Pulmonary Course Packet 08

The Ohio State University College of Medicine
Med 2 Integrated Pathway
PULMONARY
Lecture Handouts
September 9 – September 26, 2008
Block Leader:
James N. Allen, M.D.
201 Heart & Lung Research Institute
473 W. 12th Ave.
Columbus, OH 43210
Phone: 614-293-4925
email: james.allen@osumc.edu
Pulmonary 2008-2009 Course Packet Table of Contents
Title Page
Introduction 1
CPC Instructions 4
Date Lectures:
9-9-08 Structure, Function & Ventilation – Dr. J. Allen 6
9-9-08 Histology of the Respiratory System – Dr. Hitchcock 8
9-9-08 O2 and CO2 Transport - Dr. J. Allen 16
9-10-08 Diffusion – Dr. B. Allen 18
9-10-08 Arterial Blood Gases - Dr. J. Allen 20
9-10-08 Chest Radiology - Dr. King 26
9-11-08 Blood Flow & Metabolism – Dr. Haden 30
9-11-08 Ventilation & Perfusion – Dr. Haden 31
9-11-08 Examination and Diagnostic Testing - Dr. J. Allen 32
9-12-08 Mechanics – Dr. B. Allen 37
9-12-08 Pulmonary Hypertension - Dr. Haden 38
9-12-08 Pulmonary Embolism - Dr. Ali 39
9-15-08 Control of Ventilation – Dr. Essig 46
9-15-08 Sepsis and Acute Respiratory Distress Syndrome - Dr. O'Brien 47
9-15-08 Respiratory Failure - Dr. Hoffmann 52
9-16-08 Asthma - Dr. B. Allen 58
9-16-08 Anti-Asthma Medications - Dr. Fertel 59
9-17-08 Pleural Disease - Dr. Hitchcock 67
9-17-08 Upper Airway Disorders - Dr. McCallister 74
9-17-08 COPD - Dr. Diaz 80
9-18-08 Pathology of Pneumonia – Dr. Hitchcock 87
9-18-08 Lower Respiratory Infections in Adults – Dr. Schaffernocker 94
9-18-08 Lower Respiratory Infections in Children – Dr. Powell 102
9-19-08 Lung Cancer - Dr. Hitchcock 103
9-19-08 Lung Cancer - Dr. J. Allen 111
9-19-08 Interstitial & Occupational Lung Disease - Dr. Hitchcock 117
9-22-08 Immunologic and Rheumatologic Lung Disease - Dr. Weiland 125
9-22-08 Inhalational and Occupational Lung Disease - Dr. Essig 130
9-22-08 Interstitial Lung Disease - Dr. J. Allen 139
9-23-08 Chest Emergencies – Dr. Essig 145
9-23-08 Infant Lung Diseases – Dr. B. Allen 151
9-23-08 Childhood Lung Diseases – Dr. B. Allen 156
9-24-08 Approach to Cough – Dr. Wood 160
9-24-08 Approach to Dyspnea – Dr. J. Allen 163
9-24-08 Cystic Fibrosis and Bronchiectasis - Dr. B. Allen 171
2008 MED II Respiratory Module – Introduction
Date: September 9, 2008
Time: 8:30 am
Faculty: James Allen, MD; Division of Pulmonary & Critical Care Medicine
Email: james.allen@osumc.edu
This module will cover the physiology, pathology, pharmacology, histology, radiology,
and clinical diseases encountered in pulmonary medicine. In order to teach you, we have
assembled an interdisciplinary group of faculty:
Physiology – Drs. James Allen, Elizabeth Allen, Douglas Haden, and Roy Essig
Radiology – Dr. Mark King
Pathology – Dr. Charles Hitchcock
Pharmacology – Dr. Richard Fertel
Adult Pulmonary & Critical Care Medicine – Drs. James Allen, Naeem Ali,
Jennifer McCallister, Doug Haden, Philip Diaz, James O’Brien, Roy Essig,
Jeffery Weiland, Karen Wood, Troy Schaffernocker, and Stephen Hoffmann
Pediatric Pulmonary – Dr. Elizabeth Allen
Pediatric Infectious Disease – Dr. Dwight Powell
We have adopted the educational techniques of concept building and repetition in order
to enhance learning and retention. In this regard, for most major classes of disease, we
will start with a normal physiology lecture, followed in about a day by a pathophysiology
lecture, followed in about a day by clinical case presentations in a lecture setting (usually
with “live” patients who will discuss their diseases and permit questions from you),
followed in about a day by small group case studies. For some disease topics, we deleted
the clinical case presentations in the lecture setting or we deleted the small group case
studies (for time constraints, not because any of these topics are less meritorious).
The lectures will have any required reading listed on their handouts. Most readings will
be available on texts that are on-line through the Health Sciences Library website. There
is one text that is required for the module that is not available on-line from the library:
Respiratory Physiology: The Essentials by John B. West. Because physiology is
historically the most difficult part of the respiratory module, it is essential that you
acquire a copy of the text in order to assimilate the material. The most recent version is
the 8th edition (2008) that has the advantage of coming with an access to the on-line
version of the book. The 7th edition will work fine for your purposes but does not have
the on-line access.
On line, you will find the cases for the small group sessions. They are created in
PowerPoint format. These cases were created exclusively for use by students at the Ohio
State University College of Medicine. Many of the pathology images are used with
permission of Dr. Edward Klatt from his internet collection “WebPath” which can be
found on the internet at:
Page 1 of 177
www-medlib.med.utah.edu/WebPath/LUNGHTML/LUNGIDX.html
Dr. Klatt has stipulated that these images be used only for educational purposes by Ohio
State University medical students and not be disseminated elsewhere.
The case studies also include discussion points in the “notes” section of the PowerPoint
slides. These discussion points were designed to assist the faculty members leading the
small group case study sessions, however, because these points may also be useful for
your review, they are included in the student copies of the case studies, also. In order to
optimize your learning, I recommend that, when possible, you review the cases prior to
the small group sessions but not read the discussion points until after the sessions.
On September 24, 2008, your small groups will present CPCs (clinical pathologic
conferences) where you will be given 3 clinical cases and you will be asked to work
through it to arrive at a diagnosis. Your small group’s findings will be presented to a
faculty member during the CPC and the faculty member will reveal the actual diagnosis
(these will be modeled after the weekly CPCs published in the New England Journal of
Medicine). These cases will represent a pulmonary disease not discussed in detail in the
regular lectures and small groups. It will be your group’s responsibility to work through
the cases and to educate yourselves about the disease in question.
The final exam will be on September 26, 2008. Exam questions will test didactic
knowledge and your ability to integrate concepts from multiple lectures.
An example of the first type of question is:
Hilar adenopathy with diffuse reticulonodular pulmonary infiltrates are most

common in:
1. Sarcoidosis
2. Idiopathic pulmonary fibrosis
3. Emphysema
4. Pneumococcal pneumonia
Correct = 1
An example of the second type of question is:
A 35 year old woman is brought to the emergency room after being found
unconscious at a shopping mall. No medical history is available. On exam, she is
unresponsive, blood pressure 110/70, heart rate 114, and respiratory rate 24 with
clear lungs to auscultation. A chest x-ray is normal. An arterial blood gas reveals:
pH 7.14, pCO2 15, pO2 90, HCO3 10, and SaO2 98%. Laboratory studies include
sodium 140, potassium 5.4, chloride 100, serum CO2 12, creatinine 2.5, BUN 40.
Page 2 of 177
The measured osmolarity is 300 and calculated osmolarity 296. Which of the
following diseases is most likely based on these laboratory findings:
1. Ethylene glycol intoxication

2. Renal tubular acidosis
3. Diabetic ketoacidosis
4. Heroin overdose
5. Histoplasmosis pneumonia
Correct = 3
Test questions may be based on materials presented in lectures, small group discussion
sessions, handouts, CPCs, or required textbook readings. This module is fairly short (less
than 3 weeks) and there is a large amount of information covered. It is important to keep
up with the materials presented since each day builds on materials from previous days. It
is especially important to focus on physiology during the first week in order to be able to
apply the concepts presented in the physiology lectures to the more clinically-based
lectures later in the module.
Our goal for this module is for you to have a solid foundation of knowledge in the normal
respiratory system as well as the common disease processes that you will encounter in
MED III and MED IV. Please call or email us with any questions about the lecture
materials and at the end of the module, give us feedback about what was particularly
effective or ineffective about the module as it pertains to your learning.
Additionally, there will be review sessions most evenings at 6:30 (location to be

announced) when I will be available for questions about the coursework.
Jim Allen, M.D.

Professor of Internal Medicine
Division of Pulmonary and Critical Care Medicine
September, 2008
Page 3 of 177
CPC Instructions
As clinicians, we learn the most from the patients that we care for. The CPC (Clinical
Pathological Conference) has a long tradition in American medicine for teaching fellow
physicians about interesting or unusual clinical cases. In a CPC, the salient features of a
patient’s presentation are presented and a discussant (who does not know what the correct
final diagnosis is) discusses the case including the differential diagnosis, the test that
he/she proposes was used to establish a final diagnosis, and what the final diagnosis most
likely was. In a way, it is like a detective game of figuring out what is wrong with the
patient. CPCs are presented weekly in the New England Journal of Medicine and reading
through one or two CPCs in the journal is a great way to prepare yourself for your Med II
pulmonary module CPC.
When practicing physicians are faced with a difficult case that they have not encountered
before, they turn to the medical literature to help them sort out the case. Medical
education does not stop with medical school and residency, it is something we do
constantly our entire professional career. The CPCs we will use in the Respiratory
Module will help teach you how to teach yourself.
For the CPCs, each of the 8 small groups will be broken into 3 subgroups. Each subgroup
will be responsible for preparing one of three CPCs to the entire small group (with a
faculty preceptor present). Therefore, you will be responsible for teaching yourselves
about the diseases involved in the CPCs.
Each of the 3 CPCs will take 30 minutes. Plan on 5 minutes for the faculty preceptor to
introduce the case, 15 minutes for the subgroup to discuss the case, 5 minutes for the
faculty preceptor to discuss what the diagnosis actually was, and 5 minutes for questions
from the other students.
Do not procrastinate your preparations for the CPCs. You will want to be spending much
of the last week of the module studying for the exam so try to get as much of the work
done during the first and second weeks of the module. You should start meeting with
your subgroup at the beginning of the module to organize your approach to the CPC.
When presenting your CPC, you can just verbally present your findings, use Powerpoint,
use handouts, or use the whiteboard. You will be the teachers for these exercises, so use
the medium that you feel will best teach the rest of your small group the information that
you wish to convey. In past years, the subgroups that have been most effective have used
innovative and interesting ways to present their findings, usually using Powerpoint
presentations. Be creative and incorporate x-rays, pathology images, and physical
examination images that you encounter in your literature review into your presentation.
You will not be graded on whether you get the CPC right but the final exam will contain
questions about the diseases involved in the CPCs, so it will be up to your subgroup to
educate the rest of your small group about the disease. Remember though, you only have
fifteen minutes to present your findings and proposed diagnosis.
Page 4 of 177
As a general guide, use the following timetable to help you organize yourselves:
September 10 Meet with other members of your subgroup after your

regular small group session to organize your subgroup.
Designate a group leader to moderate your meetings and a
presenter who will present your subgroups findings at the
CPC on September 24th.
September 10-15 Individual students should review the cases and develop
his/her own differential diagnosis. Use standard references
to help you (UpToDate, Cecil, Harrison’s, Wikipedia, etc.).
The Prior Health Sciences Library can be a great resource
and there are a number of on-line resources through the
library that can be valuable in your research and
preparation.
September 16-19 Subgroups should meet periodically to discuss the cases
and develop the subgroup’s differential diagnosis.
September 20-23 Subgroups should prepare their presentations using verbal
presentation, handouts, and/or powerpoint slides.
September 24 The designated presenter from each subgroup will present
the subgroup’s findings to the rest of the small group.
Page 5 of 177
Physiology 1: Structure and Function; Ventilation
Time: 9:00 am
Faculty: Jim Allen, MD; Division of Pulmonary & Critical Care Medicine
Email: james.allen@osumcu.edu
Required Reading: West, John B.: Respiratory Physiology: The Essentials. Chapters 2
& 2. Lippincott, Williams, & Williams. 2008.
1. Describe the differences between the conducting zone and the respiratory zone of
the lung. Define the different airway structures and alveoli.
2. Distinguish between the alveolar acinus, the alveoli, the respiratory bronchiole
and the terminal bronchiole. Describe the relative sizes of these structures.
3. List the tissues that comprise the alveolar wall.
4. Describe the mechanisms that the lung uses to eliminate dust and debris.
5. Distinguish the bronchial and pulmonary circulations.
6. List the pressure of oxygen and carbon dioxide in air, arterial blood, venous
blood, and tissue cells. Memorize the atmospheric pressure at sea level, the
percent nitrogen in air, and the percent oxygen in air. Describe the mechanisms
that the lung uses to eliminate dust and debris.
7. Be able to calculate the partial pressure of oxygen in the alveoli. Know the normal
value for the respiratory exchange ratio (R).
8. Know the meaning of the following symbols used in pulmonary medicine (see
Appendix A from West): C, F, P, Q, R, S, V, A, D, E, I, L, T, a, c, v.
9. Given the barometric pressure, be able to calculate the PO2.
10. List the normal values for tidal volume and dead space.
11. List the major accessory muscles of inspiration. Describe the muscle contractions
that result in inspiration.
12. Show the derivation of the lung volumes including TLC, FVC, FRC (TGV), RV,
and tidal volume.
13. Define hyperventilation and hypoventilation. Describe the relation between

ventilation and PCO2.
Page 6 of 177
14. Differentiate anatomic and physiologic dead space.
15. Define minute ventilation and alveolar ventilation.
16. Explain why ventilation is greatest in the lower portions of the lung
17. Describe the physiology of the cough.
Page 7 of 177
Pulmonary Histology

Time: 10:00 – 10:50
Faculty: Charles L. Hitchcock, M.D., Ph.D., Department of Pathology
081 - Heart and Lung Research Institute
Phone: Office 247-7469
Email: charles.hitchcock@osumc.edu
Learning Objectives:
1. Recognize the structures that distinguish the various regions of the upper and lower
airway systems that conduct air.
2. Given a microscopic image of the respiratory mucosa, correlate the cellular and
acellular components with their function.
3. Given a microscopic image of the alveolar wall, define the function(s) of the
components that make up the alveolar septum.
4. What are the roles of the respiratory mucosa and alveolar macrophages in the
immune response?
5. What is the significance of the dual blood supply of the lungs?
Learning Resources:
1. Gartner, L.P. and Hiatt, J.L., Color Textbook of Histology, 3rd Edition, Saunders,
Philadelphia. Chapter 15, Respiratory System, pp 343-364.
2. Gartner, L.P. and Hiatt, J.L. (2006) Color Atlas of Histology, Lippincott, Williams &
Wilkins, Philadelphia, Chapter 12, Respiratory System, pp 235-254.
3. Ogilvie, R.W. (2006) Histology: Independent Study Exercises, MUSC Press,

Charleston, SC, Unit 15, Respiratory Tract & Lung, pp 329-354.
I. OVERVIEW
A. Structures
1. The respiratory system is divided into a conducting portion and a respiratory
portion.
2. The conducting portion includes:

a. Extra-pulmonary - nasal cavities, pharynx, larynx, trachea, and primary
bronchi
Page 8 of 177
b. Intra-pulmonary bronchial tree consisting of bronchi, distributing
bronchioles, and terminal bronchioles.
3. The respiratory portion includes: respiratory bronchioles, alveolar ducts,

alveolar sacs, and alveoli.
B. Functions
1. The conduction portion of the respiratory system conditions the air by filtering,
warming, and humidifying it.
2. The main function is the exchange of gases between the blood and the air.
3. The respiratory system is a key organ in both innate and adaptive immunity.
II. CONDUCTING PORTION

A. Respiratory Epithelium
1. This is a pseudostratified ciliated columnar epithelium. Five different cell
types, each resting on the prominent basal lamina, line airways of the
respiratory system.
2. Ciliated columnar cells, making up about 30% of the cells, are tall slender
cells with a basal nucleus and apical cilia and microvilli. The wave-like motion
of the cilia moves mucus and entrapped particles toward the nasopharynx for
elimination. The alignment of the apical basal bodies of the cilia gives rise to
a horizontal staining density on the apical surface. Their neoplastic
transformation gives rise to adenocarcinoma.
a. Kartagener syndrome is an autosomal recessive disorder resulting in

defective cilia motility – primary cilia dyskinesis – due to defects in dynein
protein in the cilia. The syndrome is also characterized by the presence of
situs inversus, chronic sinusitis, and bronchiectasis.
b. Patients have a history of chronic respiratory infections. Men are infertile

due to immotile sperm arising from abnormal dynein in their flagella.
3. Goblet (mucus) cells, making up about 30% of the lining epithelial cells, are
non-ciliated cells that extend from the basal lamina to the lumen. They
secrete mucin that humidifies the air, keeps the surface moist, and entraps
inspired particles. Their neoplastic transformation gives rise to
adenocarcinoma.
4. Brush cells are columnar cells with microvilli on their apical surface. Their
numbers are few (<3%) in the epithelium. They have been considered to be
sensory cells or goblet cells that have secreted their mucin. Their neoplastic
transformation most likely gives rise to adenocarcinoma.
Page 9 of 177
5. Basal cells that comprise about 30% of the epithelial cells, and are attached
to the basal lamina, but do not reach the lumen. They are the committed
stem cells that the replace other epithelial cells. Changes in their
differentiation give rise to squamous metaplasia and squamous cell
carcinoma.
6. Small granule cells (Kulchitsky cells) are neuroendocrine-like cells that are
distributed along the basal portion of the respiratory epithelium. They contain
electron dense granules that contain a variety of peptides that include
antidiuretic hormone, serotonin, somatostatin, calcitonin and other
neuropeptides. Their neoplastic transformation gives rise to typical and
atypical carcinoids (well and moderately differentiated neuroendocrine
carcinomas), small cell carcinoma (poorly differentiated neuroendocrine), and
large cell neuroendocrine carcinoma.
B. Nasal Cavity and Paranasal Sinuses

1. Provide a large surface area for conditioning inspired air. Olfactory mucosa
on the roof of the nasal cavity and superior concha.
C. Pharynx and Larynx

1. The nasopharynx is lined by respiratory epithelium. In contrast, stratified,
non-keratinized, squamous epithelium lines the oral pharynx and the
laryngeal pharynx.
2. The larynx is responsible for phonation and for preventing solids and liquids
from entering the trachea.
a. The larynx is a rigid tube due to the presence of the thyroid and cricoid
hyaline cartilages.
b. The epiglottis, with its fibroelastic cartilage, covers the laryngeal opening.
c. The intrinsic muscles, skeletal muscle innervated by the inferior laryngeal

nerve, link the thyroid and cricoid cartilages. Muscle contraction leads to
modulation of the voice.
3. The larynx is divided into three regions:

a. Supraglottis that includes the epiglottis, false vocal cords, and ventricles.
b. The glottis includes the true vocal cords and the commissures.
c. The subglottis lies between the true vocal cords and the bottom margin of
the cricoid cartilage.
4. The pharyngeal surface and part of the lingual surface of the epiglottis, as
well as the true vocal cords, are lined by non-keratinized stratified squamous
epithelium.
Page 10 of 177
a. Respiratory epithelium lines the remaining mucosal surfaces of the larynx.
D. Trachea
1. The tube-like trachea extends approximately 10 cm long from the larynx to its
bifurcation into the two primary (extrapulmonary) bronchi.
2. Four layers make up the tracheal wall.

a. The mucosa contains respiratory epithelium that sits on a prominent basal
lamina, loose connective tissue, and lymphatic tissue.
b. The submucosa contains denser connective tissue and mucus and serous
secreting glands.
c. C-shaped hyaline rings form the cartilaginous layer. These 16-20 C-

shaped rings prevent the collapse of the tracheal lumen. The trachealis
muscle and fibroelastic tissue fill in the open portion, posterior portion
adjacent to the esophagus. These rings can undergo ossification with
age.
d. Adventitia is the peripheral loose connective tissue layer of the trachea.
E. Bronchi
1. The trachea divides to form right and left (extrapulmonary or primary) bronchi.
The right bronchus is wider and significantly shorter than the left bronchus.
Upon entering the lungs the bronchi are called the intrapulmonary bronchi.
2. The airways within the lung undergo unequal dichotomous branching.

a. The right bronchus divides into three lobar bronchial branches while the
left divides into two lobar bronchial branches.
b. The left lung is further divided into eight bronchopulmonary segments and
the right lung into ten of these segments. Each is supplied by a segmental
bronchus (i.e. tertiary bronchi).
c. The segmental bronchus and lung parenchyma that it supplies make up a

bronchopulmonary segment. Each segment has its own blood supply and
connective tissue septa. This subunit arrangement facilitates surgical
resection.
d. The segmental bronchi further divide into smaller subsegmental bronchi

that are subsequently continuous with bronchioles.
e. Branching of the pulmonary arteries follows that of the airways as they

travel together.
Page 11 of 177
3. The wall of the bronchus decreases in diameter with each branching from
approximately 1 cm to 5mm or less.
a. Respiratory epithelium lines the mucosa. With airway segmentation there
is a decrease in the epithelial height accompanied by a decrease in the
numbers of basal cells, brush cells, and neuroendocrine cells.
b. The lamina propria of the pulmonary airways – bronchi and bronchioles –

contains three layers – lamina lucida, lamina densa, and lamina reticularis.
It is the lamina reticularis, found only in adults, that thickens in patients
with asthma and other inflammatory airway conditions.
c. The submucosa has two smooth muscle layers with a spiral orientation
running in opposite directions. Their contraction would compress the
lumen like ringing out a wet cloth. The submucosa also contains
seromucus glands, nerves and ganglia, lymphoid tissue, and irregularly
shaped hyaline cartilage plates.
d. The adventitia contains loose connective tissue that is continuous with the
accompanying branch of the pulmonary artery.
F. Bronchioles
1. Bronchioles are a direct continuation of a small subsegmental bronchus and
represent the 10th-15th generation dichotomous branching. Each bronchiole
supplies air to a pulmonary lobule.
2. Bronchiole range from 5 – 1 mm in diameter and decrease in size with further

branching to yield terminal bronchioles that in turn give rise to the respiratory
bronchioles.
3. The initial pseudostratified columnar epithelium changes to simple ciliated

columnar epithelium and even simple cuboidal epithelium in smaller
bronchioles. The occasional goblet cells seen in larger bronchioles are
replaced by Clara cells in the smaller bronchioles.
a. Clara cells are non-ciliated columnar cells whose apical dome contains
secretory granules. They secrete a surfactant component and a Clara cell
secreting protein that is protective of the bronchiolar epithelium. They also
detoxify inhaled toxins. They also serve as the reserve cell for the
bronchiole epithelium.
b. The walls lack cartilage and glands. The lamina propria contains a thin
layer of loose connective tissue rich in elastin. Surrounding this is a
helical layer of smooth muscle controlled by the parasympathetic nervous
system. The loose connective tissue of the outer layer contains elastic
fibers that radiate out to connect with other airways and accompanying
pulmonary artery branches.
Page 12 of 177
III. RESPIRATORY PORTION
A. Respiratory Lobule and Acinus
1. The respiratory lobule is a 1-2 cm in size area separated by an interlobular
septum.
a. Each lobule contains a terminal bronchiole and its distal acini (respiratory
bronchioles, alveolar ducts, alveolar sacs, and alveoli). Each lobule
contains 3 – 10 acini.
2. The respiratory acinus is considered to be the functional unit of the lung.

a. It consists of the respiratory bronchiole and all of its branches - alveolar
duct, alveolar sacs, and alveoli. This concept is important to
understanding the types of emphysema.
3. Terminal bronchioles are the most distal portion of the conducting system of
airways.
a. The lining epithelium consists of Clara cells and some ciliated cuboidal
epithelial cells.
b. The narrow lumen is surround by loose connective tissue and one or two
layers of smooth muscle.
c. Elastic fibers radiate out connecting the terminal bronchioles with other
bronchial tree members.
4. Respiratory bronchioles serve as a transition between the conducting airways

and the primary site for gas exchange.
a. The lining epithelium contains both ciliated cells and Clara cells. The wall
is interrupted by outpocketing of alveoli were the cuboidal epithelium is
replaced by Type I pneumocytes.
5. Alveolar ducts, lined by alveoli, do not have their own walls and as they
branch out they end in alveolar sacs with their clusters of alveoli.
a. Loose connective tissue intra-alveolar septa support the alveolar ducts.
b. A smooth muscle cell acts as a sphincter, controlling the opening of an

alveolus to an alveolar duct.
c. Elastic fibers tend to tie everything together. They ramify with fibers the
various components of the lobule.
B. Alveolus
1. Gas exchange between the air and the blood takes place in the 200,000,000-
300,000,000 alveoli of the lungs.
Page 13 of 177
2. The alveoli are at the terminus of the respiratory bronchiole via the alveolar
ducts and alveolar sacs. An alveolar septum separates each of the 0.2 mm
sacs from each other. The septum contains lining cell, a capillary, and loose
connective tissue that contains elastic fibers.
3. Alveolar pores (pores of Kohn) traverse the thin wall between adjacent
alveoli. These small, 7 - 9 μm in diameter, apertures are located in spaces
between the capillaries of the alveolar wall. They can provide for collateral air
circulation that would tend to prevent alveolar collapse when peripheral
branches of the bronchial tree become obstructed.
4. The surface of the alveolus in contact with the air is lined by type I and type II
alveolar cells (pneumocytes) and the occasional brush cell that are held
together by tight junctions.
a. Type I pneumocytes are squamous cells that make up approximately 95%
of the alveolar surface area.
b. Type II pneumocytes are cuboidal in shape and are interspersed among

the type I cells.
1) They bulge into the airspace and are concentrated at septal junctions.
2) Although close in number to the Type I cells, their cuboidal shape

allows them to only comprise about 5% of the surface area of the
alveoli.
3) They function as secretory cells whose lamellar bodies represent the

storage form of the phospholipids and proteins found in surfactant.
Contents of the lamellar bodies are released into the alveolar space by
means of exocytosis.
4) Surfactant forms a monomolecular layer over the alveolar epithelium,

and functions to reduce the surface tension at the cell-air interface.
5) Lack of surfactant can result in alveolar collapse during exhalation.

This is a problem in premature infants whose lungs are not sufficiently
developed to produce surfactant.
5. The thin blood-air barrier is the site of gas exchange. This barrier, averaging
0.5 μm in thicknessμm, is made up by the layer of surfactant, type
pneumocytes, epithelial basal lamina, endothelial basal lamina, and
endothelial cells. Two or more alveoli may share the same capillary.
Page 14 of 177
IV. OTHER COMPONENTS
A. Respiratory System As An Immune Organ
1. The respiratory epithelium’s lining of mucus secretions from goblet cells and
submucosal glands serves as a barrier to invading organisms. It also
contains enzymes that help to break down entrapped material.
2. The cilia propel filtered and entrapped material toward the oropharynx where
it is swallowed or spit out.
3. IgA secreted by plasma cells in the lamina propria and submucosa is

secreted into the mucosa lining.
4. Tonsil and lymphoid aggregates with the mucosa and submucosa of the
airways are critical components of the adaptive immune response to inhaled
antigens.
5. Lymphoid aggregates are found throughout the lung parenchyma within the
septal connective tissue.
6. Alveolar macrophages crawl along the surface of the alveoli just under the
surfactant layer.
a. Parenchymal lung diseases are mediated, in large part, by their secretion
of mediators, reactive oxygen species and proteolytic enzymes in
response to inhaled allergens, inert particles, and organisms.
B. Pleura
1. The pleural cavity – the space between the surface of the lungs and the
thoracic cage – is lined by a continuous two serous membrane. The visceral
pleura covers the lungs and the parietal pleura lines the inner surface of the
thoracic cage.
2. The pleura is lined by mesothelial cells that overlie a layer of connective

tissue that contains collagen and elastic fibers.
3. The pleural cavity between these two layers contains a thin film of lubricating
fluid that reduces the friction between the lung surfaces and the thoracic walls
that could occur during respiratory movements.
C. Pulmonary Circulation
1. The lungs have a dual blood supply of arteries and veins.
a. Pulmonary arteries arise from the heart and function in gas exchange.
b. Bronchial arteries arise from the thoracic aorta and intercostal arteries and
provide nutrients to the lungs.
Page 15 of 177
Physiology: O2 and CO2 Transport
Time: 11:00 am
Faculty: James Allen, MD
Email: james.allen@osumc.edu
Required Reading: West, John B.: Respiratory Physiology: The Essentials. Chapter 6.
Lippincott, Williams, & Williams. 2008.
Physiology Lecture: Mechanisms of O2 and CO2 Transport
1. Define the 2 mechanisms by which O2 is carried in whole blood.
2. Distinguish between % oxygen saturation (SaO2), oxygen content (CaO2) and

PO2. Define what normal PO2, SaO2 and CaO2 are in the arterial blood. Be able
to draw an oxyhemoglobin dissociation curve with either % Hb saturation or O2
content on the Y axis.
3. Know the approximate normal Hb in males and females. Given the constant for
the reaction of Hb with O2 and the % saturation, be able to calculate the content
of arterial oxygen in the blood.
4. Distinguish the differences in the behavior of the reaction between O2 and

hemoglobin above and below a PO2 of 60 mm Hg. Identify how this influences
the loading of O2 at the lungs and the unloading of O2 at the peripheral cells.
5. Describe the pathophysiologic mechanism of carbon monoxide poisoning,

methemoglobinemia, sickle cell anemia, and cyanide poisoning. Be able to
diagnose and treat carbon monoxide poisoning and methemoglobinemia.
6. Distinguish the effects of anemia and carbon monoxide poisoning on the O2

content, the PO2 and the O2 saturation of the arterial blood.
7. Define the primary factors influencing delivery of O2 to metabolizing cells.

Distinguish the potential influences of capillary PO2, diffusion distance,
mitochondrial or cell PO2, velocity of blood flow and metabolic rate.
8. List the common factors that shift the oxyhemoglobin dissociation curve to the
right and left. Describe the consequences of rightward vs. leftward shifts on
oxygen delivery to the peripheral tissues and oxygen uptake at the lungs,
respectively.
9. Identify conditions that increase and decrease red blood cell DPG.
Page 16 of 177
10. Define the role of myoglobin in tissue oxygen metabolism.
11. List the three primary mechanisms for CO2 transport in the blood and define the
relative significance of each.
12. Memorize the CO2 hydration reaction and the role of carbonic anydrase. Define
how PCO2 affects the acid base status of the blood and the levels of HCO3- and
H+. Memorize the normal pH and normal PCO2 of arterial blood. Define the
term “mixed venous blood” and what the PCO2 and PO2 values are for mixed
venous blood.
13. Compare and describe the differences in the shape of the oxyhemoglobin
dissociation and the CO2-blood dissociation curves. Determine how the shapes
of the curves differentially affect the arterial-venous PO2 and PCO2 differences.
14. Discuss what role the red blood cell plays in CO2 transport and H+ buffering.
Determine how CO2 loading and unloading affect O2 carrying capacity of Hb.
Contrast this with the influence of O2 on CO2 carrying capacity of whole blood.
Page 17 of 177
Diffusion

Time: 8:30 am
Faculty: Elizabeth Allen, MD
Email: beth.allen@nationwidechildrens.org
West Physiology Chapter 3: Diffusion

1. Define diffusion.
2. Memorize Fick’s law, and be able to use it to predict how alterations in the lung tissue or gas
might affect rates of diffusion.
3. Know what characteristic of CO2 and O2 explains their greatly different rate of diffusion.
4. Distinguish between diffusion limitation and perfusion limitation.
5. Identify which gas is considered to be an example of a “perfusion limited” gas, and why.
6. Identify which gas is considered to be an example of a “diffusion limited” gas, and why.
7. Identify circumstances under which oxygen transfer becomes diffusion limited.
8. Identify circumstance under which oxygen transfer is perfusion limited.
9. Describe how diffusion capacity is measured by the single breath CO method.
10. Know the relationship between diffusion capacity, rate of CO uptake and alveolar CO pressure.
11. Know the 2 steps of oxygen diffusion that affect diffusion capacity.
12. Identify factors that can affect the lung’s diffusion capacity.
West Physiology Chapter 7: Mechanics

1. Know which muscles are involved in inspiration and expiration – both at rest and during active
breathing. Identify which muscles are the “main” muscles of inspiration or active expiration.
2. Know how the diaphragm affects the thorax shape, and how it is innervated
3. Know what the term “compliance” means, and what factors can increase, or decrease, lung
compliance.
4. Know what cells make surfactant, what its key component is, and what it does for the lung
5. Explain how and why the area of “best lung ventilation” shifts depending on whether the lung is
normally inflated – or partially deflated.
6. Understand what is different about “uninhibited” chest wall versus lung movement, and what
that has to do with functional residual capacity (FRC.)
7. Describe the 3 types of air movement seen in the airways – and where each is likely to occur.
8. Memorize Poiseuille’s law and use it to predict how airway resistance changes depending on
changes in the airway.
Page 18 of 177
9. Know where in the airways resistance is highest, and why the answer to this question is NOT
the smallest airways.
10. Know how lung volume, smooth muscle constriction, and air characteristics, affect airway
resistance.
11. Know what causes airway smooth muscle constriction, or relaxation.
12. Understand why the equal pressure point limits exhalation, and under what circumstances this
limitation occurs “earlier” in exhalation.
13. Know the relative amount of work required for normal inhalation versus exhalation.
14. Know what “breathing strategies” patients use to reduce work in disease states, and why it’s
important that they develop these strategies.
Page 19 of 177
Acid-Base and Arterial Blood Gases

Time: 9:30 AM
Email: James.Allen@osumc.edu
Objectives
1. Calculate the A-a gradient.

2. Calculate the anion gap.
3. Know the normal values for pH, PCO2, HCO3, anion gap, and A-a gradient.
4. Understand buffering using the Henderson-Hasselbach equation.
5. Identify the four main acid base disturbances by analyzing the arterial blood gas.
6. List the common causes of each of the four main acid base disturbances.
7. Distinguish anion gap metabolic acidosis from non-anion gap metabolic acidosis.
8. List the common causes of anion gap and non-anion gap metabolic acidoses.
9. Distinguish chloride responsive from chloride non-responsive metabolic alkalosis.
10. List the common causes of chloride responsive and chloride non-responsive metabolic alkaloses.
11. Apply compensation rules to distinguish simple from mixed acid-base disturbances.
12. Solve common acid-base problems and create differential diagnoses base on the results of arterial
blood gas measurements, anion gap calculations, and osmolar gap calculations.
13. Describe the clinical use of pulse oximetry and pitfalls of its use in carbon monoxide poisoning
and methemoglobinemia.
14. Given the PCO2 and PO2 while a patient is breathing room air, be able to calculate the A-a
gradient.
Required Reading
West, John B.: Respiratory Physiology: The Essentials. Chapters 6 & 10. Lippincott, Williams, &
Williams. 2008.
I. Introduction
A. Lungs and kidneys work in concert to maintain a narrow range of pH in the blood (7.35-7.45).
B. Lungs
1) Major role in minute-to-minute control of pH by changes in alveolar ventilation.
a) Alveolar ventilation determines the partial pressure of CO2 in the blood
by changes in the total minute ventilation (Remember that minute
ventilation is determined by the alveolar volume and dead space volume).
b) PaCO2 = k x Rate of CO2 production
Alveolar ventilation
c) An increase in PaCO2 by 5 mm Hg can result in a two-fold increase in
minute ventilation.
2) Excrete 10 mEq of carbonic acid per minute or > 10,000 mEq per day.
3) During exercise acid excretion can increase to 40,000 mEq per day.
4) Carbonic acid is also known as a volatile acid because it can be converted to CO2
that is eliminated by the lungs.
Page 20 of 177
C. Kidneys
1) Renal tubular cells are important in maintaining proper pH by secreting or retaining
bicarbonate (HCO3-) in exchange for hydrogen ions (H+).
2) Excrete 100 mEq fixed acids per day.
3) Fixed acid refers to endogenous acid production mainly from combustion of glucose
and fatty acids.
4) Unlike the immediate ventilatory response to acid-base disturbances, the renal
response slowly evolves over 24-72 hours.
II. pH
A. The body’s major buffering system is the carbon dioxide-bicarbonate system.

1) Hydrogen ion formed from metabolically produced acids is converted to water and
carbon dioxide by carbonic anhydrase.
2) The pH results from solution of carbon dioxide in the blood and the dissociation of
carbonic acid.
H2CO3 ↔ H+ + HCO3-
B. Henderson-Hasselbach equation:
pH = pKA + log[HCO3]
[H2CO3]
In the plasma, the equilibrium of carbon dioxide and carbonic acid favors carbon dioxide.
The solubility coefficient for carbon dioxide is 0.03 mL/dL/mm Hg.
Therefore:
pH = pKA + log[HCO3]
0.03 x PaCO2
Substituting in known values, pKA of carbonic acid 6.1, bicarbonate concentration 24

mEq/L, and partial pressure of carbon dioxide 40 mmHg.
pH = 6.1 + log 24/0.03 x 40

= 6.1 + log 20
= 7.4
B. Homeostasis
1) From the Henderson-Hasselbach equation, as long as the ratio of bicarbonate to
carbon dioxide remains equal to 20, the pH will be 7.40.
2) Bicarbonate concentration is mainly determined by the kidneys.
3) Partial pressure of CO2 is determined mainly by the lungs.
4) Primary respiratory disturbance
a) Aberration in volatile acid excretion resulting in an abnormal level of
carbon dioxide.
1. Respiratory acidosis occurs if carbon dioxide cannot be excreted
and thus PaCO2 is elevated. Kidneys compensate by retaining
HCO3.
2. Respiratory alkalosis occurs if carbon dioxide is over excreted and
thus PaCO2 is decreased. Kidneys compensate by excreting HCO3.
5) Primary metabolic disturbance
a) Aberration in fixed acid excretion resulting in an abnormal serum
bicarbonate level.
Page 21 of 177
1. Metabolic acidosis determined by a decreased HCO3 level. Lungs
compensate by increasing minute ventilation and thus alveolar
ventilation to “blow off” CO2.
2. Metabolic alkalosis determined by an increased HCO3 level. The
lungs compensate by decreasing minute ventilation to retain CO2.
III. Arterial Blood Gases

A. Normal values
pH (7.35-7.45; average = 7.40)
PaCO2 (36-44 mmHg; average = 40)
PaO2 (80-100mmHg) age dependent.
Your PaO2 decreases with age and can be calculated by the following formula:
[104 – (age x 0.4)]
HCO3- (22-26 mEq/L; average = 24)
SaO2 (95-98%)
B. Evaluating arterial blood gases.

1) Look at the pH first---alkalemia is present if the pH is > 7.45 and an acidemia is
present if the pH is < 7.35.
2) Next look at the PaCO2 and HCO3 to determine the primary disturbance. For the
purpose of blood gas interpretation, use 40 mmHg as the normal value for PaCO2
and 24 mEq/L for HCO3.
3) Let’s say the pH is < 7.35 (acidemia)----Primary process is respiratory acidosis if
PaCO2 is > 40 mm Hg or metabolic acidosis if the HCO3 is < 24 mEq/L.
4) Let’s say the pH is > 7.45 (alkalemia)----Primary process is respiratory alkalosis if
PaCO2 is < 40 mm Hg or metabolic alkalosis if the HCO3 is > 24 mEq/L.
IV. Respiratory Acidosis
A. Definition
1) If an acidosis is present by pH and the PaCO2 is elevated, then a primary respiratory
acidosis exists. As the PaCO2 increases, the renal tubules are stimulated to excrete
H+ and retain HCO3-.
2) Note: There are two categories for primary respiratory disturbances, acute and
chronic, because the kidneys take several days to fully compensate. Therefore, there
are different degrees of compensation depending on when the blood is sampled.
B. Etiologies
1) Central nervous system depression (drug overdose). Depressed respiration.
2) Neuromuscular disorder (ALS, muscular dystrophy, Guillian Barre syndrome).
Inability to move the thoracic cage or diaphragm.
3) Thoracic cage abnormalities (severe kyphoscoliosis).
4) Obstructive lung disease (asthma, COPD). Airflow limitation can impair CO2
elimination by increasing dead space ventilation.
5) Obesity hypoventilation syndrome.
6) Myxedema coma (severe hypothyroidism). Central nervous system depressant.
C. Compensation
1) Acute respiratory acidosis (less than 2-3 days).
For every 10 mmHg ↑ in the PaCO2 the HCO3 ↑ by 1 mEq/L
2) Chronic respiratory acidosis (greater than 2-3 days).
For every 10 mmHg ↑ in the PaCO2 the HCO3 ↑ by 3.5 mEq/L
Page 22 of 177
V. Respiratory Alkalosis
A. Definition
1) If alkalosis present by pH and the PaCO2 is low, then a respiratory alkalosis is
present. As the PaCO2 decreases, the renal tubules are stimulated to excrete HCO3-
in exchange for H+.
B. Etiologies
1) Anxiety/pain.
2) Sepsis.
3) Central nervous system (stroke).
4) Aspirin overdose.
5) Chronic liver disease.
6) Pulmonary embolism.
7) Pregnancy.
8) Hyperthyroidism.
C. Compensation
1) Acute respiratory alkalosis
For every 10 mmHg ↓ in PaCO2 the HCO3 ↓ by 2 mEq/L
2) Chronic respiratory alkalosis
For every 10 mmHg ↓ in PaCO2 the HCO3 ↓ by 5 mEq/L
VI. Metabolic Acidosis
A. Definition
1) If pH indicates an acidosis and the HCO3 level is low then a metabolic acidosis is
present. The drop in pH stimulates chemoreceptors to increase the minute
ventilation.
2) Results when excess fixed acids are ingested or produced.
3) Note: Metabolic acidoses are separated into gap and non-gap acidosis.
a) The anion gap can be calculated by the following formula:
Na+ - (Cl- + HCO3-) = anion gap
b) Sodium is the primary cation in the extracellular space and bicarbonate and
chloride are the primary anions. The sum of chloride and bicarbonate is
less than the sodium concentration. The extra anions that are needed to
maintain electrical neutrality are not routinely measured serum electrolytes.
These extra anions are referred to unmeasured anions or the anion gap.
Extra negatively charged particles such as acids, like lactic acid or ketones,
will increase the anion gap, indicating a metabolic acidosis. The normal
anion gap is 12.
c) The presence of an elevated anion gap (> 12) always indicates the presence
of a metabolic acidosis.
B. Etiologies
1) Anion gap acidosis
a) Ketoacidosis (diabetic, starvation, alcohol).
b) Lactic acidosis (sepsis).
c) Uremia (renal failure).
d) Certain poisonings---methanol, ethylene glycol.
Page 23 of 177
i. These can be suspected if there is an increase in the osmolar gap
ii. Osmolarity = 2(sodium) + glucose/18 + BUN/2.8 + ethanol/4.6
iii. Normally the measured Osm. - calculated Osm. < 10
iv. If the osmolar gap is > 10, suspect methanol or ethylene glycol
e) Aspirin/salicylate toxicity.
2) Non-anion gap acidosis
a) Diarrhea (loss of bicarbonate through the colon).
b) Renal tubular acidosis (loss of bicarbonate through the kidneys).
c) Acetazolamide (carbonic anhydrase inhibitor).
d) Total parenteral nutrition (infusion of excess acid).
e) Pancreas transplant (plug the new pancreas into the bladder, lose
bicarbonate in the urine).
C. Compensation
1) Last 2 digits of the pH = PCO2 (easy to calculate)

2) PaCO2 = 1.5(HCO3) + 8 ± 2 (harder to calculate)
VII. Metabolic Alkalosis
A. Definition
1) If pH indicates the presence of an alkalosis and the HCO3 is elevated, then a
metabolic alkalosis is present.
2) Results from loss of acidic bodily fluids, excess alkali ingestion (antacids), or excess
renal retention of bicarbonate.
3) Note: Metabolic alkaloses are separated into chloride responsive and unresponsive
based on the urine chloride level. Chloride responsive metabolic alkalosis results
from loss of body fluids and responds to intravascular volume expansion
(intravenous replacement of fluid) with sodium chloride solution. Chloride
unresponsive due to problem with HCO3 homeostasis so does not respond to fluid
replacement.
B. Etiologies
1) Chloride responsive (urine Cl- < 10)
a) Vomiting.
b) Nasogastric suctioning.
c) Diuretic use.
2) Chloride unresponsive (urine Cl- > 10)
a) Exogenous steroids
b) Cushing’s syndrome
c) Hyperaldosteronism
d) Bartter’s syndrome
C. Compensation
1) For every 10 mEq/L ↑ HCO3 the PaCO2 ↑ by 6 mmHg
VIII. Hypoxemia
A. Causes:
i. Low alveolar PO2
ii. Hypoventilation
iii. High altitude
iv. Reduced inhaled oxygen (FiO2)
v. Diffusion impairment
vi. Interstitial lung disease
vii. Pulmonary edema
viii. Emphysema
Page 24 of 177
ix. Shunt
x. Intra cardiac shunt
xi. Intra pulmonary shunt
B. The A-a gradient (Alveolar-arterial oxygen gradient)
i. This is a way of assessing oxygenation adjusted for changes in ventilation (PCO2)
ii. A-a gradient = [150 - (5/4 x PCO2)] - PO2
iii. Normal = 4 + (age ÷ 4)
1. Therefore, normal for a 20 year old = 8 and for an 80 year old = 24
2. An increase in the A-a gradient indicates abnormal:
a. Shunt
b. Ventilation-perfusion mismatch
c. Diffusion limitation in the lung
Page 25 of 177
INTRODUCTION TO CHEST RADIOLOGY

Time 10:30 am
Faculty: Mark A. King, M.D.
Associate Professor of Radiology
Objectives:
1. Correctly identify air, water (soft tissue) and calcium density on a chest radiograph.
2. Explain the summation sign and identify an example on a chest radiograph.
3. Correctly identify the silhouette sign on a chest radiograph and explain why it occurs.
4. Know when a lateral decubitus radiograph might be used in clinical practice.
5. Correctly identify typical examples of lobar pneumonia (and identify which lobe is
involved), pneumothorax, and pleural effusion.
The Chest Radiograph

Systematic evaluation of the chest radiograph should include attention to the bones and soft
tissues, the hila, the mediastinum, the heart, and finally the lungs and pleura. Systematic
evaluation is important because it is common that more than one abnormality is present on a
CXR, and often incidental findings, those we are not looking for or expecting, are the most
important findings. If one is searching only for one abnormality, once it is found, the search is
over without complete evaluation of the radiograph.
The standard views for conventional chest radiography include:
1. PA (posterior-anterior): The film is against the chest wall, the photons enter from
posterior and travel in an anterior direction through the patient to the film.
2. AP (anterior-posterior): The film is against the patient’s back, and the photons enter from
an anterior direction and travel posteriorly through the patient to the film. Used almost
exclusively for portable examinations in patients who cannot be transported to the
radiology department.
3. Lateral: The film is (usually) against the left side of the patient, photons enter from the
right side.
4. Lateral decubitus: The patient is placed on his/her side (either right or left) with film
behind the patient. Done to take advantage of gravity, especially to detect fluid in the
pleural space.
5. Oblique: Can be done with film in front of, or behind the patient; the patient is obliquely
oriented with respect to the film. Not used very often these days: this view has been
mostly replaced by CT.
6. Apical lordotic: Film behind the patient, beam enters from the anterior direction and
travels posteriorly through the patient; the patient “leans back” against the film for this
exam. This is used to improve visibility of the lung apices. As is the case with the oblique
radiograph of the chest, this view has also been mostly replaced by CT.
Page 26 of 177
Normal Anatomy:
We will go through normal anatomy in class. Always try to keep in mind that it is important to
think of the anatomy you are seeing in a three-dimensional way: the chest radiograph is a two-
dimensional representation of a three-dimensional structure.
Radiographic Densities:
On a chest radiograph, four basic densities are visible: air (black), bone/calcium (white), fat
(dark gray) and soft tissue/water (very light gray to white). Of course, these densities are all
relative: they relate to the efficiency with which the tissue in question attenuates, or for lack of a
better term, absorbs, the x-ray photons. If all the photons make it to the film (such as is the case
with air), the film is exposed and turns black. If the photons encounter calcium in bone, many
photons are absorbed and don’t make it to the film, and the film is relatively unexposed, and
remains clear (then, when it is shown using a white light source, it appears white). Water is more
efficient at absorbing the x-ray photons than is fat, so water appears “whiter” than fat does. The
degree to which these differences are apparent is a function of image contrast, which is altered
by altering the energy of the photons delivered. The physics is complicated, and you don’t need
to know any of it (unless you decide to become a radiologist), so I won’t clutter your minds with
it. Just try to remember that, in order of decreasing efficiency in attenuating x-ray photons, the
components of the chest are represented as follows: bone (most opaque/white), soft
tissue/water, fat, then air (least opaque, most black).
Understanding these different densities is crucial to being able to interpret a chest radiograph.
Recognizing differences in opacity, or optical density, between two structures is how one
differentiates structures that are adjacent to one another. If two contiguous structures are equally
opaque, it is not possible to tell where one ends and the other begins. Fortunately, in the chest,
the lungs are relatively “black” (when filled with air) and the thoracic organs are relatively
“white” (composed mostly of water), so that the lungs outline, or highlight, the solid organs of
the thorax. When the lungs become filled with fluid (pneumonia, aspiration, drowning,
pulmonary hemorrhage, etc), or with material that has the same radiograph density as fluid (such
as a lung cancer), the lung turns white in that region and is said to be “opacified”, or “opaque”. If
this occurs in alveoli that are contiguous with a normal soft tissue structure (fluid density), the
margin between the two structures is obscured: this is called the “silhouette sign”. The silhouette
sign is a useful tool for detecting and localizing lung disease on a chest radiograph.
The Lungs:
As mentioned earlier, the lungs are radiolucent (dark) relative to other structures in the thorax.
Pulmonary artery branches and veins are visible as branching gray-white structures; bronchi,
except for the main bronchi, are generally not visible except in disease states.
Most of the diseases affecting the lung cause abnormally increased opacity: pneumonia,
pulmonary edema, interstitial lung disease, and a variety of other pathologic processes cause
increased opacity in the lung. When the lung fills with fluid (of any kind), two radiological signs
may be observed:
Page 27 of 177
1. The silhouette sign (mentioned above)
2. Air bronchogram: This occurs when air-filled (patent) bronchi are surrounded by fluid-
filled alveoli. The bronchus is visible as a dark gray tube surrounded by opaque lung
tissue.
It is generally not possible to diagnose a specific etiologic agent when pneumonia is seen on a
chest radiograph. In fact, it may be difficult to differentiate pneumonia from lung cancer on a
chest radiograph. Knowledge of the clinical findings and the patient’s history is important when
trying to assign a specific likely etiology to a chest radiographic abnormality.
Emphysema, vascular obstruction, and air trapping are examples of processes that cause
abnormally decreased opacity in the lung. In emphysema, there is less tissue per unit volume in
the lung (alveolar atrophy); in vascular obstruction (such as acute pulmonary embolism), there is
less soft tissue density per unit lung (decreased blood flow in a given volume of lung); in
diseases that cause air trapping, there is more air (radiolucent) per unit lung volume.
The Heart and Mediastinum:

There are a couple of facts one needs to know regarding the heart and mediastinum on chest
radiographs:
1. On the frontal view of the chest made in the postero-anterior projection, the transverse
diameter of the heart should not exceed the maximum transverse diameter of the thorax.
If it does, the heart is likely pathologically enlarged.
2. On the frontal view of the chest, the right heart border is the right atrium; the left heart
border is the left ventricle.
3. On the lateral view, the anterior portion of the heart is the right ventricle, and the
posterior portion of the heart is the left atrium.
4. The medial edge of the right lower lobe is superimposed over the spine, and parallels the
esophagus and azygous vein. This anatomic region is bordered by a pleural reflection and
is called the azygoesophageal recess. On the frontal view of the chest, it is a window into
the middle mediastinum (remember: it is an air/soft tissue interface) and middle
mediastinal masses are visible on the frontal film if they cause a convex bulge in the
outline of this recess.
5. On the frontal radiograph, the azygous vein should measure no more than 12mm in
diameter. If larger, the patient may have abnormally enlarged lymph nodes in this region.
The Pulmonary Hila:

The hila are difficult to evaluate, and even experienced chest radiologists may misinterpret
structures in the hila. A couple of facts regarding the hila are helpful for identifying the normal
hilum and for recognizing abnormalities of the hilum:
1. On the frontal view, the density of the two hila should be essentially the same. If one
hilum appears more opaque than the contralateral hilum, a mass should be suspected.
(See “summation sign”).
Page 28 of 177
2. On the lateral view, the right pulmonary artery appears more opaque than the left
pulmonary artery, because of the fact that the RPA crosses the mediastinum from left to
right before branching and turning to descend into the lower lobe; the course of the LPA
is relatively vertical as it ascends from the pulmonary outflow tract, then descends into
the left lung. It is seen in profile, so its radiographic density is less than that of the RPA,
which is seen en face.
3. Hilar masses cause convex bulges in the normal contour of the hilum. It takes a great deal
of experience to feel comfortable with diagnosing hilar masses, unless they are large and
cause obvious contour abnormalities.
The Pleura:
The lung is surrounded by the visceral pleura, and the chest wall is lined internally by the parietal
pleura. The intervening space contains a small amount of fluid that is dispersed throughout and,
as a result, the layers of the pleura are adherent. The lung therefore adheres to the chest wall,
essentially, and occupies the thoracic volume. The “relaxed” volume of the lung, however, is
only about the size of a fist. If air makes it way into the pleural space, the lung loses its adherent
contact with the parietal pleura, and the lung pulls away from the chest wall (pneumothorax). If
excess fluid collects in the pleural space (pleural effusion, or hydrothorax), it usually collects in
the most dependent portion of the pleural space. This causes blunting of the normally sharp
lateral and posterior costophrenic sulci.. Pleural fluid may also be “loculated”: this is diagnosed
when a pleural fluid collection occurs in a location that is not dependent, and often indicates an
inflammatory pleural fluid collection (could mean infection, or bloody effusion). Pleural
thickening by soft tissue masses (such as in spread of malignancy to the pleura), may look
exactly like a loculated pleural fluid collection: it is a pleural abnormality that occurs in a non-
dependent location, and is often localized.
Summary:
The chest radiograph is an indispensable tool for evaluating the patient with suspected
pulmonary disease. Understanding fundamental principles of thoracic anatomy, physiology, and
pathology is important when interpreting a chest radiograph.
Page 29 of 177
Blood Flow & Metabolism

Time: 8:30 am
Faculty: Douglas Haden, MD
Email: Douglas.haden@osumc.edu
Objectives for Pulmonary Circulation Lecture
1. Name the primary differences between the underlying anatomical and physical
characteristics of the pulmonary circulation vs. the systemic circulation.
2. Describe the source(s) of nutrient blood flow to the bronchi and lung parenchyma.
Describe how blood flow leaving this system can influence the final PO2 in the
arterial blood.
3. Given a set of hemodynamic values from a cardiac catheterization, calculate the

mean pulmonary artery pressure and pulmonary vascular resistance.
4. List thee primary factors that affect the passive resistance of the pulmonary
circulation.
5. Compare what makes up the “transmural pressure” across the pulmonary vascular
wall in the extrapulmonary and intrapulmonary vessels.
6. List at least 2 primary vasomediators in the pulmonary vasculature that are

sometimes used clinically.
7. Compare total pulmonary blood flow in apex of the lung vs. the lung bases in the
upright position and how this might change in the supine position. Define what
is meant by the “Dependent Region” of the lung. Describe the different “lung
zones” based upon the relative vascular and alveolar pressures.
8. Recognize the Starling Equation for fluid movement across the lung (or any other
vascular bed). Define oncotic pressure, osmotic pressure, permeability coefficient
and reflection coefficient. Be able to determine the direction of fluid movement
from one compartment to another when changes occur in capillary hydrostatic
pressure, pleural pressure, interstitital or alveolar protein concentration, lung fluid
permeability.
Page 30 of 177
Ventilation & Perfusion

Time: 9:30 am
Objectives for Ventilation-Perfusion Lecture
1. Given a clinical case presentation the student will correctly identify the cause of
hypoxemia.
2. Given the values from an arterial blood gas, the student will correctly calculate an
alveolar-arterial oxygen difference and recognize whether it is normal or
abnormal.
3. Recognize the source of the physiological alveolar-arterial oxygen gradient
4. Given a clinical case presentation the student will correctly describe the
ventilation-perfusion inequality and it’s effect on gas exchange
5. The student will be able to describe the different types of shunt
Page 31 of 177
Examination & Diagnostic Testing
Time: 10:30 AM
Objectives: By the end of this lecture and the associated small group case studies, you should be able
to:
1. Utilize information from patient’s histories in order to generate differential diagnoses of
pulmonary conditions.
2. Associate a description of patients’ physical examination findings with common lung diseases
including pneumonia, pleural effusion, interstitial lung disease, pulmonary edema, asthma, upper
airway obstruction, and chronic obstructive lung disease.
3. Analyze pulmonary function test results and use patterns of obstruction, restriction, and reduced
diffusing capacity to diagnose common lung diseases covered in this module.
4. Correctly choose procedures in pulmonary medicine in order to facilitate diagnosis in common
clinical settings. Specific procedures include: methacholine challenge testing, ventilation perfusion
scan, thoracentesis, mediastinoscopy, video-assisted thorascopic surgical biopsy, bronchoscopy,
pulmonary angiography, CT scan, PET scan, chest x-ray, and pulmonary artery catheterization.
5. Recognize flow volume loop patterns of upper airway obstruction, asthma, restriction, and normal
individuals.
6. Compare different tests of oxygenation including overnight oximetry, 6-minute walk test, and high
altitude hypoxia simulation test.
Optional Reading:
1. Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter 245: Approach to the
patient with disease of the respiratory system; David Lipson, Steven E. Weinberger.
2. Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter 246: Disturbance of
respiratory function; Steven E. Weinberger, Ilene Rosen.
3. Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter 247: Diagnostic
procedures in respiratory disease; Scott Manaker, Steven E. Weinberger.
I. Examination of the Pulmonary Patient
A. Signs and Symptoms
1) Note duration, timing, character, severity, ameliorating and exacerbating factors,

associated symptoms.
2) Most common symptoms

a) Dyspnea or shortness of breath.
i) Tachypnea—rapid respiratory rate. Distinguished from
dyspnea.
ii) Hyperventilation---increased VA so hallmark is low PaCO2
distinguished from tachypnea.
iii) Orthopnea---dyspnea in recumbent or supine position.
iv) Platypnea---dyspnea in upright position.
v) Paroxysmal nocturnal dyspnea.
b) Cough
c) Chest pain
i) Pleuritic
ii) Non-pleuritic
Page 32 of 177
d) Hemoptysis---coughing up blood.
3) Most common signs

a) Tachypnea
b) Adventitial or abnormal breath sounds.
B. History
1) Tobacco usage described in pack-years (number of packs per day x years smoked).
2) Illicit Drug use.
3) Occupational or other exposures.
4) Hobbies or home environment.
5) Travel history.
6) Family history.
7) Co-existing or previous diseases
8) Symptom specific questions:

a) Duration
b) Frequency
c) Severity
d) Quality
e) Exacerbating factors
f) Relieving factors
g) Associated factors
C. Physical Examination
1) Key features---inspection, palpation, percussion, and auscultation.
2) Normal breath sounds

a) Examples on the internet at:
i) http://www.rale.ca/Recordings.htm
ii) http://medocs.ucdavis.edu/IMD/420C/sounds/lngsound.htm
b) Vesicular---heard over small airways, duration of inspiration > expiration.
c) Bronchovesicular---heard over large airways, duration of expiration =
inspiration.
3) Abnormal breath sounds

a) Crackles = rales
i) Brief discontinuous sound heard during inspiration.
ii) Congestive heart failure, pulmonary fibrosis and pneumonia.
b) Wheezes = rhonchi
i) High or low-pitched musical sound, more continuous, heard
during inspiration, expiration or both.
ii) Asthma and COPD
c) Other
Page 33 of 177
i) Bronchial – abnormal – more expiratory than inspiratory and
more “tubular” or “hollow”. Indicates an underlying
consolidation
ii) Egophony---hear a nasal “aaa” with stethoscope when patient
says “eee” over an area of consolidation.
iii) Whispered pectoriloquy----whispered sounds accentuated
through a stethoscope over consolidation.
iv) Rubs---friction sound during inspiration and expiration,
inflamed pleural surfaces rubbing together.
II. Pulmonary Function Tests
A. Spirometry
1) Vital capacity (VC)---maximum volume of air that can be inspired or expired

Equal to IRV + VT + ERV.
2) Forced vital capacity (FVC)---volume of air measured after a maximal inspiration

then forcefully exhaled completely. Slightly less than VC measured during slow
exhalation.
3) Forced expiratory volume in one second (FEV1)---volume of air exhaled in the first
second of a FVC maneuver. Normally about 80% of the FVC.
4) FEV1/FVC----low ratio seen in obstructive lung disease. A normal ratio depends

on the patient’s age and race, for example an FEV1/FVC ratio of less than 78% may
define obstruction in a young individual but the FEV1/FVC ratio cut-off may be 72%
in an older individual. For convenience during this module, we will use 75% as the
cut-off to define obstruction. The overwhelming majority of pulmonary function
testing machines will incorporate calculations to calculate the appropriate normal
value for the FEV1/FVC ratio. For convenience during this module, we will use 75%
as the cut-off to define obstruction. Reversible airflow is defined as a 12%
improvement in the FVC or FEV1 after an inhalational challenge with a β2 agonist
such as albuterol.
B. Lung Volumes
1) Residual volume (RV)---volume of air left in the lungs after a maximal expiration.
a) Cannot empty the lungs completely.
b) Cannot be measured directly with a spirometer.
2) Functional residual capacity (FRC)---volume of air in the lungs after a normal tidal
volume breath.
a) Cannot be directly measured with a spirometer; requires additional
equipment.
b) Methods:
1. Helium dilution.
2. Body plethysmography (most commonly used by PFT labs).
c) Elevated levels indicate airtrapping (can be seen in asthma, COPD or
emphysema).
d) Airtrapping results in ↑ FRC, defined as > 120% of predicted.
3) Total lung capacity (TLC)---the sum of all lung volumes.

a) VT + IRV + ERV + RV = RV + VC = TLC
b) TLC less than 80% of predicted indicates restrictive lung disease.
Page 34 of 177
c) Elevated TLC is indicative of hyperinflation and can be seen in asthma,
COPD, and emphysema, defined as TLC > 120% predicted.
C. Diffusing Capacity (DLCO)
1) A measure of the ability of a gas to move across the alveolar-capillary membrane.
2) Dependent on solubility and molecular weight of the gas, surface area and thickness
of the membrane and transit time. Main determinant of diffusion rate is the partial
pressure gradient for the gas across the membrane.
3) Measure of diffusing capacity using carbon monoxide (CO) (most commonly used in
clinical practice)
a) CO diffuses readily.
b) Binds avidly and reversibly with hemoglobin thus there is virtually no
increase in the partial pressure. Therefore, the amount of CO in the
circulation is dependent on the properties of the alveolar-capillary
membrane itself plus the amount of available hemoglobin.
c) Uptake of CO is diffusion limited (as opposed to perfusion limited),
therefore, gas of choice for measuring diffusing capacity.
d) Gas mixture of CO and He with known concentration, patient breath
holds for 10 seconds, CO diffuses and He does not, rate of CO
disappearance is calculated from the concentration of CO in exhaled gas.
e) Normal value for single breath DLCO = 25 ml/min/mmHg.
4) Measure of diffusing capacity using nitrogen (rarely used in clinical practice).

a) Nitrogen does not bind with hemoglobin, dissolves in plasma, so partial
pressure of gas increases resulting in back pressure, limiting further
uptake of nitrogen.
b) Amount of nitrogen in circulation depends on the rate of blood flow.
Thus nitrogen is perfusion limited.
c) Single breath nitrogen wash-out.
5) Clinical factors affecting DLCO.

a) Age--- DLCO decreases with age.
b) Size of lungs----gender, body size.
c) Interstitial lung disease---- DLCO ↓ due to increased thickness of
interstitium.
d) Emphysema--- DLCO ↓ due to loss of surface area.
e) Pulmonary embolism--- DLCO ↓ due to blocked blood flow.
f) Hemoglobin--- DLCO ↓ with anemia due to less binding availability,
DLCO ↑ with polycythemia.
g) Alveolar hemorrhage--- DLCO ↑, inspired CO binds with blood in alveoli,
acting as a reservoir so more CO available for transfer.
Pulmonary Function Test Patterns in Lung Disease
FVC FEV1 FEV1/FVC TLC DLCO

Asthma/COPD ↓ or normal ↓↓ < 75% Normal or ↑ Normal
Emphysema ↓ ↓↓ < 75% ↑ ↓
Pulmonary
Fibrosis ↓↓ ↓ > 75% < 80% ↓
Pulmonary
Embolism Normal Normal Normal Normal ↓
Page 35 of 177
Additional features:
1) Hyperinflation can be seen in emphysema.
2) Airtrapping (↑ FRC) and ↑ RV due to inability to fully exhale air seen in asthma and
emphysema.
3) Neuromuscular disorders or problems with the thoracic cage results in restriction.

Differentiated from interstitial lung disease by ↑ RV and normal DLCO.
IV. Radiographic Testing
A. Standard PA and left lateral chest x-ray.
B. Computed Tomography of the chest/Spiral CT.
C. Ventilation perfusion scan.
D. Pulmonary angiography.
V. Invasive Testing
A. Bronchoscopy.
IRV IC
B. Thoracentesis/Pleural biopsy.
C. Mediastinoscopy
D. Thoracotomy
E. Video Assisted Thoracoscopic Surgery (VATS)
ERV
FRC
RV
Page 36 of 177
Mechanics

Time: 8:30 am
Email: Beth.allen@nationwidechildrens.org
West Physiology Chapter 7: Mechanics

1. Know which muscles are involved in inspiration and expiration – both at rest and during active
breathing. Identify which muscles are the “main” muscles of inspiration or active expiration.
2. Know how the diaphragm affects the thorax shape, and how it is innervated
3. Know what the term “compliance” means, and what factors can increase, or decrease, lung
compliance.
4. Know what cells make surfactant, what its key component is, and what it does for the lung
5. Explain how and why the area of “best lung ventilation” shifts depending on whether the lung is
normally inflated – or partially deflated.
6. Understand what is different about “uninhibited” chest wall versus lung movement, and what
that has to do with functional residual capacity (FRC.)
7. Describe the 3 types of air movement seen in the airways – and where each is likely to occur.
8. Memorize Poiseuille’s law and use it to predict how airway resistance changes depending on
changes in the airway.
9. Know where in the airways resistance is highest, and why the answer to this question is NOT
the smallest airways.
10. Know how lung volume, smooth muscle constriction, and air characteristics, affect airway
resistance.
11. Know what causes airway smooth muscle constriction, or relaxation.
12. Understand why the equal pressure point limits exhalation, and under what circumstances this
limitation occurs “earlier” in exhalation.
13. Know the relative amount of work required for normal inhalation versus exhalation.
14. Know what “breathing strategies” patients use to reduce work in disease states, and why it’s
important that they develop these strategies.
Page 37 of 177
Pulmonary Hypertension

Time: 9:30 am
Objectives for Pulmonary Hypertension Lecture
1. Given measurements obtained from pulmonary artery catheterization, the student

should be able to calculate mean pulmonary arterial pressure (mPAP) and
pulmonary vascular resistance (PVR) and diagnose the presence of pulmonary
hypertension.
2. Given a clinical vignette, the student should be able to correlate the most likely
cause of pulmonary hypertension (e.g. left heart disease, lung disease) with results
from pulmonary artery catheterization.
3. The student should be able to identify the common histopathological findings

observed in patients with pulmonary arterial hypertension (PAH).
4. The student should be able to relate the molecular pathogenesis of pulmonary

arterial hypertension to the pharmacological mechanisms of currently available
drug therapies.
5. Given a history suggestive of pulmonary arterial hypertension, the student should

be able to recognize key findings on physical examination and suggest
appropriate diagnostic testing.
Page 38 of 177
Thromboembolic Disease
Time: 10:30 am
Faculty: Naeem A. Ali, MD
201d DHLRI, 473 W 12th Ave
Columbus, OH 43210
293-4925, 293-4799
Email: Naeem.Ali@osumc.edu
Learning objectives: by the end of this lecture and the associated small group case studies,
you should be able to:
1. List the major risk factors for venous thromboembolism.

2. List the components of Virchow’s triad.
3. Given a clinical vignette, recognize the signs and symptoms of deep venous thrombosis
and of pulmonary embolism.
4. Given a clinical vignette, choose appropriate diagnostic tests for deep venous thrombosis.
5. Compare and contrast diagnostic studies used to diagnose pulmonary embolism including
ventilation perfusion scans, pulmonary angiography, D-dimer, and CT angiograpy.
6. Given a clinical vignette, recommend appropriate treatment for patients with venous
thromboembolism based on thromboembolism severity and results of diagnostic tests.
7. Recommend strategies to prevent venous thromboembolism in at-risk patient populations.
Learning resources:
1. Harrison’s Principles of Internal Medicine
2. Recent review articles:
a. V Tapson, “Acute Pulmonary Embolism”, N Engl J Med. 2008 Mar 6;358(10):1037-
52.
b. Bates SM, JS Ginsberg, “Clinical Practice: Treatment of deep-vein thrombosis”, N
Engl J Med. 2004 Jul 15;351(3):268-77.
3. Valuable Website: http://home.columbus.rr.com/allen/pulmonary_embolism2.htm
Outline:
Definitions:
• Deep Vein- veins that reside predominantly in the interior of the extremities. Usually are
associated with corresponding arteries.
• Pulmonary embolism- any lesion that has physiologic effects on the lung after traveling
through the systemic veins and then pulmonary arteries to lodge in the small
subsegmental pulmonary arteries.
• Thromboembolism- Any pulmonary embolism thought to result from clot formed outside of
the lung.
• Massive pulmonary thromboembolism- Any pulmonary embolism that presents acutely with
life-threatening respiratory or circulatory failure.
Page 39 of 177
• Massive DVT- Any DVT that results in venous obstruction to the extent that limb
threatening ischemia results
Epidemiology:
Prevalence
About 500,000 people suffer from thromboembolic disease on a yearly basis
Primary Cause of death in 50,000
Cause of death annually for 150,000-200,000 people
Incidence
0.1% overall (Kearon, et al, Semin in Vasc Med, 1 (1), 2001, 7-25)
2/3 are DVT only
2/3 are first events
Incidence with increasing age (Kearon, et al, Semin in Vasc Med, 1 (1), 2001, 7-25)
1% all patients >60yo
0.03% Age 40
0.1% Age 60
0.26% Age 80
Gender (Kearon, et al, Semin in Vasc Med, 1 (1), 2001, 7-25)

Age association is stronger for men
North American Studies suggest worse outcome/incidence in men
Scandinavian, British studies suggest worse outcome/incidence in women
Ethnic groups (Kearon, et al, Semin in Vasc Med, 1 (1), 2001)

In the US
African Americans at greater risk for idiopathic DVT compared to whites
Hispanic, Asian and Pacific Islanders at less risk for idiopathic DVT compared to whites
Non-whites more likely to have fatal VTE events than whites
Seasonal variation
Higher in winter months, but controversial
Pathophysiology:
Virchow’s Triad
1. Vascular injury
a. Endothelial disruption-localized injury from needle stick or cellular injury
b. Vasculitis-diffuse endothelia injury from inflammatory cells (Behcets)
2. Venous stasis
a. Local-immobilization, resolving DVT, Pregnancy
b. Systemic-Congestive heart failure
3. Hypercoagulability
a. Idiopathic-unrecognized state after testing and history
b. Inherited-abnormalities like Factor V Leiden or Prothrombin gene mutation
c. Acquired- Antiphospholipid antibody syndrome or pregnancy
Page 40 of 177
Risk Factors:
Table 1: Initial VTE event
Risk Factor Estimated Relative Risk for VTE
Inherited Conditions
o ATIII Deficiency 25
o Prot C or S Deficiency 10
o Factor V Leiden (Hetero:Homozygous) 5:50
o Prothrombin Gene Mutation 2.5
Acquired Conditions
o Surgery or Trauma 5-200
o History of Previous VTE 50
o APL Antibodies 2-10
o Cancer 5
o Age
o >50 5
o >70 10
o Pregnancy 7
o OCP 5
o HRT 2
Other
o Hyperhomocysteinemia 3
Adapted from N Engl J Med 2004;351:268-77
Table 2: Recurrent VTE

Risk Factor Prevalence (%) Relative Risk for Recurrence
after cessation of therapy
AT III 1 1-3
Prot C or S Deficiency 3 1-3
Factor V Leiden
o Heterozygous 20 1-4
o Homozygous 2 4
Prothrombin Gene Mutation 5 1-5
APL Antibody 5 2-4
Hyperhomocysteinemia 10-25 1-3
Adapted from N Engl J Med 2004;351:268-77
Clinical Presentation:
Up to 40% of patients presenting with symptoms of DVT have a simultaneous PE. (JAMA;
271:223-5)
DVT:
Classic- Typical site of nidus for thrombus formation in DVT is the lower extremity venous sinuses
of the calf muscle. Symptoms are usually pain warmth or swelling of the affected extremity. Other
sites include the pelvic veins or subclavian vein in special circumstances.
Other- Can be asymptomatic, especially after major surgery (i.e. hip arthroplasty)
Page 41 of 177
Pulmonary thromboembolism:
Classic- Pleuritic chest pain and dyspnea
If symptomatic, most frequent symptoms (Arch Intern Med 1986; 146:961-7):
(1) chest pain (88%)
(2) dyspnea (84%)
(3) cough (53%)
(4) hemoptysis (30%)
Other- Less often near-syncope, chest pressure, hypotension (weakness), respiratory failure
Setting clinical suspicion:

• Required to interpret diagnostic study results (imaging)
• Difficult to do for inexperienced clinicians
• Aided by prediction scores (Wells prediction score, most common)
Wells VTE prediction score:

Variable Score
DVT symptoms and signs 3
PE as likely or more likely than other Dx 3
• After assessing Hx, CXR, ECG, labs
HR> 100 bpm 1.5
Immobilization or Surgery in last 4 wks 1.5
Previous VTE 1.5
Hemoptysis 1
Cancer 1
Total score:
• <2.0 low pretest probability
• 2.0-6.0 intermediate pretest probability
• >6.0 high pretest probability
Dichotomized score:
• ≤ 4.0 PE unlikely
• >4.0 PE likely
Diagnosis:
DVT:
Contrast Venography- considered the gold standard and consists of cannulation of a peripheral
vein in the lower extremity and administration of contrast. Good for the diagnosis of both distal
(calf) and proximal (femoral) DVT.
Ultrasonography- Practical gold standard for the diagnosis of proximal DVT (above knee). Relies
on the fact that veins are hypoechoic and can collapsed under direct pressure during visualization.
(non-compressible=luminal filling defect=DVT)
Page 42 of 177
PE:
Diagnostic testing
• Pulmonary angiography- Considered the gold standard. Requires cannulation of a large
vein (femoral or other) and insertion of a pulmonary artery catheter. IV contrast is injected
to reveal intraluminal filling defects. Complications include bleeding risk, renal
insufficiency from IV dye and transient RBBB or other arrhythmias.
• Ventilation-Perfusion Scan- Using aerosolized particles that emit radiation and labeled
albumin, the ventilation patterns and perfusion regions of the lung are measured and
mapped over several minutes of spontaneous ventilation. The number of areas that have
ventilation without a matching area of perfusion determine the presence of an abnormality.
• CT Pulmonary angiography- Peripheral administration of IV contrast is coupled with rapid
acquisition of CT images of the chest.
Adjunctive testing
• D-Dimer- A surrogate measure of clot burden. If a clot exists in the vasculature,
endogenous fibrinolytic factors evolve degradation products of fibrin. These are measured
in serum samples and can give rapid estimates of the pre-test probability of disease.
o A study of 566 patients with suspected DVT/PE, a negative D-dimer was effective
in excluding DVT/PE if the clinical suspicion was low (N Engl J Med 2003;
349:1227-35)
o A negative D-dimer test in patients with cancer does not reliably exclude DVT and
21% of cancer patients with a normal D-dimer had a DVT compared to 3.5% of
patients without cancer (Ann Int Med 1999; 131:417-23)
• Echocardiography- Clinically used to assess the potential secondary injury to the heart
with the acute pulmonary hypertension that develops after PA obstruction. May indicate a
higher risk group for poor outcomes after the diagnosis of PE.
Diagnostic Approach to Suspected Acute Pulmonary Embolism

Clinical suspicion
Low or moderate High
ELISA Consider initiating Tx
nl abnl
No Treatment CXR
Nl or abnl nl
Chest CTA/V V/Q Scan
Positive Negative ? ? Normal Hi prob
Treatment No Further tests No Treatment

Treatment Treatment
If hi clin prob
continue
Adapted from: Tapson V. N Engl J Med 2008;358:1037-1052
Page 43 of 177
Interpreting the CT-angiogram (PIOPED II)
CT-angiography Hi Prob (Wells>6) Intermediate (Wells 2-6) Lo Prob (Wells<2)
PPV 96% 92 58
NPV 60 89 96
CT-angio+venogram Hi Prob (Wells>6) Intermediate (Wells 2-6) Lo Prob (Wells<2)

PPV 96% 90 57
NPV 82 92 97
PIOPED result comparing test performance with or without CT venography: Stein P et al. N Engl J Med
2006;354:2317-2327
Important point: Better test performance was observed when assessment for PE
and DVT were used to determine treatment.
Treatment:
• DVT: Early anticoagulation with either Unfractionated Heparin (UFH) or LMWH is the goal.
Outpatient management with LMWH, warfarin and close follow-up is acceptable in properly
selected cases. Warfarin to achieve INR 2-2.5 for at least three months is the standard.
This needs to be adjusted based on presenting and revealed risk factors.
• Massive DVT: Extended duration Heparins in the initial phase (7-14 days) with the addition
of Warfarin to achieve INR 2-2.5 for at least three months is the standard. Occasionally,
thrombolytics can be added to treat vascular compromise resulting from DVT.
• PE: Early anticoagulation with either Unfractionated Heparin (UFH) or LMWH is the goal.
Outpatient management is not pursued because of greater morbidity and mortality.
Warfarin to achieve INR 2-2.5 for at least three months is the standard. This needs to be
adjusted based on presenting and revealed risk factors.
• Massive PE: PE presenting after syncope or with vasopressor requiring hypotension or
intractable hypoxemia may be treated with thrombolytics after a careful assessment of
bleeding risk.
• Special considerations to the duration of treatment
o 3 months is the minimum
o Transient risk factor (major surgery, etc)
3 months
o Idiopathic event (no identifiable risk factor)
6 months at least
o Idiopathic event (with known hypercoagulable risk factor)
Idefinite
o Recurrent idiopathic events
Indefinite
Follow-up:
• Subjects are at the greatest for VTE recurrence in the first 6 months after cessation of
therapy.
• Subjects should get all indicated preventive health screenings after a diagnosis of VTE as
cancer incidence appears increased in those with idiopathic VTE. No additional screening
test not otherwise indicated by symptoms, age, gender or exposures are necessary.
Page 44 of 177
Prevention:
Primary prevention:
• Incidence of DVT high in medical & surgical patients (range = 15% of medical patients to
40-70% of hip surgery patients [Chest 1989; 95:37S - 51S])
• Perioperative low dose heparin reduces fatal PE by 2/3 in general, orthopedic, & urologic
surgery (NEJM 1988; 318:1162-72)
TID UFH or daily in high-risk patients

Alternatives LMWH or Pneumatic compression boots or ASA
Controversies:
• Duration of therapy for initial VTE
Some studies suggested longer duration of warfarin reduced incidence of recurrence. Longer
follow-up reveals there may only be a delay in the recurrence. Exposes patient to a longer duration
of bleeding risk.
• Low-intensity warfarin therapy
Therapy for submassive pulmonary embolism- Some authors have suggested thrombolytics may
be beneficial in patients with high clot burden but without clinical signs of massive PE. PE and
signs of right heart dysfunction may best characterize these patients. As a result the cardiac echo
has been advocated as a test to determine if a patient is at risk for subsequent deterioration. One
large study demonstrated less need for subsequent escalation of therapy after thrombolytics were
given, but study design was criticized.
• IVC Filter
Usually clinically used in cases where there are contraindications to anticoagulation. Temporary
filters have allowed filters to be used as bridge therapy during a time limited contraindication to
anticoagulation (ie surgery or transient GI bleeding). Some authors have advocated as adjunctive
therapy in patients without the reserve to tolerate a recurrent PE.
Page 45 of 177
Control of Ventilation

Time: 8:30 am
Faculty: Roy Essig, M.D.
Email: Leroy.essig@osumc.edu
Objectives
1. Define the anatomic location and the basic function of the 3 primary central
controllers of respiration
2. Define the anatomic location and the function of the primary sensing system for
arterial PCO2. Compare this to the primary sensing system for arterial pO2.
3. List and define the roles of 4 primary mechano-sensory receptor systems that
influence respiratory rhythm generation.
4. Describe the ventilatory responses to changes in pCO2. Describe influence of
modest reductions of pCO2 on ventilation vs. severe drops in pCO2.
5. Describe the ventilatory responses to changes in pO2. Distinguish the influence of
modest reductions of pO2 on ventilation vs. severe drops in pO2.
6. Be able to recognize the normal responses of PaCO2 and PaO2 to exercise and
describe the most recent hypothesis regarding how ventilation is controlled so
carefully during exercise.
Page 46 of 177
Sepsis, Acute Lung injury (ALI) and the
Acute Respiratory Distress Syndrome (ARDS)

Time: 9:30 am
Faculty: Jim O’Brien, MD, MSc
Assistant Professor
Department of Internal Medicine
Division of Pulmonary, Critical Care, and Sleep Medicine
201 Davis Heart and Lung Research Institute
Phone: 247-7707
Email: James.OBrien@osumc.edu
1. Given a clinical vignette, accurately identify patients with sepsis, severe sepsis
and septic shock, based on American-European Consensus Conference criteria.
2. Accurately recognize the risk factors, including patient demographics and co-
morbidities, for sepsis and severe sepsis.
3. Accurately recognize the most common microbiological agents and sites of
infection in sepsis.
4. Given a clinical vignette, recognize the initial diagnostic steps in identifying a
patient with sepsis and severe sepsis.
5. Given a clinical vignette, recognize the initial therapeutic measures during the
resuscitation phase for patients with severe sepsis, including timely
administration of appropriate antibiotics and goal-directed resuscitation.
6. Contrast the hemodynamic effects of vasopressor agents used in septic shock.
7. Given a clinical vignette, appropriately select patients with severe sepsis for initial
therapeutic efforts, including drotrecogin alfa (activated).
8. Given a clinical vignette, accurately identify patients with ALI/ARDS, based on
American-European Consensus Conference criteria.
9. Accurately recognize the risk factors, including patient demographics and co-
morbidities, for ALI/ARDS
10. Accurately identify the common pathologic features of ALI/ARDS.
11. Accurately identify evidence-based therapies for ALI/ARDS, including lower tidal
volume ventilation (e.g. 6ml/kg PBW) and conservative fluid management.
Learning Resources:
• Required text:
o Chapter 254 – Munford, RS. “Severe sepsis and septic shock.”
o Chapter 251 – Levy, BD, Shapiro, SD. “Acute respiratory distress
syndrome.”
• Optional, additional readings
o Definitions of sepsis, severe sepsis, septic shock, ALI/ARDS
Page 47 of 177
Bone, RC, et al. “Definitions for sepsis and organ failure and
guidelines for the use of innovative therapies in sepsis.” Chest
1992; 101: 1644-55.
Levy, MM et al. “International sepsis definitions conference.” Crit
Care Med 2003; 31: 1250-6.
Bernard, GR et al. “The American-European Consensus
Conference on ARDS. Definitions, mechanisms, relevant outcomes
and clinical trial coordination.” Am J Resp Crit Care Med 1994;
149: 818-24.
o Epidemiology of sepsis. ALI/ARDS
Angus, DC et al. “Epidemiology of severe sepsis in the United
States: analysis of incidence, outcome, and associated costs of
care.” Crit Care Med 2001; 29: 1303-10.
Martin, GS, et al. “The epidemiology of sepsis in the United States
from 1979 through 2000.” N Engl J Med 2003; 348: 1546-54.
Rubenfeld, GD et al. “Incidence and Outcomes of Acute Lung
Injury.” N Engl J Med 2005;353:1685-93.
o Pathogenesis of sepsis, ALI/ARDS
Hotchkiss, RS, Karl, IE. “The pathophysiology and treatment of
sepsis.” N Engl J Med 2003; 348: 138-150.
Ware, LB et al. “The Acute Respiratory Distress Syndrome.” N
Engl J Med 2000; 342: 1334.
o Review on treatment of sepsis, ALI/ARDS
O’Brien JM, Ali NA, Aberegg SK, Abraham E. “Sepsis:a review of
epidemiology, pathogenesis and treatment.” Am J Medicine 2007;
120: 1012-22.
O’Brien, JM, Abraham, E. “New approaches to the treatment of
sepsis.” Clin Chest Med 2003; 24: 521-548. (reprints available
from me if requested)
Balk, RA. “Optimum treatment of severe sepsis and septic shock:
evidence in support of the recommendations.” Dis Month 2004;
50(4): 168-213.
Fan, E. et al. “Ventilatory management of acute lung injury and
acute respiratory distress syndrome.” JAMA 2005; 294: 2889-96.
o Seminal articles on treatment of sepsis, ALI/ARDS
Bernard, GR et al. “Efficacy and safety of recombinant human
activated protein C for severe sepsis.” N Engl J Med 2001; 344:
699-709.
Annane, D et al. “Effects of treatment with low doses of
hydrocortisone and fludrocortisone on mortality in patients with
septic shock.” JAMA 2002; 288: 862-71.
Rivers, E et al. “Early goal-directed therapy in the treatment of
severe sepsis and septic shock.” N Engl J Med 2001; 345: 1368-
77.
NHLBI ARDSNet. “Comparison of Two Fluid-Management
Strategies in Acute Lung Injury.” N Engl J Med 2006; 354:2564-75.
Page 48 of 177
NHLBI ARDSNet. “Ventilation with lower tidal volumes as
compared with traditional tidal volumes for acute lung injury and the
acute respiratory distress syndrome.” N Engl J Med
2000;342:1301-8.
SEPSIS
A. Definitions
1. Systemic Inflammatory Response Syndrome (SIRS) – 2 or more of the
following abnormalities:
a. Tachycardia (≥90 beats/minute)
b. Temperature (≥38°C or ≤36°C)
c. Tachypnea (≥20 respirations/minute)
d. WBC count (≥12,000/mm3 or ≤4000/mm3 or >10% immature
neutrophils)
2. Sepsis = SIRS with a confirmed or presumed infectious source
3. Severe Sepsis = Sepsis with acute organ dysfunction
a. Neurologic
b. Respiratory
c. Hepatic
d. Renal
e. Coagulation
4. Septic Shock = hypotension refractory to volume resuscitation due to sepsis
5. Mortality increases with more complicated sepsis
a. Sepsis 7-17%
b. Severe sepsis 20-53%
c. Septic shock 53-63%
B. Epidemiology
1. Incidence has increased by almost 9% per year since 1979
2. In 2000, there were approximately 660,000 cases of sepsis or 240
cases per 100,000 population
3. Almost 40% of these cases involved acute organ dysfunction (severe
sepsis)
4. Mortality rate has decreased by approximately 10% since 1980, but because
of higher incidence, mortality due to sepsis has increased
a. At least the 10th leading cause of death
b. Responsible for approximately 100,000 deaths per year
5. Average cost is $22,1000 per case for a national hospital cost of almost $17
billion per year
C. Pathogenesis
1. Infectious agents
a. Variety of infectious agents and microbiological products can be
responsible.
b. Gram positive organisms the most common
c. Fungal organisms are increasing in importance
Page 49 of 177
d. Only about 30% of patients have a positive blood culture
e. Respiratory is most common source
2. Patient factors
a. Older
b. Male
c. Non-white
d. Immunosuppression – AIDS, therapeutic
e. Cancer, Cirrhosis, Alcohol abuse
f. In-dwelling catheters
g. Polymorphisms in genetic factors in innate immunity, cytokines,
etc.
D. Treatment – Supportive care

1. Antibiotics
a. Start broad
b. Inadequate initial antibiotics increase mortality 4-fold
2. Volume resuscitation
a. May require 4-8L of crystalloid (i.e. Normal saline, lactated
Ringers’)
b. Inadequate resuscitation may increase mortality
c. Early goal-directed therapy (EGDT) in the emergency department
reduced mortality in one study (NNT=7)
1. In addition to mean arterial pressure, urine output, and
central venous pressure, EGDT targeted central venous oxygen
saturation (CVO2) as a measure of oxygen delivery
2. Adjustments to CVO2 required use of blood and dobutamine
3. Vasopressors
Heart Rate Contractility Vasoconstriction
Norepinephrine 2+ 2+ 4+
Dopamine 3+ 2+ 3+
Dobutamine 2+ 4+ 1-
Phenylephrine 2- 0 4+
Epinephrine 4+ 4+ 4+
Vasopressin 1- 1- 3+
4. Renal replacement therapy (dialysis)
E. Treatment – Specific therapies

1. Drotrecogin alfa (activated) – recombinant form of activated protein C
a. Uncertain mechanism of effect – has anticoagulant, anti-
inflammatory and anti-apoptotic effects
b. Treatment improved survival (NNT=17) but greatest benefit was in
sickest patients
c. Increases risk of bleeding with almost 1% having an intracranial
hemorrhage
Page 50 of 177
ALI/ARDS
A. Definitions
1. Acute onset
2. Bilateral alveolar infiltrates
3. No evidence of elevated left atrial pressures
4. Hypoxemia
a. PaO2/FiO2 ratio ≤ 300 = Acute lung injury (ALI)
b. PaO2/FiO2 ratio ≤ 200 = Acute respiratory distress syndrome
(ARDS)
• Mortality increases with progression to ARDS
B. Epidemiology
1. Approximately 190,600 cases of acute lung injury per year in the US
2. Accounts for 74,500 deaths
3. Accounts for 3.6 million hospital days
C. Pathogenesis
1. Clinical risk factors
a. Sepsis – especially pulmonary source
b. Transfusions
c. Ventilator management
2. Patient factors
a. Older
b. Polymorphisms in genetic factors in innate immunity, cytokines, etc.
D. Treatment
1. Artificial ventilation – lower tidal volumes (i.e. 6 cc/kg predicted body
weight) improve outcome, compared to traditional tidal volumes (i.e., 12 cc/kg
predicted body weight) – NNT=12
2. Prevention of ventilator complications
a. Elevation of head of bed
b. Protocols for assessment of ventilator liberation
c. Protocols for sedation management
d. Consideration of early tracheotomy
E. Treatment – Specific therapies

1. Fluid management
a. In hemodynamically stable patients, keeping filling pressures
low reduces time on ventilator
b. Does not increase need for vasopressors or dialysis
c. No significant effect on mortality.
Page 51 of 177
Respiratory Failure
Time: 10:30 am
Faculty: Stephen Hoffmann, M.D.
Email: Stephen.Hoffmann@osumc.edu
Objectives: Critical Care -- Respiratory Failure
1. List the mechanisms of hypoxemia

2. Calculate a A-a gradient
3. List the mechanisms of hypoxemia with a normal A-a gradient
4. List the mechanisms of hypoxemia with an abnormal A-a gradient
5. Describe various types of oxygen delivery devices
Respiratory Failure is defined as the Failure to maintain adequate oxygen and carbon dioxide homeostasis.
Fundamentally it is impaired gas exchange due to failure of the respiratory system. It may acute, chronic or acute on
chronic. There are two major reasons for respiratory failure.
• Failure of respiratory pump resulting in ineffective ventilation
• Failure of gas exchanging region (alveolar-capillary membrane)
The Respiratory System is composed of many discrete anatomic structures and systems. Failure of any of them
may result in respiratory failure.
• CNS (medulla)
• Peripheral nervous system (phrenic nerve)
• Respiratory muscles
• Chest wall
• Lung
• Upper airway
• Bronchial tree
• Alveoli
• Pulmonary vasculature
• Heart and the peripheral vasculature
There are three Types of Respiratory Failure. Hypoxemic Respiratory Failure is a failure of gas exchange usually
resulting in a low PaO2 and a low or normal PaCO2 along with an elevated A-a gradient. Most commonly it is due
to ventilation/perfusion mismatch. Hypercapnic Respiratory Failure is a failure of respiratory pump where
demand exceeds supply. It is characterized by ineffective ventilation (increased PaCO2) with normal A-a gradient.
PaCO2 > 45 mmHg is present and it is frequently associated with low PaO2. Mixed Hypoxemic and Hypercapnic
Respiratory Failure is very common and is the third type.
Hypercapnic Respiratory Failure
PaCO2 is normally maintained in a narrow range by adjusting alveolar ventilation to match CO2 production.
• PaCO2 = 0.863 x Rate of CO2 Production

Alveolar Ventilation
Ventilatory failure occurs when minute ventilation is unable to keep up with production of CO2 due to: depressed
respiratory drive, inadequate neuromuscular competence or excessive respiratory system load.
Page 52 of 177
Resistive Loads Depressed Drive
Bronchospasm Drug Overdose
Airway edema, secretions, Brainstem Lesion
scarring Sleep Disordered
Upper airway obstruction Breathing
OSA Hypothyroidism
Lung Elastic
Loads
Alveolar edema
Infection Neuromuscular Muscle Weakness
Fatigue
Atelectasis
Load Competence Electrolyte
Derangement
Chest Wall Elastic Malnutrition
Hypoperfusion States
Loads Myopathy
Pleural Effusion
Pneumothorax
Rib fractures/flail chest
Tumor Impaired N-M
Obesity
Ascites
Transmission
Abdominal Distention Minute Volume Phrenic Nerve Injury
Fibrothorax Loads Cord Lesion
Sepsis Neuromuscular Blockers
Pulmonary Embolus GBS
Excess Calories Myasthenia Gravis
ALS
Adapted from Murray and Nadel, 1995 Botulism
Hypoxemic Respiratory Failure
Hypoxemic is a failure of gas exchange usually resulting in a low PaO2. The normal alveolar oxygen tension is
determined by the alveolar gas equation:
• (Barometric pressure – H2O vapor pressure)FiO2 – PaCO2/Respiratory quotient

o (BP – WVP)FiO2 – PaCO2/0.8
o (760 – 47)0.21 – 40/0.8 =
o 150 – 50 = 100 mm Hg
It is influenced by the barometric pressure, the FIO2 and the PaCO2. Normal arterial oxygen tension decreases with
age and can very roughly be estimated:
• PaO2 = 104 – (age x 0.4)
The (A-a) Gradient is the partial pressure of oxygen in the alveolus minus partial pressure of oxygen in an artery
(alveolar air equation minus the PaO2).
• [FIO2 * (Barometric pressure - water vapor) - (1.2*PCO2)] - PaO2

o [FIO2(760 - 47) - (1.2 * PCO2)] - PaO2
o [FIO2(713) - (1.2 * PCO2)] - PaO2
• At Room Air (where is most clinically relevant):
o [150 - (1.2 * PCO2)] - PaO2 = A-a Gradient
The normal A-a gradient is 8 - 12 mmHg and increases with age (roughly estimated by [Age/4 + 4]) and also
increases with increasing FIO2 ( 5-7mmHg for every 10% increase in FIO2). The A-a gradient can be used to help
distinguish the mechanisms of hypoxemia. The most common mechanisms of hypoxemia include:
• Hypoventilation
• Ventilation/perfusion mismatch
• Shunt
• Decreased inspired oxygen
• Impaired diffusion
Page 53 of 177
Impaired Diffusion is most common with interstitial lung disease. The thickened interstitium impedes diffusion of
oxygen from the alveolus to the capillary. The resulting hypoxemia is usually not significant except during states of
increased oxygen demand (exercise) probably due to the combination of impaired diffusion and the decreased transit
time of blood through alveolar capillaries due to increased cardiac output.
Decreased Inspired Oxygen occurs at altitude. Both barometric pressure and altitude have a dramatic effect on
oxygen tension. For example, Oxygen tension of inspired air:
• Sea level = 150 mm Hg
• Denver = 130 mm Hg
• Mt. Everest = 43 mm Hg
Hypoventilation (already discussed) results in hypoxemia that is always associated with hypercapnea (by
definition). Remember that alveolar ventilation determines carbon dioxide tension and the normal physiologic
response to increases in PaCO2 is to increase minute ventilation and thus alveolar ventilation.
Ventilation/Perfusion alteration is the most common cause of hypoxemia. The adequacy of gas exchange in the
lungs is determined by the balance between pulmonary ventilation and capillary blood flow. This balance is
expressed as the ventilation-perfusion (V/Q) ratio.
• Normal V/Q ratio ≅ 1
o Ideally, ventilation and perfusion matched for optimal gas exchange
• Shunt = V/Q ratio < 1
o Pure shunt: V/Q = 0
o Perfusion of nonventilated areas
• Dead space = V/Q ratio > 1
o Pure dead space ventilation: V/Q = ∞
o No perfusion to ventilated areas
Clinical Situations of High V/Q (Increase Deadspace):
• Pulmonary embolism
• Physiologic dead space can be seen in COPD
• Normal response is to increase minute ventilation
o ↑ VE not very effective for correcting hypoxemia as this cannot increase already maxed
alveolar oxygen tension
Clinical Situation of Low V/Q (Shunt):
• V/Q = 0 is represented by true right to left shunting (intracardiac defect) with venous admixture of
blood.
o Alveoli completely bypassed
• Any situation where alveoli are filled (not ventilated):
o Blood, pus, water - Alveolar hemorrhage, pneumonia, CHF, ARDS
• Atelectasis of lung
• Normal physiologic response---hypoxemic vasoconstriction
The A-a Gradient reacts differently in each of these mechanisms but can help divide the causes into two main
groups:
• Increased A-a Gradient:
o V/Q mismatch
o Impaired diffusion
o Pure Shunt (V/Q=0)
• Normal A-a Gradient:
o Decreased inspired oxygen
o Hypoventilation
Page 54 of 177
Recognizing/Diagnosis of Impending Respiratory Failure
Diagnosis depends upon clinical suspicion, followed by confirmation by ABGs and integrated with clinical
judgment and attempts to identify a specific etiology. Requires clinical judgment and assessment by a physician at
the bedside. Useful parameters include respiratory rate, mentation, pattern of breathing and patients own
assessment.
An arterial blood gas can be used to determine the presence of respiratory failure.
– Absolute values of PaO2 and PaCO2 that define respiratory failure depend on many factors.
– Generally a PaO2 < 50 - 60 torr or a PaCO2 > 50 torr represent respiratory failure.
However an assessment made only by ABG is fraught with errors.
Variation in ABGs Normal Arterial Blood Gases

Variation PaO2 PaCo2
AGE P aO2 P aCO2 A – a PO2
(mm Hg) (mmHg)
(Years) (mmHg) (mmHg) (mm Hg)
Mean 13 2.5 20 84-95 34-47 4-17
30 81-92 34-47 7-21
40 78-90 34-47 10-24
th
95 Percentile +/- 18 +/- 4 50 75-87 34-47 14-27
60 72-84 34-47 17-31
70 70-81 34-47 21-34
Range 2 – 37 0 - 12
80 67-79 34-47 25-38
Represents variation over a 1-hour period in 26 clinically stable ventilator dependent patients All values related to FIO2 = 21% at sea level
From Hess D, Agarwal NN. J Clin Monitor 1992 Adapted from Intermountain Thoracic Society Manual, 1984 44-45
Respiratory Failure Management
The three main goals in the management of respiratory failure are:

• Maintain an airway
• Correct the hypoxemia (Maintain oxygen saturation > 90% and remember oxygen delivery - an
increase in PO2 should not be used as evidence of an increase in tissue oxygenation) and acid base
status
• Most importantly identify and correct the underlying problem.
Oxygen Saturation & Oxygen Delivery
Remember oxygen content (CaO2) is a more important management measure than PO2:
CaO2 = ([Hb] * %Sat * 1.34 ml/g) + (PO2 * 0.003)
Oxygen delivery the key parameter [CaO2 * Cardiac output (CO)]. PO2 is a diagnostic/evaluative measure
Oxygen Delivery Devices

• Those that do not provide ventilation:
– Low Flow - Reservoir Devices
• Nasal cannula
• Simple face mask
• Non/partial rebreathers
– High flow delivery devices
• Venturi mask
• Dual regulator/Blenders
– CPAP
Page 55 of 177
• Those that provide ventilation:
– Mechanical ventilation
– Noninvasive Positive Pressure Ventilation (NIPPV)
• Full face mask
• BIPAP
When the patient is placed on a simple oxygen delivery device 100% oxygen is delivered from the regulator to the
patient at a selected flow (usually liters per minute). The FIO2 of the oxygen reaching the lungs is a mixture of that
100% oxygen from the wall/reservoir and the oxygen entrained from the room (21% FIO2).
Low-Flow Oxygen Delivery

Device R e s e v oi r Oxy g e n Appr o x i m a
Cap a c it y Fl o w te
(mL) (L/mi n) FIO2
Nas al Can n ula 50 1 0.21-0.24
2 0.24-0.28
3 0.28-0.34
4 0.34-0.38
5 0.38-0.42
6 0.42-0.46
Simple F ace mask 150-250 5-10 0.40-0.60
Mask -resevoir bag 750-1250
Pa r tial 5-7 0.35-0.75
Rebreat her
Non rebrea t her 5-10 0.40-1.0
Estimated based on tidal volume of 500 mL, RR of 20 and I:E of 1:2
From Shapiro BA, et al 1991
High Flow Masks provide precise FIO2 at higher flows. Flow of oxygen entrains room air prior to the patient
resulting in known FIO2 being delivered to the patient. Desirable in patients with chronic hypercapnea who are at
risk of increased CO2 retention with increases in FIO2. Continuous Positive Airway Pressure (CPAP), does not
provide ventilation but does increases FRC and can improve V/Q match. Indications include: CHF, COPD,
Atelectasis, Sleep Disordered Breathing
Devices that Ventilate
The difference between “mechanical ventilation” and “Non-Invasive Positive Pressure Ventilation (NIPPV)” is the
interface: either an Endotracheal Tube (ETT) or a face mask. NIPPV can use either a full size ventilator or a
“BIPAP” machine.
Selection Criteria for NIPPV
• Respiratory distress with moderate to severe dyspnea, use of accessory muscles of respiration, abdominal
paradox
• pH < 7.35 with PaCO2 > 45
• Respiratory rate > 25 bpm
Exclusion Criteria for NIPPV

• Absolute
• Respiratory arrest
• Cardiorespiratory instability (hypotension with impaired perfusion, serious dysrhythmia, myocardial
infarction with pulmonary edema)
• Uncooperative patient
• Recent facial, esophageal or gastric surgery
• Craniofacial trauma or burns
• High aspiration risk
Page 56 of 177
• Inability to protect airway
• Fixed anatomic abnormalities of the nasopharynx
• Relative
• Extreme anxiety
• Massive obesity
• Copious secretions
• ARDS
Page 57 of 177
Asthma
Time: 10:00 am
Email: Beth.allen@nationwidechildrens.org
Asthma Objectives
1. Describe the airway abnormalities characteristic of asthma, and their functional consequences
2. Describe typical symptoms of asthma
3. List common triggers of asthma exacerbations
4. Recognize clinical patterns that are suggestive of an asthma diagnosis
5. Describe the utility (and limitations) of tests used to assess the asthmatic patient
6. Describe typical physical exam findings of a patient experiencing an acute asthma exacerbation
7. Identify therapies used in the treatment of acute asthma exacerbations
8. Correctly categorize asthma patients regarding whether they have persistent or intermittent
asthma (i.e. whether they do or don’t warrant controller therapy.)
9. List commonly used controller therapies, and describe their primary mechanism and role in
therapy
10. Identify reasons why asthma therapy might fail.
Page 58 of 177
Therapy of Asthma
Definition of Asthma
Normal Airway Physiology
Page 59 of 177
Cells Involved in the Asthmatic Response
Page 60 of 177
Treatment of Asthma
Non-Pharmacologic Treatment
Pharmacologic Treatment
Bronchodilators
Beta2 -Receptor Agonists
Epinephrine
Isoproterenol
Page 61 of 177
Relatively selective B2 agonists
albuterol (Proventil)
terbutaline (Brethine)
pirbuterol (Maxair)
bitolterol (Tornalate)
formoterol (Foradil)
levalbuterol (Xopenex)
metaproterenol (Alupent)
arformoterol (Brovana)
salmeterol (Serevent)
isoetharine
Cholinergic Blocker
ipratropium bromide(Atrovent)
tiotropium (Spiriva)
Page 62 of 177
Phosphodiesterase inhibitor
theophylline (Aminophylline)
Anti-Inflammatory Agents
mast cell inhibitors
cromolyn sodium (Intal)

nedocromil (Tilade)
Page 63 of 177
glucocorticoids
beclomethasone (Beclovent)
budesonide (Rhinocort)
flunisolide (Aerobid)
fluticasone (Flonase)
mometasone (Asmanex)
triamcinolone (Azmacort)
prednisone
dexamethasone
Page 64 of 177
Anti IgE antibody
omalizumab (Xolair)
Inhibitors of the leukotriene system
Leukotriene Synthesis Inhibitor
zileuton (Zyflo)
Leukotriene receptor blockers
zafirlukast (Accolate)
montelukast (Singulair)
Page 65 of 177
Page 66 of 177
Pleural Disease

Time: 8:30 – 9:20
1. Describe the general mechanisms underlying pleural effusions and disorders
associated with different types of effusions.
2. Compare and contrast the morphologic and epidemiologic features of malignant

mesothelioma and solitary fibrous tumor of the pleura.
3. Recognize the clinical presentation of a pneumothorax and compare and contrast

primary and secondary spontaneous pneumothoraces as to their etiology.
Learning Resources
1. Robbins Pathologic Basis of Disease, 7th Ed., pp. 766-770.
2. Harrison’s Principles of Internal Medicine, 16th Ed., ch 245.
I. PLEURAL EFFSUION
A. General Features
1. The pleural space normally contains up to 15 mL of serous fluid that is
characterized as being acellular, clear, with low protein concentration, with a
pH and glucose levels similar to that in the peripheral blood.
2. Serous fluid enters the pleural space by normal hydrostatic pressures and is
absorbed by the subpleural lymphatics (parietal). Fluid may also enter the
space from the abdomen (thru pores in the diaphragm).
3. Lymphatics can absorb up to a 20-fold increase in fluid.
4. An accumulation of pleural fluid (effusion) occurs in the following settings:

a. Increased vascular permeability (pneumonia)
b. Increased hydrostatic pressure (e.g. in congestive heart failure)
c. Decreased plasma oncotic pressure (nephrotic syndrome)
d. Decreased lymphatic drainage (mediastinal tumor)
e. Increased intrapleural negative pressure (atelectasis)
Page 67 of 177
B. Clinical Features
1. A clinical presentation of a pleural effusion is related to the volume of fluid
and its rate of accumulation.
2. It may present as dyspnea or chest pain, or it may be asymptomatic.
a. “Pleuritic chest pain” is often unilateral, sharp and exacerbated by deep
breathing or coughing.
3. A pleural effusion is accompanied by decreased breath sounds, dullness to

percussion, decreased vocal fremitus, bronchial breathing and egophony.
4. Radiologic features vary with the amount of fluid.

a. Upright radiographs show elevated hemidiaphragm(s), blunting of the
costophrenic angle when volume > 250 mL, opacification (“white out”) of
the hemithorax with large volumes.
b. Lateral decubitus radiographs show if the fluid is free flowing.
c. Ultrasound and CT are used to evaluate loculated effusions.
C. Pathologic Features
1. Analysis
a. Thoracentesis of 30-50 mL for testing (more is better) will be diagnostic in
~ 75% of cases; even if nondiagnostic it may exclude a number of things.
i. gross appearance may be clear, cloudy/purulent, bloody, or milky.
ii. pH < 7.0 may indicate esophageal rupture
iii. glucose < 20 mg/dL may indicate rheumatoid effusion protein
iv. cell count & differential can be used to differentiate acute from chronic
inflammation.
v. cytology examination helps to rule out a malignancy
vi. culture for bacterial, acid fast and fungal infections
b. Transcutaneous pleural biopsy – may be performed for malignancy or for

culture; sometimes needed to diagnose TB.
2. Transudate vs. Exudate

a. Transudative effusions are the result of increased vascular hydrostatic
pressure (CHF) or decreased plasma oncotic pressure (nephrotic
syndrome).
b. Exudative effusions are the result of increased vascular permeability due

to infections/pneumonia or trauma.
c. Transudates have low protein content (< 3 g/dL) with a pleural fluid/serum
protein ratio < 0.5 and a pleural fluid/serum LD ratio < 0.6
Page 68 of 177
d. Exudates have high protein content (> 3 g/dL) with a pleural fluid/serum
protein ratio > 0.5 and a pleural fluid/serum LD ratio > 0.6
3. Hydrothorax is a transudate that accumulates in the pleural space. The

volume may be massive. The etiologies include:
a. Congestive heart failure (most common cause and it is usually bilateral).
b. Nephrotic syndrome (associated with reduced plasma oncotic pressure

from hypoproteinemia or salt and water retention).
c. Meigs syndrome (a combination of ascites, ovarian fibroma, and a right

sided only hydrothorax)
4. Hemothorax refers to blood in the pleural space. It is most often associated

with trauma or a ruptured aortic aneurysm. It can also be seen in patients
with hematologic disorders, malignancy, pulmonary embolus, or a collagen
vascular disease (e.g. SLE).
5. Chylothorax refers to accumulation of a milky fluid (“chyle”) or lymph due to

leakage from the thoracic duct. They are commonly left sided, but may be
bilateral.
a. Most common causes are obstruction or trauma to the thoracic duct,
surgical trauma, and obstruction from metastatic disease.
b. The fluid contains high triglyceride levels.
6. Empyema is a purulent, pleural exudate that complicates lung infections such

as those caused by pneumococci, streptococci, and staphylococci.
a. The pleural surfaces are coated by thick and shaggy fibrin layers
(fibrinopurulent) that can undergo organization. Organization (i.e. wound
healing) produces fibrous adhesions, localizing the pus so it cannot be
drained, and eventually proceeds to encase the lung in a fibrous coat
which may limit expansion.
b. The exudate is creamy yellow-green with a large number of PMNs, a pH <

7.2, a glucose < 40 mg/dL, LD > 1,000, and may grow organisms when
cultured.
7. Pleuritis refers to chronic inflammation of the pleura.

a. Inflammatory pleural exudates rich in mononuclear cells (lymphocytes and
macrophages) are seen in cases of tuberculosis, lung infarcts, lung
abscesses, and bronchiectasis.
b. Serofibrinous exudates are associated with collagen vascular diseases

(rheumatoid arthritis, SLE), uremia, metastatic involvement of the pleura,
and radiation therapy.
Page 69 of 177
8. Malignant pleural effusions are acutely exudative and bloody.
a. They are the most common cause of an exudate in persons > 60 years of
age.
b. They are commonly seen in carcinomas of the lung and breast, and, to a
lesser extent, the liver, stomach and ovaries. Lymphomas may result in
an exudate.
c. The diagnosis requires cytologic examination of an aspirate.
II. TUMORS OF THE PLEURA

A. General
1. Metastatic tumors, mainly carcinomas of the lung and breast, are the most
common tumor affecting the pleura.
2. Metastatic tumors commonly produce bloody (sanguineous) effusions, and

malignant cells can be identified by cytologic examination of the pleural fluid
obtained by thoracentesis.
3. Primary tumors of the pleura are classified as either diffuse or solitary lesions.
Mesotheliomas are diffuse or solitary fibrous tumors are localized nodules.
B. Malignant Mesothelioma
1. General Features
a. Mesotheliomas are highly aggressive malignant tumors that arise from
mesothelial cells that line pleural (65%-70%), peritoneal (30%), and
pericardial (1%-2%) surfaces.
b. Mesotheliomas are rare tumors that are most commonly associated with
an occupational history of exposure to asbestos (asbestos miners,
shipyard workers, textile workers, etc).
c. There are approximately 2,500 new cases diagnosed per year in the U.S.
in men between 50 and 70 years of age.
d. They are a common cause of worker’s compensation and medicolegal

litigation (http://www.mesothelioma-attorney.com).
e. Long latency period from exposure to onset of the tumor (30 years and
more). No relation to smoking.
2. Clinical Features
a. Patients often present with progressive dyspnea, most often due to a large
pleural effusion, and/or chronic chest pain. These may also be
accompanied by weight loss, a nonproductive cough, fatigue, and/or fever.
Page 70 of 177
b. Imaging studies, CT with contrast being the best, demonstrate a unilateral
diffuse thickening of the pleura and/or a pleural effusion.
c. Diagnosis is based on an open or on a video-assisted thoracoscopy

(VATS) biopsy.
d. Mesotheliomas are associated with a fatal clinical course.
e. Treatment may involve surgery, radiation therapy, and/or chemotherapy.

The survival rate is less than 6 months for the untreated patient.
3. Pathologic Features
a. Tumors are grossly characterized by diffuse thickening of the pleura with
complete encasement of the lung by a thick, gray-white tumor crust.
b. Mesotheliomas are histologically characterized by a proliferation of bland-

appearing mesothelial cells with minimal atypia that form tubulo-papillary
structures. Some cases may show a biphasic or predominantly
sarcomatoid (spindle cell) appearance that can be difficult to distinguish
from a sarcoma.
c. Mesotheliomas may be difficult to distinguish from metastatic

adenocarcinoma. Special stains and electron microscopy are required for
diagnosis. Abundant long, slender microvilli on the cell surface are
diagnostic by electron microscopy.
C. Solitary Fibrous Tumor

1. Solitary fibrous tumors are mesenchymal in origin and are not associated with
asbestos exposure.
2. More than 80% have a benign clinical course, but they can grow to a size that
compresses the lung and other intrathoracic structures. They are often
associated with paraneoplastic syndromes – clubbing, hypertrophic
osteoarthropathy, and hypoglycemia due to production of insulin-like growth
factor II (IGF-II). The paraneoplastic syndromes resolve with excision of the
tumor.
3. Pathologic Features
a. On gross examination, solitary fibrous tumors often appear as a polypoid,
pedunculated, fleshy mass attached to the pleural surface by a short
pedicle.
b. These tumors are histologically characterized by bland spindle cell

proliferation (no mitoses or atypia) with abundant stromal collagenization.
Page 71 of 177
III. PNEUMOTHORAX
A. General Features
1. Pneumothorax refers to the presence of air or gas in the pleural space that
forces variable degrees of partial lung collapse.
2. Pneumothorax is a potential medical emergency.
3. Primary spontaneous pneumothoraces arise in individuals without underlying

lung disease or trauma. Secondary spontaneous pneumothoraces arise in
individuals with a parenchymal lung disease.
B. Signs and Symptoms

1. Acute onset of shortness of breath and/or chest pain is the most common
presenting feature. The chest pain may be stabbing and increases with
inspiration (pleuritic). Dyspnea is more severe in patients with underlying
parenchyma lung disease.
2. Cough, anxiety, and malaise and fatigue are much less common.
3. Patients often appear diaphoretic with splinting chest wall. Cyanosis may be
seen in cases of tension pneumothorax.
4. Physical examination can demonstrate tachycardia, tachypnea, distant or

absent breath sounds, hyperresonance on percussion, decreased tactile
fremitus, and pulsus paradoxus.
C. Etiologies
1. Spontaneous pneumothorax is commonly affects young adults, usually males,
20-40 years of age, without evidence of prior lung disease. It involves the
rupture of one or more subpleural blebs, right lung > left lung. About half will
recur. This may be seen in Marfan syndrome.
2. Traumatic pneumothorax associated with a penetrating chest wound, e.g.

bullet, knife, fractured rib, or iatrogenic commonly due to a central line
catheter or following a lung biopsy.
a. Barotrauma is usually associated with Scuba diving where the gas within
the lung rapidly expands and ruptures during rapid ascent.
3. Secondary spontaneous pneumothoraces is associated with a long ist of

parenchymal lung disease that include:
a. COPD – especially bullous emphysema
b. Tuberculosis
c. Necrotizing pneumonia
d. Asthma
e. Cystic fibrosis
f. Cancer
Page 72 of 177
g. Interstitial lung disease
h. Lymphangioleiomyomatosis (LAM)
4. A tension pneumothorax is a medical emergency caused by a valve action at

the margins of a leak, trapping air under increasing pressure. This totally
collapses the lung and displaces the mediastinum contralaterally. It may be
encountered with mechanical ventilation or resuscitation.
a. There are no breath sounds.
Page 73 of 177
Disorders of the Upper Airways
Time: 9:30 am
Faculty: Jennifer W. McCallister, MD
Assistant Professor Clinical Internal Medicine
Division of Pulmonary, Allergy, Critical Care, & Sleep Medicine
Email: Jennifer.mccallister@osumc.edu
Objectives:
1. Given a clinical vignette, accurately recognize the common symptoms of
disorders of the upper airways.
2. Given a clinical vignette, accurately formulate a differential diagnosis in a patient
with upper airway complaints.
3. Given a clinical vignette, decide on the appropriate test(s) to order when
evaluating a patient with upper airway complaints.
4. Given a clinical vignette, accurately recognize patients in whom empiric
treatment for upper airway complaints is appropriate and patients in whom
additional testing is immediately warranted.
5. Describe the unified airway disease (UAD) hypothesis and when given a clinical
vignette, accurately apply the principals to the selection of treatment in patients
with upper and lower airway disorders.
6. Describe the basic mechanisms and inflammatory mediators of the allergic
response.
Upper airways
• Anatomically complicated structures that extend from the airway openings at the
nares and lips to the trachea
• Serve numerous physiologic functions including olfaction, deglutition, phonation,
coughing, and filtering, conditioning, and conveying air to the lungs
Complaints related to upper airway disorders

• Cough, hoarseness, pain, dyspnea, wheezing, stridor, swelling, nasal congestion,
rhinorrhea, dysphagia
Differential diagnosis of upper airway disorders

• Neoplastic
• Infectious
• Allergic
• Immunologic/rheumatologic
• Functional
• Idiopathic
• Endocrine
• Iatrogenic
Page 74 of 177
Rhinitis
• Inflammation of nasal mucosa with characteristic nasal symptoms
• Classified according to etiology and pattern of symptoms
o Infectious rhinitis:
Acute: viral (most common cause), bacterial
Chronic: bacterial, fungal
o Allergic rhinitis
Acute episodic
Seasonal: tree, grass, weed pollens, fungi
Perennial: dust mites, cockroaches, animal proteins
Occupational
o Perennial non-allergic rhinitis
Idiopathic (vasomotor rhinitis)
o Miscellaneous
Hormonal: pregnancy, hypothyroidism, etc.
Drug induced: rhinitis medicamentosa (decongestant nasal sprays),
antihypertensives, etc.
Mechanical: deviated septum, nasal polyps, malignancy
Granulomatous: sarcoidosis, Wegeners granulomatosis
Allergic response
• IgE mediated, requires prior sensitization
• Early phase: mediated primarily by histamine
• Late phase: mediated by prostaglandins and leukotrienes
• Priming: continuous exposure to an allergen results in persistent nasal
inflammation and symptoms with lower dose exposures
• Hyperreactivity: response to nonspecific irritants
Evaluation of patient with rhinitis

• History: identify triggers, family or personal history of atopic disease
• Physical exam: allergic salute, allergic shiners, characteristic pale, bluish color of
edematous turbinates in some patients, cobblestoning of posterior pharynx
Treatment of allergic rhinitis

• Empiric treatment usually appropriate
• Environmental measures and allergen avoidance
• Antihistamines, oral decongestants, nasal ipratropium targeted at acute
symptomatic relief
• Mainstay (i.e. treatment of choice) for chronic symptoms: intranasal
corticosteroids (ex. Flonase); addition of antihistamine and leukotriene modifiers
helpful in some cases
• Refer for allergist evaluation (skin testing, RAST) in patient with unclear
diagnosis or inadequate response to treatment
Page 75 of 177
Sinusitis
• Inflammation of one or more of the paranasal sinuses
• Most commonly infectious
• Classification
o Acute: symptoms < 4 weeks
o Subacute: (unresolved acute) symptoms from 4 to 8 weeks
o Chronic: symptoms for 8 weeks or longer despite appropriate treatment
o Recurrent: 3 or more episodes of acute sinusitis/year
• Predisposing factors (i.e. increased risk) for sinusitis
o Allergic and nonallergic rhinitis
o Immunodeficiency
Common variable immunoglobulin deficiency (CVID)
IgA deficiency
o Cystic fibrosis
o Primary ciliary dyskinesia
o Rhinitis medicamentosa
o Anatomic abnormalities
Nasal polyps
Septal deviation
Treatment of acute sinusitis

Diagnosis generally made on basis of history & physical
Decision to treat based on clinical grounds
o Suspect in patients with URI persisting beyond 10-14 days
o Consider antibiotics
Worsening symptoms after 3-5 days
Temperature > 39°C
Maxillary tooth or facial pain
Unilateral sinus tenderness
Periorbital swelling
o Avoid antibiotic therapy of uncomplicated viral URI!!
7-10 days of watchful waiting in uncomplicated case
o Direct therapy at most common pathogens
S. pneumoniae
M. catarrhalis
H. influenza
Chronic sinusitis
Symptoms similar but might be more subtle
Evaluate for predisposing conditions
Obtain imaging to include CT sinuses and osteomeatal complex
Additional pathogens
o S. aureus
o Enteric gram negatives (ex. P. aeruginosa)
o Anaerobes (Prevotella species)
o Fungi
Page 76 of 177
Invasive fungal sinusitis (ex. mucormycosis)
o Immunocompromised patients
Diabetes
Malignancy
Chronic high-dose steroids
o Symptoms
Fever, headache, epistaxis, mental status changes
o CT of sinuses with characteristic nodular mucoperiosteal thickening with
focal areas of bony destruction
o Aggressive surgical debridement and systemic antifungal therapy
indicated (immediately!)
Unified airway disease (UAD)

Upper and lower airway disease may be manifestations of a single inflammatory
process involving the respiratory tract
Both parts of the airway should be assessed and managed accordingly
Spectrum of disease
o Rhinitis alone
o Rhinitis and nonspecific bronchial hyper-responsiveness (BHR)
o Rhinitis and asthma
80% of patients with asthma have rhinitis
50% of patients with rhinitis have asthma
Both the presence and severity of rhinitis are associated with worse asthma
outcomes
Rhinitis is a risk factor for later developing asthma
Treatment of allergic rhinitis with intranasal steroids has been shown to reduce
BHR in asthmatics and improve asthma symptoms
In patients with allergic rhinitis and mild asthma, daily antihistamine therapy has
been shown to improve asthma symptoms, peak expiratory flow rates, and reduce
rescue bronchodilator use
Sinusitis is common in patients with asthma; treatment of sinusitis in these
patients has been shown to improve pulmonary function, asthma symptoms, and
pulmonary function (peak expiratory flow rates)
Nasal polyps
Inflammatory outgrowths of paranasal sinus mucosa as a result of chronic
mucosal inflammation
Primary symptoms
o Nasal congestion
o Rhinorrhea
o Hypo- or anosmia
Rarely (if ever) malignant
No single predisposing condition
Prevalence in allergic rhinitis (1.5%) similar to general population (1%)
Commonly associated with:
o Non-allergic rhinitis
Page 77 of 177
o Aspirin induced asthma (Samter’s triad)
Nasal polyposis, asthma, aspirin sensitivity
o Cystic fibrosis (CF)
Always think CF in child with nasal polyps
Treatment
o Surgery in cases of severe obstruction or recurrent sinusitis; oral
corticosteroids (ex. Prednisone) with severe obstruction or smell
disturbance
o Intranasal steroids as maintenance
Decrease size
Reduce recurrence after surgery
Angioedema
Self-limited, localized swelling of skin & mucosa
Extravasation of fluid into interstitial spaces due to increased vascular
permeability
Usually benign, but may be life threatening (laryngeal involvement, anaphylaxis)
Mechanisms
o Mast cell mediated (90% urticaria & pruritis): Allergic (food, drugs, latex,
bee stings), direct mast cell stimulation (opiates)
o Kinin mediated (urticaria & pruritis usually absent) : ACE inhibitors (ex.
Enalapril, captopril), C1 inhibitor deficiency
Hoarseness
Any change in voice quality
Laryngitis
o Acute
Viral URI or acute vocal cord strain
M. catarrhalis & H. influenza
o Chronic
Irritants: GERD, sinusitis, EtOH, smoking
Vocal cord polyps
o Result of chronic irritation
Vocal cord nodules (ex. “singer’s nodules”)
Vocal cord paralysis
o Iatrogenic (thyroid surgery, endotracheal intubation)
o Malignancy (vagus or recurrent laryngeal nerve involvement)
Trauma
Paradoxical vocal cord motion/vocal cord dysfunction
Laryngeal cancer
Hoarseness lasting > 2 weeks without firmly identifiable cause warrants
otolaryngology evaluation
Page 78 of 177
Laryngeal cancer
95% cases squamous cell carcinoma
Tendency to metastasize to cervical lymph nodes
4 times more common in males
Risk factors
o Smoking
o Alcohol
Page 79 of 177
Chronic Obstructive Pulmonary Disease – “COPD”

Time: 10:30 AM
Faculty: Philip Diaz, MD
201 HLRI; 293-4925
Email: Philip.Diaz@osumc.edu
Objectives:
1. Accurately recognize the key factors associated with the increase in COPD
prevalence
2. Accurately recognize the key pathophysiologic mechanisms contributing to the

disability associated with COPD.
3. Given a clinical vignette, accurately recognize the risk factors and common
symptoms of COPD.
4. Given a clinical vignette, decide on the appropriate test(s) to order for diagnosing
COPD.
5. Given a patient’s symptoms and the results of pulmonary function tests in a clinical
vignette, accurately assess the clinical stage of COPD and therapeutic options.
I. Epidemiology
a. Up to 30 million affected in US
b. Fourth leading cause of death
c. Projected to be 3rd leading cause of death by 2020
II. Definition
a. “COPD is a preventable and treatable disease with some significant extra-
pulmonary effects that may contribute to the severity in individual patients. The
pulmonary component is characterized by airflow limitation that is not fully
reversible. The airflow limitation is usually both progressive and associated with
an abnormal inflammatory response of the lungs to noxious particles or gases.”
Global Initiative for Chronic Obstructive Lung Disease 2006
Page 80 of 177
b. Generally involves chronic bronchitis and/or emphysema
i. Chronic bronchitis – Airways disease with inflammation, mucus
hypersecretion. Definition (based on symptoms) – “productive cough for
at least 3 months for 2 consecutive years”
ii. Emphysema – Parenchymal disease associated with destruction of alveolar
walls and “disappearance” of lung tissue. Definition (based on anatomy) –
“abnormal permanent enlargement of the airspaces distal to the terminal
bronchioles accompanied by destructive changes of the alveolar walls,
without obvious fibrosis.”
iii. Note – there is considerable overlap between these entities in individual
patients (as both are closely related to cigarette smoking). However, as
COPD gets more severe, emphysema becomes a more prominent feature.
III. Pathogenesis
a. Cigarette smoke (and other noxious stimuli) activate inflammatory processes in
the lung with damage to airway (chronic bronchitis) and lung parenchyma
(emphysema)
b. Inflammatory cells important in pathogenesis – alveolar macrophages,
neutrophils, lymphocytes (esp. CD8+)
c. Protease-antiprotease balance is hypothesized to be important in the development
of emphysema. Cigarette smoke activates alveolar macrophages and neutrophils
with subsequent secretion of proteases. Note patients with alpha-1 antitrypsin
deficiency are deficient in “protective” antiproteases leading to unchecked
proteolytic damage to lung tissue and premature emphysema.
IV. Pathophysiology
a. Airflow limitation (mainly expiratory) – two components:
i. Small airways disease - inflammation, mucus secretion and luminal
obstruction
ii. Loss of elastic recoil – less driving pressure for expiratory flow and less
“tethering’ of small airways during expiration. Instead of behaving like a
“balloon” (air comes out hard and fast when you let air out of a balloon),
lungs behave like a “paper bag”
Page 81 of 177
b. Increased work of breathing
i. Respiratory muscles may “fatigue”
ii. CO2 retention may occur in severe disease
c. Ventilation-perfusion mismatch
i. Hypoxemia is common, especially with exercise
d. Hyperinflation
i. Secondary to: decreased elastic recoil of lungs and higher functional
residual capacity, airflow obstruction during expiration and increased
residual volume (“trapped air”)
ii. Puts respiratory muscles at mechanical disadvantage and at shorter resting
muscle length – leads to respiratory muscle weakness
e. Pulmonary hypertension
i. Main cause – alveolar hypoxia causing pulmonary vasoconstriction
ii. Contributing factors – decreased cross-sectional area of pulmonary
vascular bed in emphysema; increased intrathoracic pressure transmitted
to cardiac surface
f. Systemic factors
i. Poor nutrition
ii. Deconditioning – leads to decreased oxidative capacity of skeletal
muscles, earlier onset of anaerobic metabolism with subsequent greater
acid load (lactic acid) and increased ventilatory demands (lactic acid
converted to CO2)
iii. Vicious cycle: Airflow obstruction/hyperinflation – increased work of
breathing/decreased respiratory muscle strength – dyspnea on exertion –
decreased activity – deconditioning – skeletal muscle dysfunction – earlier
onset anaerobic metabolism – more dyspnea on exertion – more
deconditioning, etc.
iv. Systemic inflammation. COPD is associated with a systemic
inflammatory state (e.g. increased inflammatory cytokines, oxidant stress).
This is felt to be important in the pathogenesis of skeletal muscle
Page 82 of 177
dysfunction as well as associated co-morbidities (cachexia, coronary
artery disease)
V. Clinical Presentation
a. Clinical profile
i. Age – usually 40’s or older at presentation
ii. Positive smoking history – at least 20 pack years (e.g. 1 pack per day for
20 years)
b. Symptoms
i. Dyspnea on exertion
ii. Cough
iii. Wheeze
c. Signs
i. Wheezing or decreased breath sounds on lung auscultation
ii. Hyperresonance and hyperinflation (barrel chest) with more severe disease
iii. Signs of pulmonary hypertension (cor pulmonale) with advanced disease –
elevated neck veins, peripheral edema
iv. Physical exam may be normal with mild-moderate disease
d. CXR
i. Flat diaphragms (hyperinflation) and enlarged pulmonary arteries
(pulmonary hypertension) with advanced disease. With severe
emphysema may see “bullae” – large air-sacs
ii. CXR often normal in mild-moderate disease
e. Pulmonary function tests
i. Air-flow obstruction on spirometry is gold standard for diagnosis –
decreased FEV1/FVC is sensitive (normal FEV1/FVC is ~0.70 or greater).
Absolute FEV1 as a percent of predicted is better predictor of severity
(e.g. FEV1 < 50% of predicted consistent with severe disease
ii. Lung volumes are usually normal to increased (i.e. increased residual
volume, functional residual capacity and total lung capacity)
iii. Decreased diffusing capacity (indicating decreased lung surface area for
gas-exchange) is reduced in emphysema
Page 83 of 177
f. Arterial blood gases
i. Hypoxemia (especially with activity) common
ii. CO2 retention and respiratory acidosis can develop with severe disease
(FEV1 < 40% of predicted)
g. *Diagnosis is based primarily on three factors:
i. Symptoms (esp. exertional dyspnea and cough)
ii. Smoking history
iii. Spirometry – air-flow obstruction
VI. Treatment
a. General principles
i. Most interventions do not affect mortality of natural history of disease
ii. Treatment is primarily symptom based
iii. Step-wise approach recommended
1. Add treatment with persistent symptoms
b. Smoking cessation
i. Can alter natural history of disease and slow rate of decline of lung
function
ii. Intervention
1. Strong (and personalized) message from physician
2. Nicotine replacement
3. Buproprion
4. Smoking cessation counseling/classes
c. Pharmacologic agents
i. Bronchodilators – central to symptomatic management. Inhaled delivery
preferred over oral
1. Inhaled beta-agonists – albuterol (short acting), salmeterol (long
acting), formoterol (long and short acting)
2. Inhaled anticholinerics – ipratroprium, tiotropium
3. Oral phosphodiesterase inhibitors – theophylline
4. May use more than one agent in individual patients
ii. Anti-inflammatory agents
Page 84 of 177
1. Inhaled corticosteroids
a. Indicated for patients with moderate-severe disease and
frequent exacerbations of disease
2. Systemic corticosteroids
a. Oral prednisone is effective for brief (1-2 week) periods
when patients have an “acute exacerbation” of symptoms
(usually worse dyspnea, cough and/or sputum production)
3. Generally avoid long term systemic steroids
iii. Antibiotics
1. Useful for “acute exacerbations”. Often used with systemic
steroids.
d. Vaccination
i. Influenza vaccine – good evidence for its effectiveness
ii. Pneumococcal vaccine – less evidence for its effectiveness in COPD, but
generally recommended
e. Oxygen therapy
i. Indicated for resting PO2 < 55 (or < 59 with polycythemia or signs of cor
pulmonale) or oxygen saturation < 88%
ii. May improve end-organ function (e.g. cognitive) and life-expectancy
f. Exercise training/pulmonary rehabilitation program
i. Addresses the “vicious” cycle that occurs in COPD
ii. Primarily involves lower extremity endurance training (e.g. treadmill)
iii. Consider in all COPD patient with persistent dyspnea despite medical
management
g. Surgical management
i. Lung volume reduction surgery
1. Involves removing ~30% of the volume of each lung surgically.
The areas most involved with emphysema are targeted
2. Consider in moderate-severe emphysema, especially if the disease
primarily involves the upper lobes
ii. Lung transplantation
Page 85 of 177
1. For severe end-stage disease (FEV1 < 25% of predicted)
VII. Prognosis
a. FEV1 most commonly used prognostic indicator
i. For example if FEV1 > 50% of predicted, little excess mortality
(compared to smokers without COPD)
ii. If FEV1 < 30% of predicted, 4 year mortality is ~40%
b. Poor exercise capacity, increased dyspnea and low body weight are also
associated with increased mortality
i. “BODE” (body mass index, obstruction, dyspnea, exercise capacity) index
recently shown to be highly predictive of survival
Page 86 of 177
Pathology of Pneumonia

Time: 8:30 – 9:20 am
1. Describe the normal pulmonary defense mechanisms and the classification for
pulmonary infections.
2. Compare and contrast the etiologic, pathologic, morphologic and clinical features of
the following pulmonary infections of bacterial pneumonia, and viral/mycoplasma
infections
Learning Resources
I. GENERAL CONSIDERATIONS
A. Impact
1. The organs of the respiratory system are the most common organs involved
by infection and are among the most common causes of morbidity and
mortality.
2. Upper respiratory infections (URIs), primarily due to coronaviruses and

rhinoviruses, are the most common type of respiratory infection.
3. Infections have an uncertain linkage to the development of chronic lung

disease. This linkage involves both innate and adaptive immune responses.
B. Routes of Infection
1. There are several routes whereby organisms can gain entry to the lungs.
a. Aspiration of oral contents is the most common
b. Inhalation of airborne droplets
c. Bacteremia
d. Direct extension of an inflammatory process from other organs.
C. Host Defense Mechanisms

1. Pneumonia may develop whenever pulmonary defenses are compromised.
The upper and lower respiratory systems have a variety of innate and
adaptive immune response mechanisms to remove inhaled particles and
organisms.
Page 87 of 177
2. Pulmonary infections are associated with inhibition of one or more host
defenses. These include:
a. Suppression of the cough reflex may lead to aspiration.
b. Injury of the mucociliary apparatus predisposes patients to pulmonary

infections. This is a common feature of chronic airway diseases such as
asthma, cystic fibrosis, ciliary dyskinesia, and chronic bronchitis.
c. Interference with phagocytic function of alveolar macrophages can lead to

granulomatous inflammation.
d. Immune deficiency, immunosuppression, and leukopenia place patients at

a markedly increased risk for all types of infections.
e. Chronic airway obstruction and accumulation of secretions impairs

removal of infectious agents and promotes their growth.
f. Pulmonary congestion and edema.
g. Chronic debilitating diseases.
3. Virulence factors of the infecting organisms are associated with an ability to

impair the innate and/or the adaptive immune response. This may include:
a. Surface capsule and/or antigen make up
b. Resistance of proteolysis
c. Toxin production
d. Increased motility
e. Production of enzymes (e.g. catalase)
f. Intracellular resistance (M. tuberculosis)
g. Fe-acquiring systems that decrease the Fenton reaction and generation of
oxygen free radicals
h. Development of antibiotic resistance
D. Classification of Pneumonia
1. Pneumonias can be classified as either interstitial or intraalveolar. Intra-
alveolar pneumonias are further classified as either bronchopneumonia with
its patchy consolidation or as lobar pneumonia where the pneumonia involves
all or a majority of a lobe.
2. Pneumonias may be classified as to their etiology (e.g. viral vs. bacterial),

staphylococcal or pneumococcal pneumonia.
a. Bacterial pneumonia has suppurative exudate rich in neutrophils,
macrophages and fibrin within the alveoli.
b. Viral pneumonia is characterized by an interstitial mononuclear

(lymphocyte and macrophage) infiltrate with minimal intra-alveolar
exudate.
Page 88 of 177
3. Classification by host response includes necrotizing pneumonia or
granulomatous pneumonia.
4. Pneumonias can be classified on the basis of the clinical setting. This

includes:
a. Community acquired acute pneumonia
b. Community acquired atypical pneumonia
c. Hospital (nosocomial) pneumonia
d. Severe acute respiratory syndrome (SARS)
5. Pneumonias are can also be classified as aspiration, abscess, or chronic.
E. Diagnosis of Pneumonia
1. The initial diagnosis and treatment of pneumonia are often empiric.
2. Failure of antibiotic therapy should result in obtaining a sputum sample for

Gram stain and culture. The quality of the sputum is important in order to
exclude a false positive result due to oral contamination. An adequate
sputum should have <10 squamous epithelial cells per low power field and
>25 leukocytes per low power field. The presence of alveolar macrophages is
also a good indicator of a deep sampling.
3. Blood cultures should be obtained upon admission to the hospital.
F. Prevention
1. Pneumococcal vaccine – polyvalent, can give every 5 years.
2. Influenza vaccine – yearly in the autumn for both you and your patients.
II. BACTERIAL PULMONARY INFECTIONS

A. Bronchopneumonia
1. Clinical features include:
a. Very common infections that tend to affect the very young and the elderly.
b. The presenting symptoms may include fever with or without chills, cough,
purulent sputum production, chest pain, dyspnea, and rapid shallow
respirations.
c. Imaging studies may be negative in early disease but later have a patchy
distribution of consolidation.
2. Common etiologic agents include: Staphylococcus, Streptococcus,

Pseudomonas, Haemophilus, Moraxella, the coliforms.
3. Gross pathologic features include:

a. Patchy areas of consolidation - slightly elevated, dry, granular, gray to
yellow, poorly-circumscribed areas - within one or more lobes.
Page 89 of 177
b. There may be a concurrent fibrinous pleuritis and/or small parenchymal
abscesses.
4. The microscopic features are those of a suppurative exudate in small bronchi,

bronchioles and adjacent alveoli that is rich in neutrophils and macrophages.
Focal parenchyma necrosis may lead to abscess formation.
5. Bronchopneumonia may resolve without lung damage or lead to organization

and scarring.
B. Lobar Pneumonia
a. Effects otherwise healthy adults, 30-50 years of age, and predominately
men (M:F=3-4:1).
b. The symptoms relate to a relatively sudden onset of fever, chills, and

blood tinged sputum.
c. Chest X-rays show lobar consolidation.
d. The incidence of lobar pneumonia is infrequent due to the effectiveness

with which antibiotics abort these infections and prevent full-blown
development of lobar consolidation.
2. 95% of cases are caused by community acquired Streptococcus pneumoniae;

most commonly associated with types 1, 2, 3 and 7.
3. The gross pathologic features include a widespread fibrinopurulent

consolidation of large areas of lobe, and a fibrinous pleuritis.
4. The microscopic features can be divided into four classic stages:

a. Congestion: this first phase occurs within the first 24 hours due to vascular
congestion & alveolar edema. The lungs are heavy and hyperemic.
b. Red hepatization: this phase occurs within 2 to 3 days and is due to

extravasation of RBCs into the purulent exudate.
c. Gray hepatization: results from lysis of the intra-alveolar RBCs while the
fibrinopurulent exudate remains.
d. Resolution: occurs with the clearing of the exudate.
5. Outcomes include:
a. The most common outcome is that of resolution of the normal pulmonary
architecture. Organizing pneumonia that results in pulmonary fibrosis is a
less likely outcome.
Page 90 of 177
b. Adverse sequelae include the formation of an abscess and/or an
empyema, as well as sepsis with resulting endocarditis, pericarditis,
and/or meningitis.
C. Pulmonary Abscess
1. An abscess represents a localized suppurative process characterized by
tissue necrosis.

a. Aspiration of oral contents gives rise to about 60% of cases, and results in
an infection due to mixed organisms and anaerobes. Aspiration may be
due to loss of consciousness, dementia, loss of the gag and/or cough
reflexes.
b. Other predisposing factors include an antecedent pulmonary infection, a

sinobronchial infection, septic emboli, or an obstructing tumor.
c. Radiologic studies demonstrate one or more lesions that may cavitate.
3. On gross examination, pulmonary abscesses appear well circumscribed

nodules with central necrosis.
4. Microscopic examination reveals a focus of pulmonary parenchyma

destruction by liquefactive necrosis. The lesion may have a fibrous limiting
wall.
5. A pulmonary abscess may result in a chronic infection or septic emboli.

These in turn can cause an empyema, suppurative pericarditis, and/or
bacteriemia.
III. MYCOPLASMAL AND VIRAL PULMONARY INFECTIONS

A. General Features
1. Viral infections usually lead to an interstitial pneumonia.
2. Viral infections are commonly associated with URIs, but pulmonary extension
may occur with debilitation, malnutrition, alcoholism, or a coexistent
cardiopulmonary disease.
3. The etiologic agents include:

a. Mycoplasma pneumoniae (primary atypical pneumonia) is the most
common cause.
b. Influenza A, B, RSV, Coxsackie, Adenovirus, ECHO virus are common

viral causes
c. Chlamydia pneumoniae and psittaci
Page 91 of 177
B. Atypical Pneumonia
a. Sometimes referred to as a “chest cold” or severe upper respiratory
infection. May also be called atypical pneumonia in contrast to “typical”
pneumonia associated with a viral infection.
b. Patients often present with an insidious onset of fever, malaise, headache,

myalgia, and a non-productive cough. Rales and rhonchi are heard on
physical examination. The course is usually mild but pandemics (esp.
1915, 1918) have occurred.
c. These pneumonias can be classified as atypical pneumonia in an

otherwise healthy patient or as a viral pneumonia in immunosuppressed or
immunocompromised patients.
d. Laboratory findings include elevated cold agglutinins (Anti-I) that are

present in > 50% of mycoplasma infections.
e. A pleural effusion may be present on chest X-rays.
2. The etiologic agents of atypical pneumonia include bacteria, viruses, and

fungi.
a. Mycoplasma pneumoniae is the most common cause of atypical
pneumonia, second only to Strep. pneumoniae in causing pneumonia, and
causes 20-25% of pneumonias in all age groups.
b. Chlamydia pneumoniae, Influenza viruses and Legionella are other

relatively common causes.
3. Gross examination of lungs from uncomplicated cases demonstrates red, firm

lungs, patchy or extensive involvement, without consolidation. Complicated
cases are associated with a secondary bacterial infection.
4. Microscopic examination may demonstrate:

a. Interstitial mononuclear (lymphocytes, macrophages) inflammation and
congestion.
b. Hyperplasia of type II pneumocytes, edema of alveolar wall and/or hyaline

membranes lining the alveolar surface of the septal wall.
c. Bronchial/bronchiolar inflammation may be present.
d. Cytopathic effects of viral infections are seen with CMV, HSV, and
measles.
e. Secondary bacterial infection may occur.
Page 92 of 177
C. Influenza
1. The influenza virus is a single-stranded RNA virus divided into five genera
with types A, B, and C causing “the flu”. These three have a very similar
structure.
2. The surface envelope is lipid bilayer with hemagglutinin (H) & neuraminidase
(N). The N and H determine the serotype based on the antibody response.
Antigenic diversity - year-to-year mutations - in the H and N genes is a means
to avoid the host immune response. Vaccines are generated against them.
3. Influenza Type A infects humans, pigs, horses, birds. Avian subtype H5N1
circulating in SE Asia, Europe, Middle East & Africa is the etiology of bird flu.
a. Humans lack immunity to the H5N1 virus. This leads to a potential of
severe disease and a pandemic. Mortality rate ~ 60%
b. Oseltamivir may be an effective drug, but resistance strains have already

been identified in humans.
c. Infection of an immunocompetent patient results in a cytokine storm

associated with cytokines IFN-α and IFN-β and cytotoxic T cells. The
result is severe interstitial pneumonia with diffuse alveolar damage.
Clinically, this is ARDS.
4. Types B & C – mostly infect kids, do not show Ag drift/shift.
D. Severe Acute Respiratory Syndrome (SARS)

1. SARS is caused by a novel coronavirus which first appeared in China
in November 2002. It is highly contagious at close contact. Those at
risk include: travelers, health care workers, and laboratorians.
2. Patients appear 2-10 days after exposure with a dry cough, malaise,
myalgias, fever, chills.
3. Approximately two-thirds resolve of the patients develop respiratory

distress with a 5-10% mortality rate.
4. Severe interstitial pneumonia with diffuse alveolar damage, secondary

to a cytokine storm, results from this infection.
Page 93 of 177
Lower Respiratory Tract Infections in Adults
Date: September 18th 2008
Time: 9:30 AM
Faculty: Troy Schaffernocker, MD; Department of Internal Medicine,
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine
Email: Troy.Schaffernocker@osumc.edu
Objectives:
1. Recognize the host defense mechanisms and pathophysiology involved in the
development of pneumonia.
2. Identify the most common pathogens responsible for “Community Acquired”
and “Health Care Associated” pneumonia.
3. Recognize the common organisms responsible for pneumonia in patients with
specific defects in host defense including hypogammaglobulinemia,
neutropenia, long term glucocorticoid therapy, and low CD4 lymphocyte
counts i.e. HIV/AIDS.
4. List the most common infectious causes of pulmonary cavities.
5. Recognize the common diagnostic testing utilized in the evaluation of the
hospitalized patient with pneumonia.
6. Select appropriate antibiotics for treatment in the setting of “Community
Acquired” (Outpatient and Inpatient) and “Healthcare Associated”
pneumonia.
7. Know the indications for administration of the pneumococcal vaccine.
8. Recognize the clinical presentation of bronchiectasis.
9. Identify the clinical presentation of pulmonary tuberculosis including primary
and post-primary disease.
10. Recommend a diagnostic approach to a patient with suspected tuberculosis.
11. Recognize the importance of drug susceptibility testing and directly observed
therapy in the treatment of pulmonary tuberculosis.
12. Recognize nontuberculous mycobacterial and fungal infections as unusual, but
identifiable causes of pulmonary infections given their often unique clinical
scenarios.
13. Identify the clinical presentation of influenza infection along with the
appropriate diagnostic and treatment measures.
14. Be aware of the indications for influenza vaccination.
Reading: Harrison’s 17th Ed. Chapter 251: Pneumonia
Supplemental Reading: Chapter 252: Bronchiectasis and Lung Abscess, Chapter

200: Pneumocystis, Chapter 158: Tuberculosis, Chapter 160: Nontuberculous
Mycobacteria, Chapter 192: Histoplasmosis, Chapter 193 Coccidiomycosis, Chapter
194: Blastomycosis, Chapter 195: Cryptococcus, Chapter 196 Candidiasis, Chapter
197: Aspergillosis, Chapter 180: Influenza.
Page 94 of 177
I. Pneumonia
a. Definition-An infection of the pulmonary parenchyma.
i. Various bacteria, viruses, and fungi may be responsible.
ii. In 1/3 of cases etiologic organism is not identified
b. Defense
i. Upper Airway
1. Sneezing
2. Swallowing
3. Expectoration
ii. 80% of cells in central airways Ciliated, pseudostratified, columnar
epithelium
iii. Alveoli
1. Alveolar Macrophages (phagocytes)
2. Lining fluid: surfactant, fibronectin, immunoglobulins which can
opsonize or lyse microbial pathogens
c. Pathophysiology
i. Alveolar Macrophages
1. Process and present microbial antigens to lymphocytes
2. Secrete cytokines
ii. Cytokines
1. Generate inflammatory response
2. Activate alveolar macrophages
3. Recruit more phagocytes and immunologic factors from plasma
iii. Inflammatory Exudate
1. Pulmonary Consolidation
2. Systemic Manifestations
a. Fever
b. Chills
c. Myalgias
d. Malaise
d. Transmission
i. Aspiration
1. Level of consciousness (alcohol, drugs)
2. Neurologic Dysfunction (seizure, stroke)
3. Mechanical Impairments (endotracheal tube, nasogastric tube)
ii. Inhalation
1. Particles >  m get deposited in nose and oropharynx
2. 5-10 m Central airways
3. <5 m can make it all the way to alveoli
iii. Hematogenous
1. Extrapulmonary Sites
a. Endocarditis
b. Vascular Catheter infections
c. Retropharyngeal infections
iv. Direct Inoculation/Contiguous Spread
1. Tracheal intubation
2. Penetration of the chest wall
e. Pathology
i. Lobar pneumonia
1. Involvement of entire lobe
Page 95 of 177
ii. Bronchopneumonia
1. Restricted to alveoli and contiguous bronchi
iii. Necrotizing pneumonia
1. mulltiple small cavities, < 2cm
iv. Lung Abscess
1. 1 or more cavities, > 2cm
f. Epidemiology
i. Community-acquired pathogens
1. Streptococcus pneumoniae
2. Haemophilus influenzae
3. Chlamydia pneumoniae
4. Legionella pneumophila
5. Mycoplasma pneumoniae
ii. Health care acquired pathogens
1. Enteric gram-negatives
2. Pseudomonas aeruginosa
3. Staphylococcus aureus
g. Physical Exam
i. Fever
ii. Purulent Sputum
iii. Signs of pulmonary consolidation
1. Dullness
2. Increased fremitis
3. Egophony
4. Bronchial breath sounds
5. Rales
h. Specific Defects in Host Defense
i. Hypogammaglobulinemia
1. Encapsulated Organisms: Streptococcus pneumoniae,
Haemophilus influenzae
ii. Neutropenia
1. Pseudomonas aeruginosa, Enterobacteriaceae, Staphylococcus
aureus, Aspergillus
iii. Long-term glucocorticoid therapy
1. Mycobacterium tuberculosis, Nocardia
iv. Cell-mediated immunity
1. CD4 count <500/mL
a. Mycobacterium tuberculosis
2. CD4 count <200
a. Pneumocystis jiroveci
b. Histoplasma capsulatum
c. Cryptococcus neoformans
3. CD4 count <50
a. Mycobacterium avium-intracellulare
b. Cytomegalovirus
i. Chest Radiography
i. Confirm the presence and location of an infiltrate
ii. Assess the extent of infection
iii. Detect pleural involvement
iv. Gauge hilar lymphadenopathy
v. Monitor response to therapy
Page 96 of 177
j. Causes of Pulmonary Cavities
i. Infectious
1. Bacteria: Oral Anaerobes, enteric aerobic gram-negative bacilli,
Pseudomonas aeruginosa, Legionella, Staphylococcus aureus,
Streptococcus pneumoniae serotype III, Mycobacterium
tuberculosis, Nocardia
2. Fungi: Histoplasma capsulatum, Coccidioides immitis,
Blastomyces
ii. Noninfectious
1. Neoplasms: Lymphoma, Squamous cell carcinoma
2. Other: Wegener’s granulomatosis, infarction, infected bullae and
cysts
k. Sample Analysis
i. Sputum
1. Gram’s staining
2. Acid-fast staining (mycobacteria)
3. Legionella direct flouresence antibody
4. Giemsa stain (Pneumocystis)
ii. Fiberoptic Bronchoscopy
1. Bronchoalveolar lavage (BAL)
2. Protected Sheath Brush
3. Transbronchial Biopsy
iii. Thoracentesis
1. Consider if significant pleural effusion
iv. Open-Lung Biopsy
l. Other Diagnostics Tests
1. Peripheral Blood Cultures (all patients)
2. If clinical suspicion
a. Antibody titers: Mycoplasma pneumoniae, Chlamydia
pneumoniae, Cytomegalovirus
b. Urine antigens: Streptococcus pneumoniae, Legionella
pneumophila, Histoplasma capsulatum
m. Clinical Considerations
i. Hospitalization
1. Mental status change
2. Tachypnea (>30/min)
3. Tachycardia (>140/min)
4. Hypotension (< 90mmHg systolic)
5. Advanced age (>65yrs)
6. Significant co-morbidity (kidney, heart, or lung disease, diabetes
mellitus, cancer)
7. Inability to take oral medication
8. Failure of outpatient management
n. Treatment
i. Outpatient:
1. Macrolides
2. Flouroquinolones
ii. Inpatient: Community Acquired-
1. General Wards: Flouroquinolone or Beta-lactamase resistant
penicillin + macrolide
2. ICU: Beta-lactamase resistant penicillin + macrolide
Page 97 of 177
iii. Inpatient: Healthcare Associated
1. Anti-pseudomonal cephalosporin, carbapenem, or penicillin +
Aminoglycoside or Flouroquinolone + Vancomycin or Linezolid
o. Prevention
i. Pneumococcal Vaccine
1. Age > 65
2. Chronic Lung, Heart, or Kidney disease
3. Immunosuppressed
4. Sickle Cell Anemia
5. Diabetes Mellitus
6. Cancer
7. HIV
II. Bronchiectasis
a. Abnormal and permanent dilation of the bronchi.
i. Often associated with chronic or recurrent infections.
ii. Can be focal or diffuse.
b. Etiology
i. Recurrent bacterial infections
ii. Mycobacterial disease – Mycobacterium Avium Complex
iii. Generalized impairment of pulmonary defense mechanisms
1. Immunoglobulin deficiency
2. Ciliary Disorders
a. Primary ciliary diskinesia
b. Kartagener’s syndrome
3. Cystic Fibrosis
a. Tenacious secretions impair bacterial clearance
c. Clinical Symptoms
i. Recurrent Cough
ii. Purulent Sputum production
iii. Hemoptysis
iv. Dyspnea
v. Wheezing
d. Diagnosis
i. High Resolution Chest CT
e. Treatment
i. Treatment of any precipitating conditions
ii. Antibiotics for acute exacerbations
iii. Preventive antibiotics in patients with recurrent exacerbations
iv. Chest physiotherapy
v. Maintain adequate hydration
vi. Inhaled corticosteroids and bronchodilators as needed
vii. Consider lung transplantation in advanced disease
III. Pulmonary Tuberculosis
i. Most commonly transmitted by droplet nuclei which are aerosolized by
coughing, sneezing, or speaking.
ii. Probability of disease contraction is dependent upon intimacy, duration,
and degree of infectiousness of contact.
b. Primary Disease
i. Initial infection with tubercle bacilli
ii. In areas of high prevalence of TB
iii. Affects Children
Page 98 of 177
iv. Mid to lower lung fields
v. Hilar Lymphadenopathy
vi. Often heals spontaneously into a calcified nodule (Ghon Lesion)
c. Post-primary disease
i. Occurs in adulthood
ii. Affects apical and posterior upper lobes most frequently
iii. Can vary from small infiltrates to extensive cavitary disease
d. Signs and Symptoms
i. Often insidious
ii. Night sweats, fever, weight loss, anorexia, malaise, weakness
iii. Cough
iv. Hemoptysis
v. Dyspnea
e. Important opportunistic infection in HIV population
f. Diagnosis
i. Chest Radiography
ii. AFB (Acid Fast Bacillus) Microscopy
iii. Mycobacterial Culture
iv. PPD Skin testing
v. Drug Susceptibility Testing [MDR (Multidrug-Resistant) TB]
g. Treatment
i. Dependent upon Drug Susceptibility
ii. Most often require 6 months of therapy
1. First two months: Four drug therapy with Isoniazid, Rifampin,
Ethambutol and Pyrazinamide.
2. Next four months: Two drug therapy with Isoniazid and
Rifampin.
iii. DOT: Directly observed therapy
h. Prevention
i. BCG Vaccine – not recommended in USA
IV. Non-tuberculous Mycobacteria
a. Most Common in Pulmonary Infections
i. M. intracellulare
ii. M. avium
iii. M. Kansasii
iv. M. Abscessus
b. NTM are ubiquitous in the environment and rarely pathogenic
c. Clinical Aspects
i. Chronic Cough
ii. Low grade fever
iii. Malaise
iv. Occaisionally hemoptysis
v. AIDS patients may develop more fulminant symptoms
d. Treatment
i. Generally 3-4 drug combination therapy based on sensitivities
ii. Duration often a year or more
V. Fungal Infections
a. Aspergillus
i. Pulmonary Syndromes
1. ABPA (Allergic Bronchopulmonary Aspergillosis): Treatment -
Steroids
Page 99 of 177
2. Aspergilloma: Treatment - Surgery
3. Angioinvasive Aspergillus: Treatment - Antifungals
4. Chronic necrotizing pulmonary aspergillosis: Treatment -
Antifungals
b. Histoplasma capsulatum
i. Soil dwelling fungus – endemic to Ohio river valley
ii. Frequent cause of pulmonary nodules, mild pneumonitis, mild
lymphadenopathy - often do not require treatment, depends on
symptoms
iii. Progressive and disseminated disease requires treatment with antifungals
– usually only occurs in immunocompromised – i.e. organ transplant,
chronic glucocorticoid therapy, chemotherapy, and HIV.
c. Coccidioidomycosis
i. Endemic to Desert Southwest
ii. Most patients with primary disease have no symptoms, or a mild flu-like
illness that lasts 1-3 weeks. No treatment is required.
iii. Immunocompromised individuals, diabetics, blacks, and pregnant
women have a high risk of dissemination and should be treated with
antifungal therapy
VI. Influenza
a. Definition
i. An acute respiratory illness caused by infection with the influenza virus.
ii. Influenza A and B are members of the genus that cause most infections
in humans.
b. Epidemiology
i. Often occurs in outbreaks
ii. Global epidemics or pandemics occur every 10-15 years – usually
Influenza A is responsible
iii. Usually isolated to the Winter months i.e. “flu season”
c. Clinical Presentation
i. Abrupt Onset (first 24 hours)
1. Fever
2. Headache
3. Chills
4. Myalgias
5. Malaise
ii. Later (Over 2-5 days)
1. Cough
2. Sore Throat
3. Coryza
d. Complications
i. Viral Pneumonia
ii. Secondary Bacterial Pneumonia
1. Staphylococcus aureus
2. Streptococcus pneumoniae
3. Haemophilus influenzae
iii. COPD or Asthma Exacerbation
iv. Respiratory Failure
e. Diagnosis
i. Clinical History
ii. Throat Swab
Page 100 of 177

1. Rapid – can have diagnosis within minutes
2. Sensitivity ~ 85%
iii. Viral culture
1. Takes 2-3 days to get results
f. Treatment
i. Supportive
ii. Antivirals – Effective in reducing duration of symptoms if started within
24 hours of symptom onset.
1. Influenza A
a. Amantadine
b. Rimantidine
2. Influenza A and B
a. Oseltamivir
b. Zanamivir
g. Prevention
i. Influenza Vaccine
1. Age 50 or older
2. Nursing Home residents
3. Chronic Pulmonary, Heart, Renal, or Liver disease
4. Diabetes
5. Immunosuppressed
6. Sickle Cell (asplenia)
7. HIV
8. Women that will be pregnant during flu season
9. Health Care Workers
Page 101 of 177

Lower Respiratory Infections in Children

Time: 10:30 am
Faculty: Dwight Powell, MD
Professor of Pediatrics
Division of Pediatric Infectious Disease
Nationwide Children’s Hospital
Objectives
1. Compare and contrast the clinical presentation, pathogens, and management of the
four main syndromes of pediatric lower respiratory tract infection: croup,
tracheobronchitis, bronchiolitis, and pneumonia.
2. Describe the seasonal epidemiology of common pediatric respiratory pathogens.
3. List the diagnostic tests available for identifying the main respiratory viruses
causing pediatric lower respiratory infections.
4. Given a clinical vignette, recognize symptoms of, recommend diagnostic testing
for and recommend treatment for pertussis.
5. List the common pathogens causing pediatric community-acquired pneumonia.
6. List the physical examination findings of pneumonia.
7. Chose correct diagnostic tests for different pathogens that cause pneumonia.
8. Given a clinical vignette, recommend appropriate antibiotics for pediatric
community-acquired pneumonia.
Page 102 of 177

Pathology of Lung Cancer

Time: 8:30 – 9:20
1. List the etiology, pathogenesis and predisposing factors for lung cancer.
2. List the histologic classifications and morphologic features of the various subtypes of
primary tumors of the lung.
3. Describe the pathogenesis of pulmonary metastasis (carcinoma metastatic to lung).
Learning Resources
I. PRIMARY PULMONARY CARCINOMA

A. Epidemiology
1. Lung cancer is a major global public health problem. It is the number one
cancer in the world relative to incidence and mortality.
2. In the U.S. this year there will be 215,000 new cases diagnosed and 162,000
deaths from lung cancer. It is the leading cause of cancer death in both men
and women.
3. There has been a sharp increase in incidence among women smokers, to the
extent that it has surpassed breast cancer as the leading cause of cancer
deaths in women.
4. The incidence varies with location, age, sex, and over time.
5. The death rate is decreasing in men but increasing in women.

Cancer Type All New Cancers All Cancer Death
Men – Lung 13% 31%
Men - Prostate 33% 19%
Women – Lung 12% 26%

Women - Breast 31% 15%
Page 103 of 177

B. Etiology
1. Cigarette smoking is the most important risk factor and increases the risk X10
compared with the general population. In men ~ 87% of lung cancers occur in
smokers (women – 85%).
a. Risk is dose dependent: exposure to 25 pack-years doubles the cancer
risk over nonsmokers.
b. The fact that lung cancer occurs in less than 15% of smokers indicates
that the etiology is multifactorial.
c. There are >1200 different carcinogens in tobacco smoke. These include

both initiator and promoter chemical carcinogens, radioactive compounds,
and various elements.
d. Part of the difference may be related to genetic differences in how the

cells metabolize the carcinogens. These include:
1) Phase I enzymes of the cytochrome p450 system that form reactive
intermediates of the various carcinogens in tobacco smoke that
damage DNA.
2) Glutathione S-transferase, a phase II enzyme that detoxifies reactive

metabolites of polycyclic aromatic hydrocarbons, has also been
proposed as a mechanism to explain the differences in susceptibility to
lung cancer among smokers.
e. Cessation of smoking reduces risk of carcinoma progressively, almost to

that of "never-smokers" after 10 - 12 years of abstinence.
2. Other exogenous carcinogens are also implicated in the development of lung

cancer include: radioactive gases and dusts (uranium workers, radon gas),
chromate, nickel, arsenic, asbestos, polycyclic aromatic hydrocarbons,
beryllium, coal, mustard gas, and iron.
3. Molecular genetic events have been identified in lung carcinogenesis

indicating a multifactorial process.
a. Changes in TP53 have been described.
b. Germline mutations of KRAS and EGFR have been identified. These

mutations within a tumor are being used to clinically segregate patients for
treatment.
c. A marker on chromosome 15 has also been identified.
d. A recent study has demonstrated 16 genes that were related to increased

or decreased survival.
Page 104 of 177

II. PATHOLOGY OF PRIMARY LUNG TUMORS
A. Clinical Features
1. Symptoms tend to occur late in the disease process. These include:
a. Cough (75%)
b. Weight loss (40%)
c. Dyspnea (20%)
d. Hemoptysis
e. Chest pain
f. Pleural effusions
g. Pneumonia
2. Signs and symptoms are closely related to tumor location.

a. Common signs and symptoms include:
1) Post-obstructive pneumonia in central lesions
2) Pleural effusions are more common with peripheral lesions
3) Hoarseness is associated with invasion of the recurrent laryngeal
nerve
4) Dysphagia is associated with invasion into the esophagus
b. Superior vena cava syndrome arises from compression of the superior

vena cava; which in 80% of the cases is caused by cancer of the right
lung. The signs and symptoms include:
1) Dyspnea
2) Swelling of the trunk, upper extremities and the face
3) Orthopnea
c. Pancoast syndrome arises from a tumor growing in the apex of the lung
that compresses the structures within the thoracic inlet including the
phrenic, recurrent laryngeal and vagus nerves; subclavian artery and
brachiocephalic vein, and brachial plexus. The signs and symptoms may
include:
1) Atrophy of muscles of the hand and arm on the involved side
2) Shoulder pain
3) Vascular compression leading to edema of the involved extremity
4) Horner syndrome – ptosis, miosis, hemianhidrosis, and enophthalmos
due to compression of sympathetic ganglia
d. Paraneoplastic syndromes occur in up to 10% of primary lung cancers.

Tumor cell derived hormones include:
1) Cushing Syndrome due to ACTH secreted by small cell carcinomas.
2) Hyponatremia due to ADH secreted by small cell carcinomas.
3) Hypercalcemia due PTH-like substances (PTH, cytokines, PGE)

secreted by squamous cell carcinomas.
4) Carcinoid syndrome due to serotonin and bradykinin secreted primarily

by carcinoid tumors.
Page 105 of 177
B. General Pathologic Features
1. Respiratory epithelium gives rise to 99% of primary lung cancers.
2. Approximately 75% of lung tumors arise in the hilar area from the first to third
order bronchi. More peripheral lesions arise from terminal bronchioles and
alveoli. Patterns of growth include:
a. Intraluminal to cause obstruction
b. Penetration of the bronchial wall with invasion of the pulmonary

parencyma
1) Grow along (near) peribronchial tissue
2) Produce an intra-parenchymal mass
c. Mixed growth pattern may be seen.
3. Lung tumors tend to have a gray-white appearance with areas of hemorrhage

and necrosis that can lead to cavitation.
a. Peripheral tumors often pucker the pleural surface.
b. Tumor may penetrate the pleura and extend into the chest wall or into the
heart, trachea, esophagus, or aorta.
c. Metastasis to the bronchial nodes is common.
d. Distant metastases involve adrenal glands, liver, brain, and bone
4. Lung carcinomas are clinically classified as either a small cell

(neuroendocrine) or non-small cell carcinomas (SCLC and NSCLC). As a
group, they are often referred to as bronchogenic carcinomas.
a. The TNM system is used for patient staging.
b. Most common histologic types associated with smoking are squamous cell
carcinoma and small cell carcinoma (highest association).
5. Non-small cell carcinomas are further divided into the following histologic
types:
a. Squamous cell carcinomas represent 25-30% of cases
b. Adenocarcinoma represent 30-40% of cases

1) Bronchioalveolar carcinoma is a special subtype
c. Large cell carcinoma represents 10-15% of cases
d. Mixed tumors are also noted
Page 106 of 177

6. Neuroendocrine carcinomas are classified on the basis of their differentiation.
These include:
a. Carcinoids well differentiated neuroendocrine carcinoma
b. Atypical carcinoid moderately differentiated neuroendocrine carcinoma
c. Small cell carcinoma poorly differentiated neuroendocrine carcinoma
d. Large cell neuroendocrine carcinoma
C. Squamous Cell Carcinoma

1. Squamous cell carcinoma represents up to 30% of primary lung tumors. It is
common in smokers and in males.
2. It most commonly occurs in the central (hilar) region due to its origin in major
bronchi. Chest X-ray often shows hilar or mediastinal shadow.
3. Premalignant changes (squamous metaplasia, dysplasia, carcinoma in-situ)

and invasive carcinoma are often seen in association with the tumor. This
implies that they arise from the basal cells of the respiratory epithelium.
Support for this comes from immunohistochemical stains.
4. Squamous cell carcinomas are grossly characterized by bulky, hard tumors

that cause bronchial obstruction and secondary obstructive pneumonia.
a. They are often exhibit extensive hemorrhage, necrosis and cavitation.
5. Classic squamous cell carcinoma is characterized by large polygonal cells

with a tendency to stratify with large hyperchromatic nuclei showing evidence
of squamous differentiation (keratinization of cytoplasm, intercellular bridges,
and formation of squamous pearls).
a. Poorly differentiated squamous cell carcinomas lack squamous pearls and
only a few cells will exhibit cytoplasmic keratinization. We use
immunohistochemical stains to help prove its differentiation.
D. Adenocarcinoma
1. At 40%, adenocarcinoma represents the most common bronchogenic
carcinoma in the United States.
a. They are associated with smoking history, but to a lesser extent than
squamous cell and small cell carcinoma. They are the most common type
of lung cancer in women and non-smokers.
2. Adenocarcinomas commonly arise subpleurally, can arise in small bronchi

and central airways. Atypical alveolar adenomatous hyperplasia serves as a
premalignant precursor.
3. Most common symptoms include pleural effusion and chest pain. Often
discovered incidentally on routine chest X-rays as an area of density in the
periphery of the lung.
4. Grossly, they tend to be well-circumscribed, gray, firm masses, often

associated with scarring of the pleura.
Page 107 of 177
5. Histologically characterized by the formation of acinar or glandular spaces
lined by atypical epithelial cells that may be mucin-secreting. May also form
papillary structures.
6. Five year survival is 27% overall, but is highly dependent on stage at the time
of diagnosis. Prognosis is worse for the less differentiated variants.
7. Bronchioloalveolar Carcinoma (BAC)

a. A special and distinctive variant of adenocarcinoma that accounts for up to
9% of all bronchogenic carcinomas. These tumors arise from small
airways beyond the last cartilage-containing bronchus. Their appearance
on imaging studies is very similar to pneumonia.
b. They are histologically characterized by a monolayer proliferation of

neoplastic cells that grow along the alveolar walls (lepidic growth pattern).
1) They resemble the normal lung but in which the airspaces are lined by
very well-differentiated tumor cells. They do not invade and destroy the
lung parenchyma nor do they distort the underlying architecture. There
is no desmoplastic response.
2) There are two histologic types: 1) alveolar lining is made up of small

cells with large nuclei reminiscent of type-II alveolar pneumocytes; and
2) lining is made up of tall, columnar mucin-secreting cells.
c. Atypical alveolar adenomatous hyperplasia serves as a premalignant

lesion that can give rise to a BAC. The tumors arise from a multipotent
cell, the bronchioalveolar stem cells, that have been identified at the
bronchioalveolar junction.
d. BACs spread through the lung via air passages and can resemble grossly
lobar pneumonia, or they can be solitary and well-circumscribed and
amenable to resection. Bilateral and multifocal lesions are also frequently
seen in these lesions.
e. Prognosis depends on whether the tumor is well-circumscribed and

solitary or multifocal and diffuse. The solitary lesions are associated with
an excellent prognosis when completely resected; the diffuse or multifocal
lesions are associated with a poor prognosis similar to conventional
adenocarcinoma.
8. Histology is helping to individualize therapy. Women with no history of

smoking who have an adenocarcinoma with specific mutations of their EGFR
(epidermal growth factor receptor) are reported to respond to treatment with
drugs that block the tyrosine kinase activity of the EGFR. A concurrent
mutation of KRAS has been reported to result in resistance to this type of
treatment.
Page 108 of 177

E. Large cell Carcinoma
1. Large cell carcinomas represent up to 15% of bronchogenic carcinomas, and
is a diagnosis of exclusion.
2. They are undifferentiated non-small cell carcinomas that lack squamous or

glandular differentiation. They contain sheets or nests of large malignant
cells with vesicular nuclei and prominent nucleoli.
3. The tumors can occur anywhere in the lung and are often associated with
early metastases and invasion of the pleura and chest wall. Their clinical
behavior is very aggressive with early mortality.
F. Small Cell Carcinoma (Poorly Differentiated Neuroendocrine Carcinoma)

1. Small cell carcinomas are neuroendocrine tumors that arise from the
neuroendocrine cells (Kulchitsky cells) that are scattered throughout the
respiratory epithelium.
2. These highly malignant tumors account for up to 25% of all bronchogenic

carcinomas. Less than 1% occur in non-smokers. Commonly associated with
ectopic hormone production.
3. They tend to arise in lobar or mainstem bronchi. On gross examination, they

are soft, gray-white tumors with extensive necrosis and frequent early spread
to regional lymph nodes.
4. Histologically, small cell carcinomas are characterized by proliferation of

small, primitive-appearing cells with scant cytoplasm and dense chromatin;
tumor cells are approximately 2-3 times the size of a small lymphocyte.
Tumor cells may histologically resemble malignant lymphocytes. An older
term for SCLC is “oat-cell” carcinoma due to small size of the cells compared
with other forms of bronchogenic carcinoma.
5. Small cell carcinomas are associated with very poor prognosis. Very good
initial response to radiation/chemotherapy, but in most cases the tumor is
disseminated at the time of diagnosis.
G. Carcinoid Tumors (Well Differentiated Neuroendocrine Carcinoma)

1. Carcinoids usually arise as a polypoid endobronchial mass. Patients are
most often non-smokers and younger than 40 years of age. Patients may
present clinically with hemoptysis.
2. Carcinoids are thought to arise from Kulchitsky cells and are closely related to
small cell carcinoma (well-differentiated variant).
3. Histologically, these tumors are characterized by their striking “endocrine”

growth pattern (nests, ribbons and festoons) composed of monotonous tumor
cells with scattered chromatin and abundant cytoplasm. They are sub
classified into “typical” & “atypical” on the basis of mitoses and necrosis.
Page 109 of 177
4. Their clinical behavior is much better than bronchogenic carcinoma. Only 15-
25% metastasize; the majority are cured by resection.
H. Hamartoma
1. Relative uncommon benign tumors containing varying amounts of
mesenchymal tissue in varying proportions, including hyaline cartilage,
adipose tissue, smooth muscle, and connective tissue that entrap respiratory
epithelium.
2. Usually found incidentally in asymptomatic patients. Radiologic studies may

demonstrate an isolated lesion; up to 14% as a “coin lesion”. Their clinical
significance is the differential diagnosis of a malignancy based on imaging
studies.
III. METASTATIC PULMONARY CANCER

A. General Features
1. The lung is the most common visceral site of metastases from other internal
organ malignancies. Thus, metastases represent the most common lung
tumors.
a. Some malignancies, e.g. breast and hepatocarcinomas, may invade the
lungs by direct extension.
2. Metastatic cancer is usually peripheral and multicentric. Most common form of

presentation is to find multiple bilateral subpleural nodules.
3. Lymphangitis carcinomatosa is a distinctive pattern of infiltration in which the

carcinoma follows the pulmonary lymphatics causing diffuse interstitial
edema. It originates from a primary carcinoma at another site, especially
those of breast and stomach. It also may arise from primary bronchogenic
carcinoma.
Page 110 of 177

Lung Cancer: Diagnosis & Treatment
Time: 9:30 AM
Objectives: by the end of this lecture and the associated small group case studies,
1. Accurately recognize the appropriate risk factors, including the epidemiology and
demographics of cigarette smoking, for lung cancer when given a patient’s
clinical history.
2. Given a clinical vignette, accurately recognize the common symptoms of lung
cancer.
3. Given a clinical vignette, accurately recognize the common symptoms of
associated with a paraneoplastic syndrome associated with lung cancer.
lung cancer.
5. Given the results of clinical and pathologic findings, accurately assess the stage of
small cell and non-small cell lung cancer.
6. Contrast the staging system used in small cell lung cancer to the staging system
used in non-small cell lung cancer.
7. Compare the treatment of limited and extensive stage small cell lung cancer.
8. Compare the treatment of non-small cell lung cancer stages I, II, IIIA, IIIB, and
IV.
9. Determine patient eligibility for lung resection based on pulmonary function tests,
quantitative ventilation perfusion tests, and pulmonary exercise tests.
10. List and define the common palliative techniques used in advanced lung cancer.
11. Recommend a diagnostic approach for solitary pulmonary nodules based on lung
cancer risk factor analysis.
Required Reading: Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter

85: Neoplasms of the lung; John D. Minna and Joan H. Schiller
A. Epidemiology:
1. 215,000 new cases per year
2. 162,000 deaths per year
3. currently the #1 cause of cancer deaths in both men and women
4. racial differences in incidence exist
5. incidence increases with age
B. Etiology:
1. tobacco smoke - 87% (90% of cases in men and 79% of cases in women)
a) risk of cancer correlates with age of smoking onset, number of cigarettes
smoked per day and duration of smoking
(1) "pack-year" = (# packs smoked per day) x (# years smoked)
b) currently 18.1% women and 23.9% of men smoke
Page 111 of 177

c) 80% of smokers start before age 18
d) for life-time heavy smokers, some studies indicate that as many as 30% of
men and 15% of women will develop lung cancer if they live long enough
2. asbestos - 5%
a) asbestos exposure without cigarette smoking = 6-fold risk
b) cigarette smoking without asbestos exposure = 11-fold risk
c) cigarette smoking with asbestos exposure = 59-fold risk
3. radon - 2%
4. environmental tobacco smoke - 1%
5. other minor risk factors:
a) arsenic
b) BCME & CMME (chloromethyl ethers)
c) chromium
d) mustard gas
e) nickel
f) vinyl chloride
g) genetic (family history of lung cancer)
C. Classification:
1. small cell
2. non-small cell
a) adenocarcinoma
b) squamous cell carcinoma
c) large cell carcinoma
d) bronchoalveolar carcinoma
D. Clinical Manifestations:
1. Common signs & symptoms:
a) anorexia
b) cough
c) chest pain
d) dyspnea
e) hemoptysis
f) supraclavicular node enlargement
g) bone pain
h) neurologic manifestations
i) hoarseness (left recurrent laryngeal nerve involvement)
j) post-obstructive pneumonia
k) ** 5-15% asymptomatic at the time of diagnosis**
2. Paraneoplastic syndromes (occur in 10% of patients):
a) clubbing and hypertrophic pulmonary osteoarthropathy
b) thrombophlebitis
c) hypercalcemia
d) hyponatremia
e) peripheral neuropathy
f) Lambert-Eaton syndrome (myasthenia gravis-like condition with
neuromuscular weakness)
E. Diagnostic Approach:
1. Radiography
a) screening chest x-rays not cost-effective and do not affect overall mortality;
however, new preliminary studies suggest that CT scans of the lungs MAY
be useful for screening - routine use must await results of more clinical
Page 112 of 177

research; currently, screening is not recommended by major professional
organizations
b) chest x-ray is overall 70-88% accurate in overall detection of lung cancer
when patients have symptoms
(1) 61-71% accurate for hilar nodes
(2) 47-60% accurate for mediastinal nodes
c) chest CT permits identification of enlarged lymph nodes, adrenal masses, and
liver metastases involving the superior portion of the liver
(1) lymph nodes and adrenal masses can be benign and if the patient is
otherwise and operative candidate, nodes and/or the adrenal glands
should always be biopsied if they appear to be abnormal by CT
2. Sputum Cytology
a) diagnostic in less than 20% of all patients with lung cancer
(1) positive in less than 5% of patients with peripheral cancers
(2) false positives do occur
b) screening with sputum cytology detects cancer earlier but due to lead time
bias, there is no survival benefit
3. Bronchoscopy
a) solitary pulmonary nodules by x-ray but not visible within the airway
(1) yield 10% if nodule is < 2 cm
(2) yield 40-50% if nodule is >2-4 cm
b) overall diagnostic accuracy for bronchoscopically visible lesions = 94%
4. Trans-Thoracic (CT-guided) Needle Aspirate
a) diagnostic yield is 43-97% if radiographically visible
5. Mediastinoscopy - often useful in establishing a diagnosis of cancer if disease is
limited to the mediastinum; also sometimes useful to provide staging of the
mediastinal lymph nodes
6. Thoracoscopy (rigid scope inserted through small chest incision)
a) can use as an initial procedure to be followed by formal thoracotomy if
necessary
b) average hospital stay for thorascopy only = 2.5 days
7. Thoracotomy (large incision permitting surgeon to get his/her hand into the chest)
F. Staging System:
1. small cell lung cancer: it is controversial whether to use the TNM system or the
limited/extensive system (most physicians use the limite/extensive system):
a) limited stage: confined to the hemithorax, mediastinum, & ipsilateral
supraclavicular lymph nodes
b) extensive stage: any distant metastasis outside of above locations
2. non-small cell lung cancer: use the TNM system for classification
a) definitions (Harrison’s, Table 75-3):
(1) Tumor (T) - based on size and location
(2) Lymph nodes (N) - based on presence and location
(3) Distant metastasis (M) - either present or absent
(b) overall 5-year survival = 14%
(c) survival correlates with stage: the lower the stage, the higher the likelihood of
cure and long term survival
(d) unfortunately, most lung cancer is diagnosed at a surgically unresectable
stage
(e) general approach – must be tailored to each individual patient
(1) history and physical examination
Page 113 of 177

(2) basic laboratory tests (CBC, chemistry profile, liver enzymes,
calcium)
(3) chest CT scan
(4) PET (positron emission tomography) scan – at many centers has
become a standard part of staging, after CT scan
(5) biopsy of any suspicious abnormalities detected by any of the above
G. Treatment:
1. small cell lung cancer -
a) limited stage - chemotherapy + radiation therapy
b) extensive stage - chemotherapy
2. non-small cell lung cancer -
a) stage I & II - surgery ("never miss an opportunity to operate on a surgically
curable lung cancer"). For patients with stage IB, IIA, and IIB, adjuvant
chemotherapy following surgery will improve long-term survival rates.
Adjuvant chemotherapy is not presently used in stage IA non-small cell
lung cancer.
(1) PFT assessment of lung function prior to surgery
(a) FEV1 > 2 L or > 60% predicted - predicts successful
pneumonectomy (removal of an entire left or right lung)
(b) DLCO > 60% predicted - predicts successful
pneumonectomy
(c) PCO2 > 45 – associated with worse outcomes
(2) V/Q assessment of lung function
(a) FEV1 x % perfusion to the lung that will remain after
pneumonectomy
(b) > 40% predicted predicts successful pneumonectomy
(3) exercise assessment of lung function
(a) maximum oxygen consumption > 20 ml/kg/min - predicts
low complication rate & low death rate
(b) maximum oxygen consumption between 10-20 ml/kg/min -
predicts increased complication rate
(c) maximum oxygen consumption < 10 ml/kg/min - predicts
increased death rate
b) stage IIIA – chemoradiotherapy with re-staging after treatment for evaluation
for possible surgery; Some IIIA tumors can be treated with an initial
attempt at surgery followed by adjuvant chemotherapy with or without
radiation therapy.
c) stage IIIB - chemoradiotherapy
d) stage IV - chemotherapy (marginally effective [adds an average of 6-8 weeks
of life] but not curative)
3. palliative treatment of lung cancer
a) external beam radiation therapy
b) endobronchial brachytherapy (high dose intrabronchial radiation therapy)
c) endobronchial stents (metal sleeve-like devices that prop open obstructed
airways)
d) endobronchial laser therapy
e) endobronchial cryotherapy (bronchoscopic destruction of tumor with a probe
that freezes tissue to -40 degrees)
f) endobronchial argon plasma coagulation (bronchoscopic destruction of tumor
using high voltage electricity to burn tumor)
Page 114 of 177

g) endobronchial photodynamic therapy (bronchoscopic destruction of tumor
using bright white light after injecting a patient with a photosynsitizing
agent that is preferentially taken up by cancer cells)
h) pleurodesis
H. The Solitary Pulmonary Nodule:
a) smallest lesion detectable with chest x-ray is 2-3 mm
b) 2-13% of those found by plan chest x-ray are malignant
c) 50-60% of those found by plain chest x-ray are benign
(1) 40-50% granulomas (rate depends on patient's geographic location - there is a
high incidence of histoplasmosis-induced benign granulomas in Ohio
(2) 5-10% benign tumors (adenomas, carcinoid tumors, hamartomas)
(3) chest CT is far more sensitive for nodules and often finds nodules not visible
on plain chest x-ray; a much higher percentage of these small nodules are
benign however, they still must be followed radiographically or biopsied
to fully exclude early cancer
d) benign calcium patterns (often better visualized with CT than plain chest x-rays):
(1) laminated
(2) diffuse
(3) central
(4) note: eccentric or speckled can be seen with malignant or benign
(a) 13% of bronchogenic cancers have CT evidence of calcification
(eccentric or speckled)
e) malignant nodules have a doubling time of 21 - 400 days
(1) a lesion which is unchanged in size for ≥ 2 years is usually benign
(2) a commonly employed strategy is to follow small nodules with serial chest
CT scans for 2 years to determine if they are likely to be benign.
f) indicators of malignancy:
(1) size
(a) 0.2% malignant if < 3 mm
(b) 0.9% malignant if 4-7 mm
(c) 18% malignant if 8-20 mm
(d) 50% malignant if > 20 mm
(2) age
(a) 3% malignant in 35-39 years old
(b) 15% malignant in 40-49 years old
(c) 43% malignant in 50-59 years old
(d) 50% malignant in > 60 years old
(3) smoking
(4) history of cancer
(5) PET scans (positron emission tomography) is a nuclear medicine test that can
differentiate benign from malignant nodules in many patients
(Standardized Uptake Value [SUV] of > 2.5 is highly suspicious for
cancer). PET is only sensitive for tumors > 8 mm in diameter
g) clinical approach to the solitary pulmonary nodule:
(1) if available compare to old x-rays (preferably > 2 years old)
(2) if old x-rays unavailable, obtain chest CT scan
(a) if very low risk of cancer after CT
- nodules < 4 mm – follow up imaging is optional
- nodules 4-6 mm – follow up CT in 12 months
- nodules 6-8 mm – follow up CT in 6-12 months
(b) if moderate risk of cancer after CT – perform PET scan
Page 115 of 177

- if PET is positive – resect
- if PET is negative – serial CT scans at least at:
3 months
6 months
12 months
24 months
(c) if high risk of cancer after CT – biopsy the nodule
- if biopsy positive – resect
- if biopsy negative – serial CT scans at least at:
3 months
6 months
12 months
24 months
Page 116 of 177

Interstitial and Occupational Lung Disease
Time: 11:00 – 11:50
1. Describe the pathogenesis of diffuse interstitial pulmonary diseases relative to the
cell types and their products.
2. Recognize the morphologic features that distinguish diffuse interstitial lung disease
fibrosis from sarcoidosis and occupational lung diseases.
3. Recognize the major morphologic features of the following disorders and correlate
them with their etiology, clinical signs and pathogenesis.
a. Coal Workers’ pneumoconiosis
b. Silicosis
c. Asbestosis-related diseases
Learning Resources
I. DIFFUSE INTERSTITIAL LUNG DISEASES (ILD)

A. General Features
1. There are many occupational respiratory diseases that involve every
component of the upper and lower respiratory system. We will focus on but a
few.
2. Patients present with dyspnea, tachypnea, and cyanosis.
3. Restrictive pulmonary function testing demonstrates decreased lung volumes,

and decreased CO diffusing capacity and compliance.
4. Imaging studies show a number of findings ranging from diffuse small

nodules, irregular lines or ground glass appearance to calcified nodules or
consolidation.
5. Long term disease leads to secondary pulmonary hypertension, right-sided

heart failure (cor pulmonale).
Page 117 of 177

6. Diffuse, chronic involvement of pulmonary connective tissue – predominantly
the interstitium of the alveolar septal walls.
7. Most common examples of ILD include:

a. Environmental/occupational exposures (25%): asbestos, silica, fumes,
gases
b. Sarcoidosis (20%)
c. Idiopathic Pulmonary Fibrosis, IPF (15%)
d. Collagen vascular diseases (10%): rheumatoid arthritis, systemic lupus
erythematosus, scleroderma, and others
B. Pathogenesis
1. Accounts for about 15% of noninfectious pulmonary disorders.
2. Histologic features include scarring with destruction of normal lung
parenchyma, which in the advanced stage is termed end-stage lung or
honeycomb lung.
a. Recall that the alveolar walls consist of basement membranes, collagen
and elastic fibers, proteoglycans, fibroblasts and few lymphocytes,
monocytes and mast cells.
b. Alveolitis is a common early finding regardless of the etiology. This

involves increased inflammatory cells (PMNs, lymphocytes, eosinophils) in
the alveolar walls and spaces. The inflammation may resolve or result in
parenchymal destruction and chronic interstitial fibrosis.
c. Direct toxic insult, inhaled dusts, blood-borne toxins, and unknown

antigens stimulate alveolar macrophages which in turn activate cells of
both the innate and adaptive immune response. These cells synthesize
and secrete IL-8 and LTB4 that are strong chemotactic agents for PMNs.
The macrophages and the PMNs release proteases and reactive oxygen
species that damage the normal pulmonary parenchyma.
d. Destruction of the type I pneumocytes leads to proliferation of type II

pneumocytes.
e. Chronic stimulation of the alveolar macrophages is associated with

release of FGF, PDGF, and TGF-β that stimulate fibrosis by attracting and
activating fibroblasts. Alveoli are replaced by cystic spaces separated by
thick bands of connective tissue. Vascular shunting occurs over time
II. PNEUMOCONIOSES
A. General Features
1. Occupational lung disorders affecting the pulmonary interstitium are mainly
pneumoconiosis (dust diseases) and hypersensitivity pneumonitis.
2. Pneumonoconioses are non-neoplastic lung reactions to organic/inorganic

particulates, chemical fumes and vapors. Although the diseases are
Page 118 of 177

declining, even in developed countries they remain common. Examples
include:
a. Coal – Anthracosis e. Tin - Stannosis
b. Silica – Silicosis f. Barium - Baritosis
c. Asbestos – Asbestosis g. Beryllium – Berylliosis
d. Iron – Siderosis
3. Air pollution (particulates) in urban centers cause increased morbidity

(asthma incidence) and mortality.
4. Occupational ILD’s result from inhaling and retaining dusts that induce
inflammation & fibrosis.
5. Only a subset of exposed persons develops disease suggesting a genetic

susceptibility component to the disease.
B. Particles and the Pathogenesis of Pneumoconiosis

1. The pathogenesis of pneumoconiosis is dependent upon the amount of dust
retained in the lung and airways.
2. The size and shape (buoyancy) of the particles is an important factor.

a. Particles of 1-5 μm are the most dangerous because they can reach the
terminal small air spaces.
b. Particles 5 -10 μm are too large to reach the distal airways.
c. Particles <0.5 μm are small enough to freely move in and out of the
airways without causing damage.
3. Particles may interact directly with interstitial cells (macrophages or

fibroblasts). If they have Fe on their surface they may stimulate oxygen free
radical formation via the Fenton reaction and thus cell injury that will result in
an inflammatory response. They may reach the lymphatics (directly or
indirectly if carried there by macrophages) and initiate an immune response.
Particles may enter the blood and there may be a systemic response.
4. Smoking may have an additive effect.
C. Coal Workers’ Pneumoconiosis (CWP)

1. CWP is a parenchymal lung disease caused by inhalation of coal mine dust,
and has been referred to black lung.
a. Risk for CWP increases with the dust level, cumulative exposure,
hardness of the coal.
b. Silica present in coal dust also contributes to the damage.
Page 119 of 177

2. Simple CWP
a. Small macules (coal nodules), < 1 cm, containing carbon-laden
macrophages in a fine network of collagen fibers.
b. They are located near respiratory bronchioles of the upper lobes or upper
zones of the lower lobes. The macule may extend to the alveoli, may show
fibrosis, and the distortion of the alveoli may lead to centrilobular
emphysema.
c. Simple CWP lacks specific clinical manifestations and is often
asymptomatic.
3. Complicated CWP (Progressive Massive Fibrosis or PMF) is characterized by

many nodules that are at least 1 cm in diameter by radiographs, or are at
least 2 cm on gross examination.
a. The coal nodules are composed of dense collagen, pigment, and the
center is usually necrotic. These lesions also disrupt lung architecture.
b. PMF clinically presents with progressive dyspnea, pulmonary

hypertension, and respiratory failure. Both obstructive and restrictive
physiology may be present (many patients also smoke).
c. Caplan’s Syndrome - is inflammation and scarring of the lungs in people

with rheumatoid arthritis who have been exposed to coal dust. It is
uncommon in the US. There may be multiple nodules that can be quite
large.
4. Anthracosis – inhaled carbon pigment in the lungs and hilar lymph nodes. It is
a very common autopsy finding in miners, urban city residents, tobacco users.
Not a disease per se, patients are asymptomatic.
D. Silicosis
1. Silica is a major component of rock and sand. It exists in both crystalline and
amorphous forms.
a. The crystalline forms include quartz, crystobalite and tridymite. Of these,
quartz is the most important form.
b. Amorphous silica includes talc, vermiculite and mica. Although these

forms of silica are much less biologically active, heavy exposure can
cause lesions in the lungs.
c. Exposure to silica occurs in miners, sandblasters, stone carvers, workers

in foundries, tunnels, quarries, and silica flour production occupations. It is
considered the most prevalent chronic occupational lung disease in the
world.
2. After inhalation, silica particles interact with alveolar epithelial cells and
macrophages to cause injury, release mediators and cause fibrosis.
Page 120 of 177

a. In the early stages, lesions are discrete nodules, often in the upper lobes.
b. In chronic silicosis, multiple nodules form both in the lungs and in the hilar
lymph nodes.
c. The nodules may form hard, collagenous scars; calcium may be

deposited, often in layers, giving an “eggshell” appearance. Some nodules
may undergo central softening and cavitation.
d. Progressive massive fibrosis (PMF) results from coalescence of the

lesions. At this point there is extensive fibrosis and lung function is
compromised.
3. There are 3 clinical forms recognized, acute, accelerated and chronic

silicosis. The differences in these forms are usually related to the intensity
(dose) of the exposure.
a. With progressive disease patients, will have increasing dyspnea; at first
the symptoms occur with exertion, but later on the symptoms will occur
even while at rest.
b. Persons with silicosis are at increased risk for fungal infections

(cryptococcosis, blastomycosis and coccidioidomycosis).
c. Silicosis is associated with an increased susceptibility to TB or other

mycobacterial infections.
d. There is no treatment for silicosis. Prevention is the best way to address

this disorder. The prognosis for patients with silicosis is not good (5-8
years) and depends on the amount of fibrosis present.
E. Asbestosis
1. Asbestos is a family of crystalline hydrated silicates that form fibers.
a. There are 2 geometric forms of asbestos: serpentine (curly and flexible
fibers) and amphibole (straight, stiff and brittle fibers).
b. Although the serpentine chrysotile fiber is the most common fiber found in
the environment, the amphiboles (crocidolite, amosite, tremolite,
anthopyhllite and actinolyte) are more pathogenic in terms of association
with mesotheliomas.
c. Again the key factors for pneumoconiosis are fiber size, shape,
concentration and solubility in the pathogenesis of disease.
d. Asbestos is found in mining and milling operations, in insulation for ships

or buildings, in the manufacturing of brake linings and clutch facings, in
cement, textiles and some fireproofing products.
Page 121 of 177

2. The inhaled fibers are deposited in the small airways and alveoli where they
are incompletely ingested by the alveolar macrophages.
a. Macrophages will coat the fiber with iron and this causes the fibers to be
visible under the microscope (ferruginous bodies).
b. The activation of the macrophages leads to the release of a number of

inflammatory mediators that, over time, will cause scarring (fibrosis).
3. Diffuse interstitial fibrosis is a hallmark feature of asbestosis. The fibrosis

begins around the respiratory bronchioles and alveolar ducts, usually in the
subpleural areas of the lower lobes (contrast this to silicosis!).
a. Eventually all lobes can be involved though. Asbestos bodies may be
found in the parenchymal lesions.
b. In addition, there is a thickening of the pleural surfaces and this can bind
the lung to the chest wall. Pleural plaques are the most common
manifestation of asbestos exposure.
c. The scarring can also involve the pulmonary vessels leading to pulmonary
hypertension. They consist of well-circumscribed areas of dense collagen
that often contain calcium. They do not usually contain asbestos bodies.
d. There is a considerable latency period, of at least 10 years, between the

exposure and the development of clinical disease. (20 years is most
common). Pleural plaques are usually asymptomatic but may be detected
on chest x-rays.
4. The clinical symptoms of asbestosis are similar to other diffuse interstitial lung
diseases.
a. Dyspnea is usually the first symptom, at first it occurs with exertion, but
later it occurs at rest.
b. The disease may remain stable or it can progress to congestive heart

failure, right-sided heart failure and death. Similar to silicosis there is no
treatment for asbestosis.
c. Workers diagnosed with asbestosis should be removed from further

asbestos exposure and should be counseled to eliminate any other factor
that can cause lung disease (e.g. quit smoking).
5. Occupational exposure to asbestos is linked to bronchogenic carcinoma,

mesotheliomas, and cancers of other sites (larynx, colon, retroperitoneum).
a. Asbestos is both a tumor initiator and tumor promoter.
b. The risk of bronchogenic cancer in asbestos workers is increased about 5

times over persons not exposed to asbestos. If an asbestos worker also
smokes, then the risk of bronchogenic cancer is even greater (estimated
Page 122 of 177

55-fold increased risk).
c. The relative risk of mesotheliomas, in asbestos workers is about 1000 fold

higher than the risk in persons not exposed to asbestos (baseline risk for
mesotheliomas is 2-17 cases per 1 million persons).
III. DIFFUSE INTERSTITIAL FIBROSES

A. Idiopathic Pulmonary Fibrosis (IPF)
1. IPF, old term is Usual Interstitial Pneumonia (UIP), tends to occur more often
in men than women and in patients over 50 years of age. Patients complain of
a slowly progressive, non-productive cough and dyspnea. Clubbing may be
seen.
a. Radiologic studies (HRT) show a patchy, subpleural reticular pattern with
subpleural cysts seen in latter stages.
2. Because the disease process involves the periphery of the lung, a surgical
biopsy – VATS – is needed
a. The disease process is patchy with abrupt transitions between normal
alveolar parenchyma to dense remodeled lung. Fibroblastic foci are seen
in the walls, not in the airspaces, at the transition between these two
areas.
b. Microscopic cysts, containing mucus and/or inflammatory cells, are noted

beneath the pleura. The interstitial mononuclear cell infiltrate is mild.
B. Nonspecific Interstitial Pneumonia (NSIP)

1. NSIP refers to a diffuse patchy interstitial pneumonia of unknown etiology.
Patients present with a complaint of a progressive cough and dyspnea.
a. The disease process involves all of the lobes to varying degrees, usually
<40%. Radiologic studies are variable and nonspecific.
2. The histologic pattern is that of a patchy, mild to moderate, uniform interstitial

lymphoplasmacytic infiltrate. When fibrosis occurs late in the disease process
it is generally mild with little or no architectural destruction or honeycombing.
C. Organizing Pneumonia
1. Lung injury often leads to airspace organization. Patients often present with
a nonproductive cough and dyspnea, and radiologic studies show patchy
airspace consolidation.
a. The etiology is highly variable or unknown (cryptogenic).
2. The histologic pattern is that of aggregates of loose fibroblasts in an immature

collagen matrix (myxoid-like) within the alveoli and bronchioles, and a
mononuclear cell infiltrate in the interstitium. The normal architecture of the
lung is maintained.
Page 123 of 177

IV. GRANULOMATOUS DISEASES
A. Sarcoidosis
1. Sarcoidosis is a systemic disease, which in the lungs has a clinical picture of
restrictive lung disease and hilar lymphadenopathy seen in up to 90% of
cases.
2. Highest incidence is among Scandinavians and African-Americans, 40 years-

of age or younger, and without a history of smoking.
3. The pathogenesis involves a type IV hypersensitivity reaction to one or more

antigens that remain unknown.
4. The microscopic examination reveals prominent, non-necrotizing granulomas

with immune type giant cells that may contain asteroid bodies and
Schaumann bodies.
a. The granulomas within the pulmonary interstitium are often fused and
associated within the pleura and around venules and bronchioles.
Interstitial fibrosis is seen in up to 15% of cases.
b. Increased CD4 (+) TH1 cells are seen in BAL samples.
B. Hypersensitivity Pneumonitis (Allergic Alveolitis)

1. Involves both Type III and Type IV hypersensitivity reactions to inhaled
extrinsic antigen, most commonly job related exposure.
a. The immune response occurs at the level of the alveoli.
2. The clinical picture is one of a restrictive process.
3. The microscopic features include a patchy, mononuclear cell infiltrate in the

interstitium, primarily around the bronchioles. Non-necrotizing, poorly formed,
granulomas are seen in up to 2/3 of cases.
a. Chronic exposure can lead to interstitial fibrosis.
Page 124 of 177

Immunologic and Rheumatologic Lung Disease
Date: September 22th, 2008

Time: 8:30AM
Faculty: Jeffrey Weiland, MD
Optional Reading: Harrison’s Principles of Internal Medicine 17th Edition (2008),

Chapters 313, 314, 316, 317, 319
Objectives:
1. List the 6 pulmonary manifestations of Rheumatoid Arthritis.
Be able to differentiate Bronchiolitis Obliterans from BOOP, clinically and
radiographically.
2. List the 6 pulmonary manifestations of Systemic Lupus Erythematosus.

Know which are more common and how they are treated.
3. Describe the clinical features of Goodpasture’s syndrome and Wegener’s

granulomatosis.
How do these syndromes differ in pathophysiology, clinical presentation and
treatment.
Outline:
I. Overview
a. These diseases encompass a broad spectrum of conditions where the
immune mediated injury is directed at either the interstitium( space
between alveolar epithelium and vascular endothelium) or the vascular
endothelium itself.
b. With certain exceptions that will be noted, the link between the
immunologic derangement and the tissue injury is poorly understood.
c. Symptoms are non-specific (cough, dyspnea).
d. Chest X-rays and pulmonary function tests, while very useful in assessing
response to therapy, are not particularly helpful in diagnosis.
Therefore
e. The astute young physician must be adept at gleaning important historical

clues and physical findings that suggest environmental exposures or the
presence of other systemic diseases.
Page 125 of 177

II. Diseases Associated with Systemic Rheumatic Disorders
a. Rheumatoid Arthritis
i. Interstitial Pulmonary Fibrosis
1. Male predominant
2. Associated with HLA B8 and HLA Dw3
3. Histology similar to UIP but usually indolent course
4. Cough dyspnea, restricted PFT’s , low diffusion
5. ? Prevalence
6. With progressive disease, always think about drug toxicity
ii. Pleuritis with or without effusion
1. Seen in 50% at autopsy
2. Effusions in only 5% (mainly males)
3. Usually asymptomatic but can present acutely with
pleuritic pain and fever/leukocytosis
4. Pleural fluid is lymphocytic with low glucose
iii. Bronchiectasis
1. Common but usually not symptomatic
2. Distinguished from interstitial fibrosis by volume of
sputum
3. Treated like other airway diseases (bronchdilators,steroids)
iv. Rheumatoid Nodules
1. Rare (<1%)
2. Usually asymptomatic, hemoptysis if cavitate
3. Single or multiple
4. Always have extensor surface nodules elsewhere
5. Caplan’s Syndrome
Bronchiolitis Obliterans Bronchiolitis Obliterans

Organizing Pneumonia
Prevalence Rare More Common
Pathology Bronchiole wall effaced by Lymphocytic infiltration of well
Granulation tissue preserved bronchiolar walls and
interstitium
PFT’s Obstruction Restriction, low DCO
CT Bronchiolitis Multifocal, patchy consolidation
Prognosis Poor Good with corticosteroids
b. Systemic Lupus Erythematosus

i. Acute Lupus Pneumonitis
1. Rare (2%)
2. May be initial manifestation of SLE
3. Acute cough, dyspnea and pleuritic pain
4. Bilateral infiltrates, cardiomegaly and effusions
5. Treatment with high dose steroids but must exclude
infection first
Page 126 of 177

ii. Diffuse Alveolar hemorrhage
1. Similar to acute lupus pneumonitis except bronchoalveolar
lavage fluid is bloody
2. Treatment with steroids but must exclude infection first
iii. Chronic Interstitial Lung Disease
1. Develops in <5%
2. Closely resembles Idiopathic Pulmonary Fibrosis except
more frequent pleuritic pain
3. Treatment with steroids
iv. Pulmonary Hypertension(PHT)
1. Once considered rare, is being reported with increasing
frequency
2. Subclinical PHT found in 10% of SLE patients
3. Frequently associated with Raynaud’s phenomenon so
potential mechanism is vasoconstriction
4. Alternative mechanism might be chronic thromboembolism
a. Antiphospholipid antibodies
5. Vasodilators, anticoagulation and immunosuppressives
have all been advocated for treatment
v. Pleural Disease
1. Most common pulmonary manifestation
a. 20% of patients at onset of disease
b. 50% at some point in their course
2. Asymptomatic or pleuritic pain which may be intractable
3. Fluid is exudates and either neutrophilic(acute) or
lymphocytic(chronic)
4. SLE cell( described here at OSU ) or antinuclear antibody
level in the fluid may be helpful in diagnosis
vi. “Shrinking Lung Syndrome”
1. Exertional dyspnea and orthopnea
2. PFT’s restricted and CXR shows high diaphragms and tiny
lungs
3. Thought to be a myopathy of the diaphragms
4. ? treatment, usually self-limited but can be severe
c. Scleroderma
i. Interstitial Pulmonary fibrosis
1. Found in up to 90% of patients at autopsy
2. Strongly associated with Scl-70 antibody
3. Genetic predisposition (HLA-DR3 and DR52a)
4. May antedate the diagnosis of Systemic Sclerosis
5. Cough, dyspnea and rales
6. Chest pain and clubbing are uncommon
7. PFT’s are restricted with low diffusion
8. Association with Bronchogenic carcinoma
9. ? Treatment
Page 127 of 177

ii. Pulmonary Hypertension
1. Concentric fibrosis of small vessels, plexiform lesions are
absent
2. Associated with CREST syndrome
3. Main symptom is dyspnea
4. CXR, CT and Bronchoalveolar lavage are normal
5. PFT’s reveal isolated reduction in diffusion
6. 2D echo can reveal pulmonary hypertension
iii. Aspiration Pneumonia
1. Due to esophageal dysmotility
d. Polymyositis/Dermatomyositis
i. Pulmonary complications in 40%
1. Non-specific interstitial pneumonitis
2. Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
3. Symptoms are cough and dyspnea
4. PFT’s are restricted with low diffusion
5. CT reveals peripheral reticular densities with patchy
ground glass infiltrates
6. Usually steroid responsive
e. Sjogren’s Syndrome
i. Diffuse lung disease
1. May be present in up to 10% of patients with Sjogren’s
2. Usually clinically silent
3. Pathology most frequently is a lymphocytic interstitial
pneumonia but may be a pseudo lymphoma or frank
lymphoma
ii. Tracheobronchial Disease
1. Xerotrachea in up to 25%
2. Relentless dry cough
3. Inflamed mucosa in trachea and bronchi
4. May respond to steroids
III. Diseases Associated with Pulmonary Vasculitis or Diffuse Alveolar Filling
a. Goodpasture’s Syndrome
i. Typically young men
ii. Present with cough, dyspnea and hemoptysis
1. CXR reveals diffuse alveolar filling
2. Microcytic anemia, hematuria, azotemia
3. May have elevated diffusion capacity on PFT’s
4. Anti-GBM antibodies
5. Close link to smoking
6. Corticosteroids, cytotoxic drugs and plasmapheresis
b. Wegener’s Granulomatosis
i. A systemic vasculitis commonly involving ears or sinuses, lungs,
kidneys and skin (ELKS)
ii. Etiology unknown
Page 128 of 177

iii. Frequency of 1 in 30,000, typically middle age , equal in men and
women
iv. Classic pathology is a “necrotizing granulomatous vasculitis”
although renal biopsies show focal segmental glomerulonephritis
with crescent formation
v. Clinical Manifestations
1. Very broad- average delay in diagnosis is 6-12 months
a. May be fulminant with diffuse alveolar hemorrhage,
renal failure and death in a matter of days
b. More typical is sub acute to chronic complaints of
upper airway problems(sinusitis, otitis)
c. Lung involvement may manifest as cough, pleuritic
pain and hemoptysis or may be an asymptomatic
lung nodule (cavitation is frequent)
d. Skin involvement is typically palpable purpura on
the lower extremities
vi. Diagnosis
1. Gold standard is biopsy of an involved organ…but
2. In the appropriate clinical setting, positive serologist for
Anti-Neutrophil Cytoplasmic Antibodies (c-ANCA) or PR-
3 are acceptable
vii. Treatment
1. Corticosteroids
2. Cytotoxic Drugs (Cyclophosphamide)
Page 129 of 177

Occupational and Inhalational Lung Disease

Time: 9:30 am
Objectives:
1. Describe the common etiologic agents of occupational asthma
2. Given a clinical vignette, accurately recognize the symptoms and describe
means of diagnosis of occupational asthma
3. Describe the pathophysiologic mechanism of carbon monoxide poisoning at
level of the red blood cell
4. Recognize the common environmental settings in which carbon monoxide
poisoning may occur
5. Given a clinical vignette, accurately recognize the symptoms and appropriate
treatment of carbon monoxide poisoning
6. Recognize that drug-induced lung disease has protean and often non-specific
signs, symptoms, radgiographic and pathologic findings
7. Given a clinical vignette, accurately recognize some of the clinical pulmonary
effects of cocaine use
I. Occupational Asthma
a. Most common occupational lung disease
b. Asthma and the workplace
i. Work-aggravated asthma
1. Exacerbated by work: exertion, dusts/fumes/odors,
temperatures
ii. Work-related asthma
1. Variant syndromes such as organic dust exposures, cotton
exposure
2. Eosinophilic bronchitis
a. Chronic cough, sputum eosinophilia, lack of airway
obstruction or bronchial hyperresponsiveness
iii. Occupational asthma
1. 2-15% cases of new adult asthma, over attributable 300
agents identified
2. Without latency
a. Asthma without an “immunologic mechanism”
i. Irritant-induced asthma
ii. Reactive airways dysfunction syndrome
(RADS)
b. 10-15% cases of occupational asthma
3. With latency
Page 130 of 177

a. Asthma with underlying “immunologic mechanism”
i. Occupational asthma
b. 85-90% cases
c. Definition of occupational asthma
i. Variable airflow limitation and airway
hyperresponsiveness
ii. Due to causes/conditions attributable to a
particular occupational environment (dust,
gas, chemical, protein) and not to stimuli
encountered outside the workplace
iii. Without preexisting history of asthma
c. Pathophysiology
i. Non-immunologic (or occupational asthma without latency or
RADS)
1. Irritant effects of agent
2. Symptoms after a single, high level of exposure such as
accidental spill, explosion, exposure in a confined space
3. Mechanism unclear
a. Bronchial mucosa injury, neurogenic and
nonspecific inflammation
b. Regeneration with airway remodeling and chronic
inflammation
c. Non-specific airway hyperresponsiveness
4. Effected occupations and causative agents
a. Chemicals, painting/spraying/fumigating
b. Agents include chlorine, sulfur dioxide, combustion
products, ammonia
ii. Immunologic (or occupational asthma with latency)
1. Agents/occupations
a. Farming, painting, plastics/chemicals
b. Agents
i. Isocyanates most common
ii. Western red cedar (plicatic acid), resins,
colophony, metal salts (platinum), latex,
flour, animal dander
iii. Often exposure to multiple agents
2. Agent acts as an antigen based on molecular weight
a. Most High-molecular weight agent acts as complete
antigen
i. Flour, lab/animal protein, latex
b. Low molecular weight agents
i. Some act as haptens
1. Platinum, trimellitic anhydride
c. Produce IgE antibodies that react with mast cells,
macrophages, eosinophils to produce inflammatory
cascade
Page 131 of 177

d. Others (isocyanates, plicatic acid) do not
consistently induce IgE antibodies and mechanism
unclear
d. Predisposing factors
i. Host factors (genetic) (HLA class II molecules, acetyl transferase,
glutathione s-transferase)
ii. Atopy
iii. Smoking history
iv. Type of agent, level of exposure, duration of exposure
e. Clinical Presentation
i. Latency period where exposed (sensitized) but asymptomatic
ii. Inflammation
iii. Upper airway symptoms (rhinoconjunctivitis)
iv. Dyspnea, wheezing, cough, rhinitis, conjunctivitis symptoms after
exposure
1. Initially, symptoms occur early (within hours) or late (4-6
hours) after exposure
2. Over time, progressive and prolonged symptoms to
exposure
3. Can ultimately develop persistent symptoms after
nonspecific stimuli
f. Diagnosis
i. RADS
1. Appropriate exposure history-massive, high level irritant
exposure
2. Lack of pre-existing asthma
3. Rapid onset of asthma symptoms (usually within 24 hours)
4. Persistence of symptoms and non-specific airway
hyperresponsiveness for at least 3 months after exposure
ii. Occupational asthma
1. Appropriate exposure history, lack of pre-existing asthma
2. Demonstration of airway hyper-responsiveness (asthma)
a. Pulmonary function tests with bronchodilators
b. Methacholine challenge testing
3. Demonstration of relation to work environment/exposure
a. Peak flow monitoring at work/away from work (20-
25% drop at work)
b. Serial methacholine challenge testing (changes in
PC20 over time)
c. Controlled environment challenge testing
4. Immunologic testing
a. Specific IgE antibodies documented by skin prick
reactions, RAST testing. Can also measure IgG
antibodies
b. Indicates prior exposure
Page 132 of 177

g. Prognosis/Treatment
i. Confirm diagnosis and removal from offending agent/environment
ii. Minimize exposure to nonspecific irritants (dusts, smoke, tobacco)
iii. Treatment similar to conventional asthma therapy
iv. Appropriate return to work and work environment
v. Most with occupational asthma do not recover completely,
persistent symptoms inn 50-90%. RADS may have better
prognosis
vi. Pulmonary function testing plateaus at 1-2 yrs after exposure
removed
II. Carbon monoxide poisoning
a. Chemistry
i. Colorless, odorless gas created by incomplete combustion of fossil
fuels
b. Epidemiology
i. Most common cause of poisoning death in the U.S. (5000-6000
deaths/year)
ii. Majority associated with exposure to automobile exhaust
(intentional and unintentional)
iii. Poorly functioning furnaces/heaters/stoves, smoke inhalation due
to fires, and exposure to methylene chloride (which is metabolized
to CO in the liver) are other important sources
1. Spike in accidental exposures during the winter months
2. Ethnic groups accustomed to cooking/heating fires indoors
in less airtight homes in their native countries
c. Pathophysiology
i. Non-irritating to upper airways
ii. Readily absorbed through the lungs
iii. Competes with oxygen for hemoglobin binding
1. Hgb has affinity for CO > 200 times as great as its affinity
for oxygen
2. Decreased blood oxygen content
3. Shift to left of oxyhemoglobin dissociation curve and
decreased oxygen unloading at tissue level
a. Particularly pronounced in developing fetus, due to
intrinsic left shift of fetal hemoglobin
4. Consequent cellular hypoxia
5. Normal COHb levels 1-3 % in non-smokers, may reach 10-
15% in smokers
iv. CO also appears to have direct cellular toxicity
1. impairs cytochrome oxidase function
2. induces nitric oxide activity and free-radical production
Page 133 of 177

d. Clinical presentation
i. Signs and symptoms nonspecific, and can mimic viral infection
ii. Initial symptoms include headache, dizziness, blurred vision,
nausea/vomiting, myalgias, difficulty concentrating, dyspnea, and
chest pain
iii. As exposure worsens, may display tachycardia, hypotension,
seizures, dysrhythmias, coma, and death
iv. “Classic” sign of cherry-red lips seen only rarely
v. Survivors may develop chronic/persistent neuropsychiatric
symptoms
e. Diagnosis
i. Requires high index of suspicion
1. Particular attention to presence of housemates with similar
symptoms
2. Presence of gas stove/furnace/water heater
ii. Carboxyhemoglobin level
1. Requires co-oximetry
a. Multiple (as many as 8) wavelengths of light
b. Standard 2-wavelength pulse oximeter cannot
distinguish between oxyhemoglobin and
carboxyhemoglobin
2. May decrease or normalize by time of presentation
iii. Environmental testing of area of exposure
1. Readily performed by all fire departments
f. Treatment
i. Removal from source of exposure
ii. Supplemental oxygen
1. Competes with CO for binding sites on hemoglobin
2. Shortens half-life of CoHb
a. 4-6 hours when breathing room air
b. 40-80 minutes when breathing 100% oxygen
c. 15-30 minutes when breathing hyperbaric oxygen
iii. Hyperbaric oxygen
1. 100% O2 given in hyperbaric chamber at 2-3 atm
2. Indications subject of ongoing debate
3. Should be considered patients with:
a. COHb > 40%
b. COHb > 15% and pregnant
c. Significant neurologic signs (focal deficits, seizures,
altered mental status, history of loss of
consciousness)
d. History of ischemic heart disease, particularly if
symptomatic
e. Persistent symptoms despite normobaric oxygen
Page 134 of 177

iv. Neuropsychiatric testing
1. Helpful in tracking long-term progression of neurologic
symptoms
2. Some have advocated use acutely to help decision-making
regarding hyperbaric therapy
3. Should be considered in all CO poisoning, even if no overt
neurologic symptoms
g. Prevention
i. Frequent inspection & maintenance of fuel-burning heating
devices
ii. Appropriate maintenance of vehicle exhaust systems and education
about the dangers of running motor vehicles in enclosed spaces
iii. Public education regarding the danger of indoor fires
iv. Use of home CO detectors
III. Drug-induced lung disease
a. Scope
i. Many hundreds of drugs known to have potential adverse effects
on the lungs
b. Mechanisms
i. Induction of oxidant injury
ii. Direct cytotoxic effects
iii. Intracellular phospholipid deposition
iv. Immune-mediated
c. Diagnosis
i. Requires high index of suspicion
ii. Physical exam, laboratory, radiographic, and pathologic findings
often non-specific
iii. Often a diagnosis of exclusion
1. biopsy may be helpful to rule out other causes
d. A few specific drugs of importance
i. Bleomycin
1. History
a. Antibiotic with antitumor activity discovered in
1966
b. Used to treat germ-cell tumors, lymphomas,
Kaposi’s sarcoma, cervical cancer, and head/neck
squamous cell cancers
2. Epidemiology
a. Pulmonary toxicity occurs in as many as 20 % of
those treated
b. Risk factors include high cumulative dose (> 400
mg), age > 70, renal dysfunction (impaired
clearance of bleomycin), concomitant oxygen
therapy, concomitant radiation, and possibly
smoking
3. Pathophysiology
Page 135 of 177

a. Still debated, but appears to caused by cytokine
induction with concomitant inflammatory response
and free-radical formation
b. Acute/sub-acute pneumonitis initially, may develop
progressive fibrosis
4. Clinical presentation
a. Dyspnea and non-productive cough typical
symptoms
b. Often gradual in onset, may occur up to 6 months
after bleomycin cessation
c. Inspiratory rales on exam, but may be normal
d. Pulmonary function tests may demonstrate
decreased diffusing capacity and decreased lung
volumes
5. Radiography
a. Non-specific, typically have bilateral alveolar or
interstitial infiltrates
6. Treatment
a. Cessation of bleomycin
b. Corticosteroids often used
i. No good randomized data exists
c. Majority recover if recognized/treated before
fibrosis develops
ii. Amiodarone
1. History
a. Iodine-based Class III antiarrhythmic
b. Used to treat a variety of atrial and ventricular
arrhythmias
c. Use has increased dramatically in last 10 years
i. Very prominent role current ACLS
guidelines
2. Epidemiology
a. Pulmonary toxicity in 4-6%
b. More common in men, age > 40, dose ≥ 400
mg/day, concomitant oxygen therapy
3. Pathophysiology
a. Exact mechanism of toxicity unclear
b. Typical pathologic finding is alveolar macrophages
and type II pneumocytes with “foamy” appearance,
due to multiple phospholipid-laden inclusions
i. Also seen in those on amiodarone without
pulmonary toxicity
4. Clinical presentation
a. Non-specific: dyspnea, cough, fevers
b. May occur within days to years of initiating
therapy, but most commonly within several months
Page 136 of 177

c. Pulmonary function tests demonstrate decreased
diffusing capacity
5. Radiography
a. Very wide variety of presentations
i. Interstitial infiltrates
ii. Pulmonary mass
iii. Cavitating lesion
iv. Alveolar infiltrates
v. Pleural effusions
vi. Radiopaque (iodine) infiltrates
6. Treatment
a. Cessation of amiodarone
b. Uncontrolled data supporting corticosteroids
c. Most recover
iii. Cocaine
1. General
a. Stimulant alkaloid derived from leaves of the coca
plant
b. Used regularly (≥ once/month) by approximately
1.5 million in the U.S.
2. Route of administration
a. Nasal insufflation (“snorting”)
i. Majority of a dose taken in this manner does
not reach the lungs, but is absorbed via the
mucous membranes of the nose/sinuses
b. Smoking
i. “Freebasing”
1. Cocaine base extracted from the salt
(cocaine HCL, typical powder form)
by precipitating it with ammonia,
then recovering the pure base from
solution with ether
2. Base then smoked via pipe
ii. “Crack” cocaine
1. Cocaine base extracted from salt by
precipitating with sodium
bicarbonate, decanting supernatant,
and allowing precipitate to dry
2. Avoids dangers (primarily fire) of
handling ether
c. Injection
i. Cocaine HCL dissolved in water and
injected
ii. Often administered with heroin
(“speedball”)
Page 137 of 177

3. Pulmonary effects
a. Smoked
i. “Crack lung”
1. Cough, carbonaceous sputum, chest
pain, dyspnea, hemoptysis, fever
within minutes-hours of use
ii. Acute bronchospasm
iii. Thermal airway injury
iv. Non-cardiogenic pulmonary edema
v. Alveolar hemorrhage
vi. COP (aka, BOOP)
vii. Pulmonary hypertension
viii. Pulmonary barotrauma (i.e., pneumothorax,
pneumomediastinum)
1. User technique may increase risk
a. Valsalva against closed
glottis after inhaling (to
increase absorption)
b. Exhaling smoke under
pressure directly into 2nd
user’s mouth (“shotgunning”)
b. Injected
i. Alveolar hemorrhage
ii. Talc granulomatosis and obstructive lung
disease due to impaction of insoluble
impurities in pulmonary microvasculature
iii. Pulmonary hypertension
iv. Pulmonary barotraumas
1. May stem from attempt to inject
directly into internal jugular or
subclavian vein (“pocket shot”)
4. Radiography
a. Non-specific, varies with type of complication
5. Treatment
a. Cessation of use
b. Supportive care as appropriate
Additional resource (if interested—not required):
Murray & Nadel’s Textbook of Respiratory Medicine, 4th ed. Chapters 60 & 67.
--available on MD Consult via Health Sciences Library website
Page 138 of 177

Interstitial Lung Disease
Time: 10:30 AM
Objectives: by the end of this lecture and the associated small group case studies,
1. Recognize common chest x-ray and high resolution chest CT scan findings of interstitial
lung disease including ground glass infiltrates and honeycomb infiltrates.
2. Recognize pulmonary function test patterns in interstitial lung disease.
3. Given a clinical vignette, identify common causes of interstitial lung disease from the
patient history.
4. Differentiate sarcoidosis and idiopathic pulmonary fibrosis based on clinical,
radiographic, and pathologic findings.
5. Given a clinical vignette, distinguish between usual interstitial pneumonitis, non-specific
interstitial pneumonitis, acute interstitial pneumonitis, and desquamative interstitial
pneumonitis based on demographic, clinical, radiographic, and pathologic findings.
6. Identify sarcoidosis and idiopathic pulmonary fibrosis by microscopic examination of
lung biopsy images.
7. Apply bronchoalveolar lavage findings to the differentiation of common forms of
interstitial lung disease including sarcoidosis, hypersensitivity pneumonitis, idiopathic
pulmonary fibrosis, allergic drug reaction, and chronic eosinophilic pneumonia.
8. Contrast the advantages and disadvantages of lung biopsy using bronchoscopy and video-
assisted thorascopic surgery.
9. Given a clinical vignette, recommend appropriate pharmacologic and non-pharmacologic
treatment for sarcoidosis, usual interstitial pneumonitis, and non-specific interstitial
pneumonitis.
Optional Reading:
1. Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter 255: Interstitial
Lung Disease, Talmadge E. King
2. Harrison’s Principles of Internal Medicine – 17th Ed (2008); Chapter 322: Sarcoidosis,
Robert P. Baughman and Elyse E. Lower
I. Pathogenesis:
A. Anatomic considerations within the lung:
1. interstitial components
2. alveolar components
3. small airway components
4. blood vessel components
B. Pathogenesis:
1. general principles:
a) inhaled injury agent – alveolar injury - interstitial fibrosis
b) circulating injury agent - endothelial injury - interstitial fibrosis
2. common causes (refer to text for a more extensive differential):
Page 139 of 177

a) collagen vascular diseases (systemic lupus erythematosus, rheumatoid
arthritis, scleroderma)
b) occupational causes (asbestos & silicosis)
c) drug reactions (methotrexate & amiodarone)
d) radiation pneumonitis
e) hypersensitivity pneumonitis
f) diseases of unknown cause; most common include sarcoidosis &
idiopathic pulmonary fibrosis
II. Clinical Presentation:
A. History:
1. symptoms: cough, dyspnea
2. duration of symptoms
3. what makes symptoms worse?
4. what makes symptoms better?
5. occupational & drug exposures?
B. Physical examination:
1. vital signs: respiratory rate, temperature
2. pulmonary exam: crackles (rales) present?
3. cardiac exam: cor pulmonale (pulmonary hypertension) present?
4. extremities: nail clubbing present? arthritis? skin rash?
III. Diagnostic Testing:
A. blood tests: occasionally useful, mainly to look for evidence of rheumatologic diseases
that can cause interstitial lung disease (such as rheumatoid arthritis, systemic lupus
erythematosus, etc.)
B. Chest x-ray: nodules? interstitial markings? alveolar markings? pleural disease?
hilar/mediastinal lymph node enlargement?
C. High resolution chest CT:
1. used for diagnosis:
a) some patterns relatively specific for certain diseases; eg.:
bronchiectasis, emphysema, Langerhan's cell granulomatosus
b) location of abnormalities can guide site of lung biopsy
2. used for disease management:
a) ground glass infiltrates: correlate with inflammation and are
potentially reversible
b) "honeycombing": correlate with fibrosis and are irreversible
C. Pulmonary function tests:
1. lung volumes - generally reduced
2. diffusing capacity - generally reduced
3. spirometry - generally normal
4. pulmonary exercise testing - typical findings include:
a) reduced maximum oxygen uptake
b) resting or exercise-induced hypoxemia
c) reduced ventilatory reserve
D. Bronchoalveolar lavage:
1. normal findings:
a) >90% alveolar macrophages
b) <10% lymphocytes most are T-cells with a usual T-helper:suppressor
ratio is between 1:1 and 2:1
c) <2% neutrophils
d) <2% eosinophils
2. important abnormal findings:
Page 140 of 177

a) increased lymphocyte percentage
(1) increased T-helper:suppressor ratio: sarcoidosis
(2) decreased T-helper:suppressor ratio: hypersensitivity
pneumonitis
(3) current immunologic theory recognizes 2 forms of T-helper
cells: Th1 & Th2 cells.
(a) Th1 cells make interleukin-2 and gamma-interferon
(b) Th2 cells make interleukin-4, interleukin-5, &
interleukin-10.
b) increased neutrophils: most cases of IPF, most other interstitial lung
diseases
(1) diagnostically, the least specific when present in increased
percentages
(2) contain a number of oxidants and enzymes with potential for
lung tissue damage
c) increased eosinophils: chronic eosinophilic pneumonia, some cases of
drug-induced lung disease
(1) eosinophils are largely controlled by interleukin-5 and other
mediators produced by Th2 lymphocytes
(2) make a variety of high pH granule contents which are
extremely toxic to parasites and normal lung tissue
E. Lung Biopsy
1. transbronchial biopsy (via a flexible bronchoscope)
a) advantages
(1) minimally invasive
(2) outpatient procedure
b) disadvantages
(1) very small tissue samples
(2) pulmonary vessels usually not present in specimens
(3) usually too small to make a pathologic diagnosis except for
sarcoidosis, some cancers, and some infections
2. video-assisted thorascopic biopsy
a) advantages
(1) larger tissue pieces than transbronchial biopsy
(2) shorter hospital stay and less post-operative discomfort than
open lung biopsy
b) disadvantages
(1) inpatient procedure requiring general anesthesia
(2) inability to palpate lung during procedure may lead to
sampling error
(3) difficult to obtain deep samples
3. open lung biopsy
a) advantages
(1) provides large samples
(2) surgeon can better identify involved portions of lung
b) disadvantages
(1) inpatient procedure requiring general anesthesia
(2) longest recovery time
IV. Diagnosis & Treatment Of Two Common Interstitial Lung Diseases:
A. Sarcoidosis:
1. diagnosis
Page 141 of 177

a) organs typically involved: lungs, skin, eyes, CNS, heart, kidney,
musculoskeletal system
b) clinical presentation:
(1) high prevalence in African Americans & Scandinavians
(2) may be asymptomatic
(3) dyspnea; dull, non-exertional chest pain
(4) occasional erythema nodosum on skin exam
(5) absence of crackles on chest auscultation
(6) lymphopenia; occasional hypercalcemia
(7) serum angiotensin converting enzyme level often elevated
(not very specific)
c) chest x-ray - many possible presentations:
(1) hilar or mediastinal lymph node enlargement
(2) interstitial infiltrates
(3) large "fluffy" nodules
(4) fibro-cavitary infiltrates
(5) chest x-ray may be normal
d) pulmonary function tests
(1) occasionally normal
(2) restriction (early)
(3) low diffusing capacity (late)
(4) occasionally mild obstruction if sarcoid granulomas involve
large/medium sized airways
e) BAL
(1) increased lymphocytes
(2) increased T-helper:suppressor ratio
f) lung biopsy
(1) transbronchial biopsy usually sufficient for diagnosis
(a) if chest x-ray interstitial markings present = 90%
yield
(b) if chest x-ray interstitial infiltrates absent = 60%
yield
(2) pathology:
(a) non-caseating granulomas
(b) multi-nucleated giant cells
(c) lymphocytic infiltrates
2. treatment
a) indications for treatment:
(1) ocular involvement
(2) pulmonary or other organ symptoms due to sarcoidosis
(3) abnormal pulmonary function tests
(4) note: an abnormal chest x-ray per se is not an indication for
treatment
b) many patients improve spontaneously without treatment
c) if symptomatic: prednisone
(1) 30-40 mg/day x 3-4 weeks
(2) taper to 10-20 mg every day or every other day x 4-6 months
(3) in prednisone-intolerant patients, methotrexate is an
alternative
d) prognosis is excellent in the majority of patients if recognized and
treated promptly and appropriately
Page 142 of 177

B. Idiopathic pulmonary fibrosis:
1. diagnosis
a) organs typically involved:
(1) lung
b) clinical presentation:
(1) usual age = 50-70
(2) subacute onset dyspnea on exertion
(3) non-productive cough
(4) dry inspiratory crackles (90%)
(5) nail clubbing in about 50%
(6) genetic (autosomal dominant) in 10-20% of cases
c) chest x-ray:
(1) basilar or diffuse interstitial changes
(2) no hilar lymph node enlargement
(3) no pleural disease
(4) high resolution chest CT is moderately specific
(a) peripheral/subpleural interstitial densities
(b) patchy "ground-glass" infiltrates
(c) small (2-4) cystic areas
d) pulmonary function tests
(1) reduced lung volumes
(2) reduced diffusing capacity
(3) low pO2
(4) low MVO2 during exercise testing
e) BAL
(1) increased lymphocytes
(a) usually an early finding
(b) when present, often predicts favorable response to
treatment
(2) increased neutrophils
(a) the more frequent finding
(b) when present, usually indicates a less favorable
response to treatment
f) biopsy
(1) thorascopic or open lung biopsy usually required
(2) histologic subtypes:
(a) usual interstitial pneumonitis (UIP): typically an
isolated lung disease occurring in older adults
(1) interstitial fibrosis
(2) absence of granulomas & vasculitis
(3) decreased type 1 pneumocytes
(4) collagen deposition
(5) temporal heterogeneity (as if the lung was
repeatedly injured over time) – some areas
of end-stage fibrosis, some areas of
interstitial thickening, and some areas of
relatively normal lung
(b) non-specific interstitial pneumonitis (NSIP):
typically a disease occurring in patients with
underlying collagen vascular disease such as
rheumatoid arthritis, systemic lupus
Page 143 of 177

erythematosus, systemic sclerosis (scleroderma),
polymyositis, etc.
(1) temporal homogeneity (as if the lung injury
occurred at one time) – all areas of the
lung in the same stage of damage
(2) relatively less collagen deposition
(3) relative absence of fibroblast foci
(c) desquamative intersitial pneumonitis (DIP): typically
a disease of young smokers
(1) large increase in alveolar macrophages in the
alveoli with abundant hemosiderin
granules
(2) relatively little fibrosis and collagen
deposition
(d) acute interstitial pneumonitis (AIP): rare and very
rapidly progressing disease resulting in respiratory
failure within days to weeks.
(1) diffuse alveolar damage with hyaline
membranes and resembling acute
respiratory distress syndrome (ARDS)
2. treatment
a) UIP treatment
(1) there is no known cure
(2) daily steroids (prednisone), cyclophosphamide, azathioprine
– minimally effective
(3) single lung transplantation
(a) last resort in patients failing other treatment
(b) must be < 60 or 65 at most transplant centers
(c) lung transplant is not easy – 25% mortality rate in the
first 2 years after transplant
(4) generally fatal with or without pharmacologic treatment with
mean survival = 5 years
b) NSIP treatment
(1) daily prednisone
(2) daily cyclophosphamide, daily azathioprine, or daily
mycophenolate
(3) prognosis: most patients will improve and have good
prospects for long term survival
c) DIP treatment
(1) smoking cessation
(2) steroids with or without cyclophosphamide or azathioprine
(3) prognosis: excellent with smoking cessation
d) AIP treatment
(1) mechanical ventilation and supportive care
(2) steroids are often used but are of questionable value
(3) prognosis: 60% mortality rate; if patients survive the initial
bout of respiratory failure, long term survival is possible
and substantial lung recovery can occur
Page 144 of 177

Traumatic Chest Emergencies
Time: 8:30
I. Objectives
a. Accurately describe the underlying pulmonary mechanics leading to
tension pneumothorax
b. Given a clinical vignette, recognize the signs and symptoms of tension
pneumothorax, and accurately describe emergency treatment
c. Accurately describe the underlying pulmonary mechanics of an open
pneumothorax
d. Given a clinical vignette, recognize the signs and symptoms of open
pneumothorax, and accurately describe emergency treatment
e. Accurately describe the pulmonary physiology that occurs in flail chest
f. Recognize the type of injury required to cause flail chest
g. Given a clinical vignette, recognize the signs and symptoms of flail chest,
and describe emergency treatment
h. Describe the anatomic basis and pulmonary physiologic basis of
diaphragmatic rupture
i. Given a clinical vignette, recognize the signs and symptoms of
diaphragmatic rupture, and describe treatment
II. Tension pneumothorax
a. Terminology
i. Pneumothorax
1. Air in pleural space
ii. Simple pneumothorax
1. Air in pleural space, associated with some degree of lung
collapse, but no compression of mediastinal structures and
no significant communication of pleural space with ouside
environment
iii. Tension pneumothorax
1. Air in pleural space of sufficient volume/pressure to cause
compression and shift of mediastinal structures, and
hemodynamic compromise
iv. Open pneumothorax
1. Air in pleural space due to communication with external
environment through open chest wall defect
b. Physiology
i. Tension pneumothorax occurs when air accumulates in the pleural
space progressively, due to ongoing air leak into pleural space
without means for air to escape
ii. Results in collapse of ipsilateral lung
Page 145 of 177

iii. Ultimately causes compression of mediastinal structures, including
SVT, heart (especially RA and RV), trachea and lower airways,
followed by contralateral shift of mediastinum
iv. Hypotension and cardiovascular collapse ultimately occur due to
compression of the low-pressure RA and RV, with consequent
inability of heart to fill with venous blood adequately
c. Etiology
i. Introduction of air into pleural space due to lung injury
1. Mechanical ventilation
a. Especially in patients with pneumonia, severe lung
injury, or those being ventilated at high pressures
2. Blast/blunt trauma to lung
3. Rib fractures that lacerate lung
4. Airway disruption/tear
5. Attempted CVC (central venous catheter) placement with
puncture of lung
ii. Introduction of air into pleural space from outside environment
1. Penetrating/avulsive injury to chest wall
d. Diagnosis
i. Symptoms
1. Shortness of breath, respiratory distress (usually severe)
2. Chest pain
ii. Signs
1. Decreased/absent breath sounds on side of pneumothorax
2. Hyperresonance to percussion
3. Palpable tracheal shift to opposite side (often subtle/absent)
4. Palpable crepitus (crackling) in chest wall due to
subcutaneous air
5. Tachycardia/hypotension
6. Hypoxemia
7. Cardiopulmonary arrest (especially PEA)
iii. Radiography
1. Air in pleural space with shift of mediastinal structures to
opposite side
2. Diagnosis is primarily a clinical one—DO NOT wait for
chest x-ray prior to initiating treatment!!! Patient may
die while you are waiting. . .
e. Treatment
i. Immediate goal is decompression of affected side and restoration
of hemodynamic stability
1. Needle decompression
a. Large bore needle (14 gauge) inserted into chest at
second intercostal space, mid-clavicular line
b. Usually results in large “whoosh” as compressed air
escapes
Page 146 of 177

c. Converts tension pneumothorax into simple
pneumothorax
d. Stopgap measure—buys you time
ii. Secondary goal is ongoing evacuation of air leaking into pleural
space
1. After decompression, still need to evacuate remaining air
and address ongoing air leak
2. Tube thoracostomy (aka, chest tube)
a. Large-bore tube inserted through chest wall into
pleural space to allow continued drainage (often
under suction) of air and fluids from pleural space
III. Open pneumothorax
a. Physiology
i. Introduction of air into pleural space due to traumatic chest wall
defect
ii. Results in lung collapse
iii. If chest wall defect is ≥ 2/3 diameter of trachea, air will
preferentially be sucked through defect into chest (rather than
drawn through trachea) during attempts at inspiration
1. Hence the moniker, “sucking chest wound”
iv. Results in inadequate ventilation of unaffected lung through
trachea
b. Etiology
i. Can occur due to any penetrating injury to chest
ii. May convert to tension pneumothorax if chest wall tissue causes
“one-way valve” effect
1. That is, air can enter pleural space on inspiration, but
cannot escape on expiration because “valve” closes and
blocks chest wall defect
c. Diagnosis
i. Symptoms
1. Shortness of breath
2. Chest pain
ii. Signs
1. Evident chest wall defect
2. May see/hear air bubbling (through blood) in wound
3. Breath sounds may or may not be decreased
a. May hear air rushing in and out of pleural space
though defect, or gurgling through blood/secretions
4. Hypoxemia
5. Hemodynamic compromise if tension physiology develops
iii. Radiography
1. Demonstrates air in pleural space
2. Usually not necessary
d. Treatment
i. Two primary goals
Page 147 of 177

1. Seal chest wall defect to prevent further introduction of air
and allow ventilation through trachea to occur normally
a. In theory, should place “3-sided” dressing that
allows air to escape pleural space but not enter
b. In reality, often difficult to achieve, and may need
to completely occlude defect
2. Evacuate air from pleural space
a. Tube thoracostomy
ii. Once patient stabilized, will need surgical closure of chest wall
defect
IV. Flail chest
a. Physiology
i. Occurs when 2 or more ribs are broken in 2 or more places,
causing a section of chest wall to “detach” from the thoracic cage
ii. Flail segment moves “paradoxically” during respiration, and can
lead to inadequate ventilation of lung
1. Flail segment moves inward on inspiration, outward on
expiration (unlike rest of chest wall)
iii. Also usually associated with:
1. Pulmonary contusion (bleeding into the lung)
2. “Splinting” and poor ventilation due to chest pain
b. Etiology
i. Usually blunt force or crush injury to chest
c. Diagnosis
i. Symptoms
1. Chest pain
a. Often severe, worse with cough and deep breathing
2. Shortness of breath
3. Hemoptysis due to concomitant lung contusion
ii. Signs
1. Palpable rib fractures
2. Paradoxical chest wall movement
3. Hypoxemia
iii. Radiography
1. 2 or more rib fractures in 2 or more places
2. Alveolar infiltrates due to pulmonary contusion
iv. Treatment
1. Primarily supportive
a. Aggressive pain control
b. Supplemental oxygen
c. Non-invasive ventilation or invasive mechanical
ventilation if needed until segment heals/stabilizes
2. Surgical repair/stabilization of flail segment only rarely
necessary
V. Diaphragmatic rupture
a. Etiology
Page 148 of 177

i. Can occur after penetrating or blunt trauma (usually the latter)
ii. Stabbings and MVA’s most common causes, respectively
1. Also reported after bouts of severe vomiting
iii. Occurs in as many as 5% of hospitalized MVA victims
iv. Approximately 10-15% escape initial diagnosis and are found
weeks-years later (greatest reported delay = 45 years)
b. Anatomy
i. Rupture typically occurs at weakest part of diaphragm, posterior
insertion of muscular portion (pars lumbalis) into central tendon
1. Site of embryologic fusion of pleuroperitoneal membrane
with septum transversum and body wall mesoderm
ii. Majority are L-sided
1. Liver protects R hemidiaphragm, and may also “seal” a R-
sided defect and prevent visceral herniation
2. R-sided rupture harder to diagnose
3. R hemidiaphragm inherently stronger
c. Physiology
i. Blunt trauma usually results in tears d/t increased intra-abdominal
pressure
1. Normal abdominal-thoracic pressure gradient = 5-15 mm
Hg
2. Rapid increase of intra-abdominal pressure of ≥ 100 mm
Hg said to be required for rupture
ii. Pressure gradient between peritoneum and chest cavity results in
herniation of abdominal contents into chest
1. Commonly herniated viscera include stomach, colon, small
bowel, and spleen
iii. Patients with emphysema or other causes of increased intrathoracic
pressure may experience herniation of lung into peritoneum
d. Signs/symptoms
i. Acute
1. Chest pain, dyspnea, cyanosis, decreased breath sounds
2. Hemodynamic compromise due to tension physiology or
due to strangulation/infarction of viscera
3. Cardiac tamponade due to viscera in pericardial sac has
been described
ii. Chronic
1. Dyspnea, abdominal pain, GERD (may be subtle)
2. Symptoms due to compromised viscera in hernia sac
3. Several reports of tension fecopneumothorax (i.e., stoll and
air in pleural space) due to perforation of colon
iii. Radiography
1. Plain x-ray may show apparent elevation of hemidiphragm,
or air-filled viscera in pleural space
2. CT scan useful in the acute setting
Page 149 of 177

a. Indentation of herniated viscera (“collar sign” d/t
impingement on torn diaphragmatic margin) highly
suggestive
3. MRI extremely accurate; probably best modality for
stable/chronic hernias
iv. Low threshold for diagnosis via surgery in trauma patients in
whom rupture is suspected
e. Treatment
i. Surgical repair
1. Either primary closure or patch over defect
2. Indicated in all cases, including “stable” chronic injury—
risk of strangulation is perpetual, and mortality increases
with delayed treatment
ii. Literature mixed regarding approach (transthoracic vs.
transabdominal)
1. Transabdominal more commonly used in acute rupture d/t
blunt trauma
a. May be done laparoscopically
2. Thoracotomy (approach through chest) often preferred for
chronic hernia (due to likelihood of adhesions in chest
cavity), large hernias (> 10 cm), or those involving the
esophageal hiatus
Additional resource (if interested, not necessary): Marx: Rosen's Emergency

Medicine: Concepts and Clinical Practice, 6th ed, Ch. 42. (available through
MDConsult through Health Sciences Library website)
Page 150 of 177

Pediatric Pulmonary – Neonatal & Congenital Disorders

Time: 9:30 am
Faculty: Elizabeth D. Allen, M.D.
Department of Pediatrics, Division of Pulmonary Medicine
Email: Beth.Allen@nationwidechildrens.org
Resources: Nelson Textbook of Pediatrics, 17th ed., 2004

Part 11, Section 1, Chapter 90
Part 18
Pediatric Pulmonology – Neonatal & Congenital Disorders Objectives

1. Describe characteristics of children which place them at increased risk for respiratory
compromise
2. List signs and symptoms of respiratory distress in the newborn
3. Describe key features of common newborn respiratory illnesses, including hyaline membrane
disease, meconium aspiration, neonatal pneumonia, and persistent pulmonary hypertension of
the newborn
4. Identify the most common problem of ventilatory control in premature infants, commonly
associated health problems, and treatment options
5. Distinguish between these illnesses, based on history, exam, and radiographic findings
6. Describe bronchopulmonary dysplasia
7. Recognize that there are a multitude of congenital malformations of the respiratory system
8. Describe key features of laryngomalacia
9. Describe key features of diaphragmatic hernia
10. Describe key features of tracheoesophageal fistula
Introduction
A. Respiratory disease is the major source of morbidity and mortality in the pediatric age group
B. Factors involved in children's susceptibility to pulmonary mortality:
1. Congenital abnormalities
2. Perinatal transition in oxygen supply
3. Tiny upper airway
4. Increased virulence of infections
1. Risky behaviors
2. Hardiness of cardiovascular system
Page 151 of 177

Categories of Childhood Respiratory Illness
A. Neonatal Respiratory Disorders
B. Congenital Abnormalities
C. Infectious Lung Diseases
D. Accidental Lung Injury
E. Asthma
F. Cystic Fibrosis
G. Misc.
Neonatal Respiratory Disorders
A. Clinical Features of Respiratory Distress in Newborns
1. Tachypnea/Apnea
2. Expiratory grunting
3. Chest wall retraction
4. Loss of muscle tone
5. Decreasing response to external stimuli
6. Bradycardia
7. Cyanosis
B. Hyaline Membrane Disease (AKA Respiratory Distress of Newborn)
1. Most common cause of newborn respiratory distress
2. Incidence correlates with prematurity
3. Surfactant deficiency causes alveolar collapse
4. Deterioration over 24-48 hours, then gradual recovery
5. Treatment: surfactant replacement, supportive care
6. Prevention: betamethasone administered to mother prior to delivery
better – reduce rates of prematurity
C. Meconium Aspiration
1. Typically term or post-term infant
2. Prenatal stress (+/- asphyxia) often involved
3. Meconium (stool) released into amniotic fluid, then inhaled
4. Airway plugging/hyperinflation/pneumonitis
5. Treatment: acute suctioning, supportive care
D. Neonatal Pneumonia
1. Any gestational age
2. May present identically to hyaline membrane disease,
with sepsis, or after a delay
3. Common organisms: Gram (-) bacteria, Grp B -Streptococcus
4. Treatment: Antibiotics, supportive care
Page 152 of 177

E. Persistent Pulmonary Hypertension of the Newborn (PPHN)
1. Elevated pulmonary vascular resistance with shunting of pulmonary blood flow to the
systemic circulation (persistent fetal circulation)
2. Associated with:
a. Severe neonatal stress (sepsis, asphyxia, etc.)
b. Pulmonary parenchymal disease
c. Lung hypoplasia
d. No obvious pulmonary defect
3. Most common in term or post-term infants
4. Treatment difficult
F. Bronchopulmonary dysplasia
1. Major form of chronic lung disease in infants
2. Especially frequent in very low birthweight infants
3. Combined effects of lung injury & arrested lung development
3. Oxygen requirement beyond 36 weeks post menstrual age (PMA), or 56 days postnatally
4. CXR findings: perihilar thickening and hyperinflation
5. Prognosis: Improvement with time – vast majority
Deaths often related to cor pulmonale (right heart failure secondary to
chronic lung disease/hypoxia), or RSV infection
G. Apnea
1. Definition: cessation of inspiratory gas flow for 20 seconds, or for a shorter period if
accompanied by bradycardia (HR <100), cyanosis or pallor.
2. Types:
a. Central
b. Obstructive
c. Mixed
3. Apnea of Prematurity
a. Common cause of apnea in newborns
b. Incidence inversely proportional to age (50% of infants < 1500 gms need
intervention)
c. Peaks between postnatal days 5 and 7
d. Normally resolves between 34-36 weeks postconceptual age
4. Problems associated with apnea (partial list)
a. RDS
b. Pulmonary mechanical problems – e.g. atelectasis
c. Infection
d. Hypotension
e. Seizures
Page 153 of 177

f. Metabolic disturbances – hypoglycemia, acidosis, hyponatremia
g. Gastroesophageal reflux
5. Therapies for newborn apnea
a. Treat underlying health problem
b. Avoid triggering reflexes
i. “Back to Sleep”
ii. Cautious suctioning
iii. Tube feedings
c. Cutaneous stimulation
d. Nasal prong oxygen > nasal cpap > mechanical ventilation
e. Methylxanthine therapy
Examples of Common Congenital malformations
A. Laryngomalacia
1. Floppy and elongated epiglottis and arytenoids
2. Most common cause of stridor (inspiratory high pitched noise) from birth
3. Resolves spontaneously over 1-2 years
4. Differential: Congenital or acquired upper airway lesions
B. Diaphragmatic hernia
1. Defect in diaphragm allows abdominal contents to migrate into chest
2. Most common form = posterolateral defect on left side, develops at roughly 6 weeks of
fetal age
3. Pulmonary hypoplasia, PPHN, and surfactant system dysfunction contribute to high
mortality
4. 25% also have congenital heart disease; 40% total with some other congenital defect
5. Management:
Intubation, oral-gastric suctioning, mechanical ventilation
ECMO (total circulatory bypass) may be needed
Surgical repair of defect
Survey for associated anomalies
C. Tracheoesophageal fistula
1. Defective separation of the trachea and esophagus during fetal development
2. Several forms – typically abnormal connection between esophagus and trachea, with
interruption of normal esophagus (“blind pouch”)
3. Clinical clues
(a) Excessive secretions
(b) Severe choking on feeding attempts
(c) Inability to pass nasogastric tube
4. Treatment: Surgical
Page 154 of 177

5. Complications: gastroesophageal reflux, persistent fistulas. Recurrent esophageal
strictures
Congenital Pulmonary Malformations
A. Pulmonary function is not needed for fetal development
B. Multiple abnormalities may occur – and unless discovered by prenatal testing – not be evident
until post birth
C. Abnormalities range from mild and temporary, to life-threatening
D. Some malformations may not cause symptoms until adulthood
Congenital pulmonary malformations typically presenting in childhood
choanal atresia pulmonary hypoplasia
laryngomalacia pulmonary sequestration
laryngeal webs, cysts pulmonary cysts
tracheomalacia esophageal atresia
tracheal stenosis diaphragmatic hernia
Neonatal and Congenital Lung Disease
A. The respiratory tract is a major source of vulnerability for children
B. Infants, particularly, are susceptible to life-threatening pulmonary disease
C. Congenital disorders are quite variable, usually (but not always) present in infancy, and range
from benign to lethal
Page 155 of 177

Pediatric Pulmonary – Beyond the Newborn Period
Time: 10:30 am
Phone: 722-4766
Resources: Nelson Textbook of Pediatrics, 17th ed., 2004

Part 18, Section 3
Chapter 61
Chapter 134
I. Pediatric Pulmonology – Childhood Objectives

1. List major sources of respiratory difficulty beyond the neonatal period
2. List ways the pediatric respiratory tract can be “accidentally” injured
3. Identify some unique features of asthma in childhood
4. Distinguish between pediatric illnesses that are likely to present with stridor, versus those likely
to present with wheezing
5. Identify at least 3 respiratory infections that can be prevented by immunization
6. Describe symptoms which can be caused by chronic aspiration, and populations at risk for this
process
7. List common sites of drowning injury in children, based on age range
8. Identify the most common reasons for hemoptysis in children, and describe methods used to
diagnose them
9. Identify common causes of chronic cough in childhood
10. List the “usual” reasons otherwise healthy children experience difficulty with shortness of
breath during exercise
Categories of Childhood Respiratory Illness

A. Neonatal Respiratory Disorders
B. Congenital Abnormalities
C. Infectious Lung Diseases
D. Accidental Lung Injury
E. Asthma
F. Cystic Fibrosis
G. Miscellaneous
Page 156 of 177

Respiratory Infections
Example: Croup (Laryngotracheobronchitis)
Major cause of acute stridor in infants & toddlers
Viral mediated
Treatment – nebulized epinephrine & steroids
Diff – epiglottitis, bacterial tracheitis, retropharyngeal abscess, foreign body, anaphylaxis
A. Viral mediated disease most common reason for acute febrile respiratory illness
1) RSV bronchoilitis major problem in infants
2) Influenza, para-influenza, adenovirus also virulent
B. Bacterial pneumonia similar to adults
1) Mycoplasma/atypicals less common < 7 yo
C. Pertussis can be life-threatening to infants, severe in young children
D. Immunizations have had significant (+) impact
1) In Use: Pertussis, H. influenza, S. pneumococcus
2) In development: RSV
E. Drug resistance increasing problem
“Accidental” Injuries
A. Foreign body aspiration
B. Food/Gastric content aspiration
C. Near drowning/drowning
Foreign Body Aspiration
A. Toddlers at increased risk
B. Peanuts, hotdogs, hard candies, small toys
C. Can result in:
1. Complete airway obstruction
2. Stridor
3. Wheeze
4. Persistent pneumonia
Chronic Aspiration
A. Food or gastric juice “down the wrong pipe”
B. Sources: abnormal swallow, gastroesophageal reflux, or both
C. Diagnostic testing; video-swallow study, pH probe, others . . .
Chronic Aspiration Symptoms
A. Recurrent pneumonia
B. Chronic cough
C. Recurrent stridor
D. “Noisy breathing” in infancy
E. Difficult to control asthma
Page 157 of 177

Populations at Risk for Aspiration
A. Infants
B. Neurologically impaired
C. History of congenital GI abnormalities
D. Pre-existing pulmonary disease
E. (Also normals!)
Near Drowning
A. Drowning: Second most common cause of injury & death in 1 mo to 14 yo children
B. Most common sites of drowning
< 1yo Bathtubs
Preschool Residential pools
Teens Ponds, lakes, ocean (EtOH)
C. In those who survive, neurologic impairment common
Pediatric Asthma : Highlights in Kids
A. Most common cause of hospitalizations, school absences, outpatient ill visits
B. 10-15% of children affected: 1/3 "outgrow"
C. Symptoms and treatment similar to adults, except for:
1. special concerns regarding inhaled steroids & growth
2. special challenges regarding administering inhaled meds
Differential Diagnosis of Wheezing in Children
A. Asthma
B. Chronic aspiration (GERD or dysphagia)
C. Large airway obstruction
1. Intrinsic anatomic problems: Tracheal stenosis, tracheomalacia
2. Acquired intra-airway obstruction: Tumors, foreign bodies
Hemoptysis
A. Top 3 Causes of pediatric hemoptysis
1. Respiratory infections (TB, Histoplasmosis)
2. Foreign bodies
3. Bronchiectasis (Cystic fibrosis, dysmotile cilia syndrome, etc.)
B. Other causes . . .
1. Lung malformations
2. Vascular abnormalities
3. Neoplasms
4. Immune-mediated syndromes
5. Left heart failure/congenital heart defects
6. Idiopathic
Page 158 of 177

C. Work-up
1. Radiographic imaging: CXR, CT scans
2. Bronchoscopy
3. Arteriography
4. Laboratory evaluations aimed at identifying underlying disorders
D. Interventions to Stop Bleeding
1. Bronchoscopic
Iced saline, topical epinephrine, fibrin & thromin mix, selective occlusion
2. Embolization
3. Lung resection
Chronic Cough
A. Top causes of chronic (> 3 weeks) cough in otherwise healthy patients
1. Asthma
2. Postnasal drip – allergy or sinusitis
3. Gastroesophageal reflux
4. (“Habit cough”)
B. Other causes
Infection, retained foreign body, cystic fibrosis, tracheoesophageal fistula,
Immunodeficiency
Shortness of Breath with Exercise
Most common causes in otherwise healthy kids:
• Exercise induced bronchospasm
• Vocal cord dysfunction
• Deconditioning
Primary pulmonary tumors
Malignant and benign forms
Very rare
Conclusion
A. The respiratory tract is a major source of vulnerability for children
B. Beyond the neonatal period, pulmonary illness due to infection, asthma, “injury,” and cystic
fibrosis are common
C. “Adult” pulmonary problems – such as interstitial lung diseases, pulmonary hypertension,
embolic disease, and cancer are seen in children – but much less commonly
Page 159 of 177

Clinical Approach to Cough
Time: 8:30 AM
Faculty: Karen Wood, MD; Division of Pulmonary & Critical Care Medicine
Email: Karen.Wood@osumc.edu
Objectives: by the end of this lecture, you should be able to:

1. Distinguish between acute, subacute, and chronic cough.
2. Recognize the common complications of cough.
chronic cough.
4. Recommend a diagnostic approach to Upper Airway Cough Syndrome as a
cause of chronic cough
5. Recommend a diagnostic approach to cough variant asthma.
6. Recommend a diagnostic approach to GERD as a cause of chronic cough.
Required Reading: Harrison’s Principles of Internal Medicine – 17th Ed (2008);

Chapter 34: Cough and Hemoptysis; Steven E. Weinberger, David A. Lipson.
1) Epidemiology:
a) 3.6% of all office based physician visits are for cough.
b) 29.5 million visits per year.
2) Definition:
a) Acute cough (< 3 weeks duration)
b) Subacute cough (3 – 8 weeks duration)
c) Chronic cough (> 8 weeks duration)
3) Mechanism:
a) Afferent Limb –
i) vagal afferent nerves receptors
(1) c-fibers
(2) RAR – Rapidly Adapting Receptors
(3) SARs – Slowly Adapting Stretch Receptors
ii) Sites of stimulation
(1) Pulmonary
(2) Esophagus
(3) Pharynx
(4) Ear
(5) Consciousness
b) Efferent Limb –
i) Deep Inspiration
ii) glottic closure
iii) expiratory effort against closed glottis with high intrathoracic volume causes
elevated intrathoracic pressures.
iv) narrowing of trachea
v) glottis opens - rapid flow rates
4) History
a) Duration of symptoms?
b) Infectious symptoms at onset?
Page 160 of 177

c) Associated symptoms of fever, dyspnea, chest pain, orthopnea, weight loss,
night sweats?
d) sputum production?
e) any evidence of asthma or allergy symptoms (wheezing, seasonal symptoms,
exercise symptoms)?
f) cigarette smoker?
g) ACE Inhibitor treatment?
h) Symptoms of GERD such as heartburn or cough after eating
i) Symptoms of post nasal drip (nasal drainage, throat clearing, nasal congestion)
j) Is the patient immunocompromised?
5) Initial Testing:
a) CXR
b) Spirometry
6) Differential:
a) Acute
i) Severe or life threatening disease
(1) Pneumonia
(2) PE
(3) Heart Failure
(4) Severe exacerbation of asthma or COPD
ii) Other Infectious
iii) Exacerbation of pre-existing condition
(1) Asthma
(2) Bronchiectasis
(3) Upper Airway Cough Syndrome (UACS)
(4) COPD
b) Subacute
i) Post infectious
ii) Exacerbation of pre-existing condition
(1) Asthma
(2) Bronchiectasis
(3) Upper Airway Cough Syndrome (UACS)
c) Chronic
i) ACE Inhibitor
ii) Smoking
iii) UACS (upper airway cough syndrome)
iv) Asthma
v) NAEB (nonasthmatic eosinophilic bronchitis)
vi) GERD (gastroesophageal reflux disease)
vii) COPD
viii) Cancer
ix) ILD
x) Bronchiectasis
xi) Aspiration
xii) Post-infectious
xiii) Tuberculosis or other infection
xiv) Habit cough
xv) Other lung disease
7) Complications of Cough
a) Embarrassment / self consciousness
b) Urinary incontinence
Page 161 of 177

c) Disturbed sleep / fatigue
d) Dizziness / Syncope
e) Chest and abdominal wall soreness
f) Rib fractures
g) Arrythmias
h) Herniations
i) Fear of serious disease
8) Approach and Treatment
a) History, PE, CXR, Spiro
i) If disease suggested – treat it!
b) If smoker – quit smoking
c) If on ACE Inhibitor – stop the treatment
d) If everything normal or still coughing evaluate and treat most common causes:
i) UACS – Upper Airway Cough Syndrome
(1) Diagnosis – empiric
(2) Treatment:
(a) Antihistamine and Decongestant
(b) nasal steroids
(c) Oral leukotriene inhibitors
(d) nasal ipratroprium
ii) Asthma
(1) Diagnosis
(a) Spirometry with bronchodilators
(b) Methacholine challenge (bronchial provocation testing)
(2) Treatment
(a) Inhaled corticosteroids
(b) Bronchodilators
(c) Leukotriene receptor antagonists
iii) NAEB
(1) Diagnosis
(a) Sputum for eosinophils
(2) Treatment
(a) Inhaled corticosteroids
iv) GERD
(1) Diagnosis
(a) Empiric Treatment
(2) Treatment
(a) Proton Pump Inhibitor
(b) Diet and Lifestyle modifications
9) Further testing that can be considered:
a) 24 hour esophageal pH monitoring
b) Swallow evaluation
c) Barium esophagram
d) Sinus CT
e) High resolution chest CT
f) Bronchoscopy
g) Echocardiogram
h) Videolaryngostroboscopy (VLS)
Page 162 of 177

Clinical Approach to Dyspnea
Time: 9:30 AM
Objectives
1. List the neural sensors that contribute to the sensation of dyspnea.
2. List the pathophysiologic conditions that contribute to the perception of dyspnea.
3. List the psychologic conditions that contribute to the perception of dyspnea.
4. Identify common causes of chronic dyspnea and list the 4 most common causes of chronic
dyspnea.
5. Identify common causes of acute dyspnea and list the 4 most common causes of acute dyspnea.
6. List the tests that are recommended in the initial evaluation of dyspnea
7. Distinguish between the different measurements of oxygenation and given a clinical scenario, be
able to choose the correct test.
8. Interpret the brain natiuretic peptide level (BNP).
9. Distinguish between cardiac and pulmonary causes of dyspnea using the cardiopulmonary exercise
test.
10. Associate the following tests with the conditions that they test for: methacholine challenge test,
eucapneic voluntary hyperventilation test, videolaryngostroboscopy test.
11. List specific strategies to reduce dyspnea by: reduce metabolic load, alter afferent information,
improve efficiency of carbon dioxide elimination, reduce ventilatory impedance, and alter central
perception.
12. Identify the main components of a pulmonary rehabilitation program.
Optional Reading
Harrison’s Principles of Internal Medicine, 17th edition 2008. Chapter 33: Dyspnea and Pulmonary Edema;
Richard M. Schwartzstein.
1. Contributions to dyspnea:
a. Origins of the sensation of dyspnea:
a. Upper airway receptors – trigeminal nerve
b. Chest wall mechanoreceptors
c. Pulmonary vagal receptors
1. Slowly adapting receptors – respond to tension in the walls
of the airways
2. Rapidly adapting receptors – stimulated by rapid changes in
lung volumes and inhaled irritants
3. C-fibers in small airways – stimulated by mechanical and
chemical factors
Page 163 of 177

d. Chemoreceptors - hypercarbia is a more powerful
contribution to the sensation of dyspnea than hypoxemia
1. Central – medulla
a. pH and PCO2
2. Peripheral – carotid bodies and aortic arch
a. PO2, pH, and PCO2
b. Contributions to the perception of dyspnea:
a. Increased ventilatory demand:
b. Anemia
c. Hypoxemia
d. Hypercapnia
e. Deconditioning
f. Respiratory muscle weakness
g. Lung hyperinflation - excessive length of inspiratory muscles
h. Airflow obstruction
c. Qualities of dyspnea:
a. Progression (from studies of methacholine challenge test
subjects): chest tightness - sensation of effort - air hunger
b. Psychologic effects:
1. Anxiety
2. Pain
3. Anger
4. Depression
2. Causes of chronic dyspnea (most common have an “*”):
a. Cardiac:
a. *Congestive heart failure
b. Coronary disease
c. Cardiac arrhythmias
d. Pericardial disease
e. Valvular disease
Page 164 of 177

b. Pulmonary:
a. *COPD
b. *Asthma
c. *Interstitial lung disease
d. Pleural effusion
e. Malignancy
f. Bronchiectasis
c. Non-cardiac/non-pulmonary:
a. Thromboembolic disease
b. Psychologic
c. Deconditioning
d. Pulmonary hypertension
e. Obesity
f. Anemia
g. Gastroesophageal reflux disease
h. Metabolic conditions (acidosis, uremia, etc.)
i. Cirrhosis
j. Thyroid disease
k. Neuromuscular disorders
l. Chest wall deformity
m. Tracheostenosis
n. Paradoxical vocal cord dysfunction
3. Assessment of chronic dyspnea:
a. Initial studies:
a. History and physical exam
b. CBC
c. Metabolic profile
d. Chest x-ray
e. EKG
f. Spirometry
g. Pulse oximetry
Page 165 of 177

b. History and physical exam - your most important tool to initially
categorize patients as most likely due to cardiac, pulmonary, and
neuromuscular etiologies
a. Orthopnea (shortness of breath when laying flat) – suggests heart
failure
b. Paroxysmal nocturnal dyspnea (shortness of breath that awakens
the patient from sleep) – suggests heart failure or asthma
c. Intermittent episodes of dyspnea – suggests myocardial ischemia
or bronchospasm
c. Oxygenation
a. Resting pulse oximetry
b. Exercise pulse oximetry:
1. 6 minute walk test
2. oxygen titration study
c. Overnight oximetry
d. Arterial blood gas
e. High altitude hypoxia simulation test
d. Pulmonary function tests
a. Spirometry: answers the question “is there obstruction?”
1. Asthma
2. COPD
3. Bronchiectasis
4. Bronchiolitis obliterans
b. Lung volumes : answers the question: “is there restriction?”
1. Interstitial lung disease
2. Respiratory muscle weakness
3. Chest wall deformity
4. Diaphragm paralysis
c. Diffusing capacity: answers the question: “is there gas diffusion
impairment?”
1. Emphysema
Page 166 of 177

2. Interstitial lung disease
3. Pulmonary vascular disease
e. Specialized tests (directed by initial evaluation)
a. Brain Natiuretic Peptide (BNP)
1. A negative study is very helpful to rule out heart failure
2. False positives (particularly in low level elevations) are
common
b. Cardiac echo
1. LV systolic function
2. LV diastolic function
3. Estimated PA pressure
4. Valvular heart disease
5. Pericardial effusion
c. Cardiac radionuclide study (ischemic heart disease)
d. Holter monitor (24 recording cardiac rhythm monitor to test for
intermittent cardiac arrhythmias)
e. Inducible asthma tests:
1. Methacholine challenge test: answers the question: “is there
occult pharmacologically-inducible asthma?”
2. Eucapneic voluntary hyperventilation test: answers the
question: “is there exercise-induced asthma?”
f. Cardiopulmonary exercise test: answers the question: “is the
dyspnea due to heart disease, lung disease, or deconditioning?”
1. Low maximum oxygen uptake = impairment
2. Achieves maximum predicted heart rate = cardiac limited
3. Achieves maximum predicted minute ventilation =
pulmonary limited
4. Four basic questions from the cardiopulmonary exercise
test:
a. Is the patient impaired?
b. Is the impairment cardiac in origin?
Page 167 of 177

c. Is the impairment pulmonary in origin?
d. Did the patient develop oxygen desaturation?
g. Videolaryngoscopy: answers the question: “is there paradoxical
vocal cord dysfunction?”
h. High resolution chest CT: answers the question: “is there
bronchiectasis or interstitial lung disease?”
i. CT pulmonary angiogram (or V/Q scan): answers the question: is
there thromboembolic disease?”
j. Cardiac catheterization
1. Left – evaluates the coronary arteries
2. Right – evaluates the pulmonary artery pressures
k. Bronchoscopy: mainly to search for tracheostenosis, to search for
occult airway tumor, or to investigate abnormal findings on
radiographs
l. Esophageal pH probe – evaluates for gastroesophageal reflux
4. Treatment of chronic dyspnea:
a. Treat the underlying disease!
b. Reduce metabolic load:
a. Exercise training
b. Supplemental oxygen during exercise - To qualify for home
oxygen, the PO2 must be less than 55 or the SaO2 must be less
than 88%. Importantly, most insurers are now requiring that you
document that the oxygen level returns to normal with
supplemental oxygen (therefore, order an oxygen titration
study!!)
c. Altering afferent information:
a. Vibration
b. Ventilator settings
c. Inhaled pharmacologic therapy
d. Fans
d. Improve efficiency of CO2 elimination:
Page 168 of 177

a. Altered breathing pattern (pursed lip breathing, etc.)
b. Improve respiratory quotient (reduce carbohydrates and increase
fat): R = number of carbon dioxide molecules generated per
every molecule of oxygen consumed
1. R for carbohydrates = 1.0
2. R for fat = 0.7
e. Reduce ventilatory demand:
a. Reduce airway resistance:
1. Bronchodilators
2. Corticosteroids
b. Reduce hyperinflation:
1. Lung reduction surgery
f. Improve inspiratory muscle strength and endurance
a. Nutrition
b. Exercise
c. Patient positioning
d. Ventilatory support (BiPAP, etc.)
e. Minimize oral corticosteroids
g. Altered Central Perception:
1. Education
2. Cognitive-behavioral approaches: relaxation, distraction
3. Desensitization
4. Pharmacologic therapy: anti-depressants, opiates, anxiolytics
5. Causes of acute dyspnea:
a. Cardiac:
a. Acute myocardial ischemia
b. Congestive heart failure
c. Pericardial tamponade
b. Pulmonary:
a. Bronchospasm
b. Pulmonary embolism
Page 169 of 177

c. Pneumothorax
d. Pulmonary infection
e. Upper airway obstruction
6. Assessment of acute dyspnea:
a. Pulse oximetry and/or arterial blood gas
b. Plasma BNP level
a. > 400 pg/ml – heart failure
b. 100-400 pg/ml – left ventricular dysfunction without
exacerbation, pulmonary embolism, cor pulmonale
c. Chest x-ray
d. CBC
e. EKG
Page 170 of 177

Bronchiectasis & Cystic Fibrosis
Time: 10:30 am
Phone: 722-4766
Resources:
Nelson Textbook of Pediatrics, 17th ed., (2004) Part 18, Section 33, Chapter 393
Harrison's Principles of Internal Medicine, 16th Ed. (2005) Part 8, Section 2, Chapter 236
CF and Bronchiectasis Objectives

1. Describe the airway abnormalities seen in bronchiectasis, and their functional consequences
2. List common causes, and treatments, for bronchiectasis
3. Identify common presenting symptoms and physical exam findings of a patient with
bronchiectasis
4. List studies used to evaluate patients suspected of having bronchiectasis, and predict test results
expected in a patient with the disease process
5. Describe the genetic abnormality, protein dysfunction, and resultant physiologic defects
associated with Cystic Fibrosis (CF)
6. Describe typical symptoms CF
7. List the organ systems commonly affected by CF
8. Identify criteria used to diagnose CF
9. Describe therapies commonly utilized to treat CF
10. List common complications of CF
BRONCHIECTASIS
Pathology
A. Permanently scarred, misshapen medium sized airways
B. May be localized, or diffuse
C. Pool secretions; once infected, ongoing inflammation
D. Often, overgrowth of vascular supply, with pulmonary-bronchial connections
Causes – Infection
A. Routine organisms
a. Viral (Adenovirus, influenza, measles)
Page 171 of 177

b. Bacterial (Staphylococcus aureus, Klebsiella, Anaerobes, TB and non-TB)
(More likely if treatment late, or partial)
B. Impaired Host Defense
a. Endobronchial obstruction (tumor, foreign body, congenital stenosis)
b. Generalized host defense problem
i. Cystic fibrosis
ii. Primary ciliary dyskinesia
iii. Immunoglobulin deficiency
Causes – “Other”
A. Toxins (Inhaled irritants – e.g. ammonia; Aspirated material – e.g. gastric contents)
B. Hyperactive immune response (allergic bronchopulmonary aspergillosis)
C. Alpha-1-antitrypsin deficiency
D. Yellow nail syndrome
Symptoms
A. Chronic/recurrent productive cough
B. Purulent sputum
C. Hemoptysis (coughed up blood)
D. Shortness of breath, wheeze, if widespread or caused by underlying disease
Findings
A. Physical Exam – Crackles, rhonchi, wheeze; clubbing
B. Radiographic
a. “tram tracks” “ring shadows” on CXR
b. Thickened bronchial walls, with airway bigger than adjacent vessel, on CT
Work-up
A. Sputum Culture
B. Radiographs and Lung function studies
C. Search for specific causes
a. Bronchoscopy
b. PPD
c. Testing for ABPA
d. Sweat test
e. Cilia biopsy
f. Immunoglobulin testing
Treatment
A. Eliminate cause, if possible
B. Improve clearance (chest therapy, mucolytics)
C. Control infection (“As needed” or chronic rotating antibiotics)
Page 172 of 177

D. Treat bronchospasticity/airway inflammation
E. If localize and severe, resection
F. If diffuse and severe, transplantation
Complications
A. Hemoptysis
B. Cor pulmonale (right heart failure due to lung disease related pulmonary hypertension)
Last Ditch Treatment
A. Local resection – especially if remaining lung healthy
B. Lung transplantation – if widespread disease
CYSTIC FIBROSIS
Overview
A. Most common lethal hereditary disease in Caucasians
B. Multisystem disease with pulmonary mortality in early adulthood
C. Autosomal recessive gene: carriers are asymptomatic
CF Pathophysiology
A. Cystic fibrosis transmembrane regulator (CFTR) gene is large
1. Over 5,000 aberrant forms
2. DeltaF508 most common abnormality
3. Genotype does not determine phenotype
B. CFTR Protein
1. Transmembrane transport protein
2. Primary function – Regulated chloride channel
3. Also affects other chloride and sodium channels at cell surface
4. Different classes of dysfunction have been identified – each with different levels of impact,
and potentially different treatments
C. Resultant pathology
1. Physical & chemical airway secretion abnormalities
- Decreased chloride secretion
- Increased sodium absorption
- Excessive water absorption
- Impaired ability to kill bacteria
2. Chronic infection
CF Typical Symptoms/Problems
A. Pulmonary
Chronic cough, recurrent pneumonia, wheezing, repeated “bronchitis”
B. GI
Meconium ileus, bulky greasy malodorous stool, poor weight gain
Page 173 of 177

C. Misc
Salty taste, rectal prolapse, severe pansinusitis, nasal polyps, pancreatitis, clubbing
D. Other complications
Intestinal obstruction syndromes Male infertility
Cirrhosis, gallstones Cor pulmonale
Diabetes Osteoporosis
CF Diagnosis
A. Typical Symptoms and/or (+) family history
B. Positive sweat chloride
C. 2 Indentifiable CFTR abnormalities confirms diagnosis; LACK does not exclude it, however
D. Newborn screening – Ohio
Immunoreactive trypsinogen (IRT) & common alleles can be measured on newborn screen
If IRT is high, then alleles are checked.
If allele(s) are identified, sweat test is performed.
If sweat test (+) then diagnosis is made
CF Pulmonary Manifestations
A. All patients, with variable onset and rate of progression
B. Airway plugging with thick mucous
C. Secondary infection with Staph. aureus, Pseudomonas sp.,
D. Asthma-like airway disease in roughly 50%
E. Chronic bronchitis, with exacerbations marked by increased cough, sputum production,
dyspnea, weight loss
F. Progressive bronchiectasis (distortion and scarring of airways)
G. Death due to respiratory insufficiency
CF Pulmonary Treatment
A. Secretion Removal
Bronchodilators & chest drainage, Mucolytics, aerobic exercise
B. Infection Control
Oral, IV and nebulized antibiotics
Isolation from other CF patients to avoid multi-resistant infection
C. Anti-inflammatory therapy (steroid, ibuprofen, azithromycin)
D. Control secondary causes of lung damage – GERD, viral infection, ABPA
E. Good Nutrition
F. Under development (anti-elastase, gene therapy, mechanistic therapies)
CF Exocrine Pancreatic Dysfunction
A. Present in 80-85% of CF patients
B. Malabsorption of fats and proteins due to enzyme deficiency
Page 174 of 177

C. Meconium ileus – obstruction in newborn period
D. Steatorrhea (oily, foul-smelling diarrhea)
E. Malnutrition/poor growth
F. Treatment: Enzyme replacement (± acid suppression), high calorie diet, vitamin supplements
Outpatient Treatment
A. Visits every 2-3 months
B. Regularly scheduled:
a. Throat or sputum cultures
b. Pulmonary function tests
c. CXR
d. Nutritional evaluation
C. Social work availability
D. “Team” review afterwards
“Simple” Home Regimen
A. Enzymes with meals and snacks, daily vitamin
B. “EAT!”
C. Twice daily chest therapy
D. Inhaled therapies – albuterol, dornase-alpha (mucolytic), inhaled tobramycin
Outpatient Exacerbation Care
A. Indications:
Increase symptoms - cough, sputum production, dyspnea
Decreasing PFT’s
Poor growth or weight loss
B. Therapy
10-21 days of atbs aimed at previous cultures
Continue standard therapy - do chest therapy!
CF: The “Clean-Out”
A. Indications -
Failure to respond to outpatient therapy for milder exacerbation
Initial presentation with severe problems
Major drop in lung function
New infiltrates on CXR
Major weight loss
Responding to outpatient therapy - but repeatedly re-flares
B. Treatment
IV antibiotics - dbl coverage
TID chest therapy
Page 175 of 177

“PIC” line
If nutritional issues: Nutrition consult, diabetes screen
Often discharge on home IV’s
CF Common Complications
A. “ Little h” Hemoptysis
Description:
Streaks of blood in sputum
Often with general increase in pulmonary sxs
Non-emergent
Treatment:
Treat the exacerbation
Make certain taking Vit K supplement (if pancreatic insufficient)
? Hold chest therapy & Pulmozyme briefly
B. “Big H” Hemoptysis
Description: > 1 cup/day bleeding
Source: overgrown bronchial arteries
Sudden onset - older patient
Risk of death 2° suffocation
Emergency!
Treatment: Embolization
C. Pneumothorax
Presentation
Acute unilateral chest pain
Shortness of breath ranging from mild to severe
Treatment
Chest tube, video-assisted thoracoscopic surgery (VATS)
D. CF Related Diabetes
Description
Combined poor production and poor response to insulin
>20% of CF patient over 25 years old
Symptoms:
Increased thirst/urination
Unexplained weight loss, fatigue
Unexpected declining lung function
Screening: Random, fasting, 2° post prandial glucoses
Treatment: Insulin replacement (for most)
E. Distal Intestinal Obstruction Syndrome (DIOS)
Page 176 of 177

Description:
Viscous mucus and stool obstruct terminal ileum and large intestine
Progressive colicky abdominal pain, nausea, anorexia
If severe: frank small intestine obstruction
Treatment:
Acutely: Go-lytely or similar electrolyte solution
Gastrografin enemas
Surgery
Chronically: More aggressive/consistent enzyme use
Routine use of cathartics
G. End Stage Care
Lung Transplantation
Nearly 1,600 CF patients have undergone lung transplantation
90% alive at one year; 50% at 5 years
Many do not survive to transplantation
Lung distribution determined by clinical score
For those who do not receive transplants; care focused on patient comfort
Reasons for Optimism
Steady improvement in CF survival curves as new therapies become available
Adults now make up >40% of living CF population – and are leading productive lives
Page 177 of 177

Pulmonary Course Packet 08

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pulmonary Course Packet 08

Uploaded by

Copyright:

Available Formats

The Ohio State University College of Medicine

Med 2 Integrated Pathway

An example of the first type of question is:

Hilar adenopathy with diffuse reticulonodular pulmonary infiltrates are most

An example of the second type of question is:

1. Ethylene glycol intoxication

Additionally, there will be review sessions most evenings at 6:30 (location to be

Jim Allen, M.D.

September 10 Meet with other members of your subgroup after your

3. List the tissues that comprise the alveolar wall.

5. Distinguish the bronchial and pulmonary circulations.

9. Given the barometric pressure, be able to calculate the PO2.

13. Define hyperventilation and hypoventilation. Describe the relation between

15. Define minute ventilation and alveolar ventilation.

17. Describe the physiology of the cough.

Date: September 9, 2008

5. What is the significance of the dual blood supply of the lungs?

3. Ogilvie, R.W. (2006) Histology: Independent Study Exercises, MUSC Press,

2. The conducting portion includes:

3. The respiratory portion includes: respiratory bronchioles, alveolar ducts,

II. CONDUCTING PORTION

a. Kartagener syndrome is an autosomal recessive disorder resulting in

b. Patients have a history of chronic respiratory infections. Men are infertile

B. Nasal Cavity and Paranasal Sinuses

C. Pharynx and Larynx

c. The intrinsic muscles, skeletal muscle innervated by the inferior laryngeal

3. The larynx is divided into three regions:

2. Four layers make up the tracheal wall.

c. C-shaped hyaline rings form the cartilaginous layer. These 16-20 C-

d. Adventitia is the peripheral loose connective tissue layer of the trachea.

2. The airways within the lung undergo unequal dichotomous branching.

c. The segmental bronchus and lung parenchyma that it supplies make up a

d. The segmental bronchi further divide into smaller subsegmental bronchi

e. Branching of the pulmonary arteries follows that of the airways as they

b. The lamina propria of the pulmonary airways – bronchi and bronchioles –

2. Bronchiole range from 5 – 1 mm in diameter and decrease in size with further

3. The initial pseudostratified columnar epithelium changes to simple ciliated

2. The respiratory acinus is considered to be the functional unit of the lung.

4. Respiratory bronchioles serve as a transition between the conducting airways

b. A smooth muscle cell acts as a sphincter, controlling the opening of an

b. Type II pneumocytes are cuboidal in shape and are interspersed among

2) Although close in number to the Type I cells, their cuboidal shape

3) They function as secretory cells whose lamellar bodies represent the

4) Surfactant forms a monomolecular layer over the alveolar epithelium,

5) Lack of surfactant can result in alveolar collapse during exhalation.

3. IgA secreted by plasma cells in the lamina propria and submucosa is

2. The pleura is lined by mesothelial cells that overlie a layer of connective

Physiology Lecture: Mechanisms of O2 and CO2 Transport

1. Define the 2 mechanisms by which O2 is carried in whole blood.

2. Distinguish between % oxygen saturation (SaO2), oxygen content (CaO2) and

4. Distinguish the differences in the behavior of the reaction between O2 and

5. Describe the pathophysiologic mechanism of carbon monoxide poisoning,

6. Distinguish the effects of anemia and carbon monoxide poisoning on the O2

7. Define the primary factors influencing delivery of O2 to metabolizing cells.

Date: September 10, 2008

West Physiology Chapter 3: Diffusion

West Physiology Chapter 7: Mechanics

Date: September 10, 2008

1. Calculate the A-a gradient.

A. The body’s major buffering system is the carbon dioxide-bicarbonate system.

Substituting in known values, pKA of carbonic acid 6.1, bicarbonate concentration 24

pH = 6.1 + log 24/0.03 x 40