Pathology

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1. 166.

Amorphous are enzymes affected in autosomal dominant disorders? atypia basophilic being uncharacteristic or lacking uniformity biopsy BOOK QUESTION: A 9-month-old child has a history of recurrent infections with multiple agents, including cytomegalovirus, Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis. A carefuly Fx and pedigree analysis show this to be a genetic disorder that is inherited in an autosomal recessive pattern. Which of the following laboratory studies is likely to be most useful in estabilshing the underlying mechanism of immunodeficiency in this infant? A) quantitative serum immunoglobulin levles B) enumeration of B cells in blood C) enumeration of CD3+ cells in blood D) tests of neutrophil function E) adenosine deaminase levels in leukocytes BOOK QUESTION: A 10-year old boy who is mentally retarded is able to carry out activities of daily living, including feeding and dressing himself. On PE he has brachycephaly and oblique palpebral fissures with prominent epicanthal folds. A transverse crease is seen on the palm of each hand. On auscultation of the chest there is a grade III/VI systolic murmur. Which of the following deseases is he most likely to develop by age 20? A) acute leukemia B) hepatic cirrhosis C) chronic renal failure D) acute myocardial infarction E) aortic dissection

having no apparent shape or organization no - instead receptors and structural proteins are involved being uncharacteristic or lacking uniformity readily stainable with basic dyes (usually hematoxylin = blue) atypia the removal of a sample of tissue, cells, or fluids from the living body for examination E) adenosine deaminase levels in leukocytes This patient is susceptible to bacterial, fungal, and firal infections and most likely has sever comined immunodeficiency (SCID). The autosomal recessive pattern of inheritance implicates adenosine deaminase (ADA) deficiency rather than mutations in the gamma chain of cytokine receptors. Low ADA levels in the leukocytes are diagnostic. The other listed options are relevant to the workup of primary immunodeficiencies, but they are not specific to SCID. see pp. 234235

3. 5. 4. 7.

115.

107.

A) acute leukemia This boy has Down syndrome (trisomy 21), one of the trisomies that can result in a liveborn infant. Although children with Down syndrome can function fairly well, they often have many associated congenital anomalies. Among the more common is congenital heart disease, including ventricular septal defect. There is also a 10-20 fold increased risk of acute leukemia. Virtually all persons with Down syndrome who live to the age of 40 will have evidence of Alzheimer disease. Hepatic cirrhosis is a feature of galactosemia. Chronic renal failure may be seen in genetic disorders that produce polycystic kidneys. Myocardial infarction at a young age suggests familial hypercholesterolemia. Aortic dissection is seen in persons with Marfan syndrome. See pp. 161-162.

106.

BOOK QUESTION: A 25-year-old woman amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft, 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities. On an abdominal MR imaging, the ovaries are small, elongated and tubular. Which of following karyotypes is most likely to be present in this patient? A) 45,X/46,XX B) 46,X,X(fra) C) 47,XXY D) 47,XXX E) 47,XX,+16 BOOK QUESTION: A 25-year-old woman gives birth to a term infant with a right transverse palmar crease, low-set ears, oblique palpebral fissures, and a heart murmur. The infant survives childhood and exhibits only mild mental retardation. Which of the following chromosomal abnormalities is most likely to be present in this child? A) haploidy B) monosomy C) mosaicism D) tetraploidy E) triploidy

A) 45,X/46,XX The features described are those of classic Turner syndrome. Persons who reach adulthood may have mosaic cell lines, with some 45,X cells and some 46,XX. A female carrier of the fragile X syndrome, X(fra), is less likely to manifest the disease than a male, but the number of triple repeat sequences (CGG) increases in her male offspring. The 47,XXY karyotype occurs in Klinefelter syndrome; affected persons appear as phenotypic males. The "superfemale" karyotype (XXX) leads to mild. (?) see pp. 165-167

108.

C) mosaicism These features are characteristic of trisomy 21, but the child is not severely affected, which suggests mosaicism. In mosaic persons, greater numbers of potentially normal cells having the proper chromosomal complement are present, which may allow infants with abnormalities of chromosome number to survive to term and beyond. Haploidy is present in gametes. Loss of an autosomal chromosome is devastating; the only monosomy associated with possible survival to term is Turner syndrome (monosomy X). Most aneuploid conditions (trisomies and monosomies) lead to fetal demise; fetuses with trisomy 21 are the most likely to survive to term. Triploid fetuses rarely survive beyond the second trimester and are virtually never liveborn. Likewise, tetraploidy accounts for many first-trimester fetal losses and is not survivable. see pp. 161-163 D) chronic renal failure is likely to occur This patient has systemic lupus erythematosus (SLE). Many persons with SLE have glomerulonepthritis and eventually develop renal failure. Blindness is uncommon in SLE. Raynaud phenomenon is associated with many autoimmune disease, but it is most troublesome in scleroderma. Although synovial inflammation is common in SLE, joint deformity is rare. The Libman-Sacks endocarditis associated with SLE tends to be nondeforming and limited and there is minimal valve damage. It is now uncommon, because of the use of corticosteroid therapy in the treatment of SLE. see pp. 213-221

114.

BOOK QUESTION: A 26-year-old woman has had bouts of joint pain for the past 2 years. She also has a rash on the cheeks and bridge of the nose. On PE there is no joint swelling or deformity, although generalized lymphadenopathy is present. Lab studies indicate anemia, leukopenia, a polyclonal gammopahty, and proteinuria. The serum ANA test result is positive at a titer of 1:1024 with a rim pattern identified by immunofluorescence. The light microscopic immunofluorescent (with antibody to IgG) appearances of a skin biopsy are shown [dark green with lighter green border]. Which of the following is the best information to give this patient about her disease? A) blindness is likely to occur within 5 years B) avoid exposure to cold environments C) joint deformities will eventually occur D) chronic renal failure is likely to occur E) cardiac valve replacement will eventually be recquired

109.

BOOK QUESTION: A 37-year-old man who is HIV positive has noticed multiple 0.5-1.2 cm plaque-like, reddish-purple skin lesions on his face, trunk and extremities. Some of the larger lesions appear to be nodular. These lesions have appeared over the past 6 months and have slowly enlarged. Molecular analysis of the spindle cells found in these skin lesions is likely to reveal the genome of which of the following viruses? A) cytomegalovirus B) Epstein-Barr virus C) adenovirus D) human herpesvirus-8 E) HIV-1 BOOK QUESTION: A 45-year-old woman has experienced difficulty in swallowing that has increased in severity over the past year. She has also experienced malabsorption, demonstrated by a 5-kg weight loss in the past 6 months. She reports increasing dyspnea during this time. On PE, her temp is 36.9C, pulse 66/min, RR 18/min and BP 145/90 mmHg. Echocardiography shows a large pericardial effusion. The Anti Nuclear Antibody test result is positive at 1:512 with a nucleolar pattern. Which of the following serious complications of the patient's underlying autoimmune disease is most likely to occur? A) meningitis B) glomerulonephritis C) perforated duodenal ulcer D) adrenal failure E) malignant hypertension BOOK QUESTION: An epidemiologic study is conducted to determine risk factors for HIV infection. The study documents that persons with coexisting sexually transmitted diseases such as chancroid are more likely to become HIV positive. It is postulated that an inflamed mucosal surface is an ideal location for the transmission of HIV during sexual intercourse. Which of the following cells in these mucosal surfaces is most instrumental in transmitting HIV to CD4+ T lymphocytes? A) CD8+ cells B) natural killer cells C) dendritic cells D) neutrophils E) plasma cells

D) human herpesvirus-8 This patient has AIDS, with Kaposi sarcoma of the skin. Kaposi sarcoma is associated with a herpesvirus agent that is sexually transmitted: human herpesvirus 8 (HHV-8), also called Kaposi sarcoma herpesvirus. Other herpesviruses are not involved in the pathogenesis of Kaposi sarcoma, although infection with these viruses can occur frequently in persons with AIDS. HIV, although present in the lymphocytes and monocytes, is not detected in the spindle cells that proliferate in Kaposi sarcoma. With the exception of the varicella-zoster virus, which is associated with dermatomally distributed skin vesicles known as shingles, skin lesions are not common manifestations of herpesviruses, which include cytomegalovirus, Epstein-Barr virus, or adenovirus infections. see pp. 246-247 E) malignant hypertension This patient has diffuse systemic sclerosis (scleroderma). The small arteries of the kidney are damaged by a hyperplastic arteriolosclerosis that can be complicated by very high blood pressure and renal failure. Meningitis and adrenal failure are not typical features of autoimmune diseases. Glomerulonephritis is a more typical complication of systemic lupus erythematosus. With scleroderma, the gastrointestinal tract undergoes fibrosis, without any tendency to perforation or ulceration. see pp. 223-225

110.

111.

C) dendritic cells Three types of cells can carry HIV: dendritic cells, monocytes, and CD4+ T lymphocytes. Mucosal dendritic cells (i.e. Langerhans cells) can bind to the virus and transport it to CD4+ cells in the lymph nodes. Whether the virus is internalized by mucosal dendritic cells is not clear. Monocytes and CD4+ T cells express CD4 and the coreceptors (CCR5 and CXCR4); therefore, HIV can enter these cells. The other listed cells cannot be infected by HIV. see pp. 238-243

116.

BOOK QUESTION: An infant born at term develops abdominal distension in the first week of life. Meconium ileus is diagnosed. The infant has persistent steatorrhea and fails to develop normally. Later in childhood, multiple respiratory tract infections lead to widespread bronhioectasis. Which of the following laboratory findings is most likely related to this child's underlying disease? A) decreased serum thyroxine level B) positive HIV serology C) elevated sweat chloride level D) increased urine homovanillic acid level E) hyperbilirubinemia BOOK QUESTION: A 38-year-old man has had headaches and nausea for the past 2 months. Lab findings show hypercalcemia and hypophosphatemia and normal serum albumin. Urine microscopic analysis shows deposition of calcium salts in the renal tubular epithelium. Which of the following processes has most likely produced this change in the kidney? A) dystrophic calcification B) renal tubular atrophy C) autophagocytosis D) metastatic calcification E) cellular aging BOOK QUESTION: An experiment introduces a "knockout" gene mutation into a cell line. The frequency of cell karyorrhexis and cytoplasmic fragmentation is increased, compared with a cell line without the mutation. Overall survival of the mutant cell line is reduced. Which of the following genes is most likely to be affected by this mutation? A) BAX B) BCL-2 C) C-MYC D) FAS E) TP53 Can hypertrophy and hyperplasia occur together? Can they both result in an enlarged (hypertrophic) organ? the cause or causes of a disease or abnormal condition characterized by swelling and taking up of fluid a deficiency of oxygen reaching the tissues of the body a deficient supply of blood to a body part a degenerative condition of a cell nucleus marked by clumping of the chromosomes, hyperchromatism, and shrinking of the nucleus describe the mechanism of cell injury by accumulation of reactive oxygen species

C) elevated sweat chloride level The findings are typical of cystic fibrosis, CF. see pp. 465-471

104.

D) metastatic calcification Deposition of calcium in normal healthy tissues as a result of prolonged hypercalcemia is called metastatic calcification. This process may occur in hyperparathyroidism. Dystrophic calcification refers to calcium deposition in injured tissues, with normal serum calcium levels. Atrophy decreases cell size but is not accompanied by calcium deposition. Autophagocytosis yields more golden-brown lipofuscin pigment in the cytoplasm, particularly in hepatocytes and myocardial fibers, a process that becomes more apparent with aging. See pp. 38-39.

105.

B) BCL-2 The BCL-2 gene product inhibits cellular apoptosis by binding to Apaf-1. The BAX gene product promotes apoptosis. The C-MYC gene is involved with oncogenesis. The FAS gene encodes for a cellular receptor for FAS ligand, which signals apoptosis. TP53 gene activity normally stimulates apoptosis, but mutation favors cell survival. See pp. 28-29.

90.

yes and yes: e.g. the uterus during pregnancy

12.

etiology hydropic hypoxia ischemia pyknosis

24. 26.

32. 52.

126.

covalent modification of cellular proteins, lipids, nucleic acids

127.

describe the mechanism of cell injury by increased permeability of cellular membranes what is the typical result? a diseased state or symptom distinctively characteristic of a particular disease or condition do all cells have MHC groups? does increased demand of the striated muscle cells in both the skeletal muscle and the heart lead to hypertrophy or hyperplasia? eosinophilic etiology excision extrinsic the form and structure (appearance) of an organism or any of its parts a group of signs and symptoms that occur together and characterize a particular abnormality having no apparent shape or oganization heterogeneous homeostasis homogeneous how do antibodies and immunoglobulins relate to each other? which cells produce and have them bound on their membrane? how do the terms etiology and pathogenesis relate to each other? how do the terms lymphocytes and leukocytes relate to each other? how does immunohistochemistry help in diagnosis and classification of tumors? how does repair by connective tissue proceed? how to the dendritic cells operate?

may affect plasma membrane, lysosomal membranes, mitochondrial membranes; typically culminates in necrosis morbidity pathognomonic - no - only nucleated cells - therefore not RBCs hypertrophy only because adult muscle cells have a limited capacity to divide

36. 44.

72.

91.

9. 11. 13. 15.

readily stainable with eosin (red) the cause or causes of a disease or abnormal condition surgical removal or resection of an entire lesion or diseased portion originating or due to causes or factors from or on the outside of a body, organ or part morphology syndrome

38.

56.

2. 17. 21.

amorphous not uniform in structure or composition the maintenance of a relatively stable internal physiological conditions under fluctuating environmental conditions of uniform structure or composition throughout - antibodies and immunoglobulins are essentially synonymous - produced by and sometimes attached to B-lymphocytes

19. 61.

82.

etiology refers to why a disease arises, pathogenesis describes how a disease develops - both are essential for not only understanding a disease but also the basis for rational treatments - leukocytes is the name for all of the white blood cells - lymphocytes are one of the several types of WBCs - distinct protein expression patterns define different entities - e.g. detection of specific monoclonal antibodies by labeling, and specific antigens like PSA and estrogen receptors starts with formation of granulation tissue and culminates in the laying down of fibrous tissue -- scar formation - capture microbes and foreign antigens --> transport to lymph nodes --> antigen presentation to naive lymphocytes --> recognition --> lymphocyte activation and proliferation into effector/plasma and memory cells characterized by swelling and taking up of fluid a deficiency of oxygen reaching the tissues of the body induced inadvertently by medical treatment or diagnostic procedures

69.

148.

144.

151.

23. 25. 33.

hydropic hypoxia iatrogenic

139.

identify some of the major cell-derived mediators of inflammation and their effects

- vasoactive amines - histamines, serotonin: main effects are vasodilation and increased vascular permeability - arachidonic acid metabolites - prostaglandins and leukotrienes: several forms exist and are involved in vascular rxns, leukocyte chemotaxis, and other rnxs of inflammation, antagonized by lipoxins - cytokines: proteins produced by many cell types, usually act at short range; mediate multiple effects, mainly leukocyte recruitment and migration; principal ones in acute inflammation are TNF, IL-1, IL-6 and chemokines - ROS: roles include microbial killing and tissue injury - NO: effects are vasodilation and microbial killing - lysosomal enzymes: roles include microbial killing and tissue injury the rate of occurrence of new cases of a particular disease in a population being studied iatrogenic originating or due to causes or factors within a body, organ or part pathologic atrophy

27.

incidence induced inadvertently by medical treatment or diagnostic procedures intrinsic is the decreased workload and loss of innervation to a limb following injury pathologic or physiologic atrophy? is the loss of hormone stimulation in menopause pathologic or physiologic atrophy? ischemia the maintenance of relatively stable internal physiological conditions under fluctuating environmental conditions morbidity morphology mortality most forms of pathologic hyperplasia are caused by excessive hormonal or growth factor stimulation - what are some examples?

34.

29. 99.

98.

physiologic atrophy a deficient supply of blood to a body part homeostasis

31. 22.

35. 37. 39. 94.

a diseased state or symptom the form and structure (appearance) of an organism or any of its parts the number of deaths in a given time or place - endometrial hyperplasia after a normal menstrual period due to disturbance between estrogen and progesterone - hyperplasia of the breast - skin warts composed of hyperplastic epithelium - growth factors may be from viral genes or those of infected cells sequelae heterogeneous B. excretion / gain (A, C, D all structural)

54. 18. 113.

a negative aftereffect not uniform in structure or composition NOTES QUESTION: Which of the following is classifiable as a functional abnormality? A. a large tumor increasing pressure in the brain B. elevated HR due to excessive secretion of thyroid hormone C. loss of renal filtration due to amyloid deposition in the kidney D. rupture of an aneurysm due to a thin, weak vessel wall.

112.

NOTES QUESTION: Which of the following is TRUE of free radicals? A. cells with high metabolic requirements are prone to injury B. formed by antioxidants C. inhibit apoptosis D. predominately cause damage by blocking metabolic pathways the number of deaths in a given time or place of uniform structure or composition throughout originating or due to causes or factors from or on the outside of a body, organ, or part originating or due to causes or factors within a body, organ or part pathogenesis pathognomonic the percentage of a population that is affected with a particular disease at a given time pleomorphism prevelance prognosis

A. cells with high metabolic requirements are prone to injury

40. 20. 16.

mortality homogeneous extrinsic intrinsic the steps in development of a disease distinctively characteristic of a particular disease or condition prevelance variation in size and shape the percentage of a population that is affected with a particular disease at a given time the prospect of survival and recovery from a disease as anticipated from the usual course of that disease or indicated by special features of the case prognosis

30.

41. 43. 48.

45. 47.

49.

50.

the prospect of survival and recovery from a disease as anticipated from the usual course of that disease or indicated by special features of the case pyknosis

51.

a degenerative condition of a cell nucleus marked by clumping of the chromosomes, hyperchromatism, and shrinking of the nucleus incidence basophilic eosinophilic biopsy a negative aftereffect pathogenesis excision a group of signs and symptoms that occur together and characterize a particular abnormality True!

28.

the rate of occurrence of new cases of a particular disease in a population being studied readily stainable with basic dyes (usually hematoxylin = blue) readily stainable with eosin (red) the removal of a sample of tissue, cells, or fluids from the living body for examination sequelae the steps in development of a disease surgical removal or resection of an entire lesion or diseased portion syndrome True or False: Hyperplasia is an adaptive response in cells capable of replication, whereas hypertrophy occurs when cells have a limited capacity to divide.

6. 10. 8.

53. 42. 14.

55.

89.

88.

True or False: in pure hypertrophy there are no new cells, just bigger cells containing increased amounts of structural proteins and organelles variation in size and shape what are 3 possible actions of a Blymphocyte?

True

46. 66.

pleomorphism - the antibodies on outside of cell can bind pathogen then engulfs and performs antigen presentation using MHC II (like macrophage) - [activated by Helper T cell that binds to MHC II] - can proliferate as PLASMA cells to produce free floating antibodies - can proliferate to form long-lasting MEMORY cells - trisomy 21 or translocation - clincial features: severe mental retardation, flat facial profile, epicanthic folds, cardiac malformations, higher risk of leukemia and infections, premature development of Alzheimer disease - oxygen deprivation / hypoxia - chemical agents - infectious agents - immunologic rxns - genetic factors - nutritional imbalances - physical agents - aging - XLA: failure of B cell maturation, absence of antibodies, caused by mutations in BTK which encodes a tyrosine kinase required for maturation signals from the pre-B cell and B cell receptors - selective IgA deficiency - X-SCID: failure of T cell and B cell maturation; mutation in the common gamma chain of cytokine receptor leading to failure of IL-7 signaling and defective lymphopoiesis - autosomal SCID: failure of T cell development, secondary defect in antibody responses; approximately 50% of cases caused by mutation in the gene encoding ADA, leading to accumulation of toxic metabolites during lymphocyte maturation and proliferation - X-linked hper-IgM syndrome: failure to produce isotype-switched high-affinity antibodies (IgG, IgA, IgE); mutation in gene encoding CD40L - clinical presentation: increased susceptibility to infections in early life - prolonged host response to persistent stimulus - caused by: microbes that resist elimination; immune responses against self and environmental antigens, and some toxic substances (e.g. silica); underlies many important diseases - characterized by persistent inflammation, tissue injury, attempted repair by scarring and immune response - cellular infiltrate consisting of activated macrophages, lymphocytes and plasma cells often with prominent fibrosis - mediated by cytokines produced by macrophages and lymphocytes (notably T lymphocytes) with a tendency to an amplified and prolonged inflammatory response owing to bidirectional interactions between these cells - epithelial barriers - phagocytes - NK cells - plasma proteins (e.g. complement) *rxn often manifested as inflammation

173.

what are characteristics of Down syndrome?

117.

What are some categories of causes of cell injury?

163.

what are some of the common primary (congenital) immune deficiency diseases?

141.

what are some of the features of chronic inflammation?

150.

what are some of the mechanisms of innate immunity?

158.

what are some of the principal mediators in immediate (typeI I) hypersensitivity (allergies)? what are symptoms of allergies? what are some systemic effects of inflammation?

- histamine, proteases; prostaglandins and leukotrienes, cytokines - responsible for immediate vascular and smooth muscle rxns and late-phase rxn (inflammation) - from annoying rhinitis to fatal anaphylaxis - fever: cytokines (TNF, IL-1) stimulate production of prostaglandins in hypothalamus - production of acute-phase proteins: C-reactive protein, others; synthesis stimulated by cytokines (IL-6, others) acting on liver cells - leukocytosis: cytokines (CSFs) stimulate production of leukocytosis from precursors in the bone marrow - in some severe infections, septic shock: fall in BP, disseminated coagulation, metabolic abnormalties; induced by high levels of TNF if stress is: severe, persistent, rapid in onset

142.

83.

what are the characteristics external stress that lead to irreversible injury and death of affected cells? what are the mechanisms by which leukocytes eliminate microbes? how can this damage normal tissues? what are the most common/best antigen presenting cell? what type of MHC group does it have? which T cells will read the MHC presentation? what are the sampling approaches for diagnosis of tumors? what are the steps of inflammatory response (the five Rs)? what are the possible outcomes due to inflammation?

137.

- leukocytes eliminate microbes and dead cells by phagocytosis - destruction is caused by free radicals (ROS, NO) generated in activated leukocytes and lysosomal enzymes - enzymes and ROS may be released into ECF - dendritic cells - MHC II - Helper T cells with CD4 receptor

71.

147.

excision, biopsy, fine-needle aspiration and cytologic smears - 1. recognition of the injurious agent; 2. recruitment of leukocytes, 3. removal of the agent, 4. regulation (control) of the response, 5. resolution (repair) - outcome of acute inflammation is either elimination of the noxious stimulus, followed by decline of the rxn and repair of the damaged tissue OR - persistent injury resulting in chronic inflammation - leukocytes are recruited (by cytokines from tissue macrophages and other cells) from blood to extravascular tissue where pathogens or damaged tissues are present, then activated to perform fxn: - loose attachment to and rolling on endothelium, mediated by selectins - firm attachment to endothelium, mediated by integrins - migration through interendothelial spaces - necrosis is when damage to membranes is ssever, enzymes leak out of lysosomes, enter the cytoplasm, and digest the cell - cellular contents also leak through plasma membrance into ECF and elicit inflammation - apoptosis is when a cell is deprived of growth factors or the cell's DNA or proteins are damaged beyond repair and the cell kills itself - characterized by nuclear dissolution and does not illicit an immune response - dystrophic calcification: deposition of calcium at sites of cell injury and necrosis - metastatic calcification: deposition of calcium in normal tissues, caused by hyperclcemia (usually a consequence of parathyroid hormone excess) - hormonal hyperplasia exemplified by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy - compensatory hyperplasia in which residual tissue grows after removal or loss of part of an organ, e.g. when part of a liver is resected mitotic activity in the remaining cells begin as early as 12 hours later eventually restoring the liver to its normal weight

133.

135.

what are the steps of leukocyte recruitment to sites of inflammation and what chemical signals promote each step?

103.

what are the two types of cell death? what are the mechanisms, morphology and roles of each in disease and physiology?

130.

what are the two types of pathologic calcification and what are the characteristics of each? what are the two types of physiologic hyperplasia and what is an example of each?

93.

92.

what are the two types of signals driving cardiac hypertrophy? in what types of cells does hypertrophy occur? what are the types of WBCs or leukocytes?

- mechanical triggers such as stretch - trophic triggers which are soluble mediators that stimulate cell growth such as growth factors and adrenergic hormones - occurs in tissues incapable of cell division - neutrophils - lymphocytes (B&T) - monocytes - eosinophils - basinophils - vasodilation induced by chemical mediators such as histamine and is the cause of erythema and stasis of blood flow - increased vascular permeability induced by histamine, kinins, and other mediators that produce gaps between endothelial cells; by direct or leukocyte-induced endothelial injury; and by increased passage of fluids through the endothelium - this increased perm. allows plasma proteins and leukocytes to enter sites of infection or tissue damage; fluid leak through blood vessels results in edema - accumulation of DNA damage (e.g. by free radicals): defective DNA repair mechanisms; conversely DNA repair may be activated by calorie restriction which is known to prolong aging in model organisms - replicative senescence: reduced capacity of cells to divide secondary to progressive shortening of chromosomal ends (telomeres) - other factors: progressive accumulation of metabolic damage; possible roles of growth factors that promote aging in simple model organisms - complement proteins: activation of the complement system by microbes or antibodies leads to the generation of multiple breakdown products, which are responsible for leukocyte chemotaxis, opsonization and phagocytosis of microbes and other particles and cell killing - coagulation proteins: activated factor XII trigges the clotting, kinin and complement cascades and activates the fibrinolytic system - kinins: produced by proteolytic cleavage of precursors, this group mediates vascular rxn and pain - neutrophils predominate in the early inflammatory infiltrate - later replaced by macrophages/monocytes

58.

134.

what are the vascular rxns in acute inflammation?

131.

what are three routes to cellular aging? what are the characteristics of each?

140.

what are three types of plasma protein-derived mediators of inflammation and what is their mechanism? what cells predominate in the early inflammatory response and by what are they later replaced? what changes in the cell characterize necrosis?

136.

119.

- changes in cytoplasm and nuclei - increased eosinophilia (i.e. pink staining from eosin dye) attributable to increased binding o eosin to denatured cytoplasmic proteins and in part to loss of the basophilia that is normally imparted by the RNA in cytoplasm - nuclear changes are all due to breakdown of DNA and chromatin and assume one of three patterns: karyolysis (fading), pyknosis (nuclear shrinkage), karyorrhexis (fragmentation) - hyperplastic process is controlled if the signals abate, it disappears - in cancer the growth control mechanisms become dysregulated or ineffective release of histamines

95.

what distinguishes pathologic hyperplasia from cancer? what do mast cells release when stimulated by injury or release of chemokines? what does persistent stimulation of collagen synthesis in chronic inflammatory diseases lead to? what happens when a cytotoxic T cell CD8 receptor binds to a body cell MHC I?

78.

146.

fibrosis of the tissue

75.

- cytotoxic T cell releases perforins to kill cells that are infected or bad

80.

what is a general role of the complement system?

- inactive, free-floating proteins that are activated by proteolytic cleavage --> nonspecific defense - CLASSICAL PATHWAY: C4 and C2 each cleaved --> C4b and C2a bind --> together act as enzyme to cleave C3 --> C3a bind to leukocytes --> triggers inflammation --> C3b binds with C4b-C2a --> cleaves C5 - ALTERNATIVE PATHWAY: spontaneous cleavage of C3 --> C3b binds to microbe surface --> binds factors --> cleaves more C3 --> eventually cleaves C5 - a disorder characterized by the extracellular deposits of misfolded proteins that aggregate to form insoluble fibrils - may result in excessive production of proteins prone to misfolding and aggregation; or incomplete proteolytic degradation of extracellular proteins - can be localized or systemic; associated with: deposits of light chain Igs/ monoclonal plasma cell proliferations, chronic inflammatory disease such as RA, Alzheimer disease, dialysis - deposits can cause tissue injury and impair normal function by causing pressure on cells and tissues - do NOT evoke an inflammatory response leukocytes - regulated mechanism of cell death that serves to eliminate unwanted and irreparably damaged cells, with the least possible host rxn -characterized by enzymatic degradation of proteins and DNA, initiated by caspases; and by recognition and removal of dead cells by phagocytes - mitochondrial/intrinsic pathway is triggered by loss of survival signals, DNA damage and accumulation of misfolded proteins (ER stress); associated with leakage of pro-apoptotic proteins from mitochondrial membrane into the cytoplasm, where they trigger caspase activation; inhibited by anti-apoptotic members of the Bcl family, which are induced by survival signals including growth factors - death receptor/extrinsic pathway is responsible for elimination of self-reactive lymphocytes and damage by cytotoxic T lymphocytes; is initiated by engagement of death receptors (members of the TNF receptor family) by ligands on adjacent cells rxn of T lymphocytes, designed to combat cell-associated microbes, e.g. phagocytosed microbes and those in cytoplasm and infected cells - cystic fibrosis is autosomal recessive disease caused by mutations in the CFTR gene encoding transmembrane regulator - principal defect is chloride ion transport resulting in high salt conc. in sweat and viscous luminal secretions in resp. and GI tracts - cardiopulmonary complications constitute the most common cause of death, pulmonary infections are frequent - pancreatic insufficiency is common along with infertility - liver disease is increasing due to improved survival - deletion of genes at chromosomal locus 22q - gives rise to malformations affecting face, heart, thymus and parathyroids - pathologic amplification of trinucleotide repeats of CGG (normally ~29; if 52-200 can expand to 4,000) causing loss-of-function (fragile X) or gain-of-function (Huntington) - most produce neurodegenerative disorders - fragile X from loss of FMR1 gene - clinical features: mental retardation, macroorchidism, abnormal facial features - caused by inherited lack of GALT enzyme leading to accumulation of galactose-1-phosphate - clinical features: jaundice, liver damage, cataracts, neural damage, vomiting and diarrhea, E. coli sepsis - imprinting involves transcriptional silencing of the paternal or maternal copies of certain genes - often due to deletion - Prader-Willi syndrome results from deletion of paternal chromosomal region 15q12 - characterized by mental retardation, short stature, hypotonia, obesity and hypogonadism - Angelman syndrom results from deletion of maternal chromosomal region 15q12 - characterized by mental retardation, ataxia, seizures and inappropriate laughter

165.

what is amyloidosis?

57.

what is another term for white blood cells? what is apoptosis? how is it characterized? and what are the two pathways?

129.

152.

what is cell-mediated immunity? what is CF?

170.

174.

what is DiGeorge syndrome? what is fragile X syndrome?

177.

172.

what is galactosemia? what is genomic imprinting? which pair of diseases result from imprinting on chromosome 15?

178.

162.

what is GVHD?

- graft-versus-host disease - when immunologically competent T cells are translanted into recipients who are immunologically compromised - acute GVHD: days to weeks, epithelial cell necrosis in liver, skin, gut --> jaundice --> bloody diarrhea --> rash - chronic GVHD: may follow acute or occur insidiously, patient develops skin lesions resembling SS and other symptoms that mick other autoimmune disorders - the development/maturation of B-lymphocytes - intentional shuffling of the variable portion of DNA for antibodies mediated by antibodies and is effective against extracellular microbes, i.e. those in circulation and mucosal lumens - a defensive host response to foreign invaders and necrotic tissue but it is itself capable of causing tissue damage - vascular rxn and cellular response; both are activated by mediators derived from plasma proteins and various cells lack of blood flow - two or more X chromosomes with on Y chromosome - clinical features: testicular atrophy, sterility, reduced body hair, gynecomastia, eunuchoid body habitus - mutation to gene encoding fibrillin FBN1 which is required for structural integrity of connective tissue - affected tissues include skeleton, eyes, CV system - clinical features: tall stature, long fingers, bilateral subluxation of lens, mitral valve prolapse, aortic aneurysm, aortic dissection - when antibodies bind to antigen on pathogen and mark them for destruction - can reduce pathogen activity - can cause coagulation the study of disease, it involves the causes of disease and the associated changes at the levels of cells, tissues, and organs which in turn give rise to the presenting signs and symptoms of the patient - phenylketonuria is autosomal recessive disorder caused by lack of enzyme phenylalanine hydroxylase consequent inability to metabolize phenylalanine - clinical features: severe mental retardation, seizures, decreased pigmentation of skin - females who discontinue treatment can give birth to children with malformations due to transplacental passage of phenylalanine metabolites - systemic lupus erythematosus - systemic autoimmune disease with manifestations including nephritis, skin lesions, arthritis, hematologic and neurologic abnormalities - underlying cause unknown; may include nuclear antigens, inherited susceptibility genes, environmental triggers - systemic sclerosis, aka scleroderma - characterized by progressive fibrosis involving the skin, GI tract, and other tissues - fibrosis may be the result of activation of fibroblasts by cytokines produced by T cells, triggers unkown - endothelial injury and microvascular disease are commonly present in the lesions of SS causing chronic ischemia can cause keloids in the skin - chemokines

62.

what is hematopoesis? what is humoral immunity? what is inflammation? what are the main components of inflammation? what is ischemia? what is Klinefelter syndrome?

153.

132.

84. 175.

169.

what is Marfan syndrome?

63.

what is opsonization?

81.

what is pathology?

171.

what is PKU?

159.

what is SLE?

160.

what is SS?

145.

what is the consequence of excessive production of ECM? what is the general name for chemicals released by damaged/injured cells?

77.

123.

what is the gross appearance of caseous necrosis? what is the gross appearance of coagulative necrosis? what is the gross appearance of fat necrosis?

- "cheese-like" friable yellow-white appearance - tissue architecture obliterated - distinctive inflammatory border = granuloma - tissues have firm texture - eosinophilic anucleate cells persist - characteristic of infarcts in solid organs except brain - leaked activated pancreatic lipases liquefy membranes of fat cells in peritoneum - released fatty acids combine with calcium to produce grossly visible chalky white areas (fat saponification) - occurs during emergency known as acute pancreatitis - antigen and antibody deposits on walls of arteries - visible by light microscopy - on H&E preparations bright pink appearance called fibrinoid - limb that has lost blood supply and bacterial infection superimposed --> coagulative necrosis + liquefactive action = wet gangrene - often evoked from hypoxic death of CNS cells - dead cells digested into a liquid viscous mass - if bacterial --> acute inflammation --> material frequently creamy yellow pus - virus entry into cells: requires chemokine receptor CD4, main targets CD4+helper T cells, macrophages, DCs - viral replication - progression through acute infection of mucosal T cells and DCs, latent infection of cells in lymphoid tissue - mechanisms of immune deficiency: loss of CD4+T cells, defective macrophages and DC fxns, destruction of lymphoid tissue (late) an intact ECM is required for tissue regeneration, and if the ECM is damaged, repair can be accomplished only by scar formation - cellular function may be lost long before cell death occurs, and the morphologic changes of cell injury (or death) lag far behind both - e.g. myocardial cells become noncontractile after 1-2 minutes of ischemia although they do not die until 20-30 minutes of ischemia have elapsed - may not appear dead by electron microscopy for 2-3 hours or by light microscopy for 6-12 hours hypertrophy - increased size of the individual cells and ultimately the entire heart - to generate the required higher contractile force metaplasia

120.

124.

125.

what is the gross appearance of fibrinoid necrosis? what is the gross appearance of gangrenous necrosis? what is the gross appearance of liquefactive necrosis? what is the HIV life cycle and pathogenesis of AIDS?

122.

121.

164.

143.

what is the importance of the extracellular matrix related to tissue repair? what is the relationship among cellular function, cell death, and morphologic changes of cell injury?

118.

86.

what is the response of the myocardium to persistent load from hypertension or stenotic valves? what is the reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type? what is the role of the CD4+ helper T cells?

100.

154.

- help B cells make antibodies, activate macrophages to destroy microbes, stimulate recruitment of leukocytes - fxns regulated by cytokines - match with MHC II - kill cells that express antigens in the cytoplasm that are seen as foreign, e.g. virusinfected and tumor cells - match with MHC I

155.

what is the role of the CD8+ cytotoxic T cells?

70.

what is the role of the helper T lymphocyte cells?

- has CD4 receptor with variable region (analogous to B cell antibody variable region) - when T cell CD4 receptor binds to MHC II becomes activated (no longer naive) - will trigger proliferation of identical effector Th cells - and triggers proliferation of identical memory Th cells - releases cytokines to "sound alarm" and trigger immune response (activates cytotoxic T cells) - activates B cells by binding to their MHC II when presenting an antigen that matches T cell CD4 receptors - invasion/injury --> chemokine release --> mast cell release of histamine --> vasodilation --> phagocyte first responders are neutrophils --> roll along capillary wall (marginalization) --> squeeze through capillary wall cells (emigration) into interstitial fluid --> - increased blood flow secondary to arteriolar and capillary bed dilation (erythema and warmth) - increased vascular permeability as a consequence of wither widening of interendothelial cell junctions of the venules or direct endothelial cell injury results in exudate of protein-rich extravascular fluid (edema) - leukocytes, initially neutrophils, adhere to endothelium via adhesion, leave and migrate to site of injury under influence of chemotactic agents - phagocytosis, killing, and degradation of the offending agent follow - genetic or acquired defects in leukocyte fxn give rise to recurrent infections - outcome may be: removal of exudate and restoration of normal tissue; transition to chronic inflammation; or extensive destruction of tissue resulting in scarring - atrophy - when a sufficient number of cells are involved the entire tissue organ diminishes in size but not dead - decrease in protein synth. because of reduced metabolic activity infarction stenotic - partial or complete monosomy of genes on short arm of X chromosome, usually 45,X, less commonly from mosaicism - clinical features: short stature, webbing of the neck, cubitus valgus, CV malformations, amenorrhea, lack of secondary sex characteristics, fibrotic ovaries - macrophages - dendritic cells - neutrophils - response initiated mostly by host T cells that recognize the foreign HLA antigens of the graft, either directly (on APCs in the graft) or indirectly (after uptake and presentation by APCs) - hyperacute rejection: pre-formed antidonor antibodies bind to graft endothelium immediately after transplantation, leading to thrombosis, ischemic damage, and rapid graft failure - acute cellular rejection: T cells destroy graft parenchyma (and vessels) by cytotoxicity and inflammatory rxns - acute humoral rejection: antibodies damage graft vasculature - chronic rejection: dominated by arteriosclerosis, probably caused by T cell rxn and secretion of cytokines aging (senile atrophy) and reduced blood supply

79.

what is the sequence of events during inflammatory response?

138.

what is the sequence of events in acute inflammation?

96.

what is the shrinkage in the size of a cell by the combination of decreased protein synthesis and increased protein degradation? what is the term for irreversible injury and cell death? what is the word that describes narrowed heart valves? what is Turner syndrome?

87.

85.

176.

64.

what kinds of cells perform phagocytosis?

161.

what leads to recognition and rejection of organ transplants (allografts)?

97.

what might cause atrophy of the brain in an 82 year old with atherosclerotic disease?

128.

what results from cell injury by accumulation of damaged DNA and misfolded proteins? what type of MHC molecules are found on macrophages? what types of MHC group do regular cells have? what types of proteins are involved with autosomal recessive disorders? when a regular cell presents proteins what reads the message? where do B cells mature? where do T cells mature? which are the most efficient antigen presenting cells? which CD receptors and MHC receptors match up? on which cells do each occur? which cells are most involved in the cellmediated response? which cells are most involved in the humoral response? which Ig production is stimulated by allergens? which molecule confers passive immunity to neonates? why does metaplasia occur? what is an example of metaplasia?

triggers apoptosis

65.

MHC II for antigen presentation

73.

MHC I

167.

enzyme proteins are frequently involved

74.

- regular cells present proteins on MHC I - read by CYTOTOXIC T cells with CD8 receptors

68.

bone marrow in the thymus dendritic cells which are located in epithelia and most tissues

67.

149.

76.

- professional antigen presenting cells (WBCs) have MHC II that bind with helper T cells with CD4 - regular body cells have MHC I that bind with cytotoxic T cells with CD8 receptor

60.

- T-lymphocytes (helper & cytotoxic) - destroys infected self-cells - B-lymphocytes (antibody producers) - identify pathogens in plasma as non-self - though can be activated/amplified by helper-T cells - IgE - found on mast cells to react to reexposure antibodies passed from mom transplacentally or via breast milk

59.

157.

156.

101.

- a cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment - epithelial metaplasia is exemplified by the squamous change that occurs in the respiratory epithelium of habitual cigarette smokers; the normal ciliated columnar epithelial cells of the trachea and bronchi are focally or widely replaced by stratified squamous epithelial cells; although the metaplastic squamous epithelium has survival advantages, important protective mechanisms are lost such as mucus secretion and ciliary clearance of particulate matter

168.

why females are less likely to have an X-linked disorder? why is epithelial metaplasia a double-edged sword?

- random inactivation of one X chromosome - the rugged stratified squamous epithelium may be able to survive the noxious chemicals in cigarette smoke that the more fragile specialized epithelium would not tolerate - but the influences that induce metaplastic change, if persistent, may predispose to malignant transformation of the epithelium

102.