C0 2 produced/0 2
consumed.
A-a gradient= PAo 2 - Pao 2=10-15 mm Hg.
t A-a gradient may occur in hypoxemia; causes
include shunting, V/Q mismatch, fibrosis
(impairs diffusion).
Oxygen deprivation
Hypoxemia(! Pao2) Hypoxia(! 02 delivery to tissue) Ischemia(loss of blood flow)

ormal A-a gradient ! cardiac output Impeded arterial Aow
High altitude Hypoxemia Reduced venous drainage
Hypoventilation Anemia
t A-a gradient CO poisoning
V/Q mismatch
Diffusion limitation
Right-to-left shunt
V/Q mismatch Ideally, ventilation is matched to perfusion (i.e., With exercise (t cardiac output), there is
V/Q =1) in order for adequate gas exchange to vasodilation of apical capillaries, resulting in a
occur. V/Q ratio that approaches l.
Lung zones: Certain organisms that thrive in high 0 2 (e.g.,
Apex of the lung-V/Q=3 (wasted T B) flourish in the apex.
ventilation) V/Q --+0 =airway obstruction (shunt). In shunt,
Base of the lung-V/Q = 0.6 (wasted 100% 0 2 does not improve Po 2 .
perfusion) V/Q --+ =blood flow obstruction (physiologic
oo
Both ventilation and perfusion are greater at the dead space). Assuming< 100% dead space,
base of the lung than at the apex of the lung. 100% 0 2 improves Po 2
5 52 SECTION Ill RESPIRATORY RESPIRATORY-PHYSIOLOGY
col transport Carbon d iox ide is transported from tissues to the In lungs, oxygenat ion of Hb promotes
lungs in 3 forms: d issociation of H+ from Hb. T h is shifts
B icarbonate (90%). equilibrium toward C0 2 formation; therefore,
Carbaminohemoglobin or HbC0 ( 5%).
2 C0 2 is released from RBCs ( Haldane effect).
C0 2 bound to hemoglobin at N-terminus of In peripheral t issue, t H+ from t issue
globin (not heme). C0 2 binding favors taut metabolism shifts curve to right, unloading 0 2
form (0 2 unloaded). ( Bohr effect).
D issolved C0 ( 5%).
2 Majority of blood C0 2 is carried as b icarbonate
in the plasma.
Blood vessel wall
Peripheral Intravascular ABC
Response to high Acute t in vent ilation, Po 2 and Pco 2

altitude Chronic t in ventilation
t erythropoietin-+ t hematocrit and hemoglobin (chronic hypoxia)
t 2,3-BPG (binds to hemoglobin so that hemoglobin releases more 0 2)
Cellular changes (t m itochondria)
t renal excret ion of bicarbonate (e.g., can augment by use of acetazolamide) to compensate for the
respiratory alkalosis
Chronic hypoxic pulmonary vasoconstrict ion results in RV H
Response to exercise t C0 2 production

t 0 2 consumpt ion
t ventilation rate to meet 0 2 demand
V/Q rat io from apex to base becomes more uniform
t pulmonary blood flow clue to t cardiac output
pH during strenuous exercise (2 to lactic acidosis)
No change in Pao 2 and Paco 2 , but t in venous C0 2 content and in venous 0 2 content
RESPIRATORY RESPIRATORY-PATHOLOGY SECTION Ill 553
RESPIRATORY-PATHOLOGY
Deep venous Predisposed by V irchow's triad: Can lead to pulmonary embolus.

thrombosis Stasis Homans' sign -dorsiAex ion of foot-+ calf pain.
Hypercoagulabil ity (e.g., defect in Use hepar in for prevent ion and acute
coagulat ion cascade proteins, most management; use warfarin for long-term
commonly factor V Leiden) prevent ion of DVT recurrence.
Endothelial damage (exposed collagen
triggers clotting cascade)
Pulmonary emboli Sudden-onset dyspnea, chest pa in, tachypnea. An embolus moves like a FAT BAT.
May present as sudden death. Approximately 9 5% of pulmonary emboli arise
Types: Fat, Air, Thrombus, Bacteria, Amniot ic from deep leg veins.
fluid, Tumor. Fat emboli -associated with long CT pulmonary angiography is the imaging test
bone fractures and l iposuction; classic triad of choice for a PE.
of hypoxemia, neurologic abnormalit ies, and
petechial rash.
Amniotic fluid emboli - can lead to DIC,
especially postpartum. rJQ.
Pulmonary embolism. Note saddle embolus in the Pulmonary thromboembolus. Lines of Zahn are
pulmonary artery.li!4 interdigitating areas of pink (platelets, fibrin) and red (RBCs)
found only in thrombi formed before death. Help distinguish
pre- and postmortem thrombi.li!4
5 54 SECTION Ill RESPIRATORY RESPIRATORY-PATHOLOGY
Obstructive lung Obstruct ion of a ir flow resulting in air trapping in the lungs. A irways close prematurely at high
diseases lung volumes, resulting in t RV and ! FVC. P FTs: ! ! FEV1, ! FVC ! FEY / FVC ratio
-+
(hallmark), V/Q mismatch.
TYPE PATHOLOGY OTHER
Chronic bronchitis A form of COPD along with emphysema. Product ive cough for> 3 months per year (not
("blue bloater") Hypertrophy of mucus-secreting glands in necessarily consecutive) for> 2 years. D isease
the bronchi Reid index (thickness of gland
-+ of small a irways.
layer/total thickness of bronchial wall)> 50%. F indings: wheezing, crackles, cyanosis (early
onset hypoxemia clue to shunt ing), late-onset
dyspnea.
Emphysema("pink Enlargement of air spaces and ! recoil result ing t elastase activity.
puffer," barrel from destruction of alveolar walls ri] II); t lung compl iance clue to loss of elastic fibers.
shaped chest) t compliance. Exhalat ion through pursed l ips to t airway
Two types: pressure and prevent a irway collapse during
Centriacinar-associatecl with smoking. respiration.
Panacinar-associatecl with cxrantitrypsin
deficiency.
Emphysema. On microscopy, enlarged alveoli are seen Emphysema. Gross specimen showing multiple cavities
separated by thin septa, some of which appear to float in the linked by heavy black carbon deposits.
alveolar spaces.li!!
Asthma Bronchial hyperresponsiveness causes reversible Can be triggered by v iral URis, allergens, and
bronchoconstriction. Smooth muscle stress.
hypertrophy, Curschmann's spirals (shed Test with methacholine challenge.
epithelium forms mucus plugs), and Charcot F indings: cough, wheezing, tachypnea,
Leyclen crystals (formed from breakdown of dyspnea, hypoxemia, ! I/E ratio, pulsus
eosinophils in sputum). paracloxus, mucus plugging.
Bronchiectasis Chronic necrotizing infection of bronchi Associated w ith bronchial obstruction, poor
- permanently clilatecl airways, purulent cil iary mot ility (smoking), Kartagener's
sputum, recurrent infections, hemoptysis. syndrome, cystic fibrosis, allergic
bronchopulmonary aspergillosis.
Restridive lung disease Restricted lung expans ion causes ! lung volumes ( ! F VC and TLC). PFTs - FEV / FVC rat io
> 80%.
Types:
Poor breathing mechanics (extrapulmonary, peripheral hypoventilation, normal A-a grad ient):
Poor muscular effort-polio, myasthen ia gravis
Poor structural apparatus-scoliosis, morbid obesity
Interstitial lung d iseases (pulmonary, lowered d iffusing capacity, t A-a grad ient):
Acute respiratory distress syndrome (ARDS)

Neonatal respiratory d istress syndrome (hyaline membrane d isease)
Pneumoconioses (anthracosis, sil icosis, asbestosis)
Sarcoidosis: bilateral hilar lymphadenopathy, noncaseat ing granuloma; t ACE and
calcium
Id iopathic pulmonary fibrosis (repeated cycles of lung injury and wound healing w ith
t collagen deposit ion)
Goodpasture's syndrome
Granulomatosis with polyangi it is (Wegener's)
Langerhans cell hist iocytosis (eosinophilic granuloma)
Hypersensitiv ity pneumonitis
Drug tox icity (bleomycin, busulfan, amioclarone, methotrexate)
Pneumoconioses Anthracosis, silicosis, and asbestosis-+ t risk of cor pulmonale and Caplan's syndrome.
Anthracosis Associated w ith coal mines ( "coal miner's Affects upper lobes.
lung").
Silicosis Associated w ith foundries, sandblasting, Affects upper lobes.
and mines. Macrophages respond to sil ica "Eggshell" calcificat ion of h ilar lymph nodes.
and release fibrogenic factors, leading to
fibrosis. It is thought that silica may disrupt
phagolysosomes and impa ir macrophages,
increasing suscept ibility to T B. Also increases
r isk of bronchogenic carcinoma.
Asbestosis Associated w ith shipbuilding, roofing, and Affects lower lobes.
plumbing. " Ivory white," calcified pleural Asbestos bodies are golden-brown fusiform rods
plaques are pathognomonic of asbestos resembling dumbbells [J.
exposure, but are not precancerous. Associated
with an t incidence of bronchogenic
carcinoma and mesothelioma.
Neonatal respiratory Surfactant deficiency leading to t surface tension, resulting in alveolar collapse. A
distress syndrome lecithin:sphingomyelin ratio< 1. 5 in amniotic fluid is predictive of neonatal respiratory d istress
syndrome. Persistently low 0 2 tension - risk of PDA. Therapeut ic supplemental 0 2 can result in
ret inopathy of prematurity and bronchopulmonary dysplasia.
Risk factors: prematurity, maternal diabetes (clue to elevated fetal insulin), cesarean delivery
(! release of fetal glucocort icoids).
Treatment: maternal steroids before birth; art ificial surfactant for infant.
5 56 SECTION Ill RESPIRATORY RESPIRATORY-PATHOLOGY
Acute respiratory May be caused by trauma, sepsis, shock, gastric

distress syndrome aspiration, uremia, acute pancreat itis, or
(ARDS) amn iot ic fluid embolism. D iffuse alveolar
damage t alveolar capillary permeabil ity
--+
protein-rich leakage into alveoli. Results

--+
in format ion of intra-alveolar hyaline

membrane fi]. Initial damage due to release of
neutrophilic substances toxic to alveolar wall,
activation of coagulation cascade, and oxygen
derived free radicals.
Acute respiratory distress syndrome. Note the alveolar

fluid and the hyaline membranes.
Obstructive vs. restrictive lung disease

Norma l Obstructive Restrictive
FEV1 FEV1 o FEV1
= 80% < 80Yo 80%
FVC FVC FVC
FEV1 FVC
8 8 8
7 FEV1 FVC 7 7
6 6 6
2:5 5 5
Q)
E
-5> 4 4 4
FEV1 FVC
0>
c
::J 3 3 3
...J
2 2 2
0 2 3 0 2 3 0 2 3
Time (sec) Time (sec) Time (sec)
Note: Obstructive lung volumes> normal (t TLC, t FRC, t RV); restrictive lung volumes< normal. In both obstructive and
restrictive, FEV1 and FVC are reduced. In obstructive, however, FEV1 is more dramatically reduced compared to FVC,
resulting in a ! FEV1/FVC ratio.
Sleep apnea Repeated cessat ion of breath ing> 10 seconds Treatment: weight loss, CPA P, surgery.
during sleep d isrupted sleep daytime
--+ --+ Hypoxia t EPO release t erythropoiesis.
--+ --+
somnolence.
Central sleep apnea -no respiratory effort.
Obstructive sleep apnea -respiratory effort
against a irway obstruction. Associated with
obesity, loud snoring, systemic/pulmonary
hypertension, arrhythmias, and possibly
sudden death.
Lung-physical findings
ABNORMALITY BREATH SOUNDS PERCUSSION FREMITUS TRACHEAL DEVIATION
Pleural effusion Dull
Atelectasis(bronchial Dull Toward side of lesion
obstruction)
Spontaneous Hyperresonant Toward side of lesion
pneumothorax
Tension pneumothorax Hyperresonant Away from side of lesion
Consolidation Bronchial breath sounds; Dull
(lobar pneumonia, late inspiratory crackles
pulmonary edema)
558 SECTION Ill RESPIRATORY RESPIRATORY-PATHOLOGY
Lung cancer Lung cancer is the leading cause of cancer SPHERE of complications:
death. Superior vena cava syndrome
Presentation: cough, hemoptysis, bronchial Pancoast tumor
obstruction, wheezing, pneumonic "coin" Horner's syndrome
lesion on x-ray film or noncalcified nodule Endocrine (paraneoplastic)
on CT. Recurrent laryngeal symptoms (hoarseness)
Metastatic cancer is most common cause. Most Effusions (pleural or pericardia!)
often from breast, colon, prostate, and bladder All lung cancer types except bronchioloalveolar
cancer. and bronchial carcinoid are associated with
Sites of metastases - aclrenals, brain, bone smoking.
(pathologic fracture), liver (jaundice,
hepatomegaly).
TYPE lOCATION CHARACTERISTICS HISTOLOGY
Adenocarcinoma Peripheral Most common lung cancer in nonsmokers and

females. Activating mutations in k-ras common.
Associated with hypertrophic osteoarthropathy
(clubbing).
Bronchioloalveolar subtype: CXR often shows Bronchioloalveolar
hazy infiltrates similar to pneumonia; excellent subtype: grows
prognos1s. along alveolar septa
.... apparent "thickening"
of alveolar walls.
Squamous cell Central Hilar mass arising from bronchus; Cavitation; Keratin pearls and
carcinoma Cigarettes (linked to smoking); hyperCalcemia intercellular bridges m.
(produces PTHrP).
Small cell (oat cell) Central Undifferentiated ..... very aggressive. Neoplasm of
carcinoma May produce ACT H, AD H, or Antibodies against neuroendocrine
presynaptic calcium channels ( Lambert-Eaton Kulchitsky cells .... small
syndrome). Amplification of myc oncogenes dark blue cells[].
common. Inoperable; treated with chemotherapy.
large cell carcinoma Peripheral Highly anaplastic undifferentiated tumor; poor Pleomorphic giant cells.
prognosis. Less responsive to chemotherapy;
removed surgically.
Bronchial carcinoid Excellent prognosis; metastasis Nests of neuroendocrine
tumor rare. cells; chromogranin
Symptoms usually clue to mass positive.
effect; occasionally carcinoid
syndrome (serotonin secretion
.... flushing, diarrhea,
wheezing).
RESPIRATORY RESPIRATORY-PATHOLOGY SECTION Ill 5 59
Lung cancer (continuecl)

TYPE LOCATION CHARACTERISTICS HISTOLOGY
Mesothelioma Pleural Malignancy of the pleura Psammoma bodies.
associated with asbestosis.
Results in hemorrhagic
pleural effusions and pleural
thickening.
Squamous cell carcinoma. Note sheets of large

molding, high mitotic rate, necrosis, and "salt and pepper" squamous cells with dysplasia and keratin "pearls: i
neuroendocrine-type chromatin.;
Pancoast tumor Carcinoma that occurs in apex of lung may Horner's syndrome -ipsilateral ptosis, miosis,
affect cervical sympathetic plexus, causing anhidrosis.
Horner's syndrome.
Superior vena cava An obstruction of the SVC that impairs blood drainage from the head ( "facial plethora"), neck
syndrome (jugular venous distention), and upper extremities (edema). Commonly caused by malignancy
and thombosis from indwelling catheters. Medical emergency. Can raise intracranial pressure (if
obstruction severe) headaches, dizziness, and t risk of aneurysm/rupture of cranial arteries.
-+
560 SECTION Ill RESPIRATORY RESPIRATORY-PATHOLOGY
Pneumonia
TYPE ORGANISM(S) CHARACTERISTICS
Lobar S. pneumoniae most frequently, Klebsiella Intra-alveolar exudate consolidation; may

-+
involve entire lung rJ.

Bronchopneumonia S. pneumoniae, S. aureus, H. influenzae, Acute inflammatory infiltrates from bronchioles
Klebsiella into adjacent alveoli; patchy distribution
involving :2: 1 lobe [l][1.
Interstitial (atypical) Viruses (influenza, RSV, adenoviruses), Diffuse patchy inflammation localized to
pneumonia Mycoplasma, Legionella, Chlamydia interstitial areas at alveolar walls; distribution
involving :2: 1 lobe [i]. Generally follows a more
indolent course.
Lung abscess Localized collection of pus within parenchyma. Air-fluid levels often seen on CXR. Often
Caused by: bronchial obstruction (e.g., clue to S. aureus or anaerobes (Bacteroides,
cancer); aspiration of oropharyngeal contents Fusobacterium, Peptostreptococcus).
(especially in patients predisposed to loss of
consciousness [e.g., alcoholics or epileptics]).
Hypersensitivity Mixed type III/IV hypersensitivity reaction to environmental antigen dyspnea, cough, chest
-+
pneumonitis tightness, headache. Often seen in farmers and those exposed to birds.
RESPIRATORY RESPIRATORY-PATHOLOGY SECTION Ill 5 61
Pleural effusions
Transudate ! protein content. Due to CHF, nephrotic syndrome, or hepatic cirrhosis.
Exudate t protein content, cloudy. Due to malignancy, pneumonia, collagen vascular disease, trauma
(occurs in states oft vascular permeability). Must be drained in light of risk of infection.
Lymphatic Also known as chylothorax. Due to thoracic duct injury from trauma, malignancy. Milky-appearing
fluid; t triglycerides.
Pneumothorax Unilateral chest pain and dyspnea, unilateral chest expansion, ! tactile fremitus, hyperresonance,
diminished breath sounds.
Spontaneous Accumulation of air in the pleural space[].
pneumothorax Occurs most frequently in tall, thin, young
males because of rupture of apical blebs.
Trachea deviates toward affected lung.
Spontaneous pneumothorax. a shows collapsed left

lung (arrow).
Tension Usually occurs in setting of trauma or lung

pneumothorax infection. Air is capable of entering pleural
space but not exiting. Trachea deviates away
from affected lung rn.
Tension pneumothorax. Note the hyperlucent left lung

field with low left hemidiaphragm and rightward mediastinal
shift.
56 2 SECTION Ill RESPIRATORY RESPIRATORY-PHARMACOLOGY
RESPIRATORY-PHARMACOLOGY
H1 blockers Reversible inhibitors of H1 histamine receptors.

1st generation Diphenhydramine, dimenhydrinate, Names contain "-en/-ine" or "-en/-ate."
chlorpheniramine.
CLINICAL USES Allergy, motion sickness, sleep aid.
TOXICITY Sedation, antimuscarinic, anti-a-adrenergic.
2nd generation Loratadine, fexofenadine, desloratadine, Names usually end in "-adine."
cetirizine.
CLINICAL USES Allergy.
TOXICITY Far less sedating than lst generation because of
entry into CNS.
RESPIRATORY RESPIRATORY-PHAR M A CO lOGY SECTION Ill 5 63
Asthma drugs Bronchoconstriction is mediated by ( l) inflammatory processes and (2) parasympathetic tone;
therapy is directed at these 2 pathways.
-agonists Albuterol -relaxes bronchial smooth muscle W2 ). Use during acute exacerbation.
Salmeterol, formoterol -long-acting agents for prophylaxis. Adverse effects are tremor and
arrhythmia.
Methylxanthines Theophylline -likely causes bronchodilation by inhibiting phosphodiesterase, t hereby ! cAM P
hydrolysis. Usage is limited because of narrow t herapeutic index (cardiotoxicity, neurotoxicity);
metabolized by P-450. Blocks actions of adenosine.
Muscarinic lpratropium -competitive block of muscarinic receptors, preventing bronchoconstriction. Also
antagonists used for COPD, as is tiotropium, a long-acting muscarinic antagonist.
Corticosteroids Beclomethasone, fluticasone -inhibit the
c:p
synthesis of virtually all cytokines. Inactivate Exposure to antigen
(dust, pollen, etc.)
N F-KB, t he transcription factor that induces
the production of T F-a, among other Moldoo
inflammatory agents. lst-line therapy for
chronic asthma.
Antileukotrienes Montelukast, zafirlukast-block leukotriene Antigen and lgE f-- Omalizumab
on mast cells
receptors. Especially good for aspirin-induced
asthma.
Zileuton -a 5 -lipoxygenase pathway inhibitor.
Blocks conversion of arachidonic acid to
leukotrienes.
Mediators
Omalizumab Monoclonal anti-IgE antibody. Binds mostly (leukotrienes, histamine, etc.)
unbound serum IgE. Used in allergic asthma
resistant to inhaled steroids and long-acting
-agonists
z -agonists. Steroids Theophylline
Antileukotrienes Muscarinic
antagonists
Bcoochodllatloo
~ !l-ago o l "

Late response: Early response:
+-0--- cAM P inflammation bronchoconstriction
j j
Bro n c h i a l tone
POE +---0-- Theophy l l i ne
AMP
Bronchial
ACh ---0-7 Adenosine Symptoms
ff
hyperreactivity
M usca ri n c Theophyl l i ne T reatment strategies in asthma
antagom sts
Bronchoconstriction
(Adapted, with perm ission, from Katzung BG, Trevor AJ. Pharmacology: Examination 8 Board Review, 5th ed. Stamford, 0: Appleton & Lange, 1 9 9 8 : 1 59 and 1 6 1 .)
Expedorants
Guaifenesin Expectorant-thins respiratory secretions; does not suppress cough reflex.
N-acetylcysteine Mucolytic-can loosen mucous plugs in CF patients. Also used as an antidote for acetaminophen
overdose.
56 4 SECTION Ill RESPIRATORY RESPIRATORY-PHARMACOLOGY
Bosentan Used to treat pulmonary arterial hypertension. Competitively antagonizes endothel in-l receptors,
decreasing pulmonary vascular resistance.
Dextromethorphan Antitussive (antagonizes N M DA glutamate receptors). Synthetic codeine analog. Has mild opioid
effect when used in excess. aloxone can be given for overdose. Mild abuse potential.
Pseudoephedrine, phenylephrine
MECHANISM Sympathomimetic a-agonistic nonprescription nasal decongestants.
CLINICAL USE Reduce hyperemia, edema, and nasal congestion; open obstructed eustachian tubes.
Pseudoephedrine also used as a stimulant.
TOXICITY Hypertension. Can also cause CNS stimulation/anxiety (pseudoephedrine).
Methacholine Muscarinic receptor agonist. Used in asthma challenge testing.

HIGH-YIELD SYSTEMS
Rapid Review
"Study without thought is vain: thought without study is dangerous."

- C onfucius
The following tables represent a collection of high-yield associations of

diseases with their clinical findings, treatments, and pathophysiology.
They serve as a quick review before the exam to tune your senses to
commonly tested cases and "buzzwords."
56 6 SECTION Ill RAPID REVIEW CLASSIC PRESENTATIONS
CLASSIC PRESENTATIONS
CLINICAL PRESENTATION DIAGNOSIS/DISEASE
Abdominal pain, ascites, hepatomegaly Budd-Chiari syndrome (posthepatic venous thrombosis)

Achi l les tendon xanthoma Familial hypercholesterolemia ( LDL receptor signal ing)
Adrenal hemorrhage, hypotension, DIC Waterhouse-Friderichsen syndrome (meningococcemia)
Arachnodactyly, lens d islocation, aortic d issection, Marfan's syndrome (fibril l i n defect)
hyperflexible j oints
Athlete with polycythemia 2 to eryth ropoietin injection
Back pain, fever, n i ght sweats, weight loss Pott's disease (vertebral tuberculosis)
Bilateral h ilar adenopathy, uveitis Sarcoidosis (noncaseating granulomas)
Blue sclera Osteogenesis imperfecta (type I collagen defect)
Bluish line on gingiva Burton's l ine ( lead poisoning)
Bone pai n , bone enlargement, arthritis Paget's disease of bone (t osteoblastic and osteoclastic
activity)
Bounding pulses, diastolic heart murmur, head bobbing Aortic regurgitation
"Butterfly" facial rash and Raynaud 's phenomenon in a young Systemic lupus erythematosus
female
Cafe-au-lait spots, Lisch nodules (iris hamartoma) Neurofibromatosis type I (+ pheochromocytoma , optic
gliomas)
Cafe-au-la it spots, polyostotic fibrous dysplasia, precocious McCune-Albright syndrome (mosaic G -protein signaling
puberty, multiple endocrine abnormalities mutation)
Calf pseudohypertrophy Muscular dystrophy (most commonly D uchenne's) : X-l inked
recessive deletion of dystroph i n gene
"Cherry-red spot" on macula Tay-Sachs (ganglioside accumulation) or iemann-Pick
(sphingomyelin accumulation) , central retinal artery occlusion
Chest pain on exertion Angina (stable : with moderate exertion ; unstable : with
mini mal exertion)
Chest pain, pericardia! effusion/friction rub, persistent fever Dressler's syndrome (autoimmune-mediated post-MI
fol lowing M I fibrinous pericarditis, l-1 2 weeks after acute episode)
Child uses arms to stand u p from squat Cowers' sign (Duchenne muscular dystrophy)
Child with fever later develops red rash on face that spreads to "Slapped cheeks" (erythema infectiosum/fifth disease:
body parvovirus Bl9)
Chorea, dementia, caudate degeneration Huntington's d isease (autosomal-dominant CAG repeat
expansion)
Chroni c exercise i ntolerance with myalgia, fatigue, painful McArdle's d isease (muscle glycogen phosphorylase deficiency)
cramps, myoglobinuria
Cold i ntolerance Hypothyroidism
Conjugate l ateral gaze palsy, horizontal d iplopia Internuclear ophthalmoplegia (damage to M LF; bilateral
[multiple sclerosis], unilateral [stroke])
Continuous "machi nery" heart murmur PDA (close with i ndomethaci n ; open or maintai n with
m isoprostol)
Cutaneous/dermal edema due to connective tissue deposition Myxedema (caused by hypothyroidism, Graves' disease
[pretibial])
RAPID REVIEW CLASSIC PRESENTATIONS SECTION Ill 56 7

Dark purple skin/mouth nodules Kaposi 's sarcoma (usually A I D S patients [ M SM]: associated
with H HV- 8 )
Deep, labored breathin g/hyperventilation Kussmaul breathing (diabetic ketoacidosis)
Dermatitis, dementia, diarrhea Pellagra (niacin [vita m i n B 3] deficiency)
Dilated card iomyopathy, edema, alcohol ism or malnutrition Wet beriberi (thiamine [vita m i n B d deficiency)
Dog or cat bite resulting in infection Pasteurella mu ltocida (cellul itis at inoculation site)
Dry eyes, dry mouth, arthritis Sjogren's syndrome (autoi mmune destruction of exocrine
glands)
Dysphagia (esophageal webs) , glossitis, i ron deficiency Plummer-Vi nson syndrome (may progress to esophageal
anemia squamous cell carcinoma)
Elastic ski n , hypermobi lity of joints Ehlers-Danlos syndrome (type III collagen defect)
Enlarged, hard left supraclavicular node Vi rchow's node (abdom inal metastasis)
Eryth roderma, lymphadenopathy, hepatosplenomegaly, Sezary syndrome (cutaneous T-cell lymphoma) or mycosis
atypical T cells fungoides
Facial muscle spasm upon tapping Chvostek's sign ( hypocalcemia)
Fat, female, forty, and fertile Cholel ith iasis (gallstones)
Fever, chills, headache, myalgia following antibiotic Jarisch-Herxheimer reaction (rapid lysis of spi rochetes results
treatment for syph ilis in toxi n release)
Fever, cough , conjunctivitis, coryza, diffuse rash Measles (Morbillivirus)
Fever, night sweats, weight loss B symptoms (staging) of lymphoma
Fibrous plaques in soft tissue of penis Peyronie's d isease (connective ti ssue d isorder)
Gout, mental retardation, self-mutilating behavior i n a boy Lesch-Nyhan syndrome ( H G PRT deficiency, X-linked
recessive)
Green-yellow rings around peripheral" cornea Kayser-Fleischer ri ngs (copper accumulation from Wilson's
disease)
Hamartomatous GI polyps, hyperpigmentation of Peutz-Jeghers syndrome ( i nherited, benign polyposis can
mouth/feet/hands cause bowel obstruction ; t cancer risk, mainly G I )
Hepatosplenomegaly, osteoporosis, neurologic Gaucher's disease (glucocerebrosidase deficiency)
symptoms
Hereditary neph ritis, sensorineural hearing loss, Alport syndrome (mutation in a chain of collagen IV)
cataracts
Hyperphagia, hypersexual ity, hyperora l ity, Kli.iver-Bucy syndrome (bilateral a mygdala lesion)
hyperdocil i ty
Hyperreflexia, hyperton ia, Babinski sign present UMN damage
Hyporeflexia, hypoton ia, atrophy, fasciculations LMN damage
Hypoxemia, polycythemia, hypercapn ia " Blue bloater" (chron ic bronch itis: hyperplasia of mucous
cells)
Indurated, ulcerated gen ital lesion Nonpainful: chancre ( 1 syph i l i s , Treponema pallidwn)
Pa inful, with exudate : chancroid (Haemophilus ducreyi)
Infant with cleft lip/palate, microcephaly or Patau's syndrome (trisomy 1 3 )
holoprosencephaly, polydactyly, cutis apl asia
568 SECTION Ill RAPID REVIEW CLASSIC PRESENTATIONS
Infant with fai lure to thrive, hepatospleno megaly, and Niemann-Pick d isease (genetic sphingomyel inase deficiency)
neurodegenera tion
Infant with hypoglycemia, fai lure to thrive, and Cori 's disease (debranch ing enzyme deficiency)
hepatomegal y
Infant with m icrocephaly, rocker-bottom feet, clenched Edwards' syndrome (trisomy 1 8 )
hands, and structural heart defect
Jaund ice, palpable d istended non-tender gallbladder Courvoisier's sign (d istal obstruction of bil iary tree)
Large rash with bull's-eye appearance Erythema chron icum m i grans from Ixodes tick bite ( Lyme
dis ease : Borrelia)
Lucid i nterval after traumatic brai n injur y Epidural hematoma (middle meningeal artery
rupture)
Male child, recur rent infections, n o mature B cells Bru ton's d isease (X-I inked agammaglobu l i nemia)
Mucosal bleeding and prolonged bleeding time Glanzmann's thrombasthenia (defect i n platelet aggregation
due to lack of Gpllb/IIIa)
Muffled heart sounds, distended neck veins, hypotension Beck's triad of cardiac tamponade
Multiple colon polyps, osteomas/soft tissue tumors, impacted/ Gardner's syndrome (subtype of FAP)
supernumerary teeth
Myopathy (infantile hypertrophic card iomyopathy) , exercise Pompe's disease ( lysosomal a-1 ,4-glucosidase deficiency)
intolerance
Neonate with arm paralysis following d i fficult bi rth Erb-Duchenne palsy (superior trunk [ C 5-C6] brachial plexus
injur y : "waiter's tip" )
No lactation postpartum , absent menstruation, cold Sheehan's syndrome (pitu itary infarction)
intolerance
ystagmus, intention tremor, scanning speech, bilateral Multiple sclerosis
internuclear ophthal moplegia
Oscillating slow/fast breath ing Cheyne-Stokes respirations (central apnea in C H F or
t intracranial pressure)
Pa inful blue fingers/toes, hemolytic anem ia Cold agglutinin disease (autoi mmune hemolytic
anem ia caused by Mycoplasma pneumoniae, infectious
mononucleosis)
Painful, pale, cold fingers/toes Raynaud 's phenomenon (vasospasm i n extrem ities)
Painful, raised red lesions on pad of fingers/toes Osler's node (infective endocard itis, immune complex
deposition)
Painless erythematous lesions on palms and soles Janeway lesions (infective endocarditis, septic embol i /
m icroa bscesses)
Painless jaundice Cancer of the pancreatic head obstructing bile duct
Palpable purpura on buttocks/legs, joint pa in, abdom inal pain I-Ienoch-Schonlein purpura (IgA vascul itis affecting ski n and
(child), hematuria kidneys)
Pancreatic, pituitary, parathyroid tumors MEN l (autosomal dom inant)
Periorbital and/or peripheral edema, proteinur i a , Nephrotic syndrome
hypoalbuminemia, hypercholesterolemia
Pink complexion, dyspnea, hyperventilation "Pink puffer" (emphysema : centriacinar [smoking], panacinar
[ a1-antitrypsi n deficiency])
RAPID REVIEW CLASSIC PRESENTATIONS SECTION Ill 569

Polyuria, renal tubular acidosis type I I , growth fai lure, Fancon i 's syndrome (proximal tubu lar reabsorption defect)
electrolyte i mbalances, hypophosphatem ic rickets
Positive anterior "drawer sign" Anterior cruciate l igament injury
Pruritic, purple, polygonal planar papules and plaques (6 P's) Lichen planus
Ptosis, miosis, anhidrosis Horner's syndrome (sympathetic chain lesion)
Pupil accommodates but doesn't react Argyll Robertson pupil (neurosyph ilis)
Rapidly progressive leg weakness that ascends following Gil Guilla in-Barre syndrome (acute autoimmune inflammatory
upper respiratory infection demyel inating polyneu ropathy)
Rash on pal ms and soles Coxsackie A, zo syph i l i s , Rocky Mounta in spotted fever
Recurrent colds, unusual eczema , h igh seru m IgE Hyper-IgE syndrome (Job 's syndrome: neutroph i l chemotaxis
abnormality)
Reel "currant jelly" sputum in alcohol ic or diabetic patients Klebsiella pnewnoniae
Reel "currant jelly" stools Acute mesenteric ischem ia (adults), intussusception ( infants)
Reel, itchy, swollen rash of nipple/areola Paget's disease of the breast (represents underlying neoplasm)
Reel urine in the morning, fragile RBCs Paroxysmal nocturnal hemoglobinuria
Renal cell carcinoma (bilateral), hemangioblastomas, von H ippel-Linclau disease (dom inant tumor suppressor gene
angiomatosis, pheochromocytoma mutation)
Resting tremor, rigidity, akinesia, postural instabil ity Parkinson's cl isease ( n igrostriatal dopam ine depletion)
Retinal hemorrhages with pale centers Roth 's spots (bacterial endocarditis)
Severe jaundice in neonate Crigler- ajjar syndrome (congen ital unconj ugated
hyperbil irubinem ia)
Severe R LQ pain w ith palpation of LLQ Rovsing's sign (acute appendicitis)
Severe RLQ pain with rebound tenderness McBurney's sign (appendicitis)
Short stature, t incidence of tumors /leukem ia, aplastic Fanconi's anem ia (genetic loss of DNA crossl ink repair; often
anemia progresses to AML)
Single palmar crease Sim ian crease ( Down syndrome)
Situs inversus, chronic sinusitis, bronch iectasis, infertil ity Kartagener's syndrome (clynein arm defect affecting cil ia)
Skin hyperpigmentation, hypotension, fatigue Addison's disease (l o adrenocortical insufficiency causes
t ACTH and t a-M S H production)
Slow, progressive muscle weakness in boys Becker's muscular dystrophy (X-Iinkecl m issense mutation in
clystrophin; less severe than Duchenne's)
Small, irregular reel spots on buccal /l ingual mucosa with Kopl ik spots (measles ; rubeola virus)
blue-white centers
Smooth , flat, moist, painless white lesions on genitals Condyl omata lata (2 syph ilis)
Spl inter hemorrhages in fingernails Bacterial endocarditis
"Strawberry tongue" Scarlet fever, Kawasaki d i sease, toxic shock syndrome
Streak ovaries, congenital heart disease, horseshoe kidney, cystic Turner syndrome (4 5,XO)
hygroma at birth, short stature, webbed neck, lymphedema
Sudden swollen/painfu l big toe joint, toph i Gout/podagra (hyperuricem ia)
Swollen gums, mucosal bleeding, poor wound heal ing, spots Scurvy (vitamin C deficiency: can't hydroxylate prol ine/lysine
on skin for collagen synthesis)
5 70 SECTION Ill RAPID REVIEW CLASSIC LABS/FINDINGS
CLINICAl PRESENTATION DIAGNOSIS/DISEASE
Swollen, hard, painfu l finger joints Osteoarthritis (osteophytes on P I P (Bouchard's nodes], DIP
(Heberden's nodes])
Systol ic ejection murmur (crescendo-decre scendo) Aortic valve stenosis

Thyroid and parathyroid tumors, pheochromocytom a MEN 2A (autosomal dom i nant ret mutation)
Thyroid tumors, pheochromocytoma, gangl ioneuromatosis MEN 2B (autosomal dom inant ret mutation)
Toe extension/fanning upon plantar scrape Babinski sign (UMN lesion)
Unilateral facial drooping i nvolving forehead Facial nerve ( LMN C N VII palsy)
Urethritis, conjunctivitis, arthritis in a male Reactive arth ritis associated with H LA-B27
Vascular birthmark (port-wine stain) Hemangioma (benign, but associated w ith Sturge-Weber
syndrome)
Vom iting blood following gastroesophageal lacerations Mallory-Weiss syndrome (alcohol ic and bul i m i c patients)
Weight loss, diarrhea, arthritis, fever, adenopathy Whipple's disease (Tropheryma whipplei)
"Worst headache of my life" Subarachnoid hemorrhage
CLASSIC LABS/FINDINGS
lAB/DIAGNOSTIC FINDING DIAGNOSIS/DISEASE
Anticentromere antibodies Scleroderma ( C REST)

Antidesmoglein (epithelial) antibodies Pemphigus vulgaris (blistering)
Anti-glomerular basement membrane antibodies Goodpasture's syndrome (glomerulonephritis and hemoptysis)
Antihistone antibodies Drug-induced SLE ( hydralazine, isoniazid, phenytoin,
procainam ide)
Anti-IgG antibodies Rheumatoid arthritis (systemic inflammation, joint pannus,
boutonn iere deform ity)
Antimitochondrial antibodies (AMAs) 1 bil iary cirrhosis (female, cholestasis, portal hypertension)
Antineutrophi l cytoplasmic a ntibodies (ANCAs) Vascul itis (c-ANCA: granulomatosis with polyangi itis
[Wegener's]; p-ANCA: m icroscopic polyangi itis, Churg
Strauss syndrome)
Antinuclear antibodies (ANAs : anti-Sm ith and anti-dsDNA) SLE (type I I I hypersensitivity)
Antiplatelet antibodies Idiopath ic thrombocytopenic purpura
Anti-topoisomerase antibodies Diffuse systemic scleroderma
An ti-tra nsglu tam i nase Ian ti -gl iadin Ian ti -endomysia 1 Cel iac di sease (diarrhea, distention, weight loss)
antibodies
"Apple core" lesion on abdominal x-ray Colorectal cancer (usually left-sided)
Azurophilic peroxidase-positive granular inclusions in Auer rods (acute myelogenous leukem ia, especi ally the
granulocytes and myeloblasts promyelocytic (M3] type)
Bacitracin response Sensitive : Streptococcus pyogenes (group A) ; resistant:
Streptococcus agalactiae (group B)
"Bamboo spine" on x-ray Ankylosing spondyl itis (chronic inflammatory arthriti s :
H LA-B27)
RAPID REVIEW CLASSIC LABS/FINDINGS SECTION Ill 57 1
LAB/DIAGNOSTIC FINDING DIAGNOSIS/DISEASE

Basophi l ic nuclear remnants in RBCs Howell-Jolly bodies (cl u e to splenectomy or nonfunction al
spleen)
Basoph ilic stippl ing of RBCs Lead poisoning or siderobl astic a nem ia
Bloody tap on LP Subarachnoid hemorrhage
"Boot shaped" heart on x-ray Tetralogy of Fallot, RVH
Branch ing gram-positive rods with sulfur granules Actinomyces israelii
Bronchogenic apical lung tumor on imaging Pancoast tumor (can compress sympathetic gangl ion and
cause Horner's syndrome)
"Brown" tumor of bone Hyperparathyroidism or osteitis fibrosa cystica (deposited
hemosiderin from hemorrhage gives brown color)
Cardiomegaly with apical atrophy Chagas' disease (Trypanosoma cruzi)
Cellular crescents in Bowman's capsule Rapidly progressive crescentic glomerulonephritis
"Chocolate cyst" of ovary Endometriosis (frequently involves both ovaries)
Circular grouping of dark tumor cells surrounding pale Homer-Wright rosettes (neuroblastoma, medulloblastoma,
neurofibrils retinoblastoma)
Colonies of mucoid Pseudomonas in lungs Cystic fibrosis (autosomal-recessive mutation in CFTR
resulting in fat-soluble vitamin deficiency and mucous plugs)
Decreased a-fetoprotein in amniotic fluid/maternal serum Down syndrome or other chromosomal abnormality
Degeneration of dorsal column nerves Tabes dorsal is (3 syphil is), subacute combined degeneration
(dorsal columns and lateral corticospinal tracts affected)
Depigmentation of neurons in substantia nigra Parkinson's disease (basal gangl ia disorder: rigidity, resting
tremor, bradykinesia)
Desquamated epithel ium casts in sputum Curschmann's spirals (bronch ial asthm a ; can result i n
whorled mucous plugs)
Disarrayed granulosa cell s in eosinophi l ic fl u id Call-Exner bodies (granulosa-theca cell tumor of the ovary)
Dysplastic squamous cervical cell s with nuclear enlargement Koilocytes ( H PV: predisposes to cervical cancer)
and hyperchromasia
Enlarged cells with intranuclear inclusion bodies "Owl's eye" appearance of CMV
Enlarged thyroid cells with ground-glass nuclei "Orphan Annie's eyes" nuclei (papillary carcinoma of the
thyroid)
Eosinoph ilic cytopl asmic inclusion in l iver cell Mallory bodies (alcohol ic l iver disease)
Eosinoph ilic cytoplasmic inclusion in nerve cell Lewy body ( Parkinson's disease)
Eosinoph ilic globule in l iver Council man body (toxic or viral hepatitis, often yellow fever)
Eosinoph ilic inclusion bodies in cytoplasm of h ippocampal Negri bodies of rabies (Lyssavirus)
nerve cells
Extracellular amyloid deposition i n gray matter of brain Senile plaques (Alzheimer's disease)
Giant B cells with bilobecl nuclei with pro m inent inclusions Reed-Sternberg cell s ( Hodgkin's lymphoma)
("owl's eye")
Glomerulus-l ike structure surrounding vessel in germ cells Schiller-Duval bodies (yolk sac tumor)
"Hair on end" (crew-cut) appearance on x-ray -thalassem ia, sickle cell anem ia (marrow expansion)
hCG elevated Choriocarcinoma, hydatidiform mole (occurs with and
without embryo)
5 72 SECTION Ill RAPID REVIEW CLASSIC LABS/FINDINGS
Heart nodules (granulomato us) Aschoff bodies (rheumatic fever)
Heteroph ile antibodies Infectious mononucleosis (EBV)

Hexagonal, double-pointed, needle-l ike crystals in bronch ial Bronchial asthma (Charcot-Leyden crystals : eosinoph ilic
secretions granules)
H igh level of o-dimers DVT, pulmonary embol ism, DIC
H ilar lymphadenopathy, peripheral granulomatous lesion in Chon complex 00 TB : Mycobacterium bacilli)
m iddle or lower lung lobes (can calcify)
" Il oneycomb lung" on x-ray or CT Interstitial pulmonary fibrosi s
Hypercoagulabil ity ( leading to migrating DVTs and vasculitis) Trousseau's syndrome (adenocarcinoma of pancreas or lung)
Hypersegmented neutrophils Megaloblastic anemia (B12 defic iency: neurologic symptoms;
folate deficiency: no neurologic symptoms)
Hypertension, hypokalem ia, metabolic alkalosis Conn's syndrome
Hypochromic, microcytic anem ia Iron deficiency anem ia, lead poisoning, thalassemia (fetal
hemoglobin sometimes present)
Increased a-fetoprotein in amniotic fluid/maternal serum Dating error, anencephaly, spina b ifida (neural tube defects)
Increased uric acid levels Gout, Lesch-Nyhan syndrome, tumor lysis syndrome, loop
and th iazide diuretics
Intranuclear eosinoph i l ic droplet-like bodies Cowdry type A bodies (1-ISV or CMV)
Iron-containing nodules in alveolar septum Ferruginous bodies (asbestosis: t chance of mesothel ioma)
Keratin pearls on a skin biopsy Squamous cel l carcinoma
Large lysosom al vesicles in phagocytes, immunodeficiency Chediak-H igashi disease (congenital fa i lure of phagolysosome
formation)
"Lead pipe" appearance of colon on barium enema x-ray Ulcerative colitis (loss of haustra)
Linear appearance of lgG deposition on glomerular basement Goodpasture's syndrome
membrane
Low seru m ceruloplasmin Wilson's disease (hepatolenticular degeneration)
"Lumpy bumpy" appearance of glomeruli on Poststrcptococcal glomerulonephritis ( i mmune complex
i m m u noAuorescence deposition of lgG and C 3b)
Lytic ("hole punched") bone lesions on x-ray Multiple myeloma
Mammary gland ( " blue domed") cyst F ibrocystic change of the breast
Monoclonal antibody spike Multiple myeloma (usually lgG or lgA)
Monoclonal gam mopathy of undetermined significance
(MGUS ; normal consequence of aging)
Waldenstrom's (M protein = IgM) macroglobulinem ia
Primary amyloidosis
Mucin-filled cell with peripheral nucleus Signet ring (gastric carcinoma)
Narrowing of bowel lumen on barium x-ray " String sign" ( Crohn's disease)
ecrotizing vasculitis ( lungs) and necrotizing Granulomatosis w ith polyangi itis (Wegener's ; c-ANCA
glomerulonephritis positive) and Goodpasture's syndrome (anti-basement
membrane antibodies)
eedle-shaped, negatively birefringent crystals Gout (monosodium urate crystals)
Nodular hyaline deposits in glomeruli Kim mels tiel-Wilson nodules (diabetic nephropathy)
ovobiocin response Sensitive: Staphylococcus epidermidis; resistant:
Staphylococcus saprophyticus
RAPID REVIEW CLASSIC lABS/FINDINGS SECTION Ill 57 3

"Nutmeg" appearance of l iver Chronic passive congestion of l iver due to right heart fa il ure
"Onion skin" peri osteal reaction Ew i ng's sarcoma (malignant round-cell tumor)
Optochin response Sensitive: Streptococcus pneumon iae; resistant: Viridans
streptococcus
Periosteum ra ised from bone, creating triangu lar area Cad man's triangle on x-ray (osteosarcoma, Ewing's sarcoma,
pyogenic osteomyelitis)
Podocyte fusion or "effacement" on electron m icroscopy M inimal change d i sease (child with nephrotic syndrome)
Pol ished, " ivory l ike" appearance of bone at cartilage erosion Eburnation (osteoarthritis resulting in bony sclerosis)
Protein aggregates in neurons from hyperphosphorylation of Neurofibrillary tangles (Al zheimer's d isease) and Pick 's bodies
protein tau ( Pick 's d isease)
Psammoma bodies Meningiomas, papillary thyroid carcinoma , mesothelioma,
papil lary serous carcinoma of the endometrium and ovary
Pseudopal isad ing tumor cells on brain biopsy Glioblastoma multiforme
RBC casts in urine Acute glomerulonephritis
Rectangular, crystal-l ike, cytoplasmic inclusions in Leyd ig cells Reinke crystals ( Leyd ig cell tumor)
Renal epithel ial casts in urine Acute toxic/viral nephrosis
Rhomboid crystals, positively bi refringent Pseudogout (calcium pyrophosphate d i hyd rate crystals)
Rib notch ing Coarctation of the aorta
Ri ng-enhancing bra in lesion in AIDS Toxoplasma gondii, CNS lymphoma
Sheets of medium-sized lymphoid cells with scattered pale, Burkitt's lymphoma (t [ 8:14] c-myc activation, associated with
tingible body-laden macrophages ( "starry sky" h i stology) EBV; " black sky" made up of malignant cells)
Si lver-staining spherical aggregation of tau proteins in Pick bodies ( Pick's d i sease: progressive dementia, changes in
neurons personal ity)
"Soap bubble" in femur or tibia on x-ray Giant cell tumor of bone (generally benign)
"Spikes" on basement membrane, " dome like" subepithel ial Membranous glomeru l onephritis (may progress to nephrotic
deposits syndrome)
Stacks of RBCs Rouleaux formation ( h i gh ESR, multiple myeloma)
Stippled vaginal epithelial cells "Clue cells" ( Gardnerella vagina/is)
"Tennis racket" shaped cytoplasm ic organelles (EM) in Birbeck granules (Langerhans cel l h i stiocytosis or
Langerhans cells histiocytosis X: eosinoph i l ic granuloma)
Thrombi made of white/red layers Lines of Zahn (arterial thrombus, layers of platelets/RBCs)
"Thumb sign" on lateral x-ray Epiglottitis (Haemophilus influenzae)
Thyroid-l ike appearance of k idney Chronic bacterial pyeloneph ritis
Tram-track appearance of capillary loops of glomerular Membranoprol i ferative glomerulonephritis
basement membranes on l i ght m icroscopy
Tri glyceride accumulation i n l iver cel l vacuoles Fatty liver disease (alcohol ic or metabol ic syndrome)
"Waxy" casts with very low urine flow Chronic end-stage renal d i sease
WBC casts in urine Acute pyelonephritis
WBCs that look "smudged" CLL (almost always B cell)
"Wire loop" glomerular capillary appearance on l ight Lupus nephropathy
microscopy
Yellowish CSF Xanthochrom ia (e.g., due to subarachnoid hemorrhage)
57 4 SECTION Ill RAPID REVIEW CLASSIC/RELEVANT TREATMENTS
CLASSIC/RELEVANT TREATMENTS
CONDITION COMMON TREATMENT(S)
Absence seizures Ethosuxi m ide
Acute gout attack NSAIDs, colchicine
Acute promyelocytic leukemia (M3) All-trans retinoic acid

ADH D Methylphenidate, amphetam ines
Alcohol abuse AA + disulfiram for patient and Al-Anon for family
Alcohol withdrawal Benzodiazepines
Anorexia SSRis
Anticoagulation during pregnancy Heparin
Arrhythmia in damaged cardiac tissue Class IB antiarrhythmic ( l idocaine, mexi letine, tocain ide)
B1 2 deficiency Vitamin B12 supplementation (work up cause with Schill ing test)
Benign prostatic hyperplasia Tamsulosin, finasteride
Bipolar disorder Lithium, valproate, carbamazepine, lamotrigine (mood
stabil izers)
Breast cancer in postmenopausal woman Aromatase inhibitor (anastrozole)
Buerger's disease Smoking cessation
Bul imia SSRis
Candida albicans Amphotericin B (systemic), nystatin (oral thrush, esophagitis)
Carcinoid syndrome Octreotide
Chlamydia trachomatis Doxycycl ine (+ ceftriaxone for gonorrhea coinfection) ,
erythromycin eye drops (prophylaxis in infants)
Ch ronic gout Probenecid (underexcretor) , allopurinol (overproducer)
Chronic hepatitis I F N-a
Chronic myelogenous leukemia lmatinib
Clostridium botulinum Antitoxin
Clostridium difficile Oral metronidazole; if refractory, oral vancomycin
Clostridium tetani Antitoxin + vaccine booster + diazepam
Crohn's disease Corticosteroids, infl ixi mab
Cryptococcus neoformans Fluconazole (prophylaxis in AIDS patients)
Cyclophospham ide-induced hemorrhagic cystitis Mesna
Cystic fibrosis N-acetylcysteine + antipseudomonal prophylaxis (tobramycin/
azithromycin)
Cytomegalovirus Ganciclovir
Depression SSRis (first-l ine)
Diabetes insipidus Desmopressin (central ) ; hydrochlorothiazide, indomethacin,
amiloride (nephrogenic)
Diabetes mell itus type 1 Dietary intervention ( low-sugar) + insul in replacement
Diabetes mell itus type 2 Dietary intervention, oral hypoglycemics, and insul in
(possible)
Diabetic ketoacidosis F l u ids, insul in, K+
RAPID REVIEW CLASSIC/RELEVANT TREATMENTS SECTION Ill 57 5

Enterococci Vancomyc i n /ampic i l l i n + a m i noglycosi de
Erectile dysfunction Sildenafil, vardenafil
ER-positive breast cancer Tamoxifen
Ethylene glycol /methanol intoxication Fomepizole (alcohol dehyd rogenase inh ibitor)
Haemophilus influenzae (B) Rifampin (prophylaxis)
General ized anxiety d isorder Buspirone
Heparin toxicity (acute) Protamine sulfate
HER2/neu-positive breast cancer Trastuzumab
Hyperaldosteron ism Spironolactone
Hypercholesterolemia Statin (fi rst-l ine)
Hypertriglyceridem i a Fibrate
Immediate anticoagulation Heparin
Infertility Leuprol ide, GnRH (pulsatile)
Influenza Rimantad ine, oseltam ivi r
Legionella pneumophila Erythromycin
Long-term anticoagulation Warfarin
Malaria Chloroqu ine/mefloqu ine (for blood sch izont), primaqu ine
(for l iver hypnozoite)
Mal ignant hyperthermia Dantrolene
Med ical abortion M i fepristone
M igraine Sumatriptan
MRSA Vancomycin
Multiple sclerosis -interferon, i m m unosuppression, natalizumab
Mycobacterium tuberculosis RIPE (rifampin, INH, pyrazinam ide, ethambutol )
Neisseria gonorrhoeae Ceftr iaxone (add doxycycline to cover l i kely concurrent
Chlamydia)
Neisseria meningitidis Penicillin/ceftriaxone, rifampin (prophylaxis)
Neural tube defect prevention Prenatal folic acid
Osteomalacia/rickets Vitamin D supplementation
Osteoporosis Bisphosphonates; calcium and vitam in D
supplementation
Patent ductus arteriosus Indomethacin
Pheochromocytoma a-antagon ists (e.g., phenoxybenzami ne)
Pneumocystis jirovecii TM P-SMX (prophylaxis in AIDS patient)
Prolacti noma Bromocripti ne (dopam i ne agonists)
Prostate cancer/uterine fibroids Leuprol ide, G n R H (continuous)
Prostate carcinoma Flu tam ide
Pseudomonas aeruginosa Antipseudomonal pen i c i l l i n + am inoglycoside
Pulmonary arterial hypertension (id iopath ic) Sildenafil , bosentan, epoprostenol
5 76 SECTION Il l RAPID REVIEW KEY ASSOCIATIONS
Rickettsia rickettsii Doxycycline, chloramphenicol (especially in context of

aplastic anemia)
Ringworm infections Terbinafine, griseofulvi n , i m idazole
Sch izophren ia (negative symptoms) 5 -HT Z A antagon ists (e.g., second-generation antipsychotics)
Schizophren ia (positive symptoms) 02 receptor antagon ists (e.g., fi rst- and second-generation
antipsychotics
SIADH Demeclocycl ine, l ithium, vasopressin receptor antagon ists
S ickle cell anemia Hydroxyurea (t fetal hemoglobin)
Sporothrix schenckii Oral potassium chloride
Stable angina Subl ingual n itroglycerin
Staphylococcus aureus M S SA : nafcillin, oxac i l l i n , d icloxac i l l i n (antistaphylococcal
penicillins); M R SA : vancomycin
Streptococcus bovis Pen icillin prophylaxis; evaluation for colon cancer if linked to
endocarditis
Streptococcus pneumoniae Penicillin/cephalosporin (system i c infection, pneumonia),
vancomyci n (men ingitis)
Streptococcus pyogenes Pen icil l i n prophylaxis
Temporal arteritis High-close steroids
Ton ic-clonic seizures Phenytoin, valproate, carbamazepine
Toxoplasma gondii Sulfadiazine + pyrimethamine
Treponema pallidwn Pen icillin
Trichomonas vagina/is Metronidazole (patient and partner)
Ulcerative colitis 5-ASA, infliximab
UTI prophylaxis TMP-SMX
Warfarin toxicity Fresh frozen plasma (acute), vitamin K (chronic)
Wegener's granulomatosis with polyangi itis Cyclophosphamide, corticosteroids
KEY ASSOCIATIONS
DISEASE/FINDING MOST COMMON/IMPORTANT ASSOCIATIONS
Actinic (solar) keratosis Precursor to squamous cell carci noma

Acute gastric ulcer associated with C N S injur y Cush i ng's ulcer (t ICP stimulates vagal gastric secretion)
Acute gastric ulcer associated with severe burns Curl ing's ulcer (greatly reduced plasma volume results i n
sloughing o f gastric mucosa)
Alternating areas of transmural inflammation and normal Skip lesions (Crohn's d isease)
colon
Aneurysm , d issecting Hypertension
Aortic aneurysm , abdom i nal and descending aorta Atherosclerosis
Aortic aneurysm, arch Tertiary syphilis (syph i l itic aortitis), vasa vasorum destruction
Aortic aneurysm , ascend ing Marfan's syndrome (idiopathic cystic medial degeneration)
RAPID REVIEW KEY ASSOCIATIONS SECTION Ill 5 77
Atrophy of the mammillary bodies Wernicke's encephalopathy (th i a m i ne deficiency causi ng

ataxia, ophthal moplegia, and confusion)
Autosplenectomy (fibrosis and sh rinkage) S ickle cell anem ia ( hemoglobin S )
Bacteria assoc iated with gastritis, peptic ulcer d isease, and H . pylori
stomach cancer
Bacterial men i ngitis (adults and elderly) Streptococcus pnewnoniae
Bacterial meningitis (newborns and kids) Group B streptococcus (newborns), S. pneumoniae/Neisseria
meningitidis (kids)
Ben ign melanocytic nevus Spitz nevus (most common in fi rst two decades)
Bleeding d isorder with Gplb deficiency Bernard-Soulier synd rome (defect i n platelet adhesion to von
Willebrand 's factor)
Brain tumor (adults) Supratentorial : metastasis > astrocytoma (i nclud ing
gl ioblastoma multiforme) > meningioma > schwannoma
Brain tumor (kids) Infratentorial : medulloblastoma (cerebel lum) or
supratentorial : cran iopharyngioma (cerebrum)
Breast cancer In filtrating ductal carci noma (in the U . S . , l in 9 women will
develop breast cancer)
Breast mass F ibrocystic change, carci noma ( i n postmenopausal
women)
Breast tumor (ben ign) F ibroadenoma
Cardiac l o tumor (kids) Rhabdomyoma, often seen in tuberous sclerosis
Cardiac manifestation of lupus Libman-Sacks endocard itis (nonbacterial , affecting both sides
of m itral valve)
Cardiac tumor (adults) Metastasis, 1 myxoma (4 : l left to right atriu m ; " ball and
valve")
Cerebellar tonsil lar hern iation Chiari malformation (often presents with progressive
hydrocephalus or syringomyel ia)
Chron ic arrhyth m ia Atrial fibrillation (associated with h igh risk of emboli)
Chronic atroph ic gastritis (autoimmune) Pred isposition to gastric carci noma (can also cause pernicious
anemia)
Clear cell adenocarcinoma of the vagi na DES exposure in utero
Compression fracture Osteoporosis (type I: postmenopausal woman ; type II: elderly
man or woman)
Congenital adrenal hyperplasia, hypotension 2 1-hydroxylase deficiency
Congen ital card iac anomaly VSD
Congenital conjugated hyperbilirubinemia (black l iver) Dubi n-Joh nson syndrome (inabi l ity of hepatocytes to secrete
conjugated bili rubin into bile)
Constrictive pericarditis Tuberculosis (developi ng world); system ic lupus
erythematosus (developed world)
Coronary artery involved i n thrombosis LAD > RCA > LCA
Cretinism Iodine deficit/hypothyroid ism
57 8 SECTION Ill RAPID REVIEW KEY ASSOCIATIONS
Cushing's syndrome Iatrogenic Cushi ng's (from corticosteroid therapy)

Adrenocortical adenom a (secretes excess cortisol )
ACTH-secreting pitu itary adenoma
Paraneopl astic Cushing's (clue to ACTH secretion by
tumors)
Cyanosis (early; less common) Tetral ogy of Fal lot, transposition of great vessels, truncus
arteriosus
Cyanosis ( late ; more common) VSD, ASD, PDA
Death in C M L Blast crisis
Death in S L E Lupus nephropathy
Dementia Alzheimer's disease, multiple infarcts
Demyel inating disease in young women Multiple sclerosis
DIC Severe sepsis, obstetric compl ications, cancer, burns, trauma,
maJor surgery
Dietary deficit Iron
Diverticulum in pharynx Zenker's d iverticulum (diagnosed by barium swallow)
Ejection click Aortic/pul monic stenosis
Esophageal cancer Squamous cel l carcinoma (worldwide); adenocarcinoma
(U.S.)
Food poisoning (exotoxin mediated) S. aureus, B . cereus
Glomeru lonephritis (adults) Berger's disease (IgA nephropathy)
Gynecologic malignancy Endometrial carcinoma (most common in U. S . ) ; cervical
carcinoma (most common worldwide)
Heart murmur, congen ital Mitral valve prolapse
Heart valve in bacterial endocard itis M itral > aortic (rheumatic fever) , tricuspid (IV dru g
abuse)
Helminth infection (U. S . ) Enterobius vermicularis, Ascaris lumbricoides
Hematoma - epidural Rupture of m iddle meningeal artery (trauma; lentiform
shaped)
Hematoma- subdural Rupture of bridging veins (crescent shaped)
Hemochromatosis Multiple blood transfusions or hereditary HFE mutation
(can result i n C I-I F, " bronze d iabetes," and t risk of
hepatocellular carcinoma)
Hepatocellular carcinoma Cirrhotic l iver (associated with hepatitis B and C and with
alcohol ism)
Hereditary bleed ing d isorder von Wil lebrand 's d isease
Hereditary harmless jaundice Gilbert's syndrome (benign congen ital unconj ugated
hyperbilirubinemia)
H LA-B27 Ankylosing spondyl itis, Reiter's syndrome, ulcerative col itis,
psonas1s
H LA-DR3 or -DR4 Di abetes mell itus type 1, rheumatoid arthritis, SLE
RAPID REVIEW KEY ASSOCIATIONS SECTION Ill 5 79
Holosystolic murmur VSD, tricuspid regurgitation, m itral regurgitation

Hypercoagulabil ity, endothel ial damage, blood stasis Vi rchow's triad (results i n venous thrombosis)
Hypertension, 2 Renal disease
Hypoparathyroidism Accidental excision during thyroidectomy
Hypopituitarism Pituitary adenoma (usually benign tumor)
Infection 2 to blood transfusion Hepatitis C
Infections in chron ic granulomatous d i sease Staphylococcus aureus, E. coli, Aspergillus (catalase positive)
Kidney stones Calcium = rad iopaque
Struvite (ammonium) = radiopaque (formed by
urease-positive organisms such as Proteus vulgaris or
Staphylococcus)
Uric acid = rad iolucent
Late cyanotic shunt (uncorrected left to right becomes right Eisenmenger's syndrome (caused by ASD, VSD, PDA; results
to left) i n pulmonary hypertension /polycythemia)
Liver disease Alcohol ic cirrhosis
Lysosomal storage disease Gaucher's d isease
Male cancer Prostatic carcinoma
Malignancy associated with non infectious fever Hodgkin's lymphoma
Mal ignancy (kids) ALL, medulloblastoma (cerebellum)
Mental retardation Down syndrome, fragile X syndrome
Metastases to bone Prostate, breast > lung > thyroid, testes
Metastases to bra in Lung > breast > gen itourinary > osteosarcoma > melanoma
> GI
Metastases to l iver Colon >> stomach , pancreas
Mitochondrial inheritance D isease occurs i n both males and females, i n herited th rough
females only
Mitral valve stenosis Rheumatic heart d i sease
Mixed ( U M a n d LMN) motor neuron d isease ALS
Myocard itis Coxsackie B
Nephrotic syndrome (adults) Focal segmental glomerulosclerosis
Nephrotic syndrome (kids) M i n imal change disease
euron migration fa ilur e Kallmann syndrome ( hypogonadotropic hypogonadism and
anosm ia)
Nosocom ial pneumonia Klebsiella, E . coli, Pseudomonas aeruginosa
Obstruction of male uri nary tract BPH
Open ing snap Mitral stenosis
Opportunistic infection in AIDS Pnewnocystis jirovecii (formerly carinii) pneumon i a
Osteomyelitis S. aureus
Osteomyel itis i n sickle cell disease Salmonella
Osteomyelitis with IV drug use Pseudomonas, S. aureus
5 80 SECTION Ill RAPID R EVI EW KEY ASSOC I ATIONS
Ovarian metastasis from gastric carcinoma or breast cancer Krukenberg tumor (mucin-secreting signet-ring cells)
Ovarian tumor (benign, bilateral) Serous cystadenoma
Ovarian tumor (malignant) Serous cystadenocarcinoma
Pancreatitis (acute) Gallstones, alcohol
Pancreatitis (chronic) Alcohol (adults), cystic fibrosis (kids)
Patient with ALL /CLL /AM L /CM L ALL : child, C L L : adult > 6 0 , A M L : adult - 6 5 , C M L : adult
30 - 60
Pelvic inflammatory d isease Chlamydia trachomatis, Neisseria gonorrhoeae
Ph iladelph ia chromosome t(9 ; 2 2 ) (bcr-abl) CML (may sometimes be associated with ALL/A M L)
Pituitary tumor Prolactinoma, somatotropic "acidoph i l ic" adenoma
Primary amenorrhea Tur ner syndrome (45,XO )
Primary bone tumor (adults) Multiple myeloma
Primary hyperaldosteronism Adenoma of adrenal cortex
Primary hyperparathyroidism Adenomas, hyperplasia, carcinoma
Primary l iver cancer Hepatocellular carcinoma (chronic hepatitis, cirrhosis,
hemochromatosis, a.1 antitrypsin deficiency)
Pul monary hypertension COPD
Recurrent inflam mation/thrombosis of small/medium vessels Buerger's disease (strongly associated w ith tobacco)
i n extrem ities
Renal tumor Renal cell carcinom a : associated with von H ippel-Lincl a u
and cigarette smoking; paraneoplastic syndromes ( E PO,
ren in, PTH , ACTH )
Right heart fa ilur e clue to a pulmonary cause Cor pulmonale
S3 (protocl iastol ic gallop) t ventricular filling ( left to right shunt, m itral regurgitation,
LV fa i lure [ C H F ] )
S4 (presystol ic gallop) Stiff/hypertrophic ventricle (aortic stenosis, restrictive
cardiomyopathy)
Secondary hyperparathyroidism Hypocalcem ia of chron ic kidney d isease
Sexually transmit ted d isease Chlamyd ia (usually coinfectecl with gonorrhea)
SIADH Small cell carcinoma of the lung
Site of diverticula S igmoid colon
Sites of atherosclerosis Abdominal aorta > coronary artery > popli teal artery
> carotid artery.
Stomach cancer Adenocarcinoma
Stomach ulcerations and h igh gastri n levels Zol l inger-Ellison syndrome (gastrinoma of duodenum or
pancreas)
t(l4; l8) Fol l icular lymphomas (b cl 2 activation)
-
t ( 8 ; 14) Burkitt's lymphoma (c- m yc activation)

t(9 ; 2 2 ) Philadelph ia chromosome, CML (bcr-abl fusion)
Temporal arteritis Risk of ipsilateral bl i ndness cl u e to thrombosis of ophthalm ic
artery; polymyalgia rheumatica
RAPID REVIEW EQ U ATION REVIEW SECTION Il l 581
Testicular tumor Seminoma

Thyroid cancer Papil lary carcinoma
Tumor in women Leiomyoma (estrogen dependent, not precancerous)
Tumor of infancy Hemangioma (usually regresses spontaneously by chi ldhood)
Tumor of the adrenal medulla (adults) Pheochromocytoma (usually benign)
Tu mor of the adrenal medulla (kids) Neuroblastoma (malignant)
Type of Hodgkin's Nodular sclerosis (vs. m ixed cellularity, lymphocytic
predominance, lymphocytic depletion)
Type of non-Hodgkin's Diffuse large cell
UTI E. coli, Staphylococcus saprophyticus (young women)
Viral encephalitis affecting temporal lobe HSV- l
Vitamin deficiency ( U . S . ) Folate (pregnant women are a t h igh risk; body stores only 3 - to
4-month supply; prevents neural tube defects)
EQ U ATION REVIEW
TOPIC EQUATION PAGE

Sensitivity Sensitivity = TP I (TP + FN) 51
Specificity Specific ity = TN I (T + FP) 51
Positive pred ictive value PPV = TP I (TP + F P) 51
Negative predictive value N PV = TN I (TN + FN) 51
Odds ratio (for case-control studies) . ale ad 52
Odd s ratio = - = -
b/d be
Relative risk a/(a + b) 52

Re I atlve
. ns. k = -->----'-
c/( c + d)
Attributable risk a _c 52
Attributable risk = __ - _
a+b c+d
Number needed to treat ! /absolute risk reduction 52
Number needed to harm ! /attributable risk 52
Body mass index weight in kg 60
BMI =
(height in meters)2
Hardy-Wei nberg equilibrium p z + 2p q + q z = l 83
p+q = l
Volume of distribution amount of drug in the body 227
VI = --:-----:----=------0...
c plasma drug concentration
Half-life 0.7 X V (I 227
-
t Yz -
CL
Drug clearance rate of elimination of dru g 227
CL = ....-
...,.-- --------=- = vel X Ke ( el i m i nation consta nt)
plasma dru g concentration
5 82 SECTION Ill RAPID REVIEW E Q U ATION REVIEW
TOPIC EQUATION PAGE

Loading dose vel 227
LD = C x
P F
Maintenance dose CL 227
MD = C x
p F
Cardiac output rate of 0 2 consumption 253
co = -
----, --- =-- - ---
arterial 0 2 content - venous 0 2 content
C O = stroke volume x heart rate 253

Mean arterial pressure MAP = cardiac output x total peripheral resistance 253
MAP = 2/3 d iastol ic + 1/3 systol ic 253

Stroke volume
SV = C O = E DV - E SV
253
HR
Ejection fraction SV E DV - E S V 2 54
EF = =
E DV E DV
Resistance . driving pressure (P) 811 (viscosity) x length 255

Resistance = =
4
flow (Q) 1t r
Net filtration pressure p net = [ ( Pc - P ) - (1tc - 1t;)] 265
Iv = n e t fl u i d flow = ( K r ) ( Pnet)
Renal clearance ex = U XV/ Px 480
Glomeru lar fi ltration rate GFR = uinulin X

V/ P i n u l i n = c i n u l i n 480
480
GFR = K r [ ( P c c - PBs ) - ( nee - nBs )]
Effective renal plasma flow v 480

ERPF = U PA H X -
)- = C PAH
I PAH
Renal blood flow RPF 480
RB F = --
1 - Hct
Filtration fraction GFR 481
FF = -
RPF
[ HCO ,' - ]
Henderson-Hasselbalch equation (for 487
extracellular pH) pH = 6. 1 + log
0 . 0 3 Pco 2
Physiologic dead space ( Paco 2 ) - P EC02 546

V0 = VT x -- =----
Paco 2
Pulmonary vascular resistance p u l m artery - p L atrium 549

p
PVR =
Cardiac output
Alveolar gas equation Paco 550
P'A07- -
_ l)I 07- - --2
R
SECTION IV
Top-Rated Review
Resources
"Some books are to be tasted, others to be swallowed, and some few to be How to Use the
chewed and digested." Database 584

-Sir Francis Bacon
Question Banks 586
"Always read something that will make you look good if you die in the
middle of it." Question Books 587
-P.J. O'Rourke
Internet Sites 588
Comprehensive 589
Anatomy, Embryology,
and Neuroscience 591
Behavioral Science 595
Biochemistry 597
Cell Biology and

Histology 599
Microbiology and
Immunology 601
Pathology 605
Pharmacology 610
Physiology 614
583
58 4 SECTION IV TOPRATED REVIEW RESOURCES
H OW TO USE T H E DATABASE
This section is a database of top-rated basic science review books, sample

examination books, software, Web sites, and commercial review courses that
have been marketed to medical students studying for the USMLE Step l.
At the end of the section is a list of publishers and independent bookstores
with addresses and phone numbers. For each recommended resource, we
list (where applicable) the Title, the First Author (or editor), the Series
Name (where applicable), the Current Publisher, the Copyright Year,
the Number of Pages, the ISBN, the Approximate List Price, the Format
of the resource, and the Number of Test Ouestions. We also include
Summary Comments that describe their style and overall utility for
studying. Finally, each recommended resource receives a Rating. Within
each section, resources are arranged first by Rating and then alphabetically
by the first author within each Rating group.
A letter rating scale with six different grades reflects the detailed student
evaluations for Rated Resources. Each rated resource receives a rating as
follows:
A+ Excellent for boards review.
A
Very good for boards review; choose among the group.
A-
B+
Good, but use only after exhausting better sources.
B
B- Fair, but there are many better books in the discipline; or low-yield
subject material.
The Rating is meant to reflect the overall usefulness of the resource in

helping medical students prepare for the USMLE Step l. This is based on a
number of factors, including:
The cost
The readability of the text
The appropriateness and accuracy of the material
The quality and number of sample questions
The quality of written answers to sample questions
The quality and appropriateness of the illustrations (e.g., graphs,
diagrams, photographs)
The length of the text (longer is not necessarily better)
The quality and number of other resources available m the same
discipline
The importance of the discipline for the USMLE Step l
Please note that ratings do not reflect the quality of the resources for
purposes other than reviewing for the USMLE Step 1. Many books with
lower ratings are well written and informative but are not ideal for boards
TOPRATED REVIEW RESOURCES SECTION IV 58 5
preparation. We have not listed or commented on general textbooks

available in the basic sciences.
Evaluations are based on the cumulative results of formal and informal

surveys of thousands of medical students at many medical schools across the
country. The summary comments and overall ratings represent a consensus
opinion, but there may have been a broad range of opinion or limited
student feedback on any particular resource.
Please note that the data listed are subject to change in that:
Publishers' prices change frequently.

Bookstores often charge an additional markup.
New editions come out frequently, and the quality of updating varies.
The same book may be reissued through another publisher.
We actively encourage medical students and faculty to submit their opinions

and ratings of these basic science review materials so that we may update
our database. (See p. xvii, How to Contribute.) In addition, we ask that
publishers and authors submit for evaluation review copies of basic science
review books, including new editions and books not included in our
database. We also solicit reviews of new books or suggestions for alternate
modes of study that may be useful in preparing for the examination, such as
flash cards, computer software, commercial review courses, and Web sites.
Disclaimer/Conflid of Interest Statement
No material in this book, including the ratings, reflects the opmwn

or influence of the publisher. All errors and omissions will gladly be
corrected if brought to the attention of the authors through our blog at
www.firstaidteam.com. Please note that USMLE-Rx and the entire First Aid
for the USMLE series are publications by the senior authors of this book;
their ratings are based solely on recommendations from the student authors
of this book as well as data from the student survey and feedback forms.
58 6 SECTION IV TOPRATED REVIEW RESOURCES Q UESTION BANKS
QUEST I ON BANKS
USMLEWorld Qbank $99-$399 Test/2000 q

USM LEWoRLD
www.usmleworl d .com
An excellent bank of wel l-constructed questions that closely mirror those found on Step l. Questions
demand multistep reasoning and are often more difficult than those on the actual exam . Offers excel
lent, detailed explanations with figures and tables. Features a number of test customization and analy
sis options. Unfortunately, the program does not allow other appl ication windows to be open for ref
erence. Users can see cumulative results both over time and compared to other test takers. Another
useful fre is that it gives a percentile score so the user can evaluate his or her performance compared
to a large pool of other users who completed the same questions. Can be accessed through iPhone or
Androic mobile apps.
Kaplan Qbank $99-$199 Test/2400 q

KAPLAN
www.kaplanmedical .com
A h igh-qual ity question bank that covers most content found on Step l, but sometimes emphasizes
recall of overly specific details rather than integrative problem-solving skills. Test content and perfor
mance feedback can be organized by both organ system and discipl ine. Includes detailed explanations
of all answer choices. Users can see cumulative results both over time and compared to other test tak
ers. Can be accessed through iPhone or Android mobile apps .
USMLE-Rx Qmax $99-$199 Test/3000 q

MEDIQ LEARNING
www. usmle-rx.com
A well-priced question bank that offers Step !-style questions accompanied by thorough explanations.
Some obscure material is omitted, making it more straightforward than other question banks. Each
explanation incl udes h igh-yield facts and references from First Aid. H owever, the proportion of ques
tions covering a given subject area does not always reflect the actual exam's relative emphasis. Ques
tion stems occasionally rely on "buzzwords." Most useful to help memorize First Aid facts. Provides
detailed performance analyses .
USMLE Consult $75-$395 Test/2 500 q

B ELSEVIER
www. usmleconsult.com
A sol id question bank that can be divided accordii1g to discipline and subject area . Questions are more
straightforward than those on actual exam. Offers concise explanations with l i nks to Student Consult
and First Consult content. Users can see cumulative results both over time and compared to other test
takers. Student Consult also offers a Robbins Pathology Test Bank ($3 5 for l month, $65 for 3 months)
featuring 5 00 U S MLE-style questions. Purchase of any question bank i ncludes use of the Scorrelator,
a tool that predicts your USMLE Step l score from your performance on the question bank. Limited
student feedback on Student Consult products.
TOPRATED REVIEW RESOURCES Q U EST I O N B O O KS SECTION IV 58 7
QUEST I ON BO OKS
First Aid Q&A for the USMLE Step 1 $44.95 Test/ 1 000 q
LE
McGraw-Hill, 2012, 765 pages, ISBN 9780071744027
A great source of approx. 1 000 questions drawn from the USMLE-Rx Step l Qmax test bank, orga
nized according to subj ect. Also features one full-length exam of 3 36 questions. Questions are easier
than those found on Step l, but provide representative coverage of the concepts typically tested. In
cl udes brief but adequate explanations of both correct and incorrect answer choices.
Kaplan USMLE Step 1 Qbook $25-00 Test/8 50 q

a+ KAPLAN
Kaplan, 2011,480 pages, ISBN 9781419550478
A resource consisting of seventeen 5 0-question exams organized by the traditional basic science dis
ciplines. S imilar to the Kaplan Qbank, and offers good USM LE-style questions with clear, deta iled
explanations; however, lacks the classic images typically seen on the exa m . Also includes a guide on
test-taking strategies.
PreTest Clinical Vignettes for the USMLE Step 1 $29-95 Test/322 q

a+ McG RAW-HILL
C l inical vignette-style questions with detailed explanations, divided into seven blocks of 46 questions
covering basic sciences. I n general, questions are representative of the l ength and compl exity of those
on Step l. I mages ( including pathology slides) are black and white and sometimes difficult to interpret.
One of the better books i n the PreTest series.
Lange Q&A: USMLE Step 1 $45-95 Test/ 1 200 q

a KING
McGraw-Hill, 2008,52 8 pages, ISBN 9780071492195
Offers many questions organized by subj ect area along with three comprehensive practice exams.
Questions are often challenging but are not always representative of Step l styl e - difficult concepts
are tested, but multistep reasoning is not. Includes detailed explanations of both correct and incorrect
answer choices. Black-and-wh ite images only.
NMS Review for USMLE Step 1 $48-95 Test/8 50 q

a LAzo
Lippincott Williams & Wilkins, 2005,480 pages+ CD-ROM, ISBN 9780781779210
A text and C D-ROM that offers 1 7 practice exams with answers. Some questions are too picky or dif
ficult. An notated explanations are well written but are sometimes unnecessarily detailed. The six pages
of color plates are helpfu l . The CD-ROM attempts to simulate the computer-based testi ng format but
is disorganized.
58 8 SECTION IV TOPRATED REVIEW RESOURCES INTERNE T SITES
INTERNET SITES
WebPath: The Internet Pathology Laboratory Free Revi ew/

http://library.med.utah.edu/WebPath/ Test/ 1 1 00 q
Features more than 2000 outstanding gross and microscopic images, clinical vignette questions, and
case studies. Includes eight general pathology exams and 1 1 system-based exams with approximately
1 000 questions. Also features 1 70 questions associated with images. Questions are useful for reviewing
boards content but are typically easier and shorter. No multimedia practice questions. Tremendous
resource, but in need of an update to retai n Step 1 usefulness.
Lippincott's 350-Question Practice Test for USMLE Step 1 Free Test/3 5 0 q

a+ LI PPINCOTT WI LLIAMS & WI LKI N S
www.lww.com/medstudent/usmle
A free, full-length, seven-block, 3 5 0-question practice exam in a format similar to that of the real Step
l. Questions are easier than those on the actual exam, and the explanations provided are sparse. Users
can bookmark questions and can choose between taking the test all at once or by section.
The Pathology Ciuy Free Review

a FRIEDLAN DER
www.pathguy.com
A free Web site containing extensive but poorly organized information on a variety of fundamental
concepts in pathology. A h igh-yield summary intended for USMLE review can be found at www.path
guy.com/meltdown.txt, but the information given is limited by a lack of images and frequent digres-
SIOnS.
Radiopaedia.org Free Casesnest

a www.radiopaedia.org
A user-friendly Web site with thousands of well-organized radiology cases and articles. Encyclopedia
entries contai n h igh-yield bullet points of anatomy and pathology. I mages contai n detailed descrip
tions but no arrows to demarcate findings. Quiz mode allows students to make a diagnosis based on
radiographic findings . Content may be too broad for boards review but is a good complement to classes
and clerksh ips.
The Whole Brain Atlas Free Review

a- JOH N SON
www.med.harvard.edu/AANLIB!I1ome.html
A collection of h igh-qual i ty brain M R and CT images with views of normal and diseased brains. The
i nterface is technologically impressive but complex, and many images are without explanations. Sub
ject matter is overly specific, l i miting its use as a boards review study tool. Useful adj unct to classes and
clerkships.
Digital Anatomist Interactive Atlases Free Review

a- UN IVERSITY OF WASHI NGTON
www9.biostr.washington.edu/da.html
A good site containing an interactive neuroanatomy course along with a three-dimensional atlas of the
brain, thorax, and knee. Atlases have computer-generated images and cadaver sections. Each atlas a lso
has a quiz in which users identify structures in the slide images; however, questions do not focus on
high-yield anatomy for Step l.
TOP-RATED REVIEW RESOURCES COMPREHENSI VE SECTION IV 58 9
COM PRE HENSIVE
First Aid Cases for the USMLE Step 1 $44.95 Review

LE
A series of more than 400 high-yield cases divided into secti ons by organ system. Each case features
a paragraph-long c l i nical vignette with relevant images, followed by questions and short, high-yield
explanations. Offers great coverage of many frequently tested concepts, and integrates subject matter in
the discussion of a si ngle vignette. A good source of questions to revi ew material outl ined in First Aid
for the USMLE Step 1.
USMLE Step 1 Secrets $39.95 Review

B ROWN
Elsevier, 2008, 740 pages, ISBN 9780323054393
Clarifies difficult concepts in a concise, easy-to-read manner. Employs a case-based format and inte
grates information well . Complements other boards study resources, with a focus on understanding
preclinical fundamentals rather than on rote memorization. S l ightly long for last-minute board cram
mmg.
medEssentials for the USMLE Step 1 $54.99 Review

MANLEY
Kaplan, 2012, 588 pages, ISBN 9781609780265
A comprehensive review divided into general principles and organ systems, and organized using high
yield tables and figures . Excellent for visual learners, but can be overly deta iled and time consuming.
Also includes color i mages in the back along with a monthly subscription to onl ine interactive exer
cises, although these are of l imited value for Step l preparation .
Deja Review: USMLE Step 1 $24.95 Review

NAHEEDY
A comprehensive resource featuring questions and answers in a two-column, quiz-yourself format simi
lar to that of the Recall series, divided according to discipl ine. Features a section of high-yield cl inical
vignettes along with usefu l mnemonics throughout. Contains a few mistakes, but remains a good alter
native to Rash cards as a last-minute review before the exa m .
Cases & Concepts Step 1 : Basic Science Review $42.95

a+
Review
(AUG H EY
Lippincott Williams & Wilkins, 2009, 400 pages, ISBN 9780781793919
One hundred sixteen cl inical cases integrating basic science with clinical data, followed by U S M LE
style questions with answers and rationales. Th umbnail and key-concept boxes h ighl ight key facts.
Limited student feedback.
Kaplan's USMLE Step 1 Home Study Program

a+
$499.00 Review
KAPLAN
Kaplan, 2008, 1900 pages, ISBN OS4005C
A resource consisting of two general principle and two organ system review books. All are highly com
prehensive, but can be overwhelmingly lengthy if they are not started very early. Although costly, the
progra m can serve as an excell ent reference for studying by virtue of its detail . Books can be purchased
at www.kaptest.com.
59 0 SECTION IV TOP-RATED REVIEW RESOURCES COM PREHE N S IVE
First Aid for the Basic Sciences: General Principles $69.95 Review
a+ LE
Excellent comprehensive review of the basic sciences covered i n year l of medical school . S imilar
to the first part of First Aid, organized by discipl i ne, and includes hundreds of ful l-color i mages and
tables. Best if started with fi rst-year coursework and then used as a reference during boards preparation.
First Aid for the Basic Sciences: Organ Systems $89.95 Review
a+ LE
A comprehensive review of the basic sciences covered i n year 2 of medical school . S i milar to the
second part of First Aid, organized by organ system, and includes hundreds of full-color i mages and
tables. Best if started with second-year coursework and then used as a reference during boards prepa
ration . Each organ system contains discussion of embryology and anatomy, physiology, pathology,
pharmacology, and a h igh-yield rapid review section.
Step-Up to USMLE Step 1 $46.95 Review

a+ M EHTA
An organ system-based review text with clinical vignettes that is useful for integrating the basic sci
ences covered in Step l. The text is composed primarily of outl ines, charts, tabl es, and diagrams, mak
ing the depth of material covered somewhat limited. Includes access to a sample online question bank.
USMLE Step 1 Recall: Buzzwords for the Boards $46.95 Review

a+ REI N H EI M E R
A review of core Step l topics presented in a two-column, qu iz-yourself format. Best for a qu ick last
minute review before the exa m . Covers many i mportant subjects, but not comprehensive or tightly
organized. Sometimes focuses on obscure details. Compare with the Deja Review series. Includes all
questions and answers i n downloadable MP3 files so that files can be used on any digital audio play
back device.
Underground Clinical Vignettes: Step 1 Bundle $ 189.95 Review

a+ SWANSON
Lippincott Williams & Wilkins, 2007, 9 volumes, ISBN 9780781763622
A bundle that i ncludes nine books. Designed for easy quizzing with a group. Case-based vignettes pro
vide a good review supplement. Best when started early with coursework or when used i n con j u nction
with another primary review resource.
USMLE Step 1 Mode Ridiculously Simple $29.95 Review

a CARL
MedMaster, 2010, 400 pages, ISBN 9780940780910
A quick and easy read. Uses a table and chart format organized by subject, but some charts are poorly
labeled . Consider as an adj unct to more comprehensive sources.
TOP-RATED REVIEW RESOURCES ANATOMY, EMBRYO LO G Y, AND NEUROSCIEN CE SECTION IV 59 1
ANATOMY, EMBRY O L O G Y, AND NEURO S C IENCE
High-Yield Embryology $32.95 Review

DU DEK
A good review of a relatively low-yield subject. Offers excellent organization with cli nical correlations.
I ncludes a high-yield l i st of embryologic origins of tissues.
High-Yield Neuroanatomy $28.95 Review(fest/50

FIX Q&A provided
Lippincott Williams & Wilkins, 2008, 160 pages, ISBN 9780781779463 online
An easy-to-read, straightforward format with excel lent diagrams and ill ustrations. Features a useful atlas
of brain section images, a glossary of important terms, an appendicized table of neurologic lesions, and
an expanded i ndex. Overall, a great resource, but more detailed than what is requ i red for Step l.
Underground Clinical Vignettes: Anatomy $2Z95 Review/

SWANSON Test/20 q
Concise clinical cases ill ustrating approximately 1 00 frequently tested diseases with an anatomic ba
sis. Cardinal signs, symptoms, and buzzwords are highl ighted. Also includes 20 additional boards-style
questions. A useful source for isolating important anatomy concepts tested on Step l.
USMLE Road Map: Gross Anatomy $31.95 Review/

WHITE Test/ l SO q
An overview of h igh-yield gross anatomy with clinical correlations throughout. Also features numerous
effective charts and cl inical problems with explanations at the end of each chapter. Features good in
tegration of facts, but may be overly detailed and offers few illustrations. Lack of Step 1 -related figures
limits usefulness. May requ ire an anatomy reference text.
High-Yield Gross Anatomy $29.95 Review

a+ D U DEK
A good review of gross anatomy with some cl inical correlations. Contains well-labeled, high-yield ra
diographic images, but often goes into excessive detail that is beyond the scope of the boards.
Atlas of Anatomy $74.95 Review

a+ G I LROY
Thieme, 2008, 672 pages, ISBN 9781604060621
A good atlas with more than 2200 high-quality, uncluttered ill ustrations. Includes cli nical correlates
and a brief i ntroduction to new topics. Radiographs, MRis, CT scans, and endoscopic views of the or
gans also included. Best if used as a reference or during coursework. Access to accompanying Web site
with more than 600 illustrations, label on/off function, and timed self-tests also provided.
592 SECTION IV TOPRATED REVIEW RESOURCES ANATOMY, EMBRYO l O G Y, AND NEUROSCIENCE
Clinical Anatomy Made Ridiculously Simple $29.95 Review

a+ GOLDBERG
An easy-to-read text offering simple diagrams along with numerous mnemonics and amusing associa
tions. The humorous style has variable appeal for students, so browse before buying. Offers good cov
erage of selected topics. Best if used during coursework. Incl udes more deta il than typically tested on
Step l.
Crash Course: Anatomy $30.95 Review

a+ G RANGER
Part of the C rash Course review series for basic sciences, integrating clinical topics. Offers two-color
illustrations, handy study tools, and Step 1 review questions. Incl udes online access. Provides a sol id
review of anatomy for Step l . Best if started early.
Rapid Review: Gross and Developmental Anatomy $39.95 Review/

a+ MOORE Test/4 5 0 q
A deta iled treatment of basic anatomy and embryol ogy, presented in an outl ine format similar to that
of other books i n the series. More detailed than necessary for boards review. Contains hi gh-yield charts
and figures throughout, in color. Includes two 50-question tests with extensive explanations, with an
additional 3 5 0 questions available onli ne.
Deja Review: Neuroscience $19.95 Review

a+ TREM BLAY
A resource that features questions and answers in a two-col umn, quiz-yoursel f format similar to that of
the Recall series. Includes several useful diagrams and CT images. A perfect length for Step I neuro
physiology and anatomy review.
USMLE Road Map: Neuroscience $31.95 Review/

a+ WH ITE Test/300 q
An outl ine review of basic neuroanatomy and physiology with clinical correlations throughout. Also
features high-yield facts in boldface along with numerous tables and figures. C l inical problems with
explanations are given at the end of each chapter. May be overly detailed for Step I review, but a good
tool to use as a reference.
Elsevier's Integrated Anatomy and Embryology $3Z95 Review

B BoGART
Part of the Integrated series that seeks to l ink basic science concepts across disciplines. Case-based and
Step 1 -style questions at the end of each chapter allow readers to gauge their comprehension of the
material. Includes online access. Best if used during coursework. Limited student feedback.
I
TOP-RATED REVIEW RESOURCES ANATOMY, EMBRY O LO G Y, AND NEUROSCIENCE SECTION IV 593
BRS Embryology $39.95 ReviewH'est

B DUDEK
An outline-based review of embryology that is typical of the BRS series. Offers a good review, but has
l i mited i l lustrations and includes much more detail than is required for Step l. A discussion of con
genital malformations is included at the end of each chapter along with relevant questions. The com
prehensive exam at the end of the book is h igh yield.
Anatomy Flash Cards $34.95 Flash cards

B G I LROY
Thieme, 2009, 376 flash cards, ISBN 9781604060720
High-qual i ty illustrations with numbered labels on one side and answers on the other for self-testing.
Occasional radiographic i mage . Best if used with coursework; too long for boards preparation. Limited
student feedback.
Clinical Neuroanatomy Made Ridiculously Simple $22.95 ReviewH'est/

B GOLDBERG Few q
MedMaster, 2007, 96 pages+ CD-ROM, ISBN 9780940780576
An easy-to-read, memorable, and simplified format with clever diagrams. Offers a quick, h igh-yield
review of clinical neuroanatomy, but does not serve as a comprehensive resource for boards review.
Places good emphasis on c l i nically relevant pathways, cranial nerves, and neurologic diseases. Includes
a C D-ROM with CT and M R i mages as wel l as a tutorial on neurologic localization. Compare with
High-Yield Neuroanatomy.
Netter's Anatomy Flash Cards $33.25 Flash cards

B HANSEN
Saunders, 2011, 324 pages, ISBN 9781437716757
Netter's i l lustrations with numbered labels on one side and answers on the other for self-testing. Each
card incl udes a commentary on the structures and a c l i nical correlation. Best if used with coursework,
but much too detailed for boards preparation. Lack of embryology correlates h ur ts Step l usefulness.
I ncludes online access with additional bonus cards and more than 300 multiple-choice questions. Ex
cellent iPhone app costs approximately the same and has additional functional ity.
PreTest Neuroscience $29.95 Test/500 q

B S I EGEL
A high-yield introduction followed by 500 questions with detailed explanations. The question format
differs significantly from that typically found on Step l. Sparse, poor-quality images.
Case Files: Gross Anatomy $33.95 Review

B Tov
McGraw-Hill, 2008, 384 pages, ISB 9780071489805
Review text that incl udes 5 3 well-chosen cases with discussion, comprehension questions, and a box of
take-home pearls. Tables are good, but schematics are black and white and not representative of S tep
l. A reasonable book to work through for those who benefit from probl em-based learning.
59 4 SECTION IV TOP-RATED REVIEW RESOURCES ANATOMY, EMBRY O LO G Y, AND NEUROSCIENCE
Rapid Review: Neuroscience $38.95 Review

a WEYH E N M EYER
A deta iled treatment of neuroscience, presented in an outl ine format similar to that of other books in
the series. Should be started early given its extensive treatment of a relatively narrow topi c . Contains
high-yield charts and figures throughout. Includes two 50-question tests with extensive explanations as
well as 2 5 0 additional questions online.
Gray's Anatomy for Students Flash Cards $36.95 Flash cards

a- D RAKE
These flash cards feature renowned Gray's illustrations on the front and labels on the back for self
testing. Notes on c l inical importance and reference to accompanying textbook given on back. Much
too detailed information on a relatively low-yield subj ect for effective boards studying. Limited student
feedback.
BRS Gross Anatomy Flash Cards $34.95 Flash cards

a- SWANSON
C l i nical anatomy cases presented i n flash-card format. Cases are too specific for boards preparation,
and anatomy basics and radiographic images are generally excluded. Best suited to students who are
already relatively well versed in anatomy.
Case Files: Neuroscience $33.95 Review

a- Tov
Includes 48 clinical cases with lengthy discussion and 3-5 multiple-choice questions at the end of each
case . Cases are well chosen, but the discussion is too lengthy. Questions are not the most representa
tive of those seen on boards.
TOP-RATED REVIEW RESOURCES BE H AV I ORAL S C I EN CE SECTION IV 59 5
BEHAV I ORAl SCIENCE
High-Yield Behavioral Science $12.95 Review

A FAD EM
An extremely concise yet comprehensive review of behavioral science for Step l. Offers a logical pre
sentation with charts, graphs, and tables, but lacks questions. Features brief but adequate coverage of
statistics. Overall, an excellent, h igh-yield resource at an unrivaled price.
BRS Behavioral Science $39.95 Review/

FAD EM Test/500 q
An easy-to-read outl ine-format review of behavioral science. Offers good, detailed coverage of essential
topics, but at a l evel of depth that often exceeds what is tested on Step l. Incorporates excellent tables
and charts as well as a short but complete statistics chapter. Features high-quality review questions, i n-
eluding a 1 00-question comprehensive exam.
High-Yield Biostatistics $28.95 Review

G LASER
A well-written, easy-to-read text that offers extensive coverage of epidemiology and biostatistics. In
cludes good review questions and tables, but somewhat lengthy given the low-yield nature of the sub
ject matter on Step l. New edition expected in 20 1 3 .
High-Yield Brain & Behavior $34.95 Revi ew

a+ FAD EM
Part of the new H igh-Yield Systems series that covers embryology, gross a natomy, radiology, h istology,
physiology, microbiology, and pharmacology as they relate to the nervous system. Written by the same
author as the High-Yield Behavioral Science and BRS Behavioral Science texts . Overa l l , provides a good
review of neuroscience and behavioral science but too much deta il for most Step 1 takers.
Underground Clinical Vignettes: Behavioral Science $27.95 Review/

a+ SWANSON Test/20 q
Concise clinical cases i l lustrating commonly tested diseases in behavioral science. Cardinal signs,
symptoms, and buzzwords are h ighl ighted. Useful for picking out i mportant points i n th is very broad
subject, but requi res supplementation from other review sources. Also includes 20 Step 1 -style ques-
tions.
Kaplan USMLE Medical Ethics $39.00

B
Review
FISCHER
Kaplan, 2009, 216 pages, ISBN 9781419553141
Includes 1 00 cases, each followed by a single question and a detailed explanation. Also offers guide
li nes on how Step 1 requi res test takers to th ink about eth ics and medicolegal questions. Unfortunately,
a lengthy review for such a l ow-yield subj ect.
59 6 SECTION IV TOPRATED REVIEW RESOURCES BE H AVIORA l S CIENCE
Deja Review: Behavioral Science $19.95 Review

B QU I N N
Features questions and answers in a two-column, qu iz-yourself format similar to that of the Recall se
ries. Coverage of some topics is too lengthy for Step l review purposes, and order of information is
nearly opposite that of First Aid. Limited student feedback.
Rapid Review: Behavioral Science $39.95 Revi ew/

B STEVENS Test/350 q
Similar in style to other books in the Rapid Review series. Provides a good but low-yield review of a
broad subj ect. I ncludes 1 00 questions and explanations along with an additional 250 questions online.
TOP-RATED REVIEW RESOURCES B I O CHEM ISTRY SECTION IV 597
BIOC H E M ISTRY
Lange Flash Cards Biochemistry and Genetics $34.95 Flash cards

A BARON
McGraw-Hill Medical, 2005, 300 flash cards, ISBN 9780071447362
Great flash cards featuring a clinical vignette on one side and concise discussion on th e other. Each
section contains 2-3 cards on biochemistry principles. Excellent resource for boards studying, but no
carrying case included.
Rapid Review: Biochemistry $39.95 Review/

PELLEY Test/350 q
Elsevier, 20 l l , 186 pages, ISBN 9780323068871
A review of basic topics in biochemistry. Presented in outl ine format, but often goes beyond the level
of detail tested on Step l. H i gh-yield disease correlation boxes are especially usefu l . E xcellent tables
and helpful figures are included throughout the text. Best if used as a reference to clarify topics. Offers
350 questions online.
Lippincott's Illustrated Reviews: Biochemistry $54.95 Review/

a+ (HAM PE Test/250 q
An excellent, integrative, and comprehensive review of biochemistry that incl udes good clinical cor
relations and h ighly effective color diagrams. Extremely deta iled and requi res significant time com
mitment, so it should be started with first-year coursework. H i gh-yield summaries at the end of each
chapter. Comes with access to the companion Web site with U S MLE-style questions.
USMLE Road Map: Biochemistry $31.95 Review

a+ MACDONALD
A clear, readable outl ine review of biochemistry with good four-color figures . H igh-yield references to
important diseases of metabolism are scattered throughout, but coverage of clinical correlations is not
comprehensive . Incl udes brief review questions at the end of each chapter. Lacks "big picture" integra
tion of related pathways. Limited student feedback.
Deja Review: Biochemistry $19.95 Review

a+ MANZO U L
Features questions and answers in a two-column, quiz-yourself format similar to that of the Recall se
ries. Includes a helpful chapter on molecular biology and many good black-and-wh ite diagrams. More
detailed than is usually tested on Step l.
BRS Biochemistry, Molecular Biology, and Genetics $42.95

&+
Review/Test
SWANSON
A highly detailed review featuring many excellent figures and clinical correlations h ighl ighted in col
ored boxes. The biochemistry portion incl udes much more detail than requ i red for Step l , but may
be useful for students without a strong biochemistry background or as a reference text. The molecular
biology section is more focused and h igh yield. Also offers a chapter on laboratory techniques and a
comprehensive, 1 20-question exa m . Questions are cli nically oriented.
59 8 SECTION IV TOPRATED REVIEW RESOURCES BI O C H E M I STRY
Underground Clinical Vignettes: Biochemistry $27.95 Review/

a+ SWANSON Test/2 0 q
Concise clinical cases illustrating approximately 1 00 frequently tested diseases with a biochemical
basis. Cardinal signs, symptoms, and buzzwords are h ighl ighted. Also i ncludes 20 additional boards
style questions. A nice review of "take-home" points for biochemistry and a usefu l supplement to other
sources of review.
Clinical Biochemistry Made Ridiculously Simple $22.95 Review

a GOLDBERG
MedMaster, 2004, 93 pages+ foldout, ISBN 9780940780309
A conceptual approach to clinical biochemistry, presented with humor. The casual style does not ap
peal to all students. Offers a good overview and integration of all metabol ic pathways. Includes a 2 3-
page clinical review that is very high yield and crammable. Also contains a unique foldout "road map"
of metabol ism. For students who already have a sol id grasp of biochemistry.
BRS Biochemistry and Molecular Biology Flash Cards $39.95 Flash cards
a SWANSON
Quick-review Rash cards covering a range of topics in biochemistry and molecular biology. Inadequate
for learning purposes, as cards provide only snippets of isolated information and conta i n some i naccu-
racies.
High-Yield Biochemistry $29.95 Review

a WI LCOX
A concise and crammable text i n outline format with good cl inical correlations at the end of each
chapter. Features many diagrams and tables. Best used as a supplemental review, as explanations are
scarce and details are l imited .
Case Files: Biochemistry $33.95 Review

a- ToY
I ncludes 5 1 clinical cases with comprehensive discussion and summary box, but too much depth and
not enough breadth for boards. Some cases will almost certainly not be tested. Questions at the end of
each case are not representative of those seen on Step l.
PreTest Biochemistry and Genetics $29.95 Test/500 q

a- WI LSON
Difficult questions with detailed, referenced explanations. Features a h igh-yield appendix, but overal l
is an overly detailed review o f a relatively low-yield subject.
TOPRATED REVIEW RESOURCES CEL L B I O LO G Y AND H I STO L O G Y SECTION IV 599
CE L L BI O LO G Y AND H I STO L O G Y
High-Yield Cell and Molecular Biology $29.95 Review

DUDEK
Cellular and molecular biology presented in an outl ine format, with good diagrams and cl inical cor
relations. Includes U S M LE-tested subj ects that other review resources do not cover in deta i l , such as
laboratory techniques and second-messenger systems. ot all sections are equally usefu l ; many stu
dents skim or read select chapters. Contains no questions or vignettes.
Rapid Review: Histology and Cell Biology $.39.95 Review/

a+ BURNS Test/3 5 0 q
A resource whose format is similar to that of other books in the Rapid Review series. Features an out
line of basic concepts with numerous charts, but histology images are l i mited . Two 5 0-question multi
ple-choice tests are presented with explanations, along with 2 5 0 more questions onl ine.
Deja Review: Histology and Cell Biology $19.95 Review

a+ SONG
ries. Sections are divided by organ system and vary in qual ity. H istology images are few and are printed
in black and white. Good for a quick review, but some sections are lower-yield than others.
Elsevier's Integrated Genetics $.37.95 Review

a ADKISON
Part of the Integrated series that seeks to l ink basic science concepts across discipl ines. C ase-based and
Step ] -style questions at the end of each chapter allow readers to gauge their comprehension of the
material . Incl udes online access. Best if used during coursework; length and comprehensiveness make
th is less useful as stand-alone Step l prep materia l .
High-Yield Genetics $28.95 Review

a DUDEK
A concise, clinically oriented summary of genetics in the popular outl ine format. Ill ustrated with sche
matic line drawings and photographs of the most clinically relevant diseases. By no means a n exhaus-
tive resource.
High-Yield Histology $26.95

B
Review
DUDEK
A quick and easy review of a relatively low-yield subject. Tables include some h igh-yield information .
Contains good pictures. The appendix features classic electron micrographs. Too lengthy for S tep 1
review.
600 SECTION IV TOP-RATED REVIEW RESOURCES CE L L B I O L O G Y AND H I STO LO G Y
BRS Cell Biology and Histology $39.95 Review/

a GARTN ER Test/5 0 0 q
Covers concepts in cell biology and histology in an outl ine format. Can be used alone for cell biology
study, but does not include enough h istology images to be considered comprehensive on that subj ect.
Includes more detail than is required for Step l , and information is less h igh yield than that of other
books in the B RS series.
Crash Course: Cell Biology and Genetics $49.95 Review

a lAMB
Part of the C rash Course review series for basic sciences, integrating clinical topics. Offers two-color il
l ustrations, handy study tools, and Step l review questions. Incl udes online access. Too much coverage
for a low-yield subj ect.
USMLE Road Map: Genetics $31.95 Revi ew

a SACK
Efficient review of genetics with an emphasis on clinical correlations. Incl udes a few questions at the
end of each chapter that are best suited to test comprehension and are not representative of Step l.
Use only if genetics is a weak subject after reviewing First Aid; otherwise, too much depth for a quick
review.
USMLE Road Map: Histology $31.95 Review

a 5H EEDLO
A concise review book with many clinical correlations. Questions at the end of each chapter are not in
clinical vignette format but are suitable for testing comprehension . Black-and-white images. Good for
a quick review of a low-yield subj ect.
PreTest Anatomy, Histology, and Cell Biology $29.95 Test/500 q

a- KLEI N
A resource containing difficult questions with detailed answers as well as some black-and-wh ite im
ages. Requires extensive time commitment, and much of the material is beyond what is requi red for
Step l. The most useful part of the book is the high-yield facts section at the beginning, which is di
vided according to discipl ine.
Wheater's Functional Histology $79.95 Review

a- YOU N G
A color atlas with i l lustrations of normal histology with image captions and accompanying text. Far too
detailed to use for boards studying given the low-yield nature of the material , but usefu l as a course
work text or boards reference.
TOP RATED REVIEW RESOURCES MI CROBI O LO G Y AND I MMUNO L O G Y SECTION IV 60 1
M ICROBIO L O G Y AND I M M UNO L O G Y
The Big Picture: Medical Microbiology $49.95 Review

CHAM BERLAI N
Excellent ful l-color atlas of pathogens and clinical signs of infection. Discussion targets quick boards
review. Especially good for visual learners. H igh-yield appendix. Incl udes 1 00 practice questions with
discussion.
Deja Review: Microbiology & Immunology $ 19.95 Review

CHEN
Features questions and answers in a two-column, quiz-yourself format similar to that of the Recall
series. Provides an excellent review of high-yield facts. Good mnemonics, but only a few images of
pathogens i n black and wh ite . Good review text on a high-yield topic.
Clinical Microbiology Made Ridiculously Simple $34.95 Review

G LADWI N
An excellent, easy-to-read, detailed review of microbiology that includes clever and memorable mne
monics. The styl e of the series does not appeal to everyone. The sections on bacterial disease are most
high yield, whereas the pharmacology chapters lack sufficient deta i l . Recommended to read during
coursework and review the concise charts at the end of each chapter during boards review. All images
are cartoons; no microscopy images that appear on boards. Requi res a supplemental source for immu
nol ogy.
Microcards Flash Cards $36.95 Flash cards

HARPAVAT
A well-organized and complete resource for students who like to use flash cards for review. Cards fea
ture th e clinical presentation, pathobiology, diagnosis, treatment, and high-yield facts for a particular
organism. Some cards also include excellent Aow charts organizing important classes of bacteria or
viruses. Overall, a good review resource, but at times it is overly detailed, requiring a significant time
commitment. Also useful as an aid with coursework.
High-Yield Microbiology and Infectious Diseases $28.95 Revi ew/

HAWLEY Test/200 q
A very concise review of central concepts and keywords, with chapters organized by microorganism .
The last few sections contain brief questions and answers organized by organ system . Also offers a use
ful chapter on "microbial comparisons" that groups organisms by shared virulence factors, lab results,
and the l ike. Some students may prefer alternative resources with more explanations.
602 SECTION IV TOP-RATED REVIEW RESOURCES M I CROBI O L O G Y AND I MMUNO LO G Y
High-Yield Immunology $28.95 Review

JOH NSON
Accurately covers high-yield immunology concepts, although at times it includes more detail than
necessary for Step 1 preparation . Good for quick review. The newest edition includes many improve-
ments.
Review of Medical Microbiology $39.95 Test/5 5 0 q

M U RRAY
A resource that features Step 1 -style questions divided into bacteriology, virology, mycology, and
parasitology. All questions are accompanied by detailed explanations, and some are paired with high
quality images. Questions are similar to those on Step 1 and provide a nice review. Supplements M ur
ray's Medical Microbiology.
Medical Microbiology and Immunology Flash Cards $35.95 Flash cards

ROSENTHAL
Flash cards covering the microorganisms most commonly found on Step l. Each card features full
color microscopic images and clinical presentations on one side and relevant bug information i n con
j unction with a short case on the other side. Also includes Student Consult online access for extra
features. Overemphasizes "trigger words" related to each bug. Not a comprehensive resource.
Lange Microbiology & Infectious Diseases Flash Cards $31.45 Flash cards
SOMERS
McGraw-Hill, 2010, 200 flash cards, ISBN 9780071628792
Contains a clinical vignette on one side and discussion on the other. Excellent condensed summaries
of pathogens, but l i mited by lack of images that will be tested on boards. Printed on thinner paper than
the Biochemistry 6 Genetics component of the series, reducing durability.
Underground Clinical Vignettes: Microbiology Vol. 1: $22.95 Review/

Virology, Immunology, Parasitology, Mycology Test/20 q
SWANSON
A resource containing 1 00 concise clinical cases that illustrate frequently tested diseases in microbiol
ogy and i mmunology. Cardinal signs, symptoms, and buzzwords are highl ighted. Also includes 20 ad
ditional boards-style questions. Best if used as a supplement to other review resources.
Underground Clinical Vignettes: Microbiology Vol. II: $22.95 Review/

Bacteriology Test/20 q
SWANSON
A resource containing 1 00 concise cli nical cases that illustrate frequently tested diseases i n microbiol
ogy and immunology. Cardinal signs, symptoms, and buzzwords are h ighl ighted. Also includes 20 ad
ditional boards-style questions. Best if used as a supplement to other review resources.
I
TOP-RATED REVIEW RESOURCES MI CRO B I O LO G Y AND I MMUNO L O G Y SECTION IV 603
Basic Immunology $64.95 Review

a+ ABBAS
A useful text that offers clear explanations of complex topics in immunology. Best if used during th e
year in conj unction with coursework and later skimmed for quick Step l review. Includes colorful dia
grams, images, tables, and a length y glossary for further study. Features online access.
Elsevier's Integrated Immunology and Microbiology $40.95 Review

a+ ACTOR
Part of th e Integrated series that seeks to link basic science concepts across discipl ines. Case-based and
Step l -style questions at the end of eac h chapter allow users to gauge th eir compre h ension of the ma
terial . Includes online access. Best if used during coursework. Limited student feedback.
Case Studies in Immunology: Clinical Companion $49.95 Review

a+ GEHA
Garland Science, 2007, 328 pages, ISBN 9780815341451
A text that was originally designed as a clinical companion to Janeway's Immunobiology. Provides a
great synopsis of the major disorders of immunity in a cl inical vignette format. Integrates basic and
clinical sciences. Features excellent images and illustrations from Janeway, as well as questions and
discussions.
Review of Medical Microbiology and Immunology $53.00 Review/

a+ LEVI N SON Test/6 54 q
A clear, comprehensive text with outstanding diagrams and tables. Includes an excellent immunology
section . The "Summary of Medically Important Organisms" ( Part IX) is high ly crammable. Can be de
tailed and dense at points, so best if started early with coursework. Includes practice questions of mixed
quality and does not provide detailed explanation of answers. Compare with Lippincott's Illustrated
Reviews: Microbiology.
Review of Immunology $33.95 Test/ 5 00 q

a+ LICHTMAN
Complements Abbas's Cellular and Molecular Immunology and Basic Immunology textbooks. C on
tains 500 boards-style questions featuring full-color ill ustrations along with explanations of all answer
choices. A good resource for questions i n a lower-yield topic. Limited student feedback.
Rapid Review: Microbiology and Immunology $39.95

a+
Review/
ROSENTHAL Test/400 q
A resource presented in a format similar to that of other books in the Rapid Review series. Contains
many excellent tables and figures, but requ i res significant time commitment and is not as high yield as
comparable review books. Includes access to companion Web site with more than 400 questions.
604 SECTION IV TOPRATED REVIEW RES OURCES MICROBIO LO G Y AND IMMUNO L O G Y
Lippincott's Illustrated Reviews: Immunology $54.95 Reviewffest/

B DOAN Few q
A clearly written, h ighly detailed review of basic concepts in immunology. Features many useful tables
and review questions at the end of each chapter. Offers abbreviated coverage of immune deficiencies
and autoimmune disorders . Best if started with initial coursework and used as a reference during Step
1 study.
Lippincott's Illustrated Reviews: Microbiology $54.95 Reviewffest/

B HARVEY Few q
A comprehensive, h ighly i l l ustrated revi ew of microbiol ogy that is similar in style to other titles in the
Illustrated Reviews series. Includes a 5 0-page color section with more than 1 5 0 clinical and laboratory
photographs. Compare with Levinson's Review of Medical Microbiology and Immunology.
Pretest: Microbiology $29.95 Review/

B KmERING Test/500 q
Incl udes a short section on high-yield facts followed by 500 questions in a c l i nical vign ette format.
Questions are more difficult than encountered on the boards and some topics discussed are not l ikely
to be tested. A good book to work through with coursework but too low yield for review purposes.
Crash Course: Immunology $49.95 Review

B N OVAK
Part of the C rash Course review series for basic sciences, integrating c l i nical topics. Offers two-color
illustrations, handy study tools, and Step 1 review questions. Includes online access. Good length and
detai l for boards review.
USMLE Road Map: Immunology $3 1.95 Review

B PARMELY
An outl ine review of i mmunology with a special focus on molecular mechanisms and laboratory tech
niques. Features abbreviated coverage of immunologic deficiency and autoimmune diseases that a re
emphasized on Step 1 . Offers a coll ection of brief review questions at the end of each chapter. Limited
student feedback.
Case Files: Microbiology $33.95 Review

B Tov
5 0 cli nical microbiology cases followed by a clinical correlation, a discussion with boldfaced buzz
words, and questions. Cases are well chosen, but the text lacks the high-yield charts and tables found
in other books i n the Case Files series. Images are sparse and of poor black-and-white qua l i ty.
(
TOP-RATED REVIEW RESOURCES PATHO L O G Y SECTION IV 605
PAT H O LO G Y
Rapid Review: Pathology $44.95 Review/

GOUAN Test/3 5 0 q
A comprehensive source for key concepts i n pathology, presented in a bulleted outl ine format with
many high-yield tables and color figures . Features detailed explanations of disease mechanisms. In
tegrates concepts across discipl ines with a strong cl inical orientation. Lengthy, so best if started early
with coursework. Includes access to online Qbank.
Pathoma $84.99 and up Review/Lecture

5ATTAR
Pathoma, 218 pages
ovel approach to pathology review, combining a focused textbook with 3 5 hours of onl ine l ectures .
Lectures combine "chalk talk" and slide formats to explain pathogenesis i n an easy-to-understand man-
ner. Excellent feedback from students.
The Big Pidure: Pathology $49.95 Review/

A KEMP Test/ 1 3 0 q
Excellent ful l-color atlas of pathologic images with distilled notes on pathophysiology and treatment.
Good for quick review and especially good for visual learners. The 1 30 questions included at the end
are more straightforward than those seen on boards, but they emphasize i mportant and tricky concepts.
BRS Pathology $39.95 Review/

A SCH NEIDER Test/4 5 0 q
An excellent, concise review with appropriate content emphasis. Chapters are organized by organ sys
tem and feature an outl ine format with bol dfacing of key facts. Includes good questions with expla
nations at the end of each chapter plus a comprehensive exam at the end of the book. Offers well
organized tables and diagrams as well as photographs representative of classic pathol ogy. Contains a
chapter on laboratory testing and "key associations" with each disease. The new edition contains excel
lent color images and access to an online test and i nteractive question bank. Most effective if started
early in conj unction with coursework, as it does not discuss detailed mechanisms of disease pathology.
Pathophysiology for the Boards and Wards $39.95 Review/

AYALA Testn 5 q
A systems-based outl ine with a focus on pathology. Wel l organized with glossy color plates of relevant
pathology and excellent, concise tables. The appendix incl udes a helpful overview of neurology, im
munology, unusual "zebra" syndromes, and high-yield pearls. Features good integration of Step !
relevant material from various subject areas. Compare with Rapid Review: Pathology.
I
606 SECTION IV TOPRATED REVIEW RESOURCES PATH O L O G Y
Lange Pathology Flash Cards $34.95 Flash cards

BARON
McGraw-Hill, 2009, 277 flash cards, ISBN 9780071613057
Flash cards with clinical vignette on one side and discussion including etiology, pathology, clinical
manifestations, and treatment on the other. Good tables to help organize diseases, but lack of images
l imits its utility. Best if used in conj unction with another resource. Printed on thinner paper than the
Biochemistry 6 Genetics component of the series, reducing durabil ity.
Deja Review: Pathology $19.95 Review

DAVIS
Features questions and answers in a two-col umn, quiz-yourself format similar to that of the Recall se
ries. Integrates pathophysiology and pathology. Includes many vignette-style questions, but only a few
images in black and white. Limited student feedback.
Lippincott's Illustrated Q&A $48.95 Review/

Review of Rubin 's Pathology Test/ 1 1 00 q
FEN DERSON
A review book featuring more than 1 1 00 multiple-choice questions that follow the Step 1 template.
Questions frequently require multistep reasoning, probing the student's ability to integrate basic sci
ence knowledge i n a clinical situation. Detailed rationales are l inked to clinical vignettes and address
incorrect answer choices. More than 300 full-color images l i nk clinical and pathologic fi ndings, with
normal lab values provided for reference. Questions are presented both online and i n print. Students
can work through the online questions either in "quiz mode," wh ich provides i nstant feedback, or i n
"test mode," which simulates the Step 1 experience. Overall, a resource that is similar i n quality to
Robbins and Cotran Review of Pathology.
Robbins and Cotran Review of Pathology $49.95 Review/

KLAn Test/ 1 1 00 q
A review question book that follows the main Robbins textbooks. Questions are more detailed, dif
ficult, and arcane than those on the actual Step 1 exam, but the text offers a great review of pathology
integrated with excellent images. Thorough answer explanations reinforce key points. Requi res signifi
cant time commitment, so best if started with coursework.
Underground Clinical Vignettes: Pathophysiology Vol. 1: $27.95 Review/

Pulmonary, Ob/Gyn, ENT, Hem/One Test/ZO q
SWANSON
Concise clinical cases i l lustrating 1 00 frequently tested pathology and physiology concepts. Cardinal
signs, symptoms, and buzzwords are h ighl ighted. Also includes ZO additional boards-style questions.
Best if used as a supplement to other sources of review.
I
TOPRATED REVIEW RESOURCES PATH O L O G Y SECTION IV 6 07
Underground Clinical Vignettes: Pathophysiology Vol. II: $27.95 Review/

Gl, Neurology, Rheumatology, Endocrinology Test/20 q
SWANSON
Lippincott Williams & Wilkins, 2007, 2 5 6 pages, ISBN 9780781764667
Concise clinical cases illustrating 1 00 frequently tested pathol ogy and physiology concepts. Cardinal
signs, symptoms, and buzzwords are h ighl ighted. Also incl udes 20 additional boards-style questions.
Underground Clinical Vignettes: Pathophysiology Vol. Ill: $27.95 Review/

CV, Dermatology, GU, Orthopedics, General Surgery, Peds Test/20 q
SWANSON
Concise clinical cases ill ustrating 1 00 frequently tested pathology and physiology concepts. Cardinal
signs, symptoms, and buzzwords are highl ighted. Also incl udes 20 additional boards-style questions.
MedMaps for Pathophysiology $39.95 Review

a+ AGOSTI
A rapid review that contains 1 02 concept maps of disease processes and mechanisms organized by or
gan system, as well as classic diseases. Useful for both coursework and Step l preparati on. Ample room
is provided for notes. A good resource for looking up specific mechanisms, especially when used i n
conj unction with other primary review sources.
Cases & Concepts Step 1: Pathophysiology Review $42.95 Review/

a+ (AUG H EY Test/ 1 5 0 q
Eighty-eight cl inical cases integrating basic science concepts with cli nical data, followed by U S M LE
style questions with answers and rationales. Thumbnail and key-concept boxes highl ight key facts.
Case Files: Pathology $33.95 Review

a+ TOY
Includes 5 0 clinical cases followed by discussion, comprehension questions, and a pathology pearls
box. Cases are well chosen and good for those who prefer problem-based learning; however, uti l i ty is
l imited by scarce and poor-quality black-and-wh ite images .
USMLE Road Map: Pathology $3 1.95

a+
Test/500 q
WETTACH
A concise yet thorough outl ine-format review of diseases that are tested on boards. Text is easy to read
and i ncludes a glossary of commonly used terms. Questions at the end of each chapter are useful only
for testing comprehension . Black-and-white images.
608 SECTION IV TOP- RATED REVIEW RESOURCES PAT H O LO G Y
PreTest Pathology $29.95

B
Test/500 q
BROWN
Difficult questions with deta iled, complete answers. High-yield facts at the beginning are useful for
concept summaries, but information can easily be obtained in better review books. Features h igh
qual ity black-and-wh ite photographs and microscopy slides, making interpretation difficult. Best used
as a supplement to other review books.
High-Yield Histopathology $27.95 Review

B DUDEK
A new book that reviews the relationship of basic histology to th e pathology, physiology, and pharma
cology of clinical conditions that are tested on Step l. Includes case studies, numerous l ight and elec
tron micrographs, and pathology photographs . Given its considerable length, should be started with
coursework.
Crash Course: Pathology $49.95 Review

B FISH BACK
Part of the C rash Course review series for basic sciences, integrating clinical topics. Offers tvvo-color
ill ustrations, handy study tools, and Step 1 review questions. Incl udes online access. Best i f started d ur
ing coursework.
Pathophysiology of Disease: Introduction to Clinical $69.95 Review/Test/

B Medicine Few q
McPHEE
An interdisciplinary text useful for understanding the pathophysiol ogy of clinical symptoms. Effectively
integrates the basic sciences with mechanisms of disease . Features great graphs, diagrams, and tables.
In view of its length , most useful if started during coursework. Incl udes a few non-boards-style ques
tions. The text's clinical emphasis nicely complements BRS Pathology.
Haematology at a Glance $40.95 Review

B M EHTA
Blackwell Science, 2009, 128 pages, ISBN 9781405179706
A resource that covers common hematologic issues. Includes color ill ustrations. Presented in a logical
sequence that is easy to read . Good for use with coursework.
Pocket Companion to Robbins and Catron Pathologic $42.95 Review

B Basis of Disease
M ITCHELL
A resource that is good for reviewing keywords associated with most important diseases. Presented in a
h ighly condensed format, but the text is compl ete and easy to understan d . Contains no photographs or
illustrations but does include tables. Useful as a quick reference.
TOP-RATED REVIEW RESOU RCES PATHO L O G Y SECTION IV 6 09
PreTest Pathophysiology $28.95 Test/500 q

B M U FSON
Incl udes 500 questions and answers with explanations. Questions are often overly specific, and expla
nations vary in qual ity. Features a brief section of high-yield topics. Good economic value.
Color Atlas o f Physiology $44.95 Review

B S I LBERNAGL
Thieme, 2009, 456 pages, ISBN 9783135450063
A text conta ining more than 1 80 high-quality illustrations of disturbed physiologic processes that l ead
to dysfunction . An alternative to standard texts, but not high yield for boards review.
61 0 SECTION IV TOP-RATED REVIEW RESOURCES P H ARMACO L O G Y
P H ARMACO L O G Y
Kaplan Medical USMLE Pharmacology $44.95

A
Flash cards
and Treatment Flashcards
FISCH ER
Kaplan, 2008, 200 flash cards, ISBN 9781427797063
Excellent, easy-to-read flash cards with drug and questions on one side and discussion on the other,
offering j ust the right amount of detail for the boards . Alternative to more traditional pharmacology
textbooks .
Deja Review: Pharmacology $19.95 Review

A GLEASON
ries. Covers most of the drugs needed for Step 1 succinctly. Incl udes cl inical vign ettes at the end of
chapters for review.
Lange Pharmacology Flash Cards $34.95 Flash cards

BARON
A total of 1 89 pocket-sized flash cards featuring cl inical vignettes involving relevant drugs, with high
yield information highlighted in bold. Information content of cards varies - too much information on
some, not enough on others. Printed on less durable material .
BRS Pharmacology Flash Cards $32.95 Flash cards

KIM
A series of flash cards that facil itate memorization of the appropriate clinical use of drugs rather than
describing mechanisms and toxicities in deta i l . ot a comprehensive review resource, but may be use
ful for those who find other pharm cards overwh elming. Considered by many to be an excellent re-
source for quick, last-minute review.
Pharmacology for the Boards and Wards $39.95 Review/

a+ AYALA Test/ 1 5 0 q
Like other books in the Boards and Wards series, the pharmacology volume is presented primarily
i n tabular format with bulleted key points. Review questions are i n Step 1 styl e . At times can be too
dense, but does a great j ob of focusing on the clinical aspects of drugs .
Crash Course: Pharmacology $49.95 Review

a+ BARN ES
Part of the C rash Course review series for basic sciences, integrating clinical topics. Offers two-color il
lustrations, handy study tools, and Step ! -style review questions. Includes online access. Gives a sol id,
easy-to-follow overview of pharmacology. Limited student feedback.
TOP-RATED REVIEW RESOURCES PHARMACO L O G Y SECTION IV 61 1
Pharmacology Flash Cards $36.95 Flash cards

a+ BRENNER
Flash cards for more than 200 of the most commonly tested drugs. Cards include the name of the
drug (both generic and brand) on the front and basic drug information on the back. D ivided and color
coded by class, and comes with a compact carrying case. Lacks figures and c l i nical vignettes.
Lippincott's Illustrated Reviews: Pharmacology $59.95 Review/

a+ HARVEY Test/200 q
A resource presented i n outl ine format with practice questions, many excellent illustrations, and com
parison tables. Effectively integrates pharmacology and pathophysiology. The new edition has been
updated to cover recent changes in pharmacotherapy. Best started with coursework, as it is h ighly de
tailed and requires significant time commitment.
Pharm Cards: Review Cards for Medical Students $37.95 Flash cards
a+ JOHAN NSEN
Lippincott Williams & Wilkins, 2010, 240 Aash cards, ISBN 9780781787413
A series of Aash cards that cover the mechanisms and side effects of major d ru gs and drug classes.
Good for class review, but the level of detail is beyond what is necessary for Step l. Lacks pharma
cokinetics, but features good charts and diagrams. Wel l l iked by students who e n j oy Aash card-based
review. Compare with BRS Pharmacology Flash Cards.
Elsevier's Integrated Pharmacology $39.95 Review

a+ KESTER
Part of the Integrated series that seeks to l i nk basic science concepts across discipl ines. Case-based and
Step \ -style questions at the end of each chapter allow readers to gauge their comprehension of the
material. Includes online access. Best if used during coursework. Limited student feedback.
Rapid Review: Pharmacology $39.95 Review

a+ PAZDERN I K
A detailed treatment of pharmacology, presented in an outl ine format similar to that of other books in
the series. More deta iled than necessary for Step l review. Contains high-yield charts and figures. I n
cludes access to the companion Web site with 4 5 0 USMLE-style questions.
Pharmacology Recall $42.95 Review

a+ RAMACHAN DRAN
Lippincott Williams & Wilkins, 2008, 592 pages+ audio, ISBN 9780781787307
A resource presented in the two-column, question-and-answer format typi cal of the Recall series. At
times questions delve into more c l inical detail than requ ired for Step l , but overall the breadth of
coverage is appropriate. Includes a h igh-yield drug summary. Incl udes questions and answers that are
recorded in MP3 format so that they can be used on any audio player.
6l2 SECTION IV TOPRATED REVIEW RESOURCES P H ARM ACO l O G Y
Underground Clinical Vignettes Step 1: Pharmacology $2Z95

a+
Review/
SWANSON Test/20 q
Concise cl inical cases illustrating approximately 1 00 frequently tested pharmacology concepts. Car
dinal signs, symptoms, and buzzwords are highl ighted. Also includes 20 additional boards-style ques
tions. Omits some i mportant drugs and lacks detail on mechanisms, so best used as a supplement to
other sources of review.
Katzung & Trevor's Pharmacology: Examination $49.95 Review/

a+ and Board Review Test/ 1 000 q
TREVOR
A well-organized text with concise explanations. Features good charts and tables; the crammable l ist
in Appendix I is especially high yield for Step 1 review. Also good for drug i nteractions and toxicities.
Offers two practice exams but no explanations of the answers . Text includes many low-yield/obscure
drugs. Compare with Lippincott 's Illustrated Reviews: Phamwcology, both of which are better suited to
complementing coursework than last-minute studying for boards.
USMLE Road Map: Pharmacology $3 1.95 Review

a I<ATZUNG
An outline review of pharmacology divided either by organ system or by disease process. Includes a
collection of brief review questions at the end of each chapter. The appendix has useful tables of com
mon side effects and drug classes . Does not contain enough deta il to serve as a comprehensive review.
BRS Pharmacology $39.95 Review/

a ROSEN FELD Test/200 q
Lippincott W illiams & Wilkins, 2009, 368 pages, ISBN 9780781789134
Features two-color tables and figures that summarize essential information for quick recall. A l ist of
drugs organized by drug family is included in each chapter. Too detailed for boards review; best used
as a reference. Also offers end-of-chapter review tests with Step 1 -style questions and a comprehensive
exam with explanations of answers. An additional question bank is available onl ine.
PreTest Pharmacology $29.95 Test/500 q

a 5 H LAFER
Good questions divided into sections by organ system and accompanied by detailed answers. Ques
tions are often more straightforward than Step 1 , while others build graph-reading skills and multistep
reasoning skills. Sections on general principles and autonomies are especially usefu l . B est used as a
resource for additional questions after other sources have been exhausted.
TOPRATED REVIEW RESOURCES P H ARMACO L O G Y SECTION IV 613
Case Files: Pharmacology $33.95 Review

B Tov
Includes 5 3 cases with detailed discussion, comprehension questions, and a box of clinical pearls. An
appealing text for students who prefer problem-based learning, but lacks the l evel of deta il typically
tested on Step 1 .
High-Yield Pharmacology $27.95 Review

B WEISS
A succinct pharmacology review presented in an easy-to-follow outl ine format. Features a drug i ndex,
key points in bold, and summary tables of high-yield facts. Lacks details on mechanisms or drug specif-
ics, so best used with a more comprehensive resource.
614 SECTION IV TOP-RATED REVIEW RESOURCES P H YS I O L O G Y
P H YSI O LO G Y
BRS Physiology $39.95 Review/

A CosTANzo Test/400 q
A clear, concise review of physiology that is both comprehensive and efficient, making for fast, easy
reading. Incl udes excellent h igh-yield charts and tables, but lacks some figures from Costanzo's Physi
ology. Features h igh-quality practice questions with explanations in each chapter along with a cl ini
cally oriented final exam. An excellent boards review resource, but best if started early in combination
with coursework. Respiratory and acid-base sections are comparatively weak.
Physiology $59.95 Text

A COSTANZO
Saunders, 2010, 493 pages, ISBN 9781416062165
A comprehensive, clearly written text that covers concepts outl ined in BRS Physiology in greater deta i l .
Offers excellent color diagrams a n d charts. Each systems-based chapter features a detailed summary
of obj ectives and a Step 1 -relevant clinical case. Includes access to online i nteractive extras. Requi res
time commitment; best started with coursework.
The Big Picture: Medical Physiology $46.95 Review/

KI B B LE Text/ 1 08 q
Well-written text supplemented by 4 5 0 illustrations. Chapters conclude with approxi mately 1 0 study
questions/answers. Consistent organization facilitates relatively quick review. Includes a 1 08-question
practice exam with answers. Best if started early with coursework.
BRS Physiology Cases and Problems $45.95 Reviewnest/

COSTANZO Many q
Sixty classic cases presented in vignette format with several questions per case. I ncludes exceptionally
detailed explanations of answers. For students interested in an in-depth discussion of physiology con
cepts. May be useful for group review.
Deja Review: Physiology $19.95 Review

a+ GOULD
Features questions and answers i n a two-column, quiz-yourself format similar to that of the Recall se
ries. Includes helpful graphs and schematics. Contains clinical vignettes at the end of each organ sys
tem similar to those seen on the Step 1 exam.
High-Yield Acid-Base Review $26.95 Review

a+ LONGENECKER
A concise and well-written description of acid-base disorders. Incl udes chapters discussing differential
diagnoses and 12 clinical cases. Introduces a multistep approach to the materi a l . A bookmark with use
ful factoids is included with the text. No index or questions.
TOP-RATED REVIEW RESOURCES P H YSIO L O G Y SECTION IV 61 5
USMLE Road Map: Physiology $26.95 Review/

a+ PASLEY Test/5 0 q
A text in outl ine format i ncorporating useful comparison charts and clear diagrams. Provides a concise
approach to physiology. C l inical correlations are referenced to the text. Questions build on basic con
cepts and include deta iled explanations. Limited student feedback.
Appleton & Lange Review: Physiology $39.95 Test/700 q

a+ PEN N EY
Step l -style questions divided i nto subcategories under physiology. Good if subject-specific questions
are desired, but may be too deta iled for many students. Some diagrams are used to explain answers. A
good way to test knowl edge after coursework.
Rapid Review: Physiology $39.95 Review

a BROWN
A resource that offers a good review of physiol ogy in a format typical of the Rapid Review series, albeit
with more images. Includes online access to 3 5 0 questions along with other extras.
Elsevier's Integrated Physiology $3Z95 Review

a CARROLL
Part of the Integrated series that seeks to l i nk basic science concepts across discipl ines. A good text for
initial coursework, but too long for Step l revi ew. Case-based and Step l -style questions are included
at the end of each chapter. Limited student feedback.
High-Yield Physiology $28.95 Review

a D U DEK
An outline review of major concepts written at an appropriate level of depth for Step l ; incl udes espe
cially detailed coverage of cardiovascular, respi ratory, and renal physiology. Features many excellent
diagrams and boxes h ighl ighting i mportant equations . Large blocks of dense text make it a slow and
disorienting read at times. Limited student feedback.
PreTest Physiology $29.95 Test/500 q

a M ETTI NG
Contains questions with deta iled, well-written explanations. One of the best of the PreTest series. Best
for use by the motivated student after extensive review of other sources . Incl udes a high-yield facts sec
tion with useful diagrams and tables.
61 6 SECTION IV TOPRATED REVIEW RESOURCES P H YS I O lO G Y
Netter's Physiology Flash Cards $35.95 Flash cards

a MULRON EY
Saunders, 2010, 2 00+ flash cards, ISBN 9781416046288
Flash cards contai n a high-quality illustration on one side with question and commentary on the other.
Good for self-testing, but too fragmented for learning purposes and not comprehensive enough for
boards. Limited student feedback.
Acid-Base, Fluids, and Electrolytes Made $22.95 Review

a Ridiculously Simple
PRESTON
A resource that covers major acid-base and renal physiology concepts. Provides information beyond
the scope of Step 1 , but remains a useful companion for studying kidney function, electrolyte distur
bances, and Auid management. Includes scattered diagrams and questions at the end of each chapter.
Consider using after exhausting more high-yield physiol ogy review resources.
Case Files: Physiology $33.95 Review

a Tov
A review text divided into 5 1 cl inical cases followed by clinical correlations, a discussion, and take
home pearls, presented in a format similar to that of other texts in the Case Files series. A few ques
tions accompany each case. Too lengthy for rapid review; best for students who enjoy problem-based
learning.
Vander's Renal Physiology $39.95 Text

a- EATON
McGraw-Hill, 2009, 2 2 2 pages, ISBN 9780071613033
Well-written text on renal physiology, with helpful but sparse diagrams and questions at the end of
each chapter. Far too detailed for Step 1 review, however. Best if used with organ-based coursework to
understand the principles of renal physiology.
Clinical Physiology Made Ridiculously Simple $19.95 Review

a- GOLDB ERG
An easy-to-read text with many amusing associations and memorabl e mnemonics. The style does not
work for everyone. Not as well illustrated as the rest of the series, and lacks some i mportant concepts.
Best used as a supplement to other review books .
Endocrine Physiology $42.95 Text

a- MOLINA
Good but lengthy text on endocrine physiology. Questions at the end of each chapter are helpful to
work th rough , but most are not representative of Step 1 questions. Provides more detailed explanations
of endocrine physiology than Costanzo offers but much too lengthy for Step 1 review. May be useful as
a coursework adj unct.
TO P-RATED REVIEW RESOURCES P H Y S I O LO G Y SECTION IV 617
Pulmonary Pathophysiology: The Essentials $42.95 Review/

a- WEST Test/ 5 0 q
A volume offering comprehensive coverage of respiratory physiology. Clearly organized with useful
charts and diagrams. Review questions at the end of each chapter have letter answers only and no ex
planations. Best used as a course supplement during the second year.
61 8 SECTIO N IV T O P - R AT E D R E V I E W R E S O U R C E S
N OT E S
SECTION IV
Commercial
Review Courses
620 SECTION IV COMMERCIAL REV IEW COURSES
COMMERCIAL REVIEW COURSES
Commercial preparation courses can be helpful for some students, but such courses are expensive and may leave
limited time for independent study. They are usually an effective tool for students who feel overwhelmed by the
volume of material they must review in preparation for the boards. Also note that while some commercial courses
are designed for first-time test takers, others are geared toward students who are repeating the examination. Still other
courses have been created for IMGs who want to take all three Steps in a limited amount of time. F inally, student
experience and satisfaction with review courses are highly variable, and course content and structure can evolve
rapidly. We thus suggest that you discuss options with recent graduates of review courses you are considering. Some
student opinions can be found in discussion groups on the Internet.
Falcon Physician Reviews
Established in 2002, Falcon Physician Reviews provides intensive and comprehensive live reviews for students
preparing for the USMLE and COMLEX. The 7-week Step 1 reviews are held throughout the year with small class
sizes in order to increase student involvement and instructor accessibility. Falcon Physician Reviews uses an active
learning system that focuses on comprehension, retention, and application of concepts. Falcon Online program
components include:
A full set of color Falcon textbooks

Hundreds of hours of lectures optimized into high-yield streaming video
On-screen PowerPoint slides
A 3-month USMLEWorld or 6-month USMLE Consult Question Bank subscription
Diagnostic exam
Available as an iPhone application
Falcon Live programs are currently offered m Dallas, Texas. The fee range 1s $2599-$6499. The all-inclusive
program tuition fee includes:
Lodging
Complimentary daily breakfast and lunch
A full set of color Falcon textbooks
Daily clinical vignettes
Daily tutoring
High-speed Internet service
Local hotel shuttle service
A 3-month USMLEWorld or 6-month USMLE Consult Question Bank subscription
For more information, contact:
Falcon Physician Reviews

4800 Regent Boulevard, Suite 204
Irving, TX 75063
Phone: (800) 683-8725
Fax: (214) 292-8568
www.falconreviews.com
COMMERCIAL REVIEW COURSES SECTION IV 62 1
Kaplan Medical
Kaplan Medical offers a wide range of options for USMLE preparation, including live lectures, center-based study,
and online courses. All of its program offerings focus on providing the most exam-relevant information available.
Live Lectures. Kaplan's LivePrep offers a highly structured, interactive live lecture series led by expert faculty as 7-,
14-, or 16-week courses. This course's advantages include interaction with faculty and peers.
Kaplan also offers LivePrep Retreat, a 6-week course during which students stay and study m high-end hotel
accommodations.
Center Study. Kaplan's CenterPrep, a center-based lecture course, is designed for medical students seeking
flexibility. Essentially an independent study course, it is offered at Kaplan Centers across the United States for 3-,
6-, or 9-month periods. Students have access to more than ZOO hours of video lecture review. CenterPrep features
seven volumes of lecture notes and a full-length simulated exam with a complete performance analysis and detailed
explanations. The course also includes a Personalized Learning System (PLS), which allows students to create a
customized study schedule and track their performance.
Online Programs. Kaplan Medical provides online content- and question-based review. Classroom Anywhere,
Kaplan's top-rated course, offers an interactive, online classroom experience with the benefit of live instruction
delivered by expert faculty from wherever Internet access is available. Kaplan's OnlinePrep on-demand video
lectures and Qbank are included in this course. This course is ideal for students who need a more comprehensive
review option, but require a flexible study schedule or are unable to travel to one of Kaplan's live lecture locations.
Kaplan's popular Qbank allows students to create practice tests by discipline and organ system, difficulty, and yield;
receive instant onscreen feedback; and track their cumulative performance. Kaplan offers Until Your Test access
allowing students to get an immediate edge in school and repeat lectures as often as they like for the next 1Z months.
Kaplan's Qbank also includes a free integrated mobile app for iPhone and Android devices so students can practice
questions on the go. Qbank demos are available at www.kaplanmedical.com.
For more information, call (800) 527-8378 or visit www.kaplanmedical.com.
Northwestern Medical Review
orthwestern Medical Review offers live-lecture review courses, videotaped lectures, and private tutoring in
preparation for both the COMLEX Level I and USMLE Step 1 examinations. Two review plans are available for
each exam: BI ZOO, a 5-day course; and NBI 300, an 8- to 15-day course. All courses are in live-lecture format,
and most are taught by the authors of the Northwestern Review Books. In addition to organized lecture notes and
books for each subject, courses include Web-based question bank access, audio COs, and a large pool of practice
questions and simulated exams. All plans are available in a customized, onsite format for groups of second-year
students from individual U.S. medical schools. Additionally, public sites are frequently offered in East Lansing, MI,
and Chicago, IL. Live courses and Center preparations are also globally available at several international sites,
including Caribbean Islands (Puerto Rico and select islands), Guadalajara (Mexico), India (several locations),
Canada (Ontario), Dubai, and other locations based on demand.
Tuition for each course is $465. Private tutoring, CBT question-bank access, and DVD materials are also available
for purchase independent of the live-lecture plans. Northwestern offers a retake option as well as a liberal
cancellation policy.
622 SECTION IV COMMERC IAL REVIEW COURSES
Northwestern Medical Review

4800 Collins Rd. #22174
Lansing, MI 48909
Phone: (866) MedPass
Fax: (517) 347-7005
Email: contactus@northwesternmedicalreview.com
www.northwesternmedicalreview.com
PASS Program/PASS Program South
USMLE and COMLEX Review Program. The PASS Program offers a concept-based, clinically integrated
curriculum to help students increase board scores, obtain residencies, and broaden their perspective of medicine.
Helpful for a wide spectrum of students, including those trying to maximize scores on the first try and those
struggling to stay in medical school. PASS accommodates all types of learners: auditory, visual, or kinesthetic, and,
with the help of small class sizes, encourages students to interact and to ask questions.
Live Lectures. PASS offers 4-week, 8-week, or extended-stay programs in Champaign, Illinois, and St. Augustine,
Florida. Facilities include computer labs, a state-of-the-art lecture hall, student lounges and study areas, and housing.
Drill sessions and small study groups take place throughout the week. Tuition (not including housing) for the 4-week
program is $2950 and for the 8-week guarantee program is $6000.
One-on-One Tutoring. Included with tuition, students receive one-on-one tutoring from an MD each week they
attend the program. Four-week students receive two sessions per week and 8-week students receive four sessions in
the first half of the program and five sessions in the second half.
PASS Program PAS S Program South

2302 Moreland Blvd. 120 Sea Grove Main Street
Champaign, IL 61822 St. Augustine, FL 32080
Phone: (217) 378-8018 Phone: (904) 209-3140
Fax: (217) 378-7809 www.passprogramsouth.com
www.passprogram.net
The Princeton Review
The Princeton Review offers two flexible preparation options for the USMLE Step 1: the USMLE Online Course
and the USMLE Online Workout.
USMLE Online Courses. The USMLE Online Courses offer the following:
75 hours of online review, including lessons, vignettes, and drills

Complete review of all USMLE Step 1 subjects
Three full-length CBTs
Seven 1-hour subject-based tests
Complete set of print materials
COMMERCIAL REVIEW COURSES SECTION IV 623
24/7 access to technical support

Three months of access to tests, drills, and lessons
More information can be found on The Princeton Review's Web site at www.princetonreview.com.
Youel's.,.. Prep, Inc.
Youel's Prep, Inc., has specialized in medical board preparation for 30 years. The company provides DVDs,
audiotapes, videotapes, a CD (PowerPrep Quick Study), books, live lectures, and tutorials for small groups as well
as for individuals (TutorialPrep ) . All DVDs, videotapes, audiotapes, live lectures, and tutorials are correlated with
a three-book set of Prep Notes consisting of two textbooks, Youel's Jewels[ and Youel's Jewels II (984 pages), and
Case Studies, a question-and-answer book (1854 questions, answers, and explanations).
The Comprehensive DVD program consists of 56 hours of lectures by the systems with a three-book set: Youel's
Jewels I and II and Case Studies. Integrated with these programs are pre-tests and post-tests.
All Youel's Prep courses are taught and written by physicians, reflecting the clinical slant of the boards. All programs
are systems based. In addition, all programs are updated continuously. Accordingly, books are not printed until the
order is received.
Delivery in the United States or overseas is usually within 1 week. Optional express delivery is also available.
Youel's Prep Home Study Program allows students to own their materials and to use them for repetitive study in
the convenience of their homes. Purchasers of any of Youel's Prep materials, programs, or services are enrolled as
members of the Youel's Prep Family of Students, which affords them access to free telephone tutoring at (800)
645-3985. Students may call 2417. Youel's Prep live lectures are held at select medical schools at the invitation of the
school and students.
Programs are custom-designed for content, number of hours, and scheduling to fit students' needs. F irst-year students
are urged to call early to arrange live-lecture programs at their schools for next year.
Youel's Prep, Inc.

P.O. Box 31479
Palm Beach Gardens, FL 33420
Phone: (800) 645-3985
Fax: (561) 622-4858
Email: info@youelsprep.com
www.youelsprep.net
Publisher Contacts
ASM Press John Wiley & Sons Parthenon Publishing/CRC Press

1 7 5 2 N Street, NW I Wiley Drive Taylor & Francis Group
Wash ington, D.C. 20036-2904 Somerset, NJ 0887 5-1 272 6000 B roken Sound Parkway, N W, Suite 300
(800) 546-24 1 6 (800) 2 2 5-5945 Boca Raton, F L 3 3487
Books@asmusa.org Fax: (7 32) 302-2 300 (800) 272-7737
IV\Vw.asmpress.org custserv@wiley.com Fax: (800) 374-340 1
www.wiley.com orclers@tayloranclfrancis.com
Elsevier Science www.crcpress.com
Order Fulfillment Kaplan, Inc.
3 2 5 1 Riverport Lane 395 Hudson Street, 4th Floor Princeton Review
Maryland Heights, MO 63043 New York, NY 1 00 1 4 2 3 1 5 B roadway
(800) 54 5-2 5 2 2 kaplanmeclical.com New York, NY 1 0024
Fax: (800) 53 5-99 35 (866) 877-7737
IV\V\V. us.elsevierhea I th .com Lippincott Williams & Wilkins www.princetonreview.com
1 6 5 2 2 Hunters Green Parkway
Exam Master Hagerstown, MD 2 1 740 Thieme Medical Publishers, Inc.
500 Ethel Court (800) 638-3030 3 3 3 Seventh Avenue
Middletown, DE 1 9709-94 1 0 Fax: (30 1 ) 22 3-2 398 ew York, NY 1 000 I
(800) 572-3627 orclers@lww.com (800) 782-3488
Fax: (302) 283- 1 222 www.lww.com Fax: (2 1 2) 947-0 1 08
customer_service@exammaster.com www.thieme.com
IV\Vw.exammaster.com MedMaster, Inc. customerservice@th ieme.com
P.O. Box 640028
Garland Science Publishing M i ami, F L 3 3 1 64
7 1 1 Thi rd Avenue, 8th Floor (800) 3 3 5-3480
New York, NY 1 0017 Fax: (9 54) 962-4508
(20 3) 28 1 -4487 mmbks@aol.com
Fax: (2 1 2) 947-3027 IV\Vw.meclmaster.net
science@garland.com
www.garlandscience.com McGraw-Hill Companies
Order Services
Gold Standard Board Prep P.O. Box 1 82604
Apollo Aud iobooks, LLC Columbus, OH 43 272-303 1
2 508 27th Street (877) 83 3-5524
Lubbock, TX 794 1 0 Fax: (6 1 4) 7 5 9-3749
(806) 773-3 1 97 pbg.ecommerce_custservmcgraw-hill.com
info@ApolloAudiobooks.com IV\vw.mhprofessional.com
\V\Vw.boarclprep.net
SECTION IV
Abbreviations and Symbols
ABBREVIATION MEANING ABBREVIATION MEANING

Io primary A0x3 alert and oriented to time, place, and person
zo secondary AOA American Osteopath ic Association
30 tertiary AP action potential, aorticopul monary, A & P [ribosomal
A-a alveolar-arterial (gradient] binding sites]
AA Alcoholics Anonymous, amyloid A A&P ribosomal binding sites
AAI\IIC Association of American Medical Colleges APC antigen-presenting cell, activated protein C
Ab antibody APP amyloid precursor protein
ABP androgen-binding protein APRT adenine phosphoribosyltransferase
ACA anterior cerebral artery APSAC anistreplase
ACC acetyl-CoA carboxylase aPTT activated partial thromboplastin time
Acetyl-CoA acetyl coenzyme A Apo apol ipoprotein
ACD anemia of chronic disease AR attributable risk, autosomal recessive, aortic regurgitation
ACE angiotensin-converting enzyme ara-C arabinofuranosyl cytidine ( cytarabine)
ACh acetylchol ine ARB angiotensin receptor blocker
AChE acetylchol inesterase ARDS acute respiratory distress syndrome
ACL anterior c ruciate l igament Arg arginine
AComm anterior communicating (artery] ARMD age-rel ated macular degeneration
ACTH adrenocorticotropic hormone ARPKD autosomal-recessive polycystic kidney disease
ADA adenosine deaminase, Americans with Disabil ities Act AS aortic stenosis
ADH antidiuretic hormone ASA acetylsalicylic acid, anterior spinal artery
ADI-10 attention-deficit hyperactivity disorder ASD atrial septal defect
ADP adenosine diphosphate ASO anti-streptolysin 0
ADPKD autosomal-dominant polycystic kidney disease Asp aspartic acid
AFP a-fetoprotein AST aspartate transaminase
Ag antigen, silver AT angiotens i n , antith rombin
AICA anterior inferior cerebellar a rtery ATCase aspartate transcarbamoylase
AIDS acquired immunodeficiency syndrome ATN acute tubular necrosis
AIHA autoimmune hemolytic anemia ATP adenosine triphosphate
AL amyloid l ight [chain] ATPase adenosine triphosphatase
ALA aminolevul inic acid AV atrioventricular
ALL acute lymphoblastic (lymphocytic) leukemia AVM arteriovenous malformation
ALP alkal ine phosphatase AZT azidothymidine
sympathetic receptors )> 2 sympathetic receptors
amyotrophic lateral sclerosis BAL B ritish anti-Lewisite (dimercaprol]
alanine transaminase BBB blood-brain barrier
American Medical Association, antimitochondrial BCC bacil l e Calmette-Cuerin
antibody BIMS B iometric Identity Management System
AJ\IL acute myelogenous (myeloid) leukemia BM basement membrane
AMP adenosine monophosphate BMI body-mass index
ANA antinuclear antibody BMR basal metabol ic rate
ANCA antineutroph il cytoplasmic antibody BP bisphosphate, blood pressure
A OVA analysis of variance BPC biphosphoglycerate
ANP atrial natriuretic peptide BPH benign prostatic hyperplasia
ANS autonomic nervous system BS B owman's space
62 6 SECTION IV ABBREVIAT IONS AND SYMBOLS

BT bleeding time COOI-I carboxyl group
BUN blood urea nitrogen COP coat protein
2
Ca + calcium ion COPD chronic obstructive pulmonary disease
CAD coronary artery disease CoQ coenzyme Q
CAF common appl ication form cox cyclooxygenase
CALLA common acute lymphoblastic leukemia antigen cp plasma concentration
cAMP cycl ic adenosine monophosphate CPAP continuous positive a i rway pressure
c-ANCA cytoplasmic antineutrophil cytoplasmic antibody CPK creatine phosphokinase
CBG corticosteroid-binding globul in CPR cardiopulmonary resuscitation
Cbl cobalamin Cr creatinine
CBS SA Comprehensive Basic Science Self-Assessment C RC colorectal cancer
CBT computer-based test, cognitive-behavioral therapy C RE ST calcinosis, Raynaud's phenomenon, esophageal
CCK cholecystokinin dysfunction, sclerosis, and teleangiectasias [syndrome]
ccs computer-based case simulation C RH corticotropin-releasing hormone
CCT cortical coll ecting tubule C RP C-reactive protein
CD cl uster of differentiation cs cl inical skills
CDK eye! in-dependent kinase C-section cesarean section
eDNA complementary deoxyribonucleic acid C SF cerebrospinal A uid, colony-sti mulating factor
CEA carcinoembryonic antigen CT computed tomography
CETP cholesterol-ester transfer protein CTL cytotoxic T lymphocyte
CF cystic fibrosis CTP cytidine triphosphate
C FTR cystic fibrosis transmembrane conductance regulator cv cardiovascular
C FX circumAex [artery] CVA cerebrovascular accident, costovertebral angle
ceo chronic granulomatous disease CVI D common variable immunodeficiency
cGMP cycl ic guanosine monophosphate CXR chest x-ray
CGN cis-Golgi network Cys cysteine
CGRP calcitonin gene-related peptide OAF decay-accelerating factor
C 111-C 11 3 constant regions, heavy chain [antibody] DAG diacylglycerol
ChAT chol ine acetyl transferase dATP deoxyadenosine triphosphate
Cl-JF congestive heart fai l ure DC I S ductal carcinoma in situ
xz chi-squared OCT distal convol uted tubul e
Cl confidence interval ddC dideoxycytidine [ zalcitabine J
CIN candidate identification number, carcinoma in situ, dell didanosine
cervical intraepithelial neoplasia DES diethylsti 1 bestrol
CIS Communication and Interpersonal Skills DHAP dihydroxyacetone phosphate
C)D C reutzfeldt-Jakob disease DIJB dihydrobiopterin
CK cl inical knowledge, creatine kinase DH EA dehydroepiandrosterone
C K-MB creatine kinase, M B fraction DHF dihydrofolic acid
CL constant region, l ight chain [antibody] OJ-IS Department of Homeland Security
CL clearance DI-IT dihydrotestosterone
CJ ch Iori de ion Dl diabetes insipidus
C LL chronic lymphocytic leukemia DIC disseminated intravascular coagul ation
CML ch ronic myelogenous ( myeloid) leukemia DIP distal interphalangeal [ joint]
CMV cytomegalovirus orr diiodotyrosine
CN cranial nerve DKA diabetic ketoacidosis
cw cyanide ion OM diabetes mell itus
c s central nervous system DNA deoxyribonucl eic acid
co carbon monoxide, cardiac output 2,4-DNP 2,4-dinitrophenol
C0 2 carbon dioxide dNTP deoxynucleotide triphosphate
CoA coenzyme A DO doctor of osteopathy
COMLEX Comprehensive Osteopath ic Medical Licensing DPG diffuse prol iferative glomeruloneph ritis
USA Examination DPM Doctor of Podiatric Medicine
COM SAE Comprehensive Osteopath ic Medical Self-Assessment DPP-4 dipeptidyl peptidase-4
Examination
OS double stranded
COMT catechol-0-methyltransferase
ABBREVIAT I O N S AND SYMBOLS SECTION IV 62 7

dsDNA double-stranded deoxyribonucleic acid F2,6BP fructose-2,6-bisphosphate
dsRNA double-stranded ribonucl eic acid FBPase fructose bisphosphatase
d4T didehydrodeoxythymidine [ stavudine J Fe fragment, c rystallizable
dTMP deoythymicl i ne monophosphate Fe R Fe receptor
DTR deep tendon reAex 5f-ci UMP 5-fluorodeoxyuricline monophosphate
2
DTs delirium tremens Fe + ferrous ion
deoxyuridine diphosphate >
Fe + ferric ion
dUDP
dUMP deoxyuridine monophosphate Fe N a
excreted fraction of filtered sodium
DVf deep venous thrombosis FEV1 forced expiratory volume in I second
EBV Epstein-Barr virus FF filtration fraction
EC ejection click FFA free fatty acid
EC F extracellular A uid FGF fibroblast growth factor
ECFMG Educational Commission for Foreign Medical Graduates FGF R fibroblast growth factor receptor
ECG electrocardiogram FIS H fluorescence in situ hybridization
EC L enteroch romaffin-like [cel l ] FLAJR fluid-attenuated inversion recovery
ECM extracel lular matrix f-met formyl methionine
ECT electroconvulsive therapy FMC foreign medical graduate
ED so median effective cl o se FM flavin mononucleotide
EDRF endothelium-derived relaxing factor FN false negative
EDTA ethylenediamine tetra-acetic acid FNI- I T R febrile non hemolytic transfusion reaction
EDV end-diastolic vol ume FP false positive
EEG electroencephalogram FIP fructose-1-phosphate
EF ejection fraction F6P fructose-6-phosphate
EGF epidermal growth factor FRC functional residual capacity
EHEC enterohemorrhagic E. coli FSH fol licle-stimulating hormone
elF eukaryotic initiation factor FSMB Federation of State Medical Boards
E LI SA enzyme-linked immunosorbent assay FTA-ABS fluorescent treponema] antibody-absorbed
EM el ectron micrograph/microscopy 5-FU 5-fluorouracil
EMB eosin-methylene blue F VC forced vital capacity
EOM extraocular muscle GABA y-aminobutyric acid
Epi epinephrine Gal galactose
EPO erythropoietin GBM glomerular basement membrane
EPS extrapyramidal system GC glomerular capillary
ER endoplasmic reticulum, estrogen receptor G-CSF granulocyte colony-stimulating factor
ERAS Electronic Residency Application Service GE gastroesophageal
ERCP endoscopic retrograde cholangiopancreatography GERD gastroesophageal reflux disease
ERP effective refractory period GFAP glial fibrillary acid protein
ERPF effective renal plasma Aow GFR glomerular filtration rate
E RT estrogen replacement therapy GGT y-gl utamyl transpeptidase
ERV expiratory reserve vol ume G I -l growth hormone
ESR erythrocyte sedimentation rate Gl-I B y-hydroxybutyrate
ES RD end-stage renal disease G l -IRH growth hormone - releasing hormone
ESV end-systolic vol ume Gl G protein, I polypeptide
ETEC enterotoxigenic E. coli Gl gastrointestinal
EtOII ethyl alcohol GIP gastric inhibitory peptide
EV esophageal vein GIST gastrointestinal stromal tumor
F bioavailability Glu glutamic acid
FA fatty acid GLUT glucose transporter
Fab fragment, antigen-binding GM granulocyte macrophage
FAD Ravin adenine dinucleotide GM-C SF granulocyte-macrophage colony stimulating factor
l'if\D+ oxidized flavin adenine dinucleotide GMP guanosine monophosphate
FAD H z reduced flavin adenine dinucleotide GnRl-1 gonadotropin-releasing hormone
FAP familial adenomatous polyposis GP glycoprotein
F l ,6BP fructose-! ,6-bisphospha te G3P glucose-3-phosphate
628 SECTION IV ABBREVIAT IONS AND SYMBOLS

e6P glucose-6-phosphate HMSN hereditary motor and sensory neuropathy
e6PD glucose-6-ph ospate dehydrogenase HMWK high-molecular-weight kininogen
ere globus pall idus externa H NPCC hereditary nonpolyposis colorectal cancer
ePi globus pal l i d us interna hnRNA heterogeneous nuclear ribonucleic acid
ePl glycosyl phosphatidyl inositol HzO water
ePP glycogen phosphorylase H zO z hydrogen peroxide
eRP gastrin-releasing peptide HPA hypothalamic-pituitary-adrenal [axis]
es e protein, S polypeptide H PO hypothalamic-pituitary-ovarian [axis]
es glycogen synthase HPV human papi l lomavirus
esH reduced glutath ione HR heart rate
esse oxidized glutath ione l-IRE hormone receptor element
eTP guanosine triphosphate H RT h ormone replacement therapy
eTPase guanosine triphosphatase I-ISV herpes simplex virus
eu genitouri nary 5-HT 5-hydroxytryptamine (serotonin)
f-1+ hydrogen ion I-ITLV human T-cell l eukemia virus
histamine receptors I-I TN hypertension
1-1,, H z
I-IAART h ighly active antiretroviral therapy HTR hemolytic transfusion reaction
I-IAV hepatitis A virus HUS hemolytic-uremic syndrome
I-IAVAb hepatitis A antibody HVA homovani l l i c acid
Hb hemoglobin I-IZV herpes zoster vi rus
f-Ib+ oxidized hemoglobin JBD inflammatory bowel disease
l-Ib- ionized hemoglobin JBS i rritable bowel syndrome
l-IB cAb hepatitis B core antibody IC inspiratory capacity, i mmune complex
H BcAg hepatitis B core antigen lea calcium current [ heart]
HBeAb hepatitis B early antibody lr funny current [heart]
H BeAg hepatitis B early antigen ICA internal carotid artery
I-IBsAb hepatitis B surface antibody ICAM intracellular adhesion molecule
l-IB sAg hepatitis B surface antigen ICE Integrated C l inical Encounter
HbC0 2 carbaminohemoglobin ICF' intracellular fluid
I-IBV hepatitis B virus ICP intracranial pressure, i nferior cerebellar peduncle
HCC hepatocellular carcinoma ID identification
hCe h uman chorionic gonadotropin IDs a dose at which pathogen produces i nfection
in 50% of population
HC03- bicarbonate
lOOM insu l i n-dependent diabetes mel l itus
Hct hematocrit
IDL i ntermediate-density l ipoprotein
I-ICTZ hydrochloroth iazide
liE inspiratory/expiratory [ ratio]
HCV hepatitis C virus
IF' immunofluorescence, i nitiation factor
HDL h igh-density l i poprotein
IFN i n terferon
HDV hepatitis D virus
lg immunoglobul i n
H&E hematoxylin and eosin
leF insulin-l ike growth factor
HEV hepatitis E virus
Hfr high-frequency recomb ination [cel l ] IK potassium current [heart]
IL interleukin
HePRT hypoxanthine-guanine phosphoribosyltransferase
lie isoleucine
Hl-lb h uman hemoglobin
IM intramuscular
HHV human herpesvirus
5-hydroxyindoleacetic acid
IiVlA inferior mesenteric artery
5-I-IlM
IMED International Medical Education Directory
HIE hypoxic ischemic encephalopathy
!Me international medical graduate
His h istidine
IMP inosine monophosphate
H IT heparin-induced thrombocytopenia
IMV i nferior mesenteric vein
HIV human immunodeficiency virus
INa sodium current [heart]
HL hepatic l i pase
IN I-I isonicotine hydrazin e [isoniazid]
l-ILA human leukocyte antigen
!NO internuclear ophthalmoplegia
HMe-CoA hydroxymethylglutaryl-c oenzyme A
lN R International ormal ized Ratio
HMP hexose monophosphate
ABBREVIAT IONS AND SYMBOLS SECTION IV 629

10 inferior orbital [muscle] LSE Libman-Sacks endocarditis
l OP intraocular pressure LT labil e toxin leukotriene
I P3 inositol triphosphate LV left ventricle, left ventricular
I PV inactivated polio vaccine Lys lysine
IR current x resistance [Ohm's law]. inferior rectus [muscle] MI-M5 muscarinic (parasympathetic) ACh receptors
I RV inspiratory reserve volume MAC membrane attack complex, minimal alveolar concentration
ITP idiopathic thrombocytopenic purpura MALT mucosa-associated lymphoid tissue
IUD intrauterine device MAO monoamine oxidase
I UG R intrauterine growth retardation tvl AO I monoamine oxidase inhibitor
IV intravenous MAP mean arterial pressure, mitogen-activated protein
IVC inferior vena cava MAS P mannose-binding lectin-associated serine protease
IVDU intravenous drug use MBL mannose-binding l ectin
)AKISTAT Janus kinase/signal transducer and activator of transcription MC miclsystolic click
[pathway] MCA middle cerebral artery
)CA juxtaglomerular apparatus MCAT Medical Coll ege Admissions Test
J VD jugular venous distention MCHC mean corpuscular hemoglobin concentration
J VP jugular venous pulse MCL medial col lateral ligament
K+ potassium ion MCP metacarpophalangeal [joint]
KatG catalase-peroxidase produced by M. tubercu losis M-C S F macrophage colony-stimulating factor
Ke elimination constant MCV mean corpuscular vol ume
Kr filtration constant MD macula clensa, maintenance close
KG ketogl utarate dehydrogenase MEN multipl e endocrine n eoplasia
K m
Michaelis-Menten constant Met methionine
KOH potassium hydroxide MgZ+ magnesium ion
KSHV Kaposi's sarcoma-associated herpesvirus MGN medial geniculate nucleus
L left MgS04 magnesium sulfate
LA l eft atrial , left atrium MGUS monoclonal gammopathy of undetermined significance
LAD left anterior descending [artery] MHC major histocompatibility complex
LAF left anterior fascicle Ml myocardial infarction
LCA left coronary artery MJF mUllerian inhibiting factor
LCAT lecithin-cholesterol acyltransferase M IT monoioclotyrosine
LCFA long-chain fatty acid MLCK myosin light-chain kinase
LC L lateral col lateral ligament M LF medial longitudinal fasciculus
LCME Liaison Committee on Medical Education MMC migrating motor complex
LCMV lymphocytic choriomeningitis virus MMR measles, mumps, rubella [vaccine]
LCX left circum Rex artery MOPP mechlorethamine-vincristine (Oncovin )-preclnisone-
LD loading close procarbazine [chemotherapy]
LD50 median l ethal close 6-M P 6-mercaptopurine
LOl-l lactate dehydrogenase M PG N membranoproliferative glomerulonephritis
LDL low-density lipoprotein M PO myeloperoxiclase
LES lower esophageal sphincter MR medial rectus [ muscle], mitral regurgitation
Leu leucine M RJ magnetic resonance imaging
LFJ.\ leukocyte function-associated antigen mRNA messenger ribonucleic acid
LFT liver function test M RSA methicillin-resistantS. aureus
LCN lateral geniculate nucleus MS mitral stenosis, mul tiple sclerosis
LGV left gastric vein MSH melanocyte-stimulating hormone
Ll-l l uteinizing hormone MSM men who have sex with men
LLQ left lower quadrant mtDNA mitochondrial D A
LM light microscopy mtRNA mitochondrial RNA
LMN lower motor neuron mTOR mammalian target of rapamycin
LP l umbar puncture MTP metatarsophalangeal [join t]
LPL lipoprotein lipase MTX methotrexate
LPS lipopolysaccharide MUAIP Medically U ncle rservecl Area and Population
LR lateral rectus [muscle] MV0 2 myocardial oxygen consumption
63Q SECTION IV ABBREVIATIONS AND SYMBOLS

MVP mitral valve prolapse PALS periarterial lymphatic sheath
N/A not applicable PAN polyarteritis nodosa
sodium ion p-ANCA perinuclear antineutrophil cytoplasmic antibody
NAD nicoti namide adenine dinucleotide Pao 2 partial pressure of oxygen i n arterial blood
NAD+ oxidized nicotinamide adenine dinucleotide PAo 2 partial pressure of oxygen i n alveolar blood
NADH reduced nicotinamide adenine dinucleotide PAP Papanicolaou [smear), prostatic acid phosphatase
NADP+ oxidized nicotinamide adenine dinucleotide phosphate PAS periodic acid Sch iff
NADPl-1 reduced nicotinamide adenine dinucleotide phosphate PBP penicill in-binding protein
NBME National Board of Medical Examiners PC plasma colloid osmotic pressure, platelet count, pyruvate
NBOME National Board of Osteopath ic Medical Examiners carboxylase
NBPME National Board of Podiatric Medical Examiners PCA posterior cerebral artery
NC no change PCL posterior cruciate l igament
NE norepinephrine Pco 2 partial pressure of carbon dioxide
NEG nonenzymatic glycosylation PComm posterior communicating [artery)
NF neurofibromatosis PCOS polycystic ovarian syndrome
Nl-13 ammonia PC P phencycl idine hydroch loride, Pneu mocystis carinii (now
iirovecii) pneumonia
N H/ ammonium
PCR polymerase chain reaction
NHL non-Hodgkin's lymphoma
PCT proximal convoluted tubule
NIDDM non-i nsulin-dependent diabetes mellitus
PCWP pulmonary capillary wedge pressure
NK natural killer [cell s)
PO posterior descending [artery)
N l\1 muscarinic ACh receptor in neuromuscular junction
PDA patent ductus arteriosus
NMDA N-methyl-D-aspartate
PDC pyruvate dehydrogenase complex
NMJ neuromuscular junction
POE phosphodiesterase
NMS neuroleptic mal ignant syndrome
PDCF platelet-derived growth factor
NN nicotinic ACh receptor in autonomic gangl ia
PDH pyruvate dehydrogenase
NRMP National Residency Match ing Program
PE pulmonary embolism
NNRTI non-nucleoside reverse transcriptase inhibitor
PECAM platel et-endothelial cell adhesion molecule
NO nitric oxide
PECOz expired air Pco 2
Nz O nitrous oxide
PEP phosphoenolpyruvate
NPI-1 neutral protamine Hagedorn
PF platelet factor
N PV negative predictive value
PF'K phosphofructokinase
NRI norepinephrine receptor inhibitor
PFT pulmonary function test
NRTI nucleoside reverse transcriptase inh ibitor
PC phosphoglycerate, prostaglandin
NSAID nonsteroidal anti-inAammatory drug
Phe phenylalanine
OM oxaloacetic acid
P; plasma interstitial osmotic pressure, inorganic phosphate
OCD obsessive-compulsive disorder
PICA posterior inferior cerebellar artery
OCP oral contraceptive pill
PID pelvic inAammatory disease
OI-l hydroxy
P l o2 Po 2 in inspired air
0 1 Iz
- dihydroxy
PIP proximal interphalangeal [joint)
1 ,2 5-01-103 calcitriol (active form of vitamin D)
PIP 2 phosphatidyl inositol 4,5-bisphosphate
25-0H 03 storage form of vitamin D
PK pyruvate kinase
3' 01-1 hydroxyl
PKD polycystic kidney disease
OMT osteopath ic manipulative tech nique
PKU phenylketonuria
OPV oral pol io vaccine
PLP pyridoxal phosphate
OR odds ratio
PLS Personalized Learning System
OS opening snap
PML progressive multifocal l eukoencephalopathy
OTC ornith ine transcarbamoylase
PMN polymorphonuclear [ l eukocyte]
OVLT organum vasculosum of the lamina terminal is
pnet net filtration pressure
P-450 cytochrome P-4 50 family of enzymes
PNET primitive neuroectodermal tumor
PA posteroanterior
PNH paroxysmal nocturnal h emogl obinuria
PABA para-aminobenzoic acid
PNS peripheral nervous system
Paco 2 arterial Po 2
Po 2 partial pressure of oxygen
PAco 2 alveolar Po 2
P04 salt of phosphoric acid
PAI-I para-aminoh ippuric acid 3
P04 - phosphate
AB BREVIATIONS AND SYMBOLS SECTION IV 63 1

POMC pro-opiomelanocorti n sec squamous cell carcinoma
PPAR peroxisome prol iferator-activated receptor SCID severe combined immunodeficiency disease
PPD pur i fied protein derivative SC) squamocol umnar junction
PPJ proton pump i n h ibitor SCM sternocleidomastoid muscle
PPRF paramedian pontine reticular formation SCN suprachiasmatic nucleus
PPV positive predictive value so standard deviation
PrP prion protein SEM standard error of t h e mean
PRPP phosphoribosylpyrophosphate SEP Spoken English Proficiency
PSA prostate-specific antigen SER smooth endoplasmic reticulum
PSS progressive systemic sclerosis S E RM selective estrogen receptor modulator
PT proth rombin time S H BG sex hormone-binding globu l i n
PTl l parathyroid hormone S lADH syndrome of inappropriate (secretion o antidi uretic
PTHrP parathyroid hormone-related protein hormone
JY! 'SD post-traumatic stress disorder SLE systemic l upus erythematosus
PTT partial thromboplasti n time SLL small lymphocytic lymphoma
PV plasma volume, venous pressure SLT Sh iga-l ike toxin
PVC polyvinyl chloride S MA superior mesenteric artery
PVR pulmonary vascular resistance SMX sulfamethoxazole
R correlation coefficient, right, R variable [group] SNc substantia nigra pars compacta
Rl Registration, Ranking, & Results [system] SNP single nucleotide polymorphism
RA rheumatoid arth ritis, right atri um SNr substantia n igra pars reticulata
RAA S reni n-angiotensin-aldosterone system SNRI serotonin and norepinephrine receptor inh ibitor
RAN K-L receptor activator of nuclear factor-K B l igand snRNP small nuclear ribonucl eoprotein
RA S reticular activating system so superior obl ique (muscle J
RBC red blood cell SOAP Supplemental Offer and Acceptance Program
RBF renal blood Aow spp. species
RCA right coronary artery SR superior rectus (muscle]
REM rapid eye movement ss single stranded
RER rough endoplasmic reticulum ssDNA si ngle-stranded deoxyri bonucleic acid
Rh rhews antigen SSPE subacute sclerosing panencephalitis
RLQ right lower quadrant S S RJ selective serotonin reuptake inhi bitor
RNA ribonucleic acid ssRNA si ngl e-stranded ribonucleic acid
RNA; ribonucleic acid interference ssss staphylococcal scalded-skin syndrome
RN P ribonucleoprotein ST Sh iga toxin
ROI reactive oxygen intermediate STD sexually transmitted disease
RPF renal plasma Aow STEM ! ST-segment elevation myocardial infarction
RPG rapidly progressive glomerulonephritis STN subthalamic nucleus
RPR rapid plasma reagin sv sinus venosus, spl enic vei n , stroke vol ume
RR relative risk, respiratory rate svc superior vena cava
rRNA ribosomal ribonucleic acid SVT supraventricular tachycardia
RS Reed-Sternberg (cells] t l /2 half-l ife
RSV respi ratory syncytial vi rus Tl tri iodothyronine
RTA renal tubular acidosis T4 thyroxine
RUQ right upper quadrant TA truncus arteriosus
RV residual vol ume, right ventricle, right ventricular TAPVR total anomalous pulmonary venous return
RVH right ventricular hypertrophy TB tuberculosis
R.x medical prescription TBG thyroxine-binding globul i n
[S] substrate concentration 3TC dideoxyth iacytidine [lam ivudine]
SA sinoatrial TCA tricarboxyl ic acid (cycle ] , tricyclic antidepressant
SM seru m amyloid-associated [ protein] Tc cell cytotoxic T cell
SAM S-adenosylmethionine TC R T-ee! I receptor
SARS severe acute respiratory syndrome TDF tenofovir disopeozil fumarate
SAT Scholastic Aptitude Test TdT terminal deoxynucl eotidyl transferase
sc subcutaneous TFCC triangular fibrocartilage complex
632 SECTION IV ABBREVIATIO NS AND SYMBOLS

T IT thyroid function test UMP uridine monophosphate
TG triglyceride UPD uniparental disomy
6-TG 6-th ioguanine U RI upper respiratory infection
TGA t rans - Golgi apparatus U SMLE United States Medical Licensing Examination
TGF transforming growth factor UTI urinary tract infection
TGN t rans - Colgi network UTP uridine triphosphate
Th cell helper T cell uv ultraviolet
THF tetrahydrofolic acid V I , Vz Vasopressin receptors
Thr threonine VA Veterans Affairs
Tl therapeutic index Val val ine
TlA transient ischemic attack vc vital capacity
TIBC total iron-binding capacity vd vol ume of distribution
T I PS transj ugular intrahepatic portosystemic shunt VD physiologic dead space
TLC total l u ng capacity V( D)j heavy-chain hypervariable region [antibody]
Tm maximum rate of transport VORL Venereal Disease Research Laboratory
TMP trimethoprim VEGF vascular endothelial growth factor
TN trigeminal neuralgia, true negative VF ventricular fibrillation
TNF tumor necrosis factor VI I variable region, heavy chain [antibody]
TNM tumor, node, metastases [staging] VHL von H ippel-Lindau [disease J
TOEFL Test of E ng! ish as a Foreign Language VIP vasoactive intestinal peptide
ToRC HeS Toxoplasma gondii, rubella, C MV, H I V, H SV-2, syph ilis VI Poma vasoactive intestinal polypeptide-secreting tumor
TP true positive VJ l ight-chain hypervariable region [antibody]
tPA tissue plasminogen activator VL ventral lateral [nucleus ] ; variable region, l ight chain
TPP thiamine pyrophosphate [antibody]
TPR total peripheral resistance VLD L very l ow density l i poprotein
TR tricuspid regurgitation VMA vanillylmandelic acid
TRAP tartrate-resistant acid phosphatase VMAT vesicular monoamine transporter
TREC T-cell recombinant excision circles vmax maximum velocity
TRH thyrotropin-releasing h ormone VPL ventral posterior nucleus, l ateral
tRNA transfer ribonucleic acid VPM ventral posterior nucleus, medial
Trp tryptophan VPN vancomycin, polymyxin, nystatin [media]
TSH thyroid-stimulating hormone V/Q ventilation/perfusion [ratio]
TSI thyroid-stimulating immunoglobul i n VRE vancomycin-resistant enterococcus
TSS toxic shock syndrome VSD ventricular septal defect
TSST toxic shock syndrome toxin VT tidal vol ume
th rombotic thrombocytopenic purpura vWF von Willebrand factor

TTP
transthyretin vzv varicella-zoster virus
TTR
WHOML "worst headache of my l i fe"
TV tidal volume
translation [factor] WBC wh ite blood cell
Tx
XR X-I i nked recessive
TXAz thromboxane A2
XX normal complement of sex chromosomes for female
UCB unconjugated bilirubin
XY normal complement of sex chromosomes for male
ucv Underground C l inical Vignettes
ZDV z idovudine [formerly AZT]
UDP uridine diphosphate
UMN upper motor neuron
S E CTION IV
Photo Acknowl edgments

Images marked with 11!1 are reproduced with permission of USMLE-Rx.com. Images marked with lll!l are reproduced with permission of Dr._
Richard P. Usatine and the Color Atlas of Fam i ly Medicine (www. usatinemedia.com ). Images marked with D are reproduced with permiSSIOn of
other sources.
Biochemistry D Syphilis: Image A. Painless chancre. Reproduced, with permission,

from Wolff K et al. Fitzpa trick's Denna tology in Genera l Medicine,
D Osteogenesis imperfecta : Image A. Osteogenesis i mperfecta.
7th eel. New York: McGraw-H i ll, 2007: Fig. 200-2.
Reproduced, with permission, from Wol ff K et al. Fitzpa trick 's
Dennatology in Genera l Medicine, 7th eel. New York: McGraw
D Syphilis: Image B. Syp h i lis clark-field microscopy. Reproduced, with
H ill, 2007: Fig. 1 39- 1 2.
permission, from the Centers for Disease Control and Prevention,
Atlanta, GA. Photo credit: W. F. Schwartz.
D Vitamin D: Image A. Rickets. Reproduced, with permission, from Dr.
Michael L. Richardson /Wiki media Com mons. 11!1 Gardnerel/a vagina/is: I mage A. Bacterial vaginosis. Reproduced,
with permission, from U SMLE-Rx.com.
D Lysosomal storage d iseases: I mage A. Gaucher's disease. Reproduced,
with permission, from Lichtman MA et al. Lich tma n 's Atlas of D Systemic mycoses: I mage A. Histoplasma caps u la twn . Reproduced,
Hema tology. New York: McGraw-Hill, 2007: Fig. V. I-1. 1 6. with permission, from the Centers for Disease Control and
Prevention, Atlanta, GA. Photo credit: D. T. McCienan.
D Lysosomal storage d iseases: I mage B. Niemann-Pick disease.
Reproduced, with permission, from Lichtman MA et al. D Systemic mycoses : Image B. B lasto myces derrn a titidis. Reproduced,
Lich tman's Atlas of Hema tology. New York: McGraw-Hill, 2007: with permission, from Brooks GF et al. Jawetz, Meln ick, 6
Fig. V.H. I 8. Adelberg's Medical Microbiology, 2 5th eel. New York: McGraw
H i ll, 20 1 0 : Fig. 4 5 - 1 8A.
Microbiology D Systemic mycoses: Image D. Pa racoccidioides brasiliensis.

Reproduced, with permission, from Wol ff K et al. Fitzpa trick 's
D Staphylococcus aureus: Image A. S taphylococcus a u reus. Derm a to logy in Genera l Medicine, 7th eel . New York: McGraw
Reproduced, with permission, from the Centers for Disease
H il l , 2007: Fig. 1 90- 1 6.
Control and Prevention, Atlanta, GA. Photo credit: Richard
Facklam.
D Cutaneous mycoses: I mage A. Ma lassezia fu rfur. Reproduced, with
permission, from Wolff K et al. Fitzpa trick's Denna tology i n
11!1 1 and 2 tuberculosis: Image A. Caseating granuloma. Reproduced, General Medicine, 7th eel. ew York: McGraw-H ill, 2007: Fig.
with permission, from USMLE-Rx.com. 1 89- l l .
11!1 Mycobacteria : Image A. Acid-fast bacil l i. Reproduced, with D Opportun istic fungal i nfections: Image A (left). Candida a lbicans
permission, from USMLE-Rx.com. pseudohyphae. Adapted, with permission, from Y. Tam be/
Wikimeclia Com mons.
D Leprosy (Ha nsen's disease) : Image A. Leprosy. Reproduced, with
permission, from Wolff K et al. Fitzpatrick 's Color Atlas and D Opportun istic fungal infections: I mage A (right) . Candida a lbicans
Synopsis of Clinical Dennatology, 5 th eel. ew York: McGraw germ tubes. Reproduced, with permission, from Brooks GF et al.
H ill, 200 5 : Fig Z Z- 5 2. Jawetz, Meln ick, 6 Adelberg 's Medica l Microbiology, 2 5th eel. 1 ew
York: McGraw-Hill, 2 0 1 0 : Fig. 4 5-2 1 .
D Neisseria: Image A. eisseria gonorrhoeae. Reproduced, with
permission, from Wolff K, Johnson RA. Fitzpa trick 's Color Atlas 11!1 Opportun istic fungal infections: Image B (left) . Aspergillus fu migatus
and Synopsis of Clinical Denna tology, 6th eel. New York: septate hyphae. Reproduced, with permission, from USM LE-Rx.
McGraw-Hill, 2009: Fig. 24- 5 2. com.
634 SECTION IV P H OTO ACK NOWLEDGME N T S
C Opportunistic fungal i nfections: Image B (right) . Aspergillus fu m iga tus C Protozoa-Others: Image A. Trypanosoma cruzi . Rep roduced, with
conidiophore. Reproduced , with permission , from B rooks GF et permission, from the Centers for Disease Control and Prevention ,
al. Jawetz, Meln ick, 6 Adelberg's Medica l M icrobiology, 2 5 th eel. Atlanta, GA. Photo credit: Mae Melvin .
New York: McGraw-Hill, 20 1 0 : Fig. 4 5-6.
C Protozoa-Others: Image B. Leish mania . Reproduced, with
C Opportun istic fungal infections: I mage C. Cryptococcus neofonnans. permission , from the Centers for Disease Control and Prevention,
Reproduced, with permission , from the Centers for Disease Atlan ta, GA. Photo credit: Francis W. Chandler.
Control and Prevention , Atlanta, GA.
C Herpesviruses: Image A. Herpes l abialis. Reproduced , with
C Opportun istic fungal infections: Image D . Mucor. Reproduced , with permission , from Wol ff K et al . Fitzpa trick 's Derm a to logy in
permission , from Wolff K et al. Fitzpa trick's Dermatology in Genera l Medicine, 7th eel. New York: McGraw-Hill, 2007: Fig.
Genera l Medicine, 7th eel. New York: McGraw-Hil l , 2007: Fig. 1 9 3-3.
1 90- l 9C.
IS.!I Herpesvi ruses: I mage B. Herpes genitalis. Reproduced , with
Pneumocystis jirovecii: Image A. Pnewnocystis jirovecii. Reproduced , permission , from Dr. Richard P. Usa tine and the Color Atlas of
with permission , from U SMLE-Rx.com . Fam ily Medicine.
C Sporothrix schenckii: Image A. Sporoth rix schenckii. Reproduced, C Herpesviruses: Image C. Herpes zoster. Reproduced , with
with permission, from the Cen ters for Disease Con trol and permission , from Fauci AS et al . Harrison 's Principles of l n temal
Prevention , Atlanta, GA. Photo credit: Lucil le K. Georg. Medicine, 1 7th eel . New York: McGraw-Hill, 2008: Fig. 1 7 3- 3 .
C Protozoa-G I infections: Image B. Giardia cyst. Reproduced , with

Herpesviruses: I mage D . CMV. Reproduced, with permission, from
permission , from the Cen ters for Disease Con trol and Prevention,
U SMLE-Rx.com .
Atlanta, GA.
C EBV: Image A. Atypical lymphocytes in E BV. Reproduced, with
C Protozoa-G I infections: Image C. E n tamoeba h istolytica .
permission, from Fauci AS et a! . Ha rrison 's Principles of l n tenwl
Reproduced , with permission , from the Centers for Disease
Medicine, 1 7th eel. New York: McGraw-Hill, 2008: Fig. 1 74-2 .
Control and Prevention , Atlanta, GA.
C Rotavi rus: I mage A. Rotavirus. Reproduced, with permission, from
C Protozoa-GI infections: Image D. E n tamoeba cyst. Reproduced , with
the Centers for Disease Con trol and Prevention , Atlanta, GA.
permission , from the Centers for Disease Control and Prevention ,
Photo credit: Erskine Pal mer.
Atlanta, GA.
C Measles vi rus: Image A. Koplik spots. Reproduced , with permission ,
C Protozoa-GI infections: Image E. Cryptosporidiu m . Reproduced, with
from Wol ff K et al. Fitzpa trick 's Derma tology in Genera l Medicine,
permission , from the Centers for Disease Control and Prevention ,
7th eel . New York: McGraw-Hill, 2007: Fig. 1 92- l .
Atlanta, GA.
C Measles virus: I mage B . Rash of measles. Adapted , with permission ,

C Protozoa-CN S infections: Image A. Toxoplasma gondii. Reproduced ,
from Wol ff K et al . Fitzpa trick 's Dermatology in Genera l Medicine,
with permission , from the Cen ters for Disease Control and
7th eel. New York: McGraw-Hil l , 2007: Fig. 1 92-3 .
Prevention , Atlanta, GA. Photo credit: L. L. Moore, Jr.
C M umps virus: I mage A. Mumps. Reproduced , with permission , from

C Protozoa-CNS infections: Image B. Naegleria fowleri . Reproduced ,
with permission , from the Centers for Disease Control and the Cen ters for Disease Control and Prevention , Atlanta, GA.
Prevention , Atlanta, GA.
Rabies virus: I mage A. Rabies virus. Reproduced , with permission ,
C Protozoa-C N S infections: I mage C. Trypanosoma ga mbiense. from U SMLE-Rx.com .

Reproduced , with permission , from the Centers for Disease
C Rabies virus: Image B. Negri bodies. Reproduced , with permission ,
Con trol and Prevention , Atlanta, GA. Photo credit: Mae Melvin.
from the Cen ters for Disease Control and Preven tion , Atlanta,
C Protozoa-Hematologic infections: Image A. Plasmodi u m trophozoite. GA. Photo credit: Daniel P. Perl.
Reproduced , with permission , from the Cen ters for Disease
C ToRCHeS infections: I mage A. Congenital syphilis facies. Reproduced ,
Control and Prevention , Atlanta, GA. Photo credit: Steven Glen n .
with permission , from Wol ff K et al. Fitzpa trick 's Derma tology in
C Protozoa-Hematologic infections: Image B. Plasmodi u m schizont. General Medicine, 7th ed . New York: McGraw-Hill, 2007 : Fig.
Reproduced, with permission , from the Centers for Disease 200-2 8 .
Control and Prevention , Atlanta, GA. Photo credit: Steven Glen n .
C ToRCHeS i nfections: Image B . H utchi nson 's teeth . Reprod uced , with
C Protozoa-Hematologic infections: Image C. Babesia . Reproduced , permission, from Wolff K et a! . Fitzpa trick 's Derm a to logy i n
with permission , from the Centers for Disease Control and Genera l Medicine, 7th ed. New York: McGraw-Hill, 2007: Fig.
Prevention, Atlanta, GA. 200-3 1 B .
P H OTO ACK N OWLED G ME N TS SECTION IV 63 5
D Red rashes of childhood : I mage A. E rythema infectiosum. D Diabetes mellitus: Image A. D iabetic retinopathy. Reproduced, with
Reproduced, with permission, from Wol ff K, Johnson RA . permission, from M c Phee S J , Papadakis MA. C u rre n t Medical
Fitzpa trick's Color Atlas and Synopsis o f Clinical Denna tology, 6th Diagnosis 6 Trea tmen t 2 0 1 1 . New York: McGraw- H i l l , 20 1 1 :
eel . New York: McGraw-Hill, 2009: Fig. 27-24A. Chapter 7 .
D Red rashes of childhood: I mage B. Hand-foot-mouth disease.

Reproduced, with permission, from Hurwitz RM et a l . Pa thology Gastrointestinal
of the Skin: Atlas of Clinical-Pathologica l Correla tio n , 2nd eel .
Stamford CT: Appleton & Lange, 1 998. li!l Gl embryology: Image A. Omphalocele. Reproduced, with
permission, from U S M LE-Rx.com.
D Peyer's patches: Image A. Peyer's patches. Reproduced, with

Pathology
perm ission, from Wikimedia Com mons.
li!l Amyloidosis: Image A. Amyloidosis. Reproduced, with permission,
from USMLE-Rx.com. D Achalasia : Image A. Achalasia . Reproduced, with permission, from
Lalwani AK. C u rren t D iagnosis 6 Trea tmen t in Otolaryngology
Head 6 Neck S u rgery, 2 n d eel . New York: McGraw- H i l l , 2008. Fig
Cardiovascular 3 5- 3A.
li!l Atherosclerosis: Image A. Atherosclerosis. Reprod uced, with
permission, from U S M LE-Rx.com . li!l Barrett's esophagus: Image A. Barrett's esophagus. Reproduced, with
permission, from USML E-Rx. com .
D Aortic dissectio n : I mage A. Aortic dissection . Reproduced, with
permission, from Bru n icardi FC et al. Schwa rtz's Principles of li!l Stomach cancer: I mage A. Signet ri ng adenocarci noma. Reproduced,
Surgery, 9th eel. New York: McGraw-Hill, 2009: Fig. 2 2- 1 8 . with permission, from U SMLE-Rx .com.
D Cardiomyopath ies: I mage A. Hypertrop h i c cardiomyopathy. D I nflammatory bowel d isease: I mage A. Croh n's disease. Reproduced,
Reproduced, with permission, from Fuster V et a l . H u rst's The with permission, from Way LW, Doherty G M . C u rrent S u rg ica l
Heart, 1 3th eel . New York: McG raw-Hill, 20 1 1 : Fig. 8 2- 3 . Diagnosis a n d Trea tment, l l th eel. New York: McG raw- H i l l , 200 3 :
69 1 .
li!l Bacterial endocard itis: Image A . S p l inter hemorrhage. Reproduced,
with permission, from U SMLE-Rx. com . li!l Inflammatory bowel d isease: Image B. Ul cerative col itis. Reproduced,
with perm ission, from U S M LE-R--.c com .
D Rheumatic fever: Image A. Aschoff body. Adapted, with permission,
from Dr. Ed Uth man/Wiki media Com mons. li!l Colorecta l cancer: Image A. "Apple core" lesion . Reproduced, with
permission, from U S M LE-Rx. com .
Endocrine D Cirrhosis a n d portal hypertension: Image A. Ci rrhosis, gross l iver.
D Cushi ng's syndrome: Image A. Ad renocortical adenoma. Adapted,

Reproduced, with permission, from B runicardi FC et a l .
Schwa rtz 's Principles o f S u rgery, 9th eel . New York: McG raw-Hill,
with permission, from Chandrasoma P, Taylor CR. Concise
Pa thology, 3 rd eel . Stamford, CT: Appleton & Lange, 1 998: Fig.
2009: Fig. 3 1 - 1 6 .
60- 3 .
D Ci rrhosis a n d portal hypertension : I mage B. Ci rrhosis, microscopic.
D Pheochromocytoma: Image A. Pheoch romocytoma . Reprod uced, Reprod uced, with perm ission, from B ru n i cardi FC et a l .
with permission, from Kantarjian l-IM et a l . MD Anderson Schwa rtz's Principles o f S u rgery, 9th eel . New York: McGraw-Hill,
Manual of Medica l Oncology . New York: McGraw-Hill, 2006: Fig. 2009: Fig. 3 1 - 1 6.
3 1-17.
li!l Alcoholic l iver disease: Image A. Macrovesicular steatosis.
li!l Hyperthyroidism: Image A . Multi nodular goiter. Reproduced, with Reproduced, with permission, from U S M LE-Rx.com .
permission, from U SMLE-Rx. com .
D Gallstones (cholelithiasis) : I mage A. Gallstones. Reproduced, with
li!l Hyperthyroidism: I mage B. Graves' disease (exophth al mos). permission, from Wikimedia Com mons.
Reproduced, with permission, from U SMLE-Rx . com .
D Acute pancreatitis : I mage A. Acute pancreatitis. Reproduced, with
li!l Thyroid cancer: Image A. Thyroid pap i l l a ry carcinom a . Reproduced, permission, from G reenberger NJ et al . C u rren t Diagnosis 6
with perm ission, from USMLE-Rx.com; i mage courtesy of Dr. Treatment: Gastroen terology, Hepatology, 6 E ndosco(Jy. New York:
Stuart Flyn n . McG raw- H i l l, 2009: Fig. 9-49.
636 SECTION I V P H OTO ACK N OWLED GMEN T S
Hematology and Oncology D Pathologic RBC forms: I mage E. Macro-ovalocyte. Adapted, with
permission, from Lichtman MA et al. Lich t m a n 's Atlas of
a Erythrocyte: Image A . Erythrocyte. Reproduced, with perm ission,
Hema tology. New York: McGraw-Hill, 2007: Fig. I.C. 88.
from Mescher AL. Junqueira 's Basic Histo logy: Text 6 Atlas, 1 2th
ed. New York: McGraw-Hill, 20 1 0 : Fig. 1 2-4A.
a Pathologic RBC forms: Image F. Ringed sicleroblasts. Reproduced,
with permission, from Lichtman MA et al. Lich t m a n's Atlas of
D Platelet (thrombocyte) : I mage A. Platelets. Reproduced, with
Hema tology. New York: McGraw-Hill, 2007: Fig. V. G. 1 2 .
permission, from Mescher AL. Ju nqueira 's Basic Histology: Text 6
Atlas, 1 2th ed. New York: McGraw-Hill, 20 1 0 : Fig. 1 2- 1 3A.
Pathologic RBC forms: I mage G . Sch istocyte/helmet cell.
Reproduced, with perm ission, from U SMLE-Rx.com.
D Neutrophil: I mage A. Neutrophil. Reproduced, with permission,
from Mescher AL. Junqueira 's Basic Histology: Text 6 Atlas, 1 2th Pathologic RBC forms: I mage H . Sickle cell. Reproduced, with
eel. New York: McGraw- H i ll, 20 1 0 : Fig. 1 2-7B. perm ission, from U S M LE-Rx.com.
D Monocyte: Image A. Monocyte. Reproduced, with permission, from Pathologic RBC forms: I mage I . Spherocyte. Reproduced, with
Mescher AL. Ju nqueira 's Basic Histology: Text 6 Atlas, 1 2th eel. permission, from U S M LE-Rx.com.
New York: McGraw-Hill, 20 1 0 : Fig. 1 2- 1 2C.
D Pathologic RBC forms: I mage J. Teardrop cel l. Reproduced, with
D Macrophage: I mage A. Macrophage. Reproduced, with permission, permission, from Fauci AS et al. Harrison 's Principles of l n temal
from Lichtman MA et al . Lichtm a n 's Atlas of Hema tology. New Medicine, 1 7th eel. New York: McGraw-H i ll, 2008: Fig. 5 8-7 .
York: McGraw-Hill, 2007: Fig. V.H. l l .
Pathologic RBC forms: I mage K. Target cell. Reproduced, with
D Eosinophi l : Image A. Eosinophil. Reproduced, with permission, perm ission, from U SMLE-Rx.com.
from Mescher AL. Ju nqueira 's Basic Histology: Text 6 Atlas, 1 2th
eel. New York: McGraw-Hill, 20 1 0 : Fig. 1 2-9B. D Other RBC pathologies: I mage A. Heinz bodies. Reproduced, with
perm ission, from Lichtman MA et al. Lich tman's Atlas of
D Basophil: I mage A. Basoph i l. Reproduced, with permission, from Hema tology. New York: McGraw-Hill, 2007: Fig. I. B.2.
Mescher AL. ]unqueira 's Basic Histology: Text 6 Atlas, 1 2th eel.
D Other RBC pathologies: I mage B. Howell-jolly bodies. Reproduced,
New York: McGraw-Hill, 20 1 0 : Fig. 1 2- 1 0A.
with permission, from Lichtman MA et al. Lich tman's Atlas of
Hema tology. New York: McGraw-Hill, 2007: Fig. I . B. 3.
D Mast cell : I mage A. Mast cell. Reproduced, with permission, from
Mescher AL. Ju nqueira 's Basic Histology: Text 6 Atlas, 1 2th eel.
Microcytic, hypoch romic (MCV < 80 fL) anemia: Image B .
New York: McGraw-H ill, 20 1 0 : Fig. 5- 5A.
-Thalassemia major. Reproduced, with permission, from
USMLE-Rx.com.
D Lymphocyte : I mage A. Lymphocyte. Reproduced, with permission,
from Mescher AL. Ju nqueira 's Basic H istology: Text 6 Atlas, 1 2th
I ntrinsic hemolytic normocytic anemia: I mage A. Sickle cell disease.
eel . New York: McGraw-Hill, 20 1 0 : Fig. 1 2- 1 1 C.
Reproduced, with perm ission, from U SMLE-Rx.com.
D Plasma cel l : Image A. Plasma cell. Reproduced, with permission,

Non-Hodgkin's lymphoma: I mage A. Burkitt's lymphoma "starry sky"
from Mescher AL . ]u nqueira 's Basic H istology: Text 6 Atlas, 1 2th
appearance. Reproduced, with permission, from U SMLE-Rx.com.
eel. New York: McGraw-Hill, 20 1 0 : Fig. 5-7.
D Multiple myeloma: Image A. Multiple myeloma lytic lesions.
D Pathologic RBC forms: Image A. Acanthocyte. Reproduced, with Reproduced, w ith perm ission, from Kantarj ian l-IM et al. MD
permission, from Fauci AS et al. Harrison 's Principles of lntemal Anderson Manual of Medica l Oncology. New York: McGraw-Hill,
Medicine, 1 7th eel. New York: McGraw-Hill, 2008: Fig. 5 8- 1 0. 2006: Fig. 8- 1 .
D Pathologic RBC forms: Image B. Basophilic stippling. Reproduced, D Multiple myeloma: I mage B . Multiple myeloma smear. Reproduced,
with permission, from Lichtman MA et al. Lich tma n 's Atlas of with permission, from Kantarj ian l-IM et al. MD Anderson
H ematology . New York : McGraw-H ill, 2007: Fig. I . B. l . Manual of Medica l Oncology. New York: McGraw-Hill, 2006: Fig.
8-4.
D Pathologic RBC forms: Image C. Bite cell. Reproduced, with
permission, from Lichtman MA et al. Lich tman's Atlas of Leukemias: Image A. Acute lymphoblastic leukemia/lym phoma.
Hema tology. New York: McGraw-Hill, 2007: F ig. I .C. 3 3. Reproduced, with permission, from U SMLE-Rx.com.
D Pathologic RBC forms: Image D. Elliptocyte. Reproduced, with Leukemias: I mage B. Small lymphocytic lymphoma/chronic
permission, from Lichtman MA et al. Lich tman's Atlas of lymphocytic l eukemia. Reproduced, with permission, from
Hematology. New York: McGraw-Hill, 2007: Fig. I .A.4. U S M LE-Rx.com.
P H OTO ACK N OWLED GMEN T S SECTION IV 63 7
li!! Leu kemias: Image C. Hairy cell leukemia . Reproduced, with li1!J Dermatologic macroscopic terms: I mage D. Plaque. Reproduced, with
permission, from U SMLE-Rx.com . permission, from Dr. Richard P. Usatine and the Color Atlas of
Fa m i ly Medicine.
li!! Leukemias: I mage D. Acute myelogenous leukemia. Reproduced,
with permission, from U SMLE-Kx.co m . li1!J Dermatologic macroscopic terms: I mage E. Vesicle. Reproduced, with
permission, from Dr. Richard P. Usatine and the Color Atlas of
li!! Leukemias: I mage E. Ch ronic myelogenous leukemia . Reproduced, Fa m i ly Medicine.
with permission, from U SMLE-Rx.com .
li1!J Dermatologic macroscopic terms: I mage F. Bulla. Reproduced, with
D Langerhans cell histiocytosis: I mage A. Birbeck granules. Reproduced,
permission, from Dr. Richard P. Usa tine and the Color Atlas of
with permission, from Lichtman MA et al. Lich tman's Atlas of
Fa m i ly Medicine.
Hema tology. ew York: McG raw-Hill, 2007: Fig. V l . C . 2 .
li1!J Dermatologic macroscopic terms: I mage G . Pustule. Reproduced, with

Musculoskeletal a n d Connedive Tissue Fa m i ly Medicine.
li!! Epidermis layers : Image A. Layers of epidermis. Reproduced, with
permission, from U SMLE-Rx.com ; image courtesy of Dr. Kurt li1!J Dermatologic macroscopic terms: I mage H . Wheal. Reproduced, with
Johnson . permission, from Dr. Richard P. Usa tine and the Color Atlas of
ta m i ly Medicine.
D Wrist bones: Image A. Wrist bones. Reproduced, with permission,
from Brunicarcli FC et al. Schwa rtz 's Principles of S u rgery, 9th eel . li1!J Dermatologic macroscopic terms: I mage I . Scale. Reproduced, with
New York: McGraw-Hill, 2009: Fig. 44-2B. permission, from Dr. Richard P. Usatine and the Color Atlas of
Fa m i ly Medicine.
li!! Osteoarthritis: Image A . Osteoarth ritis. Reproduced, with permission,
from U S M LE-Rx.com . lll1l Dermatologic macroscopic terms: I mage J . Crust. Reproduced, with
li!! Gout: Image A. Tophi in joints. Reproduced, with permission, from
Fa m i ly Medicine.
U S M LE-Rx.com .
li1!J Pigmented skin disorders: I mage A. Albinism. Reproduced, with
D Gout: Image B. Gout. Reproduced, with permission, from LeBlond
RF et al. DeGowin 's Diagnostic Exa m i n a tion, 9th eel . ew York:
Fa m ily Medicine.
McGraw-Hill, 2009: Plate 3 0 .
li1!J Pigmented skin disorders: Image B. Melasm a . Reproduced, with
li!! Sarcoidosis: Image A . Sarcoidosis. Reproduced, with permission,
from USMLE-Rx.com .
Fa m i ly Medicine.
D Polymyositis/dermatomyositis: I mage A. Gottron 's papules.

lll1l Pigmented skin disorders: I mage C . Vitiligo. Reproduced, with
Reproduced, with permission, from Wolff K et al . Fitzpa trick's
Denna tology in General Medicine, 7th eel. New York: McGraw
Fa m i ly Medicine.
Hil l, 2008: Fig. 1 5 7- 5 .
li1!J Common skin d isorders: I mage A. Verrucae. Reproduced, with

D Polymyositis/dermatomyositis: Image B . Heliotrope rash . Reproduced,
with permission, from Wolff K, Johnson RA. Fitzpa trick 's Color permission, from Dr. Richard P. Usa tine and the Color Atlas of
Atlas and Synopsis of Clin ical Denna tology, 6th eel . New York: Fa m i ly Medicine.
McGraw-Hill, 2009: Fig. 1 4- 1 6.

li1!l Common skin d isorders : I mage B. Con dyloma acuminatum .
D Myositis ossifica ns: Image A. Myositis ossificans. Reproduced, with Reproduced, with permission, from Dr. Richard P. Usa tine and
permission, from T. Dvorak/Wikimeclia Com mons. the Color Atlas of l<a m i ly Medicine.
li1!J Dermatologic macroscopic terms: Image A. M acule. Reproduced, with 1i1!J Common skin disorders: I mage C. l ntradermal mel anocytic nevus.
permission, from Dr. Richard P. Usa tine and the Color Atlas of Reproduced, with permission, from Dr. Richard P. Usatine and
Fa mily Medicine. the Color Atlas of Fam i ly Medicine.
li1!l Dermatologic macroscopic terms: Image B. Patch . Reproduced, with lll1J Common skin disorders: Image D. Junctional melanocytic nevi.
permission, from Dr. Richard P. Usatine and the Color Atlas of Reproduced, with permission, from Dr. Richard P. Usatine and
Fa m i ly Medicine. the Color Atlas of Fam i ly Medicine.
li1!l Dermatologic macroscopic terms: Image C. Papule. Reproduced, with lll1J Common skin disorders: Image E. U rticaria . Reproduced, with
permission, from Dr. Richard P. Usa tine a n d the Color Atlas of permission, from Dr. Richard P. Usa tine and the Color Atlas of
Fa mily Medicine. Fa m i ly Medicine.
638 SECTION IV P H OTO ACK N OWLED GMEN TS
111!1 Common skin d isorders: I mage F. Freckles. Reproduced, with lll!l Blistering skin disorders: Image F. Toxic epidermal necrosis with
permission, from Dr. Richard P. Usatine and the Color Atlas of slough ing of ski n on face. Reproduced, with permission, from Dr.
l<c11 n i ly Medicine. Richard P. Usat i ne and the Color Atlas of Fa m i ly Medicine.
lll!l Common skin disorders: I mage G . Atop ic dermatitis on face. lll!l Blistering skin d isorders: I mage G . Toxic epi dermal necrosis with ski n
Reproduced, with permission, from Dr. Richard P. Usa tine and slough i ng. Reproduced, w i t h permission, from D r . Richard P.
the Color Atlas of Fa m i ly Medici ne. Usatine and the Color Atlas of Fa m ily Medicine.
lll!l Common skin disorders: I mage H . Atop ic dermatitis i n antecubital

lll!l M iscel laneous skin d isorders: Image A (left) . Acanthosis nigricans with
fossa . Reproduced, with permission, from Dr. Richard P. Usatine
ski n tags. Reproduced, with permission, from Dr. Richard P.
and the Color Atlas of Fam ily Medicine.
Usa tine and the Color Atlas of Fa m i ly Medicine.
lll!l Common skin d isorders: I mage I . Allergic contact dermatitis from

lll!l Miscella neous skin d isorders: I mage A (right) . Acanthosis n igricans
nickel exposure. Reproduced, with permission, from Dr. Richard
with smooth, velvety appearance. Reproduced, with perm ission,
P. Usa tine and the Color Atlas of Fa m i ly Medicine.
from Dr. Richard P. Usatine and the Color Atlas of Fam i ly
Medicine.
lll!l Common skin disorders: Image J . Allergic contact dermatitis clue to
neomycin . Reproduced, with permission, from Dr. Richard P.
lll!l Miscellaneous skin d isorders: Image B (left). Actinic keratosis on face.
Reproduced, with permission, from Dr. Richard P. Usatine and
111!1 Common skin d isorders: Image K. Psoriasis with positive Auspitz sign . the Color Atlas of Fa m ily Medicine.
Reproduced, with permission, from Dr. Richard P. Usa tine and
the Color Atlas of Fa m i ly Medicine. lll!l M iscellaneous skin d isorders: Image B (right) . Acti nic keratoses on
hands and forearm . Reproduced, with permission, from Dr.
lll!l Common skin d isorders: I mage L. Psoriatic arthritis. Reproduced, Richard P. Usatine and the Color Atlas of Fam i ly Medicine.
with permission, from Dr. Richard P. Usatine and the Color Atlas
of Fa m i ly Medicine. lll!l M iscellaneous skin d isorders: Image C (left) . E rythema nodosum i n
patient w i t h streptococcal i n fection . Reproduced, with perm ission,
lll!l Common skin disorders: I mage M . Seborrheic keratosis with horn from Dr. Richard P. Usatine and the Color Atlas of Fa m i ly
cysts. Reproduced, with permission, from Dr. Richard P. Usatine Medicine.
and the Color Atlas of Fa m i ly Medicine.
lll!l Miscella neous skin d isorders: I mage C (right) . E rythema nodosum i n
lll!l Common skin disorders: Image N . "Stuck on" plaques of seborrheic patient w i t h leprosy. Reprod uced, w i t h permission, from Dr.
keratosis. Reproduced, with permission, from Dr. Richard P. Richard P. Usa tine and the Color Atlas of Fa m i ly Medicine.
lll!l M iscella neous skin d isorders: I mage D (left). Lichen planus
Blistering skin d isorders: Image A. Pemph igus vulgaris. Reproduced, appearance on l ight ski n . Reproduced, with permission, from Dr.
with permission, from USM LE-Rx.com . Richard P. Usatine and the Color Atlas of Fa m i ly Medicine.
lll!l Blistering skin d isorders: Image B. Bullous pemphigoid. Reproduced,

lll!l M iscellaneous skin d isorders: I mage D (right) . Lichen planus
with permission, from Dr. Richard P. Usatine and the Color Atlas
appearance on clark ski n . Reproduced, with permission, from Dr.
of Fa m i ly Medicine.
Richard P. Usatine and the Color Atlas of Fa m i ly Medicine.
C Bl istering skin disorders: I mage C. Dermatitis herpetiform is.

lll!l M iscellaneous skin d isorders: Image E (left) . Herald patch of pityriasis
Reproduced, with permission, from Fauci AS et al . Ha rrison 's
rosea. Reproduced, with permission, from Dr. Richard P. Usatine
Principles of Internal Medicine, 1 7th eel. New York: McGraw-H i ll,
and the Color Atlas of Fa m ily Medicine.
2008: Fig. 5 2-8.
lll!l Miscellaneous skin d isorders: I mage E (right) . Pityriasis rosea with

lll!l Blistering skin d isorders: Image D. Erythema multiforme.
Christmas tree distribution . Reproduced, with permission, from
Dr. Richard P. Usatine and the Color Atlas of Fa m i ly Medicine.
the Color Atlas of Fa m ily Medicine.
lll!l Blistering skin d isorders: Image E (left) . Stevens-Johnson syndrome 111!1 M iscellaneous skin d isorders: I mage F. Sunburn and impetigo.
with eye involvement. Reproduced, with permission, from Dr. Reproduced, with permission, from Dr. Richard P. Usatine and
Richard P. Usa tine and the Color Atlas of Fa m i ly Medicine. the Color Atlas of Fa m i ly Medicine.
lll!l Blistering skin d isorders: Image E (right) . Stevens-Johnson syndrome lll!l Infectious skin d isorders: I mage A. I m petigo. Reproduced, with
with lip lesions. Reproduced, with permission, from Dr. Richard permission, from Dr. Richard P. Usatine a n d the Color Atlas of
P. Usati ne and the Color Atlas of Fa m ily Medicine. Fa m i ly Medicine.
'
P H OTO ACK N OW LE D G M EN T S SECTION IV 639
lll1l lnfectious skin disorders: Image B. Bullous impetigo. Reproduced, lil!l Skin cancer: I mage K . Lentigo mal i gn a mel anom a . Reproduced,
with permission, from Dr. Richard P. Usa tine and the Color Atlas with permission, from Dr. Richard P. Usa tine and the Color Atlas
of f<cll n i ly Medicine. of Fa m i ly Medicine.
lll1l Infectious skin d isorders: I mage C. Cel l u l i tis. Reproduced, with lil!l Skin cancer: I mage L. Acrolentigi nous melanom a . Reproduced, with
permission, from Dr. Richard P. Usati ne and the Color Atlas of perm ission, from Dr. Richard P. Usatine and the Color Atlas of
Fam i ly Medicine. Fa m ily Medicine.
lll1l Infectious skin disorders : I mage D. Necrotizing fasciitis. Reproduced,

with permission, from Dr. Richard P. Usatine and the Color Atlas Neurology
of Fa mily fliledicine.
C Aneurysms: Image A. Berry aneurysm . Reproduced, with
permission, from Fauci AS et a l . Ha rrison 's Principles of / n temal
lll1l l nfectious skin disorders: I mage E. Staphylococcal scal ded ski n
Medicine, 1 7th eel. ew York: McG raw- H i l l , 2008: Fig. 269-8C.
syndrome. Reproduced, with permission, from Dr. Richard P.
Usatine and the Color Atlas of Fa m ily Medicine.
C I ntracranial hemorrhage: Image B. Subdural hematoma . Reproduced,
w i th perm ission, from Chen MY et al . Basic Radiology, 1 st eel .
lll1l Infectious skin d isorders: Image F. H a i ry leukoplakia. Reproduced,
New York: McG raw-H i l l, 200 5 : Fig. 1 2- 3 2 .
with perm ission, from Dr. Richard P. Usatine and the Color Atlas
of Fam i ly Medicine.
C I ntracranial hemorrhage: Image D . Hypertensive hemorrhage.
Reprod uced, w i th permission, from Waxman SG. Clin ical
lll1l Skin cancer: Image A. Basal cel l carcinoma with rolled borders.
Neuroa n a tomy, 26th eel. New York: McG raw-H i l l , 2009: Fig.
2 5-20.
the Color Atlas of Fa m i ly Medicine.
li!l Hydrocephalus: Image A. Normal pressure hydrocephal us.

lll1J Skin cancer: Image B. Basal cel l carcinoma w i th nonhea l i n g ulcer.
Reproduced, with permission, from U S M LE-Rx.com .
the Color Atlas of Fam i ly Medicine.
1i!1 Dementi a : Image A. Alzhei mer's disease: -amyloid deposi ts.
lll1l Skin cancer: Image C. Basal cel l ca rci noma w i th sca l i n g pl aque.
Reproduced, with permission, from Dr. Richard P. Usa tine and
C M u ltiple sclerosis: Image A. M u l tiple scl erosis. Reproduced, with
permission, from Fauci AS et a l . Ha rriso n 's Principles of lntemal
Medicine, 1 7th eel. New York: McG raw-H i l l , 2008: Fig. 3 7 5-3A.
li!l Skin cancer: Image D. Basal cell carcinoma h istology. Reproduced,
with permission, from U S M LE-Rx.com .
li!l Adult primary brain tumors: Image A. G l iobl astoma multi forme.
Reproduced, with permission, from U S M LE-Rx.co m .
lll1l Skin cancer: Image E. Squamous cell carcinoma on face.
li!l Adult primary bra i n tumors: I mage B . O l i godendrogl ioma.
lll1l Skin cancer: Image F. Squamous cel l carci noma on l i p . Reproduced,

with permission, from Dr. Richard P. Usa tine and the Color Atlas
Renal
of Fa mily Medicine.
C Neph rotic syndrome: Image A. Focal segmental glomeru losclerosis.
li!l Skin cancer: Image G . Squamous cel l carci noma histology. Reproduced, with permission, from Lerma EV et al. Curren t
Reproduced, with permission, from U S M LE-Rx.com . Diagnosis 6 Trea tment: Neph rology 6 Hypertensio n . New York:
McGraw-H i l l, 2009: Fig. 2 5- 1 B .
lll1l Skin cancer: Image H. Keratoacanthoma . Reprod uced, with
perm ission, from Dr. Richard P. Usa tine and the Color Atlas of li!l Neph rotic syndrome: Image B. Membranous nephropa thy.
Fa mily Medicine. Reproduced, with permission, from U S M LE-Rx.com .
lll1l Skin cancer: Image I . Superficial spreading melanoma. Reproduced, C Neph rotic syndrome: I mage D. Membranoprol iferative
with permission, from Dr. Richard P. Usa tine and the Color Atlas glomerulonephritis. Reprod uced, w i th permission, from Lerma
of Fa mily Medicine. EV et al . Cu rrent D iagnosis 6 Treatment: Neph rology 6
Hypertension . New York: McGraw-H i l l , 2009: Fig. 2 8- l .
lli!l Skin cancer: Image J. Nodular melanoma . Reproduced, with
permission, from Dr. Richard P. Usatine and the Color Atlas of li!l Nephrotic syndrome: Image E . Diabetic glomerulosclerosis.
Family Medicine. Reproduced, with permission, from U S M LE-Rx.com.
640 SECTION IV P HOTO ACKNOWLED GMEN TS
li! Neph ritic syndrome: I mage A. Rapidly progressive (crescentic) D Ova rian non-germ cell tumors: Image A . Mucinous cystadenom a .
glomerulonephritis. Reproduced, with permission, from Reproduced, with permission, from Chanclrasoma P, Taylor CR.
USMLE-Rx.com . Concise Pa thology, 3rcl eel .
ew York: McGraw-Hill, 1 997: Fig. 52-
10.
li! Kidney stones: Image A. Staghorn calculus. Reproduced, with
permission, from USMLE-Rx.com . D Malignant breast tumors: I mage A . Comedocarcinoma . Reproduced,
with permission, from Schorge JO et al. Wi lliams Gynecology .
li! Renal cell carcinoma : Image A. Renal cell carcinoma histology. New York: McGraw-Hill, 2008: Fig. 1 2- l l .
Reproduced, with permission, from U SMLE-Rx .com .
li! Prostatic adenocarci noma: I mage A. Prostatic adenocarcinoma .
li! Renal cell carcinoma: I mage B. Renal cell carcinoma, gross kidney. Reproduced, with permission, from U SMLE-Rx .com .
Reproduced, with permission, from U SMLE-Rx.com.
li! Transitional cell ca rcinoma: I mage A. Transitional cell carcinoma.

Respiratory
Reproduced, with permission, from U SMLE-Rx.com .
li! Pulmonary embol i : Image A. Pul monary embolism. Reproduced,
li! Rena l cysts: Image A. AD PKD. Reproduced, with permission, from with permission, from USMLE-Rx.com .
USMLE-Rx.com .
li! Pulmonary embo l i : Image B. Pul monary thromboembol us.
Reproduced, with permission, from U SMLE-Rx.com .
Reproductive
li! Obstructive l u ng d isease: I mage A. E mphysema . Reproduced, with
li! Hydatid iform mole: Image B. Molar pregnancy. Reproduced, with permission, from USMLE-Rx.com.
permission, from USMLE-Rx.com .
D Pneumoconioses: I mage A. Asbestos bodies. Reproduced, with
li! Cervical pathology: I mage A. Koilocytes in cervical condyloma . permission, from Wikimedia Commons.
li! Lung cancer: Image A. Small cell carcinoma . Reproduced, with
D Polycystic syndrome: Image A. Polycystic ovary. Reproduced, with permission, from USM LE-Rx.com .
permission, from DeCherney AH, Nathan L. Curren t Diagnosis 6
Treabnent: Obstetrics 6 Gynecology, l Oth eel . ew York: McGraw li! Lung cancer: I mage B. Squamous cell carcinoma . Reproduced, with
Hill, 2007: Fig. 40- 3 . permission, from USMLE-Rx.com.
I nd ex
A reactions to, 240 Acidic amino acids, 106 Acute disseminated

in renal filtration, 481 Acidoph ils, 287 encephalomyel itis, 445
A-a gradient, 550
as teratogens, 506 Acidosis, 254, 487, 488 Acute gastric ul cers, common/
Abacavi r (ABC ) , 189
Acetaminophen, 405 Acid reflux, 324. See i mportant associations, 576
A band in muscle con traction, 385
antidote to, 239 also Gastroesophageal reflux Acute gastritis, 327
AB blood group, 347
free radicals and, 215 disease ( G E R D ) Acute gl omerulonephritis
Abciximab, 369
reactions to, 240 AC L. See Anterior cruciate l igament diagnostic findi ngs/labs, 573
mechanism of, 349
renal papillary necrosis and, 496 (AC L) renal failure caused by, 496
as therapeutic anti body, 210
Acetazolamide, 499 Acne Acute gout attack, 574
Abdominal aorta
for glaucoma, 449 as papules, 395 Acute hemolytic transfusion
anatomy of, 312
as sulfa drug, 242 prednisone as cause, 373 reactions, 204
aneurysms of, 268
Acetoacetate, 1 13 , 303 Acoustic nerve Acute i nflammation, 214
atherosclerosis and, 580
Acetone, in diabetic ketoacidosis, 303 cisplatin/carboplatin , damage Acute inflammatory demyel inating
compensatory anastomoses, 313
Acetylation, 228 caused by, 373 polyradiculopathy.
Abdominal col ic, 353
Acetyl choline (AC h ) , 124 schwannomas and, 447 See Guillain-Barre syndrome
Abdom inal wall , 317
in Alzheimer's/l luntington's Acoustic neuroma, 412, 447 Acu te i nflammatory response, 345
defects of, 308
diseases, 461 Acromegaly, 301 Acute intermittent porphyria, 358
hernias and, 318
gastric acid regulation, 320 growth hormone and, 290 Acute kidney i n j u ry. See Acute renal
Abducens nerve, 434 fa ilure
neuromuscular blocking drugs octreotide for, 306, 341
in cavernous sinus, 436 Acute lymphoblastic l eukemia
and, 455 ACTH . See Adrenocorticotropic
extraocular muscles and, 439 as neurotransmitter, 413 hormone (ACTH) (ALL), 220, 364
bductor muscles, 383 opioid effect on, 449 ACTH peptide Acute mania
Abctalipoproteincmia, 1 16, 326, 350 REM sleep and, 61 as paraneoplastic effect, 223 antipsychotics for, 473
abl gene, 221 synthesis and signaling of, 232 ACTH-pituitary tumors, 296 l ith ium for, 474
A blood group, 347 Acetylcholine receptors, 230, 231 , 394 Actin Acute mastitis, 535
Abnormal facies, 89 Acetylcholinesterase, 232 in muscle contraction, 385 Acute mesen teric ischemia, 569
Abortion in cholinesterase toxicity, 233 and myosin, 76 Acute m igraines, 456
as eth ical situation, 58 drugs resistant to, 233 Acting out, 458 Acute myelogenous l eukemia, 365
methotrexate for, 371 neural tube defects and, 409 Actinic keratosis, 400, 403 Acute myeloid leukemia, 220
misoprostol for, 341 Acetyl chol inesterase inh ibitors associations, common/ Acute pancreatitis, 3 3 9
treatment for, 575 for Alzheimer's disease, 456 important, 576 acute respi ratory distress syndrome
Abruptio placentae, 495, 526 antidote to, 239 neoplasms associated with , 220 (ARDS) caused by, 556
Abscesses, lung, 560 Acetyl-GoA carboxylase (ACC), 97, 1 13 Actinomyces, 1 1 9, 121 associations, common/
Absence seizures, 445 ACh . See Acetylchol ine (AC h ) penici l l i n for, 176 important, 580
drugs for, 451 , 574 Achalasia, 324 sinus tract drainage, 131 gal lstones as cause, 339
Absolute risk reduction, 52 as esophageal cancer risk vs. Nocardia , 131 serum markers for, 334
ACA. See Anterior cerebral artery factor, 325 Actinomyces israelii, 175 Acute pericarditis, 275
Acanthocytcs, 350 nitric oxide secretion i n , 319 diagnostic findings/labs, 570 Acute-phase proteins, 200
Acantholysis, 396, 398 ACh E (enzyme). pigment produced by, 122 Acute poststreptococcal
Acanthosis, 396 See Acetylchol i nesterase Actinomycin D . See Dactinomycin glomerulonephritis, 492
Acanthosis nigricans, 400 Ac h illes reflex, 432 Action/willpower p h ase of addiction Acute promyelocyti c leukemia, 365,
neoplasms associated with , 220 Achil les tendon xanthoma, 566 recovery, 470 574
niacin as cause, 281 Achl orhydria Activated carriers, 99 Acute pulmonary edema, 449
stomach cancer and, 327 stomach cancer and, 327 Activated protein C (APC ) , 348 Acute pyelonephritis, 495
Acarbose, 305 i n type A gastritis, 327 Activation of T cells and B cells, renal papill ary necrosis and, 496
Accessory nerve, 434, 436 Achondroplasia, 85 196 WBC urinary casts i n , 489
Accommodation of eye, 231 , 439 AC h receptors. See Acetylcholine Active immunity, 202 Acute renal fa il ure, 496
Accu racy, vs. precision, 53 receptors Ac ute bacterial endocarditis, 128 acute tubular necrosis as cause, 496
Acebutolol , 238 Ach rondroplasia, 387 Acute cerebral edema, 421 aspirin as cause, 368
ACE inhibitors, 502 Acid-base physiology, 487 Acute chest syndrome, 356 consequences of, 497
for C l l F, 273 Acidemia, 501 Acute closed-angle glaucoma, 439 Acute respi ratory distress syndrome
contraindicated with hereditary Acid-fast bacteria Acute coronary syndrome (ARD S ) , 556
angioedema, 200 Mycobacteri u m , 1 19 abciximab for, 369 acute pancreatitis as cause, 339
for hypertension, 279 Noca rdia, 1 19 clopidogrel/ticlopidine for, 368 as restrictive lung disease, 555
name suffix, 243 sta i n for, 1 20 heparin for, 367 Acute stress disorder, 467
I N DEX
Acute transplant rejection, 208, 210 berry aneurysms and, 423 facial nerve palsy i n , 437 Alendronate, 405
Acute tubular necrosis, 496 subarachnoid hemorrhage and, 424 marijuana for, 471 Alkalemia
granular casts in, 489 Adrenal cortex, 286 neoplasms associated with, 220 diuretics as cause, 501
renal fai l ur e caused by, 496 adenoma of, 580 opportunistic infections, 579 Alkal i n e phosphatase
Acyclovir, 187 progesterone production, 520 progressive multifocal chol ecystitis and, 339
Adalimumab, 210, 406 Adrenal glands, 286 leukoencephalopathy and, 445 as serum marker, 334
ADAMTS 1 3 , 359 Adrenal hemorrhage, 566 screen ing for, 51 , 80 as tumor marker, 222
Adaptive immune system, 346 Adrenal hyperplasia, 296 Air embol i , 553 Alkal i n e tide, 321
Adaptive immunity, vs. i nnate, 19l Adrenal i nsufficiency, 529 Aki nesia Alkal i n ization of urine, 500
Addiction. stages of overcoming, 470. Adrenal medulla, 286 Parkinson's disease as cause, 569 Alkalosis, 487, 488
See also Alcohol ism tumors of, 297, 581 ALA dehydratase bul imia nervosa and, 469
Addison's disease, 297 Adrenal steroids, 291 in lead poisoni ng, 353, 358 contraction form, 501
cli nical presentation, 569 Adrenoceptors, 232 Alanine, 106 hypokalemia caused by, 487
treatlllenl for, 306 Adrenocortical adenoma, 296 Alanine aminotransferase ( B6), 101 Alkaptonuria (ochronosis), 108
Adductor longissimus, 316 Adrenocortical atrophy, 306 Alar plate, 408, 434 Alkylating agents, l72
Adenine, 64 Adrenocorticotropic hormone Albinism, 82, 108, 396 as carcinogen , 223
Adenocarcinomas, 219 (ACT I- l ) , 291 neoplasms associated with, 220 as teratogens, 506
of colon, 220 para neoplastic syndrome and, 494 Albright's hereditary Allantoic ducts, 508
diseases associ ated with, 220 secretion of, 287 osteodystrophy, 300 Allantois, 508
esophageal , 578 Adriamycin. See Doxorubicin Albumin, 323 Allergic bronchopulmonary
of esophagus, 325 Adult nephrotic syndrome, 490 plasma vol ume measurement, 480 aspergillosis, 145
of l u ng, 558 Adu l t onset diabetes. See Diabetes Albuminocytologic dissociation, 444 All ergi c contact dermatitis, 397
of pancreas, 222, 340 mel l i tus type 2 Albuterol, 563 Allergic reactions. See
pancreatic, 572 Adul t polycystic kidney disease. clinical use, 235 also Hypersensi tivity disorders
of rectum , 315 See A D P K D (adult polycystic Alcohol
basophils i n , 345
of stomach , 220, 222, 327 kidney disease) teratogenic effects, 506, 507
to blood transfusion, 204
Adu l t T-cell l eukemia Alcoholic ci rrhosis, 334, 472, 579
stomach, 580 eosi nop h il ia as result, 345
HTLV- 1 i n , 222 gal lstones and, 339
Adenocorticotropic hormone to sulfa drugs, 242
Adu l t T-ee I I lymphoma, 362 hepatocellular carcinoma and, 335
(ACTH ) All ografts, 208
Advance di rectives, 57 Alcohol ic hepatitis, 315, 334
Cush i ng's syndrome and, 296 All opurinol, 406
Aedes mosquitoes as disease Alcoholic l iver disease, ll4
gestational cortical secretion, 286 for gout, 391 , 574
vector, 1 59 Alcohol ics Anonymous, 472
signaling pathway, 294 reactions to, 241
Aerobes Alcoholism, 470, 472
Adenohypophysis, 287, 414 All-t ra n s relinoic acid
obligate, 121 in anemia algorith m , 354
Adenomas, 219 for acute myelogenous
Afferent arterioles, 479, 481 barbiturate use and, 452
of adrenal cortex, 580 leukemia, 365
constriction in, 481 cataracts and, 439
in hyperparathyroidism, 300, 580 Alopecia
prostaglandin effect on, 486 in chronic pancreatitis, 340
l iver, 335 doxorubicin as cause, 372
Afferent lymphatics, 192 cirrhosis caused by, 333, 579
Adenoma sebaceum, 85, 446 etoposide/teniposide as cause, 373
Afferent pupillary defect, 440 as esophageal cancer risk
Adenomatous polyps, 331 a-agonists
AAatoxins, 145 factor, 325
Adenomyosis, 528 for glaucoma, 449
as carcinogens, 223 essential tremors and, 417
Adenosine, 66 a2 agonists, 236, 237
African sleeping sickness, 148 gastritis caused by, 327
as antiarrhythmic, 284 gynecomastia caused by, 535 <X i-antitryps i n , 79
Afterload and preload, cardiac, 254
reactions to, 240 Agammaglobulinemia, X-l inked, 206 Korsakoff's amnesia and, 461 <X i -antitrypsi n deficiency, ll5
Adenosine dcaminase deficiency, 66, c l inical presentati on, 568 magnesium levels and, 293 hepatocel lular carci noma
207 Agars. See Stains (microbiology) Mallory-Weiss syndrome and, 324 and, 335
Adenoviruses, 1 54, 155 Agenesis in organ morphogenesis, 505 neoplasms associated with, 220 a-amylase. See Sal ivary amylase
diarrhea caused by, 1 68 Age-related macular degeneration osteonecrosis caused by, 392 a-antagon ists, 237, 238, 243
pneumonia caused by, 560 (ARM D ) , 441 as P-450 inducer, 242 for hypertension , 279
Adenylate cyclase (cAMP) Aggl utinins as P-4 50 i n h i b i tor, 242 for pheoc h romocytomas, 297
toxin effect on, 1 24 cold, 142 pancreati tis and, 580 priapism caused by, 537
Adenyl i c acid (AM P), 66 warm vs. col d , 357 sexual dysfunction and, 60 a cells, 287
Adenylyl cyclase Aggregation subdural hematoma and, 424 glucagon production, 289
in signal transduction , 231 i n platelet plug formation, 349 suicide and, 466 a-fetoprotei n (AFP)
ADI -l . See Vasopressin Aging in the eye, 438 susceptibil i ty to i n hepatocel lular carcinomas, 335
receptors for, 231 Agnosia microorganisms, 168 neural tube defects and, 409
A D H antagonists, 499 i n dementia, 462 tactile hall ucinations and, 463 as tumor marker, 222, 531
A0!- 1 0 . See Attention-deficit Agonists treatment for, 574 i n yolk sac tumors, 536
hyperactivity disorder direct and indirect, 233 wet beriberi and, 567 a-globi n
(AD H D) efficacy of, 229 withdrawal treatment, 453, 472 gene mutations, 352
Adherens junction of epithelial Agranul ocytosis Aldesleuki n , 210 a-glucosidase i n h i bitors
cells, 378 carbamazepine as cause, 452 Aldoesterone escape, 263 for diabetes m e l l i tus, 305
Adhesion, 331 , 349 clozapine as cause, 473 Aldolase B , 104 a-hemolytic bacteria, 127, 128
Adipose tissue as drug reaction, 240 Aldose reductase, 105 a-i nterferon, 210
estrogen production, 520 AH lA. See autoi mmune hemolytic Aldosterone, 291 , 485 a-methyldopa
insul i n dependency, 288 anemia kidney effects, 486 cli nical use, 236
Adjustment disorder, 467 A I DS , 158 mechanism of, 483 a-receptor
Adoption study, 50 baci l la ry angiomatosis and, 278 renal tubular acidosis ( R T A) as target of noncompeti tive
ADP, 349 bra i n l esions i n , 573 and, 488 antagon i st, 229
ADPKD (adult polycystic kidney clin ical presentation, 173 in S I AD H , 301 a-synuclein
disease) , 85, 498 diagnosis of, 1 64 signal ing pathway, 294 in Lewy bodies, 416, 443
I ND E X
a-thalassemia, 352 reactions to, 241 in traprenchymal h e morrhage cytarabine as cause, 371
l l einz bodies in, 351 as teratogens, 506 caused by, 424 as drug reaction, 240
a toxin, 125, 130 Aminopenici l l i ns, 177 Amyloidosis, 217, 489, 490 hemolytic, 209
a (type I) error, 54 Ami notransferases cardiomyopathy caused by, 272 lab val ues, 357
AIport syndrome, 77, 79, 489, 492 as serum markers, 334 multiple myeloma and, 363 l eukemias as cause, 364
clinical presentation, 567 Amiodarone Amyloid precursor protei n (APP), 217 l iver cell fai l ur e as cause, 333
Alprazolam, 453 as antiarrhythmic, 284 Alzheimer's disease and, 443 macro-oval ocytes in, 350
Al ternative hypothesis, 54 as P-4 5 0 i n h i b i tor, 242 Amyotroph ic lateral scl erosis i n multiple myeloma, 363
Al ternative pathway for complement reactions to, 240, 241 (ALS), 579 pernicious, 204
activation, 199 restrictive l ung disease caused spinal cord lesions, 429 Plummer-Vi nson syndrome as
Altitude sickness by, 555 Anaclitic depression, 459 cause, 324, 567
acetazolamide for, 500 Amitri ptyl ine, 475 Anaerobes recombinant cytok i n es for, 210
Altru ism, 459 Amlodipine, 279. See also Calcium antimicrobials for, 1 81 renal fai l ur e as cause, 497
Aluminum hydroxide, 341 channel blockers obl igate, 121 in type A gastritis, 327
Alveolar ducts, 544 Ammonia pneumonia caused by, 168 in Wilson's disease, 337
Alveolar gas equation, 550, 582 i n toxication, 107 Analgesics Anemia of c h ronic disease (AC D )
Alveolar sacs, 544 toxicity, acetazolamide and, 500 efficacy of, 229 i n a n e m i a algorithm, 3 5 5
Alveolar septum Ammoniagenesis opioid, 449 Anencephaly, 409
iron-containing nodules in, 572 i n renal tubular acidosis ( RTA), 488 Analysis of variance (ANOVA), 55 diagnostic findings/labs, 572
Alveol i Ammonium Anaphase, 74 polyhydramnios as cause, 527
in emphysema, 554 transport by alanine/gl utamine, 106 Anaphylactic and atopi c Anergy, 201
Alzheimer's disease, 443 Ammonium chl oride hypersensitivity (type 1), 1 9 5 , Anesth etics
acetylcholine levels i n , 413 for drug overdose, 228 203 benzodiazepines as, 453
amyloiditis in, 217 Ammonium magnesium phosphate Anaphylaxis, 1 52 general principles, 453
dementia caused by, 462, 578 in kidney stones, 493 as bl ood transfusion reaction, 204 i n h a l ed, 453
diagnostic findings/labs, 571 , 573 Amnesia, 461 complement and, 199 i ntravenous, 454
drugs for, 233, 456 electroconvulsive therapy as as hypersensitivity disorder, 204 l ocal , 454
cause, 466 medications for, 235 name suffix, 243
hydrocephalus in, 426
h ippocampus lesions and, 419 Anaplasia, 219 Ane u rysms, 423
neurotransmitter changes, 461
mammil lary body lesions and, 419 Anastomoses aortic , 268
Amanita phalloides
Amniotic epithel i u m , 508 gastroi ntesti nal , 313 associations, common/
reactions to, 240
Amniotic A u id Anastrozole, 540 important, 576
Amanitin, 70
abnormalities, 527 for breast cancer, 574 as Ml comp l i cations, 271
Amantadine, 455
Down syndrome markers i n , 570 Anatomy oculomotor nerve and, 441
Am bien. See Zolpidem
embol i, 553 cardiovascular, 253 saccular, 422
Amebiasis, 147
lecith i n :sph i ngomyelin ratio digestive tract, 31 1 Angel man's syndrome, 82, 83
Amenorrhea
in, 555 endocrinal , 286-288 Angina, 269
anorexia nervosa as cause, 469
Amoxapine, 475 gastro i n testinal, 309-318 cilostazol/dipyridamole as
associations, common/
Amoxici l l i n , 177 hematologic/oncologic, 344-347 prophyl axis, 369
important, 580
for Helicobacter pylori, 137 l i ver, 315 c l inical presentation, 566
in Cushi ng's syndrome, 296
Amphetamines musculoskeleta l , 378-386 coca i n e as cause, 471
pituitary adenoma as cause, 301
for AD! -1 0 , 460, 472, 574 neurological, 41 1 -443 therapies for, 280
Sheehan's syndrome and, 568
antidote to, 239 ocular, 437 treatment for, 576
Turner syndrome as cause, 524 c l i n ical use, 235 Angi na pectoris
rena l , 479
Amide anesthetics, 454 e l i m i nation of, 228 -bl ockers for, 238
reproductive, 514-523
Amifostine i n narcolepsy, 62 respiratory, 544-545 Angiodysplasia, 331
cisplatin/carboplatin and, 373 i n toxication and withdrawa l , 471 spinal, 428 Angioedema
Amikacin, 180 mechanism, 232 Ancylostoma, 1 52 AC E i n h i b i tors and, 502
Amiloride, 501 Amphotericin Ancylostoma duodenale, 151 danazol for, 541
for diabetes insipidus, 301 , 574 for Naegleria fowleri, 148 Androgen-bi nding protein (AB P ) h ereditary, 200
Amino acids, 106 l i posomal form, 185 secretion of, 517 Angiofibromas
blood-brai n barrier transport, 413 Amphotericin B , 1 8 5 Androgen i nsensitivity syndrome, 524, i n tuberous scl erosis, 446
catabol ism, 106 for Candida, 145, 574 525 Angiogenesis
clearance, 482 Ampicil l i n , 177 Androgen receptor bevacizumab effect on, 374
derivatives of, 107 for enterococci, 575 defective, diagnosing, 524 in wound heal i ng, 216
insu l i n effect on, 288 for Listeria monocytogenes, 131 Androgens, 291 , 519 Angi ography, 331
Aminoacidur i a mechanism of action, 176 female pseudohermaphroditism Angiomas
i n pregnancy, 482 for meningitis prophylaxis, 169 caused by, 524 i n Sturge-Weber syndrome, 446
Aminoacyl-tRNA, 73 reachons to, 240 production of, 286 Angiomatosis
Aminocaproic acid Ampu l l a of Vater, 316 secretion of, 538 von 1-1 ippel-1 .indau disease
as antidote, 239 Amygdala, 415 Androstenedione, 291 , 519 and, 569
as thrombolytic antidote, 368 l esions in, 419 Anemia, 352-357, 572. See Angiomyol ipomas
Ami noglycosides, 179, 180 Amylases also Pernici ous anemia diseases associated with , 220
contrai ndicated during i n acute pancreatitis, 339 algorith m to, 352 Angi osa rcomas, 219, 278, 335
pregnancy, 190 i n c h ronic pancreati tis, 340 anorexia nervosa as cause, 469 carcinogens affecting, 223
effectiveness vs. anaerobes, 121 in sal iva, 320, 322 antimicrobials causing, 176, 181 , Angiotensin I I
for enterococci, 575 as serum marker, 334 182, 1 87 kidney effects, 486
magnesium l evel s and, 293 Amyl in analogs autoimmune hemolytic, 204 mechanism of, 483, 485
mec hanism of action, 176 for diabetes me l l itus, 305 basoph i l i c stippl ing i n , 350 i n noradrenergic n ervous
protein synthesis i n h i bition by, 73 Amyloid angiopathy blood transfusions for, 360 system , 232
for Pseudomonas aeruginosa, 135 Alzheimer's disease and, 443 colorectal cancer as cause, 332 sign a l i n g pathway, 294
I ND E X
Angiotensin J l receptor bl ockers Anterior drawer sign Antidepressants, 474-476. See for del irium, 462
(ARBs), 501 i n AC L tear, 379 also MAO i n h i b i tors; S S Ris; for posartum psychosis, 465
for hypertension, 279 Anterior horn of lateral Tricyclic antidepressants prolactin and, 290
Angiotensin receptor antagonists ventricles, 426, 427 bipolar disorder and, 464 reactions to, 241
for C H F, 273 Werclnig-H offman disease and, 430 m i rtazapine, 237 for sch izophren ia, 576
Angle closure glaucoma, 439 Anterior horn of spinal cord, 428 name suffix, 243 for Tourette's syndrome, 460
Anhedonia pol ioviru s i n fection of, 430 for posJartum depression/ Anti retroviral therapy, 1 89
amphetamines as cause, 471 Anterior hypothalamus, 414 psychosis, 465 Anti-Scl-70 antibodies, 205, 395
in major depressive disorder, 465 Anterior inferior cerebellar artery priapism caused by, 537 Anti-Smith antibodies, 205, 393
Anh i drosis, in Horner's strokes and, 422 S S Ris, 243 Antisocial person a l i ty disorder, 460,
syndrome, 431 , 569 Anterior i n terosseous nerve tricyclic, 232, 243, 466 468
Ani l i n e dyes, 137 course of, 380 Anticlesmoglein antibodies, 205, 570 Anti-S SNRo antibodies, 205
as carcinogen, 223 Anterior perforated substance, 432 Anti-diuretic hormone. Anti-SSB/La a ntibodies, 205
transitional cell carcinoma Anterior pituitary, 287 See Vasopressi n Antithrom b i n , 348
and, 494 Antidotes, 239 i n coagulation cascade, 348
reproductive hormones and, 538
Anion gap, 488 Anti-dsD A antibodies, 205 deficiency i n , 360
spermatogenesis and, 519
Anion gap metabolic acidosis Antiemetics, 342 h eparin and, 367, 368
Anterior spinal artery, 427
in diabetic ketoacidosis, 303 marijuana as, 471 Anti thymocyte globul i n
occl usion of, 429
Ani ridia Antienclomysial antibodies, 205 for aplastic anemia, 355
strokes and, 422
Wilms' tumor and, 494 Antifungal drugs Antithyroid d rugs, 295
Anterior spinothalamic tract, 427
Anisocytosis, 344 name suffix, 243 Anti-topoisomerase antibodies, 570
Anterior superior
in -thalassemia, 353 Antifu ngal therapy, 184 Antitoxins
pancreaticocluoclenal
An itschkow's cells, 274 Antigen-presenting cells (APCs) for Clostridium botulinu m , 574
Ankle edema arteries, 313 B cel ls as, 346
Anterior wh i te commissure for Clostridium tetani, 574
l iver cell fai l ure as cause, 333 dendritic cells, 346 exotoxi n inducing of, 1 23
Ankylosing spondyl i tis, 392 decussation in, 428 macrophages, 345
Anterograde amnesia, 419, 461 as passive immunity, 202
Grah n's disease and, 328 M H C 11 expression, 194
Anth racosis, 555 Anti-transgl utaminase antibodies, 570
diagnostic findings/labs, 570 in T- and B-cell activation, 196
Anthrax, 131 Antitumor antibiotics, 372
H L A-B27 and, 194, 578 Antigens
Bacillus cmthracis in, 124 Anti-U I RN P antibodies, 205
therapeutic antibodies for, 210 blood types and, 347
Antianclrogens, 501 , 539 Antivascular endothel ial growth
TN F-a i n h i b i tors for, 406 HLAs, 194
factor (VEGF)
ulcerative col itis and, 328 Antianginal therapy, 280 type and memory, 198
agents, 441
Annular pancreas, 309 Anti-apoptotic molecules variations, 201
Antiviral c hemothewpy, 187
Annulus fibrosus as oncogene product, 221 Anti-glomeru l a r basement membrane
Anus
compromise of, in elise Antiarrhythmics, 283-284 antibodies, 570
carcinoma of, 222
herniation, 427 phenytoin as, 452 Anti-l -l Be antibodies, 163
derma tomes for, 431
Anopheles mosquito as disease reactions to, 240 Anti-l -l Be antibodies, 1 63
Anxiety
vector, 149 torsacles de poin tes, as reaction, 240 Anti-H B s antibodies, 163
benzocliazepi nes for, 453
Anopias, 441 Anti-basement membrane Antihelminthic therapy, 1 86
LSD use as cause, 471
Anorexia, 469 antibodies, 205 Antih istamines
MAO i n h i b i tors for, 475
amphetamines as cause, 471 Antibiotics efficacy of, 229
hypothalamus and, 414 neurotransmitter changes, 461
antitumor, 372 Anti histone an tibodies, 205, 393, 570
mari juana as cause, 471 Antihypertensive therapy, 229, 279 neurotransmitter l evels i n , 413
efficacy of, 229
treatment for, 574 Anti-l gG antibodies, 570 treatment for, 472
name suffix, 243
Anorgasmia, 60 Anti-)o- I antibodies, 205 Anxiety clisorclcrs, 466, 467
Antibodies
S S R i s as cause, 475 Antileukotrienes, 563 atypical anti psychotics for, 473
i n acute inflammation, 214
OVA, 55 2 for asthma, 563 buspirone for, 474
aga i nst presynaptic Ca + Aorta, 309
Anovulation channels, 223 Antil ipicl dru gs
common causes of, 529 potency of, 229 abdominal, 312
autoantibodies, 205 coarctation of, 266 , 267
Anoxia Antimetabol i tes, 371
B cell production of, 195 diaphragm perforation by, 545
free radicals and, 215 Anti microbial prophylaxis, 184
diversity, generation of, 197 "tree bark" appearance, 275
ANP. See Atrial natriuretic peptide Antimicrobials, 176- 190
to hepatitis viruses, 163 Aortic aneurysms, 268
(ANP) avoiding i n pregna ncy, 190
heterophile, 157 associations, common/
Antacids, 340, 341 drug name suffixes, 243
i n l upus, 393 important, 576
metabol ic alkalosis caused by, 488 Antimitochonclrial antibodies, 205, 570
scleroderma and, 395 Aortic arch derivatives, 509
Antagonists Antimuscarinic agents, 241
structure and function, 197 Aortic dissection, 268
a-antagonists, 238, 243 antidote to, 239
therapeutic, 210 Antimycin A, 102 Marfan 's syndrome and, 566
-antagonists, 238
efficacy of, 229 Anticentromere antibodies, 205, 395, Antimycobacterial drugs, 1 83 Aortic regurgitation, 259, 266
muscari n i c , 234 570 Antineoplastics, 65, 370 c l i n ical presentation, 566
Anterior arterial branching i n Gl Anticholi nergic agents Antineutroph i l cytoplasmic antibodies h eart murmur with , 258
structures, 312 antidote to, 239 (ANCAs), 570 Aortic stenosis, 259, 266, 578
Anterior cavity of eye, 437 Antichol i nergic toxicity Antinuclear antibodies, 205, 570 c l i nical presentation, 570
Anterior cerebral artery, 420, 436 medications for, 233 in l upus, 393 heart murmur with, 258
stroke effects, 422 Antichol i n csterases, 233 Antioxidants S4 and, 580
Anterior clinoid process, 436 Anticipation, i n genetics, 82 free radical i n j ury and, 215 Aortic valve, 256
Anterior communicating artery Anticoagulation, 348 Antiplatelet antibodies, 570 sclerosis of, 258
aneurysms and, 422, 423 heparin alternatives, 367 Antiprotozoan therapy, 1 86 septa 1 defect of, 267
Anterior cruciate l igament (ACL) heparin for, 367 Antipseuclomonals, 177 A0x3 . See Orientation
i n j ury, cli nical presentation of, 569 priapism caused by, 537 Anti psychotics, 473 APC/-catenin pathway
i n unhappy triad i n j u ry, 379 treatment for, 575 for bipolar disorder, 464, 472 in colorectal cancer, 332
INDEX
APC gene, 221 Argyll Robertson pup i l , 138, 173 Ascending colon Astrocytes, 41 1
i n colorectal cancer, 332 c l inical presentation, 569 angiodysplasia in, 331 in blood-brai n barri er, 413
APCs (antigen-presenting cells) syp h i l i s and, 429 Ascending colorectal cancer, 332 Astrocytomas, 577
M I-I C I I expression, 1 94 Arip i prazole, 473 Aschoff bodies, 274 diseases associated with, 220
in T- and B-cell activation, 196 ARM D. See Age-related macular diagnostic findings/labs, 572 gl ioblastoma multi forme, 447
"Ape hand," 382, 383 degeneration (ARMD ) Ascites p i l ocytic, 448
APGAR score, 59 Arms diagnosis for, 566 S- 1 0 0 marker for, 222
Aphasia, 420 dermatomes of, 380 hepatocellular carcinoma as Ataxi a
in dementia, 462 innervation of, 380 cause, 335 amantadine as cause, 455
in Pick's disease, 443 postnatal paralysis, cause of, 568 Ascorbic acid, 94 epil epsy drugs as cause, 452
strokes as cause, 422 Arnold-Ch iari malformation, 409 ASD. See Atrial septal defect (ASD ) hydrocephalus as cause, 426
Apical blebs Aromatase, 291 , 519 Aseptic meningitis in Rett's disorder, 461
pneumothorax and, 561 Aromatase i n h ibitor causes of, 1 58, 1 59 i n syph i l is, 429
Aplasia for breast cancer, 574 "Ash l eaf spots," 85, 446 Ataxia-telangiectasia, 69, 207
as organ morphogenesis error, 505 ARPKD, 498 ASO titer Atazanavir, 1 89
Aplastic anemia Arrhythmias for Streptococcus pyogenes, 129 Atel ectasis
i n anemia algori thm , 355 associations, common/ Aspartate, 64 pneumocytes and, 544
carbamazepi n e as cause, 452 important, 577 Aspart insul i n , 305 Atenolol , 238
as drug reaction, 240 potassium deficiency as cause, 487 Asperger's disorder, 461 as antiarrhythm i c , 284
Fanconi's anemia as, 569 thiazide diuretics and, 501 Aspergillosis Atheromas, 267
as side effect, 306 treatment for, 574 antimicrobials for, 185 Atherosclerosis, 268, 425
Aplastic crisis Arsenic, 1 00 bronch i ectasis caused by, 554 aneurysms and, 576
sickle cell anemia as cause, 356 angiosarcomas and, 335 H I V-associated, 1 66 common l ocations of, 580
Apnea. See Sleep apnea as carcinogen , 223 Aspergillus, 103, 121 , 175 i n diabetes m e l l i tus, 302
Apocrine glands, 378 poisoning, antidote for, 239 pulmonary hypertension as
antimicrobials for, 185
cause, 549
ApoE4 skin cancer and, 403 chronic granul omatous disease
Athetosis, 417
Alzheimer's disease and, 443 Arterial th rombus and, 207, 579
ATM gene
Apolipoprotei ns, 1 15, 1 16, 326 diagnostic findings/labs, 573 as i mmunodeficiency
defects in, 207
Aponeurosis of external obi ique, 317 Arteries infection, 205
ATN
Apoptosis, 212, 373 cerebra l , 420 i n l iver cancer, 335
in renal fai l u re , 496
APP. See Amyl oid precursor protein spi n al , 427 Aspergillus fu m igatus, 145
Atomoxetine
(APP) umbilical, 508 Aspirated foreign obj ects, 545
for A D H D , 460
Appendicitis, 329 Arteriolosclerosis, 267 Aspiration-caused infections, 168
Atonic seizures, 445
microorganisms mimicking, 167 Arteriosclerosis, 267 Aspi ration pneumonia
Atopi c dermatitis, 397
Appendix Arteriovenous malformations Klebsiella as cause, 136
Atopi c disorders
carci noid syndrome, 304 (AVMs), 85 Aspirin, 368, 404
as hypersensitivity disorder, 204
location of, 379 Arteritis for c h ildren , avoiding, 334
Atorvastati n , 281
"Apple core" lesions in colorectal headaches caused by, 446 as cyclooxygenase i n h i b i tor, 349
ATP78 gene, 337
cancer, 332, 570 Arth ritis. See a lso Rheumatoid e l i mination of, 228 ATP production, 99, 102
Appl e-green b i refringence, 217, 490 arthritis reactions to, 240 ATP synthase i n h i b i tors, 102
Apple peel atresia, 308 c l i nical presentation, 570 Reye's syndrome and, 334 Atracur i u m , 455
Appropriate absol ute infectious, 392 Asplenia Atresias, 308
polycythemia, 366 in l upus, 393 H owell-Jolly bodies i n , 351 Atria
Apraxia i n Lyme disease, 137 target cells in, 351 enlargement of, 253
in dementia, 462 osteoarth ritis, 390 Asplenic patients, 175. See primi tive, 250
Aqueductal stenosis Paget's disease of bone and, 566 also Splenectomies Atrial fibrillation, 262, 577
Ch iari I I malformation and, 409 psoriatic, 210 Babesia in, 149 digoxin for, 282
Aqueduct of Sylvi us, 426 rheumatic, 210 Streptococcus pneumoniae risk, 128 ischemic stroke and, 425
stenosis of, 426 i n S jogren's syndrome, 391 , 567 vaccines for, 121 Atrial A u tter, 262
Aqueous humor Arthus reaction , 203 Assisted suicide, 58 Atrial kick, 256
glaucoma drugs and, 449 as hypersensitivity disorder, 204 Asterixis Atrial natriuretic peptide (AN P ) , 263,
pathway for, 438 Arylcyclohexylamines l iver cell fai l ur e as cause, 333 485
Arabinofuranosyl cytidine. as i n travenous anesthetics, 454 i n renal fai l ure, 497 kidney effects, 486
See Cytarabine Arylsulfatase i n Wilson's disease, 337 signa l i ng pathway, 294
Arachidonic acid products, 404 eosinoph i l production of, 345 Asth ma, 554 Atrial septal defect (AS D ) , 265
Arachnodactyly, 85 Arylsulfatase A, 1 1 2 antichol i n ergic medications Down syndrome association, 267
diagnos is for, 566 deficiency i n , 445 for, 234 presenting signs, 258
Arach noid cell s Arytenoid cartilage -bl ockers and, 238 Atrial septu m . See I n teratrial septum
meningiomas a n d , 447 derivation of, 510 chol i nomimetic agents and, 233 Atrioventri cular (AV) node, 261
Arach noid granulations, 426 Asbestos diagnostic findings/labs, 572 Atrioventricular block, 262-263
Arachnoid mater, 436 as carcinogen , 223 drugs for, 235, 306, 563 Atrioventri cular canals, 250
ARBs, 501 . See Angiotensin II Asbestosis, 555 eosinoph i l i a caused by, 345 Atrophy, 214
receptor bl ockers (ARBs) diagnostic findings/labs, 572 C E R D and, 324 L M damage as cause, 567
Arches, branchial, 410, 509 mesoth e l i oma and, 559 as hypersensitivity disorder, 204 as motor neuron sign, 428
Arcuate fasciculus, 418, 420 as restrictive l u n g disease, 555 mast cell degranulation and, 346 Atropi n e , 234, 321
Area postrema, 413 , 414 Ascaris lumbricoides, 1 51 , 578 MAST treatment for, 235 as antidote, 239
AreAexia Ascending cholangitis methachol ine chall enge test, 233 i n cholinesterase i n h i b i tor
vincristine as cause, 373 b i l ia ry cirrhosis and, 338 pulsus paradoxus i n , 275 toxi ci ty, 233
Arenaviruses, 158 cholecystitis and, 339 therapeutic antibodies for, 210 reactions to, 241
Arginine, 107 gal lstones as cause, 339 treatment stages, 563 toxicity, 234
INDEX
Attention-deficit hyperactivi ty disorder Autonomic innervation of male sexual Bacitraci n Barium swa l l ow
(ADl-1 0), 460 response, 516 mechanism of action , 176 "bircl's beak" i n , 324
stimulants for, 472 Autonomic nervous system streptococci reactions to, 127, 570 for colorectal cancer, 332
teratogens causing, 506 l imbic system and, 415 Streptococcus agalactiae "string sign," 328
treatment for, 235, 472, 574 Autonomy, as ethical principle, 56 resistance, 1 29 Baroreceptors, 264
Attributable risk, 52, 581 Autoregulation, cardiac, 265 Streptococcus pyogenes sensitivity innervation of, 434
Atypical antidepressants, 476 Autosomal-dominant diseases, 85 to, 1 29 Barr bodies, 524
Atypical antipsychotics, 473 Autosomal-dominant i nheritance, 84 Back pain B arrel-shaped chest i n
for bipolar disorder, 472 Autosomal-dominant polycystic i n multiple myeloma, 363 emphysema, 554
Atypical depression, 465 kidney disease (ADPKD), 85 Bacl ofen B arrett's esophagus, 325
MAO i nhi bi tors for, 475 Autosomal-recessive diseases, 86 for multiple sclerosis, 444 as esophageal cancer risk
treatment for, 472 Autosomal-recessive inheritance, 84 Bacteremia factor, 325
Atypical pneumonias Autosomal trisomies, 88 Streptococcus bovis causing, 129 neoplasms associated with, 220
antimicrobials for, 180 Autosplenectomy Bacteria Bartonella , 1 19 , 139
Auditory cortex, 41 5, 418 associations, common/ with exotoxins, 124-125 Bartonella henselae. See Cat scratch
Auditory hall ucinations, 463 important, 577 growth curve, 125 disease
in sch izophrenia, 463 Avascular necrosis, 392 moti l i ty, 168, 170 bacil l a ry angiomatosis and, 278
Auditory meatus sickle cell anemia as cause, 356 spores, 130 Barts hemoglobi n , 352
as cranial nerve pathway, 435 AV bl ock. See Atrioventricular block stains, agars, and c ul tures, 1 20, Basal cell carcinomas
Auditory vestibular nerve Avoidant personal i ty disorder, 469 127 diseases associated with, 220
acoustic neuroma and, 412 Axi l l a ry lymph nodes, 192 structures, 1 18 5-Auorouraci l for, 371
Auerbach 's plexus, 31 1 Axil l a ry nerve, 382 taxonomy, 1 19 of ski n , 403
achalasia and, 324 course of, 380 Bacteria capsules. See Encapsulated Basal gangl ia, 415, 416
H i rschsprung's disease and, 330 Axons, of neuron, 41 1 bacteria in H untington's disease, 417
Auer rods, 365 mye l inization of, 41 1 Bacterial embol i , 553 lesions i n , 419
diagnostic findings/labs, 570 i n Wilson's disease, 337
Wal l erian degeneration of, 41 1 Bacterial endocarditis, 274
Auscul tation of the heart, 258 Basal lamina
Azath ioprine, 209, 371 associations, common/
Auspitz sign, 397 i n male reproductive anatomy, 517
Azetazolamide, 500 important, 578
Autistic disorder, 461 Basal nucleus of M eynert
Azithromyc in , 183 c l i n ical presentation, 569
Autoantibodies, 205 acetyl c h o l i n e synthesis, 413
for chlamydiae, 141 Bacterial genetics, 126
Autografts, 208 Basal plate, 408, 434
for mycobacteria, 183 Bacterial infectiOn risk factors
Autoimmune diseases B ase excision repair, 69
for Mycobacterium avium antib10tic use, 130
acute pancreatitis caused by, 339 Basement membrane, 479
intracellulare, 132 colon cancer, 129
erythema multi forme caused autoantibodies targeting, 205
for Neisseria, 134 cystic fibrosis, 135
by, 399 in blood-bra i n barrier, 413
Azoles, 185 in travenous catheters, 128
erythrocyte sedimentation rate charge barner and, 480
for Candida , 145 I V drug use, 1 2
and, 349 Basic amino acids, 106
Azotemia m i l i tary recrui ts and prisons, 142
neoplasms associated with, 220 Basoph i l i c stippl ing, 350
nephritic syndrome and, 492 organ transplants, 1 55
pemphigus vulgaris as, 398 in l ead poisoning, 353
prednisone for, 373 AZT prosthetic devices, 128
B asophils, 287, 345
pulmonary hypertension caused Vitamin B 1 2 deficiency and, 354 surfing, 137
antibody binding of, 198
Aztreonam , 178 Bacterial mening1tis
by, 549 in chronic myelogenous
Autoimmune hemolysis mechanism of action, 176 associations, common/
leukemia, 365
spherocytes in, 351 Azu roph i l i c granular inclusions important, 577
nuclear remnants i n RBCs, 570
Autoimmune hemolytic anemia i n granul ocytes and Bacterial pyelonephritis
bax gene (apoptosis), 2 1 2
i n anemia algorithm , 357 myeloblasts, 570 diagnostic findings/labs, 573 B blood type, 347
as hypersensitivity disorder, 204 Azygos system , 314 Bacterial vagi nosis ( BV), 139. See B-cell non-Hodgkin's lymphoma
leukemias and, 364 Azygos vein also Vagmitis therapeutic antibodies for, 210
Autoimmune hepatitis d1aph ragm perforation by, 545 c l i nical presentation, 173 B cells, 346
autoantibodies associated with, 205 Bacterial variation , 201 activation of, 196
B Bacterial virulence factors, 122
Autonomic drugs, 230-238, 2 2 adaptive nature of, 1 93
ACh receptors, 230 B 1 2 . See Vitamin B 1 2 Bactericidal medications, 179 anergy, 201
a-blockers, 237 B 1 2 deficiency Bacten ophages. See Phages class switchmg, 196
atropine, 234 H L A- D R 5 and, 194 Bacteriostatic mechcations, 1 80, 181 cytokines secreted by, 200
-blockers, 238 Babesia, 137, 149 Bacteroides, 1 19, 121 deficiencies, infections caused
central and peripheral nervous anemia caused by, 357 antimicrobials for, 182 by, 205
system effects, 230 Babesiosis, 149 lung abscesses caused by, 560 disorders of, 206-207
chol inesterase i n h 1 b1tor Babinski sign, 59, 432 BacterOides fragil is l ocal ization and pro l i feration, in
poisoning, 233 change in, as motor neuron antimicrobials for, 181 lymph node, 192
cholinomimetic agents, 233 sign, 428 as normal Aora, 1 67 major functions of, 195
G-protei n-l inked 2nd c l inical presentation, 570 "Bag of worms" appearance i n neoplasms of, 362
messengers, 231 U M N damage as cause, 567 varicoceles, 536 i n non-Hodgk i n 's lymphoma, 361
indirect agonists, 233 Bacillary angiomatosis, 278 Baker's cyst, 390 "owl's eye" appearance, 571
muscannic antagonists, 234 Baci l l i , 1 19, 121 "Ball and valve" myxoma, 577 in Peyer's patches, 323
name suffixes, 243 Bacillus anthracis, 124 "Bamboo spine" on X-ray, 392, 570 in spleen, 193
norepineph rine vs. anthrax caused by, 131 Band cells, 345 surface proteins, 201
isoproterenol, 236 spore formation of, 130 Barbiturates, 452 bcl-2 gene
sympathomimetics, 235 Bacillus bacteria, 1 19 intoxication and withdrawa l , 470 i n apoptosis, 212
sympathopleg1cs, 236 Bacillus cereus, 131 as i n travenous anesthetics, 454 translocatio n , 362
Autonomic gangha food poisoning caused by, 167, 578 name suffix, 243 i n tumors, 221
s1gnal transm1ss1on in, 230 spore formation of, 130 as P-4 5 0 i nducer, 242 bcr-abl transformati o n , 365, 366, 374
I N D EX
Becker's muscular dystrophy, 86 p 2-agonists B i lateral i n ternuclear cisplatin/carbopl atin for, 373
clinical presentation, 569 insu l i n and, 288 ophthaln1oplegia Schistosoma lwematobium i n , 152,
Becker's muscular dystrophy P-amyloid multiple sclerosis as cause, 568 222
Beck's triad of cardiac tamponade i n Alzheimer's disease, 443 B ilateral renal agenesis, 478 transitional cell carcinoma
cl inical presentation, 568 P-bl ockers, 238, 243 Bilateral renal cell carci noma and, 494
Beckwith-'vViedemann syndrome for angina, 280 von 1 -l i ppel-Lindau disease as B ladder exstrophy, 308
Wilms' tumor and, 494 as antiarrhythmics, 284 cause, 446 B l adder i ncontinence
Beclomethasone, 306, 563 as antidotes, 239 Bile, 323 multiple sclerosis as cause, 444
Bechvetting antidote to, 239 secretion of, 319 B l ast crisis, 365, 578
imipramine for, 475 for atrial A utter, 262 Bile acid resins, 281 B l astic bone lesions, 224
Bell-shaped c u rves, 54 for C H F, 273 B i l e canal icul i , 315 B l astocysts
Bel l 's palsy, 437 cocai n e and, 235 B i l e ducts, 310, 316 in fetal deve l opment, 504
c l inical presentation, 570 for essential tremors, 417 "beading" of, 338 B lastomyces
sarcoidosis and, 393 for glaucoma, 449 disease, serum markers for, 334 antimicrobials for, 185
Bence J ones protein, 363 in glomerul us/)GA, 485 obstructions of, 316 Bl astomycosis, 143
Bendazoles for hypertension, 279 Bile ductules, 315 B leeding disorders
for nematodes, 151 for Parkinson's disease, 455 B i l e salts associations, common/
Beneficence, 56 P cells, 287 in bile, 323 i mportant, 577, 578
Benign breast tumors, 533 in diabetes m e l l i tus, 303 gal lstones caused by, 339 B l eeding time ( BT), 359
Benign hepatic cysts P-gal actosidase, 134 B i l e stasis B leomyc i n , 369, 372
ADPKD and, 498 P-globin, 352 gal l stones as cause, 339 reactions to, 240
Benign melanocytic nevus H bC defect, 356 B i l iary cirrhosis, 338 restrictive lung disease caused
associations, common/ i n thalassemias, 353 autoantibodies associated with, 205 by, 555
important, 577 P-hCG diagnostic findi ngs/labs, 570 toxicities, 375
Benign prostatic hyperplasia as tumor marker, 222 primary sclerosing cholangitis B l epharoplasts
( B P H ) , 535, 579 P-hCG test, 329 and, 338 in ependymomas, 448
finasteride for, 539 B i l iary col ic, 339 B lepha rospasm, 417
P-hemolytic bacteria, 128
PSA i n , 222 B i l iary i nfection B l i ndness
P-hydroxybutyrate, 1 1 3 , 303
renal fa i l u re caused by, 496 gal lstones and, 339 temporal arteritis and, 580
P-interferon, 210
tamsulosin for, 540 B i l iary structures, 316 B l i n d studies, 53
for multiple sclerosis, 444
treah11ent for, 574 B i l iary tract disease, 338 B l istering ski n disorders, 398-399
P-lactamase i n h i b i tors, 177
urinary tract infections and, 1 69 cirrhosis caused by, 333 B l ood
P-lactamases, 1 18
Benign tumors, 219 B i l i ru b i n , 323 oxygen content, 550
P-lactams
Benzath ine penici l l i n G. i n bile, 323 viscosity of, 549
M RSA resistance to, 128
See Penicill i n G gal lstones caused by, 339 B l ood-bra i n barrier, 413
P 2-microglobul i n
Benzene in h ereditary anesthetics and, 453
i n M H C 1 , 194
reactions to, 240 hyperb i l i rubinemias, 336 astrocytes and, 41 1
P-pleated sheet
Benzoate, 107 in jaundice, 335 B l ood c ells. See also E ryth rocytes;
i n amyloidosis, 217
Benzodiazepines, 453 B i l i rubinemia Lymphocytes
P-prophage, 130
for alcohol withdrawa l , 574 conj ugated, 336 differentiation of, 344
P-thalassemia, 353
antidote to, 239 unconj ugated , 336 tumors of, 219
genetic mutations i n , 71
for cocaine i n toxication, 471 B i l i ru b i n gl ucuronide, 336 Bl ood clotting, 95
P (type 1 1 ) error, 54
conditions indicated for, 472 B 1 2 deficiency B l ood groups, 347
effect on power, 55 in anemia algorith m , 354 B l ood p H
for delirium tremens ( DTs) , 470,
Betaxolol , 238 Bioava i l abil i ty of drugs, 227 d i uretic effect on, 501
472
for glaucoma, 449 Biotin, 92 B l ood pressure. See
for epil epsy, 451
intoxication and withdrawa l , 470 Bethanechol , 233 B ipolar disorder, 464 also Anti hypertensive drugs
as inlTavenous anesthetics, 454 Bevacizumab, 374 drugs for, 451 a-blocker effect on, 237
name suffix, 243 Bezafi brate, 281 l i th ium for, 474 angioten s i n 1l and, 486
for panic disorder, 466 Bias, 5 3 , 55 treatment for, 472, 574 hypertension, 267
toxicities, 452 B icarbonate, 320, 552 B i rbeck granules, 366 mean arterial pressure ( MAP), 253
Benztropine, 455 for drug overdose, 228 diagnostic findings/labs, 573 normal, 264
c l inical use, 234 along proximal tubule, 484 " B i rd's beak" in bari u m swa l l ow, 324 preload and afterload, 254
Bereavement in sal iva, 320 B ismuth , 340, 341 resistance, pressure, Aow, 255
grief process, 60 B iceps muscle B isphosphonates, 405 B lood sol ubil i ty of anesthetics, 453
Berger's l gA gl omerulonephropathy, musculocutaneous nerve damage for osteoporosis, 387, 575 B lood-testis barrier, 413, 517
489, 492, 578 and, 382 B i te cells, 104, 350 Blood transfusions, 360
Beriberi, 90 B i ceps reA ex, 432 i n G6PD deficiency, 356 for aplastic anemia, 355
cardiomyopathy caused by, 272 B iconvex elise on CT scan, 424 B i temporal hemianopia, 301 , 441 incompati b i l i ty, compl ications
cl inical presentation, 567 B icornuate uterus, 512 berry aneurysm as cause, 423 of, 347
Berkson's bias, 53 B iguanides i n pituitary adenoma, 447 reactions to, 204
Bernard-Soul ier syndrome, 349, 359 for diabetes m e l l i tus, 305 Biva l i rudin, 367 B l ood urea nitrogen ( B U N )
bleeding disorders and, 577 B i lami nar disc BK virus, 155 i n renal fai l ur e , 496
Berry aneurysms, 78, 85, 422, 423 i n fetal development, 504 BlackAies as disease vectors, 1 51 Blood vessels
ADPKD and, 498 B i lateral acoustic schwannomas, 85 Black l iver, 336 tumors of, 219
Beryl l i osis B i lateral a mygdala lesion associations, common/ Bl ood vol ume regulation, 485
as granulomatous disease, 216 c l inical presentation , 567 important, 577 h ormones and, 486
P-agonists B i lateral h ilar adenopathy Black plague, 121 , 139 Bloody diarrhea, 168
for asthma, 563 sarcoidosis as cause, 566 Bladder, 516 B loody tap on l u m ba r puncture, 570
name suffix, 243 B i lateral h i l a r lymphadenopathy Bladder cancer B lotti ng procedures, 80
in potassium regulation, 487 sarcoidosis and, 393 carcinogens affecting, 223 " B l own p u p i l ," 441
I N DEX
"Blue babies," 265 Borderl ine personal ity disorder, 468 associations, common/ Bronch i a l obstructions, 557
"Bl ueberry muffin" rash, 171 spl i tting i n , 459 important, 577 lung abscesses caused by, 560
"Blue bloater" bronch i tis, 554, 567 Bordetella , 1 19 childhood primary, 448 B ronc h iectasis, 554, 569
"Bl ue-coned" cysts, 572 Bordetella pertussis, 124 B ranchial apparatus, 509 B ronc h i oalveolar adenocarcinoma of
Blue fingers/toes cui turing, 1 20 B ranchial arch derivatives, 510 the l ung, 558
cold agglutinin disease as Gram staini ng, 133 B ranchial arches, 410, 509 B roncl1itis
cause, 568 Bordet-Gengou agar, 1 20 B ranchial cl eft cysts, 509 chronic, 554
Blue sclera, 78 Borrelia , 1 19, 137 Branchial cleft derivatives, 509 B ronchogenic apical l un g tumor, 570
osteogenesis imperfecta as sta i n for, 120 B ranching filamentous bacteria, 1 19, B ronchogenic carcinomas
cause, 566 Borrelia hurgdor{eri, 137, 139, 175 127 carcinogens affecting, 223
BMPR2 gene antimicrobials for, 180 B RCA genes, 221 s i l i cosis and, 555
pulmonary hypertension and, 549 Borrelia recurrentis, 139 breast tumors and, 534 B ronchopneumonia, 560
B l 9 virus, 155 B osen tan, 564 B reast abscesses, 533 B ronchopulmonary dysplasia, 555
B 19 infection for pulmonary arterial acute mastitis, 535 free radicals and, 215
hereditary spherocytosis as hypertension, 575 Breast cancer, 220, 223 " B ronze" diabetes.
cause, 356 Botul inum toxin, 1 24 associations, common/ See Hemochromatosis
Body cavity fl u i d B-ee! I antibodies for, 202 important, 577 " B rown" bone tumor, 570
lymphoma, 222 in lysogenic phage, 126 benign tumors, 533 Brown pigmented sclera, 108
Body dysmorph ic disorder, 467 mechanism, 232 ch emotherapy drugs for, 374 B rown-Scquarcl syndrome, 430
Body-mass index ( B M I ), 60 neurotransmitters, effect on, 230 H ER2-overexpressing, 210 H orner's syndrome and, 431
Boerhaave syndrome, 324 Botul ism incidence and mortal i ty, 224 Bwcella, 1 19, 121 , 139
Bohr effect, 552 Clostridiu m botulinum causing, 130 lyric and blastic bone l esions Brunner's gl ands, 31 1 , 320, 321
Bombesin Bouchard 's nodes, 390 i n , 224 duodenal ulcers and, 327
as tumor marker, 222 Bounding pulses mal ignant tumors, 534 B rush-border enzyme, 105
aortic regurgitation as cause, 566 Brush border of i n testi ne, 322
Bone cancer m icrotubule i n h i b i tors for, 373
Boutonniere deformations, 390 B ruton's agammaglobulinemia, 206,
metastases to, 224, 579 oncogene for, 221
Bowel l umen, 572 568
tumor nomencl ature, 219 tamoxifen for, 540
Bowels B ruxism, 61
Bone diseases treatment for, 574, 575
incarceration of, 318 B 1 2 . See Vitamin B 1 2
achondroplasia, 387 tumor suppressor genes, 221
intussusception, 330 Budci-C h iari syndrome, 335, 566
lab values in, 388 Breast conditions, common, 535
stenosis of, 329 h epatocel l ul ar carcinoma as
osteomalacia/ri ckets, 387 B reast l umps
volvulus, 330 precursor, 335
osteopetrosis, 387 fibrocystic disease as cause, 535
B owman's capsule, 479 nutmeg l iver caused by, 335
osteoporosis, 387 Breast milk. See also Lactation
2 , 3-BPG Buerger's disease, 276
Paget's disease of bone, 387 immunogl obul i n in, 198, 202
h igh altitude effects on, 552 hypertension and, 580
polyostotic fibrous dysplasia, 388 let-cl o wn , oxytoci n for, 306
Brachial is muscle treatment for, 574
serum markers for, 334 postpartum absence, cause of, 568
musculocutaneous nerve damage Buffalo h u m p
Bone l oss prolactin sti mulation of, 290
and, 382 i n Cushi ng's syndrome, 296, 306
phosphate deficiency as cause, 487 B reast pathology, 533
B rachial plexus l esions, 381 Bulbus cordis, 250
Bone lytic lesions Breast tu mors
B rach ioraclialis muscle B u l i m i a , 469
in Langerhans cell associations, common/
radial nerve damage and, 382 bupropion and, 476
h istiocytosis, 366 important, 577
Bradycardia Mallory-Weiss syndrome and, 324
in multiple myeloma, 363 benign, 533
medications for, 234 osmotic laxative abuse i n , 342
Bone marrow B radyk i n i n , 348 mal ignant, 534 S S R i s for, 475
ablation of, 372 ACE i n h i b i tors and, 502 Breath sounds treatment for, 472, 574
B cells i n , 346 in RAAS, 485 lung physical findings, 557 Bullae, 395
macro-oval ocytes i n , 350 B RAF gene, 221 Brenner tumors, 532 i n dermatitis h e rpetiform is, 398
myelofibrosis, 366 melanoma and, 403 Bretyl ium B u l lous impetigo, 402
recovery, recombinant cytokines B-Raf kinase, 374 as antiarrhythmic, 284 B u l lous pemph igoid, 398
for, 210 Brain mechanism, 232 as hypersensitivity disorder, 204
stem cell growth and anatomy of, 418 Bridging veins " B u l l 's eye" rash , 137
differentiation, 200 autoregulation, 265 rupture of, 578 Lyme disease as cause, 568
T cell precursors i n , 195 development of, 408 in subdural hematoma, 424 B U N . See Blood urea nitrogen ( B U N )
T cells i n , 347 Brain cancer Brief psychotic disorder, 463 Bunyavi ruses, 1 58
teardrop cells i n fi l trati ng, 351 alkylating agents for, 372 Brimonicline Bupivacai n e , 454
transplant rejection , 208 metastases to, 224, 579 for glaucoma, 449 B uprenorph i n e
Bone marrow transpla n ts B rain disease Broad l igament, 515 receptor b inding, 229
for aplastic anemia, 355 isch emic, 425 B roca's aphasia, 420 B upropion, 476
for osteopetrosis, 387 Brain i n j ury B roca's area, 418, 420 for nicotine addiction, 471
for sickle cell anemia, 356 gastritis caused by, 327 strokes and, 422 reactions to, 241
Bone resorption, 387 Brain lesions. See also M otor neuron Bromocriptine, 290, 455 Burkitt's lymphoma, 362, 580
Bones signs for neuroleptic mal ignant c h romosomal translocation
"brown" tumor, 570 common, 419 syndrome ( N M S ) , 473 with , 365
cell biology of, 386 "soap bubble," 145 for pitui tary adenoma, 301 diagnostic fi ndings/labs, 573
formation of, 386 toxoplasmosis as cause, 148 for prolacti noma, 575 EBY vi rus in, 222
subperiostea l thinning of, 497 Brain stem Bronch i h erpesvirus as cause, 1 5 5 , 1 56, 1 57
Bone tumors, 389 dorsal vi ew, 433 left versus right, 545 oncogene for, 221
associations, common/ hernial compression of, 448 pulmonary artery and, 545 Burton's l i nes, 353
important, 580 ventral view, 432 Bronch ial asthma c l i nical presentation, 566
diagnostic findings/labs, 573 Brain tumors diagnostic findings/labs, 572 B uspirone, 474
"Boot-shaped" heart, 570 adult primary, 447 Bronchial carcinoid tumors, 558 for anxiety, 472, 574
I N D EX
Busulfan, 372 pacemaker action potential Caput medusae, 314 hypertension and, 267
reactions to, 240 and, 260 portal hypertension as cause, 333 variables, 254
restrictive l u ng disease caused ventricular action potential Carbachol , 233 Cardiac receptors, 264
by, 555 and, 260 for glaucoma, 449 Cardiac rhabdomyomas
toxicities, 375 Calcium homeostasis, 293 Carbamazepine diseases associated with, 220
Butorphanol, 449 Calcium oxalate stones, 493 . See for bipolar disorder, 464, 472, 574 tuberous sclerosis as cause, 446
"Butterfly" facial rash also Kidney stones for epilepsy, 451 Cardiac stress testing
l upus as cause, 566 Calcium pyroph osphate crystals as P-4 5 0 inducer, 242 medications for, 235
"Butterfly gl ioma," 447 i n pseudogout, 391 reactions to, 240, 241 Cardiac tamponade, 275
Butyrophenones Calf pseudohypertrophy as teratogen , 506 Cardiac tumors, 275
name suffix, 243 muscular dystrophy as cause, 566 for ton ic-clonic seizures, 576 associations, common/
BZ I subtype, of GABA receptor, 453 Calicivi ruses, 1 54, 158 toxicities, 452 important, 577
Cal i fornia enceph a l i tis, 1 58 Carbami nohemoglobin, 552 Cardinal l igament, 515
c
CALL A marker, 364 Carbamoyl phospha te, 65, 107 Cardinal vein , 250
Cl esterase i n h i b i tor, 199 Call-Exner bodies, 532 Carbamoyl phosphate synthetases, 97 Cardiogenic shock, 214, 271
C I esterase inhibitor deficiency. diagnostic findi ngs/labs, 570 Carbapenems, 178 Cardiomegaly with apical atrophy, 570
See H ereditary angioedema Calmodulin i n smooth muscle Carbohydrate digestion, 322 Cardiomyopath ies, 272
C3b contraction, 386 Carbolfuchsin sta i n , 120 S4 and, 580
i n splenic dysfunction, 193 Calor ( h eat), 214 Carbon dioxide wet beriberi as cause, 567
C 3 deficiency, 200 Calyces cerebral perfusion pressu re Cardiovascular system
C3 nephritic factor development of, 478 and, 421 anatomy, 253
in glomerulonephritis, 492 in pyelonephritis, 495 transport of, 552 drug name suffixes, 243
in M PGN, 491 cAM P Carbonic anhydrase, 321 , 501 drug reactions i n , 240
C5a s ignal ing pathways, 294 Carbonic anhydrase i n h i b i tors, 483 embryology, 250-252
i n leukocyte extravasation, 215 CAM P factor, 1 29 Carbon monoxide pathol ogy, 265-277
C 5-G9 deficiencies, 200
Gampylobacter, 1 19, 139 antidote to, 239 pharmacol ogy, 279-284
C282Y mutation
diarrhea caused by, 168 hemoglobin b i n ding to, 547 physiol ogy, 253-265, 255
hemoch romatosis and, 337
Campylobacter ieiuni, 136 hypoxia caused by, 550 sclerosis of, 395
CA- 1 9-9 marker, 340, 222
Gram stai n ing, 133 Carbon tetrachloride Carmusti ne, 372
CA- 1 2 5 marker, 532, 222
G u i l l a i n-Barre syndrome and, 444 as carcinogen, 223 Carnitine acyl transfe rase 1, 97
Cabergol i n e
mesenteric adenitis caused by, 167 free radicals and, 215 Carotid a rtery
for pituitary adenoma, 301
Canal of Schlemm, 438 Carboplati n , 373 atheroscl e rosis and, 580
Cachectin . See TN F-a
i n d i rect chol i nomimetics toxicities, 375 devel opmen t of, 509
Cachexia, 220
affecting, 449 Carboxyhemoglobin, 547 Carotid body and sinus
CaE DTA
c-ANCA antibodies, 205, 277 Carboxylase, 96 innervation of, 434
as antidote, 239
in glomeru l onephritis, 492 Carboxypeptidases, 322 Carotid dissection
Cafe-au-la it spots, 85, 388
Cancer. See a lso H ematology/ Carcinoembryonic antigen . See C EA ischemic stroke and, 425
diseases causing, 566
Oncology; Tumors Carcinogens Carotid massage, 264
von Reckl i nghausen's disease as
DIG and, 578 chemical, 223 Carotid sinus, 264
cause, 446
erythrocyte sedimentation rate Carcinoid syndrome, 304 , 559 Carpal tunnel syndrome, 379
Caffeine
i n , 217 treatment for, 574 Carteolol
intoxication and withdrawa l , 471
h a l l marks of, 218 Carcinoid tumors, 333 for glaucoma, 449
Calcarine fissure, 441
Cancer drugs, cell cycle, 369 octreotide for, 341 Cartilage
Calcarine sulcus, 415
Cancer epidemiol ogy, 224 Carcinoma in situ, 218 damage as d rug reaction , 241
Calci nosis
Candida , 121 Carcinomas. See also specific Caseating granuloma, 132
i n scleroderma, 395
antimicrobials for, 185 carcinomas C ase-control study, 5 0
Calcitonin, 294
bacterial endocarditis caused chemicals causing, 223 C aseous necrosis, 212
for osteoporosis, 387
by, 274 hyperparathyroidism and, 580 C aspases, 212, 213
s ignal ing pathway, 294
esophagitis caused by, 324 vs. sarcomas, 219 C aspofungi n , 1 8 5
in thyroid cancer, 299
as tumor marker, 222 as i mmunodeficiency Cardiac arrest for Candida , 145
i n fection, 205 amphetamines as cause, 471 Casts i n urine, 489
Calcitriol
PTH and, 293 Candida albiccms, 145, 175 Cardiac arrhythmias, 271 Catalase
chronic mucocutaneous diabetic ketoacidosis and, 303 free radical i n j u ry and, 215
Calcium
candidiasis caused by, 206 treatment for, 574 Catalase-positive organisms, 121 , 175
disturbances in, 487
as nosocomial infection, 174 Cardiac ci rrhosis, 273, 335 Cataplexy
in kidney stones, 493, 579
loop diuretics and, 500 treatment for, 574 nutmeg l iver as cause, 335 in narcol epsy, 62
for osteoporosis, 575 Candidiasis Cardiac cycle, 256 Cataracts, 439
in platelet plug formation, 349 antimicrobials for, 185 Cardiac function curves, 255 AI port syndrome as cause, 567
PTH and, 293 , 300 Cannabis. See Marij uana Cardiac glycosides, 77, 282 in diabetes mel l i tus, 302
reabsorption of, 483 "Cape-l ike" l oss of sensation, 410 name suffix, 243 prednisone as cause, 373
Calcium carbonate, 341 Capillaries Cardiac ischemia Catatonic sch izoph reni a, 463
Calcium channel bl ockers, 240, 279 "wire looping," 492 therapeutic antibodies for, 210 Cat bite, i n fected, 567
for angi na, 280 Capillary fl u i d exchange, 265 Cardiac muscle, 260 Catechol am i nes
as antiarrhythmics, 284 Caplan's syndrome contraction of, 386 effect on diastol ic
for atrial Rutter, 262 pneumoconioses as cause, 555 innervation of, 230 depolarization, 260
for hypertension, 279 Capsid structures, 1 53 cells as target of noradrenergic effect on stroke vol ume, 254
Calcium channels in genetic transduction, 126 signal i ng, 232 nervous system role, 230
C apsu l e of l ymp h node, 192 Cardiac ouJut (CO), 253 . See prod uction of, 286
epi l epsy d rugs an d , 451
"Capta i n 's whee\" yeast, 143 also Stroke vol ume ( SV) synthesis/tyrosine catabol ism, 108
in muscle contractions, 385
equation for, 582 in thyroid storm , 299
opioid effect on, 449 C aptopril , 502
IN DEX
Clofazimine C N S . See Central nervous system Collagen , 77 Complement, 193, 199

for mycobacteria, 1 83 (CNS) synthesis and structure, 78 activation of, 197
Clofibrate, 281 C N S lymphoma in wound healing, 216 antibody binding of, 197
gallstones and, 339 I -l l Y virus i n , 222 Collagenases, 218 deficiencies, i n fections caused
Clomiphene, 540 Coagulation cascade, 348 Collateral circulation by, 205
for polycystic ovarian Coagulation disorders, 359 gastrointesti nal system , 313 disorders of, 200
syndrome, 530 Coagulation factors Collecting ducts Compl ementation, viral , 1 5 3
reactions to, 240 deficiencies, blood transfusions development of, 478 Complement cascade, 348
Clomipramine, 475 for, 360 drugs acting on, 501 Complement pathways, 348
for obsessive-compulsive i n D I C , 360 Collecting tubules, 483 bacterial i n h ibition of, 1 28
disorder, 466 warfarin effect on, 367, 368 ADH action on, 231 Complex seizures, 445
Clonidine Coagulation pathways, 348 drugs acting on, 501 drugs for, 451
clinical use, 236 Coagulative necrosis, 212, 270 Calles' fractures, 387 Compl iance, pulmonary, 547
Cloning methods, 81 Coarctation of the aorta, 266 Col l i c u l i , 433 Compreh ensive Basic Science Self
Clonorchis sinensis, 152, 222 diagnostic fi ndings/labs, 573 Colon, 309 Assessment (G B S SA) , 1 0 , 1 1
Clopidogre l , 368 Turner syndrome association, 267 diverticula, 329 Comprehensive Osteopath i c M edical
mechanism of, 349 Cobalami n , 93 h i stology, 31 1 Self-Assessment Exa m i nation
Closed-angle glaucoma, 439 Cobbl estone mucosa, 328 Colon cancer (COMSAE), 40
Clostridia, 130 Cocaine, 454 diseases associated with, 220 Compression fractures
Clostridium, 1 19, 121 abruptio placentae and, 526 5-fluorouraci l for, 371 associations, common/
Clostridiu m botulinu m , 124, 130 -blockers and, 235 incidence of, 224 important, 577
food poisoning caused by, 1 67 cardiomyopathy caused by, 272 oncogene for, 221 Conditioning (psychology) , 458
spore formation of, 130 i n toxication and withdrawa l , 471 Streptococcus bovis and, 129 Conduct disorder, 460
mechanism of action , 232, 235 Streptococcus bovis endocardi tis Conducting zone of respi ratory
treatment for, 574
in, 274 tree, 544
Clostridiu m dif(zcile, 130 priapism caused by, 537
tumor suppressor genes, 221 Conduction aphasia , 420
antimi crobials for, 1 82 reactions to, 240
Colonic atresia, 308 Conduction velocity, of axon, 412
diarrhea caused by, 168 as teratogen , 506
Colonic flora, 1 67 Conductive h earin g l oss, 436
spore formation of, 130 Cocci bacteria, 1 19, 127
Colonic resection Condyloma a c u m inata, 397
treatment for, 574 identification of, 127
for carcinoid tumors, 333 Condylomata acuminata
vancomycin for, 179 Coccidiodomycosis
i n H i rschspru n g's, 330 clinical presentation, 173
Clostridiu m perfringens, 125, 130, 175 as granulomatous disease, 216
Colonoscopy Condyl o m a t a lata
antimicrobials for, 181 Coccidioides
for colorectal cancer screen i ng, 332 c l i nical presentation, 569
diarrhea caused by, 1 68 antim icrobials for, 185
Colon polyps, 331 Confabulation, 419
food poisoning caused by, 167 Coccidi oidomycosis, 143
Gardner's syndrome as cause, 568 Confidence i n terva l , 54, 55
spore formation of, 130 erythema nodosum and, 400
Colorado tick fever. See Coltivirus Confidential ity, 57, 58
Clostridiu m tetani, 124, 130 Coccygeal spinal nerves, 427
Colorectal cancer ( C R C ) , 332 Con fl i c t of i nterest, 58
spore formation of, 130 Codeine, 449
adenomatous polyps preceding, 331 Confluence of si nuses, 425
treahnent for, 574 Godman's triangle, 389
Croh n's disease and, 328 Confounding b i as, 53
Clotrimazole, 185 diagnostic findi ngs/labs, 573
diagnostic findi ngs/labs, 570 Congenital adrenal hyperplasia
Clozapine, 473 Codom i n ance, 82
molecular path enogenesis of, 332 associations, common/
reactions to, 240 Codon, 66
Peutz-j eghers syndrome a n d , 331 i mportant, 577
"Clue cells" "Coffee bea n " nuclei in B renner
screening for, 332 Congenital cardiac anomal ies
diagnostic findings/labs, 573 tumors, 532
tumor suppressor genes, 221 associations, common/
Clue cells in bacterial vaginosis, 139 Cognitive behavioral therapy
ulcerative col itis and, 328 i mportant, 267, 577
Cl uster NB!C personality (CBT) Colostrum Congenital conjugated
disorders, 468--469 for panic disorder, 466 immunoglobul i n i n , 198, 202 hyperbilirubinemia
Cluster headaches, 446 Cognitive disorders, 462. See associations, comm o n /
Colovesical fistulas
sumatriptan for, 456 also Delirium; Dementia diverticul itis as cause, 329 important, 577
vs. trigeminal neuralgia, 446 Cohort study, 50 Coltivirus, 1 58 Congenital heart disease, 265
Cluster of differentiation, 347 "Coi n " lesion on l ungs, 558 Coma Turner syndrome as cause, 569
"Cl uster of grapes" uterus, 525 Colchicine, 76, 406 sodium imbalance as cause, 487 C ongenital hepatic fibrosis
C M L. See C h ronic myelogenous for gout, 391 Comedocarcinoma, 534 ARPKD and, 498
leukemia for pseudogout, 391 COMLEX-USA Level I exam, 36-40 Congen ital mega c o l o n , 330
CMY (cytomegalovirus) , 155, 156 reactions to, 240, 241 Comma less, nonoverlapping genetic Congenital p e n i l e abnormalities, 513
antimicrobials for, 1 88 Cold aggl utinin disease code, 66 Congenital p h a ryngocutaneous
in chol ecystitis, 339 c l i nical presentation, 568 Common b i l e duct, 316 fistu l a , 5 1 0
diagnostic findi ngs/labs, 571 Cold aggl utinins, 142, 357 gal l stone obstruction, 339 Congenital pyl oric stenosis, 308
esophagi tis caused by, 324 Cold intolerance Common cold, 159 Conge n i t a l renal anoma l i es
h erpesviru s as cause, 1 5 5 hypothyroidism as cause, 566 Common hepatic artery, 313 in postren a l failure, 496
as i mmunodeficiency Sheehan's syndrome as cause, 568 Common h epatic duct, 316 Conge n i t a l rubella
infection, 205 Col ectomy Common il iac artery, 3 1 2 card i a c defects associated with, 267
as immunodeficiency for ulcerative col i tis, 328 Common pathway paten t ductus arteriosus ( P DA)
i n fection, 205 Colesevelam, 281 coagulation defects, 359 c aused by, 259
maternal/neonatal Colestipol , 281 Common peroneal nerve, 384 Conge n i t a l syph ilis, 138
manifestations, 171 Colic lymph nodes, 192 Common va riable Congesti ve ca rdiomyopathy, 272
ret i n i tis of, 1 88 Co l i pase i m munodeficiency, 206 Congestive heart fai l ure (CI-lf'), 273
treatment for, 574 fat digestion by, 322 Communicating hydrocephalus, 426 AC E i n h i b i tors for, 502
c-myc gene, 221 Col i tis, 328, 331 . See also Croh n's Competitive an tagonists an t i hype rten sive therapy for, 279
translocation of, 362 disease; Pseudomem branous efficacy of, 229 P-blocke rs for, 238
C nerve fibers, 412
colitis; Ulcerative col itis Competitive i n h i b i tors, 226 digoxi n for, 282
-
INDEX
Busulfan, 372 pacemaker action potential Caput medusae, 314 hypertension and, 267
reactions to, 240 and, 260 portal hypertension as cause, 333 variables, 254
restrictive l u n g disease caused ventricular action potential Carbachol, 233 Cardiac receptors, 264
by, 555 and, 260 for glaucoma, 449 Cardiac rhabdomyomas
toxicities, 375 Calcium homeostasis, 293 Carbamazepine diseases associ a ted with, 220
Butorphanol, 449 Calcium oxalate stones, 493. See for bipolar disorder, 464, 472, 574 tuberous sclerosis as cause, 446
"ButterAy" facial rash also Kidney stones for epilepsy, 451 Cardiac stress testi ng
l upus as cause, 566 Calcium pyrophosphate crystals as P-4 5 0 inducer, 242 medications for, 235
"ButterAy gl ioma," 447 i n pseudogout, 391 reactions to, 240, 241 Cardiac tamponade, 275
Butyrophenones Calf pseudohypertrophy as teratogen , 506 Cardiac tumors, 275
name suffix, 243 muscular dystrophy as cause, 566 for tonic-clonic seizures, 576 associations, common/
BZ I subtype, of GABA receptor, 453 Cal iciviruses, 1 54, 158 toxicities, 452 i m portant, 577
California encepha l i tis, 1 58 Carbaminohemogl ob i n , 552 Cardinal l igament, 515
c CALLA marker, 364 Carbamoyl phosphate, 65, 1 07 Cardinal vein , 250
C l esterase i n h i b i tor, 199 Cal i-Exner bodies, 532 Carbamoyl phosphate synthetases, 97 Cardiogen i c shock, 214, 271
Cl esterase i n h i b i tor deficiency. diagnostic findings/labs, 570 Carbapenems, 178 Cardiomegaly with apical atrophy, 570
See Hereditary angioedema Cal modul i n in smooth muscle Carbohydrate digestion, 322 Cardiomyopath ies, 272
C3b contraction, 386 Carbolfuchsin sta i n , 120 S4 and, 580
in splenic dysfunction, 193 Calor ( h eat), 214 Carbon dioxide wet beriberi as cause, 567
C 3 deficiency, 200 Calyces cerebral perfusion pressure Cardiovascular system
C3 nephritic factor development of, 478 and, 421 anatomy, 253
i n glomerulonephritis, 492 in pyelonephritis, 495 transport of, 552 drug name suffixes, 243
in M PCN, 491 cAM P Carbonic anhydrase, 321 , 501 drug reactions i n , 240
C 5a signaling pathways, 294 Carbonic anhydrase i n h i b i tors, 483 embryology, 250-252
in leukocyte extravasation, 215 CAM P factor, 129 Carbon monoxide pathology, 265-277
C 5 -C9 deficiencies, 200 Campylobacter, 1 19, 139 antidote to, 239 pharmacology, 279-284
C282Y mutation diarrhea caused by, 168 hemoglobin binding to, 547 physiol ogy, 253-265, 255
hemochromatosis and, 337 Campylobacter jejuni, 136 sclerosis of, 395
hypoxia caused by, 550
CA- 1 9-9 marker, 340, 222
Gram sta i n i ng, 133 Carbon tetrachloride C a rmustine, 372
CA- 1 2 5 marker, 532, 222
G u i l l a i n-Barre syndrome and, 444 as carci nogen, 223 Carnitine acyl transferase I , 97
Cabergoline
mesenteric adenitis caused by, 1 67 free radicals and, 215 Carotid artery
for pituitary adenoma, 301
Canal of Schlemm, 438 Carboplatin, 373 atherosclerosis and, 580
Cachectin . See TN F-a
indirect cholinomimetics toxicities, 375 development of, 509
Cachexia, 220
affecting, 449 Carboxyhemoglobin, 547 Carotid body and sinus
CaE DTA
c-ANCA antibodies, 205, 277 Carboxylase, 96 i n n e rvation of, 434
as antidote, 239
in glomeru l onephritis, 492 Carboxypepti dases, 322 Carotid dissection
Cafe-au-la it spots, 85, 388
Cancer. See also H ematology/ Carcinoembryonic antige n . See C EA ischemic stroke and, 425
diseases causing, 566
Oncology; Tumors Cmcinogens C a rotid massage, 264
von Reck l inghausen's disease as
D I G and, 578 chemical, 223 C a rotid si nus, 264
cause, 446
eryth rocyte sedimentation rate Carcinoid syndrome, 304, 559 Carpal tunnel syndrome, 379
Caffeine
i n , 217 treatment for, 574 Carteol ol
intoxication and withdrawa l , 471
h a l l marks of, 218 Carcinoid tumors, 333 for glaucoma, 449
Calcarine fissure, 441
Cancer drugs, cell cycle, 369 octreotide for, 341 Cartilage
Calcarine sulcus, 415
Cancer epidemiol ogy, 224 Carcinoma in situ, 218 damage as drug reaction, 241
Calcinosis
in scleroderma, 395 Candida , 121 Carcinomas. See also spec i fi c Caseating granuloma, 132
Calcitonin, 294 antimicrobials for, 185 carcmomas Case-control study, 5 0
for osteoporosis, 387 bacterial endocarditis caused chemicals causi ng, 223 Caseous n ecrosis, 212
signal ing pathway, 294 by, 274 hyperparathyroidism and, 580 Caspases, 212, 213
in thyroid cancer, 299 esophagitis caused by, 324 vs. sarcomas, 219 Caspofungin, 1 8 5
as tumor marker, 222 as immunodeficiency Cardiac arrest for Ca ndida , 145
Calcitriol infection, 205 amphetamines as cause, 471 Casts i n urine, 489
PTH and, 293 Candida a lbicans, 145, 175 Cardiac arrhythm i as, 271 Catalase
Calcium chronic mucocutaneous diabetic ketoacidosis and, 303 free radical i n j ury and, 215
disturbances in, 487 candidiasis caused by, 206 treatment for, 574 Catalase-positive organisms, Ill , 175
in kidney stones, 493, 579 as nosocomial infection, 174 Cardiac cirrhosis, 273, 335 Cataplexy
loop diuretics and, 500 treatment for, 574 nutmeg l iver as cause, 335 in narcolepsy, 62
for osteoporosis, 575 Candidiasis Cardiac cycle, 256 Cataracts, 439
i n platelet plug formation, 349 antimicrobials for, 185 Cardiac function curves, 255 AI port synd rome as cause, 567
PTI -1 and, 293 , 300 Cannabis. See Marij uana Cardiac glycosides, 77, 282 in diabetes m e l l itus, 302
reabsorption of, 483 "Cape-l ike" l oss of sensation, 410 name suffix, 243 prednisone as cause, 373
Calcium carbonate, 341 Capi l l aries Cardiac ischemia Catatonic schizophrenia, 463
Calcium channel bl ockers, 240, 279 "wire looping," 492 therapeutic antibodies for, 210 Cat bite, infected, 567
for angina, 280 Capi l l a ry Auid exchange, 265 Cardiac muscle, 260 Catecholarnines
as antiarrhythmics, 284 Capl an 's syndrome contraction of, 386 effect on diasto l i c
for atrial A utter, 262 pneumoconioses as cause, 555 innervation of, 230 depolarization, 260
for hypertension, 279 Capsid structures, 1 53 cells as target of noradrenergic effect on stroke vol ume, 254
Calcium channels in genetic transduction, 1 26 signal i ng, 232 nervous system rol e, 230
epilepsy d rugs and, 451 Capsule of lymph node, 192 Cardiac output (CO), 253 . See production of, 286
in muscle contractions, 385 "Captai n 's wheel" yeast, 143 also Stroke vol ume ( SV) synthesis/tyrosi n e catabolism, 108
opioid effect on , 449 C aptopri l , 502 equation for, 582 in thyroid storm, 299
I ND E X
Cat scratch disease, 139 Cel iac lymph nodes, 192 Cerebel l um , 408, 415 C h ediak-1-l igash i syndrome, 76, 207
as granulomatous disease, 2 1 6 Cel iac sprue, 326 Cerebral aqueducts, 426 diagnostic signs/labs, 572
Cauda equina bil iary cirrhosis and, 338 Cerebral arteries, cortical Chelation, 353
location of, 427 Cel iac trunk, 312, 313 distribution, 420 Chemical carcinogens, 223
Caudal fold closure fai l ure, 308 Cell biology of bone, 386 Cerebral cortex Chemoprophylaxis, 1 83
Caudal medulla Cell cycle artery distribution, 420 Chemoreceptors, 264
strokes in, 422 i n chemotherapy, 369 atrophy, i n Alzh eimer's disease, 443 innervation of, 434
Caudal regression syndrome, 506 phases of, 74 functions, 418 C hemotaxis
Caudate atrophy, 85 phases of, and tumor suppressor Cerebral edema, 421 cytokines causing, 200
Caudate degeneration genes, 221 diabetic ketoacidosis and, 303 Chemotherapy
diseases associated with, 566 Cell death Cerebral hemispheres, 408 antiviral , 1 87
Caudate nucleus via apoptosis, 212 Cerebral perfusion, 421
via i ron poisoning, 217 for pancreatic
i n Huntington's disease, 417 Cerebrospinal A u i d ( C S F), 426
Cavernous hemangiomas, 335 Cell i n j ury, 213 adenocarcinoma, 340
in brain atrophy, 426
von 1-l ippel-L i ndau disease as atrophy, 214 Chemotherapy drugs, 369-374
yellowish, 573
cause, 446 from free radicals, 215 cell cycle, 369
Cereul i de tox i n , 131
Cavernous sinus, 425, 436 necrosis, 212 potency of, 229
Ceruloplasmin
CBG. See Corticosteroid-binding reversible vs. i rreversible, 213 Ch emotoxicities, 375
low levels of, 572
globu l i n (CBG) Cell lysis Chemo-Tox man, 375
as serum marker, 334
C cells of thyroid, 294 complement and, 199 Cherry h emangioma, 278
in Wilson's disease, 337
CCK. See Cholecystokinin (CCK) hyperkalemia caused by, 487 Cervical cancer, 528, 578 C h erry-red spot on macula, 1 12
CCK B receptor, 321 Cell-mediated immunity 1- 1 PV virus i n , 222 diseases causing, 566
CO l a vs. humoral response, 202 papi l lomavirus, 1 55 C h est pain
i n Langerhans cel l i n l eprosy, 133 Cervical carcinoma in situ, 528 diseases causing, 566
h istiocytosis, 366 T cells i n , 347 C heyne-Stokes resp i rations
Cervical condyl oma, 528
CD3 vaccines inducing, 1 53 c l i nical presentation, 568
Cervical gangl ia in Horner's
inhibition of by Cell surface proteins, 201 C H F. See Congestive h eart fa i l u re
syndrome, 431
immunosuppressan ts, 209 Cell trafficking, 75 ( C H F)
Cervical mucus
C D4, 347 Cellular crescents in Bowman's C h iari malformations, 409, 577
progesterone and, 520
count for, 146 capsule, 570 Arnold-C h iari, 409
progesti n effect on, 540
H lV binding, 164 C e l l u l i tis, 402
Cervical pathol ogy, 528 syri ngomye l i a and, 410, 429
CD4+ B cells, 362 Cell wall s/cell membranes, 1 18, 215
Cervical sinus C h i ckenpox. See VZV virus
C D 5 + B cel ls, 362 bacteria lacking, 1 19
persistent, 509 Ch ief cell s
CDS, 347 bacteria with unusua l , 1 19
Cervical spinal nerves, 427 l ocation of, 321
CD 1 4, 345 toxins lysing, 125
Cestodes, 1 52 of parathyroid, 293
CD1 5 Central and peripheral nervous
Ceti rizine, 562 peps i n produced by, 320
Reed-Sternberg cells and, 361 system , 230
C fibers C h i l d abuse, 460
CD20 Central diabetes insipidus, 301
in spinal cord, 427 exception to confidential ity, 57
rituximab effect on, 374 treatment for, 306
C/,TR gene, 86 Munchausen's syndrome by
as therapeutic antibody target, 210 Central herniation. See Transtentorial
cGMP proxy, 467
CD28, 347 herniation
CD30 m a l e sexual response and, 516 physical c h i l d abuse, 460
Central nervous system (C S )
Reed-Sternberg c e l l s a n d , 361 d r u g name suffixes, 243 signaling pathways, 294 sexual child abuse, 460
C D9 5 . See aho Fas l igand ( C D9 5 ) origins of, 41 1 CGRP vs. osteogenesis imperfecta, 78
C D Ks (cycl i n dependent kinases), 74 stimulants, 472 migraine headaches and, 446 C h i l d h ood and early-onset
CEA tumor marker, 222 Central pontine myel inolysis, 419 Chagas' disease, 1 50 psychological disorders, 460
for colorectal cancer, 332 Central retinal artery occlusion, 438 achalasia and, 324 C h i l d h ood disintegrative disorder, 461
Cecum c l inical presentation, 566 cardiomyopathy caused by, 272
C h i l d h ood primary bra i n tumors, 448
angiodysplasia in, 331 Central scotoma, 441 diagnostic findings/labs, 570
C h i l dhood rashes, 172, 174, 566
1olvulus, 330 Central sleep apnea, 556 "Chain termination," i n protein
C h i l d neglect, 460
Cefaclor, 178 Central sulcus, 418 synthesis, 69
C h i meric indivi d u a l , 82
Ceidzol i n , 178 Central vertigo, 446 Chancre
" C h i pmunk" facies, 353
Cefepime, 178 Centriacinar emphysema, 554 c l i nical presentation , 567
painless, 138 x2 (ch i-square) , 55
Cefotaxime, 178 Centrilobular necrosis C h l a mydia, 580
Cefoxitin , 178 carcinogens affecting, 223 Chancroid, 173
Chlamydia
Ceftazidime, 178 Centromeres Chandel ier sign in pelvic
inAammatory disease, 173 pneumonias caused by, 560
Cetlriaxone, 178 autoantibodies targeting, 205
Charcoal yeast extract agar, 1 20, 135 C h l a mydiae, 1 19 , 1 21 , 141
as gonorr hea prophylaxis, 184 Cephalexin, 178
Charcot-Bouchard aneurysms, 423 antimicrobials for, 1 80, 181
for Haemophilus injluenzae, 134 Cephalosporins, 178
intraparenchymal h emorrhage c l i nical presentation, 173
for Lyme disease, 137 mechanism of action, 176
and, 424 forms of, 141
for meni ngitis, 169 re<Jctions to, 241
for streptococcus pnewnoniae, 576 Charcot-Leyden crystals stain for, 1 20
for Ne15sena, 134, 575
Cefuroxime, 178 c-erbB2, 374, 534 in asth ma, 554 Ch lamydia pneumoniae, 141 , 168
Celecoxib, 405 Cerebel lar hemisphere, 419 Charcot-Marie-Tooth disease, 445 antimicrobials for, 1 80
as sulfa drug, 242 Cerebellar peduncles, 422, 433 Charcot's joints, 138 Chlamydia psittaci, 141
Cel iac artery, 309 Cerebellar tons i l l a r herniation, 448 syph i l i s and, 429 Ch lamydia trachoma tis, 141 , 173
structures suppl ied by, 312 associations, common/ Charcot's triad of cholangitis, 339 pelvic inAammatory disease
Cel iac disease important, 577 Charcot's triad of multiple and, 173, 580
autoanti bodies associated with, 205 Cerebellar vermis sclerosis, 444 pneumonia caused by, 168
dermatitis herpetiformis and, 398 i n Dandy-Walker syndrome, 409 ChAT (enzym e ) . See Choline serotypes for, 141
d1agnostic findings/labs, 570 l esions i n , 419 acetyl transferase treatment for, 574
I
INDEX 65 1
Chlamydophila psittaci, 139 C horea, 417 chromosomal translocation C i rcumAex artery ( C FX ) , 253
Ch loasma, 396 basal gangl ia lesions and, 419 with , 365 C i rrhosis, l33, 578
Chloramphenicol , 179, 181 diseases associated with, 566 hydroxyurea for, 373 <Jicohol ic, 334, 472, 579
contrai ndi cated d u ring C h oreiform movements, 85 imatinib for, 374 autoantibodies associated with, 205
pregnancy, 190 C h oriocarcinomas, 531 , 536 oncogene for, 221 bl ood transfusions for, 360
mechanism of action, 176 -hCG marker for, 222 treatment for, 574 cardiac, 335
reactions to, 240 diagnostic findings/labs, 571 Chronic myeloprol iferative hemochromatosis and, 337
for Rickettsia rickettsii, 576 hydatidiform moles as cause, 525 disorders, 366 hyperaldosteronism caused by, 296
Chl ordiazepoxide, 453 methotrexate for, 371 C h ronic obstructive pulmonary neoplasms associated with, 220
Ch loride theca-l utein cysts and, 530 disease (COPD) treatment of, 500
along proximal tubule, 484 C horioreti nitis chol inomimetic agents and, 233 in Wilson's disease, 337
Chloride channels causes of, 171 hypertension and, 580 cis deletion, 352
benzodiazepi nes and, 453 C horoid , 437 medications for, 234 C isplati n , 370, 373
Chloride diuresis Choroidal neovascularization Chronic pancreatitis, 340 reactions to, 241
cisplati n/carboplatin and, 373 age-related macular degeneration associations, common/ toxicities, 375
Chloride-I-IC0 3 - antiporter, 344 and, 441 important, 580 C i talopra m , 475
Ch I ori de reabsorption (rena I ) , 484 "Christmas tree" distribution of pancreatic adenocarcinoma C itrate
Chloroquine, 186 plaques, 401 and, 340 for kidney stones, 493
for malaria, 575 Chromaffin cells, 286, 297 pancreatic i nsufficiency caused C itrate syn thase, 98
for Plasmodiu m , 149 C h romatin by, 326 Citrobacter, 134
Chlorpheniramine, 562 i n plasma cells, 346 C h ronic pyelonephritis, 495 Gram staining, 133
Chlorpromazine, 473 structure of, 64 C h ronic renal fa i l ur e , 497 C K. See Creati ne ki nase (CK)
Chlorpropamide, 305 C h ro m osome 3 waxy urinary casts in, 489 c-kit gene, 221
Chocolate agar (factors V and X), 1 20, deletion of, 494 Chronic sinusitis C K-MB test
134 C h romosome I I Kartagener's syndrome as for myocardial i n farction, 271
deletion of, 494 cause, 569 Cladribine
"Chocolate cysts," 528, 530, 570
C h romosome 1 3 C h ronic transplant rejection, 208
for h a i ry cell leukemra, 364
Cholangiocarcinoma
Wilson's disease, 337 Ch urg-Strauss syndrome, 277
Aukes and, 152 Clara cells, 544
C h ronic arrhythmia diagnostic findings/labs, 570
Cholecalciferol, 94, 294. See Clarith romyc i n
associ<Jtions, common/ as granulomatous disease, 216
also Vitami n D contraindicated dunng
i m portant, 577 Chvostek's sign, 300
Cholecystectomy, 339 pregnancy, 190
C h ronic arthritis, 392 c l i nical presentation, 567
Cholecystitis, 339 for Helicobacter pylori, 137
C h ronic atroph i c gastritis C hylomicrons, 1 1 5, 1 1 6
Cholecystokinin (CCK), 319 C l asp knife spasticity
associations, common/ impaired production of, 326
Cholel ith iasis. See Gallstones as motor neuron sign, 428
i mportant, 577 Chylothorax, 561
Cholera C lassical conditioning, 4::.8
neoplasms associated with , 220 Chymotr}1)Si n , 322
vaccine for, 202 C l assical pathway for complement
C h ronic bacterial pyelonephritis Cidofovir, 1 88
Cholera toxin, 124 activation, 199
diagnostic findings/labs, 573 Cigarette smoke
in lysogenic phage, 126 C l assic c l i n i cal pr esentations, 566-570
C h ronic bronchitis, 554 as carcinoge n , 223
Cholestasis Classic diagnostic as>ociations, 576-
C h ronic closed-angle glaucoma, 439 Cigarette smoking. See Tobacco use
as drug reaction, 240 580
C h ronic gastritis, 327 C ilastati n , 178
Cholesterol, 1 16 Classic galactose mia, 105
i n trinsic factor and, 320 reactions to, 241
in bile, 323 C i l iary body, 437 C l assic l abs/findings, 570-573
stomach cancer and, 327
excretion of, 323 C h ronic gout C i l iary gangl ion, 440 Classic treatments, 574-576
gal lstones caused by, 339 treatment for, 574 C i l iary muscles, 438 Class switc h i ng
synthesis of, 97, 1 14 Chronic granulomatous disease, 103, C i l ia structure, 76 B-c e l l , 196
Cholesterol 7a-hydroxylase, 323 175 C i l ostazol, 369 cytokines promotmg, 200
Cholesterol absorption blockers, 281 aspergi l l osis i n , 145 C i m etidine, 341 Clathrin, 75
Cholesterol drugs. See Anti l ipid drugs associations, common/ gynecomastia caused by, 535 Clavulanic acid, 177
Cholesterol ester transfer protein i mportant, 579 as P-4 5 0 i n h i b i tor, 242 aminopenicil l i n s and, 177
(CETP), 1 1 5 catalase-positive organism reactions to, 240 C l aw hand, 381 , 383
Chol esterol stones, 339 infections, 121 C i nchonism, 283 C L (clearance). See Clear ance of
Cholestyramine, 281 as immunodeficiency disease, 207 as drug reaction, 241 d rugs
Choline acetyl transferase, 232 NADP J-1 deficiency i n , 207 C i ngul ate gyrus, 415 C l earance equatron, 581 , 582
Choline, in cholinergic signal i ng. recombinant cytokines for, 210 C i ngulate herniation, 448 C l earance of drug>, 227
See Acetylchol i nesterase C h ronic hemolysis C iproAoxacin, 182 C l ear cell adenocarcinoma of the
Chol inergic drugs, 232 gallstones and, 339 as meni ngococcal prophylaxis, 184 vagma, 532
Cholinesterase i n h i b i tors Chronic hepatitis for Neisseria , 134 assocrations, common/
as antidote for neuromuscular treatment for, 574 as P-4 5 0 i n h i bi tor, 242 i m portant, 577
blocking drugs, 455 C h ronic i nAammation, 214 C i rcadian rhyth m , 6 2 Cleft l i p/palate, 5 1 1
poisoni n g of, 233 C h ronic ischemic heart disease, 269 hypothalamic regulation of, 414 Patau's syndrome as cause, Sb/
Chol inoceptors, 232 C h ronic kidney disease pineal gland and, 433 teratogens causmg, 506
Chol inomimetics, 233 G FR and, 480 C i rcle of Wi l l i s C lefts, branc h i a l , 509
for glaucoma, 449 C h ronic lymphocytic l eukemia, 364 aneurysms a t , 423 C l i mb i ng fibers, 4 t 5
Chomosomal translocations, 365 pred nisone for, 373 C i rcular bacteria. See Cocci bacteria C l i n damycm, 1 7 9 , 181
Chondrocytes C h ronic mucocutaneous candidiasis C i rculation th rough organs, 264 mechanism of actron, 176
ossification by, 386 as immunodeficiency disease, 206 C i rculatory system reactions to, 240
Chondrosarcomas, 389 C h ronic myel ogenous l eukemia, 365, autoregulation, 264 C l i n ical reflexes, 431
Chordae rupture 366 fetal, 252 Cl i nical trials, SO
mitral valve prolapse caused alkylating agents for, 372 C i rcumcision "Clock face" c e l l s in m u l tr ple
by, 259 cause of death i n , 578 squamous cell carci noma and, 537 myeloma, 363
I N DEX
Clofazimine CNS. See Central nervous system Collagen , 77 Com plement, 193, 199
for mycobacteria, 183 (CNS) synthesis and structure, 78 activation of, 197
Clofibrate, 281 C S lymphoma in wound hea l i ng, 216 a n ti body binding of, 197
gallstones and, 339 1 -1 IV virus in, 222 Collagenases, 218 deficiencies, infections caused
Clomiphene, 540 Coagulation cascade, 348 Collateral circulation by, 205
for polycystic ovarian Coagulation disorders, 359 gastrointestinal system, 313 disorders of, 200
syndrome, 530 Coagulation factors Collecting ducts Complementation, viral , 1 53
reactions to, 240 deficiencies, blood transfusions devel opment of, 478 Complement cascade, 348
Clomipramine, 475 for, 360 drugs acting on, 501 Complement pathways, 348
for obsessive-compulsive i n D I C , 360 Collecting tubules, 483 bacterial i n h i b i tion of, 128
disorder, 466 warfarin effect on, 367, 368 ADH action on, 231 Complex seizures, 445
Clonidine Coagu l ation pathways, 348 drugs acting on, 501 drugs for, 451
cli nical use, 236 Coagulative necrosis, 212, 270 Calles' fractures, 387 Compliance, pul monary, 547
Cl oni ng methods, 81 Coarctation of the aorta, 266 Col l icul i , 433 Comprehensive Basic Science Self
Clo11orchis si11e11sis, 152, 222 diagnostic findings/labs, 573 Colon , 309 Assessment ( C B SSA), 10, 1 1
Clopidogre l , 368 Turner syndrome associati on , 267 diverticula, 329 Comprehensive Osteopath ic Medical
mechanism of, 349 Cobalamin, 93 histology, 31 1 Self-Assessment Examination
Closed-angle glaucoma, 439 Cobblestone mucosa, 328 Colon cancer ( C O M SAE ) , 40
Clostridia, 130 Cocaine, 454 diseases associated with, 220 Compression fractures
Clostridium, 1 19, 121 abruptio placentae and, 526 5-Auorouracil for, 371 associations, common/
Clostridium hotuli11um, 124, 130 -blockers and, 235 incidence of, 224 i m portant, 577
food poisoning caused by, 1 67 cardiomyopathy caused by, 272 oncogene for, 221 Conditioning (psychology), 458
spore formation of, 130 intoxication and withdrawal, 471 Streptococcus hovis and, 1 29 Conduct disorder, 460
treatment for, 574 mechanism of action, 232, 235 Streptococcus hovis endocarditis Conducting zone of respiratory
Clostridiu m difficile, 130 priapism caused by, 537 in, 274 tree, 544
antimi crobials for, 182 tumor suppressor genes, 221 Conduction aphasia, 420
reactions to, 240
Colonic atresia, 308 Conduction velocity, of axon, 412
diarrhea caused by, 168 as teratogen , 506
Colonic Aora, 1 67 Conductive hearing l oss, 436
spore formation of, 130 Cocci bacteria, 1 19, 127
Colonic resection Condyloma acuminata, 397
treatment for, 574 identification of, 127
for carci noid tumors, 333 Condylomata acumi nata
vancomycin for, 179 Coccidiodomycosis
in l l irschsprung's, 330 c l i nical presentation, 173
Clostridium per{ri11gells, 125, 130, 175 as granulomatous disease, 216
Colonoscopy Condylomata lata
antimicrobials for, 181 Coccidioides
for colorectal cancer screening, 332 c l inical presentation, 569
diarrhea caused by, 1 68 antimicrobials for, 185
Colon polyps, 331 Confabulation, 419
food poisoning caused by, 1 67 Coccidioidomycosis, 143
Gardner's syndrome as cause, 568 Confidence i n terva l , 54, 55
spore formation of, 130 erythema nodosum and, 400
Colorado tick fever. See Coltiviru s Confidential i ty, 57, 58
Clostridium teta11i, 124, 130 Coccygeal spinal nerves, 427
Colorectal cancer ( C RC ) , 332 ConAict of i n terest, 58
spore formation of, 130 Codeine, 449
adenomatous polyps preceding, 331 ConAuence of sinuses, 425
treatment for, 574 Cod man's triangle, 389
Crohn's disease and, 328 Confounding bias, 53
Clotrimazole, 185 diagnostic findings/labs, 573
diagnostic findings/labs, 570 Congenital adrenal hyperplasia
Clozapine, 473 Codominance, 82 associations, common/
molecular pathenogenesis of, 332
reactions to, 240 Codon , 66 i m portant, 577
Peutz-Jeghers syndrome and, 331
"Clue cells" "Coffee bean" nuclei in Brenner screening for, 332 Congenital cardiac anomal i es
diagnostic findings/labs, 573 tumors, 532 tumor suppressor genes, 221 associations, common/
Clue cells in bacterial vaginosis, 139 Cogni tive behavioral therapy ulcerative colitis and, 328 i m portant, 267, 577
Cl uster NB/C personal ity (C BT) Col ostrum Congenital con j ugated
disorders, 468-469 for panic disorder, 466 immunoglobu l i n in, 198, 202 hyperb i l i rubinemia
Cluster headaches, 446 Cognitive disorders, 462. See Colovesical fistulas associations, common/
sumatriptan for, 456 also Del irium; Dementia diverticulitis as cause, 329 i m portant, 577
vs. trigeminal neuralgia, 446 Cohort study, 50 Coltivirus, 1 58 Congenital h eart disease, 265
Cl uster of differentiation, 347 "Coin" lesion on l ungs, 558 Coma Turner syndrome as cause, 569
"Cluster of grapes" uterus, 525 Colch icine, 76, 406 sodium i mbalance as cause, 487 Congenital h epatic fibrosis
C M L. See C h ronic myelogenous for gout, 391 Comedocarcinoma, 534 ARPKD and, 498
leukemia for pseudogout, 391 COM LEX-U SA Level l exam, 36-40 Congenital megacolo n , 330
CMV (cytomegaloviru s ) , 155, 156 reactions to, 240, 241 Comma less, nonoverlapping genetic Congenital penile abnorma l i ties, 513
antimicrobials for, 188 Cold aggluti n i n disease code, 66 Congenital pharyngocutaneous
in chol ecystitis, 339 c l i nical presentation, 568 Common bile duct, 316 fistula, 510
diagnostic findi ngs/labs, 571 Cold aggl utinins, 142, 357 gallstone obstruction, 339 Congenital pyl oric stenosis, 308
esophagitis caused by, 324 Cold intolerance Common cold, 1 59 Congenital renal anomal ies
herpesvirus as cause, 155 hypothyroidism as cause, 566 Common hepatic artery, 313 i n postrenal fai l u re, 496
as i m munodeficiency Sheehan's syndrome as cause, 568 Common h epatic duct, 316 Congenital rubella
infection, 205 Colectomy Common i l iac artery, 312 cardiac defects associated with, 267
as immunodeficiency for ulcerative colitis, 328 Common pathway patent ductus arteriosus ( PDA)
infection, 205 Colesevelam, 281 coagulation defects, 359 caused by, 259
maternal/neonatal Colestipol , 281 Common peroneal nerve, 384 Congenital syp h i lis, 138
manifestations, 171 Col ic lymph nodes, 192 Common variable Congestive cardiomyopathy, 272
retinitis of, 1 88 Co l i pase i mmunodeficiency, 206 Congestive h eart fai l ure ( C H F) , 273
treatment for, 574 fat digestion by, 322 Communicating hydrocephalus, 426 ACE i n h i bitors for, 502
c-myc gene, 221 Colitis, 328, 331 . See also Crohn's Competitive antagonists antihypertensive therapy for, 279
translocation of, 362 disease; Pseudomembranous efficacy of, 229 -blockers for, 238
C nerve fibers, 412 colitis; Ulcerative colitis Competitive i n h i b i tors, 226 digoxin for, 282
I ND E X
diuretics and, 500 Cori's disease, I l l nonproductive, 1 42 C lU- J . See Corti cotropi n-rel easing
erythrocyte sedimentation rate c l i nical presentation, 568 staccato, 141 hormone ( C RI- 1 )
and, 349 Cornea, 437, 438 whooping, 124 Cribriform plate
eryth rocyte sedimentation rate Corneal arcus, 267 Coumad i n . See Warfarin as crania l nerve pathway, 435
i n , 217 Corneal deposi ts Councilman body C ricoid cartilage
hemochromatosis and, 337 anti psychotics as cause, 473 diagnostic findings/labs, 571 derivation of, 510
hydrochloroth iazide for, 501 in Wilson's disease, 337, 567 Coun tertransference and Cricothyroid muscle
hyperaldosteronism caused by, 296 Corneal reAex, 434 transference, 458 derivation of, 510
pleural effusions caused by, 561 Corniculate cartilage Courvoisier's sign , 340 C ri-du-chat syndrome, 89
potassium-sparing diuretics derivation of, 510 cl inical presentation, 568 Crigler-N a j j a r syndrome, 336
and, 501 Coronary artery Covalent alterations c l i nical presentati on, 569
in renal fai l ure, 497 anatomy of, 253 posttranslational modi fication, 73 Crimean-Congo hemorrhagic
systolic, 254 atheroscl erosis and, 580 Cowdry A inclusions, 1 57 fever, 1 58
treah11ent of, 500 Coronary artery disease (CAD) Cowdry type A bodies Grahn 's disease, 93, 328
Congestive I iver disease, 335 diabetes mell itus and, 302 diagnostic findings/labs, 572 arth ritis and, 392
Congo sta in, 217, 490 menopause and, 523 Cowper's gland, 516 diagnostic signs/labs, 572
Conjoined tendon, 317 Coronary steal syndrome, 269 Cowpox, 1 55 gal l stones and, 339
Conjugated hyperb i l i rubinemia, 336 Coronary vasospasm COX- 1 /COX-2 enzymes as granulomatous disease, 216
Conj ugate lateral gaze palsy sumatriptan as cause, 456 aspi rin effect on, 368 i n A iximab for, 210, 342
diseases causing, 566 Coronaviruses, 158 glucocorticoids and, 306 sulfasalazine for, 342
Conj ugation (genetic ) , 126 Cor pulmonale, 273 , 549, 580 COX-2 i n h i b i tors, 405 therapeutic antibodies for, 210
Conj unctivitis pneumoconioses as cause, 555 Coxiella bumetii, 139, 140 TN F-a i n h i b i tors for, 406
adenovirus as cause, 1 55 Corpuscles, sensory, 412 spore formation of, 130 transmural inAammation and, 576
Chlamydia trachomatis as Corpus l uteu m Coxsacki e A treatment for, 574
cause, 141 cysts i n , 530 c l i nical presentation, 569 Vitamin B 1 2 deficiency i n , 354
measles as cause, 567 menstrual cycle and, 521 Coxsackie B, 579 C romolyn sodium
reactive arthritis as cause, 570 progesterone production, 520 Coxsackievirus, 140, 1 58 mast cell degranulation and, 346
Connective tissue Corrosive esophagitis c l i nical presen tati on, 172 C ross-l inking, 78
disorder of, c l i nical bisphosphonates as cause, 405 cp (target plasma concen tratio n ) . C rossover studies, 53
presentation, 567 Cortex, cerebra l . See Cerebral cortex See Plasma drug C ross-sectional study, SO
drug reactions i n , 241 Cortex, renal, 499 concentration C roup, 1 60
tumors of, 219 Corticobulbar tract, 437 Cranial fossa pulsus paradoxus i n , 275
Conn's syndrome, 296 Corti comedulla as cranial nerve pathways, 435 C rus cerebri, 432
clinical presentation, 572 scarring of, 495 Cranial nerve Ill , 441 C rusts, 395
Consent, informed, 56 Corticosteroid-b i nding globu l i n Cranial nerves, 432, 434. See C ryoprecipi tate
Constant infusion of drugs, 227 (CBG) also specific nerves i n blood transfusion therapy, 360
Constriction of pupil , 440 cortisol and, 292 lesions, 436 C rypt abscesses
Constrictive pericarditis Corticosteroids, 563 nucl ei, 434 i n ulcerative col itis, 328
associations, common/ for asth ma, 563 reAexes, 434 C rypt hyperplasia
important, 577 cataracts and, 439 Schwann cells i n , 412 celiac sprue as cause, 326
Contact dermatitis for Crohn's disease, 328, 574 i n tongue development, 410 C ryptococcal meningitis, 145
as hypersensitivity disorder, 204 osteonecrosis caused by, 392 vessel pathways and, 435 antimicrobials for, 185
Contemplation phase of addiction reactions to, 241 Craniopharyngiomas, 301 , 448, 505, Cryptococcus, 122
recovery, 470 for vascul itis, 276 577 antimicrobials for, 185
Contraceptives for Wegener's granulomatosis, 576 C RC . See Colorectal cancer (C RC ) CryJJtococcus neofonnans, 145
minors' right to treatment, 56 Corticosterone, 291 Creatine kinase ( C K ) stain for, 120
Contraction alkalosis, 501 Corticotropi n-releasing hormone in polymyosi tis/ treatment for, 574
diuretics as cause, 501 ( C lU-J ) , 289 dermatomyositis, 394 C ryptorchidism, 536
Contralateral deficit cortisone and, 292 Creatinine Cryptosporidiwn , 147
in stroke, 422 gestational cortical secretion, 286 AC E i n h i b i tors, effect on, 502 C rypts of Lieberhi h n , 31 1
Contralateral hemianopia signaling pathway, 294 clearance of, 480 C u l tures. See Stains (microbiol ogy)
strokes as cause, 422 Cortisol , 291 , 292 glomerular fi ltration rate (CFR) Cuneiform cartilage
Control of reproductive in Cush i ng's syndrome, 296 and, 480 derivation of, 510
hormones, 538 dexamethasone test effects, 296 1 1 2 blockers and, 341 C u rl ing's ulcer, 327
Conversion disorder, 467 embryological secretion of, 286 along proximal tubule, 484 "Curran t jel ly" sputu m , 175
Convertases production of, 286 in renal fai l ur e , 496 diseases causi ng, 569
in complement system , 199 signa l i ng pathway, 294 Cre-lox system , 81 C urrant j e l l y stools, 330
Coombs' test, 203, 357, 240 tumors producing, 296 Crescentic glomerulonephritis, 492 C ursc h m a n n 's spirals, 554
COP complexes, 75 Corynebacteri u m , 1 19 diagnostic findi ngs/labs, 570 diagnostic findings/labs, 570
COPD. See C h ronic obstructive Corynebacterium diphtheriae, 130 C REST syndrome, 395 Cush i ng-l ike symptoms
pulmonary disease (COPD) culturing, 120 achalasia and, 324 prednisone as cause, 373
Copper toxin of, 124 antibodies associated with, 205 Cushing reaction, 264
accumulation of, 337 i n u n i m munized c h il dren, 174 b i l i a ry cirrhosis and, 338 Cush i ng's syndrome, 223, 296, 578
antidote to, 239 Coryza diagnostic findings/labs, 570 acanthosis n i gricans and, 400
Coprola l i a i n Tourette's measles as cause, 567 Raynaud's phenomenon in, 276 anovulation i n , 529
syndrome, 460 Costimulatory signals, 196 Cretinism, 298 as drug reaction, 241
Coracobrach ialis muscle Cough associations, con1n1on/ associations, common/
musculocutaneous nerve damage ACE i n h i b i tors and, 502 important, 577 important, 578
and, 382 barking, 160 Creutzfeldt-j akob disease (Cj D ) , 167, glucocorticoicls as cause, 306
Core ethical principles, 56 dcxtromethorphan for, 449 443 Cush i ng's ulcer, 327
Cori cycle, 106 as drug reaction, 240 "Crew cut" on sku l l X-ray, 353, 356 gastric u lcers and, 576
INDEX
Cutaneous anthrax, 131 Cytochrome P-4 5 0 Decongestants " Dense deposits" i n M PGN, 491
Cutaneous edema barbiturates a n d , 452 efficacy of, 229 Dental plaque
diseases causing, 566 phenytoi n and, 452 Decussation, 428 Aora, 167
Cutaneous innervation of the Cytokeratin, 76 Deep cerebel lar nuclei , 415 Dentate l i n e , 315
hand, 380 Cytoki n e receptors Deep inguinal ring, 317 Deoxyribonucleotides, 65
Cutaneous lesions as oncogene product, 221 Deep venous th rombosis ( DVT) , 553 Dependent personal i ty disorder, 469
in adult T-cell lymphoma, 362 Cytokines, 200. See also I nterferons; diagnostic findi ngs/labs, 572 Depersonal ization disorder, 464
Cutaneous mycoses, 144 l n terleukins heparin for, 367 Depigmentation of substantia
Cutaneous photosensitivity i n cachexia, 220 Defects nigra, 416
porphyria as cause, 358 helper T cell secretion of, 196 in visual field, 441 Depolarizing neuromuscular
Cutaneous T-cell l)'mphoma recombinant, 210 Deferasi rox blockers, 455
clinical presentation, 567 regulatory T cell production of, 197 for hemochromatosis, 337 Depressan ts
CVl D. See Common variable signal ing pathway, 294 Deferoxam i n e i n toxication and withdrawa l , 470
immunodefi ciency (CV l D ) Cytolysis as antidote, 239 Depression. See also Antidepressan ts
Cyanide, 102 compl ement and, 199 for hemochromatosis, 337 anacl itic, in i n fa n ts, 459
Cyanide poisoning Cytomegalovirus. See C M V Deformation anorexia nervosa and, 469
antidote to, 239, 547 (cytomegalovirus) as organ morphogenesis error, 505 atypical, 465
hypoxia caused by, 550 Cytomegalovi rus (C MV) Degenerate/redundant genetic atypical antipsychotics for, 473
Cyanosis, 265 Guillai n-Barre syndrome and, 444 code, 66 bipolar disorder and, 464
associations, common/ Cytoplasm, 96 Dehydroepiandrosterone major depressive disorder, 465
important, 578 Cytosine, 64 ( D H EA), 291 neurotransmitter l evels i n , 413, 461
Cycl in-C D K compl exes, 74 Cytoskeletal elements, 76 Dehydrogenase, 96 PCP as cause, 471
Cyclin 0 1 translocation, 362 Cytotoxic hypersensitivity (type Delavirdi ne, 1 89 postpartum , 465
Cyclins, 74 I I ) , 195, 203 Delayed cell-mediated pseudodementia caused by, 462
Cycl ooxygenase, 349 Cytotoxic T cells, 195, 197, 347 hypersensitivity ( type screening for, 465
aspirin effect on, 368 apoptosis and, 212 IV), 195, 203 sexual dysfunction and, 60
aspirin i nhi bi tion of, 404 Delayed immune response, anti bodies sleep stages and, 62
surface proteins, 201
involved in, 198 S N R l s for, 475
i n h i b i tion of, 405 Cytotox in , 130
Del irium, 462 S S R l s for, 475
Cyclopegia Cytotrophoblast, 508
Del irium tremens ( DTs) , 470, 472 suicide and, 466
medications causing, 234
Cyclophosphamide, 372 D benzodiazepi n es for, 453 treatment for, 472, 574
0-ami nolevu l i n i c acid synthase Depressive disorder, 464
hemorrhagic cystitis i nduced D 2 receptor antagonists
gene, 353 Deprivation of affection i n
by, 575 for sch izophrenia, 576
o cells, 287 i n fa n ts, 459
reactions to, 241 Daclizumab
Delta sleep, 61 de Querva i n 's thyroiditis, 298
S IADH caused by, 301 as therapeutic antibody, 210
Del tavirus, 158 Dermacentor tick, 139
toxicities, 375 Dactinomyc in , 370, 372
Deltoid muscle Dermal edema
transitional cell carcinoma Dactyl i tis
axil l a ry nerve damage and, 382 diseases causing, 566
and, 494 i n psoriatic arthritis, 392
Deltoid paralysis, 381 Dermatitis, 396
for vascul itis, 276 sickle cell anemia as cause, 356
Delusional disorder, 463 pellagra as cause, 567
for Wegener's granul omatosis, 576 D-al a 0-ala
Delusions, 463 in septic arth ritis, 392
Cyclosporine, 209 vancomycin mechanism of, 179
in mood disorders, 464 Dermatitis h e rpetiformis, 398
for aplastic anemia, 355 Dalfopristin
in sch izoph renia, 463 eel iac sprue and, 326
as immunosuppressant, 208 mechanism of action, 176
Demeclocycline, 180, 306 Dennatologic macroscopic terms, 395
reactions to, 241 for VRE, 184
reactions to, 241 Dermatologic m i c roscopi c terms, 396
Cyclothymic disorder, 464 Danazol, 541 for S IA D H , 301 , 576 Derma tomes
Cyproheptadine for endometriosis, 528 Dementia, 443, 462 landmark, 431
for SSRI toxicity, 475 Dandy-Walker syndrome, 409 associations, common/ of upper l im bsll1ands, 380
Cystath ionine synthase, 1 09 Dantrol ene, 455 i mportant, 566, 578 Dermatomyositis/polymyositis, 205,
Cystic duct, 316 for mal ignant hyperthermia, 575 diagnostic findi ngs/labs, 573 394
gal lstone obstruction, 339 for neurol eptic mal ignant H IV-associated, 166 Dermatophytes. See also Ringworm;
Cystic fi brosis, 86, 90 syndrome ( N M S ) , 473 hydrocephalus as cause, 426 Tinea
aspergillosis i n , 145 Dapsone pellagra as cause, 567 antimicrobials for, 1 86
cell atrophy in, 214 for Pnewnocystis iirovecii, 146 Vitamin B 1 2 defici ency as Dermoid cysts, 530
diagnostic findings/labs, 570 for leprosy, 133 cause, 354 Descending colorectal cancer, 332
expectorants for, 563 for mycobacteria, 183 i n Wilson's disease, 337 Descent of testes and ovaries, 514
gal lstones and, 339 reactions to, 240 Demye l i nating and dysmyeli nating Desensitization therapy for
mecon ium ileus and, 331 Dark-field microscopy, 137 diseases, 445 phobias, 466
pancreatic insufficiency caused Darunavir, 1 89 associations, common/ Desipramine, 474, 475
by, 326 Daunorubicin, 372 important, 578 Desloratadine, 562
pneumonia i n , 175 DCC gene, 221 central pontine myel inolysis as, 419 Desm i n , 76
Pseudomonas aeruginosa i n , 121 , D cells, 319, 321 Denate nuclei, 415 Desmoglein
135, 168 D-dimers, 572 Dendrites, 41 1 autoantibodies targeting, 205
treatment for, 574 Death , bacterial, 125 Dendritic cells, 193, 346 Desmolase, 291
Cystic hygroma, 278 Debranching enzyme (a- I ,6- in T- and B-cell activation, 196 Desmoplasia, 219
Cystine gl ucosidase) , 1 1 1 Dengue, 1 58 Desmopress i n , 306
i n kidney stones, 493 Debranching enzyme ( l l l ) , 1 1 1 Denial , 458 for diabetes insipidus, 301 , 574
Cystinuria, 109 Decay-accelerating factor ( OAF), 199, De novo pyri midine and purine for von W i l lebrand's disease, 360
Cystitis 200 synthesis, 65, 97 Desmosomes, 378
medications for, 234 Decidua basal is, 508 " Dense core bodies" in carcinoid antibodies aga inst, 398
Cytarabine, 371 Decision-making capacity, 57 tumors, 333 "Desync h ronized sleep," 61
..
I
INDEX 655
Detemir insul i n , 305 Diagnostic tests excretion of, 483 associations, common/
Detoxification classic findi ngs, 570-573 magnesium for, 284 i m portant, 578
benzodiazepines for, 453 eth ical issues i n , 58 metoclopramide and, 342 blood transfusions for, 360
Developmental disorders, 461 eval uation of, 51 -53 name suffix, 243 diagnosis for, 566
Developmental m i l estones, 59 D iapedesis, 215 therapeutic i ndex (Tl ) val ue, 229 diffuse cortical necrosis caused
Dexamethasone, 306 Diaphragm toxicity, 284 by, 495
Dexamethasone test hernias of, 318 Digoxin I mmune Fab in microangiopath i c anemia, 357
cortisol effects, 296 referred pa i n for, 431 as therapeutic antibody, 210 posJa rtu m , 553
Dexrazoxane structures of, 545 Dihydropteroate synthase, 181 sch istocytes in, 350
doxorubicin and, 372 Diarrhea D i hydropyridine receptor D i ssociation, 458
Dextrins i n i rr i table bowel syndrome in muscle contraction, 385 D i ssociative amnesia, 461
carbohydrate digestion and, 322 ( I B S ) , 329 D i h ydrotestosterone ( DI - I T) , 291 , 519 D i ssociative disorders, 464
magnesium hydroxide as cause, 341 i n genital development, 513 D i ssociative fugue, 464
Dextroamphetamine
i n malabsorption syndromes, 326 Dilated cardiomyopathy, 272 D issociative identity disorder, 458, 464
as CNS stimulant, 472
microorganisms causing, 168 causes of, 1 50 D i stal convol u ted tubules, 499
Dextromethorphan, 449, 564
osmotic, 326 wet beriberi as cause, 567 devel opment of, 478
DI-IF reductase, 371
pellagra as cause, 567 Dilation of pup i l , 440 D istal renal tubular acidosis
DHT. See Dihydrotestosterone
traveler's, 341 D i lator pupillae muscle, 437, 438 ( RT'A) , 488
( DHT)
D i astole, 253 D i l tiazem, 279 . See also Calcium Distal renal tubules, 479
D iabetes insipidus, 301
D iastol i c murmur channel bl ockers Distant vision, 438
AD I -l for, 306
aortic regurgitation as cause, 566 as antiarrhythm i c , 284 Disul fi ram (An tabuse ) , 95
as drug reaction, 241 conditions associated with , 258
l ithium as cause, 474 Dimenhydrinate, 562 for alcholism, 472
Diastol ic pressure Dimercaprol Disul fi ram-l ike reacti ons, 241
treatment for, 574 normal, 264 as antidote, 239 metronidazole and, 1 82
Diabetes mel l i tus, 302 D iazepa m , 453 for lead poisoning, 353 D i uretics, 499-501
acanthosis nigricans and, 400 for Clostridium tetani, 574 Dipal mitoylphosphatidyl c h o l i n e , 544 electrolyte changes, 501
antihypertensive therapy for, 279 for epilepsy, 451
Diphenhydramine, 562 for glaucoma, 449
atherosclerosis i n , 268 for pregnancy-induced
Dipheno:---yl ate, 449 for hypertension, 279
autoantibodies associated with, 205 hypertension, 526
D i phtheria magnesium levels and, 293
-blockers and, 238 receptor bi ndi ng, 229
Corynebacterium difJhtheriae s i te of acti on, 499
cataracts and, 439 Dicloxac i l l i n , 177
causing, 130 tubulointerstitial nephritis caused
chronic pancreatitis as cause, 340 for staphylococcus aureus, 576
D i phtheria toxi n , 1 24 by, 495
drugs for, 305 Dicrotic notc h , 256
in lysogenic phage, 126 Diverticula, 329
facial nerve palsy i n , 437 D i danosine (dd l ) , 189
Diphyllobothrium latum , 93, 1 52 associations, common/
glucosuria in, 482 D i encephalon, 408
vitamin B 1 2 deficiency and, 354 i mportant, 580
hemochromatosis and, 337 D i ethylcarbamazine, 186
Diplopia as esophageal cancer risk
I I LA subtypes associated with , 194 for nematodes, 151
diseases causing, 566 factor, 325
Mucor and Rhizopus i n , 145 Di ethylstilbestrol ( DE S ) , 539, 577
Dipyridamole, 369 i n pharynx, 578
oculomotor nerve, effect on, 441 as teratogen, 506
D i rect agonists, 233 D iverticular disease, 329
osmotic damage i n , 105 vaginal carcinomas and, 532
D i rect b i l i ru b i n , 323 D i verticul itis, 329
osteomye l i tis caused by, 169 Differentiating headaches, 446
D i rect cholinomimetics D iverticulosis, 329
in pregnancy, 267, 409, 506, 555 D i ffuse corti cal necrosis, 495
D i ffuse fat necrosis for gl aucoma, 449 D i zygotic twins, 507
Pseudomonas aewginosa in, 121
acute pancreati tis as cause, 339 D i rect Coombs' test, 357 Dizziness
i n renal fa i l u re, 497 D i rect hernias, 317, 318
D i ffuse glomerular disorders, 489 vertigo, 446
renal papillary necrosis and, 496 D i rect pathway DNA (deoxyri bonucleic acid)
retinal detachment and, 441 D i ffuse goiter, 299
D i ffuse large B-cel l lymphoma, 362 of basal gangl i a , 416 bacteria l , 126
sexual dysfunction and, 60 Disaccharides blotting procedures, 80
Diabetes mel l itus type I D i ffuse prol i ferative
glomeruloneph ritis carbohydrate digestion and, 322 c h romatin structure of, 64
diabetes ketoacidosis i n , 303 deficiency of, 326 free radical i n j u ry, 215
i n l u pus, 393
H LA-D R 3 and, 578 Discoid rash h i stoncs and, 64
D i ffuse prol i ferative
symptoms of, 303 in l upus, 393 i n trons, 71
glomerulonephritis
treatment for, 574 Disease prevalence, 50 mutations i n , 67
( DPGN), 492
treatments for, 305 Disease prevention, 55 repai r of, 69
D i ffuse scleroderma, 395
vs. type 2, 303 Disk herniation, 427 rep! ication of, 68
D i ffuse stomach cancer, 327
Diabetes mel l i tus type 2 Disopyramide sequence ampl i fication, 79
Diffuse systemic scleroderma
symptoms of, 303 as antiarrhyth mic, 283 syn thesis d i rection, 69
diagnostic findings/labs, 570
treatment for, 574 D i ffusion l i mitation D isorganized sch izoph renia, 463 synthesis i n h ibition, 66
treatments for, 305 hypoxemia caused by, 550 D isorganized speech , 463 syn thesis of, 92
Diabetic glomeruloneph ropathy, 489, D i ffusion l i m i ted circulation, 549 in schizophrenia, 463 DNA gyrase, 68
491 DiGeorge syndrome. See Thymic Disorientation, 461 bacterial resi stance
Diabetic ketoacidosis, 303 aplasia ( D iGeorge syndrome) D isplacement, 458 mechanism, 1 82
clin ical presentation, 567 D igestive tract anatomy/h i stology, 31 1 Dissecting aneurysms D NA l igase, 68
treatment for, 574 Digital is associations, common/ DNA methylation, 64
Diabetic nephropathy antidote to, 239 important, 576 DNA polymerases, 68
diagnostic signs/labs, 572 effect on stroke vol ume, 254 Disseminated i ntravascular DNA repai r, 69
Diabetic renal disease gynecomastia caused by, 535 coagulation ( D I C ) , 360 in 1-J N PCC/Lynch syndrome, 332
ACE inhibitors for, 502 hyperkalemia caused by, 487 abruptio placentae and, 526 DNA repl ication, 68
Diabetic retinopathy, 302 reactions to, 240 in acute myelogenous DNNRNA/prote i n synthesis
Diagnostic associations, 576-580 Digox i n , 282 leukemia, 365 direction, 69
Diagnostic presentations, 566-570 antidote for, 210 acute pancreatitis as cause, 339 DNA topoisomerases, 68, 182
INDEX
DNA viruses, 153, 155 Drainage of lymph nodes, 192 Dynein, 76 Ectopi c pregnancy, 527
characteristics of, 154 Drawer sign" Dysarthria, 420 Chlamydia trachomatis as
repl ication, 154 ACL i n j ury as cause, 569 i n Friedreich's ataxia, 430 cause, 141
Dobutamine D ressl er's syndrome, 270, 271 in Wi lson's disease, 337 meth otrexate for, 371
clinical use, 235 c l i n ical presentation, 566 Dysen te ry Eczema, 397
Dog bite, infected, 567 Dronabinol , 471 . See also Marij uana Escherichia coli causi ng, 135 H yper-lgE syndrome as cause, 569
Dolor (pa i n ) , 214 " D rop metastases," 448 toxins causing, 124 as hypersensitivity disorder, 204
Dominant hemisphere, 418 " Drop" seizures, 445 Dysgerm inomas, 531 scales i n , 395
Dominant negative mutation, 82 Drug addiction Dyskinesia Edema, 265
Donepezi l , 233, 456 m inors' right to treatment, 56 L-dopa as cause, 456 cerebra l , 421
Dopa decarboxylase, 108 Drug allergies. See Al lergic reactions i n Wilson's disease, 337 diseases causing, 566
Dopamine, 289 Drug eli mination, 228-229 Dysl ipidemia nephrotic syndrome as cause, 490,
changes with diseases, 461 Drug-induced i n terstitial metoprolol as cause, 284 567
clinical use, 235 nephritis, 495 renal fai l u re as cause, 497 treatment of, 500
CNS stimulants and, 472 Drug-induced l upus Dysmenorrhea wet beriberi as cause, 567
direct and indirect movement antibodies associated with, 205 endometriosis as cause, 528 Edema factor, 1 24
pathways, 416 Drug intoxication and Dyspareunia, 60 Edinger-Westphal nuclei
MAO i n h i b i tors effect on, 475 withdrawa l , 470-471 endometriosis as cause, 528 in pupillary reAex, 440
as neurotransmi tter, 413 Drug metabolism, 228 Dysphagia Edrophonium, 233
prolactin and, 290 Drug names, 243 central pon tine myel inolysis as as antidote for neuromuscular
receptors for, 231 Drug overdose cause, 419 blocking d rugs, 455
in sch izophrenia, 463 mannitol for, 500 esophageal cancer as cause, 325 E DTA
Dopamine agonists Drug reactions, 240-241 Plummer-Vinson syndrome as for lead poisoning, 353
for pituitary adenoma, 301 Drugs. See also specific drugs cause, 324, 567 Educational Commission for
for Parkinson's disease, 455 efficacy vs. potency, 229 Zenker's diverticulum as cause, 329 Foreign Medical Graduates
Dopamine -hydoxylase, 108 suffixes, 243 Dysplasia, 218, 219 ( E C FM C ) , 23, 26, 26-27,
Dopamine receptors therapeutic index, 229 cervical , 528 33, 35
anti psychotics and, 473 Drusen in macular degeneration, 441 Dysplastic nevus Edwards' syndrome
in basal gangl ia, 416 D ry beriberi , 90 neoplasms associated with, 220 c l i nical presentation, 568
rol e in nervous system , 230 Dry eyes Dyspnea Edwards' syndrome, 88
Dorsal column S jogren 's syndrome as cause, 567 C E R D and, 324 EECs
nerve degeneration in, 571 Dry gangrene, 212 "pink puffer'' and, 568 delirium and, 462
Dorsal i n terosseous muscles, 383 Dry macular degeneration, 441 Dysthymia, 464, 465 E F-Z (elongation factor), 124, 130
Dorsal motor nucleus, 435 Dry mouth Dystonia, 417 Pseudomonas exotoxin A, 135
Dorsal optic radiation, 441 S jogren's syndrome as cause, 567 Dystroph i n gene (DMD), 86 Efavi renz, 1 89
Dorsal pancreatic bud, 309 D-transposition of great vessels, 266 Effective close, 229
Dorsal root gangl ion, 428 D 2 receptor antagonist, 342 E Effective refractory period ( E RP), 260
Dorsal spinal column, 41 5, 427, 428 Dubin-J ohnson syndrome, 336, 577 Early fetal development, 504 Effective renal plasma Row
Dorsolateral nucleus, 415 Duchenne's muscular dystrophy Early-onset psychological ( E RPF), 480
Dosage calculations, 227 c l i nical presentation, 566 disorders, 460 equation for, 582
Doubl e-blinded studies, 50 Duchenne's muscular dystrophy, 86 Early proximal tubules, 483 Effector functions, of regulatory T
"Double bubble" bone Ductal carci noma in situ Eastern equ ine encephalitis, 1 58 cells, 197
appearance, 389 ( D C l S ) , 533, 534 Eating disorders, 469 Efferent arteri oles, 479, 481
"Double bubble" stomach Ductus arteriosus, 252 anovulation i n , 529 constriction in, 481
distention, 331 development of, 509 Eaton's agar, 120, 142 i n diabetic
Double strand DNA repair, 69 Ductus deferens Ebola hemorrhagic fever, 158 glomeruloneph ropathy, 491
Double Y males, 524 development of, 512 Ebstein's anomaly, 474, 506 Efferent lymphatics, 192
"Down and out" gaze, 439, 441 Ductus venosus, 252 Eburnation of bone Efficacy (pharmacodynamics)
Down syndrome, 88 Duloxeti ne, 475 diagnostic findings/labs, 573 change with i nh ibitors, 226
Alzheimer's disease and, 443 Duodenal atresia, 308, 331 i n osteoarth ritis, 390 vs. potency, 229
cardiac defects associated with, 267 Duodenal l umen Eccentric hypertrophy, 272 "Eggshe l l " calcifi cation of h i l a r
cli nical presentation, 569 pancreatic amylase i n , 322 Eccri ne glands, 378 l y m p h nodes, 555
diagnostic findi ngs/labs, 570 Duodenal submucosa ECF. See Extracellular A u i d Ego defenses, 458-459
duodenal atresia and, 331 Brunner's glands in, 321 E C C . See Electrocardiogram (ECC) E I I EC (enterohaemorrhagic
H i rschsprung's disease and, 330 Duodenal ulcers, 327 Ech inococcus granulosus, 1 52 Escherich ia coli ), 135
mental retardation and, 579 compl ications of, 328 Echoth iophate toxi n of, 124
neoplasms associated with, 220 Helicobacter pylori as cause, 137 for glaucoma, 449 E h l e rs-Danlos syndrome, 77, 78
Doxazosi n , 237 Duodenum , 309, 316, 321 Echovirus, 158 berry aneurysms and, 423
Doxepi n , 475 basal electric rhythm , 31 1 Eclampsia, 526 c l i nical presentation , 567
Doxorubicin, 370, 372 blood supply to, 312 drugs for seiwre prevention, 451 subarach noid hemorrhage and, 424
cardiomyopathy caused by, 272 diverticula, 329 ECL cells, 321 Ehrlichia, 140
reactions to, 240 h istology, 31 1 Ectocervix Ehrlich ia clwffeensis, 139
toxicities, 375 hormones produced by, 319 h istology, 515 Ehrlichiosis, 139, 1 40
Doxrcycl i ne, 180 tumors of, 304 Ectoderm, 505 E IEC (enteroinvasive Escherichia
for chlamydiae, 141 vitamin/mineral absorption, 322 Ectopic acid coli), 135
for Chlamydia trachomatis, 574 Durable power of attorney, 57 Meckel 's diverticulum and, 330 Eisenmenger's syndrome, 250, 266,
for Lyme disease, 137 Dural venous si nuses, 425 Ectopic ACT H , 296 579
for Neisseria, 134 Dura maler, 436 Ectopic A D H E j aculation, 516
for Hickettsia rickettsii, 576 Dwarfism, 85 S lADI I caused by, 301 sperm pathway, 515
DPC4 gene, 221 achondroplasia as cause, 387 Ectopic erythropoietin E j aculatory ducts, 516
Dracunculus medinensis, 151 D-xylose absorption test, 322 polycythemia and, 366 development of, 512
INDEX
Ejection click E ncapsulated bacteria, 1 1 8, 121 Endotoxins, 123, 125 Eosinoph i l i c granuloma
associations, common/ polypeptide, 131 effect on macrophages, 201 as restrictive l un g disease, 555
i m portant, 578 removal by spleen, 193 LPS, i n E. coli, 135 Eosinoph i l i c nodular
Ejection fraction ( E F), 254 Encephalitis End-stage renal disease for Medi care glomerulosclerosis, 491
equation for, 582 associations, common/ quali fication, 56 Eosinoph ils, 345
Elastase, 79, 322 important, 581 E n A urane, 453 in acute i n A a m mation, 214
Elastic skin Cal ifornia, 1 58 reactions to, 241 in bullous pemph igoid , 398
Ehlers-Danlos syndrome as Eastern and Western equ ine, 1 58 Enhancer cortisol effect on, 292
cause, 567 h e rpesvirus as cause, 155 in gene expression, 70 growth and differentiation
Elastin, 79 H SV- 1 as cause, 156 Enoxacin, 1 82 of, 200
Elderly, changes in, 60 Lassa fever, 158 Entacapone, 455 E PEC (enteropathogenic
Electrocardiogram ( ECC ) , 256, 261 St. Louis, 1 58 Entamoeba Escherichia coli) , 135
angi na diagnosis, 269 of temporal lobe, 155 antimicrobials for, 182 Ependymal cells, 41 1
myocardial infarction viral causes, 155 E n tamoeba h istolytica, 147 Ependymomas, 448
diagnosis, 269, 271 Encephal opathy diarrhea caused by, 168 Ephedrine
potassium imbalance on, 487 lead poisoning as cause, 353 E n teric bacteria, 1 19 c 1 inica I use, 235
torsades de poi ntes, 261 i n renal fai l ur e , 497 lactose-fermenting, 1 20 Ephelis, 397
tracings, 262-263 Endocardial fibroelastosis Enteric nervous system, 231 Epidemiol ogy/b i ostatistics
Electroconvulsive therapy ( ECT), 466 cardiomyopathy caused by, 272 E nterobacter, 1 19, 134 cancer, 224
Electroencephalogram ( E E C ) Endocarditis, 274 Cram stai ning, 133 prevalence vs. i n cidence, 52
waveforms i n sleep stages, 61 acute bacterial, 1 28 En terobacter aerogenes statistical distribution, 54
Electrolyte disturbances, 487 cl i nical presentation, 568, 569 antimicrobials for, 178 Epi dermal appendages, 378
Electronic Residency Application h eroi n addiction and, 471 En terobacter cloacae Epi dermal hyperplasia, 396
Service ( E RAS) , 26, 33 ischemic stroke and, 425 urinary tract i n fections caused verrucae and, 397
Electron transport chain and oxidative prophylaxis for, 1 84 by, 170 Epidermis l ayers, 378
phosphorylation, 102 subacute, 1 29 Enterobius, 1 52 Epidemwphyto n , 1 44
Electron transport i n h i b i tors, 102 subacute bacterial, 128 Enterobius vennicu laris, 151 , 578 Epididymis
Electrophoresis, 79 Endocervix Enterococci, 129 development of, 512
Electroytes antimicrobials for, 177
h istol ogy, 515 Epidural hematomas, 424
diuretic effects on, 501
Endochondral ossification, 386, 387 growth in bile, 127 associations, common/
Elek's test, 130
Endocrine hormone signal ing treatment for, 575 i m portant, 578
Elephantiasis
pathways, 294 vancomycin for, 179 c l i nical presentation, 568
Wuchereria bancrofti as cause, 151
Endocrine pancreas cell types, 287 vancomyci n-resistant (VR E ) , 1 29, Epigastr i c veins, 314
1 1 -hydroxylase deficiency, 291
Endocrine system 1 84 Epigl ottis
1 1 -deoxycorticosterone, 291
anatomy, 286-289 Enterocytes, 322 "cherry red" fi n ding, 174
1 1 -deoxycortisol , 291
antipsychotic effects on, 473 Enterohemorrhagic Escherichia coli innervation of, 434
Elimination
drug reactions i n , 240 ( E H EC ) Epigl ottitis
(pharmacodynamics), 228
embryology, 286 toxin of, 124 diagnostic findings/labs, 573
clearance and, 227
kidney functions, 486 Enterohepatic circulation, 323 1-laemophilus inf/.uenz.ae as
constant for, 227
pathology, 296-304 Enteroki nase, 322 cause, 134
urine pH and, 228
pharmacol ogy, 305-306 Enteropeptidase, 322 i n u n i m mu nized c h ildren, 174
E LI SA test, 164
physiology, 289-295 Enterotoxigeni c Escherich i a col i Epilepsy, 445
E l l i ptocytes, 350
Endoderm, 505 ( ETEC), 1 24 drugs for, 451
El ongation
development of, 504 Enterotoxins, 130 drug toxicities, 452
in protein synthesis, 73
Endodermal sinus tumor, 531 Enteroviral encepha l i ti s Epinephrine
Emancipated mi nors, 56
E M B (eosi n-methylene blue) Endogenous pyrogens as i m munodeficiency a-bl ockade effects, 237
agar, 120 cytokines as, 200 infection, 205 c l i n i cal use, 235
Embol i form nucl ei, 415 Endometrial cancer, 529, 578 En terovi ruses closed-angle glaucoma and, 439
Embryogenesis progestins for, 540 meningitis caused by, 169 for glaucoma, 449
genes of importance, 504 tamoxifen and risk of, 374 Envelopes, vira l , 1 54 glycogen regulation, 1 10
Embryologic derivatives, 505 Endometrial hyperplasia, 529 env gene, 1 64 Epinephrine receptors
Embryology Endometrial prol iferation, 529 Envi ron mental i n A uence, 50 nervous system rol e , 230
cardiovascular, 250-252 Endometrioid cysts, 530 Enzyme i n h i bition, 226 Epineurium, 412
endocri nal, 286 Endometriosis, 528 Enzyme ki netics, 226 Epiploic foramen of Winslow, 310
gastrointestinal, 308 danazol for, 541 Enzyme-l inked i mmunosorbent assay Epispadias, 513
genital, 512 diagnostic findings/labs, 570 ( E L I SA) , 51 , 80 Epithelial casts
neurological, 408-410 Endometritis, 528 Enzymes i n renal fa il ure, 496
renal , 478 Endometri um i n gluconeogenesis, 1 02 Epithelial cells
reproduct ive, 504-512 progestin effect on, 540 glycolysis regulation, 100 j unctions of, 378
Embryonal carcinoma, 536 Endoneuri u m , 412 in l ipid transport, 1 1 5 in wound h eal i ng, 216
Emissions, 516 Endoperoxides, 404 oxidative/nonoxidative, 103 Epithel ial granulomas
Emotion Endoplasmic re ticulum ( E R ) , 75 terminology for, 96 sarcoi dosis and, 393
l i mbic system and, 415 Endoscopy zinc and, 95 Epithelial hyperplasia, 535
Emphysema, 79, 554 m i dazolam for, 454 eosi n-methyl ene blue ( E M B ) Epithel ial tumors, 219
panacinar, 335 Endosomes, 75 agar, 120 Epith e l i od macrophages, 214
pulmonary circulation in, 549 Endospores, 143 Eosinoph i l i a , 345 Eplerenone, 501
pulmonary compl iance i n , 547 Endoth elial cells Eosinoph i l i c casts Epoprostenol
Empty sella syndrome, 301 i n wound healing, 216 in pyel oneph ritis, 495 for pulmonary arterial
Emtricitabine ( FTC ) , 189 Endoth e l i u m Eosinoph i l i c A u i d hypertension, 575
Enalapril , 502 damage/shock t o , 1 3 5 disarrayed granul osa cells i u , 571 Epoxide reductase, 348
INDEX
Epstei n-Barr virus ( E BV), 155, 1 56, E rythropoiesis, fetal, 251 Ester anesthetics, 454 Exercise
157 E ryth ropoieti n, 210 Estradiol , 291 pulmonary response to, 552
antimicrobials for, 1 87 in anti retroviral therapy, 189 secretion of, 538 Exocytosis, 78
Burkitt's lymphoma and, 362 as paraneoplastic effect, 223 Estriol Exogenous steroids
hairy leukoplakia and, 402 hemangioblastoma production secretion of, 538 Cushi ng's disease caused by, 296
H odgkin's lymphoma and, 361 of, 448 Estrogen, 291 , 520, 539 diagnosing, 524
as immunodeficiency infection, 205 in kidney disease, 355 in bones, 386 Exons, 71
oncogenicity of, 222 kidney functions, 486 disorders of, 525 Exoptha I rnos, 299
receptor for, 201 para neoplastic syndrome and, 494 endometrial prol iferation and, 529 Exostosis, 389
Equations, rapid review, 581 -582 polycythemia and, 366, 566 gal lstones and, 339 Exotoxin A, 1 24, 125
Erb-Duchenne palsy, 381 , 382 Escherichia coli, 1 19, 121 , 134, 135 i n gen i tal development, 513 Exotoxins, 123
clinical presentation , 568 antimicrobials for, 177, 178 gynecomastia caused by, 535 bugs with, 124-125
ERC P c h ronic granulomatous disease in men opause, 523 Expectorants, 563
acute pancreatitis caused by, 339 and, 207 in menstrual cycle, 521 Expiration
in primary sclerosing chronic granulomatous disease i n oral contraceptives, 540 h eart sounds and, 258
cholangitis, 338 caused by, 579 for osteoporosis, 387 muscles contro l l i ng, 546
Erectile dysfunction , 60, 541 culturing, 120 during ovulation, 521 Expi ratory reserve volume ( E RV) , 546
drug name suffixes, 243 diarrhea caused by, 1 68 prolactin and, 290 Exponential/log phase of bacterial
treatment for, 575 food poisoning caused by, 167 reactions to, 240 growth, 125
Erections, 516 Gram staini ng, 133 secretion of, 538 External otitis. See also Otitis media
priapism, 537 LPS endotoxin, 135 signaling pathway, 294 Pseudomonas aeruginosa
Ergocalciferol , 94 meningitis caused by, 1 69 tamoxifen/raloxifene effect on, 374 causing, 135
Ergot-derived dopamine agents, 455 as nosocomial i n fection, 174 in Tu rner syndrome, 524 Extinction (operant
"Erlenmeyer flask" bones 0 1 5 7 : 1- 1 7 , 135, 1 67 Estrogen replacement therapy condi tioning), 458
in osteopetrosis, 387 pneumonia caused by, 168, 579 ( E RT), 540 Extracellular A u i d , 480
Erosions prostatitis caused by, 535 Estrone, 291 Extraocular muscles
gastrointesti nal, 31 1 toxins of, 124 secretion of, 538 cranial nerves and, 439
Erosive gastritis, 327 urinary tract infections caused Eszopiclone, 453 testing, 440
ERPF. See Effective renal plasma by, 170, 581 Etanercept, 406 Extra peritoneal tissue, 317
Aow ( E RPF) E-sel ecti n ETEC (enterotoxigenic Escherich ia Extrapyramidal system
Error types, 53, 54 in l eukocyte extravasation, 215 coli), 1 24, 135 antipsychotic effects on, 473
E rythema chronicum m igrans, 137 Esmolol, 238 Ethacrynic acid, 500 Extravascular h emolysis, 204, 354
cli nical presentation, 568 as antiarrhyth mic, 284 Ethambutol, 183 Extri nsic coagulation pathway, 348
Erythema infectiosum Esophageal atresia, 308 for Mycobacteriu m tubercu losis, 575 Extri nsic hemolytic normocytic
clinical presentation. 172, 566 Esophageal cancer, 325 for tuberculosis, 183 anemia, 357
parvovirus as cause, 155 achalasia and, 324 Ethanol Extri nsic pathway
Erythema marginatum, 129 associations, common/ acute pancreatitis caused by, 339 for apoptosis, 212
in rheumatic fever, 274 important, 578 elimi nation of, 228 warfarin and, 368
Erythema multifonne, 399 Barrett's esophagus and, 325 hypoglycemia of, 95 warfarin effects, 367
Erythema nodosum, 400 esophageal adenocarcinoma, 220 metabolism of, 95 Exudate pleural effusions, 561
C rohn 's disease and, 328 squamous cell carci noma, 220 Ethics, 56-58 Exudate vs. transudate, 216
sarcoidosis and, 393 Esophageal dysmoti l i ty Eth inyl estradiol , 539 Eye
Erythematous l esions in scl eroderma, 395 Ethosuximide anatomy of, 437
as J a neway lesions, 568 Esophageal pathol ogies, 324 for absence seizures, 574 galactosemia, 105
Erythopoietin Esophageal reAux for epilepsy, 451 muscles, 439
h igh altitude effects on, 552 1-1 7 blockers for, 341 reactions to, 241 path ology, 438-439
Eryth roblastosis fetal is, 347 pr ton pump i n h i b i tors for, 341 toxiciti es, 452 Eyelids
as hypersensi tivity disorder, 204 Esophageal strictures, 324 Ethylene glycol i n nervation of, 434
Erythrocytes, 344 Esophageal ulcers antidote to, 239, 575 xanthomas i n , 267
basophlic nuclear remnants i n , 570 Barrett's esophagus and, 325 kidney stones caused by, 493 Ezetimibe, 281
in chronic myelopro li ferative Esophageal vari ces, 324 Etoposide, 370, 373
disorders, 366 portal hypertension as cause, 333 Euch romati n, 64 F
eryth rocyte sedimentation rate, 217 Esophageal veins, 314 Eukaryotes Fab fraction of antibodies, 197
gl ucose and, 288 Esophageal web DNA repl ication i n , 68 Fabry's disease, 1 12
i n hereditary spherocytosis, 356 as esophageal cancer risk m RNA start codons, 70 Facial drooping
pathologic forms, 104, 350-351 factor, 325 RNA polymerases i n , 70 B e l l 's palsy as cause, 570
Rouleaux formation, 363 in Plummer-Vinson syndrome, 352 RNA processing i n , 71 Facial lesions, 437
spherocytosis, 85 Esophagitis, 324 tRNA, 72 Facial nerve, 434
in urinary casts, 489, 492 Barrett's esophagus and, 325 Euthanasia, 58 derivation of, 510
E rythrocyte sedimentation rate bisph osphonates as cause, 405 Eval uation of diagnostic tests, 51 palsy of, 437
( E S R) , 217, 349 Esophagus, 309 Evol ution of M l , 270 tongue innervation by, 410
Erythrocytosis, 344 anastomosis in, 314 Ewing's scncon1a, 389 Facial nerve palsy
Eryth roderma diaph ragm perforation by, 545 dactinomycin for, 372 in Lyme disease, 137
Sezary syndrome as cause, 567 diverticula, 329 diagnostic findings/labs, 573 Facial nucleus, 437
Erythrogenic toxin of Streptococcus h istology, 31 1 Exanthem subitu m . See Roseola damage to, i n AlCA stroke, 422
pyogenes E S R . See E rythrocyte sedimentation Excitatory pathway of basal Facia I spasms
in lysogenic phage, 1 26 rate ( E S R) gangl ia, 416 hypocalcemia as cause, 567
Erythromycin, 179, 1 80 Essential amino acids, 106 Excreti on rate ( renal ) Factitious disorders, 467
for Legionella fmeumophila , 135, Essential fructosuria, 104 calculation of, 481 Factor V Leiden mutation, 348, 360
575 Essential thrombocytosis, 366 Exemestane, 540 Factor Xa
reactions to, 240 Essential tremor, 417 Exenatide, 305 h eparin and, 367
"" " I
INDEX 659
Facultative in tracellular Feces Fibrinogen, 348 5-I IT 2A an tagonists

organisms, 121 stercob i l i n in, 323 clopidogrel/ticlopidine effect for sch izophrenia , 576
Fail ure to thrive Federation of State Medical Boards on, 368 5-HT1 antagonist, 342
hypothalamus and, 414 ( F S 1 B ) , 2, 23, 27, 32, 36 in D I C , 360 Fixation, 458
N i emann-Pick disease as Fed state, 1 14 in platelet plug formati on, 349 Flaccid paralysis
cause, 568 Feet receptor, 344 as motor neuron sign, 428
Falciform l igament, 252, 310 blue toes, 568 Fibrinoid necrosis, 212 i n pol i omyel i tis, 430
Fallopian tubes erythematous lesions on, 568 Fibrinolytic system , 348 spinal cord lesions as cause, 429
ectopic pregnancy in, 527 rash on soles, 569 Fibrinous pericarditis, 270, 271 Flagella , 1 18
h i stology, 515 swol len/pain ful big toe, 569 Fibroadenomas, 533, 577 Flank mass in newborns, 478
" False" diverticula, 329 Female genitals Fibroblast growth factor ( F G F ) Flank pain
False-negative ( FN ) and false-posi tive embryol ogy, 512 signaling pathway, 294 i n A D P K D , 498
( F P ) , 51 , 54 male homologues, 513 Fibroblast growth factor receptor Flask-shaped ulcers, 147
Falx cerebri, 448 Female pseudohermaph rodites, 524 (FGFR3) Flat facies, 88
Famciclovir, 1 87 Female reproductive anatomy/ achondroplasia and, 387 Flavivi ruses, 1 58
Famil ial adenomatous polyposis, 85, h i stology, 515 Fibrobl asts, 78 Flecainide
221 , 332 Femoral artery, 316, 318 cortisol effect on, 292 as antiarrhyth mic, 283
Familial dysl ipidemias, 1 16 Femoral h e rnias, 318 i n in flammation, 216 " Flesh-eati ng bacteria," 402
Familial hyperchol esterolemia, 85, Femoral neck fractu res, 387 in male reproductive anatomy, 517 Fl exor digiti m i n i m i muscle, 383
116 Femoral nerve, 316, 384 in wound heal i ng, 216 Flexor pol l icis brevis muscle, 383
cli nical presentation, 566 Femoral region, 316 Fibrocystic change of the breast, 533 Fl oppy baby syndrome
Famotidine, 341 Femoral ring, 316 diagnostic signs/labs, 572 botul inum toxin causing, 124, 130
Fanconi's anemia, 355 Femoral sheath , 316 Fibrocystic disease, 535 Werdnig- H offman disease as
cli nical presentation, 569 Femoral triangle, 316 Fi bromas, 219, 532 cause, 430
Fanconi's syndrome Femoral vei n , 316, 318 Fibromyalgia, 394 Flora, normal, 167
clinical presentation, 569 tricyclic antidepressants for, 475
Femur, 379 Fl uconazole, 185
as drug reaction, 241 Fibrosarcomas, 219
l<'enestrated capi l lary for Cry(Jtococcus neofonnans, 574
diseases associated with, 220
Farmer's lung, 204 endoth e l i u m , 480 for Candida , 145
Fibrosis, breast, 535
Fasciculata, 291 , 292 Fenestrations Fl ucytosine, 185
Fibrosis, pulmonary, 549
Fasciculation i n bra i n vasculature, 413 Fluid distributi on , 480
Fibrous plaques in penis
in amyl otrophic lateral Fenofibrate, 281 Flukes. See Trematodes
Peyronie's disease as cause, 567
sclerosis, 429 Fenoldopa m , 279 F l umazeni l
Fibula, 379
LM damage as cause, 567 Fentanyl , 449 as antidote, 239
Fick principle, 253
as motor neuron sign, 428 as i n travenous anesthetic, 454 for benzodiazepine
Fifth disease. See E rythema
Fasciculus cuneatus, 427 Ferritin intoxication, 470
infectiosum
Fasciculus gracilis, 427 i n anemia, 357 for benzodiazepi n c overdose, 453
5 0 S i n h i b i tors, 179
]<ts l i gand ( C 09 5 ) hemochromatosis and, 337 receptor binding, 229
Filgrastim , 210
apoptosis and, 212 i n sideroblastic anemia, 353 Fluorescence i n situ hybridization
Filovi ruses, 158
Fastigial nuclei, 415 Ferrochelatase ( F I S H ) , 81
Filtered load ( ren a l )
Fasting and starvation, 1 14 in l ead poison ing, 353, 358 Fl uoroqui nolones, 68, 182
calculation of, 481
Fasting serum glucose test, 302 Fert i l i zation contraindicated during
F i l tration, 481
Fast hvitch muscle fibers, 385 l ocation and timing, 523 Fil tration fraction ( FF) pregnancy, 190
lt embol i , 553 oogenesis, 522 changes i n , 481 mechanism of action , 176
Fat necrosis, breast, 535 Fetal adrenal gland, 286 equation for, 582 reactions to, 241
Fat sol uble vitamins, 90 Fetal alcohol syndrome, 506, 507 Fimbriae/p i l i , 1 1 8 5-A uorouracil ( 5-FU), 65
Fat tumors, 219 Fetal cardiac defects Fi nasteride, 538, 539 Fluoxetine, 474, 475
I tty acids l ithium as cause, 474 for benign prostatic Fluphenazine, 473
metabolism, 1 13 Fetal circulation, 252 hyperplasia, 535, 574 Flutamide, 539
oxidation, 97 Fetal component of placental Fi ngers, swollen/11ard, 570 for prostate cancer, 575
synthesis, 97 development, 508 Fi rst-order drug e l i m i n ation, 228 Fluticasone, 563
I tty casts, 489 Fetal development, 504 Fish tapeworm FM R J gene, 87
in nephrotic syndrome, 490 Fetal erythropoiesis, 251 vitam i n B 1 2 deficiency and, 354 FNHTR. See Febril e non hemolytic
Fatty l iver Fetal h emoglobi n , 547 Fissures transfusion reaction
in Reye's syndrome, 334 Fetal hydantoi n syndrome, 506 in Croh n's disease, 328 Foam cells, 1 1 2
Fatty l iver disease phenytoin as cause, 452 Fistulas Foamy cells
alcohol as cause, 334 Fetal hypothyroidism, 298 in C roh n's disease, 328 i n hemangioblastomas, 448
diagnostic findings/labs, 573 Fetal-maternal microorganism diverticulosis and, 329 Focal glomerular disorders, 489
Fatty necrosis, 212 transmission. See To RCI I e S gallstones as cause, 339 Focal segmental
I:J'ava beans i n fections Fitz-H ugh-Curtis syndrome, 134, 173 glomerul osclerosis, 490, 579
G6PD deficiency caused by, 356 Fetal-postnatal derivatives, 252 Sa-reductase Folate, 93
F (bioavailabi l i ty). See B i oavailabi l i ty Fetor h epaticus deficiency in, 513, 525 absorption of, 322
of drugs l iver cell fa i l ur e as cause, 333 testosterone effects, 519 deficiency, in anemia
Fe fraction of antibodies, 197 Fexofenadi ne, 562 5-aminosal icyl ic acid, 342 algorit h m , 354
Fe receptors, 1 28, 346 F+ x F- plasmid con j ugation, 126 5-A uorourac i l , 370, 371 forebra i n anomal ies and, 409
Febri le non hemolytic transfusion FCF gene, 504 toxicities, 375 Folate antagonists
reaction, 204 Fibra tes, 281 vitamin B 1 2 deficiency and, 354 as tera togens, 506
Febuxostat, 406 for hypertriglyccridemia, 575 5-1-l !AA Fol ic acid, 92
for gout, 391 reactions to, 241 in carcinoid syndrome, 304 neural tube defects and, 409, 575
Fecalith obstruction Fibri l l i n gene mutation, 85 5-I I T Fol i e a deux, 463
appendicitis caused by, 329 Fibrin degradation products, 348 carci noid tumors produci ng, 333 Fol l icle of lymph node, 192
I ND E X
Fol l icle-stimulating hormone " Fried egg" cells, 412 GABA receptor Gastric hypertrophy
( F S l-1), 289 i n multiple myeloma, 363 as target of competitive in M enetrier's disease, 327
as menopause test, 523 in oligodendrogl iomas, 447 antagonist, 229 Gastric i n h i b i tory peptide ( G I P ) .
secretion of, 287 Friedreich's ataxia, 430 GABA receptor agonists See G l ucose-dependent
signal ing pathway, 294 hypertrophic cardiomyopathy for multiple sclerosis, 444 insul i notropic peptide
spermatogenesis and, 519 and, 272 gag gene, 1 64 Gastric lumen, 321
Fol l i cular cysts, 530 Fried rice syndrome, 131 Gag reA ex, 434 Gastric parietal cells, 321
Foll icular lymphoma, 362, 580 " Frogl ike appearance" in Galactito l , 105 Gastric ulcers . See U lcers
chromosomal translocation anencephaly, 409 Ga lactocerebrosidase, 1 12 Gastric vessels, 310
with, 365 Frontal association areas, 418 Krabbe's disease and, 445 Gastrin, 319
oncogene for, 221 Frontal eye fields, 418 Galactokinase deficiency, 105 gastric acid regulation, 320
Fol l icular phase of menstrual l esions i n , 419 cataracts and, 439 signal ing pathway, 294
cycle, 521 Frontal lobe, 418 Galactorrhea Gastrinoma, 320
Fol l i cular thyroid carcinoma, 299 AD l iD and, 460 anti psychotics as cause, 473 treatment for, 306
Fomepizole, 95 lesions in, 419 pituitary adenoma as cause, 301 Gastritis, 327
as antidote, 239 Frontotemporal dementia. See Pick's Galactose associations, common/
for methanol intoxication, 575 disease in carbohydrate digestion, 322 i m portant, 577
Food poisoning, 57 " Frosted glass" cytoplasm, 345 metabol ism of, 105 GOX-2 i n h i b i tors for, 405
associations, common/ Fructokinase, 104 Galactose- 1 -phosphate intrinsic factor and, 320
important, 578 Fructose uridyltransferase, 105 neoplasms associated with, 220
microorganisms causing, 167 in carbohydrate digestion, 322 Galactosemia proton pump i n h ibitors for, 341
Foot drop, 384 intolerance of, 104 cataracts and, 439 stomach cancer and, 327
lead poisoning as cause, 353 metabol ism of, 104 Galantamine, 456 Gastrocol ic l igamen t, 310
Fructose- ] ,6-bisphosphatase, 97, 102 Galant reA ex, 432 Gastroepiploic arteries, 310
Foot processes
Gallbladder, 316 anastomoses between, 313
effacement of, 490 Frui ty odor, 1 13
bl ood supply to, 312 Gastroesophageal j un ction
Foramen cecum, 286 F S l -1 . See Fol l icle-sti mulating
chol ecysti tis, 339 M a l l o ry-Weiss syndrome
Foramen magnum h ormone ( FS I-I )
hormones produced by, 319 l acerations, 324
as cranial nerve pathway, 435 I<'TA-AB S test, 138
referred pain for, 431 Gastroesophageal reA ux disease
herniation, i n G h iari 1 1 F2,6BP, 100
Gallbladder stasis ( G E R D ) , 324
malformation, 409 Fumarate, 108
gal lstones caused by, 339 Barrett's esophagus caused by, 325
Foramen of Magendie, 426 Functio l aesa ( l oss of function ) , 214
Gallstone il eus, 339 as esophageal cancer risk
Foramen ovale, 251 , 252 Functional residual capacity
Gallstones, 316, 338, 339 factor, 325
as cranial nerve pathway, 435 (FRC), 546
cli nical presentation, 567 Gastrohepatic l i gament, 310
Foramen rotundum l ung-c hest wal l system and, 547
fibrates and, 281 Gastroi n testinal bleeding
as cranial nerve pathway, 435 Fundus, 321
pancreatitis caused by, 339, 580 aspirin as cause, 404
Foramen spinosum Fungi
y-gl obi n , 352 Gastroi n testinal blood supply and
as cranial nerve pathway, 435 antimicrobials for, 145, 184- 185
Gamma-hydroxybutyric acid ( G l- I B ) i n n e rvation, 312
Foramina of Luschka, 426 culturing, 1 20
i n narcolepsy, 62 Gastroi n testinal disease
Foramina of M onro, 426 cutaneous mycoses, 144
y-interferon , 210 lead poisoning as cause, 358
Forced expiratory vol ume ( FEV) i m munodefici ency infections, 168,
macrophage activation, 345 Gastroin testinal hormones, 319
i n restrictive/obstructive l ung 205 Ganciclovir, 188 Gastrointestinal l igaments, 310
disease, 556 meningitis caused by, 185 for cytomegalovi rus, 574 Gastrointestinal polyps
Forced vital capacity ( FVC ) opportunistic infections, 145 Gangl ioneuromatosis, 304, 570 Peutz-)eghe rs syndrome as
in restrictive/obstructive lung stain for, 1 20 Gangrene, 212 cause, 567
disease, 556 systemic mycoses, 143 in diabetes mel l i tus, 302 Gastrointesti nal secretory cells, 321
Forebrai n , 408 "Funny current" channels, 260 Gap j unction of epithel ial cells, 378 Gastrointestinal secretory
anomal ies of, 409 Furosemide, 500 Gardener's mydriasis, 234 products, 320
Foregut reactions to, 241 Gardr1erella vagina/is, 1 19, 139, 173 GasiTOintestinal stromal tumors
blood supply, 312 as sulfa d rug, 242 antimicrobials for, 1 82 imatinib for, 374
development of, 308 Fusiform rods diagnostic findi ngs/labs, 573 oncogene for, 221
Formoterol, 563 in asbestosis, 555 Gardner's syndrome, 332 Gastroi ntestinal system
Formylmeth ionine, 70 flusobacterium cli nical presentation, 568 anatomy, 309-318
Fornix, 415 lung abscesses caused by, 560 Gargoyl ism, 1 12 col lateral circulation , 313
Fosamprenavir, 189 Gas gangrene. See Myonecrosis drug reactions, 240
Foscarnet, 188 (i embryology, 308
Gastric acids, 320
Fosphenytoi n G6PD deficiency, 181 neutra l i zation of, 319 pathology, 324-339
for epilepsy, 451 i n anemia algorithm , 356 secretion of, 319 pharmacology, 340-342
Fossa oval is, 252 bite cells in, 350 Gastric arteries physiology, 319-323
Fovea central is, 437 Heinz bodies in, 351 anastomoses between, 313 Gastrointesti nal therapy, 340
Fragil e X syndrome, 87 hemolysis in, 240 Gastric cancer, 327, 577 Gastroparesis
mental retardation and, 579 GABA associations, common/ metoclopramide for, 342
Frame shift DNA mutations, 67 in anxiety, 461 important, 580 treatment of, 342
Francisella, 1 19, 121 benzodiazepines and, 453 bombesin marker for, 222 Gastroschisis, 308
Francisella tularensis, 139 epilepsy drugs and, 451 carci nogens affecting, 223 Gastrosplenic l igamen t, 310
Freckles, 397 in l l untington's disease, 461 diagnostic signs/labs, 572 Gastrulation, 504
Free nerve endi ngs, 412 as neurotransmitter, 413 diseases associated with, 220 GatiA oxacin, 1 82
Free radical i n j ury, 213, 215 toxins affecting, 124 f-le/icobacter pylori i n , 222 Gaucher's cells, 1 12
Fresh frozen plasma Gabapentin oncogene for, 221 Gaucher's disease, 579
i n blood transfusion therapy, 360 for epil epsy, 451 Gastric glands, 31 1 c l i nical presentation , 567
for warfarin toxicity, 576 toxicities, 452 Gastric J J + secretion, 319 Gaucher's disease, 1 12
INDEX
Gaussian curves, 54 G i ngival hyperplasia G LP- 1 analogs Glycogen phosphorylase, 97, 1 1 1

G cells, 319, 321 as drug reaction, 241 for diabetes mell i tus, 305 Glycogen storage diseases, I l l
G-C S F/G M-C S F phenytoi n as cause, 452 Glucagon , 289 Glycogen synthase, 97
in anti retroviral therapy, 1 89 Gingivostomatitis as antidote, 239 Glycolysis, 97, 288
for aplastic anemia, 355 1-JSV- 1 as cause, 1 56 i n diabetes m e l l i tus, 302 key enzymes regulating, 100
Cemfibroz i l , 281 G I ST. See Gastroin testinal stromal glycogen regulation, 1 10 Glycoprote i n l l b/l l l a
as P-4 5 0 i n h i b i tor, 242 tumors production of, 287 a s therapeutic antibody target, 210
Cencier identity disorder, 469 Gland cells signal ing pathway, 294 Glycopyrrolate
Cene expression modifications, 81 innervation of, 230 somatostatin and, 319 c l i nical use, 234
Ceneral izab i l i ty, 53 Glandular metaplasia, 325 Glucagonomas Glycosides
Generalized anxiety disorder, 467 Glanzmann's th rombasthenia, 349, i n M E 1 , 304 cardiac, 282
buspirone for, 474 359 treatment For, 306 Glycosuria
treatment for, 574 c l i nical presentation, 568 Gl ucocerebrosidase deficiency i n diabetes mell i tus, 302
vcnlafaxine for, 475 Glargi ne insul i n , 305 clinical presentation, 567 Glycosylation ( E R) , 78
General ized seizures, 445 Glaucoma, 439 Glucocorticoids, 291 , 306 G M -C S F
Genes acetazolamide for, 500 for arthritis, 390 i n terleukin Functioning a s , 200
functional organization of, 70 atropi n e as cause, 234 reactions to, 241 Cn R l -1 . See Gonadotropin-releasing
regulation of expression, 70 -bl ockers for, 238 withdrawal from, 240 hormone (Gn R H )
Genetic code Featu res, 66 in diabetes m e l l i tus, 302 Glucokinase vs. hexoki nase, 99 Goblet cells, 74, 31 1
Genetics d rugs For, 449 Gl uconeogenesis, 97, 98, 289 in respi ratory conducting zone, 544
bacterial, 126 medications for, 233, 235 cortisol effect on, 292 Goiter
Genetic s hi ft in i n Auenza viru s , 1 60 Sturge-Weber syndrome as i rreversible enzymes, 102 creti nism and, 298
Genetic terms, 82-83 cause, 446 Gl ucoronic acid i n C raves' disease, 299
Geniculate bodies, 41 5 Gleevec. See l mati nib b i l i rubin and, 323 multinodular, 299
Genital embryology, 512 Gl iadin Gl ucoronidation, 228 Goi trogens, 298
Genital herpes, 1 56 autoantibodies targeting, 205 Gl ucose Cold poisoni n g
c l inical presentation, 173 blood-bra i n barrier transport, 413 a n tidote t o , 239
Gl iadin i n tolerance. See Celiac sprue
Genital homologues, 513 i n carbohydrate digestio n , 322 Golgi apparatus, 75
G l imepiride, 305
Genital lesions clearance of, 482
G l i oblastoma multi forme, 447 in plasma cells, 346
condylomata l ata as cause, 569 growth hormone and, 290
alkylating agents For, 372 Gonadal drainage, 514
diseases causi ng, 567 i nsul i n effect on, 288
diagnostic findi ngs/labs, 573 Gonadotropi n-releasing hormone
Genital tubercles for porphyria, 358
G l i osis, 41 1 ( C n R H ) , 289
derivations of, 513 uptake of, 288
in i rreversible neuronal i n j u ry, 425 For i n fertil i ty, 575
Genitourinary system Glucose-dependent i n su l i n otropic
G l ipizide, 305 i n Kal l mann syndro m e, 525
drug reactions i n , 241 peptide, 319
G l i tazones leuprol ide as analog for, 539
Gentamicin, 180 gastric acid regulation, 320
for diabetes mel l i tus, 305 prol actin i n h ibition of, 290
GERD. See Gastroesoph ageal reAux Glucose-6-phosphatase, 102, 1 1 1
Global aphasia, 420 signal ing pathway, 294
disease ( G E R D ) Glucose-6-phosphate, 103, 1 1 1
Globose nucle i , 415 Gonadotropins
Geriatric patients G lucose-6-phosphate dehydrogenase
Globus pal l i dus, 416 progesterone and, 520
drug metabol ism by, 228 ( G H P D) , 97, 103- 1 04
Glomeru l a r diseases, 489 theca-l utein cysts and, 530
Cerstma nn-Straussler-Schein ker Gl ucose tolerance test, 302
Glomerular dynamics, 481 Gonococcal arth ritis, 392
syndrome, 167 Glucose transporters, 288
Glomeru l a r fi ltration barrier, 480 Gonorrhea, 134. See also Neisseria
Gestational diabetes Gl ucosuria, 482
Glomeru l a r fi ltration rate (GFR), 481 gonorrhoeae
treatments For, 305 Glucuronyl transferase, 335
calculation of, 480 c l i nical presentation, 173
Gestational trophoblastic tumors Glue sniffing
changes i n , 481 metabol ic acidosis caused by, 488 prophylaxis for, 1 84
-hCG marker for, 222
equation For, 582 GLUT-2/GLUT- 5 Goodpasture's syndrome, 492
GFAP mmker, 76, 41 1 , 447, 448
GFR. See Glomerular fi l tration rate Glomeru l i carbohydrate absorption and, 322 autoantibodies associated with , 205
on i m munoA uorescence, 572 Glutamate, 106, 107 c l i nical presentation, 568
( G F R)
GGT marker, 334, 470 nodular hyal i n e deposits i n , 572 opioid effect on, 449 diagnostic findings/labs, 570, 572
G H . See Growth hormone ( G I-l ) Glomeru l onephritis, 489 toxicity, in H untington 's H L A-DR2 and, 194
Chon complex associations, common/ disease, 417 as hypersensitivity disorder, 204
diagnostic findi ngs/labs, 572 i m portant, 578 Gl utamate decarboxylase as restrictive l u n g disease, 555
G H R H . See Growth-hormone azathioprine for, 209 autoantibodies targeting, 205 Gottron 's papules, 394
releasing hormone ( G H R H ) diagnostic findings/labs, 572, 573 Glutamine, 64 Gout, 391
Giant cells, 214 with nephritic syndrome, 492 Glutamine-PRPP c l i nical presentation, 569
in CNS, as H IV sign, 41 1 pharyngitis causi ng, 1 29 amidotransferase, 97 diagnostic findings/labs, 572
Giant cell tumors of bone, 389, 573 RBC urinary casts i n , 489 Glutath ione peroxidase as drug reaction, 241
Giardia Glomeru l osa mineralocorticoids, 291 free radical i n j ury and, 215 drugs For, 406
antimicrobials for, 182 Glomeru l oscl erosis, 491 Gluten i ntolerance. See Celiac sprue kidney stones and, 493
Giardia Iamblia, 147 Glomerulus Glyburide, 305 Lesch-Nyhan syndrome as
Giardiasis, 147 anatomy of, 479 Glycine, 64, 107 cause, 567
as immunodeficiency differentiation/Formation of, 478 toxins affecting, 124 l oop diuretics as cause, 500
infection, 205 Glomus tumor, 278 Glycocalyx, 1 18 niacin and, 281
Giemsa sta i n , 1 20, 137, 141 Glossitis Glycogen, 1 10 treatment For, 574
Gigantism, 301 i n orotic aciduria, 354 insul i n effect on, 288 Cowers' maneuver, 86
growth hormone and, 290 Plummer-Vi nson syndrome as insulin/glucagon/epinephrine Cowers' sign
Gilbert's syndrome, 336, 578 cause, 324, 352, 567 regulation of, 1 10 c l i nical presen tation , 566
Gingivae Glossopharyngeal nerve, 434 stai n for, 1 20 Gpl l b/J l l a , 344, 359
bluish l ine, cause of, 566 derivation of, 510 synthesis of, 97, 1 1 1 i n platelet plug formation, 349
Bur ton's l i nes, 353 tongue i n n e rvation by, 410 Glycogenolysis, 97, 1 1 1 , 289 in thrombogenesis, 349
I ND E X
G-protein-l inked 2 n d messengers, 231 Group D streptococci . as immunodeficiency 1 - l bC disease

Grade IV astrocytoma. See Enterococci; infecti on, 205 i n anemia algorithm, 356
See Glioblastoma multi forme Streptococcus bovis meningitis caused by, 169 target cells in, 351
Grafts, 2 8 Growth hormone ( G I -l ) , 289, 290, prophylaxis for, 183 1-l B eAg antibodies, 163
Graft-versus-host disease, 208 306 in unimmunized c h i ldren, 174 HbF
as hypersensitivity disorder, 204 acromegaly caused by, 301 vaccine for, 122, 169 i n thalassemias, 353
Gram stain insul i n and, 288 H ageman factor, 125 1- lb l- 1 disease, 352
Gram-negative lab algorith m , 133 secretion of, 287 " H a i r-on-end" i n X-rays, 571 H BsAg antigen , 1 63
gram negatives, 1 18, 1 19 signaling pathway, 294 l l a i ry cell leukemia, 364 H b S mutation , 356
Gram-posi tive lab algorithm , 127 Grmvth-hormone-releasing honnone TRAP marker for, 222 H bS/-thalassemi a heterozygote, 353
gram positives, 1 18, 1 19 , 127, 1 2 8 ( G H R H ) , 289 H a i ry leukoplakia, 402 I-I C C . See Human chorionic
l i mitations of, 120 signal ing pathway, 294 1-1 IV-associated, 1 66 gonadotropin ( h C G )
Grand mal seizures. See Tonic-clonic Growth retardation Haldane effect, 552 1- l CTZ
seizures renal fai l ur e as cause, 497 Half-l ife (pharamcodynamics) 227, reactions to, 240
"Granular appearance" i n glomerular G RP. See Gastrin-releasing peptide 581 1- l D L cholesterol , 1 1 5, 1 16
h istology, 492 (GRP) H a l i tosis, 329 agents affecting, 281
Granular casts, 489 GTPase H a l l ucinations, 463 estrogen effect on, 520
in acute tubular necrosis, 496 as oncogene product, 221 mari juana as cause, 471 H eadaches, 446. See also M igraine
in renal fail ure, 496 Guaifenesin, 563 in mood disorders, 464 headaches
Granulation tissue, 214 Guaneth idine in sch izoph renia, 463 H ead bobbing
in wound heal i ng, 216 mechanism, 232 Hallucinogens aortic regurgitation as cause, 566
Granules Guanine, 64 intoxication and withdrawa l , 471 1 l ead of epididymis, 5 1 6
alpha, 344 Guanylate cyclase (cGMP) Haloperidol , 456, 473 H earing l oss, 436
dense, 344 toxin effect on, 124 for del i rium, 462 in Paget's disease of bone, 387
Guanyl ic acid (GMP), 66 for Tourette's syndrome, 460 H eart. See also Cardiovascular system
Granulocytes, 344
Gubernaculum, 514 Halothane, 453 auscultation of, 258
deficiencies, i n fections caused
G u i l l a i n-Barre syndrome, 444 reactions to, 240 autoregulation, 265
by, 205
Hamartomas. See also Lisch nodules boot-shaped, 266, 570
Granulocytopenia Campylobacter jeju ni as
i n tuberous sclerosis, 446 in fetal development, 504
trimethoprim as cause, 1 82 precursor, 136
Hamartomatous gastrointesti nal hypoxia in, 213, 265
Granulomas, 214 c l i nical presentation, 569
polyps oxygen extraction, 264
Granulomatosis with polyangitis as hypersensitivity disorder, 204
Peutz-j eghers syndrome as H eart attacks. See Myocardial
(Wegener's) peripheral nerves in, 412
cause, 567 i n farction
clinical presentation, 572 Schwatm cells in, 412
Hammer toes Heart disease
diagnostic findings/labs, 570 Gummas, i n syp h il is, 173
Friedrei ch's ataxia as cause, 430 rheumatic, 579
treatment for, 576 Gustatory hallucinations, 463
H a nd-foot-mouth disease H eart embryology, 250
Granulomatous diseases, 216 Gustatory pathway, 41 5
cli nical presentation, 172 H ea rt fa i l ur e . See also Congestive
Granulosa cell tumors, 532 Gut wall , 31 1
Hands h eart fai l ure ( C I I F')
endometrial hyperplasia and, 529 Gynecologic tu mor
blue fingers, 568 associations, common/
Granulysin, 197 epidemiology, 529
dermatomes of, 380 important, 580
Granzyme, 197 Gynecomastia, 295, 535
distortions of, 383 diabetic ketoacidosis and, 303
Granzyme B, 212 as drug reaction, 240
erythematous lesions on, 568 magnesium hydroxide as cause, 341
Grapefru it j u ice l iver cell fai l ur e as cause, 333
innervation of, 380 nutmeg l iver caused by, 335
as P-450 i n h i b i tor, 242 spi ronolactone and, SOl muscles of, 383 H eart murmurs, 258, 259
Graves' disease, 295, 298, 299 palm crease, 569 associations, common/
c l i nical presentation, 566 H
rash on palms, 569 i mportan t, 578, 579
Gray baby syndrome, 181 , 190, 240 1 - 1 1 blockers, 562 Hansen's disease. See Leprosy in bacterial endocarditis, 274
Gray matter reactions to, 241 l -lan tavirus, 158 carci noid tumors as cause, 333
amyloid deposition i n , 571 1-1 I B visas, 27, 31 Haptoglobin causes of, 566, 570
Gray matter of spinal cord, 427 1 -1 2 antagonists i ntravascular h emolysis and, 354 in hypertroph i c
synapses in, 428 name suffix, 243 H a rdy-Weinberg l aw, 581 cardi omyopathy, 272
Gray/wh i te matter j unction, 224 H 6 3 D mutation Hardy-Weinberg population in patent ductus arteriosus
Great cerebral vei n of Galen, 425 hemoch romatosis and, 337 genetics, 83 ( PDA) , 267
Greater horn of hyoid HMRT ( l l igh ly active antiretroviral Hartnup's disease, 109, 482 H eart nodules, 572
derivation of, 510 therapy) , 189 Hashimoto's thyroiditis, 298 H eart sounds, 256, 258
Great vessels 1-/aemoph i/us, 1 19 autoantibodies associated with, 205 mufAed, cause of, 568
D-transposition of, 266 1-Jaemophi/us ducreyi, 173 H LA-DR5 and, 194 spl i tting, 257
malformation, 474 Haemoph ilus influenzae, 1 3 4, 175 lymphoma and, 299 Heat-labile toxi n (LT), 1 24
Grief, 60 antimicrobials for, 177, 178, 181 neoplasms associated with, 220 H eat-stable toxi n ( ST), 1 24
Griseofulvin, 76, 186 culturing, 120 1- lassall's corpuscles, 193 H eavy-chain antibodies, 197, 362
contraindicated during diagnostic findi ngs/labs, 573 H austra H eberdcn's nodes, 390
pregnancy, 190 Gram staini ng, 133 in ulcerative colitis, 328 H e i n z bodies, 1 04, 351
as P-450 inducer, 242 i m mune response to, 198 H awthorne. effect, 53 i n C6PD deficiency, 356
for ringworm i n fections, 576 pneumonias caused by, 1 68, 560 Hay fever l lel icase, 68
Gross cirrhosis, 333 postvi ral , 168 J-I LA-D R2 and, 194 J-lelicobacter, 1 1 9
Group A streptococci . rifampin prophylaxis for, 134 as hypersensitivity disorder, 204 1-/elicobacter pylori , 1 22 , 1 37
See Streptococcus pyogenes treatment for, 575 1-1 bA 1 test, 302
c antimicrobia ls for, 182
(group A strep) 1-Iaemoph iltts inf/.uenzae type B I lbA2 test, 353 associations, common/
Group B streptococci . antiphagocytic factor, 121 H band i m portant, 577
See Streptococcus agalactiae genetic transformation, 1 26 i n muscle contraction, 385 Gram sta i n ing, 133
(group B strep) l gA protease secretion, 122 1-1 BeAg antibodies, 1 63 oncogenicity of, 222
INDEX
stomach cancer and, 327 1- le m i n eglect i n coagulation cascade, 348 pulmonary hypertensi on as
type B gastritis caused by, 327 strokes as cause, 422 for deep venous thrombosis, 553 cause, 549
ulcers and, 327 H e m i paresis for pregnancy anticoagulation, 574 H epatosplenomegaly
l l c l i otrope rash , 394 multiple sclerosis as cause, 444 reactions to, 241 b i l i a ry cirrhosis as cause, 338
H ELLP syndrome, 526 H e m isection of spinal cord, 430 thrombocytopenia induced by, 367 Gaucher's disease as cause, 567
H elmet cel ls. See Schistocytes H e m i spheres (cerebel lar) toxicity treatment, 575 N iemann-Pick disease as
Helminthic infections l esions i n , 419 vs. warfarin, 368 cause, 568
associations, common/ H emoc h romatosis, 337 H epatic adenomas, 335 Sezary syndrome as cause, 567
important, 578 associations, common/ H epatic arteries, 310, 313 Hepatotoxicity
eosinoph ils and, 345 important, 578 Hepatic ci rrhosis anesthetics as cause, 453
Helminths cardiomyopathy caused by, 272 pleural effusions caused by, 561 H epcidin
antihelminthic therapy, 1 86 ci rrhosis caused by, 333 H epatic cysts i n anemia of c h ro n i c disease, 355
H elper T cells, 195, 196, 347 free radicals and, 215 ADPKD and, 498 H epevirus, 1 58
activation of, 196 hepatocellular carcinoma and, 335 Hepatic ducts, 316 H E R2 gene, 221
cytokines secreted by, 200 H LA-A3 <mel , 194 H epatic encephal opathy H E R2-overexpressing breast cancer
in granulomatous disease, 216 lab values, 357 lactulose for, 342 th erapeutic antibodies for, 210
surface proteins, 201 H emoglobin, 547 H epatic fibrosis H E R-2-positive breast cancer, 374
H emaggl utinin, 160 fetal, affinity for oxygen , 548 ARPKD and, 498 " H erald patc h ," 401
H emangioblastomas, 85, 223 , 448 modifications, 547 H epatic necrosis H e rcepti n . See Trastuzumab
von l l i ppel-Linclau disease as H emogl obin Barts, 352 acetaminophen as cause, 405 H e reditary angioedema, 200
cause, 446, 569 l lemoglobin C . See H bC H epatic steatosis, 334 danazol for, 541
l l emangiomas, 219, 278, 581 l l emoglobinuria, paroxysmal H epatic TC l i pase ( H L) , 1 1 5 H e reditary bleeding disorders
clinical presentatio n , 570 nocturnal, 200, 354 l l epatitis, 162 associations, common/
von l l ippel-Linclau disease as Hemolysis alcohol ic, 315 i m portant, 578
cause, 446 gallstones and, 339 H e reditary e l l iptocytosis, 350
alcohol ism and, 472
l l ematemesis H emolytic anemia, 352, 354 Hereditary harmless jaundice
aplastic anemia and, 355
in Mallory-Weiss syndrome, 324, azath ioprine for, 209 associations, common/
autoi mmune, 205
cold agglutinin disease as i m portant, 578
472 as drug reaction, 240
cause, 568 l l ereditary h e morrhagic
portal hypertension as cause, 333 hepadnavirus as cause, 155
folate deficiency and, 354 telangiectasia (Osler-Weber
l lematochezia heroin addiction and, 471
pyruvate kinase deficiency as Rendu syndrome ) , 85
angioclysplasia as cause, 331 interferons for, 189
cause, 356 H e reditary hyperb i l i rubi nemias, 336
colorectal cancer as cause, 332 neoplasms associated with , 220
i n Wilson's disease, 337 Hereditary motor and sensory
diverticulosis as cause, 329 oncogenicity of, 222
l l emolytic jaundice, 335 neuropathy ( H M S N ) .
l l ematologic system recombinant cytoki nes for, 210
H emolytic-uremic syndrome See C h a rcot-Marie-Tooth
drug reactions i n , 240 as reportable disease, 57
(1-1 U S ) , 135, 1 68 disease
l l ematology/Oncol ogy serological markers, 163, 334
Hemoph i l i a , 348, 359 H e reditary nephritis
anatomy, 344-347 treatment for, 574
H emorrhage Alport syndrome as cause, 567
pathology, 350-366 H epatitis A ( H AV), 1 58, 1 62
acute pancreatitis as cause, 339 H e reditary nonpolyposis colorectal
pharmacology, 367-375 antibodies to, 1 63
i n tracranial , 424 cancer ( I I N PCC/Lynch
physiol ogy, 347-349 vaccines for, 153, 202
ulcers as cause, 328 syndrome), 69, 332
H ematomas, 424 H epatitis B ( H BV), 155, 162, 173, 175, H e reditary spherocytosis, 85, 351 , 356
l lemorrhagic cysti tis
associations, common/ 335 in anemia algorith m , 354
as drug reaction, 241
important, 578 H e morrhagic cysts, 530 antibodies for, 202 bl ood viscosity in, 255
c l i nical presentation, 568 H emorrhagic fevers, 158 hepatocel lular carci noma and, 578 H e reditary thrombosis
l l ematopoiesis l lemorrhagic i n farcts, 213 i n membrana-pro l i ferative syndrome leading to
in kidney disease, 355 l lemorrhagic stroke, 425 glomerulonephritis, 491 hypercoagulabil ity, 360
l lematopoietic stem cells berry aneurysm as cause, 423 as nosocom ial i n fection, 174 l l eritab i l i ty, 50
mutation i n , 356 l lemorrhoids, 315 serological markers, 1 63 H ermaphroditism, 525
H ematoxyl in and eosin ( H &E) sta in external, 3 1 5 vaccine for, 153 H e rnation syndromes, 448
ol igodendrogl ia and, 412 i n ternal , 3 1 4 , 3 1 5 Hepatitis C ( H CV), 1 58, 162, 187, 335 Hernias, 318
H ematuria portal hypertension as cause, 333 blood transfusions and, 579 H e roi n , 449
i n ADPKD, 498 Hemosiderin-laden macrophages, 273 hepatocellular carci noma and, 578 addiction to, 471
l l enoch-Schiinlein purpura as H e m osiderosis, 337 l ichen planus and, 401 gynecomastia caused by, 535
cause, 568 H emostasis in membrana-pro l i ferative H e rpes genital is. See Genital herpes
in renal cell carcinoma, 494 platel ets in, 344 glomeru l onephritis, 491 l l e rpes labial is, 156
in transitional cell carcinoma, 494 H enderson-1 -l asselbalch H epatitis D ( H OV), 1 58, 162 H e rpes simples vi rus 2 . See H SV-2
l l eme equation, 487, 582 H epatitis E ( I-l EV), 158, 162 H e rpes si mplex
metabolism of, 323 H enoch-Schonlein disease Hepatocellular carcinoma. See Liver facial n e rve palsy in, 437
for porphyria, 358 Berger's disease and, 492 cancer l l erpesvi ruscs, 1 54, 155, 1 56
synthesis of, 353, 358 H enoch-Schiinlein purpura, 277 l lepatocellular jaundice, 335 G u i l l a i n-Barre syndrome and, 444
Hemianopia c l i nical presentation, 568 H epatocellular steatosis, 95 Tzanck test for, 1 57
with macular sparing, 441 l lepadnavirus, 1 54, 1 55 1-lepatocytes, 74, 1 10, 315 H e rpes zoster. See Zoster
strokes as cause, 422 ll eparan sulfate alcohol abuse and, 334 H e sc h i 's gyrus, 418
l lemiball ismus, 417 i n glomerular fi ltration barrier, 480 llepatoduodenal l igament, 310 H essel bach's triangle, 318
subthalamic nucleus l esions H epari n , 367 H epatoencephalopathy, 334 Heteroch romat i n , 64
and, 419 for anticoagulation, 575 H epatolenticular degenerati on. H e te rogeneous nuclear RNA
Hemichol inium antidote to, 239 See Wilson's disease ( h n R1 A), 71
mechanism, 232 antithrombin activation, 348 H epatomegaly H e teroph i l e antibodies, 1 57 , 572
H emiclesmosomes, 378 antithromb i n deficiency and, 360 i n C H F, 273 H eteroplasmy, 82
antibodies against, 398 in basophils, 345 diagnosis for, 566 l lexagonal c rystals, 1 09
I ND E X
H exokinase vs. glucoki nase, 99 b i ndi ngs, 1 64 H ormones vaccine for, 1 53

1 -l exosaminidase A, 1 1 2 cervical carcinoma and, 528 acidoph ilic, 287 warts caused by, 397
HFE gene c l i nical l atency, 165 basoph i l i c , 287 H umoral i m m u n e response
hemochromatosis and, 337 dementia caused by, 443 , 462 endocrine, 294 B cells in, 346
1 -! fr X p- plasmid con j ugation, 126 diagnosis of, 164 gastrointesti nal, 319 vs. cell-mediated response, 202
H G P RT diseases associated with , 165 hypothalamic-pitui tary vaccines inducing, 153
azath ioprine activation, 371 h a i ry leukoplakia and, 402 regulation , 289 H umor, as ego defense, 459
deficiency in, 567 hydrocephalus and, 426 renal , 486 H u nger
H I-IV vi ruses Kaposi's sarcoma and, 278 steroid, 295 hypothalamic regulation of, 414
1-1 I- IV-6, 155, 1 56, 172 maternal/neonatal thyroid, 295 H u n ter's syndrome, 1 12
H H V-7, 155 manifestations, 171 H ormone-sensi tive l i pase, 1 1 5 H untington 's disease, 417
1 -1 !-IV-8, 155, 1 56, 222 microgl ia and, 41 1 Horn cysts c l i nical presentation, 566
H iatal hernias, 318 non-H odgkin's lymphoma and, 361 in seborrheic keratosis, 397 drugs for, 456
H igh altitude oncogenicity of, 222 Horner's syndrome, 431 neurotransmitter levels i n , 413, 461
hypoxemia caused by, 550 prophylaxis for, 184 Brown-Sequard syndrome Huntington's disease, 82, 85
physiological response to, 552 screen ing for, 51 , 80 and, 430 1-l urler's syndrome, 1 12
pul monary hypertension caused structural genes, 1 64, 189 cl inical presentation, 569 H lirth l e cells, 298
by, 549 therapy for, 189 cl uster headaches as cause, 446 H U S (hemolytic-uremic syndrome)
H igh-density l i poprotein. See H DL time course of infection, 165 as lung cancer compl ication, 558 Sh iga toxin i n , 124
chol esterol H L A genes, 194 pan coast tumor as cause, 559 H u tc h inson's teeth, 138, 171
H igh endothelial venules of lymph H LA-A 3 , 337 Horner-Wright rosettes Hyal ine casts, 489
node, 192 HLA-B27, 392, 578 diagnostic findings/labs, 570 H yal i n e mem brane disease
H igh-frequency recombination ( H fr) H LA-D R 3 /D R4, 390, 578 Horseshoe kidney, 478 as restrictive lung disease, 555
cel l , 126 H LA-DR 5 , 298 Turner syndrome as cause, 569 Hyal i n e membranes
H ighly active anti retroviral therapy in M I -I C , 194 Hot A ashes i n acute respi ratory distress
( HAART), 189 subtypes associated with clomiphene as cause, 540 syndrome (ARDS ) , 556
H i lar lymphadenopathy, 572 diseases, 194 in menopause, 523 H yaloid canal, 437
H i ndbrain, 408 H M G-CoA reductase, 97 " H ourglass stomach," 318 Hydatidiform mol es, 525
H i ndgut 1 -! M C-CoA reductase inhibitors, 281 H owell-Jolly bodies, 351 -hCG m arker for, 222
blood supply, 312 1- l M G-CoA synthase, 97 diagnostic findings/l abs, 570 diagnostic findings/labs, 571
development of, 308 l -I M P shunt, 97, 98, 103 postsplenectomy, 193 Hydralazine, 279
H ip dislocation I -I MWK, 348 in sickle cell anemia, 356 reactions to, 241
gluteal nerves and, 384 " Hobnai l " liver, 334 I-I ox genes. See 1 -i omeobox genes 1- l ydroceles, 318, 537
H i ppocampus, 415 H odgkin's lymphoma, 579 H PV virus. See H uman Hydrocephalus, 426
lesions in, 419 associations, common/ papil l omavirus ( 1- l PV) causes of, 148
1-l i rschsprung's disease, 330 i 1 1 1 porta n t, 581 1-I SV- 1 vi rus Dandy-Walker syndrome
H i rsutism bleomycin for, 372 amygdala l esions and, 419 and, 409
i n menopause, 523 diagnostic findings/labs, 571 H SV virus ependymomas as cause, 448
phenytoin as cause, 452 EBV virus i n , 222 anti microb ials for, 187, 1 88 h eadac h es caused by, 446
polycystic ovarian syndrome as herpesvirus as cause, 155, 157 erythema multi forme caused medull oblastomas as cause, 448
cause, 530 vs. non-1-i odgkin's, 361 by, 399 H ydrocephalus ex vacuo, 426
i n women, 295 prednisone for, 373 H SV- 1 , 155, 156, 324, 581 H ydroch loroth iazide, 501
H i rudin, 367 1 -l oloprosencephaly, 409 I I SV-2, 155, 1 56, 171 , 173 for diabetes insipidus, 301 , 574
H i stami nase 1-lol osystolic murmurs identification, 1 57 Hydrocortisone, 306
eosinoph il production of, 345 associations, common/ meningitis caused by, 169 Hydrolases, 218
H i stamine receptor bl ockers, 340, 341 i m portant, 579 5-I IT. See Serotoni n Hydrolysis
H istamine receptors, 231 , 321 1-lomans' sign, 553 I -ITLV- 1 virus, 222, 362 i n drug metabol ism, 228
antipsychotic effects on, 473 Homatropine HTLV virus, 158 H ydron ephrosis, 493
H istamines, 321 c l i nical use, 234 HTR. See Acute h emolytic i n fetus, 478
in basoph ils, 345 H omeobox genes, 504 transfusion reactions kidney stones as cause, 493
gastric acid regulation, 320 Homer-Wright rosettes H uman chorionic gonadotropin polycythemia and, 366
signa l i ng pathway, 294 in medulloblastomas, 448 (hCG), 523 H ydroperoxides, 404
H istidine, 107 H omocysteine in choriocarci nomas, 536 H ydrops fetal is, 171 , 352
1-1 istiocytosis X vitamin B 1 2 deficiency and, 354 el evated, 571 pa rvovi rus as cause, 172
diagnostic findings/labs, 573 Homocysteine methyl transferase, 93, i n pregnancy, 523 Hydroxocobal a m i n
as restrictive lung disease, 555 109 secretion i n fetal development, 504 as antidote, 239
l l istology 1 -lomocystinuria, 82, 109 signal ing pathway, 294 Hydroxyapatite
digestive tract, 31 1 H omogentisic acid oxidase, 108 as tumor marker, 531 bisphosphonate effect on, 405
female reproductive system , 515 H omonymous hemianopia, 441 H umanized monoclonal H ydroxychl oroquine
H istone acetylation/methyl ation, 64 1 -! omovani l l i c acid ( I-IVA), 297 antibodies, 202 reactions to, 241
Histoplasma Homunculus, 418 H uman l eukocyte antigen ( l-I LA). Hydroxylase deficiencies, 291
antimicrobials for, 185 " Honeycombed uterus," 525 See H L A genes Hydroxylation ( E R), 78
H istoplasmosis, 143 " Honeycomb l ung," 572 Human papi l lomavirus ( H PV) H ydroxylysine, 78
erythema nodosum and, 400 H ook of hamate causes of, 155 l-lydroxyure;1, 65, 373
as granulomatous disease, 216 claw hand caused by, 383 cervical carcinoma and, 528 for sickle cell anemia, 356, 576
H istrionic persona l i ty disorder, 468 H ookworms, 1 51 diagnostic findi ngs/labs, 570 vitamin B 1 2 deficiency and, 354
H ives, 397 H orizontal diplopia 1-1 PV-6, 173 H yoid artery
as hypersensitivity disorder, 204 diseases causing, 566 1-I PV- 1 1 , 173 development of, 509
as wheals, 395 H ormone replacement therapy oncogenicity of, 222 H yperactivity. See Attention-deficit
H IV virus, 1 58, 164, 173 ( H RT), 540 squamous cell carcinoma hyperactivity disorder
bacillary angiomatosis and, 278 estrogens for, 539 and, 537 (AD I-I D )
INDEX
l lyperacute transplant rejection, 208 rena I fai l u re as cause, 497 mal ignant, 279 Hypogonadism
Hyperaldosteronism thiazide di uretics and, 501 medications for, 235, 236, 237 diagnosing, 524
associations, common/ Hyperkalemic rena l tubular acidosis nephritic syndrome a n d , 492 estrogens for, 539
i m portant, 580 ( RTA) , 488 pheoch romocytoma as cause, 286 hypogonadotro p i c
diuretics for, 501 H yperkeratosis, 396 portal, 314 hypogonadism, 524
secondary, 296 verrucae and, 397 prednisone as cause, 373 Klinefelter's syndrome as cause, 524
treatment for, 575 H yperl ipidemia, 85 pregnancy-induced, 526 testosterone for, 539
Hyperammonemia, 107 nephrotic syndrome as cause, 490 RBC urinary casts in, 489 H ypograstic n e rve
Hyperb i l i rubinemias, 335, 336 signs of, 267 in renal fai l ur e , 496 male emissions and, 516
H ypercalcemia, 223 , 487, 493 thiazide di uretics and, 501 therapies for, 279 H ypokalemia, 487
acute pancreatitis caused by, 339 Hypermagnesemia, 487 treatment for, 501 , 575 adrenal enzyme deficiency as
bisphosphonates for, 405 H ypernatremia, 487 H ypertensive crisis cause, 291
calcium carbonate as cause, 341 1-lyperora l i ty MAO i s as cause, 475 antacids as cause, 341
in hyperparathyroidism, 300 Kl liver-Bucy syndrome as l lypertensive hemorrhage, 424 causes of, 487
in multiple myeloma, 363 cause, 567 l lyperthermia Conn's syndrome as cause, 567
neuromuscular blocking drugs as H yperosmolarity treatment for, 575 hyperaldosteronism as cause, 296
cause, 455 hyperkalemia caused by, 487 H yperthyroidism , 299 l oop diuretics as cause, 500
para neoplastic cytokines in, 223 H yperparathyroidism, 300 vs. hypothyroidism, 298 Hypokalemic metabol i c alkalosis, 501
thiazide diuret ics and, 501 associations, common/ treatments for, 306 H ypomagnesemia, 487
H ypercalcuria i m portant, 580 Hypertonia H ypomanic episodes, 464
in hyperparathyroidism, 300 i n renal osteodystrophy, 497 U M damage as cause, 567 H yponatremia, 487
H ypercapnia Hyperphagia l lypertriglyceridcmia, 1 16 central pontine myel inolysis and, 419
"blue bloater" as cause, 567 hypothalamus and, 414 acute pancreatitis caused by, 339 in S IA D H , 301
l lyperchloremic metabolic acidosis Khiver-Bucy syndrome as treatment for, 575 thiazide diuretics and, 501
acetazolamide as cause, 500 cause, 567 Hypertroph ic cardiomyopathy, 272 H ypo-osmolarity
Hyperchol esterolemia, 1 89 H yperphosphatemia, 487 Friedreich's ataxia as cause, 430 hypokalemia caused by, 487
nephroti c syndrome as cause, 568 in renal osteodystrophy, 497 heart murmur with, 258 H ypoparathyroidism, 300
treatment for, 575 Hyperpigmentation Hypertroph i c osteoarthropathy associations, common/
Hyperchylomicronemia, 1 1 6 Addison's disease as cause, 569 adenocarci noma of the lung i mportant, 579
l lypercoagulabil ity, 360, 572 busulfan as cause, 372 and, 558 Hypophosphatemia
associations, common/ H yperplasia, 218, 219 l lypcrtroph ic ventricles a l u m i nu m hydroxide as cause, 341
important, 579 congenital b i lateral adrenal, 291 S4 and, 580 in hyperparathyroidism, 300
Hypercortisolism hyperparathyroidism and, 580 H yperuricemia H ypophosphatemic rickets, 84, 488
iatrogenic, causes of, 1 85 Hyperplastic polyps, 331 clinical presentation, 569 Fancon i 's syndrome as cause, 569
1- lyperdocility Hyperprolactinemia diuretics as cause, 500 H ypophysis, 436
Kl i.iver-Bucy syndrome as anovulation in, 529 niacin and, 281 H ypopituitarism , 301
cause, 567 H yperrcAexia thiazide diuretics and, 501 associations, common/
Hyperemia UM damage as cause, 567 Hyperventilation i mportant, 579
i n myocardial infarction, 270 1 - l ypersegmented neutrophils, 572 cerebral edema, treatment for, 421 H ypoplasia
1-lyperAexible joints, 78 Hypersegmented PMNs, 93 diabetic ketoacidosis as cause, 567 as organ morphogenesis error, 505
Ehlers-Danlos syndrome as Hypersensitivity pneumonitis, 204, "pink puffer" and, 568 I I yporeAexia
cause, 567 560 Hypnagogic hall ucinations, 62, 463 LMN damage as cause, 567
Marfan 's syndrome and, 85, 566 as restrictive lung disease, 555 Hypnopompic hall ucinations, 62, 463 H ypospadias, 513
l lypergam maglobul inemia Hypersensitivity reactions, 203 H ypnotics, nonbenzodiazepine, 453 H yposplenia
sclerosing cholangitis and, 338 all ergic contact dermatitis, 397 l lypoalbuminemia H owell-J ol l y bodies i n , 351
Hyperglycemia. See also D iabetes B cells and, 195 alcoholic ci rrhosis and, 334 H ypotension
mell itus to bl ood transfusions, 204 nephrotic syndrome as cause, 568 Addison's disease as cause, 297
in Cushing's syndrome, 296 disorders of, 204 l l ypocalcemia adrenal enzyme deficiency as
in diabetes mel l i tus, 302 mast cells and, 346 acute pancreatitis as cause, 339 cause, 291
in diabetic ketoacidosis, 303 to meth ic i l l i n , 177 as blood tranfusion risk, 360 associations, common/
as drug reaction, 240 to penici l l i n , 176 clinical presentation, 567 i m portant, 577
glucagon and, 289 rheumatoid arth ritis as, 390 hyperparathyroidism and, 580 in Beck's triad, 568
insu l i n and, 288 Hypersexual ity in Khiver-Bucy hypoparathyroidism and, 300 cerebral watershed zones and, 420
osmotic damage from , 105 syndrome, 419, 567 i n osteopetrosis, 387 diagnosis for, 566
prednisone as cause, 373 Hypertension, 267. See also Portal H ypochondriasis, 467 H ypothalamic drugs, 306
1-Jyper-lgE syndrome (Job's syndrome) hypertension; Pul monary MAO i n h i b i tors for, 475 H ypothalamic-pituitary hormone
cl i nical presentation, 569 hypertension H ypoc h romia regulation, 289
as immunodeficiency disease, 206 ACE i n h i b i tors for, 502 in 13-thalassemi a , 353 H ypothalamus, 414
Hypcr-lgM syndrome, 207 in ADPKD, 498 in i ron deficiency, 352 blood-brai n barrier and, 413
Hyperinsul inemia adrenal e nzyme deficiency as Hypoch romic anemia, 352-353, 572 Horner's syndrome and, 431
acanthosis nigricans and, 400 cause, 291 1-lypofibrinogenemia in 1\AA S , 485
Hyperkalemia, 487 aneurysms and, 576 erythrocyte sedimentation rate reproductive h ormones and, 538
ACE inhibitors as cause, 502 ARPKD as cause, 498 and, 349 spermatogenesis and, 519
Addison's disease as cause, 297 associations, common/ Hypoglossal canal H ypothenar muscle, 383
adrenal enzyme deficiency as i mportant, 579 as cranial nerve pathway, 435 H ypotheses, statistical, 54
cause, 291 berry aneurysms and, 423 l lypoglossal nerve, 434 H ypothyroi dism, 298
as blood transfusion risk, 360 13-b lockers for, 238 lesion in, 436 c l i nical presen tation, 566
causes of, 487 Conn's syndrome as cause, 572 H ypoglycemia cretinism and, 577
i n diabetic ketoacidosis, 303 hydroch loroth iazide for, 501 Cori's disease as cause, 568 as drug reaction, 240
neuromuscular blocking drugs as i ntraparenchymal hemorrhage glucagon and, 289 vs. hyperthyroidism, 298
cause, 455 and, 424 insul i n and, 288 treatments for, 306
INDEX
l lypoton ia complement activation, 199 I mmune responses I n di rect agonists, 233

LMN damage as cause, 567 compl ement b inding, 197 anergy, 201 I n di rect b i l i ru b i n , 323
H ypoven tilation in cytotoxic hypersensitivity, 203 an tigen variation, 201 I ndirect c h o l inomimetics
hypoxemia caused by, 550 Fe receptors, 128 a11toanti bodies, 205 for glaucoma, 449
Hypovolemic shock, 214 functions of, 195 bacterial toxin effects, 201 I n di rect Coombs' test, 357
l l ypoxanth ine, 66, 406 heparin-induced blood transfusion reactions, 204 I n di rect inguinal h e rn i as, 318
l l ypoxanth ine-guanine thrombocytopenia ( l-I lT) cell surface proteins, 201 I n di rect pathway
phosphori bosyltransferase and, 367 compl ement, 199 of basal gangl i a , 416
( 1- l C PRT), 66 in multiple myeloma, 363 cytokines, 200 I ndomethaci n , 405
l l ypoxemia, 550 in multiple sclerosis, 444 grafts, 208 for diabetes i nsipidus, 301 , 574
"blue bloater" as cause, 567 in pemph igus vulgaris, 398 hypersensitivity, 203-204 for gout, 391 , 406
Hypoxia, 550 Rh factor and, 347 immune deficiencies, 206-207 for patent ductus arteriosus
pulmonary, 265 l gi\11 anti bodies, 142, 1 63 , 198 immunodeficiency infections, 205 ( P DA) , 252, 267, 575
l lypoxic ischemic in autoimmune hemolytic i nterferons, 201 I n fant deprivation effects, 459
encephalopathy, 213 anemia, 357 passive vs. active, 202 I nfantile polycystic kidney disease.
l l ypoxic vasoconstriction b i l i ary cirrhosis and, 338 transplant rejections, 208 See ARPKD
pulmonary hypertension caused blood groups and, 347 vaccination and, 202 I n farcts, 213, 271
by, 549 complement activation, 199 I m munizations. See Vaccines I n fections
complement binding, 197 l mmunocompromised pati ents i n anemia algorith m , 357
in cytotoxi c hypersensitivity, 203 acyclovir as prophylaxis for, 187 I n fectious arth ritis, 392
I band functions of, 195 foscarnet for, 188 I nfectious mononucleosis
i n muscle contraction, 385 hyper- l gM syndrome, 207 ganciclovir for, 188 c l i nical presentation, 568
I B D. See I n fl ammatory bowel disease in splenic dysfunction, 193 microorganisms affecting, 1 68 diagnostic fi ndings/labs, 572
( I B D) I L- l I n fectious skin disorders, 402
I mmunofl uorescence, in nephritic/
I buprofen, 405 toxins affecting, 1 23 I n fective endocarditis
nephrotic syndromes, 490-
reactions to, 240 I L-2 c l i nical presentation, 568
491 , 492
l butil ide I n ferior cerebell a r peduncle
i n h i bition of by I mmunofl uorescent stai n i ng, 203
as antiarrhyth mic, 284 strokes i n , 422
immunosuppressants, 209 I m munoglobul i n
lCAM-1 I n ferior col l i c u l i , 415, 433
receptor deficiency, 207 isotypes of, 198
in leukocyte extravasation, 215 I nferior epigastric artery
toxins affecting, 125 for vascul itis, 276
1-<:ell disease ( i nclusion cell disease), 75 hernias and, 318
I L-8 I mmunoh istochemical stai n s for
I cells, 319, 321 I nferior epigastric vessels, 317, 318
in l eukocyte extravasation, 215 intermediate filaments, 76
I C F. See I n tracell ular fluid I n ferior gl uteal nerve, 384
I L- 1 2 receptor deficiency I mmunologic memory
l cterohemorrhagic l eptospirosis. I n ferior mesenteric artery
as immunodefici ency disease, 206 antigens and, 198
See Wei l 's disease structures suppl ied by, 312
I leal atresia, 308 I m munol ogy
I dentification, as ego defense, 458 I n ferior mesenteric lymph nodes, 192
I l eocecal valve immune responses, 1 99-209
I diopath i c anemia, 355 I n ferior mesenteric vei n , 314
gallstone obstruction, 339 immunosuppressants, 209-210
Idiopath ic facial nerve palsy. I n ferior pharyngeal constrictor
Ileum lymph ocytes, 193-198
See Bel l 's palsy Zenker's divertic u l u m , 329
basal electric rhythm , 31 1 lymphoid structures, 192-193
Idiopath ic hypercalciuria I n ferior sagital sinus, 425
hydroch loroth iazide for, 501 h istology, 31 1 l mmunomodulators
I nferior vena cava, 310
Idiopath i c thrombocytopenic purpura vitami n/mineral absorption, 322 signal ing pathway, 294
diaph ragm perforation by, 545
as hypersensitivity disorder, 204 Ileus I mmunosuppressan ts I n ferti l i ty
Idiopath ic thrombocytopenic purpura gal l stone as cause, 339 azath iopri ne, 209 clomiphene for, 540
( ITP), 359 I l iac crest cycl osporine, 209 endometriosis as cause, 528
diagnostic findings/labs, 570 l umbar puncture at, 379 muromonab-C D 3 ( O KT 3 ) , 209 Kartagener's syndrome as
I DL, 1 1 5, 1 16 II iac lymph nodes, 192 recombinant cytokines, 210 cause, 569
lduronate sulfatase, 1 12 l matinib, 374 sirol i mus (rapamyc i n ) , 209 Klinefel ter's syndrome and, 524
I fosfamide, 372 for chronic myelogenous tacrol imus ( FK-506), 209 l euproti de for, 539
reactions to, 241 l eukemia, 365, 574 th erapeutic antibodies, 210 mumps as cause, 161
l gA antibodies, 198 I midazole I m pacted teeth pituitary adenoma as cause, 301
blood transfusions and, 204 for ringworm infections, 576 Gardner's syndrome as cause, 568 treatment for, 575
deficiency i n , 206, 207 l m ipenem, 178 I M P dehydrogenase, 187 I n flammation, 21 2-217, 214
dermatitis herpetiformis and, 398 mechanism of action, 176 I mpetigo, 402 acute vs. chronic, 214
in multiple myeloma, 363 reactions to, 241 crusts i n , 395 amyl oidosis and, 217
nephropathy of, 277 I m i pramine, 475 sunburn and, 401 apoptosis and, 212
secretion of, 323 for enuresis, 61 I mplantation of ferti l i zed egg, 523 atrophy and, 214
l gA nephropathy, 492 I mmature ego defenses, 458-459 I mpl ied consent, 56 cell i n j u ry and, 213
l gA protease, 122, 128, 134 I mmature teratomas, 531 I mprinting, 82, 83 characteristics of, 214
l gC antibodies I m m ediate immune response, I nactivated vaccines, 202 erythrocyte sedi mentation rate
deposition on glomerular antibodies involved in, 198 I n appropriate absolute ( E S R) , 217
basement membrane, 572 Immediate phase of wound polycythemia, 366 free radical i n j u ry and , 215
lgD antibodies, 198 heal i ng, 216 I ncidence of common cancers, 224 granulomatous disease and, 216
lgE anti bodies, 198 I mmune complex hypersensitivity Incomplete penetrance, 82 hypoxia and, 213
functions of, 195 ( type I l l ) , 195, 203 I ncontinence. See B l adder infarcts, 213
l lyper-IgE syndrome, 206 C 3 deficiency and, 200 incontinence i ron poisoni ng and, 217
mast cell binding of, 346 Immune complex ( I C ) Increased survival vs. early l eukocyte extravasat i o n , 215
as therapeutic anti body target, 210 deposition in kidney, 492 detection, 53 necrosis and, 212
lgC anti bodies, 1 63 , 198 I mmune deficiencies, 66, 206 I ndia ink stai n , 1 20, 145 shock a n d , 214
in autoimmune hemolytic infections i n , 205 " I ndian file" cell s in breast transudate vs. exudate, 216
anemia, 357 neoplasms associated with , 220 tumors, 534 wound healing and, 216
IN DEX
I nflammatory bowel disease I nsul i n-dependent diabetes mellitus I nterosseous muscles, 383 I nu l i n
( I B D ) , 328, 392. See ( ID D M ) . See D iabetes atrophy of, 382 extr<1cel lular fl u i d vol u m e
also C rohn's disease; mell i tus type I I n tersti tial cell of Leydig, 517 measurement, 480
U l cerative col itis I nsul i n-dependent organs, 288 I n terstitial fibrosis GFR calculation with , 480
as colorectal cancer risk factor, 332 l nsul i nomas sarcoidosis and, 393 along proximal tubul e , 484
H LA-B27 and, 194 i n M E N I , 304 I n terstitial fluid pressure, 265 I n vasive aspergi l l osis
I n flammatory breast tumors, 534 I nsul i n resistance I n terstitial nephritis H IY-associated, 166
l n fl iximab, 342, 406 acromegaly and, 301 aspirin as cause, 368, 404 I nvasive cancers
for Croh n's disease, 328, 574 cortisol as cause, 292 causes of, 181 of breast, 534
as therapeutic antibody, 210 in diabetes mell i tus type 2 , 303 as drug reaction, 241 of cervix, 528
for ulcerative colitis, 328, 576 growth hormone ( C H ) and, 290 N SAJ Ds as cause, 405 I odide
I n fl uenza B in polycystic ovarian syndrome, 530 I n terstitial pneumonia, 560 as teratogen , 506
Reye's syndrome and, 334 l n tegrase i n h i b i tors, 189 I l l Y-associated, 1 66 Iodine deficiency, 298
I n fl uenza virus, 1 58, 160 l n tegrin, 215 I n terstitial pulmonary fi brosis creti nism and, 577
antimicrobials for, 1 87 I n tention tremor, 417 diagnostic findings/labs, 572 J od-Basedow phenomenon
genetic shift/drift, 160 cerebel lar l esions and, 419 I n terstitial vol ume, 480 and, 299
pneumonia caused by, 168, 560 multiple sclerosis as cause, 429, I n terventricular foramen, 250 l odoqu inol
treatm ent for, 575 444, 568 I n terventri cular septum for E n tamoeba h istolytica , 147
vaccine for, 1 53, 1 60, 202 I n teratrial septum development, 251 development, 250 ion channels, 260
vi ral reassortment and, 1 53 I n tercel lular bridges I n terviews for residency, 34 l pratrop i u m , 563
Informed consent, 56 in squamous cell carcinoma of the I n testinal atresi a , 308 c l i n i cal usc, 234
Infraspinatus muscle, 379 I n testinal disorders, 331 I psilateral b l i ndness
l ung, 558
Infundibulum, 432 I n testi nal obstruction temporal arteritis and, 580
I n tercostal muscles
I ngu inal canal , 317, 516 from superior mesenteric artery I psilateral hypoglossal dysfunction
in respi ration, 546
I ngu inal l igaments, 316, 318 ( S MA) syndrome, 312 strokes as cause, 422
I n terferons, 189. See also Cytoki nes
dermatome for, 431 I n testinal peristalsis. See Peristal sis Ipsilateral l eptomeni ngeal angiomas
c l i n i cal uses for, 210
I nguinal lymph nodes, 192 I n testi nal stomach cancer, 327 in Sturge-Weber syndrome, 446
i nterferon-a, 241
I ngu i nal ring I n timal fibrosis of pulmonary arteries I P3
interferon-y, 216
hernias in, 318 pulmonary hypertension as signaling pathways, 294
interferon-y, 200
IN I-I cause, 549 I ris, 437
mechanism of, 201
for Mycobacterium tuberculosis, 575 I n tracellular fl u i d , 480 darkeni ng, caused by
natural killer cel l s and, 194
Inhaled anesthetics, 453 I n tracellular organisms, 121 l atanoprost, 449
l n terl eukins, 200. See also Cytokines
l n h ibin I ntracranial calcifications I ritis, 438
helper T cell i n h i b i tion, 196
secretion of, 517 causes of, 148 I ron
i m munologic memory and, 198 absorption of, 322
spermatogenesis and, 519 I ntracranial hemorrhage, 424
natural killer cells and, 194 hemochromatosis caused by, 337
I n h ibitors, 226 I n tracranial neoplasms, 223
I n terlobular artery, 479 toxicity of, 94, 217, 239
of complement system, 199 I n tracranial pressure
I n termediate filaments, 76 I ron deficiency. See a lso Anemia
In hib itory neurotransmi tters i n acute cerebral edema, 421
I n termediate horn of spinal i n anemia algorith m , 352
toxins affecting, 124 in hydrocephal us, 426
cord, 427 lab values, 3 5 7
I n h i b i tory pathway of basal mannitol as therapy, 500
I n termediate zone of l iver, 315 I n tracytoplasmi c eosinop h i l i c in Pl um m e r-Vi nson syndrome, 352
gang! ia, 416
I n termediolateral col umn of spinal incl usions, 334 I ron deficiency anemia
I nitiation
cord I n tradermal nevi , 397 colorectal cancer as cause, 332
in protein synthesis, 73
l lorn er's syndrome and, 431 I n traductal papi l lomas, 533 diagnostic findings/labs, 572
I n nate immune system
I nternal auditory meatus
vs. adaptive immune system , 19.3 I n traocular pressure P l u m mer-Vinson syndrome as
dendritic cells in, 346 acoustic neuroma and, 412 mannitol as therapy, 500 cause, 567
I nosinic acid ( I M P) , 66 as cranial nerve pathway, 435 l ntraparenchymal h e morrhage, 424 I ron studies, 3 7
I nsecticides I n ternal capsul e I n trauterine growth retardation, 59 in anemia of c h ronic disease, 355
toxicity of, 233 strokes i n , 422 I n travascular h emolysis, 204, 354 i n hemochromatosis, 337
I nsol uble fibrin mesh, 349 I n ternal carotid artery, 436 I n travenous anesthetics, 454 I rritable bowel syndrome ( I BS), 329
l ns01nnia I n ternal il iac lymph nodes, 192 I n travenous cath eters Ischemia, 213, 550
benzodiazepines for, 453 I nternal j ugular vein , 425 bacterial risk of, 128 in l iver, 3 1 5
nonbenzodiazepine hypnotics I n ternal medullary lamina, 415 I n traventricular hemorrhage, 59 R B G urinary casts i n , 489
for, 453 I n ternal oblique, 317 I n trinsic coagul ation pathway, 348 rena l , 496
I nspiration I n ternational Medical Education I ntrinsic factor, 93, 320 Ischemic brain disease/stroke, 425
heart sounds and, 258 D irectory ( I M E D ) , 26, 29 location of, 321 I schemic col i tis, 331
Kussmaul's sign, 275 I n ternational medical graduates vitamin B 1 2 and, 322 Ischemic h eart disease
muscles controll ing, 546 ( I MGs), 26-36 I n trinsic hemolytic normocytic manifestati ons, 269
I nspiratory capacity (I C ) , 546 E C F M G , 26-27 anemia, 356 Ischemic stroke
I nspiratory reserve vol ume ( I RY), 546 EIZAS , 26-37, 33-34 I n trinsic pathway thrombolytics for, 368
Insulin, 288 the Matc h , 26-27, 32-36 for apoptosis, 212 Ischial spine
for diabetes m e l l i tus, 303 , 305, 574 residency, 26, 32-35 coagulation defects, 359, 360 pudendal n erve block at, 379
gl ucagon and, 289 U S l i censure, 26-27 heparin and, 368 I sl ets of Langerhans, 287
glycogen regulation by, 1 10 U S M L E Step I , 26-29, 32 I ntrinsic renal fai l ur e , 496 h ormones produced by, 319
hyperkalemia caused by deficiency U S M LE Step I passing rates, 10 I ntri nsic tyrosi n e ki nase l socarboxazid, 475
of, 487 U S M LE Step 2 C K, 26-30 signaling pathways, 294 l soci trate dehyd rogenase, 97, 98
hypokal emia caused by, 487 U S M L E S tep 2 C S , 26-28, 30-31 , I ntrons vs. exons, 71 lsoflurane, 453
production of, 287 33-34 I ntussusception, 330 I solation of affect, 458
secretion of, 288 U S M L E Step 3, 27, 31 -32, 34 c l i nical presentation, 569 Isoniazid, 183
signaling pathway, 294 I n ternuclear ophthal moplegia, 442 Mecke l 's diverticulum as as P-4 5 0 i n h i b i tor, 242
somatostatin and, 319 c l i n i cal presentation, 566 cause, 330 reactions to, 240, 241
I N DEX
I soproterenol J o i n t hypermobi l i ty, 78, 85 as P-4 5 0 i n h i b i tor, 242 tibial nerve a n d , 384
blood pressure effects, 236 E h lers-Danlos syndrome as reactions to, 240 u n happy triad i n j u ry, 379
clinical use, 235 cause, 567 Ketogenesis, 97 Knock-out mouse, 81
heart rate effect, 236 J ugular foramen, 425 a-Ketogl utarate dehydrogenase, 98 KOI-1 prep, 144
vs. norepinephrine, 236 as cranial nerve pathway, 435 Ketone bodies, I ll , 288 Koilocytes, 528
l sosorbide dinitrate, 280 Jugular vein , 425 in diabetic ketoacidosis, 303 diagnostic fi n di ngs/labs, 570
l sotretinoin, 90 distention of, 273 , 549 production of, 289 Koilocytosis
lsovol umetric contraction and J ugular venous pulse (J VP ) , 256 Ketorolac, 405 verrucae and, 397
relaxation periods, 256 Kussmaul's sign, 275 Key associations, 576-580 Kopl i k spots, 161 , 174
I traconazole, 146, 185 Junctional nevi , 397 Kidney c l i nical presentation, 569
I UG R Junction, gray/wh i te matter, 224 thyroid-l ike appearance of, 573 Korsakoff's amnesia, 461
tera toge n s causi ng, 506 justice, as eth ical principle, 56 Kidney disease, 355 Korsakoff's psychosis, 472
IVC J uveni l e onset diabetes. See Diabetes lead poisoning as cause, 358 Krabbe's disease, 1 12, 445
invasion by renal cell mell itus type I Kidneys, 309. See also Renal system k-ras mutation
carcinoma, 494 Juvenile polyposis syndrome, 331 anatomy and glomcmlar i n adenocarcinoma of l ung, 558
IV dmg use as colorectal cancer risk factor, 332 stmcture, 479 colorectal cancer and, 332
osteomyel itis and, 579 Juvenile polyps, 331 autoregulation, 265 Krebs cycle, 101
tricuspid valve and, 578 J uxtaglomerular apparatus ( J GA), 485 bl ood flow, 264 Kmkenberg tumor, 327, 532, 580
lvermecti n , 1 86 -blocker effects on, 238 cortical infarction of, 495 Kulch i tsky cells, 558
for Onchocerca volvulus, 1 51 juxtaglomerular cells, 481 embryology of, 478 Kupffer cells, 315, 336
IV i mmune globul i n s endocrine functions, 486 Kur u , 167
for Guillain-Barre syndrome, 444 K hormones acting on, 486 Kussmaul's sign, 275, 303, 567
" I vory-l ike" bone, 573 Kal l ikrein horseshoe, 478 Kwashiorkor malnutrition, 96
" I vory wh i te" pleural plaques, 555 bradykinin activation, 348 hypoxia i n , 213 Kyphoscol iosis
Ixodes tick as disease vector, 137, 139, in leukocyte extravasation, 215 infarction, 213 Friedric h 's ataxia as cause, 430
149 Kallmann syndrome, 525, 579 insul i n effect on, 288 Kyphosis
Kaposi 's sarcoma, 173 , 278 multicystic dysplastic, 478 osteoporosi s as cause, 387
A I D S and, 220 Kidney stones, 493
}AK2 mutations associations, common/ L
c l i n i cal presentation, 567
in chronic myeloprol i ferative important, 579 Labetal o l , 238
herpesvims as cause, 155, 156
disorders, 366 calcium/phosphate as cause, 487 Labi l e cell type, 74
I- I I- I V-8 virus i n , 222
Janeway lesions, 274 chronic pyelonephritis and, 495 Labioscrotal swell ing
i nterferons for, 1 89
Jarisch-1-lerxheimer reaction, 138 Crohn 's disease and, 328 derivations of, 513
recombinant cytokines for, 210
clinical presentation, 567 renal fai l ur e caused by, 496 Laboratory tests
Kappa opioid receptor, 449
J aundice, 335 renal tubular acidosis and, 488 classic findi ngs, 570-573
Kartagener's syndrome, 554
alcohol i c cirrhosis and, 334 struvite, 170 Labor induction drugs, 341
clinical presentation, 569
associations, common/ Kidney transplants, 479 Lab val ues
Kartagener's syndrome, 76
important, 578 immunosuppressan ts for, 209 i n bone disorders, 388
Karyolysis, 212, 213
biliary cirrhosis as cause, 338 Killed vaccines, 153, 202 renal fai l ur e , 496
Karyorrhexis, 212, 213
as Courvoisier's sign, 568 Kill ian's triangl e , 329 in renal osteodystrophy, 497
Karyotyping, 81
Crigler-Na jjar syndrome as Kimmelstici-Wi lson nodules, 491 Lacrimal glands
Kawasaki disease, 276
cause, 336, 569 in diabetes m e l l i tus, 302 i n nervation of, 434
aspirin for, 334
extravascular hemolysis as cause, 354 diagnostic signs/labs, 572 Lacrimation reflex, 434
hepatocellular carcinoma as c l i nical presentation, 569
Kinase, 96 Lactase deficiency, 105, 326
cause, 335 Kayser-Fleischer ri ngs
Kines i n , 76 Lactation, 523. See also B reast milk
l i ver cell fai l ur e as cause, 333 cl inical presentation, 567
Kinin pathways, 348 Lactic acid dehydrogenase (B3), 101
pancreatic cancer as cause, 568 in Wilson's disease, 337 "Kissing disease" . See Mononucleosis Lactic acidosis
Jaw jerk reflex, 434 K cells, 319, 321 Klebsiella, 1 19, 122, 134, 136, 175 metformi n as cause, 305
Jaw muscles, 437 Ke (elimi nation constant). i n alcoholldrug users, 168 Lactiferous si nuses, 533
JC vims, 155 See E l i m i nation constant of Cram sta i n i ng, 133 Lactobacillus
J e j u nal atresia, 308 dmgs kidney stones caused by, 493 as normal fl ora, 167
J e j unum Kerati n-fi l l ed cysts nosocomial pneumonia and, 579 Lactose-fermenting enteric
histology, 31 1 in seborrheic keratosis, 397 pneumonias caused by, 560 bacteria, 134
hormones produced by, 319 Keratinocytes Klebsiella pneu moniae c u l turing, 120
vitamin/mineral absorption , 322 i n wound heal i ng, 216 antimicrobials for, 178 Lactose i n tolerance, 105
J ervell and Lange-N ielsen Keratin pearls, i n squamous cell anti ph agocytic factor, 121 Lactose tol erance test, 326
syndrome, 261 carcinoma of l ung, 558, 572 cl inical presentation, 569 Lactulose, 1 07, 342
)CA. See J uxtaglomemlar apparatus Keratoacanthoma, 403 as immunodeficiency Lacunar i n farcts, 422
( J GA) Keratoconj unctivitis infection, 205 Lacunar strokes, 417, 425
J i mson weed toxicity, 234 herpesvirus as cause, 155 urinary tract i n fections caused Lag phase of bacterial growth , 125
jo-1 I-ISV- 1 as cause, 156 by, 170 Lambert-Eaton syndrome, 223, 394,
autoantibodies targeting, 205 Kernicterus Kl inefelter's syndrome, 524 558
job's syndrome. See 1- lyper-lgE i n C rigl er-Naj jar syndrome, type gynecomastia and, 535 Lamina propria, 31 1
syndrome ( Job's syndrome) I, 336 Klumpke's palsy, 381 , 382 celiac spme and, 326
J ob's syndrome. See 1-lyper-lgE i n neonatal jaundice, 335 Kl umpke's total claw, 383 Peyer's patches in, 323
syndrome ( Job's syndrome) sulfonamides as cause, 181 Khiver-Bucy syndrome, 419 Lamivudine ( 3TC ) , 189
J od-Basedow phenomenon, 299 Ketamine, 454 c l i nical presentation, 567 Lamotrigi ne
John Cunningham ( J C ) virus Ketoacidosis Km. See M ichael is-Menten kinetics for bipolar disorder, 574
progressive multifocal i n diabetes mel l i tus, 303 Knees for epilepsy, 451
leukoencephalopathy Ketoconazole, 185, 291 , 539 anatomy of, 379 reactions to, 241
and, 445 gynecomastia caused by, 535 dermatome for, 431 toxicities, 452
I N DEX
Lancefield grouping of Left heart fai l ure, 273 . See chronic myelogenous Limbus, 437
e n terococci, 129 also Congestive heart fai l ure leukemia, 221 Linea alba, 317
Landmark derma tomes, 431 (CHF) cloxorubicin for, 372 L i n ear ul cers, 328
Langerhans cell h istiocytosis, 366, L e ft h epatic duct, 3 1 6 etoposide/teniposicle for, 373 Lines of Zah n , 553
573 Left h o rn o f sinus venosus, 250 h a i ry cel l , 222 diagnostic findings/l abs, 573
Langerhans cells, 346 Left main coronary artery ( LCA), 253 kidney stones and, 493 L i neweaver- Burk plot, 226
Lansoprazole, 341 Left shift microtubule i n h i b i tors for, 373 L i nczol id, 179
Large cell carcinoma of l u ng, 558 hemoglobin-oxygen dissociation radiation exposure and, 220 mechanism of action, 176
Large vessel atherosclerosis curve, 547 recom binant cytokines for, 210 for VRE, 1 84
in diabetes m e l l i tus, 302 " Left-sided appendicitis". vs. lymphoma, 361 Linitis plastica, 327
Laryngeal cancer See D iverticulitis Leukemoid reaction, 361 Linkage disequ i l ibrium, 82
carcinogens affecting, 223 Left ventric l e ( LV) Leukocyte adhesion deficiency ( type Li pase
Lassa fever, 1 58 fai l ure, after M l, 271 1 ) , 207 in acute pancreatitis, 339
Latanoprost Legionella , 1 19, 121 Leukocyte alkal i n e phosphatase i n chronic pancreatitis, 340
for glaucoma, 449 culturing, 1 20 i n chronic myelogenous fat digestion by, 322
Late cyanotic shunt as nosocomial infection, 174 leukemia, 365 as serum marker, 334
associations, common/ pneumon ias caused by, 560 in l eukemoid reaction, 361 Lipid A, 125
important, 579 sil ver sta i n , 1 20 Leukocyte esterase test, 169, 170 i n outer wall of Cram-negative
Late-l ook bias, 53 Legionella pnewnophila , 135. See Leukocyte extravasation, 215 bacteria, 1 18
Lateral area of hypothalamus, 414 also Legionnai res' disease Leukocytes, 344 Lipid-loweri ng agents, 281
Lateral arterial branch i ng i n C l antimicrobials for, 1 80 in chronic myeloproliferative L i p i ds
structures, 312 Cram stain l i mitation, 1 20 disorders, 366 free radical i n j u ry and, 215
Lateral cerebel lum treatment for, 575 differentiation, 344 Lipid sol u b i l i ty of anesthetics, 453
functions of, 41 5 Legionnaires' disease, 135. See smudged l ook, 573 Lipid transport, key enzymes, 1 15
Lateral condyle, 379 also Legionella pnewnophila urinary casts, 573 Lipodystrophy, i n H IV, 189
I .eiomyomas, 219, 529, 581 Leukocytosis Lipoid nephrosis. See M i nimal
Lateral corticospinal tract, 427, 428
Leiomyosarcomas, 219, 529 i n diabetic ketoacidosis, 303 ch ange disease
strokes i n , 422
Leishmania donova ni, 150 diverticulitis and, 329 L i polysis, 289
Lateral fol d closure fai l ur e , 308
Leishmaniasis, 1 50 Leukopenia cortisol effect on, 292
Lateral geniculate nuclei ( LC N ) , 415,
antimicrobials for, 1 86 i n aplastic anemia, 355 i n diabetes m e l l i tus, 302
440, 441
Lens, 437, 438 cytarabine as cause, 371 L i pomas, 219
Lateral medulla
Lens subl uxation, 109 trimcthoprim as cause, 182 Li popolysaccharicles. See
strokes in, 422
Lentiform nucleus, 416 Leukotrienes, 404 also Endotoxins
Lateral medullary syndrome, 422
Lepirudi n , 367 in basophils, 345 effect on macrophages, 201
Lateral meniscus, 379
Lepromatous l eprosy, 133 cortisol effect on, 292 i m mune response to, 198
Lateral pontine syndrome, 422
Leprosy, 133, 139 Leuprolicle, 539 Lipoprotei n functions, 1 16
Lateral rectus muscle
erythema noclosum and, 400 for infertil ity, 575 L ipoprotein l i pase ( L PL), 1 1 5, 1 16
crania I nerves and, 439
as granul omatous disease, 216 for prostate cancer/uterine Liposarcomas, 219
M LF syndrome and, 442
rifampin for, 1 83 fi broicls, 575 L ipoxygenase pathway, 404
Lateral striate artery Liquefactive necrosis, 212
Leptin Levator pal pebrae muscle
stroke effects, 422 Lisch nodules, 85
hypothalamus and, 414 innervation of, 434
Lateral ventricles, 426, 448 Leptomeni ngeal angiomatosis, 278 neurofibromatosis as cause, 566
Levator vel i palatini muscle
Law of Laplace, 544 Leptospira , 1 19, 137, 139 derivation of, 510 von Reckl inghausen's disease as
LC MV (lymphocytic Leptospira interrogans, 1 37 Levetiracetam cause, 446
choriomeningitis virus) , 1 58 Leptospirosis, 137, 139 for epilepsy, 451 Lisinopril , 502
LDL cholesterol Lesch-Nyhan syndrome, 66 LevoAoxaci n , 182 Lispro insul i n , 305
agents affecting, 281 c l i n i cal presentation, 567 Levothyroxine, 306 Listeria, 1 19, 121
estrogen effect on, 520 diagnostic findings/labs, 572 Lewy bodies, 416 meningitis caused by, 1 69
LDL receptor, 85, 1 1 5, 1 16 gout and, 391 diagnostic findi ngs/labs, 571 Listeria monocytogenes, 131
L-clopa/carbiclopa, 455, 456 Leser-Trelat sign, 397 Lewy body dementia, 443 actin rockets, 131
" L ,eacl pipe" appearance of colon, 572 Lesions Leydig cells, 517, 537 antimicrobials for, 177
Lead poisoning bra i n , 418, 419 in genital embryol ogy, 512 as -hemolytic bacteria, 1 28
in anemia algori thm, 358 facial , 437 i n Kl inefel ter's syndrom e, 524 L i th i u m , 474
antidote to, 239 geni tal , 567, 569 spermatogenesis and, 519 for bipolar disorder, 464, 472, 574
basoph i l i c stippling in, 350 nerve, 380 tumors of, 573 reactions to, 240, 241
clinical presentation, 566 ski n , 395, 396 L l-1 . See Lutei nizing hormone ( L l-1 ) for S lADl -1 , 576
diagnostic findings/labs, 570, 572 Lesser horn of hyoid Li bman-Sacks endocardi tis, 393, 577 as teratogen , 506
mechanism of, 353 derivation of, 510 Lichen planus, 401 therapeutic index (TI ) val ue, 229
Lead-time bias, 53 Lesser omentum, 310 c l i nical presentation, 569 Liver
Lecithinase, 130 Lesser sac, 310 Lidocaine, 283, 454, 574 anatomy of, 315
Leci th i n-chol esterol acyltransferase Letha I close, 229 Li-Fraumeni syndrome bl ood supply to, 312
( LCAT), 1 1 5 Leucovorin tumor suppressor genes, 221 eosi nop h i l ic cytopl asmic cell
Lecithins as methotrexate antidote, 371 Ligament of the ovary, 515 incl usions, 571
as pulmonary surfactant, 544 Leukemias, 364-365 Ligaments h istol ogy of, 3 1 5
Lecithin-to-sph ingomyel i n ratio, 544 acute lymphoblastic l eukem ia, 220 in female reproductive system , 515 hypoxia i n , 213
Lectin pathway for complement acute myeloid leukemi a , 220 gastroi n testinal , 310 i n farction, 213
activ<Jtion, 199 adult Tcel l l eukemia, 222 Ligamentum teres, 310 necrosis i n free radical i n j u ry, 215
Left anterior descending artery alkylating agents for, 372 Ligand-gated ion channels plasma markers of pathol ogy, 334
( LAD), 253 allopurinol for, 406 nicotinic ACh receptors as, 230 proportion of cardiac output, 264
Left gastric artery, 313 antimetabol ites for, 371 Light chain, of antibody, 1 97 tumors of, 335
Left gastro-omental artery, 313 carcinogens affecting, 223 Limbic system , 415 zones of, 315
I N DEX
Liver cancer, 223 , 335, 580 i n Barrett's esophagus, 325 Lupus nephropathy, 578 Hash i moto's thyroiditis and, 299
a-fetoprotein marker for, 222 G E R D and, 324 diagnostic findi ngs/labs, 573 Helicobacter {Jylori in, 222
associations, common/ Lower extremity nerves, 384 Luteal phase of menstrual cycle, 521 vs. leukemia, 361
important, 578, 580 Lower motor neuron lesions, 428 Lutei nizing hormone ( Ll l ) , 289 microtubule i n h i b i tors for, 373
Buclci-Ch iari syndrome and, 335 Brown-Sequarcl syndrome and, 430 disorders of, diagnosing, 524 oncogenes for, 221
carcinogens affecting, 223 c l i nical presentation, 567 ovulation and, 521 Lyse cell membranes, 125
cirrhosis and, 333 of facia I nerve, 437 in polycystic ovarian syndrome, 530 Lysogeny, specia l i zed
diseases associated with , 220 in pol iomyel itis, 430 secretion of, 287 transduction, 126
hemochromatosis as cause, 337 in Werclnig-1 -l offman disease, 430 signal ing pathway, 294 Lysosomal a- 1 ,4-gl ucosiclase (acid
metastases to, 224, 579 Lower quanclrantic anopia, 441 Lye ingestion mal tase) , 1 1 1
oncogenic microbes in, 222 LPS endotox in , 135 esophageal strictures caused Lysosomal storage diseases, 1 12
polycyth emia and, 366 LSD by, 324 associations, common/
serum markers for, 334 i n toxication and wi thdrawa l , 471 Lyme disease, 137, 175 important, 579
i n Wilson's disease, 337 L T B+ antimicrobials for, 1 80 Lysosomal trafficking regulator
Liver cell fai l ure, 333 in l eukocyte extravasation, 215 atrioventricular bl ock caused gene, 207
Liver disease Lumbar puncture, 379 by, 263 Lysosomes, 75
acanthocytes in, 350 bloody tap, 570 Borrelia bu rgdorferi as cause, 139 Lyssavin1s
alcohol ic, 334 l ocation of, 427 c l i nical presentation, 568 diagnostic findi ngs/labs, 571
in anemia algorith m , 354 Lumbar spinal nerves, 427 facial nerve palsy i n , 437 LYST gene, 207
associations, common/ Lumbrical muscles of the hand, 383 Lymphadenopathy, 172 Lytic bone lesions, 224, 572
i mportant, 579 distortions of, 383 phenytoin as cause, 452 in Langerhans cell
dosage calculations with, 227 "Lumpy-bumpy" glomeru l i , 492, 572 region-specific, causes of, 160 h i stiocytosis, 366
serum markers for, 334 Lung abscesses, 560 Sezary syndrome as cause, 567 in multiple myeloma, 363
target cells in, 351 Lung cancer, 558-559 Lymphangiosarcoma, 278 Lytic phages, 126
Liver enzymes, 334 bombesin marker for, 222 Lymphatic drainage of gonads, 514
Liver toxicity carcinogens affecting, 223 Lymphatic pleural effusions, 561 M
acetaminophen as cause, 405 cisplati n/carbopl atin for, 373 Lymphatics, 316 MacConkey's agar, 1 20, 134
carbamazepi n e as cause, 452 incidence and mortal i ty, 224 Lymphedema " Mach i nery" h eart murmur
Liver transplants lytic bone l esions i n , 224 in Turner syndrome, 569 diseases causing, 566
rej ection, 208 oncogene for, 221 Lymph nodes, 192 Macroangiopath i c anemia, 357
Live vaccines, 153, 202 smal l cel l , 223 , 580 drainage sites, 192 Macrocytic anemia
Living will (written advance squamous cel l , 223 T cells in, 195 algorith m to, 354
directive), 57 Lung disease Lymphoblasts M acrol i cles, 1 80
L-myc gene, 221 respi ratory acidosis caused by, 488 in l eukemias, 364 mechanism of action, 176
Loading close, 227, 582 Lung relations, 545 Lymphocytes, 346. See a lso B cells; as P-4 5 0 i n h i b i tor, 242
Loa loa, 151 Lungs T cells protein syn thesis i n h i b i tion by, 73
Lobar pneumon ia, 560 autoregulation, 265 antibody structure and M acroorc h i clism, 87
Lobes and chest wal l , 547 function, 197 Macro-oval ocytes, 350
of bra i n, 418 infarction, 213 antigen type and memory, 198 Macrophages, 193 , 345
Lobu lar carcinoma, 533 l obes of, 545 atypical, in Epstein-Barr virus, 1 57 an tibody b indi ng, 197
Lobules, 533 physical findings, 557 I I L A subtypes associated with cytokines secreted by, 200
Local anesthetics, 454 physiologic dead space i n , 546 diseases, 1 94 endotoxin effect o n , 201
Lockjaw (trismus), 130 V/Q mismatch i n , 551 immunoglobu l i n i sotypcs, 198 i n granulomatous disease, 216
Locus ceruleus Lung vol umes, 546 innate vs. adaptive immunity, 193 i n spl een, 193
norepinephrine synthesis, 413 Lupus, 393. See a lso SLE-I ike MHC I and II, 194 surface proteins, 201
Locus heterogeneity, 82 syndrome natural kil ler cells, 194 in T- and B-cell activation, 196
LofAer's media, 120 associations, common/ i n urinary casts, 489, 495 in wound heal i ng, 216
LofAer's syndrome important, 577 Lymphogranuloma venereum, 141 Macrovesicular steatosis, 334
cardiomyopathy caused by, 272 autoantibodies associated with, 205 clinical presentation, 173 Macula, 441
Lomustine, 372 c l i nical presentation, 566 Lymphoid cells Macula aclherens, 379
I .one Star tick, 139 constrictive pericarditis and, 577 "starry sky" appearance, 573 Macula clensa, 479, 485
Long thoracic nerve, 383 death, cause of, 578 Lymphoid hyperplasia Macular degeneration
Loop di uretics, 499, 500 diagnostic findi ngs/labs, 570 appendicitis caused by, 329 age-related (AR M D ) , 441
reactions to, 241 diffuse prol iferative Lymphoid neoplasms, 364 central scotoma as sequela, 441
Loop of Henle, 483 , 499 glomerulonephritis caused Lymphoid structures Macules, 395
Lopinavir, 189 by, 492 lymph nodes, 192 Magnesium
Loratacline, 562 endocarditis and, 274 sinusoids of spl een, 1 93 as antiarrhythm i c , 284
Lorazepa m , 453 erythrocyte sedimentation rate thymus, 193 deficiency, reasons for, 293
for epilepsy, 451 i n , 217 Lymphomas. See also Burki tt's disturbances i n , 487
Loss of orientation, 461 H L A- D R2 and, 194 lymph oma; H odgkin's PTH and, 293
Lou Gehrig's disease . 1-1 L A-DIU and, 578 lymphoma; non-J -I oclgki n 's reabsorption of, 483
See Amyotrophic lateral as hypersensitivity disorder, 204 lymphoma Magnesium ci trate, 342
sclerosis (ALS) membranous glomeru l onephritis alkyl ating agents for, 372 Magnesium hydroxide, 341 , 342
Lovastati n , 281 caused by, 490 allopur i n ol for, 406 Magnes i u m sulfate
Low birth weight, 59 microangiopath ic anemia i n , 357 antimetabol ites for, 371 for pregnancy-i n clucecl
Low-density l i poprotein. See L D L Raynaud's phenomenon in, 276 associations, common/ hypertension, 526
cholesterol sn RNP antibodies in, 71 important, 580 Main pancreatic duct, 316
Liiwenstein-Jensen agar, 120 Lupus-l ike syndrome diseases associated with, 220 Maintenance close, 227, 582
Lower esophageal sph i ncter ( L E S ) hydralazine as cause, 279 doxorubicin for, 372 Mai ntenance phase of addiction
achalasia a n d , 324 phenytoin as cause, 452 etoposicle/teni posicle for, 373 recovery, 470
I N DEX
M ajor apol i poproteins, 1 1 5 Mandibular l i gament M ean M eAoquine, 186

Major depressive disorder, 464, 465 derivation of, 510 in normal distri butions, 55 for malaria, 575
electroconvulsive therapy for, 466 Mania, 464 statistical tests of, 55 for Plasmodi u m , 149
tricyc l i c antidepressants for, 475 atypical antipsychotics for, 473 Mean arterial pressure ( MA P ) , 253 M egakaryocytes
Major h istocompati b i l i ty complex. M a n n i to l , 499, 500 equation for, 582 in idiopath i c thrombocytopenic
See M I- I C I and M H C l l Mantle cell lymphoma, 362 Measles. See Rubeola ( m easles) viru s purpura ( ITP), 359
Major papilla, 309 c h romosomal translocation acute disseminated platel ets and, 344
Malabsorption syndromes, 90, 93, 326 with, 365 encephalomye l i t i s and, 445 M egal oblastic anemia, 65, 352, 354
Croh n's disease and, 328 MAO-B i n h i bitor, 456 cl i nical presentation, 567, 569 cytarabine as cause, 371
0-xylose test for, 322 MAO i n h i b i tors, 474, 475. M ebendazole/th iabendazol e, 76, 1 86 diagnostic findings/labs, 572
pancreatic adenocarcinoma See Monoamine oxidase " Mechanic's hands," 394 as drug reactio n , 240
and, 340 i n h i b i tors Meckel 's cartilage macro-oval ocytes i n , 350
Malaria, 149 for anxiety, 472 derivation of, 510 phenytoin as cause, 452
anemia caused by, 357 for atypical depression, 465 Meckel 's divertic u l u m , 329, 330, 508 Meigs' syn drome, 532
sickle cell anemia and, 356 Maple syrup urine disease, 109 M econ i u m i l eus, 86, 331 M eissner's corpuscles, 412
treatment for, 575 M aproti l i n e , 474, 476 M edial cerebell u m M eissner's plexus, 31 1
Malar rash Marasmus, 96 functions of, 4 1 5 l l i rschsprung's disease and, 330
in dermatomyositis, 394 M arble bone disease, 387 Medial col lateral l i gament ( M C L ) !Vlelanocytes
in l upus, 393 Marburg h e morrhagic fever, 158 in unhappy triad i n j u ry, 379 in pigmented ski n disorders, 396
Malassezia furfu r, 144 Marcus Cunn pupil, 440 Medial condyl e, 379 Melanocytic n evus, 397
Male cancer Marfanoid habitus, 82, 304 Medial geniculate nucleus Melanomas, 220
associations, common/ M arfan's syndrome, 79, 82, 85 ( M G N) , 415 diseases associated with, 220
important, 579 aneurysms and, 268, 576 Medial hypertrophy hydroxyurea for, 373
Male/female gen ital homologues, 513 aortic dissection and, 268 mal ignant, 210
pulmonary hypertension as
Male genitals S- 1 00 marker for, 222
Berry aneurysms and, 423 cause, 549
embryology, 512 of ski n, 403
cardiac defects associated with, 267 M edial lemniscus, 415
female homologues, 513 tumor suppressor genes, 221
c l i nical presentation, 566 strokes i n , 422
Male-pattern baldness Melanotrop in ( M S H )
subarachnoid hemorrhage and, 424 Medial longitudinal fasciculus ( M LF)
fi nasteride for, 539 secretion of, 287
Marijuana effects of lesion i n , 442
Male pseudohermaphrodi tes, 524 signaling pathway, 294
gynecomastia caused by, 535 Medial medullary syndrome, 422
Male reproductive anatomy, 515 Melarsoprol , 1 86
i n toxication and withdrawal, 471 Medial meniscus
Malformation in organ for Trypanosoma, 148
sch i zophrenia and, 463 in un happy triad i n j u ry, 379
morphogenesis, 505 Melasma, 396
M ascu l i nization Medial nucle i , 415
Mal ignant breast tumors, 534 M elaton in
adrenal enzyme deficiency as M edial pterygoi d muscle, 437
Mal igmnt hypertension secretion of, 433
cause, 291 derivation of, 510
microangiopath ic anemia in, 357 Melena
" Mask of pregnancy," 396 Medial rectus muscle
RBC urinary casts in, 489 Meckel 's diverticulum as
M asseter muscle, 437 cranial nerves and, 442
treatment for, 279 cause, 330
derivation of, 510 M LF syndrome and, 442
Mal ignant hyperthermia portal hypertension as cause, 333
Mast cells, 346 Medial temporal l obe Memantine, 456
anesthetics as cause, 453
antibody binding of, 198 seizures in, 445 Membrane attack complex
dantrolene for, 455
degranulation, eosinoph i l s and, 345 Medial umbil ical l igaments, 317 ( MAC ), 1 97
treatment for, 575
Mastication muscles, 437 Median claw, 383 Membrane, cel l . See Cell membrane
Mal ignan t lym phomas
Mastitis, 533 Median, i n normal distributions, 54 Membranoprol i ferative
diseases associated with, 220
acute, 535 M edian nerve, 382 glomeruloneph ritis
Mal ignant melanoma
recombinant cytokines for, 210 MAST treatment for asth ma, 235 in carpal tunnel syndrome, 379 ( M PG N ) , 491 , 573
Mal ignant tumors, 219 "the Match ," 26, 32-35 course of, 380 Membranous glomerular
Mali ngering, 467 Maternal "blues," 465 lesion of, 383 disorders, 489
Mall eus Maternal component of placental Mediastinal mass Membranous glomerulonephritis
derivation of, 510 deve l opment, 508 acute lymphoblastic leukemia diagnostic findings/labs, 573
Mallory bodies, 334 Maternal-fetal mic roorganism as, 364 in lupus, 393
diagnostic findings/labs, 571 transmission . See ToRC H e S Medicai d vs. Medicare, 56 Membranous neph ropathy, 490
Mallory-Weiss syndrome, 324, 472 i n fections Medroxyprogesterone Membranous oss i fi cation, 386
clinical presentation, 570 M aternal PKU, 108 for polycystic ovarian M e mbranous urethra, 479
Mal nutrition , 96 Mature ego defenses, 459 syndrome, 530 M e mbranous ventri cular septum , 250
"Maltese cross" in blood smear Mature teratomas, 531 Medulla, 433 Memory. See a lso Alzheimer's disease;
test, 149 Maxilla ry artery cranial nerve nuclei i n , 434 Amnesia
MAlT lymphoma development of, 509 decussation i n , 428 l i m b i c system and, 415
type B gastritis and, 327 Maxil lary nerve, 436 development of, 408 Memory, i m munologic.
Maltose MCA. See Middle cerebral artery Medulla (adrenal ) , 286 See I mmunologic memory
carbohydrate digestion and, 322 McArdle's disease, I l l innervation of, 230 M E N . See Multiple endocrine
Mammary gland cysts, 572 c l i nical presentation, 566 tumors of, 297 neoplasia
Mamm i l lary bodies, 415, 432 M c Burney's point, 329, 379 Medulla ( lymph node) , 192, 193 Menetrier's disease, 327
amnesia and, 461 M c B u rn ey's sign Medulla ( renal ) , 479, 499 M e n iere's disease
atrophy, common associations c l i n i cal presentation, 569 Medul lary breast tumors, 534 peri pheral vertigo caused by, 446
with , 577 McCune-Al bright syndrome, 388 Medullary cords of lymph node, 192 M e n i ngiomas, 447, 577
l esions i n , 419 c l inical presentation, 566 Medullary cystic disease, 498 diagnostic findings/labs, 573
necrosis of, caused by M cells Medul l a ry pyramids, 479 Psammoma bodies i n , 223
alcoh ol ism , 472 i n Peyer's patches, 323 Medullary thyroid carci noma, 299 Meni ngitis
Mandibles M C L. See Medial col lateral l igament in MEN 2A, 304 age groups, common causes by, 1 69
derivation of, 510 (MCL) Medulloblastomas, 448, 577, 579 antimi crobials for, 181
I N DEX
Meningitis (C011timwd) M esometrium, 515 Methotrexate, 65, 370, 371 M i c rocytosis

aseptic, causes of, 158, 1 59 M esonephric duct, 512 elimination of, 228 in -thalasse m i a , 353
Coccidioidomycosis as cause, 143 Mesonephros, 478 folate deficiency and, 354 eryth rocyte sed i m e n tation rate
cryptococcal , 145, 185 M esosalpinx, 515 for hydatidiform moles, 525 and, 349
CSF findings, 169 M esothe l i omas, 559 reactions to, 240 in i ron deficiency, 352
funga l , antimicrobials for, 185 carcinogens affecting, 223 for rheumatoid arthritis, 390 M i crogl ia, 41 1
Haemophilus influenzae as diagnostic findi ngs/labs, 573 toxicities, 375 M i crohematuria
cause, 134 Psammoma bodies i n , 223 MethoxyA urane, 453 sickl e cel l anemia as cause, 356
headaches caused by, 446 Mesothel i u m , 31 1 Methylation, 64 M i c roorganism h i n ts, 175
HIV-associated, 166 M esovarium, 515 Methyldopa M i crosate l l i te i nstab i l i ty pathway
hydrocephal us as sequela of, 426 Mestranol, 539 reactions to, 240 i n col orectal cancer, 332
Listeria monocytogenes as Meta-analysis, 55 Methylene blue, 547 M icroscopic c i rrhosis, 333
cause, 1 28, 131 M etabol ic acidosis, 487, 488 as antidote, 239 M i c roscopic polyangi itis, 277, 492
microorganisms causing, 169 aspirin as cause, 368 Methyl malonic acid diagnostic fi ndi ngs/labs, 570
picornavirus as cause, 1 59 renal fai l ur e as cause, 497 vitamin B 1 2 deficiency and, 354 M i c rosomal triglyceride transfer
prophylaxis for, 183, 1 84 M etabol ic alkalosis, 487, 488 Methylphenidate protein ( MTP) gene, 1 16
Streptococcus agalactiae as acetazolamide for, 500 for ADl-1 0, 460, 472, 574 Microsporum , 144
cause, 1 29 Conn's syndrome as cause, 567 as C N S stimulant, 472 M icrosurgcry
Streptococcus pnewnoniae as hyperaldosteronism as cause, 296 Methylxan th ines, 563 of peripheral nerves, 412
cause, 128 th i azide di uretics and, 501 for asth ma, 563 M icrotubule, 76
in unimmunized c h i ldren, 174 Metabol ic enzymes, 97 Metoclopramide, 342 M icrotubule i n h i b i tors, 373
vaccines for, 1 22 Metabol ic fuel use, 1 14 reactions to, 241 M icrovi l l i
Meningocele, 409 Metabol ic pathways, 98 Mctoprolol, 238 i n digestive tract, 31 1
Meni ngococcemia Metabol ism as antiarrhythmic, 284 M i dazol am, 453
clinical presentation, 566 drug, 228 Metronidazole, 182 as i n travenous anesthetic, 454
Meni ngoencephal itis heme, 323 for Clostridium diflicile, 130, 574 M idbra i n
Naegleria fowleri as cause, 148 Metabol ism sites, 96 for Entamoeba h istolytica , 147 cranial nerve nuclei i n , 434
M eningomyelocele, 409 Metachromatic l eukodystrophy, 1 12, for Giardia , 147 development of, 408
Menometrorrhagia, 521 445 for Gardnerella vagina/is, 139 M i d d l e cerebe l l ar peduncle, 432, 433
Menopause, 523 Metalloproteinases, 218 for 1 -/elicobacter pylori, 137 strokes i n , 422
early, caused by Turner M etamyelocytes mechanism of action , 176 Middle cerebral a rtery ( M CA), 420
syndrome, 524 in chronic myelogenous reactions to, 241 effects of stroke on vision, 422, 441
hormone replacement therapy leukemia, 365 for Trichomonas vagilwlis, 1 50, 576 M iddle cranial fossa
for, 540 Metanephric mesenchyme, 478 Metrorrhagia, 521 cranial nerve pathways i n , 435
Menorrhagia M etanephros, 478 Metyrosine M i d d l e meningeal a rtery
endometriosis as cause, 528 Metaphase, 74 mechanism, 232 epidural h e matoma i n , 424
Menstrual cycle, 521 Metaplasia, 219 Mexiletine pathway in sku l l , 435
abnormal , 521 Metaplastic columnar for arrhyth mia, 283 , 574 rupture of, 578
endometriosis and, 528 epithel i u m , 325 Meyer's loop, 441 M i dgut
Mental retardation Metaproterenol MCUS, 363 blood supply, 312
associations, common/ c l inical use, 235 M H C I and M H C I I , 194 development of, 308
i mportant, 579 M etastases, 218 B cells and, 346 M i fepristone, 540
Lesch-Nyhan syndrome as to bone, 222, 224 dendritic cells and, 346 for abortio n , 575
cause, 567 to bra i n , 224 macrophages and, 345 M igl i tol, 305
in Rett's disorder, 461 common/important, 579 T cells and, 347 M igra i n e headaches, 446
Sturge-Weber syndrome as to l iver, 224 toxins affecting, 125 drugs for, 451
cause, 446 of lung cancer, 558 M I . See Myocardial i n farction sumatriptan for, 456
teratogens causi ng, 506 to heart, 275 Michael is-Menten kinetics, 226 treatment for, 575
tuberous sclerosis as cause, 446 Metastatic calcifications M iconazol e, 185 M igrating motor compl exes ( M MCs)
Wil ms' tumor and, 494 phosphate as cause, 487 for Tinea versicolor, 1 44 moti l i n and, 319
Meperidine, 449 Metastatic melanoma M icroangiopath ic anemia M i gration (leukocyte
Mepivaca ine, 454 vemurafenib for, 374 i n anemia algorith m , 357 extravasation), 215
6-mercaptopurine (6-M P), 65 Metencephalon, 408 thromboti c thrombocytopenic M i gratory polyarth ritis
Mercury poisoning Metformi n , 305 purpura as cause, 359 Crohn 's disease and, 328
antidote to, 239 M ethachol ine, 233, 564 Microarrays, 80 M igratory thrombophlebitis, 340
Merkel's disks, 412 asthma test with, 554 M icrobiology M il estones of development, 59
Merl i n protein, 221 M ethadone, 449, 471 antimicrobials, 176- 190 M i l k i n tolerance. See Lactase
Meropenem, 178 for opioid dependence, 470 bacteriology, 1 27- 141 deficiency
Mesencephalon, 408 Methanol i n toxication c l i nical bacteriology, 1 18-126 M ineralocorticoids, 291
Mesenchymal tumors, 219 treatment for, 239, 575 hosts, 137 M ineral/vitamin absorption, 322
Mesenteric adenitis Methemoglobin mycology, 143-146 M i nimal alveolar concentration
similarity to appendicitis, 167 antidote to, 239 parasitology, 147- 151 (l'vlAC ) , 453
Yersinia en terocolitica as cause, 136 Methemoglobinemia, 547 reservoirs, 136 M i nimal change disease, 489, 490, 579
Mesenteric arteries, 312 Meth ici l l i n systems, 1 67-175 diagnostic findings/labs, 573
Mesenteric lymph nodes, 192 mechanism o f action, 176 virology, 1 53-166 M i nocycl ine, 1 80
Mesenteric nodes reactions to, 241 M icrocephaly as meningococcal prophylaxis, 1 84
in Wh ipple's disease, 326 Meth i c i l l i n-resistant S. au reus. teratogens causing, 506 M i nor pap i l l a , 309
Mesentery, 31 1 See M RSA trisomy 1 8 as cause, 568 M i nor patients, 56
Mesna Meth i mazol e, 295, 306 M icrocytic anemia, 352-353, 572 M i osis, 231 , 440
for hemorrhagic cystitis, 575 reactions to, 240 algorithm to, 352 H o rn e r's syndrome as cause, 431 ,
M esoderm, 505 M eth ionine, 70, 93 lead poisoning as cause, 358 569
I ND E X
M i rtazapine, 237, 474, 476 Monozygotic twins, 507 M ucosal spots Aexor pol l icis brevis, 383
M iscarriage Monte I u kast, 563 Kopl ik spots as, 569 infraspi natus, 379
bicornuate uterus as cause, 512 Mood disorders, 464 M ucositis opponens digiti m i n i m i , 383
M ismatch repair, 64, 69 Mood stab i l i zers, 472 in l upus, 393 opponens pol licis, 383
M i soprostol , 321 , 340, 341 Moon facies methotrexate as cause, 371 respi ratory, 546
Missense DNA mutations, 67 i n Cush ing's syndrome, 296, 306 Mucus subscapularis, 379
M i tochondria, 96 Morbillivirus secretion of, 321 supinator, 382
autoantibodies targeting, 205 c l i n i cal presentation, 567 "Muddy brown " casts i n acute tubular suprasp i natus, 379
high altitude effects on, 552 M oro reAex, 59, 432 necrosis, 496 teres mi nor, 379
inheritance of, 84, 579 Morp h i n e , 449 M U l l erian duct, 512 triceps, 382
myopath ies of, 84 as i n travenous anesthetic, 454 Multicystic dysplastic kidney, 478 M uscles of masticatio n , 434, 437
M i tosis, 74 receptor bindi ng, 229 M u lti-infarct dementia, 443 Muscle tone
M itral regurgitation, 259, 579 Morphogenesis Multinodular goiter, 299 changes i n , as motor neuron
heart murmur with, 258 errors i n , 505 Multiple endocri ne neopl asia, 85, 304 sign, 428
in rheumatic fever, 274 Mortal i ty of common cancers, 224 M I N I , 568 Muscular dystrophy, 86
tuberous sclerosis as cause, 446 Mosaic bone patte rn , 387 MEN 2A, 570 c l i n i cal presentation , 566, 569
M i tral stenosis, 259, 579 Mosaicism, 82 MEN 2 B, 82, 570 Muscularis externa, 31 1
associations, common/ Mosqu i toes as disease vectors, 149, oncogenes for, 221 Muscularis mucosae, 31 1
i mportant, 579 151 , 1 59 Zol l i nger E l l ison syndrome Muscular ventricular septu m , 250
heart murmur with, 258 M ossy fibers, 41 5 and, 304 Musculocutaneous nerve, 382
pulmonary hypertension caused Motil i n , 319 Multiple myeloma, l6l, 580 Musculoskeletal system
by, 549 Motion sickness amyloidosis and, 490 anatomy and physiol ogy, 378-386
in rheumatic fever, 274 H 1 blockers for, 562 diagnostic signs/labs, 572 drug reactions i n , 241
M i tral valve, 256 medications for, 234 M G U S as precursor, 363 pathol ogy, 387-403
M itral valve prolapse, 85, 259, 578 M otor cortex, 41 5, 416, 418 as plasma cell cancer, 346 pharmacol ogy, 404-406
ADPKD and, 498 Multiple personal ity disorder. M u tagenic antimicrobials, 190
face area, 437
M i ttelschmerz, 521 See D i ssociative identity
strokes i n , 422 Mutations i n D NA, 67
Mivacurium, 455 disorder
Motor i m pa i rment MVP. See M i tral valve prolapse
M ixed amphetamine salts Multiple sclerosis, 444
in ADI -ID, 460 Myasthenia gravis, 394
as CN S stimulant, 472 clinical presentation, 568
Motor n e uron signs, 428 edrophon i u m challenge test
M ixed connective tissue disease demye l i nating disease and, 578
Movement disorders, 417 for, 233
autoantibodies associ<Jted with, 205 H L A-DR2 and, 1 94
MoxiAoxac i n , 1 82 as hypersensitivity disorder, 204
Mixed motor neuron disease as hypersensitivity disorder, 204
M PG N . See Membranoprol iferative medications for, 233
associations, common/ ol igodendrogl ia i n , 412
glomeru l onephritis ( M PG ) as restrictive l un g disease, 555
important, 579 recombinant cytokines for, 210
M prote i n , 122 Mycobacteria, 1 19, 121 , Ill
M ixed platelet and coagulation spinal cord lesions, 429
spike i n multiple myeloma, 363 anti m i crobials for, 183
disorders, l60 treatment for, 575
MRI Gram sta i n l imitation, 120
M L F syndrome, 442 Multivitamins
multiple sclerosis diagnosis, 444 Mycobacterium aviwn-
multiple sclerosis as cause, 444 macular degeneration and, 441
M RNA, 70, 71 , 72 intracell ulare, 132
M M R vaccine, 1 53 Mumps, 158, 1 60, 161
M RSA anti m i crobials for, 1 83
Mob i tz type I and 1 1 atrioventricular acute pancreatitis caused by, 339
as cause of nosocomial and Mycobacterium kansasii, 132
bl ocks, 262 serum markers for, 334
community-acqu i red Mycobacterium leprae, 133, 139
Modafinil vaccine for, 202
i n fections, 128 Munchausen's and Munchausen's by anti m i crobials for, 1 83
for narcolepsy, 62
treatment for, 575 proxy syndromes, 467 as granulomatous disease, 216
as P-4 5 0 inducer, 242
vancomyc i n for, 179, 1 84 Mu opioid receptor, 449 Mycobacterium tu bercu losis, 121 , 132.
Mode, in normal distributions, 54
M S H . See Melanotropi n Murmurs. See H eart murmurs See also Tuberculosis
Modes of inheritance, 84
Molecular motor proteins, 76 M 3 receptor, 321 Muromonab-C D 3 , 209 antimicrobials for, 1 83
Molecular pathenogenesis of mTO R i n h i b i tor, 209 as immunosuppressant, 208 culturing, 1 20
C RC , 3l2 MTX, 92 as therapeutic antibody, 210 as granulomatous disease, 216
Moles, 397 Mucicarm i n e , 120 M urphy's sign, 339 as obl igate aerobe, 121
as papules, 395 Mucinous cystadenocarci nomas, 532 Muscari nic antagonists, 2l4, 340, 563 osteomyel itis caused by, 169
Moll uscum contagiosum, 155 M u cinous cystadenomas, 532 for asth ma, 563 prophylaxis for, 183
Monckeberg arteriosclerosis, 267 Mucins for multiple sclerosis, 444 rifampin for, 1 83
Monoamine oxidase i n h i b i tors. i n sal iva , 320 M uscarinic receptors, 230 treatment for, 575
See MAO i n h i b i tors M ucoepidermoid carcinoma, 324 antipsychotic effects on, 473 Mycology, 143- 1 46. See also Fungi
phentolamine and, 237 Mucopolysaccharidoses, 1 12 Muscle conduction to myc oncogenes, 558
Monoclonal gammopathy of Mucor, 145, 175 contraction , 385 Mycop lasma, 1 19
undetermined sign i fi cance antim icrobials for, 185 M uscle contraction, 385 G ram sta in l i m i tation, 120
( M C U S ) , 363 . See M C U S Mucormycosis, 145 of skeletal/cardiac muscle, 386 pncumonias caused by, 560
Monocytes, l45 diabetic ketoacidosis and, 303 Muscle fi bers, l85 Mycoplasma pnewnoniae, 142, 1 68
Mononuclear cells M u cosa Muscles anemia triggered by, 357
in chronic inAammation, 214 bleeding of, 568 abductor digiti m i n i m i , 383 antimicrobials for, 1 80
Mononucleosis cobblestone, 328 abductor pol l icis brevis, 383 cul hning, 120
anemia triggered by, 357 gastrointesti nal , 31 1 biceps, 382 e rythema multi forme caused
c l inical presentation, 568 hormones produced by, 319 brachial is, 382 by, 399
diagnostic findi ngs/labs, 572 necrosis of, 331 brach i oradialis, 382 Mycoses
herpesvirus as cause, 155, 1 56, 1 57 M ucosal cells cardiac, 260 antimi crob ials for, 185
Monosaccharides HC03 produced by, 320 coracobrac h i a l i s , 382 cutaneous, 144
carbohydrate digestion and, 322 M ucosal pseudopolyps deltoid, 382 systemic, 14l
Monospot test, 157 in ulcerative col itis, 328 Aexor digiti m i n i m i , 383 Mycosis fungoides, 362
I NDEX
Mydriasis, 231 , 440 NAD H , 102, 1 13 Negative symptoms of neuroendoc r i n e , 558

epinephrine as cause, 449 NAD P I- 1 , 104 i n sch izophrenia, 463 i n non- 1 -i odgk i n 's l ymphoma, 362
medications causing, 234 A D P I I oxidase, 103 Neglect of c h i l dren, 460 eoplastic progressi o n , 218
Myelencephalon, 408 NAD PI- I oxidase deficiency. Negri bodies, 162 Neostigmi n e , 233
Myel i n , 41 1 See C h ronic granulomatous of rabies, 571 as antidote for neuromuscular
Myel inated nerve fibers, 412 disease Neisseria, 1 19, 121 blocking drugs, 455
Myelofibrosis, 366 Naegleria fowleri, 148 antimicrobials for, 178, 1 82 Nephritic syndrome, 492
teardrop cells i n , 351 Nafci l l i n , 177 C 5-C9 deficiencies and, 200 in glomeru l a r diseases, 489
Myeloid neoplasms, 365 for Staphylococcus aureus, 576 genetic transformation , 126 Nephritis
Myeloid stem cells N a l-IC0 3 l gA protease secretion, 122 AI port syndrome as cause, 567
in aplastic anemia, 355 as antidote, 239 as i m munodeficiency asp i r i n as cause, 368, 404
Myelomeningocele Nail-bed hemorrhage, 274 i n fection, 205 i n terstitial, causes of, 181
Chiari II malformation and, 409 Naked viral genome infectivity, 154 Neisseria gonorrhoeae, 134, 173. See loop diuretics as cause, 500
Myel osuppression Naked viruses, 1 54 also Gonorrhea l upus as cause, 393
antitumor antibiotics as cause, 372 Nal idixic acid, 1 82 culturi ng, 1 20 N SA I Ds for, 405
etoposide/teniposide as cause, 373 Naloxone Gram staini ng, 133 Neph roblastoma. See Wilms' tumor
methotrexate as cause, 371 as antidote, 239 infectious arthritis caused by, 392 Neph rogenesis, 478
microtubule inhibitors as cause, 373 for opioid toxicity, 449, 470 osteomyelitis caused by, 1 69 Nephrogenic diabetes insipi dus, 301
Myenteric plexus, 31 1 Naloxone + buprenorphine, 471 pelvic inAammatory disease caused hydrochl oroth iazide for, 501
achalasia and, 324 Naltrexone by, 173, 580 l i th i u m as cause, 474
Mylohyoid muscle as antidote, 239 treatment for, 575 treatment for, 306
derivation of, 510 for opioid toxicity, 449, 470 Neisseria meningitidis, 134 Neph rol ithiasis
Myocardial infarction , 213, 269 Naphthalene anti m icrobials for, 181 cell atrophy i n , 214
-blockers for, 238 as carcinogen , 223 anti phagocytic factor, 121 N eph ron physiology, 483
compl ications of, 271 Naproxen, 405 bacterial meningitis and, 577 Nephropathy
diagnosis of, 271 for gout, 406 culturing, 120 i n diabetes mell i tus, 302
ECG indicators, 261 , 269, 271 Narcissistic personal ity disorder, 468 Gram stai n i ng, 133 Nephrosis
evolution of, 270 Narcolepsy, 62 as immunodeficiency diagnostic findings/labs, 573
heparin for, 367 medications for, 235 infection, 205 Nephrotic syndrome , 490-491
symptoms of, 270 sti mulants for, 472 meningitis caused by, 1 69 associations, common/
th rombolytics for, 368 Narrow-angl e glaucoma, 439 treatment for, 575 i mportant, 579
types of infarcts, 271 Nasal decongestants, 235 Waterhouse-Friderichsen charge barrier i n , 480
Myocarditis Nasal Aora, 1 67 syndrome caused by, 134, 297 D I C as cause, 360
associations, common/important, 579 Nasal polyps, 86 Nematodes ( roundworms), 1 51 fatty urinary casts i n , 489
causes of, 158 asocil ia ry branch, of trigeminal Neomycin, 180 in glomerular diseases, 489
Myoclonic seiwres, 445 nerve, 434 Neonatal hyperb i l i rubinemia, 336 h yperaldosteronism caused
drugs for, 451 Nasopharyngeal carcinoma Neonatal jaundice, 335 by, 296
Myoclonus, 417 E BV vi rus in, 222 Neonatal respi ratory distress pleural effusions caused by, 561
in Creutzfeldt-j akob disease, 443 h erpesvirus as cause, 1 56, 157 syndrome, 555 treatment of, 500
S S Ris as cause, 475 Natal izumab as restrictive l ung disease, 555 Neph rotoxicity, 241
Myocytes, cardiac, 260 for multiple sclerosis, 444, 575 Neonatol ogy anesthetics as cause, 453
Myofibroblasts National Board of M edical Examiners APGAR score, 59 cisplatin/carboplatin as cause, 373
in wound heal ing, 216 ( N B M E ) , 2, 23 early developmental, 59 N e rves
Myoglobinuria National Residency Matching low birth weight, 59 c ranial, 432, 434, 435, 436
acute tubular necrosis and, 496 Program, 26, 32-35 reA exes of th e neonate, 59 of extraocular muscles, 439
diseases associated with , 566 Native American origin Neoplasia, 218-224, 219 l esions of, 380
Myometrial tumors, 529 gal lstones and, 339 benign vs. mal ignant tumors, 220 of lower extremities, 384
Myometrium Natural killer cells, 193, 194 cachexia, 220 myel i nated fibers, 412
placental attachment to, 526 surface protei ns, 201 cancer epidemiology, 224 spinal , 427, 431
Myonecrosis, 168 N E . See Norepi neph rine ( N E ) chemical carcinogens, 223 unmyel inated fibers, 412
toxins causi ng, 125, 130 N e a r vision , 438 definitions of, 219 of upper extrem i ties, 382
Myopathies Necator, 152 disease conditions associated Nervous system , 230
as drug reaction, 241 Necator america nus, 151 with , 220 Net fi ltration pressure equation, 582
Pompe's disease as cause, 568 Necrosis, 212 headaches caused by, 446 N e ural c rest, 505
Myopia coagulative, 270 metastases, 224 1-1 i rschsprung's disease and, 330
retinal detachment risk and, 441 intestinal adhesions and, 331 neoplastic progression, 218 migration of, 250
M yos in of l iver, free radicals and, 215 oncogenes, 221 origins of, 41 1
in muscle contraction, 385 rena l , 496 oncogenic microbes, 222 Schwa11 1 1 cell production, 412
Myositis ossificans, 394 Necrotizing enterocolitis, 59, 331 para neoplastic effects of Neural c rest cells, 1 08
Myxedema, 298, 299 Necrotizing fasciitis, 402 tumors, 223 formation of, 408
c l i nical presentation, 566 Necrotizing glomerulonephritis psammoma bodies, 223 Neural development, 408
treatments for, 306 diseases causi ng, 568 renal fai l ur e caused by, 496 Neural muscarinic pathways
Myxomas, 275 Necrotizing vasculi tis tumor grade vs. stage, 219 ch olecystokin i n and, 319
Myxomatous degeneration diseases causi ng, 572 tumor markers, 222 N eural pl ate
mitral valve prolapse caused Negative charge barrier (plasma tumor nomenclature, 219 formation of, 408
by, 259 fi l tration ), 480 tumor suppressor genes, 221 Neural tube
Negative predictive value ( N PV), 51 , Neoplasms formation of, 408
N 581 intraprenchymal hemorrhage Neural tube defects, 409-410
N-acetylcysteine, 563 Negative rei nforcement, 458 caused by, 424 di agnosti c findi ngs/labs, 572
as antidote, 239 Negative selection ( thymus) , 193 lymphoid, 364 prevention of, 575
for cystic fibrosis, 574 Negative-stranded vi ruses, 1 59 myel oid, 365 valproic acid as cause, 452
INDEX
Neural tumors I L-8 recru itment of, 200 Nodes o f Ranvier N ormocytic anemia, 355
S- 1 00 marker for, 222 in l eukemoid reaction, 361 myel i n and, 41 1 algori thm to, 354
euraminidase inhibitors, 187 in l eukocyte extravasation, 215 Nodular sclerosis, 581 N orovi rus, 1 58
inAuenza virus, 1 60 in myocardial infarction , 270 in H odgkin's disease, 361 diarrhea caused by, 168
Neuroblastomas, 286, 297, 581 reactive oxygen i n termediates, 103 Noise-i nduced hearing loss, 436 Northern blot, 80
bombesin marker for, 222 in wound h eal ing, 216 N-ol igosaccharides, 74, 75 Nortripty l i n e , 475
oncogenes for, 221 Nevi rapine, 1 89 Nomenclature of glomerular N osocom ial infections, 168, 174
Neurocutaneous disorders, 446 Nevus Aammeus, 278. See Port-wine disorders, 489 Nosocomial pneumonia
Neuroectoderm, 41 1 , 505 stains Nonbenzodiazepine hypnotics, 453 associations, common/
Neuroendocrine cel l s NFl gene, 221 Noncaseating granulomas i m portant, 579
tumors of, 333 von Reckl i nghausen's disease c l i nical presentation, 566 N otochord, 252, 408
Neurofibrillary tangles i n Alzheimer's and, 446 in Croh n's disease, 328 postnatal derivative of, 505
disease, 443 NF2 gene, 85, 221 Noncom municating N ovobioci n , 572
Neurofibromas N 1 14CI hydrocephalus, 426 staphylococci reaction to, 127
von Reckl inghausen's disease as as antidote, 239 Noncompetitive an tagonists N P J- 1 insul i n , 305
cause, 446 N i aci n , 91 , 281 effi cacy of, 229 N RT l s/N N RTls, 1 89
Neurofilaments, 76 reactions to, 240, 241 Noncompetitive i n h i b i tors, 226 N SAIDs, 404, 405
Neurogenic bladder N icoti nic AC h receptors, 230 Nondepolarizing neuromuscular for acute gout attack, 574
multiple sclerosis as cause, 444 N i emann-Pick disease, 1 12 bl ockers, 455 for arth ritis, 390
Neurohypophysis, 287 c l inical presentation, 566, 568 Nonenzymatic glycosylation of asp i r i n , 404
hypothalamus and, 414 N i fedipine, 279. See also Calcium glomerular basement gastric ulcers caused by, 327
Neuroleptic mal ignant syndrome channel bl ockers membrane, 491 gastritis caused by, 327
( N M S ) , 455, 473 N i furtimox, 1 86 Nonerosive gastritis, 327 for gout, 391 , 406
Neuroleptics. See Anti psychotics for Trypanosoma cnt;:i, 150 Non hemolytic anemia, 352, 354, 355 for migra i n e headaches, 446
Neurologic drug reactions, 241 N ight terrors Non-Hodgkin's lymphoma, 362 for pseudogout, 391
Neurology benzodiazepi n es for, 453 diseases associated with, 220 reactions to, 240, 241
anatomy and physiology, 41 1 -443 N i kolsky's sign, 398 1-1 IV-associated, 166 in renal fi l tration, 486
embryology, 408-410 N i modipine
vs. H odgkin's, 361 tubulointersti tial nephritis caused
pathol ogy, 443-448 as vasospasm treatment, 424
rituximab for, 374 by, 495
pharmacol ogy, 449-456 N i pples, 533
therapeutic antibodies for, 210 Nucl eoside, 64
euromuscular blocking drugs, 455 dermatome for, 431
Nonhomologous end joini ng, 69 Nucleosome, 64
N euromuscular j unction rash, causes of, 569
Non-i nsu l i n-dependent diabetes Nucleotide excision repa ir, 69
diseases of, 394 N i ssl bodies, 74
mellitus ( N I O D M ) . Nucleotides, 64
signal transmission i n , 230 N i ssl stains, 41 1
See Diabetes m el l i tus type 2 Nucleus accumbens
synapses i n , 428 microgl ia and, 41 1
Non keratin ized stratified squamous CABA syn thesis, 413
Neuronal atrophy, 426 N i tazoxamide
epithel i u m , 31 1 Nucleus ambiguus, 435
Neuron migration fa i l ures for Cryptosporidiwn, 147
Nonmaleficence, 56 Nucleus cuneatus, 428
associations, common/ N i trates
Non-megal oblastic anemia, 352 Nucleus gracilis, 428
important, 579 for angina, 280
Non megaloblastic macrocytic Nucleus pul posus, 505
Neurons, 41 1 N i tric oxide, 319
anemias, 354 formation of, 408
Neuropathy erections and, 516
Nonoxi dative reaction, 103 herniation of, 427
diabetic, 302 N i trite
Nonsense DNA mutations, 67 Nucleus sol itarius, 435
optic, 183 as antidote, 239
Noradrenergic drugs, 232 N u l l hypothesis, 54, 55
europhysins, 287 poisoning caused by, 547
N i trite test, 1 69, 170 Norepinephrine Number needed to harm or treat, 52,
Neuropores, 409
Neurosyp h i l i s N i trofu ran toi n in anxiety/depression, 461 581
clinical presentation, 569 reactions to, 240 atypical antidepressan ts effect "Nutmeg l i ver," 273 , 335, 573
Neurotransmi tters, 413 . N i troglyceri n , 280 on, 476 Nystagmus
See also specific for angina, 576 blood pressure effect, 236 Fried reic h 's ataxia as cause, 430
neurotransmitters N i troprusside, 279 clinical use, 235 multiple sclerosis as cause, 429,
astrocytes and, 41 1 N i trosam i n es CNS sti mulants and, 472 444, 568
botul inum toxin effect, 230 as carcinogen, 223 erecti ons and, 516 PC P use as cause, 471
changes in psychological stomach cancer and, 327 heart rate effect, 236 phenytoin as cause, 452
diseases, 461 N itrosoureas, 372 vs. isoproterenol , 236 Nystatin, 185
in H untington 's disease, changes N i trous oxide, 453 MAO i n h i b i tors effect on, 475 for Ca ndida albicans, 574
i n , 456 N izatidi ne, 341 as neurotransmitter, 413 in Thayer-Marti n (VPN)
toxins affecting, 124 N M DA-R binding opioid effect on, 449 media, 1 20
Neutralization (antibody) , 199 i n H untinton's disease, 417 receptor bindi ng, 229
of vi ruses, 199 release of, 232 0
N M DA receptors
Neutropenia, 175 a rylcycloh exyl amines and, 454 S N R i s effect on, 475 Oat cell carcinoma of the l ung, 558
interferons as cause, 1 89 memantine as agonist, 456 syn thesis and sign a l i n g of, 232 Obesity
ticlopidine as cause, 368 N-myc gene, 221 tramadol effect on, 450 acanthosis nigricans and, 400
Neutrophil chemotaxis N-myc oncogene tricyc l i c antidepressan ts and, 475 B M I i n , 60
complement and, 199 neuroblastomas and, 297 Norepinephrine ( N E ) diabetes m e l l i tus and, 303
Ncutrophils, 193, 345 N N RT l s (non-nucleoside reverse cortisol a n d , 292 as esophageal cancer risk
in acute i nAammation, 214 transcriptase i n h i b i tors), 189 Norepinephrine receptors factor, 325
in alveolar spaces, 560 NO nervous system rol e , 230 gallstones and, 339
in anemia, 354 in anti-aggregation of platel ets, 349 1orAoxaci n , 1 82 medications for, 235
in chronic myelogenous Nocardia , 1 19, 121 , 122 Normal pressure hydrocephal us, 426 renal cell carci noma and, 494
l eukemia, 365 antimic robials for, 181 dementia caused by, 443 Obl igate aerobes, 121
hypersegmented, 572 vs. Actinomyces, 131 Normoch romic anemia, 354 Obl igate anaerobes, 121
I NDEX
Obl igate intracellular organisms, 121 , "Ol ive" mass in epigastric region, 308 reactions to, 240 Osteogenesis imperfecta, 77, 78
141 Omalizumab, 563 transferrin and, 357 c l i nical presentation , 566
Obl ique muscles as therapeutic anti body, 210 Orally administered drugs Osteogen i c sarcoma, 389
in respiration, 546 Omental foramen, 310 bioavailabi l i ty of, 227 Paget's disease of bone as
Obl iterative cardiomyopathy, 272 O meprazol e , 321 , 341 Ora serrata, 437 cause, 387
0 bl ood group, 347 Omphalocele, 308 Orbicularis ocu l i muscle Osteomalacia/rickets, 94, 387
Observational study, 50 Onchocerca volvulus, 1 51 innervation of, 434 lab values, 388
Observer-expectancy effect, 53 Oncogenes, 221 Orch itis, 161 phosphate deficiency as cause, 487
Obsessive-compulsive disorder Oncogenic microbes, 222 Organ morphogenesis treatment for, 575
(OC D ) , 466, 469 Oncology. See Hematology/Oncology errors in, 505 vitamin D deficiency as cause, 294
atypical antipsychotics for, 473 Ondansetron, 342 Organ of Corti Osteomas, 219
clomipramine for, 475 "Onion ski n " hearing loss and, 436 Osteomyel itis, 169
SSRls for, 475 bile d u c t fibrosis, 338 Organogenesis, 504 associations, common/
Tourette's syndrome and, 460 bone appearance, 389 teratogens duri ng, 506 important, 579
treatment for, 472 in mal ignant hypertension, 267 Organophosphates, 233 Staphylococcus aureus causi ng, 128
Obstructive bil imy disease periosteal reaction , 573 antidote to, 239 Osteonecrosis (avascular
alkal ine phosphatase marker Onychomycosis Organ rejection . See Transplant necrosis), 392
for, 222 antimicrobials for, 1 86 rej ection Osteonecrosis of j aw
Obstructive hydrocephalus, 426 Oogenesis, 522 Organ transplants bisphosphonates as cause, 405
Obstructive jaundice, 335 0-oligosaccharicles, 75 rejection, WBC urinary casts as Osteopath i c medical students, 36-40
Obstructive I iver disease Open-angl e glaucoma, 439 sign, 489 U S M L E S tep I passing rates, 1 0
serum markers for, 334 Opening snap Orientation, 461 Osteopetrosis ( marble bone
Obstructive lung diseases, 554 associations, common/ Origin of repl ication, 68 disease) , 387
pulmonary hypertension caused important, 579 Ornith ine transcarbamoylase (OTC ) lab val ues, 388
by, 549 Operant conditioning, 458 deficiency, 107 Osteoporosis, 387
vs. restrictive l u ng disease, 556 Ophthal mic nerve, 436 Oropharyngeal Aora, 1 67 bisphosphonates for, 405
Obstructive sleep apnea, 556 Ophthalmopathy Orotic acid, 65, 107 compression fractures and, 577
Obturator nerve, 384 i n Craves' disease, 299 Orotic aciduria, 65 in Cushi ng's syndrome, 296, 306
Occipital cortex Ophthal moplegia in anemia algorithm , 354 as drug reactio n , 241
strokes i n , 422 multiple sclerosis as cause, 444 Orphan Annie's eyes, 299, 571 Gaucher's disease as cause, 567
Occipital lobe, 418 Opiates Orthomyxoviruses, 158, 160 heparin as cause, 367
Occipital sinus, 425 as i n travenous anesthetics, 454 Orthopnea, 273 hormone replacement th erapy
Occl usion of anterior spinal Opioid analgesics, 449 Osceomas for, 540
artery, 429 Opioids Gardner's syndrome as cause, 568 lab val ues, 388
OC D. See Obsessive-compulsive antidote to, 239 Oscillating breath ing m enopause and, 523
disorder (OC D ) intoxication and withdrawa l , 470 as Cheyne-Stokes respi rations, 568 prednisone as cause, 373
Ochronosis, 108 respi ratory acidosis caused by, 488 Osel tamivir, 187 ral oxifene for, 540
Octreotide, 306, 341 Opponens digiti minimi muscle, 383 for inA uenza, 575 treatment for, 575
for carcinoid syndrome, 304, 574 Opponens poll icis muscle, 383 Osler's nodes, 274, 568 Osteosarcomas, 219, 389
for carcinoid tumors, 333 Opportunistic Fungal infections, 145 Osler-Weber-Rencl u syndrome, 85 diagnostic findings/labs, 573
Ocular pathology. See Eye Oppositional defiant disorder, 460 Osmolarity diseases associated with, 220
Oculomotor nerve, 434, 436, 440 Oprelveki n , 210 ADH regulation of, 485 tumor suppressor genes, 221
epidural hematoma and, 424 Opsonization , 197, 198 of A u i cl compartments, 480 Otitis media. See a lso External otitis
extraocular muscles and, 439 by complement, 199 mannitol and, 500 Haemophilus influen;:.ae as
palsy of, 422 Optic canal potassium and, 487 cause, 134
Oculosympathetic pathway as cranial nerve pathway, 435 in proximal tubule, 500 Streptococcus pneumoniae as
Horner's syndrome and, 431 Optic ch iasm, 432, 436, 441 regulation of, 485 cause, 128
Odds ratio (OR), 50, 52 pitui tary adenomas and, 447 Osmotic diarrhea, 326 Ototoxicity, 241
OAoxacin, 182 Optic elise, 437 Osmotic diuresis l oop diuretics as cause, 500
Okazaki fragment synthesis, 68 Optic gliomas in diabetes mell itus, 302 Ouabai n , 77
Olanzapine, 473 von Reckl i nghausen's disease as Osmotic fragi l i ty test, 356 Ovarian arteries, 312
Olfaction cause, 446 Osmotic l axatives, 342 Ovarian cancer
l imbic system and, 415 Optic nerve, 415, 434, 437, 441 Osteitis deformans. See Paget's disease associations, common/
Olfactory bulb, 432 Optic neuritis of bone important, 580
Olfactory hallucinations, 463 multiple sclerosis as cause, 444 Osteitis fibrosa cystica, 300, 386 CA- 1 2 5 marker for, 222
Olfactory nerve, 434 Optic neuropathy lab val ues in, 388 cisplati n/carboplatin for, 373
Olfactory tract, 432 ethambutol as cause, 183 Osteoa rth ri tis, 390 Krukenberg's tumor, 327
Ol igoclonal bands Optic pathway gl iomas, 85 clinical presentation, 570 microtubule i n h i b i tors for, 373
in multiple sclerosis, 444 Optic tract, 432, 440, 441 COX-2 i n h i b i tors for, 405 oncogene for, 221
Oligodendrogl ia, 41 1 , 412, 447 Optoc h in Osteoblastic cells serous pap i l l a ry
myel inization by, 41 1 streptococci reactions to, 1 27 PTH and, 293 cystadenocarcinoma, 223
Oligohydramnios, 527 Streptococcus pneumoniae Osteoblasts, 386 tumor suppressor genes, 221
i n Potter's syndrome, 478 sensitivity to, 128 i n osteomalacia/rickets, 387 Ovaries
Ol igomenorrhea, 521 viriclans streptococci resistance in Paget's disease of bone, 387 "chocolate cysts," 530, 570
Ol igosaccharide hydrolases, 322 to, 128 Osteochondromas, 389 cysts, 530
Ol igosaccharicles Optoc h i n response, 573 Osteoclastomas, 389 descent of, 514
carbohydrate digestion and, 322 Oral advance directive, 57 Osteoclasis estrogen production, 520
Oligospermia Oral candidiasis, 185 ossi fication by, 386 h istol ogy, 515
sulfazalazine as cause, 342 Oral contraceptives, 540 in osteopetrosis, 387 l igaments i n , 515
Ol iguria melasma caused by, 396 Osteodystrophy premature ovarian fail ure, 529
nephritic syndrome and, 492 progestins i n , 540 aluminum hydroxide as cause, 341 reproductive hormones and, 538
I N DEX
tumors of, 531 -532 Pa i n l ess hematuria i n bladder Papi l l edema, 439 hyperparathyroidism and, 300
venous and lymphatic cancer, 494 in hydrocephalus, 426 kidney effects, 486
drainage, 514 Pai n (sensation ), 428 Papillomas, 219 signal ing pathway, 294
OVLT, 413 Pal e infarcts, 213 Papillomavirus, 154. See a lso Human vitami n D and, 294
blood-brain barrier and, 413 " Pa l i sading" nuclei in ski n cancer, 403 papill omavi rus ( H PV) Parathyroids, 293
Ovotestis, 525 Pal ivizumab, 160 Papovavirus. See Pap i l l omavirus; fai l u re to develop, 206
Ovulation, 521 Palmar crease i n Down syndrome, 569 Polyomavirus Parathyroi d tumors
progesterone and, 520 Palmar in terosseous muscles, 383 Pap smear in M E N I , 304, 568
progestin/estrogen effect on, 540 Palmar reA ex, 432 cervical carci noma and, 528 in ME 2A, 304
prolactin and, 290 Palpable Rank mass Papul es, 395 Paraumbilical veins, 314
stimulation, via S E RMs, 540 i n renal cell carcinoma, 494 in dermatitis herpetiformis, 398 Paraventricular nucleus
"Owl's eye" inclusions, 1 56, 1 66, 361 , in Wil ms' tumor, 494 l ichen planus as cause, 569 oxytocin synthesis, 414
571 PALS . See Periarterial lymphatic Para-aortic lymph nodes, 192 Parenchymal th i n n i ng, 493
Oxacil l i n , 177 sheath Paracoccidioidomycosis, 143 Parietal cells
for Staphylococcus aureus, 576 Panacinar emphysema, 554 Paracortex of lymph node, 192 autoantibodies to, 327
Oxalate crystals, 493 . See also Kidney a 1 -antitrypsi n deficiency as Paradoxical aciduria, 501 gastric, 321
stones cause, 335 " Paradoxical sleep," 61 Gl secretory products, 320
Oxazepam , 453 p-ANCA, 205, 277 Paraesophageal hernias, 318 Parietal layer of Bowman's
Oxidation diagnostic findings/labs, 570 Para foll icular cells, 294 capsule, 479
in drug metabol ism, 228 in glomerulonephritis, 492 Paragonimus westennani, 152 Parietal layer of glomerular
Oxidative burst, 103 Pancoast tumor, 559 Parakeratosis, 396 capsule, 481
Oxidative phosphorylation diagnostic findings/labs, 570 Paralysis Parietal lobe, 418
poisons, 102 H orner's syndrome and, 431 in central pontine myel inolysis, 419 Parietal peritoneum, 317
Oxidative reaction , 103 as l u n g cancer compl ication, 558 in Ch iari II malformation, 409 Parinaud syndrome, 433
Oxybutynin Pancreas, 316, 321 facial, 437 Parki nson-l ike syndrome
clinical use, 234 blood supply to, 312 G u i l l a i n-Barre syndrome as as drug reaction, 241
Oxygen cell types, 287 cause, 444 Parki nson's disease, 416
as antidote, 239 embryology, 309 as motor neuron sign, 428
cl i nical presentation, 569
cerebral perfusion pressure Gl hormones and, 319 neuromuscular blocking drugs for
diagnostic findings/labs, 570, 571
and, 421 serum markers of pathology, 334 inducing, 455
dopa m i n e l evels i n , 413
for cluster headaches, 446 tumors of, 304 i n pol iomyel itis, 430
drugs for, 455
Oxygen content of blood, 550 Pancreas divisum, 309 spinal cord lesions as cause, 429
L-dopa/carbidopa for, 456
Oxygen deprivation, 550 Pancreatic amylase, 322 in stroke, 422
medications for, 234
Oxygen-hemoglobin dissociation Pancreatic cancer of vertical gaze, 433
neurotransmitter changes, 461
curve, 548 adenocarcinomas, 223, 340 Paralytic ileus
resting tremors i n , 417
Oxytoci n , 306 adenocarcinomas, marker for, 222 vincristine as cause, 373
Parotid gland
hypothalamus production of, 414 c l i n i cal presentation, 568 Paramedian ponti n e reticular
innervation of, 434
lactation and, 523 diagnostic findi ngs/labs, 572 formation ( PPRF), 61
sal iva secretio n , 320
secretion of, 287 MEN I as cause, 568 lesions i n , 419
tumors i n , 324
signa l i ng pathway, 294 tumor suppressor genes, 221 Paramesonephric duct, 512
Parotitis, 161
Pancreatic ducts, 309, 316 Paramyxovi ruses, 1 58, 160
p bulimia nervosa and, 469
Pancreatic endocrine tumors Para neoplastic syndromes, 223, 580
Paroxetine, 475
p 5 3 gene i n M E N I , 304 renal cell carci noma and, 494
Paroxysmal nocturnal
colorectal cancer and, 332 Pancreatic insufficiency, 326 Paranoia
Pancreatic l i pase, 1 15 hemoglobinur i a , 354
P-4 50 i nhi bi tor, 341 amphetamines as cause, 471
Pancreaticoduodenal arteries, 313 L S D use as cause, 471 i n anemia algorith m , 356
P-4 50 interactions, 242
Pancreatic pseudocysts, 339 marijuana as cause, 471 c l inical presentation, 569
P-4 5 0 system , 315
Pancreati c secretions, 322 Paranoid persona l i ty disorder, 468 OAF deficiency as cause, 200
PABA synthesis, 1 81
Pacemaker action potential , 260 Pancreatic tumors, 316, 319 Paranoid sch izophreni a , 463 Pars compacta
Pacemakers Pancreatitis, 339, 340 Parap h i l i a of substantia nigra, 416
for atrioventricular block, 263 acute respi ratory distress syndrome transvestism a s , 469 Partial agonists
Pacinian corpuscles, 412 (ARDS) caused by, 556 Parasite h i nts, 152 efficacy of, 229
Packed RBCs, i n blood tranfusion alcoholism and, 472 Parasi tes, 147- 1 51 Partial seizures, 445
therapy, 360 associations, common/ cestodes, 1 52 Partial thromboplastin time ( PT T), 359
Paclitaxel, 76, 370, 373 i m portant, 580 eosinoph i l i a caused by, 345 Parvovirus, 1 54, 1 5 5
Paget cells, 534 gallstones as cause, 339 i m munodeficiency i n fections, 205 Parvovi rus B 1 9
Paget's disease of bone, 387 pancreatic insufficiency caused nematodes, 151 c l i nical presentation, 172, 566
alkal ine phosphatase marker by, 326 protozoa, 147- 150 PAS (periodic acid-Sch i ff) stain, 120,
for, 222 serum markers for, 334 trematodes, 1 52 175
bisphosphonates for, 405 Pancuroni u m , 455 variations i n , 201 Passive abduction
clinical presentation , 566 Pancystol i c murmur Parasympathetic gangl ia i n sph i ncters i n M C L tear, 379
lab val ues, 388 conditions associated with, 258 hormones produced by, 319 Passive immunity
neoplasms associated with, 220 Pancytopenia, 355 Parasympathetic nervous system , 230, vs. active i m munity, 202
osteosarcoma and, 389 Panic disorder, 466 414 in infancy, 198
Paget's disease of the breast, 533-534 treatment for, 472 receptor types in, 231 Pasteurella , 1 19
c l i nical presentation, 569 Pannus formation, 390 Parasympathetic receptors, 231 Cram staining, 133
PAH clearance Pan tothenate, 91 Parath ion, 233 Pasteurella nwltocida, 139, 175
ERPF esti mation with, 480 Pap il lary thyroid carcinoma, 219, 299, Parathyroid hormone ( PT H ) , 293, 483 c l i n i cal presentation, 567
Pai n disorder, 467 571 ' 573, 581 in bones, 386 osteomyel i tis caused by, 1 69
Painful crisis psammoma bodies in, 223 calcitonin and, 294 Patau's syndrome, 88
sickle cell anemia as cause, 356 radiation exposure and, 220 calcium and, 300 c l inical presentation, 567
I ND E X
Patches, skin, 395 Chlamydia trachoma/is as Perforation i n type A gastritis, 327

Patch test for antigens, 203 cause, 141 ulcers as cause, 328 vitamin B 1 2 deficiency and, 354
Patellar reAex, 432 Neisseria gonorrhoeae as cause, 134 Perforin, 197, 212 Peroxidase, 295
Patent ductus arteriosus ( PDA) , 171 , Pelvic nerve Performance anxiety, 60 Peroxidation
259, 265, 267 erections and, 516 Perfusion in i ron poisoning, 217
clinical presentation, 566 structures suppl ied by, 312 cerebn1 l , 421 Peroxisome, 75
congenital rubella and, 267 Pelvis ( renal ) , 479 V/Q mismatch, 551 Persistent cervical sinus, 509
i ndomethacin for, 405 development/embryology, 478 Perfusion l i m i ted circulation, 549 Persistent fetal ci rcul ation , 59
medications for, 252 Pemphigus vulgaris, 398 Perianal disease Persistent truncus arteriosus (TA), 250
misoprostol for, 341 acantholysis and, 396 Crohn's disease and, 328 Persona l i ty disorders, 468-469
treatment for, 575 autoantibodies associated with , 205 Periarterial lymphatic sheath Personal ity traits, 468
Patent foramen ovale, 251 diagnostic findings/labs, 570 ( PALS), 193 Pertussis tox i n , 1 24
ischemic stroke and, 425 as hypersensitivity disorder, 204 Pericardia! effusions Pervasive developmen tal
Patent urachus, 508 Penicillamine diseases causmg, 566 disorders, 461
Pathologic grief, 60 as antidote, 239 as l ung cancer complication, 558 Pes cavus
Pathologic RBC forms, 350-351 reactions to, 241 Pericarditis Friedreich's ataxia as cause, 430
Pathology for Wilson's disease, 337 acute, 275 Petit mal seizures. See Absence
breast, 533 Penicill i n , 176 associations, common/ se1zures
cardiovascular, 265-277 for Actinomyces, 131 important, 577 Peutz-)eghers syndrome, 331
cervical , 528 gram-negative bugs and, 134 fibrinous, 270, 271 c l i nical presentation, 567
endocrinal , 296-304 for i ntrapartum prophylaxis, 129 in l upus, 393 as colorectal cancer risk factor, 332
esophageal , 324 mechanism of action, 176 in renal fai l ure, 497 Peyer's patches, 31 1 , 323
eye, 438 for Neisseria men ingitidis, 575 Pericentral vein zone of l iver, 3 1 5 Peyronie's disease, 537
gastroi n testi na I , 324-339 Peri neur i u m , 412 c l i nical presentation, 567
for Pseudomonas aewginosa, 135,
hematologic/oncologJC, 350-366 575 Periodic acid-Sch i ff stai n , 1 20 P5 3 gene, 221
i nAammation, 212-217 for a 1 -antitrypsi n deficiency, 335 PC 1 2 , 404
reactions to, 240, 241
musculoskeletal , 387-403 for Wh ipple's disease, 326 in anti-aggregation of platel ets, 349
resistance, causes of, 142
neoplasia, 218-224 Periorb i tal edema, 492 pH
secretion of, i n h ibiting, 406
neurological, 443-448 nephrotic syndrome as cause, 567 i n kidney stones, 493
for StrefJiococcus bovis, 576
penile, 537 Peripartum cardiomyopathy, 272 Phages
for Streptococcus pnewnoniae, 576
prostate, 535 Peripheral edema, 273 lysogenic, 126
for Streptococcus pyogenes, 576
psych iatric, 459-471 nephrotic syndrome as cause, 567 lytic, 126
for Treponema pallidwn, 576
rena I, 489-498 Peripheral lymphoid tissue Phagocytes, 345-346
Penicill i n G
reproductive, 524-537 B cells in, 346 dysfunction in, 207
for Neisseria , 134
respi ratory, 553-560 Peripheral nerves, 41 1 , 412 microgl ia as, 41 1
for syp h il is, 138, 1 84
Pavlov, 458 Peripheral nervous system toxins affecting, 124
Penicil l ins
PCL. See Posterior cruciate l igament origins of, 41 1 Phagocytosi s
tubuloi n terstitial nephritis caused
( PCL) Peripheral neuritis receptors enhancing, 201
by, 495
Pco 2 vincristine as cause, 373 Phagosomes
cerebral perfusion and, 421 Penis
Peripheral neuropathy tuberculosis i n h ibition, 132
PCP cancer of, and 1-1 PV virus, 222
alcoholism and, 472 Pharmaceuticals. See D ru gs
intoxication and withdrawa l , 471 derma tomes for, 431
drugs for, 451 Pharmacoki netics and
PCWP. See Pulmonary capillary fibrous plaques, Peyronie's disease duloxetine for, 475 pharmacodynamics
wedge pressure as cause, 567 vitamin B 1 2 deficiency as dosage calculations, 227
Pearson's correlation coefficient, 55 Pentamidine cause, 354 drug metabol ism, 228
Peau d'orange ski n , 534 for Pnewnocystis iiroveci, 146 Peripheral vascular occlusive disease efficacy vs. potency, 229
PECAM - 1 as Tl\11 P-SMX substitute, 184 i n diabetes m e l l i tus, 302 e l i m i nation of drugs, 228
in leukocyte extravasation, 2 1 5 Pentobarbital , 452 Peripheral vertigo, 446 enzyme kinetics, 226
Pectinate l ine, 315 Pcntose phosphate pathway, 103 Periplasm, 1 18 receptor b i n di ng, 229
relation to lymph drainage, 192 P E P carboxykinase, 102 Periportal zone of l i ver, 315 therapeutic i ndex, 229
Pectus excavatum, 85 Pepsin , 320 Perirenal space, 309 Pharmacology. See Drugs
Pediatric psychiatry, 459-460 Pepsinogen , 320 Peristalsis autonomic drugs, 230-238
Pediatrics l ocation of, 321 motil i n and, 319 cardiovascular, 279-284
abuse/neglect, 57 secretion of, 319 Peritoneum, 309 endocri nal , 305-306
APGAR score, 59 Peptic ulcer disease, 327 Peritonitis gastro i n testi n a l , 340
early developmental m i l estones, 59 Brunner's glands i n , 321 appendicitis and, 329 hematologic/oncologic, 367-375
eth ical issues i n , 58 Peptic ulcers diverticu l i tis and, 329 musculoskeletal , 404-406
intraventricular hemorrhage, 59 cholinomimetic agents and, 233 Peri umbil ical metastasis, 327 neurological , 449-456
necrotizing enterocol itis, 59 i n Cushing's syndrome, 306 Perivascular pseudorosettes pharmacok i n etics and
persistent fetal circulation, 59 H 2 blockers for, 341 in ependymomas, 448 ph armacodynamics, 226-229
RDS i n , 59 misoprostol for, 341 Periventricular hemorrhage psyc h i atric , 472-476
Peduncles, cerebellar, 415 portal hypertension as cause, 333 alcoholism as cause, 472 ren a l , 499
Pel lagra prednisone as cause, 373 Periventricular plaques reproductive, 538-541
clinical presentation, 567 proton pump i n h i b i tors for, 341 i n multiple sclerosis, 444 respiratory, 562-564
H artnup's disease as cause, 482 Peptidoglycan (bacterial Permanent cell types, 74 toxicities and side effects, 239-241
Pelvic fractures structure), 1 1 8 Permeability barrier, 412 Pharyngeal apparatus, 509.
femoral nerve damage, 384 Peptostreptococcus Pernicious anemia See B ranch i a l apparatus
Pelvic i n Aammatory disease lung abscesses caused by, 560 H LA- D R 5 and, 194 Pharyngeal pouches
( PID), 173 Percutaneous transl uminal coronary as hypersensitivity disorder, 204 developmental fai l u re, 206
associations, common/ angioplasty intrinsic factor and, 320 Pharyngitis
i mportant, 580 abciximab for, 369 neoplasms associated with, 220 Streptococcus /Jyogenes causing, 1 29
INDEX
toxins caus ing, 124 Phosphofruc tokinase- ! , 97, 98 Pituitary adenomas, 290, 301 , 447 Plasmodiu m malariae, 149
in unimmunized children , 174 Phosphol ipase A Pitui tary drugs, 306 Plasmodiu m vivax/ova le, 149
Phase 1-phase IV clinical trials, 50 fat digestion by, 322 Pituitary gland, 287 Platelet-derived growth factor
Phenacetin Phosphol i pase A7 Pitui tary gonadotrophs ( PDGF)
transitional cell carcinoma glucocorticoicis and, 306 reproductive hormones and, 538 signal ing pathways, 294
and, 494 Phospho l i pase C Pituitary hormone regulation, 289 Platelet disorders, 359
Phenelzine, 475 in signal transduction, 231 Pituitary hormone repl acement Platelet dysfunction
Phenobarbital , 452 Phospho! ipids, 1 16 therapy i n renal fai l ur e , 497
for Crigler-N aj jar syndrome, type in b i l e , 323 name suffix, 243 Platelet factor 4 ( P F4 ) , 367
I I , 336 Phosphoribosylpyroph osphate Pituitary infarction Platelet p l ug formation, 349
elimination of, 228 ( PRPP), 65 c l i nical presentation , 568 defects i n , 359
for epilepsy, 451 Phosphorylase, 96 Pituita ry tumors in von Wi l lebrand's disease, 360
reactions to, 241 Photophobia adenomas, 579 Platelets, 344
toxicities, 452 i n rabies, 1 62 associations, common/ in bl ood transfusion therapy, 360
Phenothiazines Photosensitivity important, 580 in chronic myeloproliferative
name suffix, 243 in l upus, 393 i n ME I , 304, 568 disorders, 366
Phenotypic mixi ng, 1 53 Phototherapy Pityriasis rosea, 401 in wound heal ing, 216
Phenoxybenzamine, 237, 297 for Crigler-Najjar syndrome, type PKD I /PKD2 gene, 85, 498 Pleiotropy, 82
for pheochromocytoma, 575 I , 336 Placebo control groups, 53 Pleomorp h i c adenoma, 324
receptor binding, 229 for jaundice, 335 Placenta Pleomorph i c bacteria, 1 19
Phentolamine, 237 Phrenic arteries, 312 abruptio placentae, 526 Pleura
Phenylalanine, 107 Phrenic nerve blood Row, 252 mesothelioma i n , 559
gastrin stimulation, 319 diaphragm and, 545 development of, 508 Pleural effusions, 557, 561
Phenylalanine hydroxylase, 108 Phyll odcs tumors, 533 estrogen production , 520 as lung cancer compl ication , 558
Phenylbutyrate, 107 Physiologic dead space in l ungs, 546, maternal-fetal blood barrier, 413 in mesothel ioma, 559
Phenylephrine, 564 582 placenta accreta, 526 Pleural plaques, 555
a-blockade effects, 237 Physiologic neonatal jaundice, 335 placenta previa, 527 Pleuritis
c l i nical use, 235 Physiology progesterone production, 520 in l upus, 393
Phenylethanolamine N-methyl cardiovascular, 253-265 reta ined tissue from , 527 Pleuroperitonea! membrane
transferase, 108 endocrinal , 289-295 Plague, 121 , 139 defective development, 318
Phenylketonuria ( PKU), 82, 108 gastrointestinal, 319-323 Plantar reAex, 432 Pl i cae circulares, 31 1
Phenytoi n, 92, 452 hematologic/oncologic, 347-349 Plaques Ploidy, viral , 1 54
elimi nation of, 228 musculoskeleta l , 378-386 in Alzheimer's disease, 443 Plummer-Vi nson syndrome, 324, 352
for epil epsy, 451 neurological, 41 1 -443 l ichen planus as cause, 569 c l i nical presentation, 567
.
erythema multi forme caused rena l , 480-48 8 in multiple sclerosis, 444 neoplasms associated with , 220
by, 399 respiratory, 546-552 Plaques, ski n , 395 PM ! . (progressive multifocal
folate deficiency and, 354 Physostigmine, 233 Plasma l e ukoencephal opathy), 155
as P-4 5 0 i nducer, 242 for glaucoma, 449 i n blood transfusion therapy, 360 Pneumaturi a
reactions to, 240, 241 Physostigmine sal icylate Plasma cells, 346 diverticul itis and, 329
as teratogen , 506 as antidote, 239 Plasma col loid osmotic pressure, 265 Pneumoconioses, 555
for tonic-clonic seizures, 576 Pia mater, 436 Plasma drug concentration Pneumocystic pneumonia
toxiciti es, 452 Pick's disease, 443 cl earance and, 227 as i mmunodeficiency
Pheochromocytomas, 223 , 286, 297, dementia caused by, 462 elimi nation and, 228 i n fection, 205
581 diagnostic findings/labs, 573 in renal clearance calculation, 480 Pneumocystis
in MEN ZA, 304 hydrocephalus and, 426 target, 227 stain for, 120
in MEN Z B , 570 Picornaviruses, 154, 1 58, 159 volume of distribution and, 227 Pneumocystis iirovecii, 146
presurgical medical PI D. See Pelvic i nAammatory disease Plasma markers of l iver and pancreas A I D S and, 579
management, 237 ( P I D) pathol ogy, 334 antimicrobials for, 1 82
in Sturge-Weber syndrome, 446 Pigmented i ris hamartomas, 85. Plasma membrane, 1 1 8 in immunocompromised
treatment for, 575 See Lisch nodules composition of, 76 pati ents, 168
von H ippel-Lindau disease as Pigmented skin disorders, 396 in muscle contraction, 385 treatment for, 575
cause, 446, 569 Pigment-producing bacteria, 122 Plasmapheresis Pneumocytes, 544
von Reckl i nghausen's disease as Pigment stones, 339 for Crigl er-N a j j a r syndrome, type Pneumonia, 557, 560
cause, 446 Pil i/fimb riae, 1 1 8 I, 336 adenovirus as cause, 155
Ph iladelphia chromosome, 365, 366, " P i l l-ro l l i n g tremor" of Parki nson's for C u i l l a i n-Barre syndrome, 444 associations, common/
580 disease, 417 Plasma protein concentration i m portant, 579
associations, common/ P i l ocarpine, 233 changes i n , 481 atypical, microbia Is for, 1 80
important, 580 for glaucoma, 449 Plasma renin causes of, 168
imatinib effect on , 374 Pilocyti c astrocytomas, 448 hyperaldosteronism and, 296 Chla mydia trachomatis as
Phl ebotomy Pindolol, 238 Plasma vol ume, 480 cause, 141
for hemochromatosis, 337 Pinea I body, 433 Plasmids, 1 18 h erpesvirus as cause, 1 56
Phobias, 466 Pineal gland, 433 conj ugation of, 1 26 H l V-associated, 1 66
treatment for, 472 Pi nealomas, 433 DNA, 1 26 Mycoplasma pneumoniae as
Phosphatase, 96 Pink eye. See Conj unctivitis Plasm i n , 348 cause, 142
Phosphate "Pink puffer," 554 Plasminogen , 348 Pnewnocystis iirovecii as cause, 146
disturbances in, 487 c l i n ical presentation, 568 thrombolytic effect on, 368 Pseudomonas aerugi nasa i n , 121
PTH and, 293 Pinworms, 151 Plasmodium Streptococcus agalactiae as
in renal tubular acidosis ( RTA) , 488 Piogl itazone, 305 antimicrobials for, 1 86 cause, 1 29
Phosphate homeostasis, 293 Pi peraci l l i n , 177 stain for, 120 Streptococcus pneumoniae as
Phosphodiesterase I l l i n h i b i tor mechanism of action, 176 Plasmodium {a lcipanun , 149 cause, 128
cilostazol/dipyridamole as, 369 for Pseudomonas aeruginosa , 135 antimicrobials for, 1 86 system i c mycoses as cause, 143
I NDEX
Pneumonic "coin" l esion, 558 development of, 408 Potassium channels Croup B strep screeni ng, 1 29
Pneumothorax, 557, 561 neurotransmitter production i n , 413 opioid effect on, 449 hepari n use i n , 367
Pneumovax vaccine, 1 22 strokes i n , 422 pacemaker action potential l abor induction drugs, 306, 341
PN I-l. See Paroxysmal nocturnal Pontiac fever, 135 and, 260 lactation , 523
hemoglobinuri a " Pope's bl essing," 381 , 383 ventricular action potential l ithium i n , 474
P N S . See Peripheral nervous system Pop l i teal artery and, 260 melasma i n , 396
Podagra, 391 atherosclerosis and, 580 Potassium iodide minors' right to treatment, 56
clinical presentation , 569 Pop l i teal lymph nodes, 192 for sporotrichosis, 146 oligohydramnios, 478
Podiatric medical students, 41 -43 Porphobil i nogen deaminase for Sporothrix schenckii, 576 postpartum mood disturbances, 465
Podocytes, 479 i n porphyria, 358 Potassium shifts, 487 premature contractions, 235, 540
fusion of, 573 Porphyria cutanea tarda Potassium-sparing diuretics, 499, 501 progesterone i n , 520
role in glomerular fi l tration, 480 mechanism of, 358 Potato agar. See Bordet-Cengou agar teratogens, 506
Poikilocytosis, 344 Porphyrias, 358 Potency (pharmacodynamics) termination, via mifepristone, 540
in -thalassemia, 353 barbi turates and, 452 change with inh i b i tors, 226 toxoplasmosis during, 148
pol gene, 1 64, 1 89 Portal hypertension, 314, 331 vs. efficacy, 229 transferrin in, 357
Pol iomyelitis, 410 ARPKD as cause, 498 Potter's syndrome, 478 Pregnancy-induced hypertension, 526
as immunodeficiency Portal hypertensive gastropathy, 333 ARPKD and, 498 Pregnenolone, 291
i nfection, 205 Portal triad, 310 oligohydramnios as cause, 527 Prekal l ikrei n , 348
restrictive lung disease in, 555 Portal vein , 310 Pott's disease, 132, 169 Preload and afterload, 254
spinal cord lesions, 429 Portosystemic anastomoses, 314 cl inical presentation, 566 Premature i n fa n ts, 59
vaccine for, 153, 158, 202 Portosystemic shunts, 333 Pouches, branch ial, 509 necrotiz i n g enterocol itis and, 331
Pol iovirus Port-wine stains, 278, 570 Poupart's l igament. See I nguinal Premature ovarian fai l ure, 529
infection of spinal cord, 430 in Sturge-Weber syndrome, 446 l i gaments Prcmotor area, 418
in unimmunized c h i l d ren, 174 Positional testing, for vertigo, 446 Power ( I - ), 55 Preparation/determination phase of
Polyarteritis nodosa, 204, 276 Posi tion sense, 428 Poxvirus, 1 54, 155 addiction recovery, 470
Polycystic l iver disease, 85 Positive predictive value ( P PV), 51 , PPAR-y nuclear transcription Preprocoll agen , 78
Polycystic ovarian syndrome, 510 581 regul ator, 305 Prcrenal azotemia, 496
anovulation i n , 529
Posi tive reinforcement, 458 PPD test Preseni l i n- l /preseni l i n-2
clomiphene for, 540
Positive selection of T cells, 195 as hypersensitivity reaction, 204 Alzheimer's disease and, 443
endometrial hyperplasia and, 529
Positive selection ( thymus), 193 Prader-Wi l l i syndrome, 82, 83 Presentations, classic , 566-570
ketoconazole for, 539
Postcapi l lary venules of lymph Pral idoxime Pressure (sensatio n ) , 428
spironolactone for, 539
node, 192 as antidote, 239 Pressures in l u ngs, 547
Polycythemia, 223, 166
Posterior cerebral artery, 420, 422 in chol inesterase i n h i b i tor Pressure/volume curve, 256
blood viscosity i n , 255
Posterior communicating artery, 422, toxicity, 233 Pretest probabi l i ty, 51
"blue bloater" as cause, 567
441 Pramipexole, 455 Pretibial myxedema, 299
erythrocyte sedimentation rate
Posterior cranial fossa, 435 Praml i ntide, 305 Prevalence vs. incidence, 52
in, 217, 349
Posterior cruciate l igament ( PCL) Pravastati n, 281 Priapism, 537
eryth ropoietin i n j ection and, 566
tibial attachment site, 379 Praziquantel , 186 trazodone as cause, 476
hepatocellular carcinoma as
Posterior descending/i n terventricular Prazos i n , 237 Primaqui n e
cause, 335
artery ( PO), 253 Precision, 53 reactions t o , 240
in renal cell carcinoma, 494
Posterior fossa malformations, 409 Precocious puberty Primary amyloidosis
Polycythemia vera, 366
Budd-Ch iari syndrome and, 335 Posterior horn of l ateral diseases associated with, 566 diagnostic signs/labs, 572
Polydactyl ism, 88 ventricles, 426, 427 Precontemplation phase of addiction multiple myeloma and, 363
Polyethyl ene glycol , 342 Posterior hypothalamus, 414 recovery, 470 Primary b i l iary ci rrhosis, 338
Polyhydramnios, 527 Posterior inferior cerebellar artery, 422 Predictive value, 51 diagnostic findings/labs, 570
in anencephaly, 409 Posterior nucle i , 415 Predn isone, 306, 373 Primary c i l ia ry dysk i n esia, 76
Polymenorrhea, 521 Posterior pituitary, 287, 414 Preeclampsia, 526 Primary glomerular disease, 489
Polymerase chain reaction ( PC R) , 79 Posterior spinal arteries, 427 Pregangl ionic sympathetic fibers, 286 Primary hemostasis
Polymyalgia rheumatica, 393, 580 Posterior spinothalamic tract, 427 Pregnancy, 523 platelets in, 344
Polymyositis/dermatomyosi tis, 205, Postpartum depression, 465 aminoaciduria in, 482 Primary hypera ldosteronism, 296
394 Postpartum psychosis, 465 amniotic Auid abnormal ities, 527 Primary hyperparathyroidism, 300
Polymyxin Postradiation fibrosis anemia i n , 352 Primary pulmonary hypertension, 549
in Thayer-Martin (VPN) cardiomyopathy caused by, 272 antibiotics to avoid in, 190 Primary sclerosing cholangitis, 338
media, 1 20 Postrena I fa i I ure, 496 anticoagulation treatment, 574 Primary somatosensory cortex, 415
Polyomavirus, 1 54, 155 Poststreptococcal glomerulonephritis anti hypertensive medication Primase, 68
Polyostotic fi brous dysplasia, 388 diagnostic signs/labs, 572 for, 279 Primi tive atria, 250
diagnosis for, 566 as hypersensitivity disorder, 204 anti-Rh antibodies and, 347 Pri m itive neuroectodermal tumors
Polyps Posttranslational modifications, 7l B udd-C h iari syndrome and, 335 ( P N ETs), 448
colonic, 331 Post-traumatic stress disorder, 467 compl ications of, 526-527 Primitive reA exes, 432
Polysaccharides SS R l s for, 475 diabetes during. See Diabetes Primitive ventricle, 250
bacterial capsules, 1 18 treatment for, 472 during pregnancy Primaqui n e
glycocalyx, 1 1 8 Postural tremor. See Essential tremor diabetes mell itus type I i n , 409 for Plasmodit1m vivax/ovale, 149
Polyuria Postviral infections, 1 68 D I C i n , 360 Pringle maneuver, 310
F'a nconi 's syndrome as cause, 569 Potassium ectopic, 527 PR i n terval , 261 , 262
Pompe's disease astrocytes and, 41 1 epil epsy drugs and, 452 Prinzmeta l 's angi n a , 269
c l i nical presentation, 568 for diabetic ketoacidosis, 574 eryth rocyte sedimentation rate calcium channel blockers for, 279
Pompe's disease, 1 1 1 disturbances i n , 487 in, 217, 349 sumatriptan contra i ndicated
Pons, 432 diuretics and, 501 estrogen l evels i n , 520 in, 456
central pontine myel inolysis, 419 insul i n effect on, 288 folate deficiency and, 354, 409 Prions, 167
cranial nerve nuclei i n , 434 along proximal tubule, 484 glucosuria in, 482 in C reutzfeldt-jakob disease, 443
I ND E X
Probenecid , 406 for glaucoma, 449 Prothrombin time ( PT) Pseudopolyps

cidofovi r toxicity prophylaxis, 188 kidney functions, 486 warfarin and, 367 in ulcerative colitis, 328
for gout, 574 N SAJ D effect on, 405 Prothrom b i n time ( JY f) Pseudovi rion, 1 53
as sui fa drug, 242 patent ductus arteriosus ( P DA) tests, 359 Psittacosis, 139
Procainamide and, 252 Proton pump i n h i bitors, 340, 341 P 1 6 gene, 221
as antiarrhythmic, 283 Prostate, 516. See also Benign for Helicobacter pylori, 137 Psoriasis, 397
reactions to, 241 prostatic hyperplasia ( B P H ) Protoporphyrin 1-1 I A-B 2 7 and, 1 9 4 , 578
Proca ine, 454 pathol ogy, 535 i n lead poisoni ng, 358 hyperkeratosis/p arakeratosis in, 396
Procarbazi n e Prostate cancer, 535, 536, 579 Protozoa, 150 methotrexate for, 371
reactions t o , 241 adenocarcinoma, 536 antiprotozoan therapy, 186 as plaque, 395
Procedure bias, 53 blastic bone l esions i n , 224 CNS infections, 148 scales i n , 395
Processus vagi nal is, 514 estrogens for, 539 diarrhea caused by, 168 TN F-a i n h i bitors for, 406
fa i l u re to close, 318 Autamide for, 539 G J infections, 147 Psoriatic arthritis, 392
Procoagulation , 348 incidence and mortal ity, 224 hematologic infections, 149 psoriasis and, 397
Procollagen, 78 leuprotide for, 539 Proximal colon therapeutic anti bodies for, 210
Progesterone, 291 , 520 PSA marker, 222 i n H N PCC!Lynch syndrome, 332 Psych iatric treatments, 472
in menstrual cycle, 521 treatment for, 575 Proximal convoluted tubules, 481 , Psychi atry
secretion of, 538 Prostate-specific antige n . See PSA 483, 499 pathology, 459-471
signa l ing pathway, 294 marker for prostate cancer Proximal ileum, 31 1 pharmacology, 472-476
Progestins, 540 Prostatic acid phosphatase ( PAP) Proximal renal tubular acidosis psychol ogy, 458-459
in oral contraceptives, 540 as prostate cancer marker, 222 ( RT A) , 488 Psychoactive drug intoxication and
Progressive hereditary nephritis, 79 as tumor marker, 536 Proximal tubules withdrawal , 470-471
Progressive multifocal Prostatic urethra, 479 amino acid reabsorption, 482 Psychoactive drugs
leukoencepha lopathy Prostatitis, 535 glucose reabsorption in, 482 gynecomastia caused by, 535
( P M L) , 445
PSA in, 222 relative concentrations along, 484 Psychology, 458-459
Proinsul i n , 288
Prosthetic devices PSA marker for prostate cancer, 222, conditioning, 458
Projectio n , as ego defense, 458.
bacterial risk with, 128 536 ego defenses, 458-459
See Transference and
Protamine Psammoma bodies, 223 transference, 458
countertransference
as antidote, 239 in meningioma, 447 Psychomotor ep i lepsy
Prokaryotes
Protamine sulfate, 367, 368, 575 in ovarian tumors, 532 olfactory hall ucinations i n , 463
DNA repl ication in, 68
Protease i n h i b i tors, 1 89 i n thyroid cancer, 299 Psychosis
m RNA start codons, 70
I gA, 122, 128, 134 P-selectin antipsychotics for, 473
RNA polymerases i n , 70
name suffix, 243 in l eukocyte extravasation, 215 LSD use as cause, 471
tRNA, 72
reactions to, 240, 241 Pseudoappendicitis, 1 68 PC P use as cause, 471
Prolact i n , 289, 290
Proteases Pseudodiverticula, 329 postpartum , 465
estrogen and, 520
granzyme , 197 Pseudoephedrine, 564 prednisone as cause, 373
lactation a n d , 523
protein digestion by, 322 Pseudogout, 391 signs of, 463
para neoplastic syndrome and, 494
Proteasomal degradation diagnostic findings/labs, 573 Psychotherapy
secretion of, 287
posttranslational modification, 7l Pseudohermaphroditism, 524 for postpartum depression, 465
signal ing pathway, 294
Proteasome, 75 adrenal enzyme deficiency as Psychotic disorders, 462
Prolactinoma, 301 , 447, 580
Protein kinases cause, 291 JY rl I . See Parathyroid hormone
treatment for, 575
i n signal transduction, 231 Pseudohypoparathyroidism, 300 ( PT! l )
Pro l i ferative glomerular disorders, 489
Proteins Pseudomembranes, gray, 174 JYr J !-rel ated peptides
Prol iferative phase of wound
catabol ism of, 302 Pseudomembranous col itis as para neoplastic effect, 223
heal i ng, 216
free radical i n j u ry, 215 aminopenicil l ins as cause, 177 JY r H r P
Prometric testing centers, 5, 6, 7,
Protein A, 122, 128 clindamycin as cause, 181 paraneoplastic syndrome
16, 17
Protein C , 348, 360 as drug reaction, 240 and, 494
Promoter
Protein S, 348, 360 vancomycin for, 179 Ptosis
in gene expression, 70
synthesis of, 69, 73 Pseudomonas, 1 19, 121 i n H o rner's syndrome, 431
Proneph ros, 478
in transudate vs. exudate, 216 bacterial endocarditis caused Horner's syndrome as cause, 569
Propafenone
Protein synthesis i n h ibitors, 179 by, 274 J Y I[ ( i n trinsic pathway), 368
as antiarrhyth mic, 283
name suffix, 243 antimicrobials for, 177, 178, 182 Puberty
Prophase, 74
Proteinuria in cystic fibrosis, 570 apocrine gland activation, 378
Prophylaxis, antimic robial, 184
nephritic syndrome as cause, 492 Gram staining, 133 precocious, caused by granulosa
Propofol
nephrotic syndrome as cause, 490, as immunodeficiency cell tumor, 532
as intravenous anesthetic, 454
567 infection, 205 precocious, caused by Leydig cell
Propranolol, 238
renal papi l lary necrosis as osteomyel itis and, 579 tumors, 537
as antiarrhythmic, 284
cause, 496 Pseudomonas aemginosa, 121 , 135, 175 precocious, caused by pol yostotic
for migraine headaches, 446
Proteolysis as nosocomial infection, 174 fibrous dysplasia, 388
Proprioception
cortisol effect on, 292 nosocomial pneumonia and, 579 Pudendal nerve block, 379
cerebell u m and, 415
Proteolytic processing, 78 osteomyel itis caused by, 1 69 P u lmonary anth rax, 1 3 1
loss of, with stroke, 422
Proteus, 1 19, 122 pigment produced by, 122 Pu l monary arteries, 544
Propylth iourac i l , 295, 306
Gram sta i n i ng, 133 toxin of, 1 24 bronchus and, 545
reactions to, 240
Proteus mirabilis treatment for, 575 development of, 509
Prosencephalon, 408 hypertension of, 575
antimicrobials for, 177, 178 urinary tract infections caused
Prospective study, 50 stenosis of, 267
kidney stones caused by, 493 by, 170
Prostacyc l i n , 404 Pulmonary capillary wedge
as nosocomial infection , 174 Pseudomonas species, 86
Prostaglandins, 321 , 404
u r i na ry tract i nfecti ons caused Ps eu d omyxoma peritonei , 532 pressure, 264
aspirin effec t on , 368, 404 Pseudop al isadin g tumor cel l s , 447 , Pu l monary circu l ation, 549
by, 170
cortiso I effect on, 292 573 Pulmonary compliance, 547
atio n , 320 Prothrombi n gene mutation, 360
gastric acid re gul
I NDEX
Rocky Mountain spotted fever, 139 Sacrococcygeal area tumors, 531 Sch i l l ing test, 93 Secondary syp h i l i s
clinical presentation, 569 S-adenosyl-meth ionine, 93 for B 1 2 deficiency, 574 c l inical presentation, 569
Rocuronium, 455 Salicylates Schistocytes, 350 Secretin, 319
Rod bacteria. See Baci l l i antidote to, 239 in -thalassemia, 353 gastric acid regulation , 320
Rol l i ng (leukocyte extravasation ) , 215 respiratory a l kalosis caused by, 488 in D I C , 360 location of, 321
Romberg maneuver Sal iva, 320 in macroangiopathic anemia, 357 Secretion rate (renal )
syphilis and, 429 Salivary amylase, 322 Schistosoma, 1 52 calculating, 481
Rom berg test, 138 starch digestion by, 322 Schistosoma haematobiu m , 152 Secretions, bodily
Rooting reflex, 432 Sal ivary glands oncogenicity of, 222 immunoglobul i n in, 198
Ropinirole, 455 innervation of, 434 Schistosoma mansoni, 1 52 Secretory l gA, 323
Rose gardener's disease, 146 tumors of, 324 Schizoaffective disorders, 463 Sedatives
Rosenthal fibers Salk pol io vaccine, 153, 202 Schizoaffective persona l i ty respiratory acidosis caused by, 488
in pilocytic astrocytomas, 448 Salmeterol, 563 disorder, 469 "Seed and soil " theory of
Roseola c l i n ical use, 235 "Schizo" disorders, 469 metastasis, 2 1 8
cli nical presentation , 172 Salmonella , 1 19, 121 Sch izoid persona l i ty disorder, 468, 469 Segmental a rtery of ki d n ey, 479
herpesvirus as cause, 155, 1 56 antimicrobials for, 177, 1 82 Sch izoph renia, 463, 469 Segmented viruses, 1 59
Rosigl itazone, 305 antiphagocytic factor, 121 anti psychotics for, 473 Seizures, 445
Rostral fold closure fai l ure, 308 diarrhea caused by, 168 auditory hall ucinations and, 463 amphetamines as cause, 471
Rosuvastatin, 281 food poisoning caused by, 1 67 dopamine l evels i n , 413 calcium defi ciency as cause, 487
cl inical presentation , 569 Gram sta i n i ng, 133 neurotransmitter changes, 461 as d rug reactio n , 241
Rotator cuff muscles, 379 as immunodeficiency treatment for, 472, 576 drugs for, 451
Rotavi rus, 158, 159 infection, 205 Schizophreniform disorders, 463 drug toxicities, 452
diarrhea ca11scd by, 168 mesenteric adenitis caused by, 167 Schizol)pal persona l i ty disorder, 468, S S Rls as cause, 475
Rotenone, 102 osteomye l i tis caused by, 1 69, 356, 469 Sturge-Weber syndrome as
Roth 's spots, 274 579 Schwa 1m cells, 41 1 , 412 cause, 446
cl inical presen tation, 569 vs. Shigella , 136 Guillain-Barre syndrome and, 444 treatme n t for, 574, 576
Rotor's syndrome, 336 Salmonella typhi, 136 myel inization by, 41 1 tuberous scl erosis as cause, 446
Rough endoplasmic reticulum Salpingitis
Schwannomas, 412, 447, 577 Selectins, 2 1 5
( R E R) , 74. See N i ssl sta in i n pelvic inflammatory disease, 173
SCI D. See Severe combined Selection b i a s , 53
Nissl sta i n for, 41 1 Saltatory conduction , 41 1
i m munodeficiency disease Selection of T cells, in thymus, 193
Rouleaux formation , 363 Sample size, effect on power, 55
( SC I D ) Selective estrogen receptor
diagnosti c findings/labs, 573 Sampl ing bias, 53
Sclera, 437, 438 modulators ( S E RMs), 540
Round l igament of the uterus, 515 SandAy as disease vector, 1 50
blue, cause of, 566 Selective lg deficiency, 206
Roundworms. See Nematodes SandAy/Rift Val l ey fevers, 158
Scleral icterus Selective seroto n i n reuptake
( roundworms) Saponification, 212
l iver cell fail ure as cause, 333 i n h i b i tors ( S S RJs)
Rovsing's sign Saqu i n avir, 1 89
Scleral venous sinus, 437 for anorexia, 574
RPF. See Renal plasma Row ( RPF) Sarcoidosis, 94, 393
Scl erodactyly for bul i m i a , 574
RRNA, 70 cardiomyopathy caused by, 272
in scleroderma, 395 for depression, 574
RSV. See Respi rato ry syncytial vi rus c l i n ical presentation, 566
Scleroderma, 395 name suffix, 243
( RSV) erythema nodosum and, 400
achalasia and, 324 sexual dysfu nction and, 60
RU-486 (mifepristone), 540 facial nerve palsy i n , 437
autoantibodies associated with, 205 Selegi l i n e , 455, 456, 475
Rubel la, 160 as granulomatous disease, 216
c l inical presentation, 172 as restrictive lung disease, 555 diagnostic findings/labs, 570 Sele n i u m sulfide
heart sounds i n , 259 Sarcoma botryoides, 532 Sclerosing adenosis, 533, 535 for Tinea versicolor, 144
maternal/neonatal Sarcomas Scl erosing cholangitis Self-mutilation
manifestations, 171 vs. carcinoma, 219 ulcerative colitis and, 328 in borderl ine p ersonal ity
in unimmunized c h i l dren, 174 methotrexate for, 371 Sclerosis disorder, 468
Rubeola (measles) virus, 1 58, 160 radiation exposure and, 220 i n osteoarthritis, 390 Lesch-Nyhan syndrome as
c l i nical presentation, 172, 569 Sa reo meres Scopolamine cause, 567
in unimmunized c h i l dren, 174 i n muscle contraction , 385 c l i nical use, 234 Selsun. See S e l e nium sul fi d e
vaccine for, 202 Sarcoplasmic reticulum Scores on U S M L E Step I exam, 12 S e m i nal ves i c l es, 479, 516
Rubor (redness), 214 i n muscle contractions, 385 Scorpion sting developm e n t of, 512
Rugae of stomach Sargramostim, 210 acute pancreatitis caused by, 339 Seminifero11s tubules, 5 1 6
hypertrophy of, 327 SARS, 1 58 Scotch tape test for pinworms, 151 i n Klinefe lter's syndrome, 524
Russell's sign, 469 Sartorius muscle, 316 Scotomas spermatogenesis a n d , 519
" Rusty" sputu m , 128 "Saturday night palsy" (wrist macular degeneration and, 441 Semi nomas, 536, 581
RVH . See Right ventricular drop) , 381 , 382 in papi l l edema, 439 Semust i n e , 372
hypertrophy ( RVH ) "Sausage fingers," 392 Scrotum, 516 Sen i l e osteoporosis, 387
Ryanodine receptor Savants, autistic, 461 Scurvy, 78, 94 Senile plaques, 443
in muscle contractions, 385 Scalene muscles c l i n i cal presentation, 569 diagnosric fi n d i ngs/labs, 571
i n respi ration, 546 Seasonal affective disorder, 465 Sensitivity, 51
5 Scales, 395 Sebaceous glands, 378 Sensitivity equatio n , 581
S- 1 00 marker, 222, 403 , 447 Scanning speech, in multiple Seborrh eic keratosis, 397 Sensori neural hearing loss, 436
S- 1 00 protein sclerosis, 444 Secobarbital, 452 Sensory corpusc l e s , 412
in Langerhans cell Scapula, winged, 381 Secondary b i l iary cirrhosis, 338 Sensory cortex, 418
h istiocytosis, 366 Scarlet fever Secondary general ization , of strokes in , 422
Sabe r sh i ns, 138, 171 c l i n ic'd presentation, 172, 569 seizure, 445 Se p a ra tion anxiety di order, 460
Sabin pol io vacci ne, 153, 202 Streptococcus pyogenes causing, 129 Secondary glomerular disease, 489 Sepsis
Sabouraud's agm, 120, 145 S cells, 319, 321 Secondary hyperparathyroidism, 300 DIG as cause, 360, 578
Sacc u l a r 'l l l e u rysm s , 422, 423 Sch i l l e r-Duva l bodies, 531 , 536
Sac ra l s p i n a l nerves, 427 Secondary pulmonary as im munod eficien cy
diagnostic findi ngs/la bs, 571
hypertensi on, 549
in fection , 205
INDEX
Probenecid, 406 for glaucoma, 449 Prothrombin time ( PT) Pseudopolyps

cidofovi r toxicity prophylaxis, 188 kidney functions, 486 warfarin and, 367 i n ulcerative colitis, 328
for gout, 574 N SAJ D effect on, 405 Prothrombin time (PT) Pseudovi rion , 1 53
as sulfa drug, 242 patent ductus arteriosus ( P DA) tests, 359 Psittacosis, 139
Procainamide and, 252 Proton pump i n h i b i tors, 340, 341 P 16 gene, 221
as antiarrhyth mic, 283 Prostate, 516. See also Benign for /-/ el icobacter pylori, 137 Psoriasis, 397
reactions to, 241 prostatic hyperplasia ( B P H ) Protoporphyrin H L A-B27 a n d , 1 94, 578
Procai n e , 454 pathology, 535 i n l ead poisoning, 358 hyperkeratosi s/parakeratosis in, 396
Procarbaz i n e Prostate cancer, 535, 536, 579 Protozoa, 150 methotrexate for, 371
reactions t o , 241 adenocarcinoma, 536 antiprotozoan therapy, 186 as plaque, 395
Procedure bias, 53 blastic bone lesions in, 224 C N S infections, 148 scales i n , 395
Processus vagi nal is, 514 estrogens for, 539 diarrhea caused by, 168 TN F-a i n h i b i tors for, 406
fai l ure to close, 318 Autamide for, 539 Gl infections, 147 Psoriatic arth ritis, 392
Procoagulation, 348 incidence and morta l i ty, 224 hematologic infections , 149 psoriasis and, 397
Procol lagen, 78 leu protide for, 539 Proximal colon therapeutic anti bodies for, 210
Progesterone, 291 , 520 PSA marker, 222 i n H NPCC/Lynch syndrome, 332 Psych iatric treatments, 472
in menstrual cycle, 521 treahnent for, 575 Proxi mal convoluted tubules, 481 , Psych i a try
secretion of, 538 Prostate-specific antige n . See PSA 483 , 499 pathology, 459-471
signaling pathway, 294 marker for prostate cancer Proximal ileum, 31 1 pharmacol ogy, 472-476
Progestins, 540 Prostatic acid phosphatase ( PAP) Proximal renal tubular acidosis psychol ogy, 458-459
in oral con traceptives, 540 as prostate cancer marker, 222 ( R T A), 488 Psychoactive drug intoxication and
Progressive hereditary nephritis, 79 as tumor marker, 536 Proximal tubules withdrawa l , 470-471
Progressive multifocal Prostatic urethra, 479 amino acid reabsorption, 482 Psychoactive drugs
l eukoencephalopathy Prostatitis, 535 glucose reabsorption in, 482 gynecomastia caused by, 535
( PM L) , 445 PSA in, 222 relative concentrations along, 484 Psychology, 458-459
Proi nsu l i n , 288 Prosthetic devices PSA marker for prostate cancer, 222, conditioning, 458
Projection, as ego defense, 458. bacterial risk with, 1 28 536 ego defenses, 458-459
See Transference and
Protamine Psammoma bodies, 223 transference, 458
countertransference
as antidote, 239 i n meningioma, 447 Psychomotor epil epsy
Prokaryotes
Protamine sulfate, 367, 368, 575 i n ovarian tumors, 532 olfactory hallucinations in, 463
D A repl ication i n , 68
Protease i n h i b i tors, 189 in thyroid cancer, 299 Psychosis
m RNA start codons, 70
lgA, 122, 128, 134 P-selectin anti psychotics for, 473
RNA polymerases in, 70
name suffix, 243 i n l eukocyte extravasation, 215 L S D use as cause, 471
tRNA, 72
reactions to, 240, 241 Pseudoappendicitis, 1 68 PC P use as cause, 471
Prolactin, 289, 290
Proteases Pseudodiverticula, 329 postpartum , 465
estrogen and, 520
granzyme, 197 Pseudoephedrine, 564 prednisone as cause, 373
lactation and, 523
prote i n digestion by, 322 Pseudogout, 391 signs of, 463
para neoplastic syndrome and, 494
Proteasomal degradation diagnostic findings!labs, 573 Psychotherapy
secretion of, 287
posttranslational modification, 7l Pseudohermaphroditism, 524 for pos)artum depression, 465
signaling pathway, 294
Proteasome, 75 adrenal enzyme deficiency as Psychotic disorders, 462
Prolacti noma, 301 , 447, 580
treatment for, 575
Protein kinases cause, 291 PT!- 1 . See Parathyroid hormone
Prol iferative glomerular disorders, 489 i n signal transduction, 231 Pseudohypoparathyroidism, 300 ( PT H )
Prol iferative phase of wound Proteins Pseudomembranes, gray, 174 PTI- 1-related peptides
heal ing, 216 catabol ism of, 302 Pseudomembranous col itis as para neoplastic effect, 223
Prometric testing centers, 5, 6, 7, free radical i n j u ry, 215 aminopenici l l ins as cause, 177 PTH rP
16, 17 Protein A, 122, 128 cli ndamycin as cause, 1 81 para neoplastic syndrome
Promoter Protein C , 348, 360 as drug reaction, 240 and, 494
in gene expression, 70 Protein S , 348, 360 vancomycin for, 179 Ptosis
Pronephros, 478 syn thesis of, 69, 7l Pseudomonas, 1 19, 121 i n H o rner's syndrome, 431
Propafenone in transudate vs. exudate, 216 bacterial endocarditis caused H o rn e r's syndrome as cause, 569
as antiarrhythmic, 283 Protein synthesis i n h ibitors, 179 by, 274 lYf T ( intrinsic pathway), 368
Prophase, 74 name suffix, 243 antimicrobials for, 177, 178, 182 Puberty
Prophylaxis, antimicrobial , 184 Protei nuri a in cystic fibrosis, 570 apocrine gland activation, 378
Propofol nephritic syndrome as cause, 492 Gram stai n i ng, 133 precocious, caused by granulosa
as intravenous anesthetic, 454 nephrotic syndrome as cause, 490, as immunodeficiency cell tumor, 532
Propranolol, 238 567 infection, 205 precocious, caused by Leydig cell
as antiarrhyth mic, 284 renal pap i l l a ry necrosis as osteomye l i tis and, 579 tumors, 537
for migraine headaches, 446 cause, 496 Pseudomonas aeruginosa, 121 , 135, 175 precocious, caused by polyostotic
Proprioception Proteolysis as nosocomial i n fection, 174 fi brous dysplasia, 388
cerebel l u m and, 41 5 cortisol effect on, 292 nosocomial pneumonia a n d , 579 Pudenda l nerve block, 379
loss of, with stroke, 422 Proteolytic processi ng, 78 osteomyelitis caused by, 1 69 Pulmonary a n th rax, 131
Propyl th iourac i l , 295, 306 Proteus, 1 19, 122 pigment produced by, 122 Pulmonary arteries, 544
reactions to, 240 G ram sta i n i ng, 133 toxin of, 1 24 bronchus and, 545
Prosencephalon, 408 Proteus m irabilis treatment for, 575 development of, 509
Prospective study, 50 antimicrobials for, 177, 178 urinary tract infections caused hypertension of, 575
Prostacyc l i n , 404 kidney stones caused by, 493 by, 170 stenosis of, 267
Prostaglandins, 321 , 404 as nosocomial infection, 174 Pseudomonas species, 86 Pu lmonary capi l l a ry wedge
aspirin effect on, 368. 404 urinary tract infections caused Pseudomyxoma peritonei , 532 pressure, 264
cortisol effect on, 292 by, 170 Pseudopal isading tumor cells, 447, Pulmonary circulation, 549
gastric acid regulation, 320 Proth romb i n gene mutation, 360 573 Pulmonary compliance, 547
I NDEX
Pulmonary edema Pyoderma gangrenosum Raltegravir, 189 Rectu m , 309

in C l-I F, 273 ulcerative col itis and, 328 Random error, 53 anastomosis in, 314
di uretics as cause, 500 Pyogenic granuloma, 278 Randomization, 53 blood supply to, 312
as Ml compl ication, 271 Pyogenic infections Ranitidine, 341 cancer of, 224
opioids for, 449 C3 deficiency as cause, 200 Rapamycin. See S i rol imus Rectus abdominis muscle, 317, 318,
pulmonary compl iance i n , 547 Pyogenic osteomye l i tis Raphe nucleus 546
in renal fai l ure, 497 diagnostic findi ngs/labs, 573 5-HT production, 413 Rectus muse I es
treatment of, 500 Pyramidal decussation , 432 Rapidly progressive M L F syndrome and, 442
Pul monary embol ism, 553 Pyramidal is muscle, 317 glomerulonephritis Recurrent l a ryngeal nerve
diagnostic findings/labs, 572 Pyramid (bra i n stem), 432 (RPGN), 492 compression of, 253
heparin for, 367 Pyrantel pamoate, 1 86 Rapid review, 565-582 Red bl ood cells. See E ryth rocytes
Pulmona1y fibrosis for nematodes, 151 classic clinical/lab findings, 570- Red curran t jelly stools
bleomycin as cause, 372 Pyrazi namide, 183 573 diseases causi ng, 569
busulfan as cause, 372 for Mycobacterium hlbercu losis, 575 classic presentations, 566-570 Red infarcts, 213
diagnostic findings/labs, 572 reactions to, 241 equations, 581 -582 Red man syndrome, 179
as drug reaction, 240 for tuberculosis, 183 key associations, 576-580 Red rashes of c h i l d hood, 172, 174, 566
pulmonary compl iance i n , 547 Pyridostigmine, 233 Rapprochement, 59 Reduction
as restrictive lung disease, 555 Pyridoxine, 91 ras gene, 221 i n drug metabolism, 228
Pulmonary hypertension, 549 for sideroblastic anemia, 353 Rashes Reduvi id bug as disease vector, 150
associations, common/ Pyrimethamine, 148, 1 86, 576 "blueberry muffi n " (CMV), 171 Reed-Stern berg cells, 361
i mportant, 580 Pyrimidines, 64, 65 of c h ildhood, 172 diagnostic findings/labs, 571
bosentan for, 564 Pyrogens diaper (Candida albicans), 145 Reflex bradycardia, 236
pulmonary circulation i n , 549 cytokines as, 200 diffuse macular ( 1-1 1-lV-6) , 1 56 angiotensin I I effect on, 485
Pulmonary hypoplasia Pyruvate carboxylase, 101 , 102 maculopapular (measl es), 161 ReA exes
i n Potter's syndrome, 478 Pymvate dehydrogenase, 98, 100, 101 petech ial (CMV), 171 clinical, 432
Pulmonary infarction, 213 Pymvate k inase, 98, 356 "slapped cheeks" ( B 19 virus), 155 cranial nerve, 434
Pulmonary surfactant, 544, 555 Pyruvate metabol ism, 101 truncal (rubel l a ) , 1 60 frontal l obe lesions and, 419
Pul monary vascular resistance Pyuria primitive, 432
Rate-determining enzymes of
( PVR), 549, 582 in drug-induced intersti tial ReA u x ( G I )
metabol ic processes, 97
Pulmonary vei n , 544 nephritis, 495 neoplasms <lssociated with, 220
Rathke's pouch , 287
Pulmonic regurgitation Regenerative nodules
craniopharyngiomas and, 448, 505
heart murmur with, 258 Q i n cirrhosis, 333
Rational ization, 459
Pulmonic stenosis, 578 Q fever, 139, 1 40 Regional spec i fi cation of developing
Raynaud's phenomenon, 276
heart murmur with, 258 QRS complex, 261 bra i n , 408
calcium channel blockers for, 279
Pulsatile parathyroid hormone QT interva l , 261 Regression, as ego defense, 459
clinical presentation, 568
for osteoporosis, 387 ziprasidone and, 473 Regular insul i n , 305
in l upus, 393, 566
"Pulsel ess disease," 276 QT prolongation, 1 80 Regulation of cerebral perfusion, 421
in scl eroderma, 395
Pulsus paradoxus, 275 Qual itative platelet defects Regul ation of gene expression, 70
RBC path ologies, 351 . See
Punishment, 458 blood transfusions for, 360 Regulation of spermatogenesis, 519
also Erythrocytes
Pupillary constrictor muscle, 440 Quantifying risk, 52 Regul atory T cells, 197, 347
RBCs. See E ryth rocytes
Pupillary control , 440 Quellung reaction, 121 Reichert's cartilage
H.b gene, 221
Pupillary reAex, 434, 440 Quetiapine, 473 derivation of, 510
Reabsorption and secretion rate Rei d i n dex, 554
Pupils, 437 Quinidine
as antiarrhyth mic, 283 (renal ) , 481 Reinke crystals, 537
innervation of, 434
as P-4 5 0 i n h i bitor, 242 Reaction formation, 459 diagnostic findings/labs, 573
unreactive, cause of, 569
reactions to, 240, 241 Reactions to drugs, 240-241 Reiter's syndrome, 173, 392
Purines, 64, 65, 406
Quinine, 1 86 Reactive arth ritis, 392 I-I L A-B27 and, 194, 578
Pur i n e salvage, 66
Purkin j e cells of cerebel l u m , 162 reactions to, 241 clinical presentation, 570 Relapse phase of addiction
Purkinje fibers Quinupristin Reactive gliosis recovery, 470
cerebellum and, 41 5 mechanism of action, 176 i n ischemic stroke, 425 Relative polycyth emia, 366
Purple skin/mouth nodules for VRE, 184 Reactive oxygen i n termediates Relative risk ( RR), 50, 52, 581
Kaposi's sarcoma as c<mse, 567 Q waves (ROis), 103 Rel iab i l i ty, 53
Purpura in myocardial infarctions, 271 Reactive oxygen species Remodel ing phase of wound
1-l enoch-Schonlein, 568 chronic granul omatous disease heal i ng, 216
Pustules, 395 R and, 207 REM sleep, 61
Putamen, 416 RAAS. See Renin-angiotensin Reassortment, vira l , 1 53 acetylchol i n e levels i n , 413
p value in statistics, 54 aldosterone system Recall bias, 53 benzodiazepines and, 453
PVC (polyvi nyl chloride) Rabies virus, 1 58, 162 Receptor-associated tyrosine kinase Renal angiomyol ipoma
angiosarcomas and, 335 antibodies for, 202 signal ing pathways, 294 tuberous sclerosis as cause, 446
P waves, 261 vaccine for, 153, 202, 445 Receptor binding, 229 Renal angiomyo l i pomas, 85
Pyelonephritis, 169, 495 Radial nerve, 382 Receptors Renal arteries, 312, 479
kidney stones as cause, 493 course of, 380 cardiac, 264 stenosis of, 502
renal papillary necrosis and, 496 Radial pulse chol i nergic, 232 Renal blood Row
WBC urinary casts i n , 489 i n Klumpke's palsy, 382 gastric, 321 equation for, 582
Pyknosis, 212, 213 Radiation exposure noradrenergic, 232 ERPF and, 480
Pyloric sphincter, 321 neoplasms associated with, 220 Recombinant cytoki nes, 210 Renal cell carcinoma, 494, 580
Pyloric stenosis osteosarcomas and, 389 Recombinant vaccines, 1 53 carci nogens affecting, 223
congenital, 308 Radioimmunosorbent assay, 203 Recombination, viral, 1 53 polycythemia and, 366
Pyocyanin Radiopaque kidney stones, 493 Rectal suction b iopsy, 330 recombinant cytokines for, 210
Pseudomonas aerugi nos a Ragged red fibers, 84 Rectosigmoid colorectal cancer, 332 von 1-l ippel-Lindau disease as
production of, 135 Ral oxifene, 374, 540 Rectosigmoid polyps, 331 cause, 446, 569
I N DEX
Renal clearance calculation, 480 Reserpine, 456 Retrograde amnesia, 419, 461 Rickettsia rickettsii, 139, 140
Renal cortex, 499 mechanism, 232 Retroperitoneal structures, 309 treatment for, 576
Rena I cysts, 498 reactions to, 241 Retrospective study, 50 Rickettsia typhi, 139, 140
Renal disease Residency, 26, 27, 32 Retroviruses, 1 58 Riedel 's thyroi ditis, 298
diagnostic findi ngs/labs, 573 i n terviews for, 34 Rett's disorder, 461 Rifampin, 183
dosage calculations with, 227 Residual sch izoph ren ia, 463 Reverse transcriptase, 1 64 for f-JaemofJh ilus influenzae, 134,
hyperparathyroi dism and, 300 Residual vol ume ( RY), 546 Reverse transcriptase i n h i b i tors, 1 89 575
hypertension and, 267, 579 Resistance equation, 582 Reye's syndrome, 334 mechanism of action, 176
Renal epithel ial casts in urine, 573 Resistance, pressure, Aow, 255 aspirin as cause, 368, 404 as men i ngococcal prophylaxis, 184
Renal fail ure, 496 Resistant bacteria R group for mycobacteria, 1 83
acute tubular necrosis as cause, 496 antimicrobials for, 1 84 penici l l i nase resistance, 177 for Mycobacteriu m tubercu loSIS, 575
i n ADPKD, 498 Respi ratory acidosis, 487, 488 Rhabdomyomas, 219, 275, 577 for Neisseria, 134
aspirin as cause, 368, 404 Respi ratory alkalosis, 487, 488 diseases associated with , 220 for Neisseria meni ngitidis, 575
consequences of, 497 aspirin as cause, 368 Rhabdomyosarcomas, 219 as P-4 5 0 i nducer, 242
lab values for, 496 Respi ratory burst (oxidative burst), 103 dactinomyci n for, 372 for tuberc u l osis, 183
N SAI Ds as cause, 486 Respi ratory distress syndrome Rhabdoviruses, 1 58 tubulointerstitial nephnti s caused
Renal ischemia ( RD S ) , 59 R hemoglobin, 547 by, 49 5
acute tubular necrosis and, 496 Respiratory quotient, 550 Rheumatic fever, 274 Right gastric artery, 3 1 3
N SAI Ds as cause, 405 Respiratory syncytial virus ( RSY), 1 58, diagnostic criteria, 129 R i g h t gastro-omental artery, 3 1 3
Renal medulla, 479, 499 1 60, 560 diagnostic findi ngs/labs, 572 R i g h t heart fai l ur e , 273 . See
Renal osteodystrophy, 300 antimicrobials for, 187 as hypersensitivity disorder, 204 also Congestive heart fai l ll l e
lab values, 497 Respi ratory system streptolys i n 0 toxin i n , 125 (CI IF)
renal fai l u re as cause, 497 anatomy, 544-545 valvular lesions, 259 associations, common/
drug reactions i n , 240 Rheumatic h eart disease, 579 important, !180
Renal papi llary necrosis, 496
pathology, 553-560 Rh eumatoid arth ritis, 390
sickle cell anemia as cause, 356 Right h epatic duct, 316
pharmacology, 562-564 amyloidosis and, 490
Renal pelvis Right horn of sinus venosus, 250
physiology, 546-552 b i l iary cirrhosis and, 338
development/embryology, 478 Right lymphatic duct, 192
Respi ratory tract i nfections COX-2 i n h i b i tors for, 405
Renal plasma Aow ( RPF), 481 Righ t parietal lobe
C3 deficiency as cause, 200 diagnostic findi ngs/labs, 570
changes i n , 481 l esions i n , 419
as i mmunodeficiency eryth rocyte sedi mentation rate
relationship with estimated renal Right s h i ft
infection, 205 and, 349
plasma A ow ( E RPF), 480 h emoglobin-oxygen dissociation
Respi ratory t ree, 544 HLA-DR3 and, 578
Renal reabsorption and secretion c u rve, 548
Respiratory zone of respiratory H LA-D R4 and, 194
rate, 481 Right-sided endocarditis
tree, 544 as hypersensitivity disorder, 204
Renal secretion, 481 h eroin addiction and, 471
Resting tremor, 417 i n A iximab for, 342
Renal staghorn calcul i , 109 Right-to-left shunt
Parkinson's disease as cause, 569 methotrexate for, 371
Renal system . See also Kidneys hypoxemia caused by, 550
Restrictive cardiomyopathy, 272 rituximab for, 374
anatomy, 479 Right ventricular hypertrophy ( RYH)
S4 and, 580 therapeutic antibodies for, 210
drug reactions i n , 241 h igh altitude and, 552
Restrictive l u n g disease, 555 T F-a i n h i b i tors for, 406
embryology, 478 R i l uzole
vs. obstructive l u n g disease, 556 Rheumatoid factor, 205
pathology, 489-498 for amylotrop h i c late ral
sarcoidosis and, 393 Rh factor, 347
pharmacol ogy, 499 sclerosis, 429
Reta ined placental tissue, 527 Rhinovirus, 1 58, 1 59
physiology, 480-488 ret gene, 85, 221 Rhi;:opus, 145, 175 Rimantadine
Renal tubular acidosis ( RTA) , 488, multiple endocrine neoplasias diabetic ketoacidosis and, 303 for i n A uenza, 575
569 ( M E N ) and, 304 Rhombencephalon, 408 Ringed sideroblasts, 350
Renal tumors Reticular activating system , 419 Rhomboid crystals, 573 Ring-enhancing bra i n lesion, 5 73
associations, common/ Reticular cel l s Ribavi rin, 187 Ringworm, 144
important, 580 l ocation of, i n lymph n o d e , 192 contraindicated during treatment for, 576
Renal \asculature Reticul i n , 77 pregnancy, 190 Rinne test, 436
innervation of, 230 Reticul ocytes, 344 RiboAavin , 91 Risk, quanti fi cation of, 52
Renal vein Reticul ocytosis Ribonuclease, 201 Risperidone, 473
in transplan tation, 479 i n anemia algorithm, 354 Ribonucleotide reductase, 65, 66 Ristocetin assay, 360
Reni n , 486 Reti na, 437 hydroxyurea effect on, 373 Risus sardonicus, 130
Ren in-angiotensin, 286 Retinal artery occlusion, 438 Ri bonucleotides, 65 Ri todrine, 540
Reni n-angiotensin-aldosterone Retinal deposits Ribosomal rR A, 73 c l in i cal use, 235
system, 485 antipsychotics as cause, 473 Ribosomes, 1 18 R i tonavir, 1 89
Renshaw cells, 130 Retinal detachment, 441 antimicrobial therapy, 179 as P-4 5 0 i n h ibitor, 242
Reovi ruses, 1 54, 158 Retinal hamartomas, 85 ribosomal subunit, 176 Rituximab, 374
Reperfusion i n j u ry, 213 Retinal hemorrhage Rice-water diarrhea, 1 24 as th erapeutic anti body, 2 1 0
free radicals and, 215 Roth 's spots and, 569 Rickets/osteomalacia, 94, 387 Rivastigmine, 456
Repl ication fork, 68 Retinal pigment epithel i u m Fanconi's syndrome as cause, 569 River b l i n d ness, 1 51
Replication, viral, 1 54 hypertrophy of, 332 lab values, 388 RNA, 70-73
Reportable diseases, 56 Reti nitis, 438 renal tubular acidosis and, 488 m RNA, 1 89
Repression, as ego defense, 459 I l l Y-associated, 166 treatment for, 575 processing of, 71
Reproductive hormones, 538 Retinoblastomas, 82 vitamin D deficiency as cause, 294 synthesis of, 92
Reproductive system osteosarcoma and, 389 Rickettsia, 1 19, 121 transfer RNA, 180
anatomy, 514-523 tumor suppressor genes, 221 antimicrobials for, 1 80 RNA polymerases, 70, 159
drug reactions in, 240 Retinopathy Gram stai n l i m i tation, 120 R NA viruses, 154, 158
cmb1yol ogy, 504-512 c h loroqu i n e as cause, 186 stain for, 1 20 Robertsonian translocation, 68
pathology, 524-537 diabetic, 302 Rickettsial diseases, 140 Rocker-bottom feet, 88
pharmacol ogy, 538-541 of prematurity, 215, 555 Rickettsia prowa;:ekii, 139, 140 trisomy 1 8 as cause, 568
I NDEX
Rocky Mountain spotted fever, 139 Sacrococcygeal area tumors, 531 Sch i l l i ng test, 93 Secondary syph i l i s
c l inical presentation , 569 S-adenosyl-methionine, 93 for 13 1 2 deficiency, 574 c l i n i ca l presentation, 569
Rocuronium, 455 Salicylates Schistocytes, 350 Secretin , 3 1 9
Rod bacteria. See Baci l l i antidote to, 239 i n -thalassemia, 353 gastric acid regulation, 320
Rol l i ng (leukocyte extravasation ) , 2 1 5 respi ratory alkalosis caused by, 488 in D I G , 360 l ocation of, 321
Romberg maneuver Sal iva, 320 in macroangiopath ic anemia, 357 Secretion rate ( renal )
syph il i s and, 429 Sal ivary amylase, 322 Schistosoma, 1 52 calculati ng, 481
Romberg test, 138 starch digestion by, 322 Schistosoma haematobiwn, 1 52 Secretions, bod i l y
Rooting reAex, 432 Salivary glands oncogenicity of, 222 immunoglob u l i n i n , 1 9 8
Ropinirole, 455 i n nervation of, 434 Schistosoma mansoni, 152 Secretory l gA, 323
Rose gardener's disease, 146 tumors of, 324 Schizoaffective disorders, 463 Sedatives
Rosenthal fibers Salk pol io vaccine, 153, 202 Schizoaffective persona l i ty respiratory acidosis caused by, 488
in pilocytic astrocytomas, 448 Salmeterol, 563 disorder, 469 "Seed and soil " theory of
Roseola cl inical use, 235 "Sch izo" disorders, 469 metastasis, 218
cl inical presentation , 172 Salmonella , 1 19, 121 Sch izoid personal i ty disorder, 468, 469 Segmental artery of kidney, 479
herpesvi rus as cause, 155, 1 56 antimicrobials for, 177, 1 82 Sch izophrenia, 463, 469 Segmented viruses, 1 59
Rosigl i tazone, 305 antiphagocytic factor, 121 anti psychotics for, 473 Seizures, 445
Rostral fold closure fai lure, 308 diarrhea caused by, 168 auditory hall ucinations and, 463 amphetam i n es as ca use, 471
Rosuvastatin, 281 food poisoning caused by, 1 67 dopamine levels i n , 413 calcium deficiency as cause, 487
clinical presentation , 569 Cram sta i n i ng, 133 neurotransmitter changes, 461 as drug reaction, 241
Rotator cuff muscles, 379 as immunodeficiency treatment for, 472, 576 drugs for, 451
Rotavirus, 158, 159 i n fection, 205 Schizophreniform disorders, 463 drug toxicities, 452
diarrhea caused by, 1 68 mesenteric adenitis caused by, 167 Schizotypal persona l i ty disorder, 468, S S Ris as cause, 475
Rotenone, 102 osteomyelitis caused by, 1 69, 356, 469 Sturge-Weber syndrome as
Roth 's spots, 274 579 Schwann cells, 41 1 , 412 cause, 446
clinical presentation, 569 vs. Shigella , 1 36
Cuillain-Barre syndrome and, 444 treatment for, 574, 576
Rotor's syndrome, 336 Salmonella typhi, 136
m)'elinization by, 41 1 tuberous sclerosis as cause, 446
Rough endoplasmic reticulum Salpi ngitis
Schwannomas, 412, 447, 577 Selectins, 215
(RER), 74. See issl stai n i n pelvic inAammatory disease, 173
S C I D. See Severe combined Selection b i as, 53
N issl stai n for, 41 1 Saltatory conduction, 41 1
immunodeficiency disease Selection of T cells, i n thymus, 193
Rouleaux formation, 363 Sample size, effect on power, 55
( S C I D) Selective estrogen receptor
diagnostic findi ngs/labs, 573 Sampl ing bias, 53
Scl era, 437, 438 modulators ( S ERMs), 540
Round l igament of the uterus, 515 SandAy as disease vector, 150
blue, cause of, 566 Selective lg deficiency, 206
Roundworms. See Nematodes SandAy/Rift Val l ey fevers, 158
Scleral icterus Selective serotonin reuptake
(roundworms) Sapon ification, 212
l iver cell fai l u re as cause, 333 i n h i b i tors ( S S R l s)
Rovsing's sign Saqu inavir, 1 89
Scleral venous sinus, 437 for a n orexia, 574
RPF. See Renal plasma Aow ( RPF) Sarcoidosis, 94, 393
Sclerodactyly for bul i m i a , 574
Rl A, 70 cardiomyopathy caused by, 272
in scl eroderma, 395 for depression, 574
RSV. See Respiratory syncytial virus c l i nical presentation, 566
Scleroderma, 395 name suffix, 243
( RSV) erythema nodosum and, 400
achalasia and, 324 sexual dysfunction and, 60
RU-486 (mifepristone), 540 facial nerve palsy i n , 437
autoantibodies associated with, 205 Selegil i ne, 455, 456, 475
Rubella, 160 as granulomatous disease, 216
diagnostic findings/labs, 570 Selenium sulfide
clinical presentation, 172 as restrictive l ung disease, 555
Sclerosing adenosis, 533, 535 for Tinea versicolor, 144
heart sounds i n , 259 Sarcoma botryoides, 532
Sarcomas Sclerosing cholangitis Self-mutilation
materna 1/neona ta I
manifestations, 171 vs. carcinoma, 219 ulcerative col itis and, 328 i n borderl ine personality
in unimmunized ch ildren, 174 methotrexate for, 371 Sclerosis disorder, 468
Rubeola (measles) virus, 1 58, 1 60 radiation exposure and, 220 i n osteoarthritis, 390 Lesch-Nyhan syndrome as
c l i nical presentation, 172, 569 Sarcomeres Scopolamine cause, 567
in unimmunized c h ildren, 174 i n muscle contraction , 385 cli nical use, 234 Selsun. See Selenium sulfide
vaccine for, 202 Sarcoplasmic reticulum Scores on U S M L E Step l exa m , 12 Seminal vesicles, 479, 516
Rubor ( redness), 214 i n musc l e contractions, 385 Scorpion sting development of, 512
Rugae of stomach Sargramosti m , 210 acute pancreatitis caused by, 339 Seminiferous tubules, 516
hypertrophy of, 327 SARS, 1 58 Scotch tape test for pinworms, 1 51 i n Kl inefel ter's syndrome, 524
Russell 's sign, 469 Sartorius muscle, 316 Scotomas spermatogenesis and, 519
" Rusty" sputum, 1 28 " Saturday night pal sy" (wrist macular degeneration and, 441 Seminomas, 536, 581
RVH . See Right ventricular drop ) , 381 , 382 in pap i l l edema, 439 Semustin e , 372
hypertrophy ( RVH ) "Sausage fingers," 392 Scrotum, 516 Senile osteoporosis, 387
Ryanodine receptor Savants, autistic, 461 Scurvy, 78, 94 Senile plaques, 443
in muscle contractions, 385 Scalene muscles clinical presentation, 569 diagnostic findings/labs, 571
in respi ration, 546 Seasonal affective disorder, 465 Sensitivity, 51
s Scales, 395 Sebaceous glands, 378 Sensitivity equation, 581
S- 1 00 marker, 222, 403, 447 Scanning speec h , i n multiple Seborrheic keratosis, 397 Sensorineural hearing l oss, 436
S- 1 00 protei n sclerosis, 444 Secobarbital , 452 Sensory corpuscles, 412
i n Langerhans cell Scapula, wi nged, 381 Secondary b i l iary cirrhosis, 338 Sensory cortex, 418
h i stiocytosis, 366 Scarlet fever Secondary genera l i zation, of strokes in, 422
Saber shins, 138, 171 c l i n i cal presentation, 172, 569 seizure, 445 Separation anxiety disorder, 460
Sabin pol io vaccine, 153, 202 Streptococcus p)'ogenes causing, 129 Secondary gl omerular disease, 489 Sepsis
Sabouraud's agar, 1 20, 145 S cells, 319, 321 Secondary hyperparathyroidism, 300 DJC as cause, 360, 578
Saccular aneurysms, 422, 423 S c h i l l er-Duval bodies, 531 , 536 Secondary pulmonary as i mmunodeficiency
Sacral spinal nerves, 427 diagnostic findings/labs, 571 hypertension, 549 i n fection , 205
I N DEX
Streptococcus agalactiae SCLT! for pulmonary arterial "Slapped ch eeks" ras h , 1 5 5 , 172, 566
causing, 129 i n carbohydrate digestion, 322 h)1Jertension, 575 Sleep. See also RE M sleep
Septal defects Shaken baby syndrome S i l encer hypothalamic regulation of, 414
diseases associated with, 267 subdural hematoma and, 424 i n gene expression , 70 stages of, 60
Septal nucleus, 413 Shared psychotic disorder, 463 Si lent DNA mutations, 67 Sl eep apnea, 556
Septic arth ri tis, 392 " S h awl and face" rash , 394 S i l icosis, 555 pulmonary h)1Jertension caused
Septic shock, 214 S H BG as granulomatous disease, 216 by, 549
diffuse cortical necrosis and, 495 estrogen effect on, 520 S ilver sta i n , 120, 135, 146 pulsus paradoxus in, 275
S E RMs, 374 Sheehan's syndrome, 301 Simian crease Sleep patterns
Seronegative clinical presentation, 568 cl i nical presentation, 569 of depressed patients, 62
spondyloarth ropath ies, 392 S h iga-l ike tox i n , 124, 135, 168 Simple seizures, 445 in the elderly, 60
Serosa/adventitia, 31 1 in lysogenic phage, 126 drugs for, 451 Sleep terror disorder, 62
Serotonin Sh iga tox i n , 124, 168 Si mvastatin, 281 Sleepwalking
in anxiety/depression , 461 Shigella, 1 19 Single nucleotide polymorph isms benzodiazepines for, 453
atypical antidepressants effect anti m icrobials for, 177, 182 ( S Ps), 80 S L E-like syndrome . See a lso Lupus
on, 476 diarrhea caused by, 168 Single strand DNA repair, 69 as drug reaction, 241
MAO i nhi bi tors effect on, 475 Gram staini ng, 133 Singl e-stranded binding proteins, 68 SLE (systemic l upus e rythematosus) .
mirtazapine and, 476 vs. Salmonella , 136 S i n oatrial node See Lupus
as neurotransmitter, 413 toxi n of, 1 24 as target of noradrenergic Sl iding h iatal hernias, 318
opioid effect on, 449 S h i ngles. See Zoster signal ing, 232 S l ow twitch muscle fibers, 385
S N R l s effect on, 475 Shock, 214 Si noatrial ( SA) node, 261 Small bowel obstruction
tramadol effect on, 450 mannitol for, 500 Sinuses, dural , 425, 436 adhesion as cause, 331
tricyclic antidepressan ts and, 475 medications for, 235 Sinus infections Small cell carci noma of the l u ng, 223,
Seroton in receptors S hort gastric arteries, 313 C3 deficiency as cause, 200 394, 558, 580
sumatriptan and, 456 Shoul ders, i n nervation of, 380 Sinusitis Small i ntestine
Serotonin-specific reuptake Kartagener's syndrome as hormones produced by, 319
S h u n ts (cardiac ) , 265
cause, 569 Small lymphocytic lymphoma, 364
inhibitors. See S S R i s S lAD H , 223, 301
Streptococcus pnewnoniae S m a l l pox vacci ne, 153
Serotonin syndrome associations, common/
causing, 128 acute disseminated
S S R i s as cause, 475 i mportant, 580
Si nusoids, 315 encephal omyel itis and, 445
Serous cystadenocarcinomas, 532, 580 carbamazepi n e as cause, 452
Si nusoids of spl een, 193 Smoking. See Tobacco use
ovarian, 223 demecl ocyc l ine, 180
Sinus venosus ( SV), 250 Smooth endopl asmic reticulum
Serous cystadenomas, 532, 580 as drug reaction, 241
Sipple's syndrome, 304 ( S E R), 74
Serous pericarditis, 275 l ith i u m for, 474
S i rolimus, 209 Smooth muscle
Serratia, 1 19, 121 , 134 treatment for, 306, 576
Sister M ary J oseph 's nodule, 327 autoanti bodies targeting, 205
Gram staini ng, 133 Sialvl-Lewisx l eukocyte, 215
S i tus inversus, 569 Gl hormones and, 319
Serratia marcescens S i c k l e cell anemia
6-mercaptopurine, 371 G-protei n-l i nked receptors and, 231
antimicrobials for, 178 in anemia algorith m , 356
toxicities, 375 hypertrophy, in asth ma, 554
pigment produced by, 122 autosplenectomy and, 577
for ulcerative colitis, 328 innervation of, 230
urinary tract infections caused diagnostic fi n di ngs/labs, 571
6-th ioguan ine, 371 tumors of, 219
by, 170 erythrocyte sedi mentation rate
60S ribosome, 1 24 "Snowstorm" appearance of
Sertol i cells, 517, 537 i n , 217, 349
S i ze barrier (plasma fi l tration), 480 uterus, 525
in genital embryol ogy, 512 hydroxyurea for, 373
S jogren's syndrome, 391 S N Rls, 474, 475
spermatogenesis and, 519 osteomye l itis and, 579
autoantibodies associated with, 205 for general ized anxiety
Sertraline, 475 osteonecrosis caused by, 392 cli nical presentation, 567 disorder, 467
Serum iron priapism and, 537 Skeletal muscle, 1 10 S n R N Ps, 71
in anemia, 357 renal papi l l a ry necrosis and, 496 autoregulation, 265 " Soap bubble" bone appearance, 389
Serum sickness, 203 sickle cells i n , 351 vs. cardiac muscle, 260 "Soap bubble" brain lesions, 145
as hypersensitivity disorder, 204 treatment for, 576 contraction of, 386 " Soap bubble" in femu r/t ibia, 573
1 7a-hydroxylase deficiency, 291 Side effects of drugs, 239-241 innervation of, 230 SOAP ( Supplemental Offer and
1 7-hydroxypregnenolone, 291 metabol ism and, 228 insu l i n dependency, 288 Acceptance Progra m ) , 35
Severe combined i mmunodeficiency P-4 5 0 interactions, 242 Skewed curves, 54 Social anxiety disorder, 466
disease ( SC I D), 66, 207 S ideroblastic anemia, 353 Skin S S R i s for, 475
SevoA urane, 453 i n anemia algori th m , 350 autoregulation, 265 treatment for, 472
Sex chromosome disorders, 524 diagnostic findi ngs/labs, 570 bl istering disorders, 398--399 Social Security Act, 56
Sex hormone-binding globu l i n lead poison ing as cause, 353 disorders of, 397, 400-401 Sodium
( S H BG ) , 295 S igmoid colon, 580 epidermis l ayers, 378 along proximal tubule, 484
Sex hormones diverticula, 329 epithel ial cell j unctions, 378 disturbances i n , 487
disorders of, diagnosi ng, 524 diverticulosis in, 329 hyperpigmentation, cause of, 569 reabsorpt ion of, 483
production of, 286 volvul us, 330 infectious disorders of, 402 Sodium channel blockers, 283, 284
Sexual abuse S igmoid si nus, 425 l esions of, 395, 396 Sodi u m channels
dissociative identity disorder Signal ing pathways pigmentation disorders, 396 epilepsy drugs and, 451
and, 464 of endocri ne hormones, 294 sclerosis of, 395 l ocal anesthetics and, 454
Sexual development, T anner stages of steroid hormones, 295 Skin cancer, 403 pacemaker action potential
of, 521 S ignet ring carcinoma carcinogens affecting, 223 and, 260
Sexual dysfunction, 60 diagnostic signs/labs, 572 squamous cell carcinomas, 220 Schwann cells and, 412
Sexually transmi tted diseases. S i gnet ring cells sunburn and, 401 sulfonyl u rea effect on, 305
See STDs (sexually in stomach cancer, 327 Skin Aora, 167 ventricular action potential
transmi tted diseases) S i ldena fi l , 541 Skin test for allergies, 203 and, 260
Sezary syndrome, 362 for erectil e dysfunction, 575 Skip l esions, 328 Sodi u m-dependent transporters
clin ical presentation, 567 male sexual response and, 516 transmural inAammation and, 576 in a m i n o acid clearance, 482
I NDEX
Sodium oxybate Sphingol ipidoses, 1 12 Spongiform cortex Staphylococcal scalded skin

in narcolepsy, 62 Sphingomyel i n ase, 1 12 in Creutzfeldt-j akob disease, 443 syndrome ( S S S S) , 402
Sodium-potassium pump, 77 Spider nevi Spongiform encephalopathy, 1 67 Staphylococcus, 1 19
Sodium reabsorption (renal ) , 484 l iver cell fail ure as cause, 333 Spontaneous pneumothorax, 557, 561 in alcohol/d ru g users, 168
Sodi um retention "Spike and dome" appearance in Spores, 1 1 8 as i mmunodefi ciency
renal fail ure as cause, 497 nephrotic syndrome, 490 bacterial , 130 infection, 168, 205
Sodium sti bogluconate, 1 86 Spina bifida sterilization of, 130 kidney stones caused by, 493
for Leishmania donovani, 1 50 Dandy-Walker syndrome and, 409 Sporolhrix schenckii, 146 postvi ral , 168
Solid hJmors diagnostic findings/l abs, 572 treatment for, 576 Staphylococcus au reus, 86, 103, 121 ,
alkylating agen ts for, 372 Spina bifida occul ta, 409 Sporotrichosis, 146 128, 175
bevacizumab for, 374 Spinal accessory nerve Sprue, 90, 93 acute mastitis caused by, 535
doxorubicin for, 372 l esion i n , 436 Spur cells, 350 antimicrobials for, 177
etoposide/teniposide for, 373 tongue innervation by, 410 Sputum bacterial endocarditis caused
microtubule i n h i b i tors for, 373 Spinal arteries, 427 desquamated epithe l i u m casts by, 274
Somatic nerve Spinal cord , 427 in, 571 as 13-hemolytic bacteria, 128
ejaculation and, 516 cranial nerve nuclei in, 434 Squamocol umnar (epith e l i a l ) cellulitis caused by, 402
Somatic nervous system , 230 development of, 408 junction (SCJ or Z l i n e ) , 325 chronic granulomatous disease
Somatization disorder, 467 hemisection of, 430 Squamous cell carci noma and, 207, 579
Somatoform disorders, 467 lesions, 429, 431 acti nic keratosis and, 400, 576 effect on leukocytes, 201
Somatostatin, 306, 319, 340 l ower extent, 427 associated cancer, 222 food poison ing caused by, 167, 578
for carcinoid tumors, 333 syringomyelia i n , 410 carcinogens affecting, 223 impetigo caused by, 402
gastric acid regulation, 320 Spinal nerves, 427 c l i n ical presentation , 572 infectious a rth ritis caused by, 392
glucagon and, 289 derma tomes, 431 diseases associated with, 220 l un g abscesses caused by, 560
growth hormone and, 290 Spinal tap of esophagus, 325, 578 as normal Aora, 1 67
insu l i n and, 288 xanthoch romic, 424 osteomye l i tis caused by, 169, 579
H IV-associated, 166
production of, 287 Spinal tracts, 427 p igment produced by, 122
of l ung, 558
Somatotropic adenoma, 580 anatomy and functions, 428 pneumonias caused by, 560
of penis, 537
Somatotropi n , 290 Spinothalamic col umns, 415 Protein A expression, 122
of rectu m , 315
Sonic hedgehog gene, 504 Spinothalamic tracts, 427, 428 toxic shock syndrome, 125
of ski n , 403
Sorbitol , 105 syringomyel ia, 429 toxins of, 125
of transitional epithel i u m , 222
cataracts and, 439 syringomyelia, damage in , 410 treatment for, 576
of vagi na, 532
Sorbitol dehydrogenase, 105 Spirochetes, 1 19, 137 Staphylococcus bovis
SRY gene, 512, 513
Sotalol Spironolactone, 501 , 538, 539 treatment for, 576
SSRis, 475
as antiarrhythmic, 284 for C H F, 273 Staphylococetts epidennidis, 122, 128
for atypical depression, 465
reactions to, 240 gynecomastia caused by, 535 diagnostic signs/labs, 572
conditions indicated for, 472
Southern blot, 80 for hyperaldosteronism, 296, 575 endocarditis and, 274
for general ized anxiety
Southwestern blot, 80 for polycystic ovarian syndrome, 530 as normal A ora, 1 67
disorder, 467
Space constant, of axon, 41 1 reactions to, 240 novobiocin sensitivity, 127
for obsessive-compulsive
Space of Disse, 315 Spitz nevus osteomyel itis caused by, 169
disorder, 466
SparAoxacin, 182 benign melanocytic nevus and, 577 Staphylococcus saprophyticus, 122
for panic disorder, 466 diagnostic signs/labs, 572
Spasticity Spleen
benzodiazcpi n cs for, 453 for post-traumatic stress novobiocin resistance, 127
blood supply to, 312
as motor neuron sign , 428 embryology, 309 disorder, 467 urinary tract i n fections caused
Spatial neglect syndrome, 419 platelets i n , 344 for social phobia, 466 by, 170, 581
Specialties, median U S MLE Step I sinusoids of, 193 ss RNA vi ruses, 1 54 Starl ing curve, 254
score and, 1 2 Splenectomies, 193 . See also Asplenic Stable angina Starl ing forces, 265
Specific gravity patients treatment for, 576 "Starry sky" appearance i n B u rkitt's
in transudate vs. exudate, 216 for hereditary spherocytosis, 356 Stable (quiescent) cell types, 74 lymphoma, 362
Specificity, 51 , 581 Splenic artery, 313 Stages of sleep, 60 Start and stop codons, 70, 73
Sperm Splenic fl exure Staghorn cal c u l i , 493 " Startl e myocl onus" in C reutzfel dt
pathway for, 515 blood supply to, 312 Stains (microbiology), 120 jakob disease, 443
Spermatic cord, 317 hypoxia in, 213 charcoal yeast extract, 135 Starvation, 1 14
Spermatic f<1scia Splenic sequestration crisis chocolate agar (factors V and Statins , 281
indirect inguinal hernias and, 318 sickle cell anemia as cause, 356 X), 134 for hypercholesterolemia, 575
Spermatoceles, 537 Splenic vein , 314 Eaton's, 142 reactions to, 241
Spermatocytes, 517 Splenomegaly immunoh istochemical, 76 Stationary phase of bacterial
Spermatogenesis, 517 i n chronic myelogenous KO H prep, 144 growth, 125
cryptorchidism effect on, 536 leukemia, 365 M acConkey's, 134 Statistical distribution, 54
prolactin and, 290 i n C M L, 365 Sabouraud's, 145 Statistical hypotheses, 54
regulation of, 519 h ereditary spherocytosis as special requi rements, 1 20 Status epilepticus, 445
Sertol i cells and, 517 cause, 356 Standard deviation, 53 benzodiazepines for, 453
Spermatogonia, 517 portal hypertension as cause, 333 Standard error of the mean ( S E M ) , 55 drugs for, 451
Sphenoid sinus, 436 Splenorenal l igament, 310 Stapedial artery Stavudine (d4T), 189
Sphenoparietal sinus, 425 Spl iceosomes, 71 development of, 509 STDs (sexually transmitted
Spherical tau protein aggregates Splicing of pre-m RNA, 71 Stapedius muscle diseases) , 173
in Pick's disease, 443 Splinter hemorrhages, 274 derivation of, 510 antimicrobials for, 1 80
Spherocytes, 351 bacterial endocarditis as cause, 569 innervation of, 434 associations, common/
Spherocytosis, 85 Spl itting, 257 Stapes i mportant, 580
Sph i ncter of Oddi , 316 Spl itting, as ego defense, 459 derivation of, 510 exception to confiden tial ity, 57
cholecystokinin and, 319 in borderl i n e personal i ty Staphylococcal enterotoxin m i n ors' righ t to treatment, 56
Sph incter pupillae, 437, 438 disorder, 468 heat stab i l i ty, 1 23 protozoa as cause, 150
I N DEX
Steady state of drugs, 227 diagnostic findings/labs, 570 therapeutic hyperventilation Sucralfate, 340, 341
Steatorrh ea, 90, 326 as immunodeficiency for, 421 Sudden cardiac death , 269
"Stellate" morphology of breast infection, 205 th rombolytics for, 368 coca i n e as cause, 471
tumors, 534 meningitis caused by, 1 69 Stroke vol ume ( SV), 253, 254, 582. Suffixes for drug names, 243
Stenosis, 308 Streptococcus bovis, 129 See also Cardiac output (CO) S u i cide, 60
Step 1 Content Outl ine, 1 1 as colorectal cancer risk factor, 332 Strongyloides stercora/is, 151 bipolar disorder a n d , 464
Steppage ga it, 384 endocarditis and, 274 Struma ova r i i , 531 cocai n e use and, 471
Stercob i l i n , 323 Streptococcus m u tans, 128 Struvite, 493 , 579 major depressive disorder and, 465
Sterility. See I n ferti l i ty as normal Aora, 167 ST segment, 261 risk factors, 466
Sternocleidomastoid muscle Streptococcus pneumoniae, 128 Study types, 50 sch izoph renia and, 463
innervation of, 434 in alcohol/drug users, 1 68 Sturge-Weber disease, 278, 446 S u l bactam , 177
in respi ration, 546 as a-hemolytic bacteria, 127 Stylohyoid l igament, 510 Sulcus l im i tans, 434
Steroid hormone signa l i ng antimicrobials for, 181 Stylohyoid muscle, 510 S u l fa allergy
pathway, 295 as anti phagocyte, 121 Styloid process, 510 thiazide diuretics and, 501
Steroid receptors bacterial meni ngitis and, 577 Stylopharyngeus musc l e Sulfadiazine, 181
signal ing pathways, 294 diagnostic findi ngs/labs, 573 derivation of, 5 1 0 for toxopl asmosis, 148
Steroids genetic transformation, 126 innervation of, 434 for Toxoplasma gondii, 576
acute pancreatitis caused by, 339 l gA protease secretion, 122 Subacute endocardi tis S u l fa drugs, 242
adrena l, 291 as i m munodeficiency bacteria l , 128 acute pancreatitis caused by, 339
exogenous, diagnosing, 524 infection, 205 enterococci causing, 129 e ryth ema multiforme caused
for neonatal respi ratory distress meningitis caused by, 169 Streptococcus bovis causing, 129 by, 399
syndrome prevention, 555 optoc h i n sensitivity, 127 Subacute thyroiditis, 298 C6PD deficiency caused by, 356
for polymyosi tis/ penici l l i n for, 176 Subarachnoid h emorrhage, 423 , 424 reactions to, 240, 241
dermatomyositis, 394 pneumonia caused by, 168, 560 clinical presentation , 570 S u l famethoxazole, 181
for pseudogout, 391 treatment for, 576 diagnostic findings/labs, 570, 573 S u l fasalazine, 342
for sarcoidosis, 393 h eadaches caused by, 446 for rheumatoid arth ritis, 390
Streptococcus pyogenes
synthesis i n h ibition, 539 Subarachnoid space, 436 as sulfa drug, 242
cel l u l i tis caused by, 402
for temporal arteritis, 576 extent of, in spinal cord, 427 for ulcerative col itis, 328
diagnostic findi ngs/labs, 570
Stevens-J ohnson syndrome, 399, 452 in meningocele/ Sulfation, 228
effect on l eukocytes, 201
as drug reaction, 241 meni ngomyelocel e , 409 Sui fisoxazole, 181
impetigo caused by, 402
Stimulants Subcapular sinus of lymph node, 192 S u l fonamides, 92, 181
necrotizing fasciitis caused by, 402
of CNS, 472 Subcutaneous fat lesions, 400 contraindicated during
treatment for, 576
intoxication and withdrawa l , 471 Subcutaneous nodules, 129 pregnancy, 1 90
Streptococcus pyogenes (group A
Stimulus, in classical Subdural hematomas, 424 mechanism of action, 176
strep ), 125, 129
conditioning, 458 associations, co1ntnon/ for Nocardia, 131
bacitracin sensitivity, 127
St. John's wort important, 578 as P-4 5 0 i n h i b itor, 242
as -hemolytic bacteria, 128
as P-4 5 0 i nducer, 242 Subendocardial infarcts, 271 reactions to, 240, 241
c l i nical presentation, 172
St. Louis encephal itis, 158 Subfalcine herniation. See C ingulate as sulfa drug, 242
eryth rogenic toxin of, 126
Stomach, 321 herniation tubulointerstitial nephritis caused
M protein expression, 122
basal electric rhyth m , 31 1 Subl i mation, as ego defense, 459 by, 495
penici l l i n for, 176
blood supply to, 312, 313 Subl i ngual glands Sulfonyl ureas
diverticula, 329 rheumatic fever caused by, 274 for diabetes mell i tus, 305
innervation of, 434
h istology, 31 1 Stre(Jtococcus sanguis, 128 reactions to, 241
sal iva secretion, 320
hormones produced by, 319 Streptococcus viridans group. as sulfa d rug, 242
Subl uxation of lenses, 85
Stomach cancer. See Gastric cancer See Viridans group Submandibular glands Sumatripta n , 456
Stomach p i I, 320 streptococci innervation of, 434 for cl uster h eadaches, 446
Stool Streptogramins sal iva secretion, 320 for m i gr<1 i n e , 575
fatty. See Steatorrhea mechanism of action, 176 Submucosa, 31 1 for m igra i n e headaches, 446
Stool occul t bl ood for VRE, 1 84 Submucosal nerve plexus, 31 1 reactions to, 240
in diverticu l i tis, 329 Streptoki nase Submucosa of ileum Summary of pathways, 98
test for, 332 antidote to, 239 Peyer's patches i n , 323 S un b urn, 401
Straigh t si nus, 425 Streptolys i n 0, 125 Subscapularis muscle, 379 Sun exposure
Stratum corneum, 396 Streptomyc in , 180 Substance abuse, 470 skin cancer and, 403
Stratum granulosum, 397 for mycobacteria, 1 83 dementia caused by, 462 " Sunset eyes" i n papi l l edema, 439
Stratum spinosum, 397 Streptozoci n , 372 osteomyelitis and, 579 Superantigens
Strawberry hemangioma, 278 Stress testing teratogenic effects of, 506 effect on lymphocytes, 201
"Strawberry tongue" medications for, 235 tricuspid valve and, 578 S u perantigens causing shock, 125, 128
diseases causing, 569 Striated muscle, tumors of, 219 Substance P Superficial inguinal lymph nodes, 192
in Kawasaki disease, 276 Striatu m , 416 migra i n e h eadaches a n d , 446 Superior cerebellar peduncles, 433
Streak ovaries atrophy i n H unti ngton's opioid effect on, 449 Superior cervical gangl ion
Turner syndrome as cause, 569 disease, 417 Substantia nigra, 416 H o rn e r's syndrome and, 431
Streptococcus, 1 19 strokes in, 422 neuron depigmentation in, 571 Superior col l icul i , 433
Chediak-H igashi syndrome "String sign" in Parkinson's disease, 416 Superior gl uteal nerve, 384
and, 207 on barium swal low, 328 Subthalamic nucleus, 41 6 Superior mesenteric artery
infectious arth ritis caused by, 392 diagnostic signs/labs, 572 in hemiball ismus, 417 ( S MA) , 312
Streptococcus agalactiae (group B Strokes lesions in, 419 Superior mesenteric lymph
strep) , 129, 175 cilostazolldipyridamole as Succi mer nodes, 1 92
antiphagocytic factor, 121 prophylaxis, 369 as antidote, 239 Superior mesenteric vein , 314
bacitracin resistance, 127 effects of, 422 for lead poisoning, 353 Superior obl ique muscle
bacterial meningitis and, 577 heparin for, 367 Succinylcholine, 455 cranial nerves and, 439
as -hemolytic bacteria, 128 ischemic, 425 Sucking reAex, 432 Superior ol ive, 415
INDEX
Superior ophthalmic vei n , 425 congenital syph i l i s facies, 171 TBG. See Thyroxine-binding globul i n "Tennis-racket" shaped cytoplasmic
Superior orbital fissure dementia caused by, 443 (TBG) organelles, 573
as cranial nerve pathway, 435 as granulomatous disease, 216 TCA cycle, 97, 101 Tenofovi r (TDF), 1 89
Superior rectal vein , 314 gummas in, 173 TCAs. See Tricycl i c antidepressa n ts Ten osynovitis
Superior sagi tal sinus, 425 J arisch-Herxheimer reaction T-cell leukemia, 1 58 i n septic arthritis, 392
Superior vena cava syndrome, 559 and, 567 T-cel l lymphoma Tension h eadaches, 446
as lung cancer compli cation , 558 l upus causing false positive for, 393 i n celiac sprue, 326 Tension pneumothorax, 557, 561
Superoxide dismutase maternal/neonatal T-cell receptor (TC R), 201 Tensor tympan i , 510
amylotroph ic lateral sclerosis man ifestations, 171 T cells, 346, 347. See Lymphocytes Tensor vel i palati n i , 510
and, 429 pal m and sole rash in, 1 40 activation of, 196 Tentoriu m cerebell i , 448
free radical i njury and, 215 penic i l l i n for, 176 adaptive nature of, 193 Teratogens, 506
Supinator muscle prophylaxis for, 184 anergy, 201 ACE i n h i b i tors as, 502
radial nerve damage and, 382 tabes dorsal is caused by, 429 atypical, Sezary syn drome as antimicrobials as, 1 80, 1 86, 1 87, 190
Suppression, as ego defense, 459 thoracic aortic aneurysms and, 268 cause, 567 Aouroquinolones as, 182
Suppurative pericardi tis, 275 Syp h i l itic heart disease, 275 bacterial toxin effect on, 201 meth i mazole as, 306
Suprach iasmatic nucleus, 62, 414 Syringomyelia, 410, 429 cytokines secreted by, 200 Teratomas, 531 , 536
Supraclavicular node Horner's syndrome and, 431 cytokines stimulating Terazos i n , 237
enlarged, Ehlers-Danlos syndrome Systematic errors (bias), 53 differentiation of, 195, 200 for benign prostatic hyperplasia
as cause, 567 Systemic l upus erythematosus. cytotoxic T cells, 195, 197, 201 , 212 ( B P I-I ) , 535
metastasis to, 327 See Lupus deficiencies, i nfections caused Terbinafine, 186
Supraoptic nucleus Systemic mycoses, 143 by, 205 for ringworm infections, 576
vasopressi n synthesis, 414 dimorph ic, 143 i n delayed (type I V) Terbutal ine, 540
Suprarenal arteries, 312 Systole, 256 hypersensitivity, 203 cl inical use, 235
Suprarenal gland, 309 Systol ic e j ection murmur differentiation and maturation, 193 Teres minor muscl e, 379
Supraspinatus muscle, 379 conditions associated with , 258 disorders of, 206-207 Terminal bron c h ioles, 544
Supraventricular tachycardia diseases causing, 570 helper T cells, 195, 196, 201 , 21 6 Terminal i l e u m
antiarrhyth mics for, 284 Systolic heart fai l u re l ocation of, in lymph node, 192 angiodysplasia i n , 331
ejection fraction ( E F ) i n , 254
-blockers for, 238 major functions of, 195 Term i nation
Systol ic murmur
Suramin, 1 86 neoplasms of, 362 i n protein synthesis, 73
conditions associated with , 258
for Trypanosoma, 148 posi tive and negative selection, 195 Tertiary hyperparathyroidism, 300
Surface ectoderm , 505 T regulatory T cells, 197 Tertia ry syph i l i s
Surface F protein, 160 in spleen, 193 aneurysms and, 576
t 1 12 (half-l ife ) . See Half-l ife
Surfactant, 544, 555 surface proteins, 201 Testes, 516
(pharmacodynamics)
Surgery TC R descent of, 514
t(8; 1 4), 580
eth ical issues i n , 58 toxins affecting, 125 embryology, 512
t(9; 2 2 ) , 580
Surrogates, 57 TdT marker, 364 progesterone production, 520
t( l 4; 1 8 ) , 580
Suspensory l igament of the Teardrop cells, 351 reproductive hormones and, 538
Tabes dorsalis, 429
ovaries, 515 in myelofibrosis, 366 undescended, 536
SVT'. See Supraventricular Teeth , impacted venous and lymphatic
in syph il is, 138, 173
tachycardia Gardner's syndrome as cause, 568 drainage, 514
Tachycardia
Sweat Tegmentum yolk sac tumors in, 531
PC P use as cause, 471
secretion of, 378 Tacrol imus ( F K-506), 209, 240 of brain stem, 434 Test icular arteries, 312
Sweat glands Tactile hall uci nations, 463 Telangiectasia, 85 Testicular atrophy
innervation of, 230 Taenia solium, 1 52 in scleroderma , 395 alcohol i sm and, 472
Swimmer's ear. See External otitis Tail of epididymis, 516 Tel encephalon, 408 hemochromatosis as cause, 337
Sydenham's chorea, 1 29 Takayasu's arteritis, 276 Tellurite plate, 120 l iver cell fai l ur e as cause, 333
Sylvian fissure, 418 Tamoxifen, 374, 540 Telomerase, 68 Testicular cancer
Sympathetic chain lesion for breast cancer, 575 Telophase, 74 a-fetoprote i n m arker for, 222
cli nical presentation, 569 reactions to, 240 Temazepam , 453 bl eomycin for, 372
Sympathetic nervous system , 230, 414 Tamsulos i n , 535, 540, 574 Temperature (sensatio n ) , 428 cisplatin/carboplatin for, 373
receptor types i n , 231 Tanner stages of sexual hypothalamic regulation of, 414 Testicular fem i nization , 524, 525
Sympathetic receptors, 231 development, 521 Temporal arteritis, 276 Testicular lymphoma, 537
Sympathetics, i n spinal cord, 427 Tantrums, 458 associations, common/ Testicular tumors
Sympathomimetics, 235 Tapeworms. See Cestodes important, 580 associations, common/
Sympathoplegics, 236 T A PVR See Total anomalous
.
erythrocyte sedimenation rate important, 581
Symphysis, 516 pulmonary venous return i n , 217 germ cel l , 536
Synapses (TAPVR) eryth rocyte sedi mentation rate non-germ cel l , 537
spinal tracts and, 428 Tarasoff decision, 57 in, 349 Testing extraocular muscles, 440
Synctiotrophoblast, 508 Tardive dyski nesia treatment for, 576 Testis-determining factor, 512
Syndrome of i nappropriate antipsychotics as cause, 473 Temporal bone Testosterone, 291 , 519, 539
antidiuretic hormone as drug reaction, 241 fracture of, and epidural disorders of, 525
secretion. See SlADH Target cell s hematoma, 424 disorders of, diagnosing, 524
Syngeneic grafts, 208 i n -thalassemia, 353 Temporal branc h , of facial nerve, 434 exogenous, 519
Synovitis postsplenectomy, 193 Temporal is muscle, 437, 510 secretion of, 517, 538
in septic arthritis, 392 Tartrate-resistant acid phosphatase Temporal lobe, 418 signaling pathway, 294
Synthesis ( RER), 78 (TRAP), 222, 364 aphasias affecting, 420 spermatogenesis and, 519
Syph il is, 138 Taxols, 373 Tender hepatomegaly Tetanospasmin toxin, 124, 130. See
aneurysms and, 576 Tay-Sachs disease, 1 12 h epatocellular carcinoma as also Clostridium tetani
chancre i n , 171 c l inical presentation, 566 cause, 335 Tetanus toxin
clinical presentation, 173, 569 Tazobactam, 177 Teniposide, 373 antibodies for, 202
INDEX
Tetany ! Thoracic spinal nerves, 427 Thyroid hormones, 295 as esophageal cancer risk
electrolyte i m balance as 3 -hydroxysteroid dehydrogenase, 291 Thyroiditis, 298 factor, 325
cause, 487 Th ro m b i n Thyroid-sti mulating hormone lung cancer and, 558
Tetrabenazine, 456 h eparin and, 367 (TSI I ) , 289, 295 nicotine i ntoxication and
Tetracaine, 454 Thromboangi itis obl i terans, 276 i n hypothyroidism/ with d rawal , 471
T e tracyclines, 179, 180 Thrombocytes, 344 hyperthyroidism, 298, 299 pancreatic adenocarci noma
contraindicated during Thrombocytopen ia, 344 secretion of, 287 and, 340
pregnancy, 190 abciximab as cause, 369 signal ing pathway, 294 renal cell carci noma and, 494
expired, reactions to, 241 i n aplastic anemia, 355 Thyroid storm , 299 renal tumors and, 580
mechanism of action, 72, 176 blood transfusions for, 360 Thyrotoxicosis, 298, 299 teratogenic effects of, 506
pediatrics contra indications, 1 80 cytarabine as cause, 371 Thyrotropi n-rel easing hormone transitional cel l carci noma
reactions to, 241 heparin as cause, 367 (TRl l ) , 289, 295 and, 494
as teratogens, 506 recombinant cytokines for, 210 signal i ng pathway, 294 Tobramycin , 1 80
Tetrahydrofolate (Ti l F ) , 92 Thrombocytosis Thyroxine-binding globul i n Tocainide
Tetralogy of Fal l ot, 250, 265, 266 postsplenectorny, 193 (TB G ) , 295 as antiarrhythm i c , 283
cyanosis i n , 578 Thro m boemboli Tiagabine, 451 for arrhythmia, 574
diagnostic findings/labs, 570 pulmonary hypertension caused Tibia, 379 Tocolysis, 231
22q l l syndrome association, 267 by, 549 Tibia ! nerve, 384 Togavi ruses, 1 58, 160
Tetrazolium sta i n , 270 Thromboembol ism Ticarci l l i n , 177 Tolbutamide, 305
Thalamic C f)-type calcium channels nephrotic syndrome and, 490 for Pseudomonas aentginosa , 1 3 5 Tolcapone, 455
epilepsy d rugs and, 451 Throm bogenesis, 349 Ticlopidine, 368 Tongue
Thalamus, 415 Thrombolytics mechanism of, 349 development of, 410
development of, 408 mechanism of, 368 h a i ry l eukopl akia on, 402
Tics, 460. See also Tourette's
synapses in, 428 Thrombolytic therapy innervation of, 434
syndrome
Thalassemias, 353 free radicals and, 215 Tonic-clonic seizu res, 445
Tidal vol ume (TV), 546
in anemia algorith m , 356 Thromboplasti n , 348 drugs for, 451
Tight binding ( l eukocyte
basoph i l i c stippling in, 350 Thrombopoi eti n , 210 phenytoin for, 452
extravasation ) , 215
diagnostic findings/labs, 572 Th rombosis, 577, 580 treatment for, 576
Tight junctions
target cells in, 351 Thrombotic stroke, 425 Tonic seizures, 445
in blood-bra in barrier, 413
Thal idomide Thromboxane Tophus
of epithelial cells, 378
as teratogen, 506 aspirin effect on, 404 in gout, 391
Timel ine for study, 12-16
Thayer-Martin media, 1 20 Thrombus embol i , 553 Topi ramate
Timolol , 238
Theca-l utein cysts, 530 Thrush for epilepsy, 451
as antiarrhyth m i c , 284
T hemoglobin, 547 antimic robials for, 185 toxicities, 452
for glaucoma, 449
Thenar atrophy, 382 Candida albicans as cause, 145 Topoisome rase I I
Tinea, 144
Thenar muscle, 383 'Th u m b sign" on X-ray, 573 etoposide/teniposide effect on, 373
Tinea versicolor, 144
Theophyl l i ne, 563 Thymi c aplasia ( Di Ceorge ToRC H e S infections, 171
Ti nnitus
adenosine-blocking effect, 284 syndrome), 89 cytomegalovirus ( C MY), 156
aspirin as cause, 368, 404
antidote to, 239 hyperparathyroidism caused 1- l SY, 1 57
Tiotropium
therapeutic index (Tl ) valu e , 229 by, 300 parvovi rus, 1 55
c l i nical use, 234 rubella, 1 60
Th erapeutic antibodies, 210 as i mmunodeficiency
Tl P S . See Transj ugular i n trahepatic Torsades de poi n tes, 261
Therapeutic index, 229 disease, 206
Therapeutic privil ege, 56 pmacortex development i n , 192 portosystem i c shunt (TI PS) magnesi um for, 284
Th iamine Thymi c cortex Tissue factor, 348 sodium channel bl ockers
amnesia and, 461 T cells in, 193 Tissue plasmi nogen activator ( t PA) and, 283
deficiency, 472 Thymi c hyperplasia antidote to, 239 Total anomalous pul m onary venous
for Wern icke-Korsakoff myasthenia gravis and, 394 for strokes, 425 return (TA PVR), 265
syndrome, 472 Thymi dylate syn thase, 371 Tissue transgl utami nase antibody Total body water, 480
Thiamine pyroph osphate (TPP), 90 Thymine, 64 serum levels, 326 Total i ron-binding capacity (TI BC)
Th iazides, 499 Thymoma T M P-SMX i n anemia, 357
for C H F, 273 myasthenia gravis and, 394 as H IV prophylaxis, 1 84 i n sideroblastic anemia, 353
diuretics, 501 Thymus, 193 for Pnewnocystis jirovecii, 146, 575 Total l u n g capacity (TLC ) , 546
for kidney stones, 493 antigens and, 198 for urinary tract infections, 576 Total peripheral resistance (TPR), 255
reactions to, 241 fai l u re to develop, 206 as UTI prophylaxis, 1 84 hypertension and, 267
as sulfa drug, 242 leukemic i n fi l tration of, 364 TN F (tumor necrosis factor) in shock, 214
Thiazol idi nediones T cells in, 195, 347 endotoxin inducing of, 123 Touch (sensation ), 428
for diabetes mel l i tus, 305 Thyroglobu l i n , 295 TN F-a, 132 Tourette's syn drome, 460
Th ick ascending l i mb, 500 autoanti bodies targeting, 205 in granulomatous diseases, 216 anti psyc h otics for, 473
Th iopenta l , 452 Thyroglossal duct cysts, 298 as therapeutic antibody target, 210 atypical antipsychotics for, 473
as i ntravenous anesthetic, 454 Th yrogl ossa I ducts, 286 TN F-a i n h i bitors, 406 obsessive-compulsive disorder
Thioridazine, 473 Thyroid cancer, 299 for rheumatoid arth ritis, 390 and, 466
Th iosulfate associations, common/ tuberculosis reactivation by, 121 treatment for, 472
as antidote, 239 important, 581 TNM stagi ng system, 219 Toxic epidermal necrolysis, 399
for cyanide poisoning, 547 calcitonin marker for, 222 Tobacco use. See a lso Nicotine Toxicities, 239-241
30S in h i bi tors, 179 M E N 2B as cause, 570 abruptio placentae and, 526 antichol i nergic, 233
Thombotic thrombocytopenic papil l a ry, 220, 223 berry aneurysms and, 423 an tidotes, 239
purpura (TrP), 359 psammoma bodies i n , 223 bronch iectasis caused by, 554 of chemotherapy drugs, 375
Thoracic aortic aneurysms, 268 radiation exposure and, 220 Buerger's disease and, 580 P-4 5 0 i nteractions, 2 42
Thoracic duct, 192 Thyroid cartilage, 510 bupropion for, 476 Toxi c megacolon
diaphragm perforation by, 545 Thyroid development, 286 cataracts and, 439 ulcerat ive col itis and, 328
Thoracic outlet syndrome, 382 Thyroi d disorders, 529 as colorectal cancer risk factor, 332 Toxic multinodular goiter, 299
I NDEX
Toxic shock syndrome Tr;msposition (genetic), 126 Trigeminal pathway, 415 Tuberc u l osis, 132. See also
as Staphylococcus a u reus cause, 128 Transposition of great vessels Triglycerides, 1 16 Mycobacterium tubercu losis
clinical presentation, 569 cyanosis and, 578 agents effecting, 281 amyloidosis and, 490
toxin causing, 125 Transsexual ism, 469 insu l i n effect on, 288 antimic robials for, 1 83
Toxins Transtcntorial herniation, 448 Trigone, 479 aspergil l omas after, 145
effect on lymphocytes, 201 Transthyreti n, 217 Tri iodothyronine, 306 constrictive pericarditis and, 577
endotoxins, 123, 125 Transudate pleural effusions, 561 Tri methopri m , 65, 182 cord factor virulence, 132
exotoxins, 123, 124- 125 Transudate vs. exudate, 216 folate deficiency and, 354 eryth ema nodosum and, 400
HUS, 1 24, 168 Transversal i s fascia, 317 mechanism of action, 176 exception to confidentia l i ty, 57
in lysogenic phage, 126 Transverse si nus, 425 Tri mming as granulomatous disease, 216
Toxocara canis, 151 Transversus abdominis muscl e, 317 posttranslational modification, 73 inA iximab as reactivating
Toxoid vaccine, 130 i n respi ration, 546 Trinucleotide repeat disorders, 87 agent, 342
Toxoplasma gondii, 148 Transvestism, 469 Freid rich's ataxia, 430 milary, 132
diagnostic findings/labs, 573 Tranylcypromine, 475 l l unti ngton's disease, 417 Pott's disease, 132, 1 69
maternal/neonatal Trapezius muscle Trismus, 130 P P D test for, 204
manifestations, 171 innervation of, 434 Trisomy 1 3 , 567 prophylaxis for, 1 83
treatment for, 576 TRAP marker for leukemia, 222, 364 Trisomy 1 8, 568 reactivation of, 121 , 132
Toxoplasmosis, 148 Trastuwmab, 374 TRNA, 70, 72, 73 rifampin for, 1 83
antimicrobials for, 1 86 for breast cancer, 575 charging, 72 s i l i cosis and, 555
tPA, 368. See Tissue plasminogen as therapeutic antibody, 210 structure, 72 symptoms of, 132
activator (tPA) toxicities, 375 Troch l ear nerve, 434, 436 treatment for, 575
in coagulation cascade, 348 Traumatic h emolysis extraocular muscles and, 439 Tuberous sclerosis, 85, 446
TPR. See Total peripheral resistance sch istocytes in, 350 Tro{Jheryma whipplei. See Whipple's neoplasms associated with, 220
(TPR) Travel er's diarrhea, 341 rhabdomyomas and, 275
disease
Trabecula of lymph node, 192 Trazodone, 474, 476 Tubocurari ne, 455
Trophoblastic disease
Trabecular meshwork, 438 Treacher Coll i ns syndrome, 510 Tubular adenomas, 331
hydatidiform moles as c;mse, 525
Trachea, 286, 544, 545 Treatments, classic, 574-576 Tubular carcinoma, 533
Trophoblasts
deviation, in pneumothoraxes, Trematodes ( Aukes) , 152 Tubul i n
hCC secretion, 523
561 Tremors, 417 stab i l i zation of, 406
Trophozoites, 147
Tracheoesophageal anomal i es, 308 'T'rendelenburg sign , 384 Tubulointerstitial fi brosis
Tropical sprue, 326
Tramadol , 450 Treponema, 1 19, 137 medullary cysti c disease as
Tropicamide
"Tram-track" appearance i n Cram stain l i m i tation, 120 cause, 498
cli nical use, 234
M PCN, 491 , 573 Treponema pa llidum , 138, 173 Tubulointerstitial inAammation
Tropoelastin, 79
Transcription factor as granulomatous disease, 216 WBC urinary casts in, 489
Trousseau's sign, 300
as oncogene product, 221 treah11ent for, 576 Tubulointerstitial nephritis, 495
Trousseau's syndrome, 340
trans deletion, 352 Treponemes, 120 Tularemia, 139
Transduction (genetic), 1 26 T R I I . See Thyrotropin-releasing Tumor lysis syndrome
"True" diverticula, 329
Transference and hormone (TRI-1 ) diagnostic findings/labs, 572
True hermaphroditism, 525
countertransference, 458 Triamcinolone, 306 Tumor necrosis factor. See TN F-a
True negative (TN) and true positive
Transferrin Triamterene, 501 Tumor necrosis factor alpha.
(TP), 51
in anemia, 357 Triazolam, 453 See cl F-a
Transfer RNA, 1 80 Triceps muscle Truncus arteriosus, 250, 265
Tumors. See also Hematol ogy/
Transformation (genetics), 126 radial nerve damage and, 382 22q l l syndrome association, 267
Oncology
Transfusion reactions, 347. See Blood Triceps reA ex, 432 cyanosis and, 578
bra i n , 447-448
transfusion reactions Trichomonas Trypanosoma brucei, 148
cardiac, 275
Transfusion therapy antimicrobials for, 182 antimicrobials for, 186 grade vs. stage, 219
hematoc h romatosis and, 337 Trichomonas vagina lis, 1 50, 173 Trypanosoma cn1zi, 150 in i n fancy, 581
Transient ischemic attacks, 425 trcah11ent for, 576 antimicrobials for, 186 in women, 581
cil ostazol/dipyridamole as Trichomoniasis diagnostic findi ngs/labs, 570 markers for, 222
prophylaxis, 369 clinical presentation, 173 Trypanosoma gambiense, 148 metastatic, 224
Transitional cell carcinomas, 494 Trichophyton, 144 Trypanosoma rhodesiense, 148 nomenclature for, 219
carcinogens affecting, 223 Tricuspid atresia, 265 Trypanosomes, 148- 1 49 oncogenes associated with, 221
Transjugular intrahepatic portosystemic Tricuspid regurgitation, 259, 579 an tigen variation of, 201 para neoplastic effects of, 223
shunt (TIPS), 314 Tricyc l i c antidepressants, 475 stain for, 1 20 vascular, 278
Transketolases, 1 03 antidote to, 239 Trypsi n , 322 Tumor suppressor genes, 74, 221
Translocations, 362, 364, 365 mechanism, 232 Trypsinogen, 322 Tumor (swel l i ng), 214
Transmural esophageal rupture, 324 name suffix, 243 Tryptophan, 107 Tunica albuginea, 516
Transmural infarcts, 271 For panic disorder, 466 gastrin stimulation, 319 Tunica vaginalis, 514
Transorgan static pressure, 547 reactions to, 241 1- lartnup's disease and, 482 l esions, 537
Transpeptidase, 1 18 TriAuoperazine, 473 TS I I . See Thyroid-stimulating Turcot's syndrome, 332
antibiotics, 176 Trigeminal nerve, 434 hormone (TS I -1 ) Turner syndrome, 524, 580
bacterial structures, 1 18 derivation of, 510 TSST- 1 . See Toxic shock syndrome cardiac defects associated
Transplant rejection, 208 I I SV latency, 1 56 T-test, 55 with, 267
B cells and, 195 mastication muscles and, 437 TrP/H U S clinical presentation, 569
immunosuppressants for, 209-210 migrain e h eadaches and, 446 m icroangiopath ic a n e m i a i n , 357 and coarctation of the aorta,
T cells and, 195, 203 motor lesion, 436 sch istocytes in, 350 266
WBC urinary casts in, 489 sumatriptan effects on, 456 T-tubu l c membrane cystic h ygroma and, 278
Transporters tongue innervation by, 410 in muscle contraction, 385 h orseshoe kidney and, 478
sodium-dependent, 482 Trigemi nal neuralgia T l 2, 310 T wave, 261
Transport of ammonium by alanine vs. cl uster headaches, 446 Tuber cinereum, 432 2 1 -hydroxylase deficiency, 291 , 577
and glutamate, 106 drugs for, 451 Tuberculoid leprosy, 133 22q l l deletion syndromes, 89, 267
I N DEX
Twin concordance study, 50 eryth rocyte sedimentation rate U rea cycle, 97, 106, 107 U S M LE Step l exa m , 1 -24
Twinning, 507 and, 349 Ureaplasrna, 122 Biometric Identi ty Management
TXA2 I I LA-B 2 7 and, 578 U rease-positive bugs, 1 22 System ( B I M S ) , 16
aspirin effect on, 368 i n A iximab for, 342 Urease test, 170 clin ical review books, 18
in platelet plug formation , 349 neoplasms associated with, 220 U remia clinical vignettes, 21 -22
Tympanic membrane primary scleros i ng cholangitis gastritis caused by, 327 compu ter-based test ( C BT), 3-4,
hearing loss and, 436 and, 338 renal fa il ure as cause, 497 4, 8
Type 1 diabetes. See Diabetes sulfasalazine for, 342 U reteral orifice, 479 disa b i l i ty acco m m odations, 1 5
m e l l i tus treatment for, 576 Ureteric bud, 478 disab i l i ty accomoclations, 43-44
Type I muscle fibers, 385 U lcers, 327. See a lso Peptic ulcer multicystic dyspl astic kidney i n ternational medical graduates
Type I renal tubular acidosis disease and, 478 (IMC), 26-36
( RT'A), 488 asp i r i n as cause, 368 Potter's syndrome and, 478 keyboard shortcuts, 4
Type 2 diabetes. See Diabetes associations, common/ U reters, 309, 479, 516 N B M E/US M LE Resources, 1 0- 1 1
mellitus type 2 i m portant, 576, 580 constriction i n , 481 N B PM E , 41 -43
Type 2 muscle fibers, 385 bismuth/sucralfate for, 341 course of, 479 osteopath i c medical students, 36-
Type 2 renal tubular acidosis compl i cations of, 328 development of, 478 40
( RTA), 488 COX-2 i n h i b i tors for, 405 Urethra, 516 podiatric medical students, 41 -43
Type -! renal tubular acidosis esophagitis and, 324 U reth ritis practice tests, 5, 10, 1 8
( RT'A), 488 Aask-shapecl, 147 reactive arth ritis as cause, 570 proh i b i ted i tems, 4, 1 6- 17
Type A bl ood gastrinoma as cause, 320 Uric acid, 66 question format, 4, 8
stomach cancer and, 327 gastrointestinal , 31 1 increased l evels of, 572 registration and schedul i ng, 5-7
Type A gastritis, 327 1-1 2 blockers for, 341 i n kidney stones, 493 retesting, 22-23
Type B gastritis, 327 1-/e/icobacter pylori as cause, 137 kidney stones and, 579 scores, 7-10, 1 1
Type I collagen, 77 i n MEN 1, 304 reabsorption i n h ibition, 406 study materials, 1 5 , 17-19
Type I error, 54 N SA l Ds as cause, 405 Uricline, 65 testing agencies, 23-24
T ype I hypersensitivity. Zol l i nger-Ell ison syndrome as Uricline glucoronyl transferase, 323 test-taking strategies, 19-23
See Anaphylactic and atopic cause, 304 Uricline monophosphate, 354 time all otted, 3, 7, 1 9
sensitivity Ul nar claw, 383 Urinary alkal i n i zation, 500 t i m i n g considerations, 2 8
Type I I collagen, 77 Ulnar nerve, 382 Urinary casts, 489 U S M L E B u l l etin of I n formation,
Type I I error, 54 course of, 380 Urinary incontinence 20 1 3 , 6, 10, 1 1
T ype I I hypersensitivity. See Cytotoxic U m b i l ical arteries/veins, 508 hydrocephalus as cause, 426 U S M LE Step 2 C K exa m , 26, 28,
hypersensitivity ( type l l ) U m b i l ical cord, 508 Urinary tract 29-30, 30
Type I l l coll agen , 77 U m b i l i cal l igaments, 317 transitional cell carci noma in, 494 U S M LE Step 2 CS exa m , 26, 28,
Type l l l hypersensitivity. See I m mune Umbilicus Urinary tract infections ( UTis), 169 30-31 , 34
complex hypersensitivity anastomosis i n , 314 i n ADPKD, 498 U S M LE Step 2 exa m , 33
(type I l l ) dermatome for, 431 antim icrobials for, 181 , 182 U S M LE Step 3 exa m , 27, 31 -32, 34
Type I I osteoporosis, 387 Uncal h e rniation, 448 associations, common/ U terine contractions
Type I I pncumocytes, 544 oculomotor nerve and, 441 i m portant, 581 medications for, when
Type I osteoporosis, 387 Uncinate process microorganisms causing, 170 premature, 235
Type I pneumocytes, 544 formation of, 309 prophylaxis for, 1 84 ritodrine/terbutal i n e for, 540
Type IV collagen, 77 Unconj ugatecl staghorn calc u l i and, 493 U terine fibroids
Twe IV hypersensitivity. See Delayed hyperb i l i rubinemia, 336 treatment for, 576 leuprol ide for, 539
cell-mediated hypersensitivity Uncoupl ing agent, 102 Urinary urgency treatment for, 575
(type IV) Uncus, 448 medications for, 234 U terine rupture
Types of studies, 50 Undifferentiated lymphoma Urine hydatidiform mole as cause, 525
Typhoid fever, 136 oncogene for, 221 alkal i n i zation of, 493 U teropelvic j unction, 478
Typhus, 139, 140 Undifferen tiated sch izophrenia, 463 b i l i rubin i n , 335 U terus
Tyramine U n happy triad knee i n j u ry, 379 concentration of, 480 bicornuate, 512
MAO i nhi bi tors and, 475 Unimmun izecl c h i l dren, bugs electrolytes in, 501 h istology, 515
medication for toxicity, 237 affecting, 174 Aow rate, 480 l igam e n ts in, 515
Tyrosinase, 108 U n iparental clisomy, 83 osmola l i ty, i n renal fai l ur e , 496 Uveitis
Tyrosine, 108 Universal donor blood group, 347 reel, causes of, 569 sarcoidosis as cause, 566
in noradrenergic signal i ng, 232 Un iversal electron acceptors, 99 sodium, in renal fa i l u re , 496 ulcerative col itis and, 328
Tyrosine catabolism, 108 U niversal genetic code, 66 Urine p l- 1 and drug e l i m i n ation, 228 U wave, 261
Tyrosi ne hydroxylase, 108 U nmye l inated nerve fibers, 412 U robi l i n , 323
Tyrosine kinase Upper extrem i ty nerves, 380, 382 Urob i l i nogen, 323, 335 v
as oncogene product, 221 Upper motor neuron l esions, 428 Urogenital diaph ragm , 479 V600E mutation, 374
Tzanck test, 157 Brown-Sequarcl syndrome and, 430 U rogenital folds Vaccines, 122, 202
c l i nical presentation , 567 derivations of, 513 for diphtheria, 130
u of facial nerve, 437 Urogenital si nuses, 478 for endotoxins, 1 23
U D P-glucoronyl transferase Upper quadran tic anopia, 441 derivations of, 513 C u i l l a i n-Barre syndrome and, 444
U D P-gl ucuronyl transferase, 181 Urachal cysts, 252 Urokinase for 1-/aemoph ilus influenzae, 134
in Crigler-Na jja r syndrome, type U rachal duct, 508 antidote to, 239 for 1-/aemophilus influenzae type
I , 336 Urach us, 252 U roporphyri n B, 1 69
in G i lbert's syndrome, 336 Urac i l , 64 in porphyria, 358 for l l BV, 155
in jaundice, 335 U rate crystals U roporphyri nogen decarboxyl ase for i n A uenza, 160
Ulcerated genital lesions in gout, 391 porphyria and, 358 l ive vs. killed, 202
diseases causing, 567 Urate-l owering therapy, 406 Urticaria, 397 for meni ngococci , 134
Ulcerative col itis, 328 Urea U S M LE Step I Computer-based for polio, 1 58
arthritis and, 392 along proximal tubule, 484 Content and Sample Test viral, 153
diagnostic signs/labs, 572 Urea breath test, 137 Questions, 10 Vacci n i a , 155
I NDEX
Vagal nuclei, 435 Vasoactive peptides Ventricular septum . Viral i m m u n i ty, M H C , 194
Vagina migrain e headaches and, 446 See I n terventricular septum Vi ral i m mu n odeficiency
atrophy, i n menopause, 523 Vasoconstriction Ventricular system , 426 i n fections, 205
clear cell adenocarcinoma of, 577 l ocal anesthetics and, 454 Ventricular tachycardia, 261 , 283, 284 Vi ral i n fectivity, 154
Aora of, 167 pulmonary hypoxia as cause, 265 Ventromedial area of Viral protein syn thesis, 201
histology, 515 Vasodilation hypothalamus, 414 Vi ral repl ication, 154
tumors of, 532 hypoxia as cause, 265 Verapam i l , 279. See also Calcium Vi ral structure, 1 53
Vaginal candidiadis Vasodilators channel blockers Viral vaccines, 153
antimicrobials for, 185 coronary steal syndrome and, 269 as antiarrhythmic, 284 Vi ra I variations, 201
Vaginal clear cell adenocarcinoma, 506 effect on afterload, 254 reactions to, 241 Virchow's node, 327
Vaginismus, 60 Vasogenic edema, 413 Vermis (cerebel lar) cl i nical presentation, 567
Vaginitis, 1 50. See also Bacterial Vasopressi n , 306, 485 lesions i n , 419 Virchow's triad, 553, 579
vaginosis ( BV) diabetes insipidus and, 301 Verrucae, 397 Viridans group streptococc i , 128
Vaginosis. See Bacterial vaginosis hypothal amus production of, 414 Vertebral crush fractures, 387 as a-hemolytic bacteria, 127
( BV) kidney effects, 486 Vertebral disk herniation, 427 bacterial cndocarditis caused
Vagus nerve, 321 , 434 mechanism of, 483 Vertebral tuberculosis by, 274
derivation of, 510 as paraneoplastic effect, 223 c l i nical presentation, 566 diagnostic findi ngs/labs, 573
diaph ragm perforation by, 545 in RAAS , 485 Vertigo, 446 as normal Aora, 167
l esion i n , 436 receptors for, 231 Verumontanum, 479 optoc h i n resistance, 1 27, 1 28
structures supplied by, 312 secretion of, 287 Vesamicol Virion, 1 59
tongue innervation by, 410 signal ing pathway, 294 mechanism , 232 Virology, 1 53
Valacyclovir, 1 87 Vasopressin receptor antagonists Vesicles, 395 Vi ruses
Valganciclovir, 188 for S lADI I , 576 i n dermati tis herpetiform is, 398 diarrhea caused by, 168
Val idity of test measurements, 53 Vasospasm Vesicourachal diverticul u m , 508 DNA, 1 53-156
Valproate diffuse cortical necrosis caused Vesicoureteral reAux in i m munocompromised
for bipolar disorder, 574 by, 495 pyelonephritis and, 495 patients, 1 68
as teratogen, 506 as sequela of subarachnoid Vesicular trafficking proteins, 75 i n A uenza, 160
for tonic-clonic seizures, 576 hemorrhage, 424 Vestibular nerve negative-stranded, 159
Valproic acid Vd. See Vol u m e of distribution of peripheral vertigo and, 446 RN A , 154, 1 58
for bipolar disorder, 464, 472 drugs Vestibulocochl ear nerve, 434 segmented, 159
for epilepsy, 451 V(O)J recombination, 193, 197 acoustic neuroma and, 412 vaccines, 1 53
reactions to, 240 VORL false positives, 138 VHL gene, 85 Virus ploidy, 154
toxicities, 452 Vecuroni u m , 455 von H ippel-Lindau disease Visceral i n fections, 1 50
Valsalva maneuver VECF and, 446 Visceral l a rva migrans, 1 51
heart murmurs and, 258 bevacizumab effect on, 374 V H L syndrome. See von H i ppel- Visceral mal ignancy, 220
Vancomyci n, 179 VECF i n h i b i tors Lindau disease Visceral n e rve
for Clostridium diffzcile, 130 as treatment for macular Vibration (sensati o n ) , 428 ejaculation and, 516
for enterococci , 575 degeneration, 441 Vibrio, 1 19 Visceral peritoneum, 310
Cram-negative bugs and, 134 Veins, umbil ica l , 508 Vibrio cholerae, 1 24, 136 Visual cortex, 418, 441
in Thayer-Martin (VP ) Velocardiofacial syndrome, 89 diarrhea caused by, 168 strokes i n , 422
media, 1 20 Vemurafenib, 374 Cram staini ng, 133 Visual field defects, 441
mechanism of action, 176 for skin melanoma, 403 Vibrio parahaemolyticus, 167 Visual hal l uci n ations, 463
for meningitis, 169 Ven lafaxine, 475 Vibrio vulnificus, 167 Vital capacity (VC ) , 546
for M RSA, 1 84, 575 Venodilators Vigabatrin Vitami n A
reactions to, 240, 241 effect on preload, 254 for epil epsy, 451 fat sol ubil ity of, 90
for Streptococcus pnewnon iae, 576 Venous drainage of gonads, 514 Vi l l i as teratogen , 506
Vancomycin-resistant enterococci Venous thromboembolism blunting of, i n cel iac sprue, 326 Vitami n B
(VRE) , 1 29 warfarin as prophylaxis, 367 i n digestive tract, 31 1 deficiency i n , dementia caused
Vardenafil , 541 Venous thrombosis, 579 Villous adenomas, 331 by, 443
for erectile dysfunction, 575 Ventilation, at h igh altitude, 552 as colorectal cancer risk factor, 332 Vitamin B 1 (th iamine), 90.
male sexual response and, 516 Ventral anterior nucleus, 415 Vimentin, 76 See Th iamine
Varenicl ine Ventral l ateral nucleus, 415 Vinblastine, 373 Vitamin B z (riboAavin ) , 91
for nicotine addiction, 471 Ventral pancreatic bud, 309 Vinca alkaloids, 369 Vitamin B 3 ( n i a c i n ) , 91
Variable expression, 82 Ventral posterolateral nuclei, 415 Vincristine/vinblasti ne, 76, 373, 375 Vitamin B 5 (pantothenate), 91
Variceal bleeds synapses i n , 428 Vinyl chloride Vitami n B 6 (pyridox i n e ) , 91
octreotide for, 341 Ven tral posteromedial nuclei, 415 as carcinogen, 223 I N H supplementation, 183
Varicella. See VZV vi rus Ventral tegmentum "Violin string" adhesions, 173 Vitamin B7 ( b i oti n ) , 92
Varicoceles, 514, 536 dopamine production, 413 V l Pomas, 319 Vitamin B 9 (fo l i c acid), 92
Vascular bi rthmarks, 570 Ventricles in M E 1 , 304 Vitamin B 1 z n e uropathy, 429
Vascular disease development of, 426 octreotide for, 341 Vitamin B 1 z , 93
oculomotor nerve and, 441 primitive, 250 V I P (vasoactive peptide), 319 absorption of, 322
Vascular smooth muscle stifffl,ypertroph ic, 580 Viral encepha l i tis deficiency i n , 354
AN P effect on, 485 Ventricular action potential , 260 associations, common/ i n trinsic factor and, 320, 322
Vascular tumors, 278 Ventricular fibrillation, 262 important, 581 Vitamin C, 78, 94
Vascul itis, 276-277 sudden cardiac death caused Viral envel opes, 1 54 as anti dote, 239
diagnostic findings/labs, 570 by, 269 Viral genetics, 153 kidney stones caused by, 493
intraprenchymal h emorrhage Ventricular free wall rupture, 270 Vi ral genomes, 153, 154. See also scurvy and, 569
caused by, 424 Ventricular septal defect (VS D ) , 259, 0 A vi ruses; RNA vi ruses Vitamin 0, 94, 294. See
Vas deferens, 479, 516 265, 577 Viral h epatitis also Cholecalciferol
Vasoactive i n testinal polypeptide Down syndrome association , 267 ci rrh osis caused by, 333 deficiency, 387
(VI P), 319 as Ml complication, 271 serum markers for, 334 hydroxylation, 497
I
I N DEX 693
1 ,2 5-(0!-Ih vitamin 0 Vulvovaginitis Wernicke-Korsakoff syndrome, 90, Xanth i n e oxidase i n h i b i tors, 406
kidney functions, 486 Candida a lbicans as cause, 145 419, 472 for gout, 391
for osteomalacia/ri ckets VZV virus, 1 55, 1 56 Wernicke's aphasia, 420 Xanthochromia, 573
prevention, 575 acute disseminated Wernicke's area, 418, 420 Xanthochromic spinal tap, 424
for osteoporosis, 575 encephalomyelitis and, 445 strokes and, 422 Xanthomas, 267
signal ing pathway, 294 antimicrobials for, 187 Wernicke's encephal opathy, 472 Xenografts, 208
Vitamin deficiency c l i n i cal presentation, 172 mammil lary body atrophy and, 577 Xeroderma pigmentos u m , 69
associations, common/ herpesvirus as cause, 155 Western blot, 51 , 80, 1 64 neoplasms associated with, 220
important, 581 as i m munodeficiency Western equine encephal itis, 158 Xerophthalmia, 391
Vitamin E , 94 i n fection, 205 West N i l e virus, 1 58 Xerostomia, 391
deficiency, 429 Reye's syndrome and, 334 Wet beriberi , 90 Xiphoid process, 431
Vitamin K, 95 vacci n e for, 1 53 , 202 c l i nical presentation, 567 X-I inked agammaglobulinemia, 206
amphotericin suppl ementation, 185 vesicles i n , 395 Wet gangrene, 212 X-I inked dominant i n heritance, 84
as antidote, 239 vYet macular degeneratio n , 441 X-I i nked recessive disorders, 86
in coagulation cascade, 348 w "Wet, wobbly, and wacky," 426 X-I i nked recessive i n h e ritance, 84
deficiency, 348, 359 WAG R complex, 494 Wharton's jelly, 508 XO disorder, 524
deficiency, medication causes "Wa i ter's tip" palsy, 381 , 382 Wheals, 395 X-rays, teratogenic effects of, 506
of, 178 'vYaiver of i n formed consent, 56 Wheat i n tolerance. See Cel iac sprue XXY disorder, 524
for warfarin overdose, 367, 368 Waldenstrom's Wh i ff test , 173 XYY disorder, 524
Vitamin/mineral absorption , 322 macroglobulinemia, 363 Whipple procedure, 340
Vitamins. See also specific vitamins Wal deyer's ring, 166 Whipple's disease, 175, 326 y
fat sol uble, 90 "Walking" pneumonia, 142 c l i nical presentation, 570 Yel l ow fever, 1 58, 1 59
free radical i n j u ry and, 215 Wallenberg's syndrome, 422 stain for, 120 vaccine for, 1 53 , 202
water sol uble, 90 Wal lerian degeneration, 41 1 Wh i te blood cells (WBCs). Yel l ow ski n , jaundice as cause, 335
Vitell i n e ducts, 330, 508 Warfarin, 95, 367 See Leukocytes Yersinia, 1 19
Vitelline fistula , 508 for anticoagulation, 575 Whooping cough Yersinia enlerocolitica , 1 24, 136
Vitil igo, 396 antidote to, 239, 367 Bordetella pertussis i n , 124 diarrhea caused by, 168
VLDL, 1 1 5, 1 16 i n coagulation cascade, 348 Wide-angl e glaucoma, 439 mesenteric adenitis caused
VMAT i nhi bi tors, 456 for deep venous thrombosis, 553 Will iams syndrome, 89 by, 1 67
Vmax See M ichael is-Menten ki netics vs. hepari n , 368 Wilms' tumor, 366, 494 Yersinia pestis, 121 , 139
Volume of distribution of drugs, 227, protein C/S defici ency and, 360 dactinomycin for, 372 Yolk sac tumors, 531 , 536
581 as teratogen , 506 tumor suppressor genes, 221 diagnostic findi ngs/labs, 571
Volumes, l ung, 546 therapeutic i ndex (TI ) val ue, 229 Wilson's disease, 337
Volvulus, 308, 330 toxicity, treatment for, 576 c l i nical presentation, 567 z
Vomiting blood Warm aggl utinin, 357 dementia caused by, 443 Zafirl ukast, 563
Mallory-Weiss syndrome as Warth i n 's tumor, 324 diagnostic signs/labs, 572 Zal eplon, 453
cause, 570 Warts (verrucae), 397 hepatocellular carci noma and, 335 Zanamivir, 187
von Gierke's disease, 1 1 1 Waterhouse-Friderichsen serum markers for, 334 Zenker's diverticu l u m , 329, 578
gout and, 391 syndrome, 134, 297 Wi nged scapul a , 381 , 383 as esophageal cancer risk
von H ippel-Lindau disease, 85, 446, c l i nical presentation, 566 Winter's formul a , 487 factor, 325
580 Water reabsorption, 484 "Wire l oop" gl omerular Zero-order d rug el i m i nation , 228
clinical presentation, 569 Watershed areas, in infarct, 213 appearance, 573 Zidovudine (ZDV), 1 89
hemangioblastomas and, 448 Watershed zones in cerebral "Wire looping" of capill aries, 492 Zieh l-Neelsen sta i n , 120
in renal cell carcinoma, 494 cortex, 420 Wiskott-Aldrich syndrome, 207 Zileuton, 563
von Reckl i nghausen's disease, 82, Water sol uble vitamins, 90 Withdrawal from psychoactive Zinc, 95
85, 446 Watery diarrhea, 168 drugs, 470-471 Ziprasidone, 473
cli nical presentation, 566 Waxy casts, 489, 573 Wnt-7 gene, 504 Z-l i n e , 325
pheoch romocytomas and, 297 Weakness, as motor neuron sign, 428 Wolff-Chaikoff effect, 295, 298 Zol l i nger-E l l ison syndrome, 304, 580
schwannomas and, 447 Webbed neck in Turner Wol ffian duct, 512 duodenal ulcers and, 327
tumor suppressor genes, 221 syndrome, 569 Woolsorters' disease, 131 gastrin i n , 319
von Willebrand factor (vWF) Weber test, 436 "Worst headache of l i fe," 423, 424, 570 proton pump i n h i bitors for, 341
receptor, 344 Wegener's granulomatosis, 277, 492. Wound healing, 216 Zol pidem, 453
in platelet plug formation, 349 See Granulomatosis with Wright's sta i n , 137 Zona fasciculata. See Fasciculata
von Willebrand's disease, 349, 360, 578 polyangi itis (Wegener's) Wrist bones, 379 Zonula adherens, 379
Voriconazol e, 185 autoantibodies associated with, 205 Wrist drop, 381 , 382 Zonul a occludens, 379
VPN media, 120 diseases, 216 lead poisoning as cause, 353 Zoonotic bacteria, 1 39
V/Q mismatch, 550, 551 as restrictive lung disease, 555 Writer's cramp, 417 Zoster, 1 56
VRE (vancomycin-resistant Wei l 's disease, 137 Written advance di rective, 57 antimicrobials for, 1 87
en terococci ), 129, 184 Wenckebach atrioventricular WT 1 gene, 221 , 494 facial nerve palsy i n , 437
VSD. See Ventricular septal defect block, 262 Wuchereria bancrofti, 1 51 herpesvirus as cause, 155
(VS D) Werdnig-Hoffman disease, 430 Z-score, 54, 55
Vulva spinal cord lesions, 429 X Zygotes, 504
Paget's disease i n , 534 Wermer's syndrome, 304 Xanth ine, 66, 406 Zymogens, 322
NOTES
About the Auth ors
Tao Le, M D, M H S
Ta o d eve l o p e d a passion fo r m e d i c a l education a s a medical stu d e nt. He cu rrently ed its m o re t h a n 1 5 titl s in

the First Aid series. In a d d ition, h e i s the fo u n d e r of the USMLE-Rx o n l i n e video and test b a n k s ri s a s w II s
a cofo u n d e r of the Underground Clinical Vignettes series. As a m e d i c a l stu d e nt, he was ed itor- i n -ch i ef of th
U n iversity of C a l ifo r n i a , S a n Fra ncisco (UCSF) Synapse, a u n iversity news p a p e r with a weekly circu lation of 9000.
Ta o earned his m e d i c a l degree fro m UCSF i n 1 996 a n d co m p l eted his res i d e n cy tra i n i n g i n i nt rna I m e d i c i n e at
Ya l e U n iversity a n d fe l l ows h i p tra i n i n g at J o h n s H o p k i n s U n iversity. At Ya l e, he was a regu l a r gue t I ctu r r on
the U S M LE review cou rses and a n adviser to the Ya l e U n ive rsity S c h o o l of M e d i c i n e cu rricu l u m co m m ittee. Tao
su bseq u e ntly we nt on to cofo u n d Medsn, a medical e d u cati o n tech n o l ogy v ntu re, a n d served as its c h i f m d i
ca l officer. H e i s cu rrently co n d u ct i n g research i n a sth m a e d u cation at t h e U n ive rsity o f Lo u i svi l l e.
Vikas Shushan, MD
Vikas i s a writer, editor, entrepreneur, a n d telera d i o l ogist. In 1 990 h e con ceived and a u t h o red t h e o r i g i n a l First
Aid for the USMLE Step 1 . H i s entrepren eurial end eavo rs i n c l u d e a softwa re co m pa ny, a stu d e n t-focu ed m d i
ca l p u b l i s h e r (S2S), a n e-lea r n i n g company (medschool .co m/M edsn), a n d a n E R te l e ra d i o l ogy practice (24/7
R a d i o l ogy) . Fi rmly a n c h o red to the Left Coast, Vikas co m p l eted a b a c h e l o r's d g ree in bioch m i stry at the U n iv r
sity of C a l ifo r n i a Berke l ey; an MD with thesis at UCSF; a n d a d i agnostic ra d i o l ogy r i d e n cy at U C LA. H i s eel cti c
i nterests i n c l u d e tech n o l ogy, i nform ati cs, i n dependent fi l m, p h otograp hy, w o r l d m u s i c, S o u t h A i a n d iasporic
culture, and avo i d i n g a day j o b . Always fi n d i ng the l o n g shortcut, Vikas i s a n adv ntu re r, k n ow l e d ge s k r, and
occasional i n n ovator. H e enj oys n ovice status as a kiteboarder a n d sea p l a n e p i l ot, a n d striv to r a i e h i s c h i l d re n
a s g l o b a l citizens.
Vivek T. Kulkarni
Vivek i s cu rrently a fou rth-ye a r stu dent at the Ya l e School of M e d i c i n e , where h e i s p u rs u i n g a co m b i ned M D/
M H S d eg ree. He g rew up in the s u b u rbs of C h i cago a n d g ra d u ated from Wa h i n gto n U n iversity i n St. Louis i n
2 0 0 9 with b a c h e l o r of a rts degrees i n mathe matics a n d c h e m i stry. Vivek i s d o i n g h i s rn a t r of h e a lth s c i nc s
rese a rch i n outcomes eva l u ation, studyi ng hospita l perfo r m a n ce a n d its m e a s u re m nt. H i s future plan includ
res i d e n cy tra i n i n g i n i nte r n a l m e d i c i n e a n d a career a s a c l i n i c i a n-ed u cator.
Matthew M. Sochat
Matthew is cu rrently a fo u rth-ye a r stu dent at the Wa rren A l p e rt M e d i ca l S c h o o l of B rown U n ivers ity. He i a N w
Eng la nd e r t h rough a n d th rough, g rowi ng up in New H a m ps h i re a n d atte n d i n g t h e U n iversity of M assach usetts
A m h e rst, where he earned d u a l d egrees in b i o c h e m i stry a n d the classics. Th i s yea r he is a p p lyi n g to n e u ro l
o g y resi d e n cy progra ms, p l a n n i n g o n becom i n g a c l i n i cia n-ed u cator. I n h i s s p a re ti me, M atth ew nj oys s k i i n g,
coo k i n g/ b a k i n g, trave l i n g, the company of friends/l oved o n es, a n d c o m i n g u p with h e l pfu l p u n s/ m n m o n ies.

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....... .. .. fnO!tt lobly ew.. ol lllt l)llbefh ?
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w i t h d eta i l e d exp l a n at i o n s
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USMLE Step 1
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yo u r su bsc r i pti o n .
See website for terms a n d co n d i t i o n s .
www . u s m l e- rx . c o m
Review/USMLE
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A STUDENT-TO-STUDENT GUIDE

..,.. Advice from students who aced the 2012 exam

..,.. 1200+ frequently tested facts and mnemonics

..,.. Hundreds of high-yield color images and diagrams throughout

..,.. Student ratings of more than 300 review products

MAT THEW M. S OCHAT

Milan I New Delhi I San Juan I Seoul I Singapore I Sydney I Toronto

First Aid for the USMLE Step 1 2013: A Student-to-Student Guide

This book was set in Electra LH by Rainbow Graphics.

This book is printed on acid-free paper.

Contributing Authors vii How to Contribute XVII

Associate Authors viii How to Use This Book xix

Faculty Reviewers ix Common USMLE Laboratory Values XXI

Preface xi Basic Science Discipline Cross-Reference

SECTION I G UIDE TO EFFICIE NT E XAM PREPAR ATIO N 1

Introduction 2 Clinical Vignette Strategies 21

USMLE Step 1-The Basics 2 If You Think You Failed 22

Defining Your Goal 12 If You Failed 22

Timeline for Study 12 Testing Agencies 23

Study Materials 17 References 23

SECTION I SUPPLEMENT SPECIAL SIT UATIO NS 25

SECTION II HIGH-YIELD GE NERAL PRI NCIPLES 45

How to Use the Database 46 Immunology 191

Behavioral Science 49 Pathology 211

Biochemistry 63 Pharmacology 225

Cardiovascular 249 Psychiatry 457

Endocrine 285 Renal 477

Gastrointestinal 307 Reproductive, 503

Hematology and Oncology 343 Respiratory 543

Musculoskeletal, Skin, and Connective Tissue 377 Rapid Review 565

SECTION IV TOP-RATED REVIEW RESO URCES 583

How to Use the Database 584 Microbiology and Immunology 601

Question Books 587 Pharmacology 610

Internet Sites 588 Physiology 614

Comprehensive 589 Commercial Review Courses 619

Anatomy, Embryology, and Neuroscience 591 Publisher Contacts 624

Behavioral Science 595 Abbreviations and Symbols 625

Biochemistry 597 Photo Acknowledgments 633

Cell Biology and Histology 599

Index 641 About the Authors 695

JACOB BARANOSKI MAX C. PETERSEN

JEFFREY HOFMANN CAROLINE A. WALKER

OLGA LAUR SAMANTHA X. Y. WANG

WALTER F. WIGGINS, PhD

GORAN MICEVIC PETER ZHAO

FADY AKLADIOS AMY MORENO

ADITYA BARDIA, MD, MPH

Universidad Central del Caribe

KATHARINE JOO JINYU (JANE) ZHANG

CHARLES DELA CRUZ, MD SHANTA KAPADIA, MD

Yale School of Medicine Yale School of Medicine

EMILY R. ESPOSITO, PhD BERTRAM KATZUNG, MD, PhD

ANTHONY GLASER, MD, PhD

RAJESH JARI, MD, MBA

KURT JOHNSON , PhD

SANJIV SHAH, MD ADAM WEINSTEIN, MD

Lou isville Tao Le

Study and test-taking strategies for the U S M LE Step 1

New facts, mnemonics, diagrams, and illustrations

High-yield topics that may appear on future Step 1 exams

www. firstaidteam . com

Alternatively, you can e-mail us at: firstaidteam@yahoo . com.

Return t o Sections I I a n d I I I frequ n t ly during yo ur preparation a n d fi l l yo ur shurt-te m memory w it h remaining