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1199 Cards in this Set

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1 Bone marTow cells from an organ donor are cultured in vitro at 3JOC in the presence of recombinant erythropoietin. A photomicrograph of a typical "burst-fonning unit" is shown in the image. This colony, commiued to the eryuu ocyre pathway of differentiation, represents an example of which of the following physiologic adaptations Lo transmembrane signalin g? ***(A) An·ophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypertrophy ***(E) Metaplasia
1 The answer is C: Hyperplasia. Hyperplasia is defined as an increase m the number of cells in an organ or dssue. Uke hypertrophy (choice D}. it is often a response to trophic signals or increased functional demand and is commonly a normal process. E1ylhroid hyperplasia is typically seen in people living at high aldtude. Low oxygen tension evokes the producdon of erythropoietin , which promotes the survival and proliferation of erylhwid precursors in the bone marrow. The cellular and molecular mechanisms that are responsible for hyperplasia clearly rela te to the control of cell p roliferation (i.e., cell cycle). None of the other choices describe increased numbers of cells. ***Diagnosis: Erythropoiesis, hyperp lasia
2 A 50-year-old clu-onic alcoholic presents to the emergency room with 12 hours of severe abdominal pain. The pain radiates to the back and is associated \ViLl1 an urge to vomit. Physical examination discloses exquisi te abdominal tenderness. LaboraLOJY studies show elev;ued semm amylase. vVhich of the following morphologic changes would be expected in the peripancreatic tissue of this patient? ***(A) Coagulative necrosis ***(B) Casem1s necrosis ***(C) Fat necrosis ***(D) Fibrinoid n ecrosis ***(E) Liquefactive necrosis
2 The answer is C: Fat necrosis. Saponification of fat detived from peripancreatic fat cells exposed to pancreatic enzymes is a typical feature of fat necrosis. Lipase, released from pancreatic acinar cells during an attack of acute pancreatitis, hydrolyzes fat into fatty acids and glycerol. Free fatty acids bind with calcium w fonn soaps, which is a process known as saponification Entry of calcium ions into the injured dssue reduces the level of calcium in blood. Hypocalcemia is, therefore, a typical finding in patients who had a recem bout of acll[e pancreatitis. Patients with acute pancreatitis experience sudden-m1Set abdominal pain, distention, and vomiting. The other choices are not typically seen in petipancreatic tissue following acute pancreatitis, although bquefactive necrosis (choice E) may be observed. ***Diagnosis: Acute pancreatitis
3 A 68-year-old man with a history of gastroesophageal reflu.x disease suffers a massive stroke and expires. The esophagus at autopsy is shown in the image. Histologic examination of lhe abnom1al tissue shows imestine-Uke epithehum composed of goblet cells and surface cells simHar to those of incompletely imestinalized gastric mucosa. There is no evidence of nuclear atypia. Which of lhe roUowing tenns best desc1ibes this morphologic response to persistent injury in the esophagus of this patient? ***(A) Acyplcal hyperplasia ***(B) Complex hyperplasia ***(C) Glandular metaplasia ***(D) Simple hyperplasia ***(E) Squamous metaplasia
3 The answer is C: Glandular metaplasia. The major adaptive responses of cells w sublethal injury are atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, and intracellular storage. Metaplasia is defined as the conversion of one differentiated cell pathway to another. ln this case, the esophageal squamous epithelium is replaced by columnar epith elium as a result of chronic gastroesophageal reflux. The lesion is characte1ized histologically by intestine-like epithelium composed of goblet cells and celts similar to those of incompletely intestinalized gastric mucosa. Squamous metaplasia (choice E) occurs in Lhe bronchial epithelium of smokers, among other examples. Choices A, B, and D are preneoplastic changes that are most often described in. the uterine endometrium of postmenopausal women. ***Diagnosis: Barrett esophagus, metaplasia
4 ACT scan of a 43-year-old \voman with a parathyroid adenoma and hyperparathyroidism reveals extensive caldum deposits in the lungs and kidney parenchyma. These radiologic findings are besL explained by which of the following mechanisms of disease? ***(A) Aneriosclerosis ***(B) DysLrophic calcificaLion ***(C) Granulomatous inflammation ***(D) Metastatic calcification ***(E) Tumor embolism
4 The answer is D: Metastatic calcification. Metastatic calcification is associated \.Vith an increased sennn calcium concentration (hypercalcemia). AbnosL any disorder that increases serum calcium levels can lead to calcification in the alveo lar septa of the lung, renal tu bules , and blood vessels. 111e patiem in this case had a parathyroid adenoma that produced large quantities of pa rathyroid honnone. Other examples of metasmtic calcificmion include multiple opacities in the cornea of a child given large amounts of vitamin D and pan ially calcified alveolar septa ln the lungs of a patient with breast cancer metastatic to bone. Breast can cer metastaSes to bone are often osteolytic and, therefore, accompanied by h ypercalcemia. Dystrophic calcification (choice B) has us migin in direct cell injury. Aneriosclerosis (choice A) is an example of dystrophic calcification. ***Diagnosis: Hyperparathyroidism, meLastatic calci.ficaLion
5 A 75-year-old woman wiLh Alzheimer disease dies of congesLive heart failure. The brain ar autopsy is shown in Lhe image. This patients brain exemplifies which of the foUowing responses to chronic injury? ***(A) Anaplasia ***(B) Atrophy ***(C) Dysplasia ***(D) HypeqJlasia ***(E) Hypertrophy
5 The answer is 8: Atrophy. Clinically, atrophy is recognized as diminution in the size or function of an organ. lt is often seen in areas of vascular insufficiency or chronic inflammation and may result from disuse. An·ophy may be thought of as an adaptive response to stress, in \.Vhicl1 the cell shuts down its di(fe rentiated functions. Reduction in the size of an organ may re flect reversible cell atrophy or may be caused by irreversible loss of cells. For example, atrophy of the brain in Lhis patient with Alzheimer disease is secondary to extensive cell death, and the size of the organ cannot be restored. This patients brain shows marked atrophy of the frontal lobe. The gyri are thilmed, and sulci are widened . Anaplasia (choice A) represems Jack of differentiated features in a neoplasm. ***Diagnosis: Alzheimer disease, atrophy
6 A 68-year-old woman with a history of heavy smoking and repeated bouts of pneumonia presents with a 2-\veek history of fever and productive cough A chest X-ray reveals a right lower lobe infiltrate A transbronchial biopsy confirms pneumonia and further demonstrates preneoplastic changes within the bronchial mucosa. Which of the following best characterizes the morphology of this bronchial mucosal lesion? ***(A) Abnormal pauern of cellular maturation ***(B) Increased numbers of otherwise normal cells ***(C) Invasiveness through Lhe basement membrane ***(D) Transfonnation of one differentiated cel1 type to another ***(E) Ulceration and necrosis of epithelial cell!s
6 The an-swer is A: Abnormal pattern of (ellular maturation. Cells that compose an epithelium exhibit uniformity of size and shape, and they undergo maturation in an orderly fashion (e.g., from plump basal cells to flat superficial cells in a squamous epithelium). When we speak of dysplasia, we mean ucat this regular appearance i.s disturbed by ( l ) variations in the size and shape o[ the cells: (2) enlargement, irregularity, and hyperchromatism of the nuclei; and (3) disorderly arrangemem of the cells within the epitheli1.1m. Dysplasia of dee bronchial epiucellum is a reaction of respiratory epithelium to carcinogens in wbacco smoke. It is pmemially reversible if the patiem swps smoking bm is considered preneoplastic and may progress to carcinoma. Choices B, D, and E are not preneoplastic changes. Invasiveness (choice C) connotes malignam behavior. ***Diagnosis: Pneumonia, dysplasia
7 A 64-year-old man with long-standing angina pectoris and arterial hypertension dies of spontaneous intracerebral hemorrhage. At autopsy, the heart appears globoid. The lefL vennide measures 2.6 em on cross section (shown in the image). This adaptation to chronic injmy was mediated p1imarily by changes in the intracellular concentration of which of the foliO\vi.ng components? ***(A) DNA ***(B) Glycogen ***(C) Lipid ***(D) mRNA ***(E) \Va ter
7_ The answer is D: mRNA. Hypenrophic cardiac myocytes have more cytoplasm and larger nuclet than normal celts. Although the elucidation o[ the ceUular and molecular mechanisms underlying the hypertrophic response is still actively pursued, it is clear that the final steps include increases in mRNA, rRNA, and protein. Hypenrophy resuli:S from r.ranscriprional regulation. Aneuploidy (chmce A) is nm a featu re of myofiber hypertrophy. 'vVater influx (choice E), which is typical of hydropic swelling in acme injury, is not a common feature of hypertrophy ***Diagnosis: Hypertrophic heart disease, hypertrophy
8 A 24-year-old woman contracts toxoplasmosis during her pregnancy and delivers a neonate at 3 7 weeks of gestation with a severe malfomtation of the central nervous system. MRI studies of the neonate reveal porencephaly and hydrocephalus. An X-ray fi lm of the head shows irregular densities in the basal ganglia. These X-ray findings are best explained by which of lhe following mechanisms of disease? ***(A) Amniotic fluid embolism ***(B) Dystrophic calcification ***(C) Granulomawus inflammation ***(D) Metastatic calcification ***(E) Organ immaturity
8 The answer is B: Dystrophic calcification. Dystrophic calci6cadon refl.ects underlying cell injury. Serum levels of calcium are normal, and the calcium deposits are located in previously damaged tissue. lnnautetine Toxoplasma infection affects approximately 0.1% of all pregnancies. Acute encephalitis in the fetus afflicted with TORCH syndrome may be associated with foci of necrosis that become calcified. Microcephaly, hydrocephalus, and microgyria are frequent complications of these inr.rau terine infections. Metastatic calcification (choice D) reflects an underlying disorder in cakium metabolism. ***Diagnosis: Dystrophic calcification
9 A 30-year-old man with AIDS-dementia complex develops acute pneumonia and dies of respiratory insufficiency. At autopsy. rnany central nervous system neurons display hydropic degeneration. This manifestation of sublethal neuronal injury was most likely mediated by impairment of which of the following cel1ular processes? ***(A) DNA synthesis ***(B) Upid peroxidation ***(C) Miwtic spindle assembly ***(D) Plasma membrane sodium transpon ***(E) Ribosome biosynthesis
9 The answer is D: Plasma membranesodium transport. Hydropic swelling reflecrs acute, reversible (sublethal) cell injury It results fTom impairment of cellular volume regulation, a process that controls ionic concentrations in the cytoplasm. This regulation, particularly for sodium, involves ( 1) the plasma membrane, (2) the plasnca membrane sodium pump, and (3) the supply of ATP. Injurious agents may imerfere with these membrane-regulated processes. Accumulation of sodium in the cell leads to an increase in water content to malmain isosmotic conditions, and the cell then swells. Lipid peroxidadon (choice B) is often a feature of irreversible cell injury. The other choices are unrelated to volume control. ***Diagnosis: Acute reversible injury
10 A 62-year-old man is brought to the emergency room in a disotiemed state. Physical examination reveals jaundice, splenomegaly, and ascites. Serum levels of ALT, AST, alkaline phosphatase, and bi lirubin are all elevated. A liver biopsy demonstrates alcoholic hepatitis with Mallory bodies. These cytoplasmic structures are composed of interwoven bundles of which of the following protelns' ***(A) 0.1-Antitrypsin ***(B) (3-Amyloid (A(3) ***(C) Intermediate filamenLS ***(D) Prion protein (PrP) ***(E) a.-Synuclein
10 The answer is C: Intermediate filaments. Hyaline is a term that refers to any material that exhibits a reddish, homogeneous appearance when stained with hematoxylin and eosin (H&E). Standard tem1inology includes hyaline anenolosclerosis, alcoholic hyali11e in the liver, hyaline membranes in the lung, and hyaline droplets in various cells. Alcoholic (Mallory) hyaline is composed of cytoskeletal imennediate filamenrs (cywkeratins), whereas pulmonary hyaline membranes consist of plasma proteins deposited in alveoli. Stmcturally abnonnal a.,-andrrypsln molecules (choice A) accumulate in the liver of patienrs with fJ.1-amitrypsin defidency. a. -Synuclein (choice E) accumulates in neurons in the substantia nigra of patients with Pa rkinson disease. ***Diagnosis: Alcoholic liver disease
11 A 65-year-old man suffers a heart attack and expires. Examination of the lungs at auwpsy reveals numerous pigmented nodules scatte red throughout the parenchyma (shO\vn in the image). What is the appropriate diagnosis? ***(A) Anthracosis ***(B) Asbestosis ***(C) Hemosiderosis ***(D) Sarcoidosis ***(E) Sillcosis
11 The answer is A: Anthracosis. Amhrncosis refers to the storage of carbon particles in the ltmg and regional lymph nodes. These panicles accumulate in alveolar macrophages and are also o·ru1sponed to hilar and mediastinal lymph nodes, where the indigestible matenal is stored indefinitely within Lissue macrophages. Although the gross appearance of the lungs of persons with anthracosis may be alarming, the condition is innocuous. Workers \Vho mine hard coal (anthracite) develop pulmonary fibrosis, owing to the presence of toxic/fibrogenic dusts such as silica. This type of pneumoconiosis is more properly classified as anthracosilicosis. Hemosiderosis (choke C) represents intracellular storage of iron (hemosiderin). The other choices are not associated with dark pigmentation in Lhe lung ***Diagnosis: Pneumoconiosis, anthracosis
12 A 32-year-old woman whh poorly controlled diabetes mellims delivers a healthy boy at 38 weeks of gestation As a result of maternal hyperglycenlia during pregnancy, pancreatic islets in the neonate would be expected co show which of Lhe following morphologic responses to injury? ***(A) Alrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Metaplasia ***(E) Necrosis
12 The answer is C: Hyperplasia. lnfanrs of diabetic mothers show a 5% to 10% incidence of major developmen tal abnormalities, including anomalies of the heart and great vessels and neural tube defects. The frequency of these lesions relates to the control of maternal diabetes during early gestation. Dming fetal developme11t , the islet cells of the pancreas have proliferative capacity and respond to increased demand for insulin by undergoing physiologic hyperplasia_ Femses exposed LO hyperglycemia in utero may develop hyperplasia of the pancreatic ~ cells, which may secrete insulin autonomously and cause hypoglycemia at binh. Metaplasia (choice D) is defined as the conversion of one differentJaLed cell pathway to another. ***Diagnosis: Diabetes mellitus
13 A 59-year-old female alcoholic is brought to the emergency room with a fever (38. f 0 C/l03°F) and foul-smelling breath. The patiem subsequently develops acULe bronchopneumonia and dies of respiratory msufficiency. A pulmonary abscess is identified at aULopsy (shown in the image). Histologic examination of the wall of this lesion would most likely demonstrate which of the following pathologic changes? ***(A) Caseous necrosis ***(B) Coagulative necrosis ***(C) fat necrosis ***(D) Fibrinoid necrosis ***(E) UquefaCLive necrosis
13 The answer is E: Liquefactive necrosis. When the rate of dissolmion of the necrotic cells is faster than the rate of repair, the resulting morphologic appearance is te rmed liquefactive necrosis. The polymorphonuclear leukocytes of the acme inflammatory reaction are endowed with potent hydrolases that are capable o [ digesting dead cells. A sharply localized collection or these acute inflammatory cells in response [0 a bacterial infection produces rapid death and dissolution of tissue. The resu It is often an abscess defined as a cavity formed by liquefactive necrosis in a solid tissue. Caseous necrosis (choice A) is seen in necrotizing granulomas. In coagulative necrosis (choice B), the outline of the cell is retained. Fat (choice C) is not present in the lung parenchyma. Fibrinoid necrosis (choi ce D) is seen in patien ts \Vith necrotizing vasculitis. ***Diagnosis: Puhnonary abscess, liquefactive necrosis
14 A 20-year-old man from China is evaluated for persistent cough, night S\"leaLS, low-grade fever, and general malaise. A chest X-ray reveals findings "consistent wilh a Ghon complex." Sputum culLUres grow acid-fast bacilli. Examination of hilar lymph nodes in Lhis patient would most likely demonstrate which of the follov.ring pathologic changes? ***(A) Caseous necrosis ***(B) Coagulative necrosis ***(C) Fat necrosis ***(D) Fibrinoid necrosis ***(E) Liquefactive necrosis
t4 The answer is A: Caseous necrosis. Caseous necrosis is a characteristic of primary tuberculosis, in which the necrotic cells fail to retain their cellu lar outlines. They do not disappear by lysis , as in liquefactive necrosis (ch oice E), but persist indefinitely as amorphous, coarsely granular, eosinophilic debris. Grossly, this debtis resembles clumpy cheese, hence the name caseous necrosis. Primaty tuberculosis is often asymptomatic or presents with nonspecific symptoms, such as low-grade fever, loss of appetite, and occasional spells or coughing. The Ghon complex includes parenchymal consolidation and ipsilateral enlargement o[ hilar lymph nodes and is often accompanied by a pleural effusion. Fibnnoid necrosis (choice D) is seen in patients with necrouzing vasculitis. ***Diagnosis: Tuberculosis, Mycobacterium tuberculom
15 A 31-year-old woman complains of increased vaginal discharge of 1-month duration. A cervical Pap smear is shown in the image. Superficial epithelial cells are identified witl1 anows. When compared to cells from the deeper intermediate layer (top), the nuclei of Lhese superficial cells exhibit which of the following cytologic feam res? ***(A) Karyolysis ***(B) Karyorrhexis ***(C) Pyknosis ***(D) Segmentation ***(E) Vi ral inclusion bodies
15 The answer is C: Pyknosis. Coagulative necrosis reters to light microscopic alterations in dying celJs. When stained with the usual combination of hematoxylin and eosin, the cytoplasm of a necrotic cell is eosinophilic. The nucleus displays an initial dumping of chromatin followed by its redistribution along the nuclear membrane. In pyknosis, the nucleus becomes smaller and stains deeply basophilic as chromatin clumping continues. Karyorrhexis (choice B) and karyolysis (choice A) represent further steps in the fragmentation and dissolution of the nucleus. These steps are not evident in the necrotic cells shown in this Pap smear. ***Diagnosis: Cervical intraepithelial neoplasia, pyknosis
16 A 30-year-old woman suffers a tonic-clonic seizure and presents with deli1ium and hydrophobia. The patient stales that she was bitten on the hand by a bat about l momh ago. The patient subsequently dies of respiratory failure. VLral particles are found throughout the brainstem and cerebellum at autopsy. ln addition to direct vi ral cytotoxicity, the necrosis or virally infected neurons in this patient was mediated primarlly by which of the following mechanisms? ***(A) Histamine release from mast cells ***(B) Humoral and cellular immunity ***(C) Neutrophil-mediated phagocytosis ***(D) Release of oxygen radicals from macrophages ***(E) Vasoconstriction and ischeml8
16 The answer is 8: Humoral and cellular immunity. Both humoraJ and cellu lar anns of the immune S)1Stem protect against the hamuul effects of viral infections. Thus, the presentation of viral proteins to the immune system immunizes the body against the invader and elicits both killer cells and the production of antiviral antibodies. These anns of the immune system eliminate virus-infected cells by either inducing apoprosis or directing complement-mediated cytolysis_ In this patiem, the rabies virus entered a pe1ipheral nerve and was transported by retrograde axoplasmic flow to the spinal cord and b rain. The infl ammation is centered in the brainstem and spills into the cerebellum and hypothalamus. The other choices are seen in acme inflammation, but they do nm represent antigen-specific responses tO viral infections. ***Diagnosis: Rabies
17 A 52-year-old woman loses her right kidney following an auto· mobile accident. ACT scan of the abdomen 2 years later shows marked enlargement of the left kidney. The renal enlargement is an example o[ which of the following adaptations? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypemophy ***(E) Metaplasia
17 The answer is D: Hypertrophy. Hypertrophy is a response to trophic signals or increased functional demand and is commonly a normal process. For example, if one kidney is rendered inoperative because of vascular occlusion, the contralateral kidney hypertrophjes to accommodate increased demand. The molecular basis of hypertrophy reflects increased expression of growth-promoting genes (protooncogenes) such as myc,Jos , and ra.s . Hyperplasia (choice C) of renal tubular cells may occur, but enlargement of the kidney in this patient is best referred to as hypertrophy (Le., increased organ size and function). ***Diagnosis: Hypertrophy
18 An 82-year-old man has profound bleeding fTom a peptic ulcer and dies of hypovolemic shoe k The liver at autopsy displays centrilobular necrosis. Compared to viable hepatocytE$, the necrotic cells contain higher intracellular concemrations of which of [he following? ***(A) Calcium ***(B) Cobal[ ***(C) Copper ***(D) lron ***(E) Selemum
18 The answer is A: Calcium. Coagulative necrosis is characterized by a massive influx of calcium imo the ceU. Under nonnal circumstances, the plasma membrane maintains a s teep gradiem of calcium ions, whose concentration in inters titial fluids is 10,000 times higher than thm inside the cell. Irreversible cell injury damages the plasma membrane, which then fails w maintain this gradient, allowing the influx of calcium into the cell. The other chokes would most likely be released upon cell death. ***Diagnosis: Coagulative necrosis
19 A 2.8-year-old woman is pinned by falling deb1ts during a hurricane. An X-ray film of the leg reveals a compound fracmre of the right tibia. The leg is immobilized in a casL for 6 ·weeks. vVhen the cast is removed, the patiem nQ[ices that her rig]1[ leg is weak and visibly smaller in circumference than the left leg. Which of the following terms best describes tllis change in the patients leg muscle? ***(A) Atrophy ***(B) Hyperplasia ***(C) Metaplasia ***(D) Ischemic necrosis ***(E) lneversible cell injury
19 The answer is A: Atrophy. The most common fonn of atrophy follows reduced functional demand. for example, after immobilization of a limb in a cast as treatmem for a bone fracru re, muscle cells atrophy. and muscular s trength is reduced. The expresston of differemimion genes is repressed. On reswration of normal conditions, atrophic cells are fully capable of resuming their differentiated functions; size increases to nonnal, and specialized hmcdons, such as p rotein synthesis or comractile force, rerum to their original levels. Ischemic necrosis (ch oice D) is typically a complication of vascular insufficiency. In-eversible inJury to skeletal muscle (choice E) would be an unlikely complication of bone fracture. ***Diagnosis: Atrophy, bone fracmre
20 A 70-year-old man is hospitalized after suffering a mild stroke. While in the hospital, he suddenly develops crushing substernal chest pain. Analysis of serum proteins and ECG con.finn a diagnosis of acute myocardial infarction. The patient subsequemly develops an anhythmia and expires. A cross section of the left vemricle at autopsy is shown in the image Histologic examination of the affected heart muscle would demonstrate whkh of the following morphologic changes7 ***(A) Caseous necrosis ***(B) Coagulative necrosis ***(C) Fat necrosis ***(D) Fibrinoid necrosis ***(E) Uquefactive necrosis
20 The answer is B: Coagulative necrosis. Ischemic necrosis of cardiac myocytes is the leading cause of death in the Western world. In brief, the interruption of blood supply to the bean decreases the delivery of 0 2 and glucose. l.ack of 0 2 impairs mitochondtial electron transport, thereby decreasing ATP synthesis and facilitating the production of reactive oxygen species. Mitochondrial damage promotes the release of cytochrome c to the cytosol, and the ce ll dies. The moq:>hologic appearance of the necrotic cell has traditionally been tem1ed coagulative necrosis because of its similatity w the coagulation of proteins that occurs upon heating. ***Diagnosis: Myocardial infarction, coagulative necrosis
21 Which of the following hiswlogic featu res would provide definitive evidence of necrosis in the myocardium of the patiem described in Question 20? ***(A) Disaggregation of polyribosomes ***(B) Increased imracellular volume ***(C) Inllux of lymphocytes ***(D) Mitochondrial swelling and calcification ***(E) Nuclear fTagmemation
21 The answer is E: Nuclear fragmentation. Nuclear fragmentation (karyorrhexis and karyolysis) is a hallmark of coagulative necrosis. Choices A, B, and 0 are incorrect because they are fearures of both reversibly and ineversibly injured cells. Lymphocytes (choice C) are a hallmark of chronic inflammation. ***Diagnosis: Myocardial infarction
22 A 90-year-old woman with mild diabetes and Alzheimer dis· ease dies in her sleep. At autopsy, hepatocytes are noted to contain golden cytoplasmic granules that do not stain with Prussian blue. Which of the following best accounts for pigment accumulation in the liver of this patient? ***(A) Advanced age ***(B) Alzheimer disease ***(C) Congestive heart fai]ure ***(D) Diabetic keLOacidosis ***(E) Hereditary hemochromawsis
22 The answer is A: Advanced age. Substances that cannot be metabolized accumulate in cells. Examples include (I) endogenous substrates that are not processed because a key enzyme is missing (lysosomal storage diseases), (2) insoluble endogenous pigments (Lipofuscin and melanin), and (3) exogenous paniculates (silica and carbon}. lipofuscin is a "wear and tear" pigment of aging that accumulates in organs such as the brain, hean, and liver. None of the other choices are associated with lipofuscin accumulation. ***Diagnosis: Aging, hpofuscin
23 Which of the following mechanisms of rusease best describes the pathogenesis of pigment accumulation in hepatocytes in the patient described in Question 22? ***(A) Degradation of melanin pigments ***(B) Inhibition of glycogen biosynthesis ***(C) Malabsorption and enhanced deposition of iron ***(D) Peroxidation of membrane lipids ***(E) Progressive oxidation of bilirubin
23 The answer is 0: Peroxidation of membrane lipids. Lipofuscin is found in lysosomes and contains peroxidation products of unsaturated fatty acids. The presence of this pigment is thought w reflect continuing llpid perm.'. i dation of cellular membranes as a result of inadequate defenses against activated oxygen radicals. None of the other mechanisms of disease leads to the formation and accumulation of li pofuscin granules. ***Diagnosis: Lipofuscin, intracellular swrage disorder
24 A 45-year-old man presents with increasing abdominal girth and yellow discoloration of his skin and sclera. Physical examination reveals hepatomegaly and jaundice. A Pntssian blue stain of a liver biopsy is shown in the image What is the major intracellular iron storage protein in this patiem's hepawcytes? ***(A) Bilirubin ***(B) Haptoglobin ***(C) Hemoglobin ***(D) Hemosiderin ***(E) Transferrin
24 The answer is D: Hemosiderin. Hemosiderin is a partiaJly denatured form of ferritin that aggregates easily and Ls recognized microscopically as yellow-brmvn granules in the cytoplasm, which turn blue with the Prussian blue reaction. In hereditary hemochromatosis, a genetic abnormality of iron absorption in the small intestine, excess iron is s tored mostly in the form of hemosiderin, primarily in the liver. Hemoglobin (choice C) is the iron-containing pigmem of RBCs. Bilirubin (choice A) is a product of heme catabolism that may accumulate in liver cells but does not srain wi.lh Prussian blue_ Transferrin (choice E) binds serum iron. ***Diagnosis: Hereditary hemochromatosis
25 A 60-year-old man \Vith ch ronic cystitis complains of urinary fTequency and pelvic discomfort. Digital rectal examination is unremarkable. Biopsy of the bladder mucosa reveals foci of glandular epithelium and chronic Jnnammatory cells_ No cytologic signs of atypia or malignancy are observed. Whkh of the follo.,ving terms best describes the morphologic response to chronic injury in this patient? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypemophy ***(E) Metaplasia
25 The answer is E: Metaplasia. Metaplasia of transitional epithelium to glandular epithelium is seen in patients with chronic innammation of the bladder (cystitis glandularis). Metaplasia is considered to be a protective mechanism, but it is not necessarily a ham1less process. For example, squamous metaplasia in a bronchus may protect against injmy produced by tobacco smoke, but it also impairs the production of mucus and ciliary clearance of debris. Funhermore, neoplastic transfo rmation may occur in metaplastic epithelium Lack of cytologic eVIdence for atypia and neoplasia rules out dysplasia (choice B) ***Diagnosis: Chronic cystitis, metaplasia
26 A 60-year-old man is rushed to the hospitaJ with acme liver failure. He undergoes successful orthotopic liver transplamalion: however, the transplanted Liver does not produce much bile for the first 3 days. Poor graft f1.mc tion in this patient is thought LO be the resuh of "reperfusion injury." Which of the following substances was the most likely cause of reperfusion injury in this patients transplanted liver? ***(A) Cationic proteins ***(B) Free ferric iron ***(C) Hydrochlorous acid ***(D) Lysosomal acid hydrolases ***(E) Reactive oxygen species
26 The answer is E: Reactive oxygen species. lschetnialreperfusion (l!R) injury is a common clinical problem that atises in the setting of occlusive cardiovascular disease, infection, transplantation, shock, and many other circumstances. The genesis of liR injury relates w the inte1play between transient ischemia and the re-establishment of blood flow (reperfusion)_ Initially. ischemia produces a type of cellular damage that leads w the generation of free radical species. Subsequently, reperfusion provides abundant molecular oxygen (0 ,) w combine with fTee radicals to fonn reactive oxygen specles. 0>..-ygen radicals are fmmed inside cells through the xanthine oxidase pathway and released from activaled neutrophils. ***Diagnosis: Myocardial infarction
27 A 68-year-otd woman with a history of hyperlipidemia dies of cardiac arrhythnua following a massive hearr attack. Peroxidation of which of the following molecules was primati ly responsible for causing the loss of membrane imegrity in cardiac myocytes in this patiem? ***(A) Cholesterol ***(B) Glucose transport proteins ***(C) Glycosphingolipids ***(D) Phospholipids ***(E) Sodium-potassium ATPase
27 The answer is D: Phospholipids . During lipid peroxidation, hydro>..'yl radicals remove a hydrogen atom from the unsaturated fatty acids of membrane phospholipids. The lipid radicals so f01med reacL with molecular o:-... ygen and form a hpid peroxide radical. A chain reaction is initiated. lipid peroxides are unstable and break dow·n into smaller molecules. The destruc· tion of the unsaturated fatty acids of phospholipids results in a loss of membrane integrity. The other choices represent targets for reactive oxygen species, but protein cross-linking (choices B and E) does not lead to rapid loss of membrane integrity il1 patients with myocardia] infarction. ***Diagnosis: Myocardial infarction
28 A 22-year-old construction worker sticks himself with a sharp , rusty nail. Within 24 hours, the wound has enlarged to become a 1-cm sore that drains thick, purulent matetial. This skin wound illustrates ·which of the following morphologic types of necrosi5? ***(A) Caseous necrosis ***(B) Coagulative n ecrosis ***(C) Fat n ecrosis ***(D) Fibnnoid necrosis ***(E) Liquefactive necrosis
28 The answer is E: Liquefactive necrosis. Polymorphonuclear leukocytes (segmented nemrophils) rapidly accumulate at sites o[ injury They are loaded with acid hydrolases and are capable o[ digesting dead cells. A localized collection of these inOammatory cells may create an abscess with central liquefaction (pus). Uquefacdve necrosis is also commonly seen in the brain. Caseous necrosis (choice A) is seen in necrotizing granulomas. Fat necrosis (choice C) is typically encountered in patients with acute pancreatitis. Fibrinoid necrosis (choice D) is seen in patients with necrotizing vasculitis. ***Diagnosis: Abscess, acme inflammation
29 A 4 2-year-old man undergoes liver biopsy for evaluation of the grade and stage of his h epatitis C virus infection. The biopsy reveals swollen (ballooned) hepatocytes and moderate lobular innammatory activity (shown in the image). The arrow identifies an acidophilic (Counci1man) body. Which of the following cellular processes best accounts for the presence or scattered acidophilic bodies in this liver biopsy? ***(A) Aggregation of intermediale filament proLeins ***(B) Apopwtic cell dealh ***(C) Coagulative necrosis ***(D) Collagen deposition ***(E) Intracellular viral inclusions
29 The answer is B: Apoptotic cell death. Apoptosis is a programmed pathway o[ cell death that is triggered by a variety of exn·acelJular and intracellular signals. lt is often a selfdefense mechanism, desu-oying cells that have been infected with pathogens or those in which genomic alterations have occun ed. Arter staining with hematoxylin and eosin, apopLOtic cells are visible under the light microscope as acidophilic (CounCilman) bodies. These deeply eosinophilic su-ucrures represent membrane-bound cellular remnants that are extruded into the hepatic sinusoids. The other choices do not appear as acidophilic bodies. ***Diagnosis: Viral hepatitis
30 Which of the following biochemical changes characterizes the fo rmation of acidophilic bodies in the patient described in Question 29? ***(A) Fragmenration of DNA ***(B) Loss of tumor suprnessor protein p53 ***(C) Mitochondrial swelling ***(D) Synthesis of arachidonic acid ***(E) Triglyceride accumulation
30 The answer is A: Fragmentation of DNA. Fragmentation of DNA is a hallmark of cells undergoing both necrosis and apoptosis, but apoptotic cells can be detected by demonstrating nucleosomal "]addering. n This pattern of DNA degradation is characteristic of apoptotic cell death. It results from the cleavage or chromosomal DNA at nucleosomes by endonucleao:;es. Since nucleosomes are regularly spaced along the genome, a pauem of regular bands can be seen when fragments of cellular DNA are separated by electrophoresis. The other choices are associated with cell injmy, but they do nm serve as distinctive markers of programmed cell death. ***Diagnosis: Viral hepatitis
31 A 56-year-old woman with a history of hyperlipidemia and hypenension develops progTessive, right renal artery stenosis. Over time, this patients right kidney is Likety LO demonstrate which of the following morphologic adaptations to partial ischemia? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypertrophy ***(E) Neoplasia
31 The answer is A: Atrophy. Inter fe rence with blood supply to tissues is known as ischemia. Total ischemla results in cell death. Panial ischemia occurs after incomplete occlusion of a blood vessel or in areas of inadequate collateral circulation. This results in a chronically reduced oxygen supply, a conclition often compatible with cominued cell viability Under such circumstances, cell atrophy is common. For e..'<ample, it is frequently seen around !he inadequately perfused margins of infarcrs in the hean, braiJ1, and kidneys. None of the other choices desc1ibe decreased organ size and funccion. ***Diagnosis: Renal artery stenosis
32 A 5-year-old boy suffers blum trauma to the leg in an automobile acndem. Six months later, bone u·abeculae have formed v.<ithin the striated skeletal muscle at 1.he site of tissue injury. This pathologic condition is an example of which of the fol lowing morphologic adaptations lo injury? ***(A) An·ophy ***(B) Dysplasia ***(C) Metaplasia ***(D) Metastanc calcification ***(E) Dystrophic calcification
32 The answer is C: Metaplasia. Myositis ossificans is a disease characterized by formation of bony trabeculae within sui ated muscle. lt represents a form of osseous metaplasia (i.e., replacement of one differentiated tissue with another type of nonnal differentiated tissue) Although dystrophic calci fica tion (choice E) frequently occurs at sites of prior injUJy, it does not lead lO the formation of bone trabeculae. ***Diagnosis: Myositis ossificans, metaplasia
33 A +3-year-old man presents with a scaly, erythematous lesion on. the dorsal smface of his left hand. A skin biopsy reveals atypical keratinocytes filling the entire thickness of the epiderntis (shown in the image) The arrows point to apoptotic bodies. 'Which of the following proteins plays the most in1ponam role in mediating programmed cell death in this patient's skin cancer? ***(A) Catalase ***(B) Cymchrome c ***(C) Cytokeratins ***(D) Myeloperoxi dase ***(E) Superoxide dismutase
33 The answer is B: Cytochrome c. The miwchondrial membrane is a key regulator of apopwsis. When mitochondrial pores open, cytochrome c leaks out and activates Apaf-1 , which convens procaspase-9 to caspase-9, resulting in the activation of dmvns tream caspases {cysteine proteases). These effector caspases cleave target proteins, including endonucleases nuclear proteins, and cytoskeletal proteins to mediate the va1ied morphological and biochemical changes that accompany apoptosis . Reactive oxygen species (related to choices A, D, and E) are uiggers of apoptosis, bUl they do not mediate programmed cell death. ***Diagnosis: Apopmsis, squamous cell carcinoma o£ skin
34 A 16-year-old girl with a history of suicidal depression swallows a commercial soiYent. A liver biopsy is performed w assess !.he degree of damage to the hepatic parenchyma. Histologic examinarion demonstrates severe swelling of the cemrilobular hepatocytes (shown in the image). Which of the follmving mechanisms of disease best accounts for the reversible changes nored in this liver biopsy? ***(A) Decreased stores of imraceUular ATP ***(B) Increased storage of triglycerides and free fatty acids ***(C) lmracytoplasmic rupture oflysosomes ***(D) Mitochondrial membrane permeability tTansition ***(E) Protein aggregation due to increased cytosolic pH
34 TheanswerisA:DecreasedstoresofintracellularATP. Hydropic swelling may result from many causes, including chemicaJ and biologic wxjns, infections. and ischemia. lnjmious agen ts cause hydropic swelling by (1) increasing the penneabiliry of the plasma membrane w sodium; (2) damaging the membrane sodium-potassium ATPase (pump); or (3) interfering with the synthesis of ATP, thereby depriving the pump of its fuel. The mher choices are inconect because they do not regulate concentrations of intracellu lar sodium. ***Diagnosis: Hydropic swelling, hepatotoxicily
35 A 40-year-old man is pulled from the ocean after a boadng accident and resuscitated. Six hours later, the patiem develops acme renal failure. Kidney biopsy reveals evidence of kaiyorrhexis and karyolysis in renal tubular epithelial cells. Whkh of the following biochemical evems preceded Lhese pathologic changes? ***(A) Activation of Na•fl<+ ATPase ***(B) Decrease in intracellular calcium ***(C) Decrease in intracellular pH ***(D) Increase in ATP production ***(E) In crease in intracellular pH
35 The answer is(: Decrease in intracellular pH. During periods of ischemia, anaerobic glycolysis leads w the overproduction of lactate and a decrease in intracellular pH. Lack of 0 , during myocardial ischemia blocks the production of ATP Pyruvate is reduced to lactate in the cytosol and lowers intracellular pH. The acidification of the cytosol initiates a downward spiral of events that propels the cell toward necrosis. The other choices point to changes in the opposite direction of what would be expected in irreversible cell injury. ***Diagnosis: Acute mb ular necrosis
36 A 58-year-old man presents \Vith symptoms of acme renal failure. His blood pressure is 220/130 mm Hg (malignam hypertension). While in the emergency room, the patient suiiers a stroke and expires. Microscopic e:<amination of the kidney a£ autopsy is shown in the image Which of the following morphologic changes accoums for the red material in the wall of Lhe anery? ***(A) Apoprosis ***(B) Caseous necrosis ***(C) Fal necrosis ***(D) Fibrinoid necrosis ***(E) liquefactive necrosis
36 The answer is D: Fibrinoid necrosis. FibJinoid necrosis is an alteration of injured blood vessels, in which the insudation and accumulation of plasma proteins cause the wall to stain lntensely with eosin. The other choices are not typically asso· dated directly with vascular injury. ***Diagnosis: Malignant hypertension, fibrinoid necrosis
37 A 10-year-old girl presents with advanced features of progeria (patient shown in the image). This child has inherited mutations in the gene that encodes which of the following types of intracellular proteins? ***(A) Helicase ***(B) lanlin ***(C) Oxidase ***(D) Polymerase ***(E) Topoisomerase
37 The answer is B: Lamin. Hutchinson-Gilford progeria is a rare genetic disease characterized by early cataracts, hair loss, arro· phy of the skin, osteoporosis, and atherosclerosis. This phe· notype gives the impression of premature aging in ch ildren. Progeria is one of many diseases caused by mulations in the human lamin A gene (LMNA). Lamins are intennediate filament proteins that fom1 a fibrous meshwork beneath the nuclear envelope. Defective lamin A is thought to make the nucleus unstable, leading to cell injury and death. Mutations in the other genes are not linked to Hutchinson-Gilford progeria syndrome. ***Diagnosis: Progeria
38 A 32-year-old woman develops an Addisonian crisis (acme adrenal insufficiency) 3 months after suffering mas.sive hemorrhage during the delivery of her baby. A CT scan of the abdomen shows small adrenal glands. Which of the following mechanisms of disease best accoums for adrenal atrophy in this patient? ***(A) Chronic inflammation ***(B) Chronic ischemia ***(C) HemotThagic necrosis ***(D) Lack of trophic signals ***(E) Tuberculosis
38 The answer is D: Lack of trophic signals. Atrophy of an organ may be caused by intenuption of key trophic signals. Postpartum in farction of the anterior pitui.tary in this patient resulted in decreased production of adrenocorticotropic hormone (ACTH, also termed corticotropin). Lack of corticotropin results in atrophy of the adrenal cortex, which leads to adrenal insufficiency: Symptoms of acute ad renal insufficiency (Addisonian crisis) include hypotension and shock, as well as weakness, vomiting, abdominal pai11, and lethargy. The otJ1er choices are unlikely causes of postpartum adrenal insufficiency: ***Diagnosis: Sheehan syndrome, adrenal insufficiency
39 A +7-year-old man vvith a history of heavy smoking complains of chronic cough. A "coin lesion" is discovered in his right upper lobe on chest X-ray. Bronchoscopy and biopsy fall to identify a mass, but the bronchial mucosa displays squamous metaplasLa. What is the most likely outcome o[ this morphologic adaptation if the patient stops smoking? ***(A) Atrophy ***(B) Malignant transfonnadon ***(C) Necrosis and scarring ***(D) Persistence throughout life ***(E) Reversion w nonnal
39 The answer is E: Reversion to normal. Metaplasia is almost invariably a response to persistent inj ury and can be thought of as an adaptive mechanism. Prolonged exposure of the bronchi to tobacco smoke leads w squamous metaplasia of the bronchial epithelium. Unlike malignancy (choice B) and necrosis with scarring (choice C), metaplasia is usually fully reversible. lf the source of injury in this patient is removed (the patient stops smoking), then the merap11sdc epithelium \vil1 eventually return 1.0 nonnaL ***Diagnosis: Chronic bronchitis, metaplasia
40 A <50-year-old fanner presems "''llh multiple patches of discoloration on his face Bjopsy oflesional skin reveals actinic kerarosis. Which of the following terms best describes this response of the skin to chronic sunlight exposure? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hyperu-ophy ***(E) Metaplasia
40 The answer is 8: Dysplasia. Actinic keraLOsis is a fom1 of dysplasia in sun-exposed skin. HislOiogically, such lesions are composed of atypical squamous cells, which vary in size and shape. They show no signs of regular maturation as the cells move from the basal layer of the epidermis to the surface. Dysplasta is a preneoplastic lesion, in the sense that it is a necessa1y stage in the multistep evolution to cancer. However, unlike cancer cells, dysplastic cells are not entirely amonomous, and the histologic appearance of the tissue may still revert to normal. None of the other choices represent preneoplastic changes in sun-e}..-posed skin. ***Diagnosis: Actinic keratosis, dysplasia
41 A 59-year-old \VOmaJ1 smoker complains of intermittent blood in her urine. U1inalysis confirms 4+ hematuria. A CBC reveals increased red cell mass (hematocrit). ACT scan demonstrates a 3-cm renal mass, and aCT-guided biopsy displays renal cell carcinoma. Which of the following cellular adaptations in the bone marrow best e>..-plains the increased hematocrit in this patient? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) HyperLTophy ***(E) Metaplasia
41 The answer is C: Hyperplasia . Renal cell carcinomas often secrete erythropoietin. This hormone s timulates the growth of erythrocyte precursors in the bone manow by inhibiting programmed cell death. Increased hematocrit in this patient is the result of bone marrow hyperplasia affecting the erythroid lineage. The other choices do not represem physiologic responses to e1ythropoietin. ***Diagnosis: Renal cell carcinoma, hypellJiasia
42 A 33-year-old woman has an abnormal cervical Pap smear. A cervical biopsy reveals that the epithelium lacks nom1al pohuicy (shown in the image). Individual cells display hyperchwmatic nuclei, a larger nucleus-m-cytoplasm ratio, and disorderly tissue anangement. Whkh of the following adaptadons to chronic injury best describes these changes in the patients cervical epithelium? ***(A) Alrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypertrophy ***(E) Metaplasia
42 The answer is 8: Dysplasia. The distinction between severe dysplasia and early cancer of the cervix is a common diagnostic problem for the pathologist. Both are associated wuh disordered growth and maruranon of the tissue. Sintilar ro the development of cancer, dysplasia is believed to result from mut.arions in a proliferating cell population. When a particular mmation confers a growth or survival advantage. the progeny of the affected cell will tend to predominate. In turn, their continued proliferation provides the opportunity for funher mut.ations. The accumulation of such mutations progressively distances the cell from nonnal regulawry constralnts and may lead to neoplasia. None of the other choices are associated 'Yvilh lack 0 r normal tissue polarity. ***Diagnosis: Cervical imraepithehal neoplasia, dysplasia
43 A 24-year-old woman accidentally ingests carbon tetrachlolide (CCl_.) iJ1. the laboratory and develops acute Liver failure. 'vVhich of the following cellular proteins was d irectly involved in the development of hepatotoxicity in this patient? ***(A) Acetaldehyde dehydrogenase ***(B) Alcohol dehydrogenase ***(C) Glucose-6-phosphate dehydrogenase ***(D) Mtxed function oxygenase ***(E) Superoxi de dismutase
43 The answer i.s D: Mixed function oxygenase. The membolism of CCI4 is a model system for wxicologic studies. CCl4 is first metabolized via the mixed fl.mCLion oxygenase system (P450) of the liver to a chloride ion and a hlghly reactive nichloromethyl free radical. Like the hydroxyl radical, this radical is a potent initiator of lipid peroxidation, which damages the plasma membrane and leads to cell death. The other choices are not involved in the fom1ation of the trichloromethyl free radical in liver cells. ***Diagnosis: Hepatic failure, hepatotoxicicy
44 A 30-year-old woman presents v.rith a 2-month hiswry of fatigue, mild fever, and an erylhematous scaling rash. She also notes joint pain and swelling, primarily involving the small bones of her fingers. Physical examination reveals erythema LOLlS plaques with adherem silvery scales that induce punctate. bleeding points when removed. Biopsy of lesionaJ skin reveals markedly increased thickness of the. epidermis (shown in the image). Which of the following ten11s best describes this adaptation to chronic injury Ln this patient witl1 psoriasis? ***(A) Atrophy ***(B) Dysplasia ***(C) Hyperplasia ***(D) Hypenrophy ***(E) Metaplasia
44 The answer is C: Hyperplasia. Psoriasis is a disease of the dernlis and epidermis that is characterized by persistem epidem1al hyperplasia. It is a chronic, frequemly famHial disorder d1at fearures large, etythemawus, scaly plaques, commonly on the dorsal extensor cutaneous surfaces. There is evidence to suggest tha t de regulation of epidem1al proliferation and an abnormality in the microcirculation of the dem1is are responsible for the development of psmiatic lesion s. Abnormal proliferation ofkeratinocytes is thought w be related ro defective epidennaJ cell surface receptors and aiLered intracellular signaling. The oth er choices do not describe increased numbers of othenl\rJse normal epidem1al cells. ***Diagnosis: Psoriasis, hyperplasia
45 A 2-+-year-old woman with chronk depression ingests a boule of acetaminophen tablets. Two days later, she is jaundiced (elevated serum biHrubin) and displays symptoms of encephalopathy, including impairmem in spatial perception. ln the liver, toxic metabolites of acetaminophen are generated by which of the following organelles? ***(A) Golgi apparatus ***(B) Mitochondria ***(C) Nucleus ***(D) Peroxisomes ***(E) Smooth endoplasmic reticulum
45 The answer is E: Smooth endoplasmic reticulum. Carbon reuachloride and acetaminophen are well-studied heparotoxins. Each is metabolized by cymchrome P450 of the mL'<edfunction oxidase system, located in the smooth endoplasmic reticulum. These hepatotoxins are metabolized diffe rently, and it is possible to relate the subsequent evolution of lethal cell injury w the specific features of this metabolism. Acetaminophen, an important constituent of many analgesics, is innocuous in recommended doses, but when consumed to excess it is highly toxi.c Lo the liver. The metabolism of acetaminophen to yield highly reactive quinones is accelerated by alcohol consumption , an effect mediated by an ethanol-induced increase in cytochrome P450. ***Diagnosis: Hepatotmncity, necrosis
46 A 45-year-old woman presents with a 2-momh history of fatigue and recunent fever. She also complains o[ tenderness below the right costal margin and dark urine. Physical examination reveals jaundice and mild hepatomegaly. The serum is positive for hepatitis B virus amigen. Which of the following best describes the meclumism of indirect virus-mediated hepatocyte cell death in this patient? ***(A) Accumulation of abnormal cytoplasmic proteins ***(B) Immune recognition of viral antigens on the cell surface ***(C) Generation of cytoplasmic free radicals ***(D) Impaired plasma membrane Na•tK• ATPase activity ***(E) Interference with cellular energy generalion
46 The answer is B: Immune recognition of viral antigens on the cell surface. Viral cytotoxicity is either direct or indirect (immunologically mediated). Viruses may injure cells directly by subverting cellular en?ymes and depleting the cell's nutriems, thereby dismpting the nonnal homeostatic mechanisms. Some viruses also encode proteins that induce apopwsis once daughter virions are maL ure. Vmtses may also injure cells indtrectly through activation o[ the immune system. Both humoral and cellular arms of the inmmne system prmecL against the ha.rmful e[fects of viral infections by eliminating infected cells. In brief, the presemation of viral proteins to the immune system in the comext of a self major histocompatibility complex on the cell surface immunizes the body against Lhe invader and elicits both killer cells and amhrJral amibodies. These arms or the immune system eliminate virus-infected cells by inducing apoptosis or by lysing the virally infected target cell \Vith complement. None of the other choices describe mechanisms of indirect viral cytotoxic it)~ ***Diagnosis: Hepalitis, viral
47 You are asked to presem a grand rounds seminar on the role of abnormal proteins in d isease. ln this connection , intracellular accumulation o[ an abnormally folded p rotein plays a role in the pathogenesis of which of the followi ng diseases? ***(A) AA amyloidosis ***(B) Al amyloidosis ***(C) a 1-Antitrypsin deficiency ***(D) Gaucl1er disease ***(E) Tay-Sachs disease
47 The answer is C: a.1-Antitrypsin deficiency. Several acquired and inherited diseases are characterized by imracellular accumulation o£ abnormal proteins. The deviant tertiary structure of the protein may result from an inhe1ited mmation that alters the nonnal primary amino acid sequence, or may reflect an acquired defect in protein folding. a 1 -Amiuypsi11 deficiency is a heritable disorder in whkh mmadons in the gene for o:1-antitrypsin yield an insoluble protein. The mutant protein is not easily exponed_ lt accumulates in liver cells, causing ceiL injury and cin-hosis_ Pulmonary emphysema is another complication of a.1-ml titrypsin deficiency Choices A and B are amyloidoses that represent extracellular deposiLS of fibrillar proteins arranged in ~-pleated sheet. Choices D and E are lysosomal storage diseases that represent intracellular deposits of unmetabolized sphingolipids. ***Diagnosis: n 1-Amitrypsin deficiency
48 A 38-year-old woman shows evidence of early cataracts, hair loss, atrophy of skin, osteoporosis, and accelerated atherosclerosis. This patient has most likely inherited mutations in both aUeles of a gene that encodes which of the follmving types of intracellular proteins? ***(A) Deaminase ***(B) Helicase ***(C) Oxidase ***(D) Polymerase ***(E) Topo1somerase
48 The answer is B: Helicase. \.Verner syndrome is a rare autosomal recessive disease characte1ized by early cataracts, hair loss, atrophy of the skin, osteoporosis, and accelerated atherosclerosis. Affected persons are also at risk For development of a variety of cancers. Unlike Hutchinson -Gilford progeria, patiems with Werner syndrome typically die in the fifth decade from either cancer or cardiovascular disease. Werner syndrome is caused by mutations in the WRN gene, which encodes a protein with multiple DNA-dependent enzymatic functions, including proteins v .. ith ATPase, helicase, and exonuclease activity. Hutchinson-Gilford proge1ia is caused by mutations in the human lamin A gene, which encodes an imermediate filamem protein that form a fibrous meshwork beneath the nuclear envelope. Mutations in the other choices are noL associated \"'ith \>Verner syndrome_ ***Diagnosis: Werner syndrome
49 A 28-year-old man with a history of radiation/bone man-ow transplantation for leukemia presents with severe dianbea~ He subsequently develops septic shock and expires. Microscopic e.,'(amination of the colon epithelium at autopsy reveals 11umerous acidophmc bodies and small cells with pyknotic nuclei. Which of the following proteins most likely played a key role in triggering radiation-induced cell deaLh in this patients colonk mucosa7 ***(A) Cywchrome P450 ***(B) P-Catenin ***(C) E-Cadherin ***(D) P-Select in ***(E) p53
49 The answer is E: p53. ApopLOsis detect.s and destroys cells t.hat harbor dangerous mut.at.ions, thereby maintaining genet.ic consistency and preventing the development of cancer. There are several means, t.he most. imponant of which is probably p53, by which the cell recognizes genomic abnonnalities and assesses whe1:her they can be repaired. lf the damage to DNA is so severe that it ca1m01: be repaired, the cascade of even ts leading w apoptosis is activated, and the cell dies. This process protects an organism from the consequences of a nonf- t.mctional cell or one that. cannot control its own proliferation (e.g., a cancer cell). After it binds to areas of DNA damage, p53 activat.es prot.eins that arrest the cell in G 1 of t.he cell cycle, allowing time for DNA repair to proceed. It also directs DNA repair enzymes lO the site of injury. If t.he DNA damage cannot be repaired, p53 activates mechanisms that terminat.e in apoptosis. There are several pathways by which p5.3 induce apoptosis. This molecule dowmegulates transCJiption of t.he antiapoplotic prot.ein Bcl-2, while il upregulates lransCJiption of the proapoptotic genes bax and b ak. Cytochrome P450 (choice A) is a member of the m1xed function oxidase system. P-Catenin (choke B) is a membrane protein associated with cell adhesion molecules. Seleclins (choices C and D) are celJ adhesion molecules involved in leukocvte recirculation. ' ***Diagnosis: Apoptosis
f A 22-year-old woman nursing her newborn develops a tender erythematous area around the nipple of her left b reast. A thick, yellow fl uid is observed to drain from an open fissure. Examination of this breast fluid under the light microscope will most likely reveal an abundance of which of the following inflammatory cells? ***(A) B lymphocytes ***(B) Eosinophils ***(C) Mast cells ***(D) Neurropluls ***(E) Plasma cells
1 The answer is D: Neutrophils. The thick, yellow fiuid draining from the breast fissure in this patiem represents a purulent exudate. Purulent n.'Udates and effusions are associated with pathologic conditions such as pyogenic bacte1ial infection.c:;, in which the p redominant cell type is the segmemed neutrophil (polyn10111honuclear leukocyte). Mast cells (choice C) are granulated cells that contain recepwrs for lgE on the1r celJ surface. They are additional cellular sources of vasoactive mediators, panicularly in response to allergens. B lymphocytes (choice A) and plasma cells (choke E) are mediators of chTOnic inflammation and provide antigen-specific immunily to infectious diseases. ***Diagnosis: Acme mastitis
2 Which of the following mediators of in flammation facilitates chemota..xis, cytolysis, and opsonization at the site of irillammation in the patient d escribed in Question 1? ***(A) Complement proteins ***(B) Dden.sins ***(C) Kallikrein ***(D) Kinins ***(E) Prostaglandins
2 The answer is A: Complement proteins. Complement proteins act upon one another in a cascade, generating biologically active fmgments (e.g., C5a, C3b) or complexes (e .g., C567). These products of complement activation cause local edema by increasing the pem1eabllity of blood vessels. They also promme chemotaxis of leukocytes and lyse cells (membrane auack complex) and act as opsonlns by coating bacteria. Although the other choices are mediators of inflammation, they have a more restricted set of functions. Kinins (choice D) are rom1ed foUowing tissue trauma and mediate pain transmission. None of the other choices are involved in opsoruzarion or cytolysis. ***Diagnosis: Acute mastitis
3 A 63-year-old man becomes febrile and begins expectorating large amounts of mucopurulent sputum. Sputum cultures are positive for Gran1-positive diplococci . Which of the fol1owiJ1g mediatOTs of inflammation provides potent chemotactic factors [or the directed migration or inflammatory cells into the alveo 1 ar air spaces of this patient? ***(A) Bradykinin ***(B) Histamine ***(C) Myeloperoxidase ***(D) N-formylated peprides ***(E) Plasmin
3 The answer is D: N·formylated peptides. The most potent chemotactic factors for leukocytes at the site or injury are (l) complement proteins (e.g., C5a); (2) bacte1ial and mitochondtial products, particularly low molecular we1ght N-formylated peptides; (3) products of arachidonic acid metabolism (especially LTB4); and (4) chemolcines (e.g., imerleukin-1 and interferon-)'). Plasmin (choice E) is a fibrinolytic enzyme generated by activated Hageman factor (clotting factor Xll). Histamine {choice B) is one of the primary mediators of increased vascular permeabillty. None of the other choices are chemotactic agents. ***Diagnosis: Pneumonla
4 A 59-year-old man suffers a massive hean attack and e>.:pires .....__ 24 hours later due to ventricular arrhythmia. HislOloglc examination of the affected heart muscle at autopsy would show an abundance of '"lhich of the follo\llfing mflammatory cells? ***(A) Fibroblasts ***(B) Lymphocytes ***(C) Macrophages ***(D) NeULrophils ***(E) Plasma cells
4 The answer is D: Neutrophils. During acute inllammarion, neurrophils (PMNs) adhere w the vascular endmhelium. TI1ey flatten and migmte from the vasculature, through the endothelial cell layer, and into the surrounding tissue. About 2-f hours after the onset of infarction, PMNs are observed to infi ltrate necrotic tissue at the periphery of the lnfarct. Their function is to clear debris and begin the process of wound healing. Lymphocytes (choice B) and plasma cells (choice E) are mediators of chronic in Fl ammation and provide antigenspecific immunity to in reclious diseases. Fibroblasts {choKe A) and macrophages (choice C) regulate scar tissue fom1ation at the site of infarction. ***Diagnosis: Acute myocardial infarction
5 A 5-year-old boy punctures his thumb with a rusty nail. Four hours later, the thumb appears red and swollen. Initial S\VeUing of the boy's thumb is primarily due to which of the following mechanisms? ***(A) Decreased intravascular hydrostatic pressure ***(B) Decreased intravascular oncotic pressure (() Increased capillary permeability ***(D) Increased intravascular oncotic pressure ***(E) Vasoconsniction of anerioles
5 The answer is(: Increased capillary permeability. Forces that .____ regulate the balance of vascular and tissue fluids include (l) hydrostatic pressure, (2) oncolic pressure, (3) osmotic pressure, and ( 4) lymph fiow. During inilanunation, an increase in the permeability of the endothelial cell barrier results in local edema. Vasodilation of arterioles exacerbates fluid leakage, and vasoconstriction of postcapillary venules increases the hydrostatic p ressure in the capilla1y bed (thus, not choice A), potentiating the fonnation of edema. Vasodilation of venules decreases capillary hydrostatic pressure and inhibits the movemem of fluid into the extravascular spaces. Acme inflammation is not associated with changes in plasma oncotic pressure (choices Band D). ***Diagnosis: Inflammatory edema
6 \Nhich of rhe following serum proteins activates the complement, coagulation, and fib rinolytic systems at t.he site of injury in the patient described in Question 5? ***(A) Bradykinin ***(B) Hageman factor (() Kallikrein ***(D) Plasmin ***(E) Thrombin
6 The answer is B: Hageman factor. Hageman factor (clouing factor XU) provides a key source of vasoactive mediators. Activation of this plasma protein at the site of tissue injury stimulates (l) conversion of plasminogen to plasmin, which induces 6btinotysis; (2) conversion of p rekallikrein to kallikrein, which generates vasoactive peptides of low molecular weight referred w as kinlns; (3) activation of the alternative complemem pathway; and ( 4) activation of the coagulation system. Although the other choices are mediators o[ inflammation, they have a more restricted set of func tions. ***Diagnosis: Jnflammadon
7 An 80-year-old woman presems with a 4-hour history of fever, shaking chills, and disorientation. Her blood pressure is 80/40 mm Hg. Physical examination shows diffuse purpura on her upper arms and chest Blood cultures are positive for Gramnegative organisms. Which of the following cytokines is primalily involved in the pathogenesis of direct vascular injury in this patient with septic shock? ***(A) lnterferon-y ***(B) lnterleukln-1 (() Platelet-derived growth factor ***(D) Transforming growth facto r-~ ***(E) Tumor necrosis factor-a
7 The answer is E: Tumor necrosis factor-a. (TN F-a) . Septicemia (bacteremia) denotes the clinical condition in which bacteria are found in the circulation. It can be suspeCLed clinically, but the final diagnosis is made by culmring Lhe organisms from the blood. In patients with endowxic shock, lipopolysaccharide released from Gram-negative bacteria stimulates monocytes/ macrophages to secrete large quamities of TNF-a.. This glycoprotein causes direct cytotoxic damage to capillary endothelial ceTis. The other choices do nor cause direct vascular i njmy ***Diagnosis: Septic shock
8 A 24-year-old intravenous d rug abuser develops a 2-day hisLO t)' of severe headache and feve r. His temperature is 38.JOC (103"'F). Blood cultures are positive for Gram-positive cocci. The patient is given intravenous antibiotics, but he deteliorates rapidly and dies. A cross section of the brain a[ amopsy (shown in [he image) reveals rwo encapsulated cavities. Which of the following te rms best characterizes this pathologic finding? ***(A) Cnrordc inflammation ***(B) Fibrinoid necrosis ***(C) Granulomatous inflammation ***(D) Reactive gliosis ***(E) Suppurative inflammation
8 The answer is E: Suppurative inflammation. Suppurative inflammation describes a condition in which a purulemexudate is accompanied by significant liquefactive necrosis. It is the equivalent of pus. The photograph shows two encapsulated cavi£ies in the brain. These abscesses are composed of a central cavity filled with pus, surrounded by a layer of granulation tissue. Chronic inflammation {choice A) is nonsuppurative. Fibrinoid necrosis (choice B) is observed in areas of necrotizing vasculitis. Granulomatous inflammation (choice C) is seen in patients with tuberculosis. Reactive gliosis (choke D) is a nonnal response of the brain to injury and infection but is not visible on the cut surface of the brain at autopsy ***Diagnosis: Cerebral abscess
9 A 36-year-old woman with pneumococcal pneumonia develops ....__ a right pleural effusion. The pleural fluid displays a high specific gravity and contains large numbers of polymorphonuclear (PMN) leukocytes. Which of the following best characteiizes this pleural effusion? ***(A) Fibrinous exudate ***(B) Lymphedema ***(C) Purulem exudate ***(D) Serosanguineous exudate ***(E) Transudate
The answer is C: Purulent exudate. The pleural effusion encountered in this patiem represents excess O.uid in a body cavicy. A Lransudate denotes edema fluid with low protein comem, whereas an CA'1.tdate denotes edema fluid with high protein content. A pumlent e.~:udate or efl'usion contains a prominent cellular componem (PMNs). A serous exudate or effusion is characterized by the absence of a prominem cellular response and has a yellow, strawli.ke color. Fib1inous exudme (choice A) does not contain leukocytes. Serosanguineous e>..'Udate (choice D) comains RBCs and has a red tinge. ***Diagnosis: Bactetial pneumonia, pleural effusion
10 A 33-year-old man presents with a 5-week history of calf pain and swelling and low-grade fever. Serum levels of creatine kinase are elevated. A muscle biopsy reveals numerous eosinophils. What ls the most likely etiology of this patients myalgia? ***(A) Autoimmune disease ***(B) Bacterial infection ***(C) Muscular dystrophy ***(D) Parasitic infeCLion ***(E) Viral infection
10 The answer is D: Parasitic infection. Eosinophils are particularly evident during allergic-type reactions and parasitic infestations. Infections with Tnchinclla are accompanied by eosinophilia, and skeletal muscle is typically infiltrated by eosinophils. Patients with muscular dystrophy (choice C) show elevated serum levels of creatine kinase, but eosinophils are not seen on muscle biopsy Bacterial infections (choice B) are associated with neutrophilia, and affected tissues are infiltrated with PMNs. Viral infections (choice E) are associated with lymphocytosis, and affected tissues are infiltrated \Vith B and T IymphocyLes. Polymyositis, an autoimmune disease (choice A), does not featu re eosinophils. ***Diagnosis: Trichinosis
11 A 10-year-old boy \Vith a history o[ recurrent bacterial infecrions presents with fever and a productive cough. Biochemical analysis of his nemrophils demonstrates that he has an impaired ability to generate Teactive oxygen species. This patient most likely has inherited mutations in the gene that encodes which of the following proteins? ***(A) Catalase ***(B) Cytochrome P450 ***(C) Myeloperoxidase ***(D) NADPH oxidase ***(E) Superoxide dismutase
11 The answer is D: NAPDH oxidase. The imponance of oxygendependent mechanisms in the bacterial killing by phagocytic cells is exemplifted in chronic granulomatous d isease of childhood. Children with this disease suffer from a hereditary deficiency of NADPH oxidase, resulting in a failure to produce superoxide anion and hydrogen peroxide during phagocytOsis Persons with this disorder are susceptible ro recurrent bacterial infections. Patients deficient in myeloperoxidase (choice C:) cannot produce hypochlorous acid {HOCl) and e..'.'perience ru1 increased susceptibility m infections with the fun gal pathogen Ca11dida. Catalase (choice A) converts hydrogen perox1de to water and molecular oxygen. ***Diagnosis: Chronic granulomatous disease
12 A 25-year-old woman present'> \Vith a history of recu rrent shortness of b reath and severe wheezin g. Laboratory studies demonstrate that she has a deficiency of Cl inhibitor, an esterase inllibiwr that regulates the activation or the classicaJ complemem pathway. What is the diagnosis? ***(A) Chronic granulomatous disease ***(B) Hereditary angioedema ***(C) Myeloperoxidase deficiency ***(D) Selective lgA deficiency ***(E) vViskmt-Aldrich syndrome
12 The answer is 8: Hereditary angioedema. Deficiency of Cl inhibitor, with excessive cleavage of C4 and C2 by Cls, is associated with the syndrome of hereditary angioedema. This disease is characterized by episodic, painless, nonpitting edema of soft tissues. lt is the result of chronic complement activation, with the generation of a vasoactive peptide from C2, and may be life threatening b ecause of the occurrence of laryngeal edema. Chronic granulomatous disease (choice A) is due to a hereditary deficiency of NADPH oxidase. Myeloperoxidase deficiency (choice C) increases susceptibility to infections with Ca11 dida. Selective lgA deficiency (choice D) and Wiskott· Aldrich syndrome (choice E) are congenital immunodeficiency disorders associated ·...vith defects in lymphocYle function. ***Diagnosis: Hereditary angioedema
13 A 40-year-old man complains of a 2-week history of increasing abdominal pain and yellow discoloration o[ his s-clera. Physical examination reveals right upper quadrant pain. Laboratory s tudies show elevated serum levels of alkaline phosphatase (520 U/dl ) and bilirubin (3.0 mgldl). A liver biopsy shows ponal fibrosis, with scattered foreign bodies consistent with schtstosome eggs. Which of the following inflammatory cells ts most likely to predominate in the portal tracts in the liver of this patiem? ***(A) Basophils ***(B) Eosinophils ***(C) Macrophages ***(D) Monocytes ***(E) Plasma cells
13 The an:swe-r is 8: Eosinophils. Eosinophils are recruited in parasitic infestations and would be expected LO predominate in the ponal tracts or the liver in patients with schistosomiasis. Eosinophils contain leukotrienes and platelet -activating factor, as well as acid phosphatase and eosinophil major basic protein. Plasma cells (choice E) are differentiated B lymphocytes that secrete large amounts of monospecific immunoglobulin. ***Diagnosis: Schistosomiasis, eosinoph1ls
14 A 41-year-old woman complains of excessive menstrual bleeding and pelvic pain o[ 4 momhs. $he uses an intrauterine device for contraception. Endometrial biopsy (shown in the image) reveals an excess of plasma cells {arrows) and macrophages within the stroma. The presence of these cells and scattered lymphoid follicles within the endometrial stroma is evidence of which of the follmvmg conditions? ***(A) Acute inflammation ***(B) Chronic inflammation ***(C) Granulation tissue ***(D) Granulomatous inflammation ***(E) Mensnu ation
14 The answer is B: Chronic inflammation. Inflammation has historically been referred to as either acme or chronic, depending on the persistence of the injury, clinical symptoms, and the nature of the inflammatory response. The cellular componems of chronic inflammation are lymphocytes, antibodyproducing plasma cells (see arrows on photomicrograph), and macrophages. The chron ic inflammatory response is o ften prolonged and may be associated with aberrant repair (i.e , fibrosis) Neutroph ils are featured in acute inflammation (choice A) and menstruation (choice E). Choices C and D do not exhibit the histopathology shown in the image. ***Diagnosis: Chronic endometritis
15 A 62-year-old woman undergoing chemotherapy for breast cancer presents ·with a 3-day history of fever and chest pain. Cardiac catheterization reveals a markedly reduced ejecrion fTaction with nonnal coromny blood now. A myocardial biopsy is obtained, and a PCR test for coxsackievims is positive. Hiswlogic examination of this patients myocardium will most likely reveal an abundance of which of the following inflammatory cells? ***(A) EosinophHs ***(B) Lymphocytes ***(C) Macrophages ***(D) Mast cells ***(E) Neutrophils
15 The answer is 8: Lymphocytes. This patient with viral myocarditis will show an accumulation of lymphocytes in the affected heart muscle. NaJve lymphocytes encounter antigen-presenting cells (macrophages and dendritic cells) in the secondary lymphoid organs. ln response to this cell-cell interaction, they become activated, circulate in the vascular system, and are recruited to petipheral tissues (e.g., heart). The other choices are not characteJistic responders to viral infections, although acute inflanunation may be observed in lytic infections. ***Diagnosis: Viral myocarditis
16 A 58-year-old woman with long-standmg diabetes and hypertension develops end-stage renal disease and dies in uremia. A shaggy fibtin-tich exudate is noted on the visceral pericardium at autopsy (shown in the image). 'vVhich of the following best explains the pathogenesis of this fibtinous exudate? ***(A) Antibody binding and complement activation ***(B) Chronic passive congestion ***(C) Injury and increased vascular permeability ***(D) Margination of segmented nemrophils ***(E) Thrombosis of penetrating corona1y arteries
16 The answer is (: Injury and increased vascular penneability. Binding of vasoactive mediators to specific recepwrs on endothelia] cells results in contraction and gap formation. This break in the endothelial ban ier leads w the leakage of intravascular Quid into the extravascular space. Direct injury to endothelial cells also leads w leakage of imravascular fluid. A fibrinous exudate contains large amoums of fibrin as a result of activation of the coagulation system. \ 71/hen a fibrinous exudate occurs on a serosal surface, such as the pleura or pericardium, iL is referred to as fibrinous pleuriLis or fibrinous pericarditis. Although the other choices describe aspects of inflammation, they do not address the pathogenesis o( edema formation with activation of the coagulation system. ***Diagnosis: End-s~.age kidney disease , fibrinous pericarditis
17 A 68-year-old man presents with feve r, shaking chills, and shortness of breath. Physical examination shows rates and decreased breath sounds over both lung fields. The patient exhibits grunting respirations, 30 to 35 breaths per minute, ~rith flaring of the nares. The sputum is rusty yellow and displays numerous polymorphonuclear leukocytes. Which of the following mediawrs of inflammation is chiefly responsible for the development of fever in this p<Hient? ***(A) Arachidonic acid ***(B) lmerleukin-1 ***(C) Leukmriene B 4 ***(D) Prosracyclin (PGI) ***(E) Th romboxane A!
17 The answer is B: lnterleukin-1. Release of exogenous pyrogens by bacteria, viruses, or injured cells stimulates the production of endogenous pyrogenssuch as IL-l a, IL-l~. and TNF-a. IL-l is a 15-kDa protein that stimulates prostaglandin synthesis in the hypothalamic the rmoregulatory centers, thereby altering the "thermostat" that conu·ols body temperarure. l nhlb1tors of cyclom.:ygenase (e.g, aspirin) block the fever response by inhibiting PGE2 synthesis in the hypothalamus. Chills, rigor (profound chills with shivering and piloerectton), and sweats (mallow hem dissipaUon) are sympLoms assoctated with fever. The other choices are mediawrs of inflammation, but they do not directly conuol body temperature ***Diagnosis: Bacterial pneumonia
18 Spmum culLUres obtained from the patient described in Question 17 are positive for Strepwcoccus pneu moniae. Removal of bacteria from the alveolar air spaces in this patiem involves opsonization by complemem, an imponanr su~p in mediating which of the following leukocyte functions? ***(A) Chemotaxis ***(B) Diapedesis ***(C) Haptotaxis ***(D) Margination ***(E) Phagocymsis
18 The answer is E: Phagocytosis . Many inOammatory cells are able to recognize, intemalize, and digest foreign materials, microorganisms, and cellular debris. This process is lermed phagocytosis, and Lhe effector cells are knovm as phagocytes. PhagocytosisofmostbiologicagentsisenhancedbyLheircoaLing \Vith specific plasma components (opsonlns), particularly immunoglobulins or the C3b fragment of complement. The other functions are not enhanced by opsonization. ***Diagnosis: Bacterial pneumonia
19 Which of the following mediators of in flammation is primarily responsible for secondary lnjUJy to alveolar basement membranes and lung parenchyma in the patiem described in Questions l 7 and 18? ***(A) Complemem proteins ***(B) Fibrin sp1it products ***(C) Immunoglobulins ***(D) lnterleukin-1 ***(E) Lysosomal enzymes
19 The answer is E: Lysosomal enzymes. The primary role of neutrophHs in inflammation is host defense and debridement of damaged tissue. However, when the response is extensive or unregulated, the chemical mediators of inOammation may prolong tissue damage. Thus, the same neutrophil-de!ived lysosomal enzymes that are benefidal when active imracellularly can be harmful when released w the extraceUular environment. The other choices are less likely to cause direct injury w the lung in a patient \Vith pneumonia. ***Diagnosis: Bacterial pneumonia
20 Which of the following proteins inhibits fibtinolysis, activation of the complemem system, and protease-mediated damage in the lungs of the patiem described in the previottS questions? ***(A) Acid phosphatase ***(B) Lactofenin ***(C) Lysozyme ***(D) 0: 1-Macroglobulin ***(E) Myeloperoxidase
20 The answer is D: ~-Macrog lobulin . Proteolytic enzymes that are released by phagocytic ceUs during inflammation arc regulated by a family of protease inhibitors, including a 1-antitrypsin and a 2-macroglobulin. These plasma-derived p roteins inhibit plasmin-activated fibrinolysis and activation of the complement system and help protect against nonspcci fie tissue injmy during acute inflammation. Lysozyme (choice C) is a glycosidase that degrades the peptidoglycans of Grampositive bacterial cell walls. Myeloperoxidase (choice E) is contained within nemrophil granules. ***Diagnosis: Bacterial pneumonia
21 A 35-year-old woman presents with a 5-day history o [ a painful sore on her back Physical examinauon reveals a 1-cm abscess over her left shoulder. Biopsy of the lesion shows vasodilation and leukocyte margination (shown ln the image). What glycoprote]n mediates initial tethering of segmented neulrophHs lo endothelLal cells in this skin lesion? ***(A) Cadherin ***(B) Ent.actin ***(C) I me grin ***(D) Laminin ***(E) Select in
21 The answer is E: Selectin. Setectins are sugar-binding glycoprmeins that mediate the initial adhesion of leukocytes to endothe!Jal cells at snes of mllammarion. E-se lectins are found on endothelial cells, P-selectins are found on platelets, and L-selectins are found on leukocytes. E-seleClins are stored in Weibel-Palade bodies of resting endothelial cells_ Upon aCLivation, E-selectins are redisuibuted along the luminal surface of the endothelial cells, where they mediate the initial adhesion (tetheling) and rolling of leukocytes. After leukocyte..'> have come to a rest, imegJ.ins (choice C) mediate transendothelial cell migration and chemotaxis. Cadhetins (choice A) medhne cell-cell adhesion, but they are not involved in neutrophil adhesion LO vascular endmhelium. Emactin (choice B) and laminin (choice D) are basement membmne proteins. ***Diagnosis: Carbuncle
22 A 14-year-old boy receives a laceration on his forehead during an ice hockey game. vVhen he is first attended to by the medic, th ere is blanching of the skin around the wound. Which ofLhe following mech anisms accounts for this transient reaction to neurogenic and chemical stimuli at the site of injury? ***(A) Constriction of postcapillary venules ***(B) Constriction of precapUlary arterioles ***(C) Dilation of postcapillary venules ***(D) Dilation of precapillaty anetioles ***(E) Ischemic necrosis
22 The answer is 8: Constriction of pre(apillary arterioles. The initial response of anetioles to neurogenic and chemical stimuli is transient vasoconstriction. However, shonly thereafter, vasodilation (choice D) occurs, with an increase in blood flow to the inflamed area. nus process is referred to as active hyperemia_ None of the other choices cause transient skin blanching. ***Diagnosis: Laceration
23 An 8-year-old girl with asthma presents with respiratmy disn·ess. $he has a history of allergies and upper respiratory tract infections. She also has history of wheezes associated with exercise. Which of the following mediators of inflammation is rhe most powerful stimulator of bronchoconstriction and vasoconsuiction in this patient? ***(A) Bradykinin ***(B) Complement proteins ***(C) Interleukin-1 ***(D) Leukorrienes ***(E) Tumor necrosis factor-a.
23 The answer is D: Leukotrienes. Asthma is a chronic lung disease caused by increased responsiveness of the airways to a vatiety of stimuli. Chemical mediators released by chronic lnflam.matory cells in the lungs of these patients stimulate bronchial mucus production and bronchoconsttiction. Among these mediators are leukoo-ienes, also 1<nown as slow-reacting substances of anaphylaxis. They are derived from arachidonic acid through the lipoxygenase pathway Leukorrienes stimulate contraction of smooth muscle and enhance vascular permeability They are responsible for the development of many of the clinical symptoms associated with asthma and other allergic reactions. Although the other choices are imponant mediators of inflammation, they do not play a leading role in the development of bronchoconstriction ln patients with bronchial asthma. ***Diagnosis: Asthma
24 Which of the following preformed substances is released from mast cells and platelets, resulting in increased vascular permeability in the lungs of the pat1cnt described in Question 23? ***(A) Bradykinin ***(B) Hageman factor ***(C) Histamine ***(D) Leukmrienes (SRS-A) ***(E) Th romboxane A2
24 The answer is(: Histamine. When lgE-sensitized mast cells are stimulated by antigen, prefom1ed mediators of inflammation are secreted into the extracelJular tissues. Histamine binds to specific H1 receptors in the vascular wall, inducing enclothellal cell contraction, gap formation, and edema. Massive release of histamine may cause circulatory collapse (anaphylactic shock). Bradykinin (choice A) and Hageman facto r (choice B) are plasma-dertved mediators. The other choices are not preformed molecules bm are symhesized de novo following edt activacion. ***Diagnosis: Asthma
25 A 75-year-old woman complains of recent onset o[ chest pain, fever, and productive cough with rust-colored spumm. A chest X-ray reveals an infiltrate in the right middle lobe. Sputum cultures are positive for Streptococcus pneumoniae. Phagocytic cells m this patient's affected lung tis..c;ue generate bacteriocidal hypochlorous acid using which of the follml\ing enzymes? ***(A) Catalase ***(B) C)'clooxygenase ***(C) Mydoperoxi dase ***(D) NADPH oxidase ***(E) Superoxide dismmase
ZS The answer is C: Myeloperoxidase. Myeloperoxidase camlyzes the conversion of Hp2, in che presence of a halide (e.g., chlmide ion), to form hypochlorous acid. This powerful oxidant is a major bactericidal agent produced by phagocytic cells. Patients deficient in myeloperoxidase cannot produce hypochlorous acid and have an increased susceptibility to recurrent infections. Catalase (choice A) cacabolizes H20r Cyclooxygenase (choice B) mediates the conversion of arachidonic acid to prostaglandins. NADPH oxidase (choice D) is involved in oxygen-fl-ee radical formation during the neurrophil respiratory burst. Superoll.ide dismutase (choice E) reduces the superO}I.'lde radical to H20 r ***Diagnosis: Bacterial pneumonia
26 A 28-year-old woman cuts her hand while dicing vegetables i11 the kitchen. The wound is cleaned and sutured. Five days later, the site of injury contains an abundance or chronic inOammawry cells that actively secrete ilu erleukin-1 , tumor necrosis facwr-a , interferon-a., numerous arachidonic add derivatives , and va tious enzymes. Name these cells. ***(A) B lympboc)'tes ***(B) Macrophages ***(C) Plasma cells ***(D) Smoolh muscle cells ***(E) T lymphoc)'tes
26 The answer is 8: Macrophages. The macrophage is the pivotaJ cell in regulating chronic Ln.flammation. Macrophages, which are derived from cLrculating monocytes, regulate lymphocyte responses to antigens and secrete a variety of media~ors that modulate the proliferation and function of fibroblasts and endothelial cells. None of the other ceUs have this wide spectnnn of regulatory functions . ***Diagnosis: Laceration , wound healing
27 A 68-year-old man with prostate cancer and bone metastases presents with shaking chills and fever. The peripheral \VBC coum is 1,000/J.!L (normal = 4,000 w 11,000/!ll-). Which of the following terms best desctibes this hematologic finding? ***(A) Leukocytosis ***(B) Leukopenia ***(C) Neutrophilia ***(D) Pancytopenia ***(E) Leukemoid reaction
27 The answer is B: Leukopenia. Leukopenia is defined as an absolute decrease in the circulating WBC count. lt Ls occasionally encountered under conditions of chronic inOammation, especially in patients who are malnourLshed o r who su ffer from a chronic debilitating disease. Leukopenia may also be caused by typhoid fever and certain viral and ticketlSial infections. LeukocytosLs (choice A) is defined as an absolute increase in the circulating WBC count. Neutrophilia (choice C) is defined as an absolute increase in the circulating neutrophil coum. Pancytopenia (choice D) refers ro decreased circulating levels of all formed elements in the blood. ***Diagnosis: Prostate cancer
28 A 25-year-olcl machinist i.5 injured by a metal sliver in his left hand. Over the next few days, the wounded area becomes reddened, tender, swoUen, and fee ls wann to the touch. Redness at the site of injury in this patient is caused primatily by which of the following mechanisms? ***(A) Hemon hage ***(B) Hemostasis ***(C) Nemrophilmargination ***(D) Vasoconstriction ***(E) Vasodilation
28 The answer is E: Vasodilation. Vasodilation of precapillary anerioles increases blood flow at the site of tissue injury. This condition (active hyperemia) is caused by the release of specific mediators. Vasodilalion and hyperemia are ptimaril y responsible for the redness and warmth (rubor and calor) at sites of injury. The other choices do nor regulate active hyperemia. ***Diagnosis: Acute in n.ammation
29 The patiem described in Question 28 goes w the emergency room to have the sliver removed. Which of the following mediators of inflammation plays the most imponam role 111 stimulating platelet aggregation at the site of injury fo ll ovving this minor surgical procedure? ***(A) Leukotriene C4 ***(B) Leukorriene D + ***(C) Prostaglandin E, ***(D) Prostaglandin 12 ***(E) TI1romboxane A2
29 The answer is E: Thromboxane A2 . Platelet adheren ce , aggregation, and degranulation occur wh en platelets come in contact with fibrillar collagen or thrombin {after activation of the coagulation system). Platelet degranulation is associated with the release of serotonj n, which directly increases vascular permeability. ln addition, the arachidonic acid metabo11te thromboxane A2 plays a key role in the second wave of platelet aggregation and med iates smooth muscle constriction. Prostaglandins E2 and 12 (choices C and D) inhibit inflammatory cell fu nctions. Leukotrienes C~ and D~ (choices A and B) induce smoorh muscle contraction. ***Diagnosis: Acute in nammation
30 Twenty-fou r hours later, endothelial cells at the site of i.njuty in the patient described in Questions 28 and 29 release a chemical mediator that inhtbits furtl1er platelet aggregation. Name this mediator of inflammation. ***(A) Plasmin ***(B) Prostaglandin (PGI2 ) ***(C) Serownin ***(D) Thrombin ***(E) Thromboxane A2
30 The answer is B: Prostaglandin (PGI2 ) . PG12 is a derivative of arachidon ic acid mat is formed in the cyclooxygenase enzyme pathway. It promotes vasodiJation and bronchodilation and also in hibits platelet aggregation. It activates adenylyl cyclase and increases intracellular levels of cAMP. Its action is diametrically opposite to that of thromboxane A2 (ch oice E), wh ich activates guanylyl cyclase and increases intracellular levels of cGMP. Plasmin {choice A) degrades fibrin. Serotonin (choice C) is a vasoactive amine. Thrombin (choice D) is a protease that mediates the con version of fibrinogen ~o fibrin. ***Diagnosis: Acute inOammation
31 A 37 -year-old man >vixh AIDS is admitted w the hospilal with a 3-week hiswry of chest pain and shortness of breath. An X-ray film of the chest shows bilateral nodularities of the lungs. A CT-guided lung biopsy is shown in the image. The multinucleated cell in the center of this field is most likely derived from which of the foUowing inflammalOry cells? ***(A) Basophils ***(B) Capillary endothelial cells ***(C) Macrophages ***(D) M}rofibroblasts ***(E) Smooth muscle cells
31 The answer is C: Macrophages. Granulomas are collections of epithelloid cells and multinucleated giam cells that are fanned by cytoplasmic fusion of macrophages. ·when the nuclei are arranged around Lhe periphery of the cell in a horseshoe pauem (see photomicrograph), the ce ll is termed a Langhans giant cell. Frequently, a foreign pathogenic agent is identified \vjthin the cytoplasm of a multinucleated giant cell, in which case the label foreign body giam cell is used. The other cells do not fonn multinucleated giam cells in granulomas ***Diagnosis: AlDS, granulomatous inflammation
32 A 45-year-old woman with autoimmune hemolytic anemia presents \\'ith increasing fatigue. Which of the following mediators of inflammation is primarily responsible for antibody-mediated hemolysis in this patien t? ***(A) Arachidonic acid metabolites ***(B) Coagulation proteins ***(C) Complement proteins ***(D) Kallikrein and kinins ***(E) Lysophospholipids
32 The answer is C: Complement proteins. Activation of the complement cascade by me classical or alternative pathway leads to the cleavage of complement fragments and the formation of biologically active complexes. The C5b fragmem aggregates with complement proteins C6, C7, C8, and C9, resulting in the polymerization of the membrane attack complex (MAC). 1v1AC lyses cells by inserting into the lipid bilayer, fanning a pore, and destroying me pem1eability barrier of the plasma membrane. Kallikrein and kinins (choice D) are formed following tissue trauma and mediate pain transmission. None of the other choices mediate hemolysis . ***Diagnosis: Hemolytic anemia, amoinmmne disease
33 A 59-year-old alcoholic man is brougl1t to the emergency room with a fever (38.rCil03°F) and foul-smelling breath. A chest X-ray reveals a pulmonary abscess in the right lower lobe. The patient subsequently develops acute bronchopneumonia and dies. Microscopic examination of tl1e lungs at autopsy is shown in the image. Activation of phospholipase ~ in these intra-alveolar cells resulted in the fom1ation of which of the follo\ving mediators of inflammation? ***(A) Arachidonic acid ***(B) cAMP ***(C) cGMP ***(D) Diacylglycerol ***(E) Inositol trisphosphate
33 The answer is A: Arachidonic acid. Cellular sources of vasoactive mediawrs are (1) derived fTom the metabolism of arachidonic acid (prostaglandins, thromboxanes, leukotrienes, and platelet-activating facto r), (2) prefom1ed and srored in cyroplasmic granules (histamine, serotonin, and lysosomal hydrolases), or (3) generated as normal regulators of vascular f1.mction (nitric oxide and neurokinins). The photomicrograph shows polymorphonuclear leukocytes responding to a bacterial pneumonia. Free arachidonic acid in these acute inflammatory cells is derived from membrane phospholipids (prin1arity phosphalidylcholine) by stimulus-induced activation of phospholipase A1 . Phospholipase A2 activation does not generate the other inflammatory medialOrs listed. ***Diagnosis: BaC(erial pneumoma
34 A lO~year-old girl presents with a 2-week hismry of puffiness around her eyes and swelling of the legs and ankles. Laboratory s tudies show hypoalbuminemia and proteinuria The u rinary sedimem contains no inflammatory cells or red blood cells. Which of the following tenus describes this pad em's peripheral edema? ***(A) Effusion ***(B) Exudate ***(C) Hydropic change ***(D) Lymphedema ***(E) Transudate
34 The answer is E: Transudate. According to the Starling principle, the interchange of Ouid between vascular and extravascular compartments resullc; from a balance of forces that draw fluid into the vascular space or out into tissues. These forces include (l) hydrostatic pressure, (2) oncotic pressure (reOects plasma protein concentration), (3) osmotic pressu re, and (4) lymph now \..Vhen the balance of these forces is altered, the net result is rluid accumulation in the interstitial spaces (i.e, edema). Although edema accompanies acute inOammation, a variety of noninflammatory conditions also lead to the fom1arion of edema. for example, obsuuction of venous outflow or decreased light ventricular function results in a back pressure in the vasculature, thereby increasing hydrostatic pressure. l oss of albumin (kidney disorders, this case) or decreased synthesis of plasma proteins (liver disease, malnutrition) reduces plasma oncOlic pressure. Noninfla1mnatmy edema is refe1Ted w as a transudate. A transudate is edema fluid with a low protein comem. An exudate (choice B) is edema fluid \Vilh a high protein and lipid concentration that frequently contains inflammatmy cells. An effusion (choice A) represems excess Ouid in a body cavity such as the peritoneum or pleura. Lymphedema (choice D) is u.c;ually associated with obstruction of lymphatic flow (e.g., surgery or infection). ***Diagnosis: Nephrotic syndrome, noninflammatory edema
35 A 25-year-old woman develops a sore, red, hot, swollen left knee. She has no history of trauma and no famihal history of joint disease . Fluid aspirated from the joint space shows an abundance of segmented neutrophils. Transendothelial migration of acute inOammatmy cells imo this patiem:S joint space was mediated ptimarily by which of the following families of prO[eins? ***(A) Entactins ***(B) Fibrillins ***(C) Fibronectins ***(D) I me grins ***(E) Laminins
35 The answer is D: 'lntegrins. Chemokines and other proinflammatory molecules activate a family of cell adhesion molecules, namely the integrins. Molecules in this fami ly participate in cell-cell and cell-substrate adbesions and eel] signaling. lntegrins are involved in leukocyte recruitmem to sites of injury in acute inflammation. The other choices are extracellular matrix molecules that maintain LL-;sue architecture and facilitate wound healing. ***Diagnosis: Gonococcal anhritis
36 Aspirin is effem ve in relieving symptoms of acute inflammation in Lhe patient described in Question 35 because it inrubits wruch of the following enzymes? ***(A) Cyclooxygenase ***(B) MyeloperoxMase ***(C) Phospholip ase~ ***(D) Protein kinase C ***(E) Superoxide dismmase
36 The an.swer is A: Cyclooxygenase. Arachidonic acid is metabolized by cycloOA'Ygenases (COX-1 , COX-2) and lipoxygenases(5-LOX)mgenerateprostanoidsandleukoLrienes, respectively. The early inflammatmy prostanoid response is COX-1 dependent. COX-2 becomes d1e major source of prostanoicls as inflammation progresses. Inhibition of COX is one mechanism by which nonsteroidalami-mflammatorydrugs (NSAIDs), includlng aspirin, indomethacin, and ibuprofen. exen Lheir potent analgesic and anti-inflammatory effects. NSAlDs block COX-2- induced fom1ation of prostaglandins, thereby mitigating pain and inflammation. Myeloperoxidase (choice B) catalyzes the conversion of H10 2 , in the presence of a halide (e.g. , chloride ion) to form hypochlorous acid. This poweJ{ul oxidant is a major bactericidal agent produced by phagocytic cells. Superoxide dismutase (choice E) reduces the superoxide radical to H 20 2 . ***Diagnosis: Gonococcal anhntis
37 A 50-year-old woman is ruscovered w have metastatic breast cancer. One week after receiving her first dose of chemotherapy, she develops bactetial pneumonia. Which of the fol lowing best explains this patiems susceptibility to bactetial infection? ***(A) Depletion of serum complemem ***(B) lmpai red neutrophil respiratory burst ***(C) Inhibition of clQ[ting factor activation ***(D) Lymphocytosis ***(E) Neutropen ia
37 The answer is E: Neutropenia. The importance of protection afforded by acme inflammatmy cells is ernphas1zed by the frequency and severity of infections in persons with defective phagocytic cells. The most cmmnon defect is iatrogenic nemropema secondaq to cancer chemotherapy Chemotherapy would not be expected Lo deplete semm levels of complement (choice A) or alter the respiratory burst withil1 activated neutrophils (choice B). ***Diagnosis: Bactenal pneumonia
38 A 53-year-old man develops weakness, malaise, cough with bloody sputum, and night sweats. A chest X-ray reveals numerous apical densities bilaterally. Exposure to Myco bacterium t~.tberculos is was documemed 20 years ago, and M. tuberculosis is identified in the sputum. The patient subsequently dies of respiratory insufficiency. The lungs are e.xammed at autopsy (shown in the image). Wl1ich of the following best characterizes th e histOpathologic features of this pulmona1y lesion7 ***(A) Acute suppurative inflammatlon ***(B) Chronic inflammation ***(C) Fat necrosis ***(D) Fibrinoid necrosis ***(E) Granulomatous inflammation
38 TheanswerisE: Granulomatous inflammation. The photograph shows a necrotizing granuloma due to M. LUberwlosis. The necrotic center is surrounded by histiocytes, giant cells, and fibrous tL<;sue. Granulomatous inflammation is elicited by fungal infections, tuberculosis, leprosy, schistosomiasis, and the presence of foreign material. ll is characteristically associated with caseous necrosis produced by M. i1!berculosis. The other choices ffia}' be seen as secondary features in granulomatous inflammation. ***Diagnosis: Pulmonary tuberculosis
39 A 59-year-old man experiences acute chest pain and is rushed to the emergency room. Laborawry scudies and ECG demonsmue an acute myocardial infarction; however, coronary anety angiography perfom1ed 2. hours later does not sho>v evidence of thrombosis. Intravascular thrombolysis that occurred in this padem was mediated by plasminogen activators that were released by which of the following cells? ***(A) Cardiac myocyte..<; ***(B) Endmhelial ce1Js ***(C) Macrophages ***(D) Segmemed neutrophils ***(E) Vascular smooth muscle cells
39 The answer is B: Endothelial cells . The vascular endothelium has the ability to promote or inhibit tissue perfusion and inflammatory ceU infltLx through multiple med1anisms. For example, endothelial cells in the vicinity of the thrombus produce tissue-type plasminogen activators, which activate plasmin and initiate thrombolysis (fibtinolysis). None of the other ceUs produce significant quantities of plasminogen activators. ***Diagnosis: Myocardial infarction, hemostasis
40 Which of the following mediators of inOammation causes relaxation of vascular smooth muscle ceUs and vasodilation of arterioles at the site of myocardial infarction in the patient described in Question 39? ***(A) Bradykinin ***(B) Histamine ***(C) Leukmrienes ***(D) Ninic oxide ***(E) Thromboxane A,_
40 The answer is D: Nitric oxide. Nitric oxide (NO), which was previously knm.vn as endothelium-de rived relaxing factor, leads to relaxation of vascular smooth muscle cells and vasodilation of arterioles. NO also inhibits plateleL aggregation and mediates the kUling of bactetia and tumor cells by macrophages. Histami.ne (choice B), leukotrienes (choice C), and thromboxane A2 (choke E) stimulate Lhe contraction of smooth muscle cells. ***Diagnosis: Acute myocardial infarction
41 A 68-year-old coal miner \Vith a history of smoking and emphysema develops severe air-Gow obstruction and expires. Autopsy reveals a "black lung,n \Vilh coal-dust nodules scattered throughout the parenchyma and a central area of dense fibrosis. The coal dust entrapped \\lithin this miners lung 'vas sequestered primarily by which of the folio•ving cells7 ***(A) Endothelial ceUs ***(B) Fibroblasts ***(C) Lymphocytes ***(D) Macrophages ***(E) Plasma cells
41 TheanswerisD: Macrophages. Coal workers'pneumoconiosis reflects the inhalation of carbon particles. The character istic pulmonary lesions of simple coal workers pneumoconiosis include non palpable coal-dusl macules and palpable coaldust nodules, bO£h of which are typically multi ple and scatt.ered throughout the lung as 1- lO 4-mm black foci. Nodules consisL of dust-laden macrophages associated with a fibrotic stroma. NoduJes occur when coal is admixed with fibrogenic dusLs such as silica and are more properly classified as anthracosilicosis. Coal-dust macules and nodules appear on a chest radiograph as small nodular densities. The other choices are not phagocytic cells. ***Diagnosis: Anthracosillcosis, coal workers' pneumoconiosis
42 A 40-year-old man presents with 5 clays of productive cough and fever. Psettdomona.s aeruginosa is isolated from a pulmonmy abscess. The CBC shows an acute effect characterized by marked letlkocytosis (50,000 \NBCJ~LL) , and the differential count reveals numerous immature cells (band forms). Which of the follm.ving terms best describes these hematologic findings? ***(A) Leukemoid reaction ***(B) Leukopenia ***(C) Myeloid metaplasia ***(D) Myeloproliferadve disease ***(E) Neutrophilia
42 The answer is A: Leukemoid reaction. Circu laring levels of leukocytes and Lheir precursors may occasionally reach ve1y high levels (>50,000 WBOp L). Such a situation, referred w as a leukemoid reaction , is somedmes difficuh to difreremiate from leukem]a. 111 contrast to bacterial infecdons, viral infections (including infectious mononucleosis) are characterized by lymphocytosis, an absolute increase in the number of circulating lymphocytes. Parasitic infestations and certain allergic reactions cause eosinophilia, an increase in the number of circulating eosinoph ils. Leukopenia is defined as an absolu te decrease in the circulating WBC count. Myloid metaplasia (choice C) and myeloproliferative disease (choice D) are chronic disorders of the hemaLOpoietic system. Although technically correct, neutrophiUa (choice E) by itself does not demonstrate immaLure cells (band forms) and usually refers to lower levels of increased nemrophi.ls. ***Diagnosis: Pulmonary abscess
43 A 19-year-old woman presents with 5 days of fever (38°0101 "F) and sore throat. She repons that she has felt fatigued for the past week and has difficulty swallowing A physical examination reveals generalized lymphadenopathy If this patiem has a viral infection. a CBC will most likely show which of the following hemawlogic findings? ***(A) Eosinophilia ***(B) Leukopenia ***(C) Lymphocytosis ***(D) Neutrophilia ***(E) Tl1 rombocythemia
43 The answer is C: Lymphocytosis. Peripheral blood lymphocytosis is defined as an increase in the absolute peripheral blood lymphocyte count above the normal range (<4,000/j..LL in children and 9,000/j..LL in infants) The principal causes of absolute peripheral blood lymphocytosis are (l) acute vi ral infections (infectious mononucleosis, whooping cough, and acute infection lymphocytosis), (2) chronic bacterial infections (tuberculosis, brucellosis), and (3) lymphoproltferative diseases. The mher choices are not features of acute viral infections. ***Diagnosis: Infectious mononucleosis
44 A 40-year-old woman presents with an 8-month history of progressive gene ralized itching, weight loss, fa tigue, and yellow sclerae. Physical examination reveals mUd jaundice The anti mitochondrial antibody test is positive. A liver biopsy discloses p ericluctal inflammation and b lle duc t injury (shown in the image). Which of the follO\ving inflammato ry ce lls is the principal mediator of destntClive cholangitis in thls pariem? ***(A) Eosinophils ***(B) B lymphocytes ***(C) T lymphocytes ***(D) Mast cells ***(E) Neurrophils
44 The answer is C: T lymphocytes. Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by destruction of intrahepatic bile ducts {nonsuppurative desmtctive cholangitis). PBC occurs principally in middle-aged women and is an amoimmune disease. Most paLiems with PBC have at least one other disease usually classed as autoimmune (e.g., thyroiditis, rheumawid arthritis, sclerodetma, Sjogren syndrome, or systemic lupus erythematosus). More than 95% of patients with PBC have circulating amimitochondrtaJ antibodies. The cells sunounding and infiltrating the sites ofbile duct damage are predominantly suppressor/cytotoxic (CDS•) T lymphocytes, suggesting that they mediate the destruction of the ductal epithellum. Macrophages and B lymphocytes (choice B) are associated with periductal inflammauon but do not mediate epithelial cytotoxicity. Eosinoph ils (choice A) have no role in primaty immune-related mechanisms. The other inflammatory cells (choices D and E) do not participate in the pathogenesis o[ PBC. ***Diagnosis: Primary biliary cirrhosis, chronic inflammation
45 A 25-year-old woman presents with a 2-week history of febri le illness and chest pain. She has an erythemarous, macular facial rash and tender joints, particularly in her left wrist and elbow A CBC shows mild anemia and thrombocytopenia. Conicosteroids are prescribed for the paliem. This medication induces the synthesis of an inhibitor of which of the following enzymes in inOammatory cells? ***(A) Upo>-'Ygenase ***(B) Myeloperoxidase ***(C) Phospholipase~ ***(D) Phospholipase C ***(E) Superoxide dismmase
45 The answer is C: Phospholipase A1. Corticosteroids are widely used to suppress the tissue destrunion associated with many chronic inOammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. Corticosteroids induce the synthesis of an inhibitor of phospholipase A2 and block Lhe release of arach1donk acid from the plasma membranes of inflammatory cells. Although corticosteroids are \~o,ridely used to suppress inflammatory responses, the prolonged administration of these compounds can have deleteriouseffens, including atrophy of the adrenal glands. Myeloperoxidase (choice B) catalyzes the con version or H20r in the presence of a halide {e.g., chloride ion) to form hypochlorous acid. This powerful oxidam is a major bactericidal agent produced by phagocytic ceUs. Superoxide dismUlase (choice E) reduces the superoxide radical to Hl02 . ***Diagnosis: Systemic lupus erythemawsus
46 The pad em described in Question 45 is noted to have increased serum levels of ceruloplasmin, fibrinogen, a.1-rnacroglobulin, serum amyloid A protein, and C-reactive protein. Together, these markers belong to which of the following families of proteins? ***(A) Acute phase proteins ***(B) Anaphylato>.ins ***(C) Inhibitors of platelet activation ***(D) Protease inhibito rs ***(E) Regulawrs of coagulation
46 The answer is A: Acute phase proteins. These proteins are synthesized primarily by the liver and are released imo the circuladon in response to an acme inflammawry challenge. Changes in the plasma levels of acute phase protelns are mediated p1imatily by cytokines (IL-l, ll-6 , and TNF-a). Increased plasma levels of some acute phase prmeins are reflected in an accelerated erythrocyte sedimentation rate , which is an index used clinically to moniwr the activity of many inflammatory diseases. None of the other choices describe the set of serum markers listed in tills question. ***Diagnosis: Systemic lupus erythematosus
1 A 74-year-old woman presents with acute chest pain and shortness of breath. Cardiac catheterization demonstrates occlusion of the left anterior descending coronary anery. Laboratory studies and ECG are consistent with acute myocardial infarCLion. Which of the following is the most likely pathologic finding in the affected heart muscle 4 weeks later7 ***(A) Capillary-rich granulation tissue ***(B) Collagen-rich scar tissue ***(C) Granulomawus inflammation ***(D) Neurrophils and necrotic debris ***(E) Vascular congestion and edema
1 The answer is B: Collagen-rich scar tissue. Pathologic findings in congestive hean failure include microscopic signs of coagulative necrosis approximately 24 hours after the on..set of vascular occlusion. Polymorphonuclear leukocytes and macrophages predominate during the next 2 w 5 days (choice D). Toward the end of the first week, the infarct is invaded by capillaryJicll granulation tissue (cl1oice A). Ultimately, the necrotic myocardium is replaced by collagen-rich scar tissue (weeks to months). Granulomatous inOammation (choice C) does not occur after an ischemic myocardial infarct. Vascular congestion and edema (choice E) are features of acme inflammation. ***Diagnosis: Myocardial infarction
2A 4-year-old boy falls on a rusty nail and punctures his skin. The wound is cleaned and covered with sterile gauze. Which of the following is the initial evenr in the healing process? ***(A) Accumulation of acute inflammatory cells ***(B) Deposition of proteoglycans and collagen ***(C) Differentiation and migration of myofibroblasts ***(D) Formation of a fibrin clot ***(E) Macrophage-mediated phagocytosis of cellular debris
2 The answer is D: Formation of a fibrin clot. The initial phase of the repair reaction , which typically begins wi th hemon-hage, involves the fomlati on 0 r a fibrin clot that fills the gap created by the wound. A thrombus (clot), referred to as a scab after dqing om, forms on the wounded skin as a barrier to invading microorganisms. lt also prevents the loss of plasma and tissue fluid . Formed p1imarily from plasma fibrin, the thrombus is rich in fibronectin. The thrombus also contains contracting platelets, whkh are an initial source of growth facwrs. Much later, the thrombus undergoes proteolysis, after which it is penetrated by regenerating epithelium. The scab then detaches. Accumulation of acute i11 ilammawry cells (ch oice A) might occur after fo rmation of the initial fibrin clot. Collagen fonnation (choice B) and macrophage activity (choice E) occur much later. Myofrbroblasrs (choice C) begin to accumulate in the wound around the 3rd day. ***Diagnosis: Wound healing
3 An 82-year-old man dies 4 years after developing congestive heart failure. He had a history of multiple myocardial infarcts over the past 10 years. A trichrome stain of heart muscle at autopsy is shown in the image. What is the predominant type of collagen found in this mature scar tissue? ***(A) l)rpe 1 ***(B) Type n ***(C) Type TV ***(D) Type V ***(E) Type Vl
3 The answer is A: Type I collagen. A mature scar is composed primarily of Lype 1 collagen. By comrast, the early matrix of granulation tissue contains prmeoglycans, glycoproteins, and type lll collagen. Eventually, the temporary matrix is removed by a combination o[ extracellular and intracellular digestion, and the definitive matrix is deposited. Extracellular crossJill king of the newly synthesized type 1 collagen progressively increases wound strength. Collagen type II (choice B) is found in cartilage. Collagen type IV (choice C) is found in basement membranes. Collagen types V and Vl (choices D and E) are found in various organs. ***Diagnosis: Myocardial infarction
4 A 25-year-old woman sustains a deep, open laceration over her right foreann in a motorcycle accident. The wound is cleaned and sutured . Which of the following cell types mediates contraction of the wound to facilitate heallng? ***(A) Endothelial cells ***(B) Fibroblasts ***(C) Macrophages ***(D) Myofibroblasts ***(E) Smooth muscle cells
4 The answer is D: Myofibroblasts. The myofibroblast is the cell responsible for wound contraction as well as the defomling pathologic process tenned wound contracture. These cells ex1)ress a.-smooth muscle actin, desmin, and vimentin, and they respond to pharmacologic agents thal cause smooth muscle to contract or relax. Myofibroblasts exert their contractile effects by forming syncytia, in whkh the myofibroblasts are bound together by tight junctions. By contrast, fibroblasts (choice B) tend to be solitary cells, surrounded by collagen fibers. Endothelial cells (choice A) respond to growth factors and form capillaries, which are necessary for the delivery of nutrienrs and infiammatOJy cells. Neither macmphages (choice C) nor smooth muscle cells (choice E) mediate wound contraction. ***Diagnosis: Wound contraction
5 Duling the next 3 months, the wound heats with fonnation ,___ of a linear scar. Which of the following nutritional factors is required for proper collagen assembly in the scar tissue of the patient described in Question 47 ***(A) Folic acid ***(B) Thiamine ***(C) Vitamin A ***(D) Vitamin C ***(E) Vitamin E
5 The answer is D: Vitamin C. Vitamin C (ascorbic acid) is a "-- powerful, biologic reducing agent that is necessary for the hydroxytaoon of protine residues in coUagen. Most of the clinical features associated with vitamin C deficiency (scurvy) are caused by the formal:ion of an abnormal collagen that lacks tensile strength Patients with vitamin C deficiency exhibit poor >vound healing. Dehiscence (bursl:ing open) of previously healed wounds may also occur. None of the other choices are required for collagen assembly. ***Diagnosis: Wound healing
6 A 70-year-old woman with diabetes develops an ulcer on her ,___ right leg (shown in the image). The ulcer bed is covered with granuLation tissue. Whkh of the fo11owing are 1:he p1inciple cellular compon ents found in the bed of this wound? ***(A) Fibroblasrs and endothelial cells ***(B) Myofibroblasts and eosinophils ***(C) NeU£rophils and lymphocytes ***(D) Plasma cells and macrophages ***(E) Smooth muscle cells and Merkel cells
6 The answer is A: Fibroblasts and endothelial (ells. Granulation tissue has two major components: cells and proliferating capillaries. The cells are mostly fibroblasts, myofibroblasts, and macrophages. fibroblasts and myofibroblasts derive from mesenchymal stem cells. Capillaries arise fmm adjacent blood vessels by division of endothelial cells ln a process termed angiogenesis. Macrophages are a principal source of growth factors and ~ue recognized for their phagocytic functions. Granulal:ion tissue is fluid laden, and its cellular consl:ituems supply antibacterial antibodies and gro>vth factors. Once repaiT has been achieved, most of the newly formed capillaries are obliterated and then reabsorbed, leaving a pale avascular scar. Although the other inOammatOJ)' cells listed may be found in this healing wound, they do not constitute the principal components of granulation tissue. ***Diagnosis: Diabetic ulcer, granulation tissue
7 Which of the fo llowing proteins helps stimulate healing and angiogenesis in the wound of the patiem described in Question 6? ***(A) o.1-Antitrypsin ***(B) Caspase-9 ***(C) Lysozyme ***(D) o.2-Macroglobulin ***(E) Metalloproteinase
7 The answer is E: Metalloproteinase. Matrix metaHoproteinases (M1v!Ps) are crucial components in wound heaJjng because they enable cells to migrate by degrading matrix proteins. Members of t.hts protein ramHy include collagenase, srromelysin, and gdatinase. 1n addition to enhancing ceU migration, MMPs can cUsn.tpt cell-cell adhesions and release bioactive molecules stored in the matrix. MMP activity can be minimized by binding LO specific proteinase inhibi tors such as a 1-antiuypsin (choice A) and a 1-macroglobulin (choice D). Lysozyme (choice C) is a secretmy product of neutrophils Lhat degrades bacte1ial cell walls. ***Diagnosis: Diabetes mellitus
a A 68-year-old man pTesents for repair of an abdominal aortic aneurysm. Severe complicated atherosclerosis is noted at surgery, prompting concern for embolism of atheromatous matelial to the kidneys and Dlher organs. lf the patie!1l were to develop a renal conical infarct as a result of surgery, which of the following would be the most likely outcome7 ***(A) Chronic in l1ammation ***(B) Granulomamus inflammation ***(C) Hemangioma fonnation ***(D) Repair and regeneration ***(E) Scar formation
8 The answer is E: Scar formation. A large infarCL of the k1dney will heal by fibrosis (scar fonnarion) In most renal diseases, there is destruction of the exnacellular matrix framework. Repair and regeneration (choice D) ts then incomplete, and scar formation is the expected outcome. The regenerative capacity o[ renal Lissue is m<udmal in cortical tubules, less in medullruy mbules, and none.x:tsLent in glomerulL Recent data suggest that renal mbule repair occurs due to the proliferation of endogenous renal progenitor (stem) cells. Chronic inflammation (choice A) precedes scar fonnation. Granulomawus inOammanon (choice B) is not a compUcation of renal cortical in farction. Hemangiomas (choice C) are common benign tumors of endotheUal cells that usually occur in the skin. ***Diagnosis: Infarction; embolism, atheroembolus
9 A 40-year-old woman presents with a painless lesion on her ligh t ear lobe (shown in the image)_ She reports that her ea rs were pierced 4 months ago. Which of the following best e.'<plains the pathogenesis of this lesion7 ***(A) Clonal expansion o[ smooth muscle cells ***(B) Exuberam fom1ation of granulation tissue ***(C) Increased growth of capillary endothelial cells ***(D) Increased turnover of extracellular matrix proteoglycans ***(E) Maturation arrest of coUagen assembly
._9_ The answer is E: Maturation arrest of collagen assembly. Keloid is an e>.'Uberam scar that tends w p rogress beyond the she of initial injury and recurs after excision. Dark-skinned persons are more fTequemly affected by keloi.ds than light~skinned people. Keloids are characterized by changes in the ratio of type Ill to type l collagen, suggesting a maturation arrest""" in the h ealing process. Funher support for maturation arrest as an explanation for keloids and hypertrophic scars is the overexpression of fibronectin in these lesions. Keloids are unsightly, and attempts at surgical repair are always problematic. The other choices do not address the pathogenesis of keloids. ***Diagnosis: Keloid
10 A 58-year-old woman undergoes lumpecwmy for breast cancer. One month following surgery, she notices a fi rm 0.3-cm nodule along one edge of the surgical incision. Biopsy of this nodule reveals chronk inflammatory cells, multinucleated giant cells, and extensive fibrosis. The multinucleated cells in this nodule most likely fmmed in response to which of the following pathogenic stimuli? ***(A) Bacterial infection ***(B) Foreign material ***(C) Lymphatic obstruction ***(D) Neoplastic cells ***(E) VLral infection
10 The answer is B: Foreign material. Granulomatous inOammation is a subtype of chronic inflammation, which develops when acute inflammatory cells are unable to digest the injutious a gem (e.g .• suture or talc). Fusion of macro phages within the lesion results in the formation of multinucleated giant cells. None of the other choices elicit this type of granulomatous reaction. ***Diagnosis: Granulomatous inflammation
11 A 57-year-old man with a history of alcoholism presents with yellow discoloraLion of his skin and sclerae. Laboratory studies show elevated serum levels of liver enzymes (AST and ALT) A Lrichrome stain of a liver biopsy is shown in the image. A similar pattern of regeneration and fibrosis would be expecLed in the liver of a patiem with which of the following conditions? ***(A) Actne toxic liver injury ***(B) Chronic viral h epatitis ***(C) Fulminant hepatic necrosis ***(D) Hepawcellular carcinoma ***(E) Th ron1bosis of the portal vein
11 The answer is B: Chronit: viral hepatitis. Chronic liver injuty (e.g., chronic viral hepatitis) is associated with the development ofbroad col1agenous scars within the hepatic parenchyma. This is termed cirrhosis. Hepatocytes fom1 regenerative nodules that lack central veins and expand to obsnuct blood vessels and bile flow Ponal hypenension and jaundice ensue, despite adequate numbers of regenerated but disconnected hepatocytes. Acme toxic liver injury (choice A) is genera11y reversible. Fulminant hepatic necrosis (choice C), if the patiem survives, usually regenerates. Hepatocellular carcinoma (choice D) may be associated with rumor fibrosis but nm with regeneration. Portal vein tlu·ombosis (choice E) does not cause hepatic fibrosis but may be a complication of embolism. ***Diagnosis: Alcoho1ic 1iver disease, cirrhosis
12 A 10-year-old boy trips at school and scrapes the palms of his hands. TI1e wounds are cleaned and coveTed with s terile gauze. \~ich of the following Lerms best characterizes the healing of these superficial abrasions? ***(A) Fibrosis ***(B) Grrumlation tissue ***(C) Primary intention ***(D) Regeneration ***(E) Secondary intention
12 The answer is D: Regeneration. Su perficial abrasions of the skin heal by a process of regeneration. It is mediated by stem cells or stabile cells that are able to progress through the cell cyde and fully restore normal tissue organization and function. Cellular migration is the predominant means by which the wound surface is reepithelialized. Fibrosis (choice A) refers to abenant healing with deposition of collagen-rich scar tissue. Granulation tissue (choice B) forms during the repair of deep wounds. Primary and secondmy intennons (choices C and E) arc fearures of healing in deeper wounds. ***Diagnosis: Superfi cial abrasion
13 'vVhich of the follmving cellular processes helps reswre nom1al epith elial structure and funccion in the patiem described in Qu estion 12? ***(A) Collagen and fibronectin-rich extracellular matrL-..: deposition ***(B) Comact inhibition of epithelial cell growth and motility ***(C) Myofibroblast differentiation and syncytia forma tion ***(D) Platelet activation and intravascular coagulation ***(E) Prolife ration of capillary endothelial cells (angiogenesis)
13 The an-swer is B: Contact inhibition of epithelial growth and motility. Mamration of the epidermis requires an intact layer of basal cells that are in diJ·ect contact with one anod1er. lf this contact is disrupted, basal epithelial cells at the wound margin become actiYated and evemua1ly reestablish contact with oilier basal cells through extensive cell migration and mitosis. \Vhen epithelial continuity is reestablished, migration and cell division cease, and the epidermis resumes its nom1al cycle of maturation and shedding. This process of epithelial grovvth regulation is referred to as "contact inhibition of growth and motility" The other choices describe responses to deep wound healing ***Diagnosis: Superficial abrasion, regeneralion
14 A 34-year-old woman has a benign nevus removed from her back under local anesthesia. \Vhich of the following families of cell adhesion molecules is the principal component of the provisional marrL-x that fonns dming early wound healing' ***(A) Cadherins ***(B) fibronectins ***(C) lntegrins ***(D) Lam1nins ***(E) SeleCLins
14 The answer is 8: Fibronedins. Fibronectins. are adhesive glycoprmeins that are widely distribmed in stromal connective tissue and deposited at the si te of tissue mjury During the initial phase of healing, fibronectin in the extravasated plasma is cross-linked to fibrin, collagen, and other extracellular matrix componems by the action of nansglmaminases. This cross-linking proVIdes a provisional stabilization of the wound during the first several hours. Fibronectin, cell debTis, and bacterial products are chemoam actams for a variety of cells that are recruited to the wound site over the next several days. Selectins (choice E) are sugar-binding glycoproteins that mediate the initial adhesion or leukocytes to endothelial cells at si tes of innammation. They are found at the cell surface and are not pan of the extracellular matrix. Cadherins (choice A) and integrins (choice C) are cell adhesion molecules. Like the selectin family of cell adhesion proteins, they are found at the cell surface and are not part of the extracellular matr Lx. ***Diagnosis: Wound heallng
15 Which of the following fammes of glycoproteins plays the most important role in regulating the migration and differentiation of leukocytes and connective tissue celts during wound healing in Lhe patient described in Question 14? ***(A) Cadherins ***(B) FibriUins ***(C) lmegrins ***(D) Laminins ***(E) Selectins
15 The answer is C: lntegrins . The locomotion of leukocytes i.s powered by membrane extensions called lamellipodia. Slower moving cells, such as fibroblasts, extend fingerlike membrane pronusions called filopodia. The leading edge of the cell membran e adheres lO the extracellular mauLx through tra115membrane adhesion receptors termed integJins. These cell surface glycoproteins transmit mechanical and chemical signals, thereby regulating cellular survival, proliferation, differemiadon, and migration. The motility or epithelial cells is also regtllated by imegrin receptors. Cadherins (choice A) are ceU-celJ adhesion molecules. Fibrillins (choice B) are smtcrural molecules that interact with elastic fib r ils. Lamil1ins (choice D) are basement membrane glycoproteins Selec tins (choice E) mecliate the recruitment of neutrophils in acme inflammation bm do not mediate directed cell migration at the site of tissue injury. ***Diagnosis: Wound healing
16 A 29-year-old cm·pemer receives a traumatic laceration w her ldt arm. vVhich of the following is the most important facror that determines whether this wound will heal by primary or secondary intention? ***(A) Apposition of edges ***(B) Depth of wound ***(C) Metabolic sLams ***(D) Skin site affected ***(E) Vascular supply
16 The answer is A: Apposition of edges. Healing by primary inten tion occurs in wounds wi th closely apposed edges and rn]nimal tissue loss. Such a wound requires only nunimal ceJJ proliferation and neovascularization to heal, and the result is a small scar. Healing by secondary intention occurs in a gouged wound, in which the edges are far apart and in which there is substantial tissue loss. This wound requires wound contraction, extensive cell proliferation, and neovascularization (granulation tissue) to heaL Granulation tissue is eventually resorbed and replaced by a large sear that is functionally and esthetically unsatisfactmy. The other choices are important detern1Jnants of the oULcome of wound healing, btu they do not provide a point of distinction between primary and secondary intentions healing. ***Diagnosis: Healing by primary intention
17 Activated fibroblasts, myofibroblasts, and capillary sprouts are most abundam in the wound of the patient desc1ibed in Question 16 at which of the fo llowing times after injury? ***(A) 3 to 6 hours ***(B) 12 to 2+ hours ***(C) 3 to 5 days ***(D) 8 to 10 days ***(E) 2 \<Veeks
17 The answer is C: 3 to 5 days. Activated fibroblasts, myofibroblasts, and capillary sprouts are abundant in healing wounds 3 to 5 days following injury Activated fibroblasts change shape from oval to bipolar as they begin to fonn collagen and synthesize a variery of extracellular matrix proteins. Neur.rophils accumulate In the wound 12 lO 24 hours after injury (choice B) . Mature scar tissue would be visible 2 weeks following injury (choice E). ***Diagnosis: Healing by primal) ' intention
18 A 9-year-old boy receives a deep laceration over his right eyebrow playing ice hockey. The wound is cleaned and sutured. Which of the following desctibes the principal function of macropha.ges that are present in the wound 24 to 48 hours after injury? ***(A) Antibody production ***(B) Deposition of collagen ***(C) Histamine release ***(D) Phagocytosis ***(E) ·wound contraction
18 The answer is D: Phagocytosis. Macrophages an ive at the site of injmy shorLly after neutrophils, bm they persist in the wound for days longer. Macrophages remove debris and orchestrate the fom1ation of granulation tissue by releasing cywkines and chemoattractants. None of the other choices are functions of tissue macrophages. For example, plasma celts produce antibodies (choice A), and myofibroblasts mediate wound contraction (choice E). ***Diagnosis: Laceration
19 Which of the followin g collagens is deposited fiTSl dming wound healing in the padem described in Question 18? ***(A) Type 1 ***(B) Type II ***(C) Type Ill ***(D) Type N ***(E) Type V
19 The answer is C: Type Ill. Concurrent with fibrinolysis , a temporary matrix composed of prOLeoglycans, glycoproteins, and type HI collagen is deposited. The secretion of type lll collagen is a forerunner to the fo rmation of t)rpe l collagen {choice A), which will impan greater tensUe strength to the wound. TGF-~ enhances the synthesis of collagen and 6bronectin and decreases metalloprOLeinase transcription and matrix degradation. Extracellular cross-linking of newly synthesized collagen further increases the mechankal s trength of the wound. Type 11 collagen (choice B) is found in canilage. Type lV collagen (choice D) is found in basement membranes. ***Diagnosis: Laceration
20 A 16-year-old boy suffers a concussion during an ice hockey game and is rushed to the emergency mom. A CT scan of the brain reveals a cerebral contusion of the left fromal lobe. The boy lies comatose for 3 days but eventually regains consciousness. Which of the following cells is the principal mediator of scar formation in the central nervous system of this patient? ***(A) Fibroblasts ***(B) Glial cells ***(C) Nemons ***(D) Oligodendrocytes ***(E) Schwann cells
20 The answer is B: Glial cells . Damage to the brain or spinal cord is followed by growth of capillaries and gliosis (i.e., the proliferation of asLrocytes and microglia). Gliosis in the cemral ne1vous system is the equivalem of scar formation elsewhere; once established, iL remams permanemly. In spinal cord injulies, a.'<onal regeneration can be seen up to 2 weeks after injury. After 2 weeks, gliosis has taken place and auempts at axonal regeneration end. ln the central nervous system, axonal regeneration occurs only in the hypOlhalamohypophysial region, where glial and capillary ban iers do not interfere with axonal regeneration. Axonal regeneration seems to require contact with exu·acellular fluid containing plasma proteins. The other cells listed do not prollferate significantly in response Lo brain or spinal cord injury. ***Diagnosis: Cerebral contusion, gliosis
21 A 30-year-old firefighter suffers e}..'tensive third-degree burns over his arms and hands. This patient is at high risk for developing which of the following complications of wound healing? ***(A) Contracture ***(B) Dehiscence ***(C) Incisional hernia ***(D) Keloid ***(E) Traumatic neuroma
21 The answer is A: Contracture. A mechanical reduction in the size of a wound depends on the presence of myofibroblasts and sustained cell contraction. An exaggeration of these processes is te rmed contracture and results in severe defonnity of the wound and surrounding tissues. Comracrures are particularly conspicuous in the healing of se1ious burns and can be severe enough to compromise the movement of joints. ***Diagnosis: Comracmre
22 A 23-year-old man suffers a cmsh injury of his foot, which becomes secondarily infected. He undergoes a below-the-knee amputation. Six momhs later, the patient complains of chronic pain at the site of amputation. A firm nodule is identified at the scar site. A biopsy of the nodule demonstrates haphazard growth of nerves (shown in the image). Which of the following is the most likely diagnosis? ***(A) Ganglloma ***(B) Ga nglioneu rom a ***(C) Hamanoma ***(D) Neural nevus ***(E) Neuroma
22 The answer is E: Neuroma. Neurons in the peripheral nervous system can regenerate their a;'{ons, and under ideal circumstances, interruption in the continuity of a peripheral ne1ve results in complete functional recovery However, if the cut ends are not in perfect alignment or are prevented from establishing continuity by inflammation, a rraumatic neuTOma results. This bulbous lesion consists of disorganized axons and proliferating Schwann cells and fibroblasts. In this patients biopsy, the original nerve (lower left) enters the neuroma. The nerve is surrounded by dense collagenous tissue , which appears dark blue in this trichrome stain. Ganglioma (choice A), ganglioneuroma (choice B), and hamartoma (choice C) are benign neoplasms. ***Diagnosis: Tmuma£ic neuroma
23 A 34-year-old man presems with a 5-day history of a painful sore on his hand. Physical examination reveals a 0.5-cm abscess on the extensor surface of the left hand that drains a thick, purulem material. Diapedesis of leukocytes into and around this patients infected wound occurs primarily at which of the following anatomic locations? ***(A) Lymphatic capillaries ***(B) Postcapillary venules ***(C) Precapillary anerioles ***(D) SmaU dermal arteries ***(E) Small dennal veins
23 The answer is B: Postcapillary venules . One of the earliest responses following tissue injury occurs within the microvasculature at the level of the capillary and postcaplllary venule. 'vVithin this vascular network are the major componen ts of the inOammatory response, including plasma, platelets, erythrocytes, and circulating l eukocytes. Following injury, changes in the structme o[ the. vascular wall lead tO activation of endothelial ce.U.s, loss of vascular integtity, leakage of fluid and plasma components from the intravascular compartment, and emigration of erythrocytes and leukocytes from the vascular space into the extravascular tissue. (diapedesis). Leukocyte recmitment in the postcapillary venule is initiated by i.meraction of leukocytes with endothelial cell su rface selectin molecules. Leuko<::ytes do not typically undergo diapedesis at the other anawmic locations listed. ***Diagnosis: Carbuncle, margination
24 A 35-year-old pregnam woman with a history of chronic gasn·itis presents to the emergency room complaining of acute abdominal pain. Physical examjnation reveals hepatomegaly, ascites, and mild jaundice. The patient subsequently develops acute hepatic failure and expires. Autopsy reveals thrombosis of the hepatic veins (Budd-Ch1ari syndrome). During t]le autopsy, a lesion is identified in the distal stomach and examined by light microscopy (shov.rn in tl1e image). Which of the following best describes this incidental finding at autopsy? ***(A) Carcinoma ***(B) Contracture ***(C) Diverticulum ***(D) Granuloma ***(E) Ulcer
24 The answer is E: Ulcer. lncidemal findi ngs are frequently encountered at autopsy. In this case, a pep tic ulcer is identified in the distal stomach. Histologic examination shows focal destrunion of the mucosa and full- thickness replacement of the muscularis with collagen-rich connective tissue (see photomicrograph) Gasrric ulcers are usually single and less than 2 em in diameter. Ulcers on the lesser curvature are commonly associated whh chronic gasuilis (this patient), whereas those on the greater curvature are often related to NSAIDs. Grossly, chronic peptic ulcers may closely resemble gastric carcinoma (choice A). Thus, the endoscopist must take multiple biopsies from the edges and bed of any gasnic ulcer. Although contraccion and scan ing of gastric u1cers (choice B) may occur and may cause pyloric stenosis, the hiswpathologic findings do not suggest this complication. Divenicula of the stomach (choice C) are rare and, if present, are usually Uned by a normal gasuic mucosa. Granuloma (choice D) features inflammawry cells tha t are not observed. ***Diagnosis: Gastric ulcer, peptic ulcer disease
1 A 35-year-old man a5ks for advice regarding seasonal eye itching and runny nose. Recurrent conjunctivitis in thJs patient is most likely caused by which of the following mechanisms of disease? ***(A) Auroinununity ***(B) Bacterial infection ***(C) Chemical toxicity ***(D) Hypersensitivity ***(E) Viral infection
1 The answer is D: Hypersensitivity. Although rile incorrect choices may cause eye irritation, seasonal conjunctivitis is typically caused by allergies to pollens that are released during a particular Lime of the year. Allergic rhinitis (hay fever) is the most common type I bypersensitivily disease in adulLS. It may be caused by pollen, house dust, animal dandmff, and many other al lergens. Antigens inhaled react with lhe lgE atlached to basophils in the nasal mucosa, thereby uiggerlng the release of vasoactive substances sLOred in cytoplasmic granules. Histam. ine , the main mediawr released fmm mast cells, increases the permeabil.ity of mucosal vessels, causing edema and sneezing. ***Diagnosis: Conjunctivitis, hypersensltivity reaction
2An 8-year-old boy presen£S with periorbitaJ edema and throbbing headaches. His parents repon that the boy had a "sn·ep throatM 2 weeks ago. Urinalysis shows 3+ hemarmia. A renal biopsy shows hypercellular glomeruli, and electron microscopic examination of glomemli discloses subepithelial humps. ""Which o[the following best explains the pathogenesis" of glomemlonephtitis in this patiem? ***(A) Amineutrophil cytoplasmic amoamibodies ***(B) Deposition of circulating immune complexes ***(C) Directly cytotoxic IgG and lgM antibodies ***(D) lgE-mediated mast cell degranulation ***(E) T cell-mediated delayed hypersensidvity reaction
2 The answer is 8: Deposition of circulating immune c>Omplexes. Type lll hypersensitivity reactions are characterized by immune complex deposition, complemem fi"lffition, and localized inO.ammation. Antibody d.ire~cred against either a circulating amigen or an antigen that is deposaed in a tissue can give rise to a type m response. Diseases that seem w be most clearly anribmable to the deposition of immune complexes are systemic lupus erythematosus, rheumawid arthritis, and varieties of glomemlonephritis. Strepwccocal infection in this case led to the deposition of amigens and amibod.ies in glomerular basemem membranes, resulting in clinical features of nephritic syndrome (e.g., hematuria, oliguria, and hypenension). Poststreptococcal illnesses do not include any of the other choices. ***Diagnosis: Postinfectious glomerulonephritis
3 A 21-year-old woman p resents with a J -mon th history of malaise, joint pain, weight loss, and sporadic fever. The patient appears agitated. Her temperature is 38°C (101 °F). Other physical findings include malar rash , erythematouspink plaques with telangiectatic vessels, oral ulcers, and nonhlanching purpunc papules on her legs. Laboratory studies show elevated levels of blood urea nitrogen and creatinine. Antibodies directed to which of the following ami.gens would be expected in the semm of this padem7 ***(A) C-ANCA (ami-protelnase-3) ***(B) Double-stranded DNA ***(C) P-ANCA (an ti-myeloperoxidase) ***(D) Rheumatoid factor ***(E) Scl-70 (anti-topoisomerase I)
3 The answer is 8: Double-stranded DNA. Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease that may involve almost any organ but characteiistically affects the kidneys, joints, serous membranes, and skin. Autoantibodies are formed against a variery of self-antigens. The most important diagnostic autoantibodies are those against nuclear amigens-in panicular, antibody to double-stranded DNA and to a soluble nuclear antigen complex that is pan of the spliceosome and is tenned Sm (Smith) antigen. High titers of these nvo autoantibodies (tenned antinuclear antibodies) are nearly pathognomonic for SLE. Antibodies to rheumatoid factor (choice D) are seen in patients wilh rhemnawid arthritis. Antineutrophil cytoplasmic antibodies (choices A and C) are seen in patients wiLh small vessel vasculitis (e.g., \Vegener granulomalosis). ***Diagnosis: Systemic lupus erythematosus
4 Serum levels of complement proteins may be reduced dming the active phase of disease Ln the patient desc1ibed in Quesrion 3 due to which of rhe foUo\ving mechanisms of disease? - ***(A) Binding of complement LO immune complexes ***(B) Decreased complement protein biosynthesis ***(C) Defective activation of the complement cascade ***(D) Increased minary excretion of immunoglobulins ***(E) Stimulation of t11e acme phase response
4 The answer is A: Binding of complement to immune complexes. Acquired deficiencies of early complement components occur in patients with autoimmune diseases, especially those associated with circuJating immune complexes kg., systemic lupus erythemawsus [$LEI). Antigen-antibody complexes fom1ed in the circulation during the active stage or these diseases lead to a marked reduction in circulating levels of complemem proteins (hypocomplementemia). None of the other choices mediates hypocomplementemia in patients with SLE. ***Diagnosis: Systemic lupus erythematosus
5 A 45-year-old woman complains of severe headaches and difficulty swallowing. Over the past 6 months, she has noticed small, red lesions around her moULh as well as thickening of her skin. The pat.lem has "stone facies.. on physical examination. Which of the following antigens is the most common and most specific target of autoantibody in patie:ms with this disease? ***(A) C-ANCA (anti-proteinase-3) ***(B) Double-stranded DNA ***(C) P-ANCA (ami-myeloperoxidase) ***(D) Scl-70 (anti-ropoisomerase I) ***(E) 5$-NSS-B
5 The answer is D: Scl-70 {anti-topoisom~rase I). Sclerodenna is an amoimmune disease of connective tissue. Circulating male fetal cells have been demonstrated in blood and blood vessel walls of many women with scleroderma \Vho bore male children many years before the disease began Accordingly, it has been suggested that sclerodem1a in these patients is stmtlar to graft-versus-host disease. Antinuclear antibodies are common but are usually present in a lower tiler than in patients with SLE. Antibodies virtually specific for sclerodenna include (l} nucleolar autoantibodies (primarily against RNA polymerase); (2) amibodies to Scl-70, a nonhistone nuclear protein topoisomerase; and (3) amicemromere antibodies, which are associated with the "CREST" variant of the disease. The Scl-70 autoantibody is most common and specific for the diffuse form of scleroderma and is seen in rO% of patients. Autoantibodies to double-stranded DNA (choice B) are seen in patients with SLE. Autoantibodies to SS-NSS-B (choice E) are seen in patients wiLh SjOgren syndrome. ***Diagnosis: Scleroderma
6 A skin biopsy in the patiem described in Question 5 would most likely show a pe rivascular accumulation of which of the following extracellular mallix proteins? ***(A) Collagen ***(B) Elastin ***(C) Entactin ***(D) Fibronectin ***(E) laminin
6 The answer is A: Collagen . Scleroderma is characterized by vasculopathy and excessive collagen deposition in the skin and internal organs, such as the lung, gastrointestinal tract, healt, and kidney. The disease occurs four times as often in women as in men and mostly in persons aged 25 to 50 years. Progressive systemic sclerosis i.s characterized by widespread excessive collagen deposition. There is emerging evidence for the e>..'J)ansion of fibrogenic clones of fibroblasts. These clones display augmented procollagen synthesis, including increased circulating levels of Lype lU collagen aminopropeptide. Ti.ssue levels of the other proteins are not significantly altered in patients with scleroderma. ***Diagnosis: Scleroderma
7 Dming the physical examination of a 22.-year-old man, a purified protein derivative isolated from Mycobaaeritm1 wberculosL~ is injected imo Lhe skin. Three days later, the injection site appears raised and indurated. Which of the following glycoproteiJ1s was directly involved in antigen presentation during the init]ation phase of delayed hypersensitivity in this patient? ***(A) CD4 ***(B) CD8 ***(C) Class [ HLA molecules ***(D) Class II HLA molecules ***(E) GlyCAM-l
7 The answer is D: Class II HLA molecules. Delayed-type hypersensitivicy is de fined as a tissue reaction involving lymphocytes and mononuclear phagocytes, which occurs in response to a soluble protein antigen and reaches greatest intensity 24 to 48 hours after initiation. ln the initial phase, foreign protein antigens or chemical ligands interact with accessory cells beating class li HI..A molecules. Protein amigens are actively p rocessed into shon peptides within phagotysosomes and are presented on the cell surface in conjunction with the class 11 HLA molecules. The latter are recognized by CD4. T cells (choice A), which become activated to synthesize an array of cytokines. The cytokines recruit and activate lymphocytes, monocytes, fibroblasts, and other iJ1flammaLOry cells. Suppressor T celts are CD8+ (choice B). Class I HI..A molecules {choice C) provide targets for cell-mediated cytotoll."icity. GlyCAM-1 (choice E) is a cell adhesion molecule involved in lymphocyte trafficking. ***Diagnosis: Delayed-type hypersensitivity
8 A 54-year-old woman is involved in an automobile accident and requires a blood transfusion. Five hours later, she becomes febrile and has severe back pain. Laboratory sllldies show evidence of imravascular hemolysis. h is discovered that type A Rh+ blood was given by mistake w this type B Rh+ patient. Which of rhe follo•ving best e-xplains the development of intravascular hemolysis in this patient? ***(A) Antibody-dependent cellular cytotoxicity ***(B) Antibody-mediated complement fi:xadon ***(C) Delayed-type hypersensitivity ***(D) Immune complex disease ***(E) Immediate hypersensitivity
8 The answer is B: Antibody-mediated complement fixation. Type 11 hypersensitivity reactions are mediated by antibodies directed against fixed an tigens. ln this case, prefonned antibodies in the patients blood auached to foreign antigens (oligosacchalides) on the membranes of the transfused erythrocytes. At sufficiem densit)~ bound immunoglobulms fix complemem. Once aCLivated, the complement cascade leads to the desrruction of the target cell through [ormation of a membrane ;;mack complex. This type of complemem-medimed cell lysis occurs in autoimmune hemolytic anemia. Antibody-dependent cellmediated cytotoxicity (ADCC, choice A) involves cytolytic leukocytes that attack antibody-coated target cells. ADCC may be involved in the pathogenesis of some autoimmune diseases (e.g., autoimmune thyroiditis). Delayed-Lype hypersensitivity (choice C) occurs over a period of days and does not involve preformed antibodies. ***Diagnosis: Hemolytic anemia, jaundice
9 A 40-year~old man complains of having yellow skin and sclerae , abdominal tenderness, and dark urine. Physical examination reveals jaundice and mild hepatomegaly. Laboratory stu dies demonstrate elevated serum bilintbin (3.1 mgfdl), decreased serum albumin (2.5 gfdL), and prolonged prothrombin Lime (17 seconds). Serologic tests reveal amibodies to hepatitis B core antigen (IgG anti-HBc.Ag). The senun is also posiuve for HBsAg and HBeAg Which of the fo llo'Ning glycoprO[eins serves as the principal cell surface receptor for viral antigens on B lymphocytes in this patient' ***(A) CD4 ***(B) CDS ***(C) HLA class 1 molecules ***(D) HLA class 1I molecules ***(E) Membrane immunoglobulm
9 The answer is E: Membrane immunoglobulin {mig) . The clinicopathologic findings presemed here indicate that rhis patient is a chrome HBV carrier with active hepatitis. Humoral immune responses to specific viral antigens tn this patient involve the activation and differen tiation of B lymphocytes into antibody-secreting plasma cells. Analogous to T cells, B cells express an antigen-binding receptor, namely mtg. This immunoglobulin bears the same antigen specificity as the soluble immunoglobulin that is ultimately secreted. Class I Hl.A molecules (choice C) provide targets for CD8• T cells in cell-meruated cytotoxiclty. Class ll HLA molecules (choice D) are recognized by CD4'" T cells, which become activated to synthesize an array of cytoklnes. ***Diagnosis: Humoral immunity, chronic hepatitis
10 What glycoprotein on virally infected hepatocytes provides a target for cell-mediated cytotoxicity in the patient described in Question 9? ***(A) CD4 ***(B) CD8 (C} Class l HLA molecules ***(D) Class II HLA molecules ***(E) GlyCAM-1
10 The answer is C: Class I HLA molecules. Class I molecules of the major histocompatibility complex present foreign peptides and are recognized by cytotoxic T lymphocytes dming graft reiection or d uring cell-mediated killing of virus-infected cells. All tissues e.,xpre.ss class [ molecules, whereas class Il molecules (choice D) are displayed ptimati ly on macrophages and B lymphocytes. CD4 and CDS (choices A and B) are cell surface markers of helper and killer T lymphocytes, respectively. GlyCA.M-1 (choice E) facilitates lymphocyte recirculation by provtding a recepmr for leukocyte attachment to high endothelial venules. ***Diagnosis: Chronic hepatitis B
11 A 45-year-old woman presents with a 1-year history of dry mouth and eyes_ A biopsy of a minor salivary gland reveals infiltrates of lymphocytes forming focal genninal centers. 'vVhich of the following cellular organelles is a target for autoantibodies in this patient? ***(A) Centromere ***(B) Lysosome ***(C) Nucleus ***(D) Peroxisome ***(E) Plasma membrane
11 The answer is C: Nucleus. Sjogren syndrome (SS) is an autoimmune disorder characterized by keratoconjun ctivitis sicca and xerostomia in the absence of other connective tissue disease. The production of autoantibodies, particularly aminuclear antibodies directed against DNA or nonhistone proteins, typically occurs in patients with SS. Autoantibodies to soluble nuclear nonhistone proteins, especially tl1e antigens SS-A and SS-B, are found in half of patients with primary $Sand are associated with more severe glandular and extraglandular manifestations. Autoantibodies to DNA or hjstones are rare. Organ -specific autoantibodies, such as those directed against salivary gland antigens, are distinctly uncommon. Autoantibodies Lo centromere proteins (choice A) are seen in the CREST variant of progressive systemic sclerosis. ***Diagnosis: Sjogren syndrome
12 An 8-month-old boy with a history of recurrent pneumonia is found to have almost no circulating lgG. Cellular immunity is normal. His brother had this same disease and died of echovims encephalitis. His parents and sisters have normal serum levels of lgG. What is the appropriate diagnosis? ***(A) DiGeorge syndrome ***(B) Isolated lgA deficiency ***(C) Severe combined immunodeficiency ***(D) WiskoLt-Aldrich syndrome ***(E) X-lin ked agammaglobulinemia of Bruton
12 The answer is E: X-linked agammaglobulinemia of Bruton. The congenital disorder Bruton X-linked agammaglobulinemia appears in male infams at 5 to 8 momhs of age, the period during which maternal antibody levels begin to decline. The infant suffers from recunem pyogenic infections and severe hypogammaglobulinemia. There is an absence of both mature B cells in peripheraJ blood and plasma cells in lymphoid tissues. The genetic defect, located on the long arm of the X cl1rornosome, is an inactivating mutarion of the gene for B-cell ryrosine ldnase, an enzyme critical to B-lymphocyte maturation. Vviskott-Aldrich syndrome (choice D) is also an X-lin ked genetic disease but is characterized by defects in both B-cell and T-cell functions (i .e. , humeral and cellular immunity). DiGeorge syndrome (choice A) is a developmental disorder characte1ized by thymic and parathyroid aplasia. ***Diagnosis: X-linked agammaglobulinemia of Bmwn
13 A 52-year-old woman with a history of systemic hypenension and chronic renal failure undergoes kidney transplantation, but the graft fails to produce urine. A renal biopsy is diagnosed as "hyperacute transplant rejection." Graft rejection in this padem is caused primarily by which of the following mediators of immunity and inflammation? ***(A) Cywroxic T lymphocytes ***(B) Helper T lymphocytes ***(C) Mononuclear phagocytes ***(D) Natural killer cells ***(E) Prefo rmed antibodies
13 The answer is E: Preformed antibodies. Hyperacute rejection occurs within minutes to hours after transplantation. It is manifested clinically as a sudden cessation of u rine output, along with fever and pain in the area of Lhe graft site. This immediate rejection is mediated by preformed antibodies and complement activation products. Lymphocytes and macrophages (choices A, B, and C) are associated with acute and chronic graft rejection. ***Diagnosis: Hyperacme grafr rejection
14 A 30-year-old woman complalll5 of impaired speech and frequent aspiration of food. Physical examinadon reveals diplopia and drooping eyelids. A mediastinal mass is removed and diagnosed as thymoma. The symptoms of muscle weakness in Lhis padem are caused by antibodies directed against which of the following cellular componems? ***(A) Acetylcholine receptor ***(B) Calcium channel ***(C) Desmogkin-3 ***(D) Rheumatoid factor ***(E) Thyroid-stimulating honnone (ISH) receptor
14 The answer is A: Acetylcholine receptor. Myasthenia gravis is a type li hypersens1tivity disorder caused by antibodies thar bind to the acerylcholine recepwr. These antibodies interfere with the transmission of neural impulses at the neuromuscular junction, causing muscle weakness and easy fatigabilh:y External ocular and eyelid muscles are most often affected, but the disease is often progressive and may cause death by respiratory muscle paralysis. Autoantibodies to desmoglein-3 (choice C) are found ln patients w'ilh pemphigus vulgaris, an autoimmune bl istering skin disorder. Antibodies to the TSH receptor (choice E) are seen in patients with Graves hyperthyroidism. Antibodies to calcium channels (choice B) are found in patients with Eaton-Lambert syndrome. This paraneoplastic syndrome also manifests as muscle weakness but is usually associated with smaU cell carcinoma of the lung. Rheumatoid factor (choice D) represents multiple antibodies directed against the Fe ponion of IgG and is seen in pariems \Vith rheumatoid arthritis and many other collagen vascular diseases. ***Diagnosis: Myasthen ia gravis, thymoma
15 A 31-year-old man wlth AIDS complains of difficulty swallowing. Examination of his oral cavity demonsu-ates whitish membranes covering much of his tongue and palate. Endoscopy also reveals several whitish, ulcerated lesions in the esophagus. These pathologic find ings are fundamentally caused by loss of which of the following immune cell"> in this patient? ***(A) B lymphocytes ***(B) Helper T lymphocytes ***(C) Killer T lymphocytes ***(D) Monocytes/macrophages ***(E) Natural killer (NK) cells
15 The answer is B: Helper T lymphocytes. The relentless progression of HlV infection is now recognized as a continuum that extends from an initial asymptomatic state to the immune depletion that characterizes patients with oven AID$. The fundamental lesion is infection of CD4+ (helper) T lymphocytes, which leads to the depletion of this cell population and impaired immune function. As a result, patients with AID$ usually die of opportunistic infections. HN does infect the monoc)'le/macrophage Uneage (choice D), but infected cells exhibit little if any cytotoxicity. NK cell activity (choice E) is also decreased in AIDS. This defect may contribute to the appearance of malignant mmors and the viral infections that plague these padems. The suppression of NK cell activity has been related to a decrease in the number of NK cells and to a reduction in lL-2 levels due to the loss of Co 4· cells. ***Diagnosis: AIDS
16 Which of the following en zymes converts the HIV genome imo double-stranded DNA in h ost cells in the patient described in Question 15? ***(A) DNA polymerase (Pol- l ) ***(B) DNA polymerase (Pol-2) ***(C) lmegrase ***(D) Reverse transcriptase ***(E) Topoisomerase
16 The answer is D: Reverse transcriptase. The primary etiologic agent of AIDS is HIV- 1, an enveloped RNA retrovirus that contains a reverse mmscrtptase (RNA-dependent DNA polymerase). After it enters into the cytoplasm of a T lymphocyt e, the virus is uncoated, and its RNA is copied into double-stranded DNA by retroyjral reverse trat15Cliptase. The DNA derived from the virus is imegrated imo the host genome by the vinl imegrase protein (choice C), thereby producing the latent proviral fom1 of HIV-1. Viral genes are replicated along with host chromosomes and, therefore, persist for the life of the cell. ***Diagnosis: ArDS
17 A 20-year-old woman with a history of asthma and aller· gies undergoes skin testing to identify potential allergens in her environmem. A positive skin reaction to ragweed in this patient would be mecUated by which of the following classes of immunoglobulin? ***(A) lgA ***(B) IgD ***(C) IgE ***(D) IgG ***(E) IgM
t7 The answer is C: lgE. Immediate-type hypersensitivity is manifested by a localized or generalized reaction that occurs within minutes after exposure to an antigen or "allergen" to which th e person has previously been sensitized In its generalized and most severe Form, immediate hypersensitivit}' reactions are associated \vi th bronchoconstriction, airway obstruction, and circulatory collapse, as seen in anaphylactic shock. Type I hypersensitivity reactions feature the formation oflgE antibodies that bind avidly to Fc-epsilon (Fe-E) receptors on mast cells and basophils The high-avidity bLnding of tgE accounts for the term cytophilic antibody. Once exposed to a specific allergen that has resulted in the formation of IgE, a person is sensitized. Subsequent responses to the allergen induce an immediate release of a cascade o[ proinilammatmy mediators. These meciJators are responsible for smooth muscle contraction, edema formation, and the recruitment of eosinophils. None of the other immunoglobulin classes mediates immediate hypersensitivity. ***Diagnosis: Asthma
18 A 53-year-old woman complains of progressive weight loss, nervousness, and sweating (patiem shown in me image). Physical examinmion reveals tachycardia and exophthalmos. Her thyroid is diffusely enlarged and warm on palpadon. Se rum levels of Lhymid-stimulaling hormone (TSH) are low, and levels of thyroid hom1ones (T3 and T} are markedly elevaled. Which of me following mechanisms of disease best e}qJlains the pathogenesis of this patiems thyroid candid on? ***(A) Antibody-dependent ceUular cytotoxicity ***(B) Cytopathic autoantibodies ***(C) Delayed-type hypersensitivity ***(D) Immedtate hypersensitivity ***(E) Immune complex disease
18 The answer is B: Cytopathic autoantibodies. Graves disease is a rype 11 hypersensitivity disorder caused by antibodies to the T$H receptor on follicular cells of the thyroid. Antibody binding to the T$H receptorstimulates a release of teu·aiodothyronine (T) and triiodothyronine (T) from the thyroid imo t:he circulation. Circulating T~ and T 3 suppress TSH production in the pi tuitary Sweating, weight loss, and tachycardia are evidence of the hypem1etabolism typical of hypenhyroidism. Graves disease also causes exophthalmos. Delayed-type hypersensitivity (choice C) is seen in patients with poison ivy and graft rejection. Immune complex disease {choice E) is caused by deposition of immune complexes and complement activation. ***Diagnosis: Graves disease
19 A 12-month-old infant with a history of recurrent infections, eczema, generalized edema, and easy bruising is diagnosed with an X-hnked, recessive , congenital immunodeficiency. The CBC shows thrombocytopenia. What is the most likely diagnosis? ***(A) DiGeorge syndrome ***(B) Isolated lgA deficiency ***(C) Severe combined immunodeficiency ***(D) Wiskott-Aldrich syndrome ( E) X-linked agammaglobulinemia of Bruton
19 The answer is D: Wiskott-Aidrich syndrome. This rare syndrome is characterized by (1) recurrent infections, (2) hemorrhages secondary to thrombocytopenia , and (3) eczema. It typically manifests in boys within the first Cewmomhs of life as petechiae and recurrent infections (e.g., dianhea). It is caused by numerous distinct mmarions in a gene on the X chromosome that encodes a protein called WASP (WiskottAldlich syndrome protein), which is ex1Jressed at high levels in lymphocytes and megakaryocyres. WASP binds members of the Rho family of GTPases. WASP itself comrols the assembly of actin filaments that are required to form microvesicles. X-linked agammaglobulinemia of Bruton (choice E) is not associated with thrombocytopenia and eczema. Choices A, B, and Care not X-linked genetic diseases. ***Diagnosis: Wiskon-Aldrich syndrome
20 A 24-year-old woman with leukemia receives an allogeneic bone marrow transplant. Three weeks later, she develops a skin rash and diarrhea. Liver function tests show elevated serum levels of AST and ALT. A skin biopsy discloses a sparse lymphocytic infiluate in the dermis and epidermis, as well as apoptotlc cells in the epidermal basal cell layer. Skin rash and dianhea in this patient are caused ptimalily by which of the follm"~.•ing cells? ***(A) Donor lymphocytes ***(B) Donor plasma cells ***(C) Fixed tissue macrophages ***(D) Recipient lymphocytes ***(E) Recipient plasma cells
20 The answer is A: Donor lymphocytes. The advem of transplantation of bone man-ow into patients whose immune system has been ablated or into otherwise immunodeficient patients has resulted in the complication of graft-versus-host disease (GVHD). GVHD occurs when lymphocytes in the grafted tissue recognize and react to the recipient. GVHD can also occur when an ilmmmodefiCiem patient is u·ansfused with blood comailung HlA-incomparible lymphocytes. The major organs affected in GVHD include the skin, gastroimesrinaltTact, and liver. Cli11icall>; GVHD manifesl5 as rash, dianhea, abdominal cramps, anemia, and liver dysfunction. None of the other cells mediates GVHD. ***Diagnosis: Graft-versus-host disease
21 A 20-year-old gardener presents to his family physician for treatment of what he describes as "poison ivy.·· The patients hands and anns appear red and are covered with oozing blisters and crusts. Which of the following best describes the pathogenesis of these skin lesions? ***(A) Cytotm.:ic antibody production ***(B) Delayed-type hypersensitivity ***(C) Deposition of amiglmen antibodies ***(D) Deposition of circulating immune complexes ***(E) IgE-mediated mast cell degranulation
21 The answer is B: Delayed-type hypersensitivity. "Poison ivy" is a type IV hypersensitivity reaction to plants of the RJut~ genus. This I -lymphocyte-mediated allergic contact dc1matitls presents as urticaria and bullous eruption. Blisters rupture and heal with CJusts, usually without scarring. Deposition of antigluten antibodies (choice C) occurs in patients with dennatitis herpettform.is. IgE-mediated mast cell degranulation (choice E) is pan of the response to poison ivy (hypersensitivity reactions overlap), but tllis immediate respon.r;e does not explain the pathogenesis of delayed hypersensitivity in this patient. ***Diagnosis: AJlergic contact dennatitis
22 A 9-month-old girl ·with a histmy of recurrem pulmona1y infections is found to have a congenital deficiency of adenosine deaminase, which is associated with a vinual absence of lymphocytes in her peripheral lymphoid organs. What is the appropriate diagnosis? ***(A) Bruton X-linked agammaglobulinemia ***(B) DiGeorge syndrome ***(C) Isolated lgA deficiency ***(D) Severe combined immunodeficiency ***(E) Wiskott-Aldrich syndrome
22 The answer is D: Severe combined immunodeficiency (SCID ). SOD is a group of disorders of I and B lymphocytes that are characterized by recunent viral, bacterial, fungal, and protozoal infecLions. Many infants with SCID have severely reduced volumes oflymphoid Lissue and an immature thymus that lacks lymphocytes. In some patienlS, lymphocytes fail to deve lop beyond p re-B cells and pre-T cells. About one half of these severely immunodeficient children lack adenosine deaminase (ADA) ADA deficiency causes the accumulation of intermediate products that a re toxic to lymphocytes. These children cannot survive beyond early infancy unless they are raised in a sterile environmem ("'bubble children"). None of the other chmces a re associated with ADA deficiency ***Diagnosis: Severe combined immunodeficiency
23 A 50-year-old man complains of fever, weight loss, abdominal pain, and bloody mine. Physical examination reveals red-purple discoloration or Lhe skin. Serologic findings are inconclusive, but a positive P-ANCA test suggests an aULoimmune disease. Biopsy oflesional skin discloses fibrinoid necrosis of a small muscular arrery (shown in the image). Which of Lhe following immune responses best explains the pathogenesis of inflammation and necrotizing vasculitis in this patiem? ***(A) Antibody-dependem cellular cywtm.:icity ***(B) Cytopathic autoantibodies ***(C) Delayed-type hypersensitivity ***(D) Immediate hypersensitivity ***(E) Immune complex disease
23 The answer is E: Immune complex disease. Immune comple..x (type Ill) hypersensitivity reactions cause vasculitis. Antigenantibody complexes are eith er formed in the circulation and deposited in tJ1e tissues or formed in situ. lmmune complexes induce a localized inflammatory response by fixing complement, which leads to Lhe recmitment of n eutrophils and monocytes_ The vasculitis in patients •Nith polyarteritis nodosa involves small 1.0 medium-sized muscular arteries. The diagnosis is usually made by b iopsy of the skin, muscle, pe1iphe ral nerves, or the most affected imemal organ (the kidney tn this case). The most prominent morphologic feamre of the affected anery is an a rea of fibrinoid necrosis (see photomicrograph). Oilier examples of type Ill hypersensitivity reactions include Henoch-Schonlein purpura (vascular lgA deposiLS) and vasculitis associated wiLh hepatitis C infection_ The otJ1er choices are uncommon mediarors of vasculitis in patients with polyaneriLis nodosa. ***Diagnosis: Polyaneritis nodosa
Z4 A neonate develops spastic contractions on the second postpartum day Laboratory studies show hypocalcemia MRI studies demonstrate aplasia of the thymus and parathyroid glands. 'vVhat is the appropriate diagnosis? ***(A) Adenosine deaminase deficiency ***(B) Common variable immunodeficiency ***(C) DiGeorge syndrome ***(D) Transient hypogammaglobulinemia of infancy ***(E) Wiskott-Aldri.ch syndrome
24 The answer is C: DiGeorge syndrome. DiGeorge syndrome is a chromosomal defect that results in developmemal anomalies of the bran chial (pharyngeal) pouches and organs that develop from these embryonic structures (thymus, parathyroids, and aonic arch). These children present with tetany caused by hypoparathyroidism and deficiency of cellular immunity TI1ey also have characteristic facial features ("angry took"). In th e absence of a thymus, T-cell maruration is imenupted at me pre-I stage. DiGeorge syndrome has been corrected by transplanting thymic tissue. None of the other choices are associated v.rixh thymic aplasia. ***Diagnosis: DiGeorge syndrome
25 A 50-year-old woman complains of imenniltem tingling and pain in the tips of her fingers. She also reports joi.m and muscle pain. Physical examination reveals lymphadenopathy. Laborawry studies show hypergammaglobulinemia. The antinuclear amibody test is positive, bm there is no evidence of antibodies against double-stranded DNA. Urinalysis ls normal. The patient responds wellw steroids. vVhich of the following is the most likely diagnosis? ***(A) Graves disease ***(B) MLxed connective tissue disease ***(C) Myaslhenia gravis ***(D) Sclerodenua ***(E) Sjogren syndrome
25 The answer is B: Mixed connective tissue disease (MCTD). MCm has features of other common autoimmune diseases (e.g. , SLE and sclerodem1a) but appears to be distinct. Patients typically have au loami bodies to ribonucleo proteins, but unlike SLE, they do not have antibodies to Sm amigen or double-stranded DNA. Some patients with MCTD develop symptoms of scleroderma or rheumatoid arthritis, suggesting that MCTD may be an intennediate stage in a gen etically determined progresswn. Whether MCTD rep resents a distinct entity or simply an overlap of symptoms in patients with otl1er types of collagen vascular diseases remains an open question. lmermiuem episodes of ischemia of tJ1e fingers , marked by pallor, paresthesias, and pain, are refened to as Raynaud phenomenon. None of the other choices feature this constellation of signs and symptoms. ***Diagnosis: MLxed connective tissue disease
26 A 25-year-old woman complains oflow-grade fever, fatigue, and persistem rash over her nose and upper chest. She also notes pain in her knees and elbows. A skin biopsy shows dermal innammati.on and granular deposits oflgG and C3 complement along the basement membrane at the epidermal/dermal junedon. Urinalysis reveals microscopic hematuria and proteinuria. The aminuclear antibody test is positive. The development of thromboembolic complications (e.g., deep venous thrombosis) in this patient is commonly associated v.rilh elevated serum levels .of antibodies to which of the follo\ving antigens? ***(A) ABO blood group antigens ***(B) Class U HLA molecules ***(C) Clotting facto rs ***(D) Fibrinolytic enzymes ***(E) Phospholipids
26 The answer is E: Phospholipids. One thi rd of patients \<Vith systemic lupus erythematosus (SLE) possess elevated concentrations of amiphospholipid antibodies. This phenomenon predisposes these patients to thromboembolic complications, including stroke, pulmonary embolism, deep venous thrombosis, and portal vein thrombosis. The clinical course of SLE is highly variable and typically exhibits exacerbations and remissions. Wllh the recognition of mild fo nns of the disease , improved amihypenensive medications, and the use of immunosuppressive agents, the overall 10-year survival rate approaches 90%. Antibodies against clotting factors (choice C) or fibrinolytic enzymes (choice D) are not involved in the clotting tendency associated with SLE. ***Diagnosis: Systemic lupus erythematosus
27 A 30-year-old woman is found to have a congenital immunodeficiency that has remained largely asymptomatic throughout her life. \Vhich of the following is the most llkely diagnosis? ***(A) Adenosine deaminase deficiency ***(B) Chronic mucocmaneous candidiasis ***(C) PUJine nucleoside phosphorylase deficiency ***(D) Selective IgA deficiency ***(E) vVL-;kott-Aldrich syndrome
27 The answer is D: Selective lgA deficiency. Selective lgA deficiency is the most common primaty immunodeficiency syndrome, with an incidence of 1:700 among Europeans. Although patients are often asympwmatic, they occasionally present with respiratory or gastrointestinal infections of varying severity. They also display a strong predilection for allergies and collagen vascular diseases. Patients with lgA deficiency have normal numbers of lgA·bearing B cells, and th eir varied defects result in an inability to symhesizc and secrete lgA subclasses. Patients with chronic mucocutaneous candidiasis (choice B) show an increased susceptibility to Cm1dida infections an.d also may exhibit various endocrine disorders (e.g., hypoparathyroidism and Addison disease). The other choices are associated with severe immunodeficiency ***Diagnosis: Selective lgA deficiency
28 A 60-year-old woman with type 2 diabetes and end-stage renal disease receives a kidney transplanl. Three weel<s later, the patient presents with azotemia and oliguria. lf this patient has developed acute renal fa ilure, which of the following pathologic find ings would be expected on renal biopsy? ***(A) Arterial intimal thickening and vascular stenosis ***(B) Glomerulosclerosis ***(C) Interstitial infiltrates of lymphocytes and macro phages ***(D) Neurrophilic vasculitis and fibrinoid necrosis ***(E) Tubular atrophy and i.mersLitial fibrosis
28 The answer is C: Interstitial infiltrates of lymphocytes and macrophages. Transplant rejection reactions have been traditionally categorized imo hyperacute, acute, and chronic rejection based on the clinical tempo of the response and on the mechanisms involved. Acme rejenion is characte1ized by an abrupt onset of azotemia and oliguria, which may be associated with fever and graft tenderness. A needle biopsy would be expected to show (l) interstitial infiltrates of lymphocytes :md macrophages, (2) edema, (3) lymphocytic rubulitis, and ( 4) tubular necrosis. Neutrophilic vasculitis and fibrinoid necrosis (choice D) are seen in hyperacute rejection. Arterial intimal thickening (choice A), glomerulosclerosis (choice B), and tubular atrophy (choice E) are seen in chronic graft rejection. ***Diagnosis: Acme graft rejection
29 A 12-year-old boy presents with a 5-day history of sore throaL. His temperature is 38. 7"C (103°F) Physical examination reveals in flamed tonsils and swollen cervical lymph nodes. Trafficking and recirc ulation of blood-borne lymphocytes through the cervical lymph nodes in this patient occurs prinunily at which of the fo llov.ling locations? ***(A) Afferent l)'mphatic vessel ***(B) EITerent lymphatic vessel ***(C) Hassan corpuscles ***(D) High endothelial venules ***(E) Peyer patches
29 The answer is D: High endothelial venules (HEVs) . B and T lyrnphocytes circulate via Lhe vascular system to secondary lymphoid organs and tissues. Included among these tissues are lymph nodes, mucosa-associated lymphoid tissues, and spleen. ln the case or lymph nodes, lymphocyte trafficklng occurs through specialized postcapiUary venules termed high endothelial venules (HEVs). HEVs express an array of specific cell .adhesion molecules (e.g., CD3l) that allow lymphocyte binding and diapedesis. The cuboidal shape of HEY cells reduces now-mediated shear forces and specialized imercellular connections facilitate egress of lymphocytes out of the vascular space. Afferent and effe rent lymphatic channels (choices A and B) do not possess HEVs. Hassall corpuscles (choice C) are found in the meduUa of the Lhymus. Peyer patches (choice E) are organized lymphoid tissues found in the small imestine. ***Diagnosis: Lymphadenopathy, streptococcal pharyngiLis
30 A 28-year-old woman with a history of drug abuse presents with an infectious mononucleosis-like syndrome and lymphadenopathy. Blood tests subsequently indicate that she is HN-positive. Which of the following lymphocyte-associated proteins mediates the entry of HlV imo host cells in this patient? ***(A) CD4 ***(B) CD8 ***(C) GP4l ***(D) GP120 ***(E) LFA-1
30 The answer is A: CD4. The HIV-1 genome consists of two identical 9. 7 -kb single su·ands of RNA enclosed within a core of viral proteins. The core i.s enveloped by a phospholipid bilayer derived from the host cell membrane, in which are found vi.rally encoded glycoproteins (gpl20 and gp41). In addition to the gag. pol. and env genes--characteristic of all replication-competent RNA viruses-HIV-1 contains six Olher genes that code for proteins involved in replication . The specific target cells for HJV-1 are CD4+ helper T lymphocytes and mononuclear phagocytes, although infection of other cells occurs. The HIV envelope glycoprotein gpl20 (either on the free virus or on the surface of an infected cell) binds CD4 on the surface of helper T lymphocytes. The binding of gpl20 to CD4 allows gp4lto insert into the cell membrane of the lymphocyte, thereby promoting fusion of the viral envelope with the lymphocyLe. En try of HIV-1 in to a target cell in vivo also requires viral binding to a coreceptor, ~-chemokine receptor 5 (CCR-5). Choices C and D (gp4l and gp 120) are involved in viral replication, but they are present on the viral envelope. Choice E {l fA-1) i5 a member of the leukocyte imegrin family that is involved m cell-cell adhesion. ***Diagnosis: Acquired immunodeficiency
1 A 25-year-old man presems 1 week after discovering that his left testicle is twice the normal size. Physical examination reveals a nomender, testicular mass that cannot be transilluminated. Serum levels of alpha-fetoprotein and human chorionic gonadotropin are normaL A hemiorchiectomy is perfonned, and histologic examination of the surgical specimen shows embryonal carcinoma. Compared to normal adult somatic cells, this genn cell neoplasm would most likely show high levels of expression of which of the following proteins? ***(A) Desmin ***(B) Dystrophin ***(C) Cytochrome c ***(D) P sel eC£in ***(E) Telomerase
....._1_ The answer is E: Telomerase. Somatic cells do not normally express telomerase, which is an ~nzyme that adds repetitive sequences w maintain the length of the telomere. Thus, \Vith each round of somatic cell replication, the telomere shortens. The length of relomeres may act as a "molecular clock" and govern the lifespan of replicating cells. Because cancer cells and embryonic cells ex1)ress high levels of telomerase, the reactivation of this enzyme may be imponam for maintaining stem cell proliferation. Most human cancers show activation of the gene for the catalytic subunit or telomerase: huma11 telomerase reverse tTanscriptase. P selectin {choice D) is a cell adhesion molecule lhat mediates the margination of neutrophils during acute inflammation. The other choices are not involved in malignant transformation. ***Diagnosis: Embryonal carcinoma
2 A 25-year-old woman presents for a gynecologic examination. The cervical Pap smear shows "kollocytic atypia" characterized by perinuclear halos and w1inkled nuclei (shown in the image). A cervical biopsy reveals invasive squamous cell carcinoma. Molecular tests for human papil1omavirus (HPV) in the tumor cells are positive. Which of the follo·wing mechanjsms of disease best explains the role ofHPV in the pathogen· esis of neoplasia in this patient? ***(A) Activation of cellu lar oncogenes ***(B) Enhanced transcription of relomerase gene ***(C) Episomal viral replicatiorr ***(D) Inactivation of tumor suppressor proteins ***(E) Insertional mmagenesis
2 The answer is D: Inactivation of tumor suppressor pro· t.eins. Unlike RNA Lmnor viruses, whose oncogenes have normal ce llular counterparts, rhe transfo rming genes of DNA viruses are nm homologoU5 wirh any cellular genes. This conundrum was resolved wilh the discovery that the gene products of oncogenic DNA viruses inactivate rumor suppressor proteins. For example, prO[eins encoded by the E6 and E7 genes of HPV16 bind p53 and pRb. The other choices are involved in Lhe pathogenesis of neoplasia, bm they are not specific for HPV. ***Diagnosis: Cervical intraeptlhelial neoplasia, HPV infection
3 The patiem desctibed in Question 2 undergoes a hysterecwmy. ln addition lOa focus or invasive carcb1oma, the pathologisL idemtfies dysplastic squamous ce lls occupying the emire thickness of the cervical epithelium, with no evidence of epithelial maturation. The basal membrane in these areas appears imact. Which of the following tem1s best describes this cerncal lesion? ***(A) Alypical hype rplasia ***(B) Carcinoma in siru ***(C) Carcinomatosis ***(D) Complex hyperplasia ***(E) Koilocylic atypia
3 The answer is B: Carcinoma in situ. Most carcinomas begin as localized growths confined to rhe epithelium in which rhey arise. As long as these early cancers do not penetrate the basemem membrane on which the epithellum rests, such tumors are labeled carcinoma in situ. When the in situ tumor acquires invasive potential and extends directly through the underlying basement membrane, it is in a position to compromise neighboring tissues and metastasize. Carcinomatosis (choice C) is a clinical term used to desc1ibe widespread dissemination of cancer. Koilocytosis (choice E) implies the presence of squamous cells with pe1inuc lear halos and nuclear changes. lt is indicative of human papillomavims infection and canies an increased risk of carcinoma. Atypical and complex hyperplasia (choices A and D) refer to proliferative lesions of the glands within the uterine endomeuium. ***Diagnosis: Cervical carcinoma, carcinoma in situ
4 A 62-year-old woman presents with a breast lump that she discovered 6 days ago. A breast biopsy shows lobular carcinoma in situ. Compared to normal epithelial cells of the breast lobule, these malignant cells 'vould most likely show decreased expression of which of the follov.ring proteins? ***(A) Desmin ***(B) E-cadherin ***(C) Lysyl hydroxylase ***(D) P sel ectin ***(E) Telomerase
4 The answer is B: E-cadherin. Cadherlns are Ca2+-dependem transmembrane glycoproteins that mediated cell-cell adhesion. E-cadherin is expressed on the surface of all epithelia and mediates ceU adhesion by "zipper-like" interactions. Overall, cadherins suppress invasion and metastasis. Thus, it is perhaps not surprising that the expression of E-cadherin is reduced in most carcinomas. Desmin (choice A) is an intermediate fi lament protein found in cells of mesenchymal origin. Lysyl hydroxylase (choice C) is involved in the posttranslational modifLcation of collagen. P selectin is a cell adhesion molecule that mediates the margination of neutrophils dming acute inflammation. Telomerase (choice E) is increased in certain malignancies ***Diagnosis: Breast cancer
5 An 80-year-olcl man complains of lower abdominal pain, increasing weakness, and fatigue. He has lost 16 lb (7 3 kg) in the past 6 momhs. The prostate-specLfic antigen test is elevated (8.5 nglml). Rectal examination re,·ea ls an enlarged and nodular prostate. A needle biopsy of the prostate disci oses invasive prostatic adenocarcinoma. Histologic grading of this parienl's carcinoma is based primarily on which of the following Clitetia' ***(A) Capsular involvement ***(B) E.xtem of regional lymph nodes involvemem ***(C) Pulmonary metastases ***(D) Resemblance to nom1altissue of origin ***(E) Volume of prosta£e involved by mmor
5 The answer is D: Resemblance to normal tissue of origin. To esmblish cmeria for Lherapy, many cancers are classified according lO hiswlogic gradmg schemes or by staging protocols Lhat dese1ibe the extent of spread. Cancer grading reflects cellular characteristics. Low-grade tumors are well differentiated, whereas high-grade rumors lack differendated features (anaplasia). The general correlation between cywlogic grade and the behavior of a neoplasm is not invariable. Ind eed, there are many examples of rumors of low cytologic grades that exhibit substantial malignant properties. The other chokes pertain to cancer staging. ***Diagnosis: Prostate cancer
& A 50-year-old woman presents with a lump in her breast. A 4-cm firm and fixed mass is noted on breast examination. Excisional biopsy reveals malignant cells lhat fonn glandlike stmcmres and solid nests, surrounded by a dense collagenous stroma. A connective tissue stain (trichrome) of the biopsy is shown in the image. Which of the following descriptive terms best describes the blue areas observed in this specimen? ***(A) Colloid carcinoma ***(B) Comedocarcinoma ***(C) Desmoplastic change ***(D) Medullary carcinoma ***(E) Papillomatosis
6 The answer is C: Desmoplastic change. Seconda1y descr iptors are used to refer to a tumors morphologic and functional characteristics. Papillomatosis (ch oice E) describes frond-like structures. Medullary (choice D) signifies a soft cellu1ar tumor, whereas scirrhous or desmoplastic implies dense fibrous stroma. Colloid carcinomas (choice A) secrete abundant mucus. Comedocarcinoma (choice B) is an intraduCLal neoplasm in which necrotic material can be e>.'J)ressed from the ducts. ***Diagnosis: Breast cancer
7 A 65-year-old man complains of muscle weakness and a dry cough for 4 months. He has smoked two packs of cigarettes daily for 45 years. A chest X-ray shows a 4-cm cemral, left lung mass. Laboratory srudies reveal hyperglycemia and hypertension. A transbronchial biopsy is diagnosed as sma!J cell carcinoma. Metastases w the liver are detected by CT scan. 'vVhich of the following might account for the development of hyperglycemia and hypertension in this patient? ***(A) Adrenal metastases ***(B) Paraneoplasdc syndrome ***(C) Piruitary adenoma ***(D) Pi tuitary metastases ***(E) Thrombosis of the renal anery
7 The answer is 8: Paraneoplastic syndrome. Cancers may pro- ,__ duce remote e!Tects, collectively termed paraneoplastic syndromes. For example, rhe secrnion of corticotropin (ACTH) by a mmor leads to clinical featu res of Cushing syndrome, including hyperglycemia and hypenension. ConicOLropin production is most commonly seen \Vith cancers of the lung, particularly small cell carcinoma. Adrenal and piruitary metastases (choices A and D) would lead to loss of adrenal function (Addison disease). Although pituitary adenoma (choice C) is a possible cause of Cushing syndrome, this choice would be unlikely in a patiem with lung cancer. ***Diagnosis: Small ceO carcinoma of lung, paraneoplastic syndrome
8 A 60-year-old man presents with a 4-momh history of increasing weight loss, wheezing, and shormess of breath. He has smoked two packs of cigarettes a day for 40 years. His past medical history is significant for emphysema and chronic bronchitis. A chest X-ray shows a 10-cm mass in the left lung. Bronchoscopy discloses obstruction of the left main stem bronchus. A biopsy is obtained (shown in the image). lmmunohistochemkal studies of Ll1is biopsy specimen would most likely show strong expression of which of the following tumor markers? ***(A) Alpha-fetoprotein ***(B) Calretinin ***(C) Carcinoembryonic antigen ***(D) Cytokeratins ***(E) Synapwphysin
8 The answer is D: Cytokeratins. Tumor markers are products of malignant neoplasms that can be detected in cells or body fh.lids. Useful rumor markers include immunoglobulins, fetal proteins, enzymes, hormones, and cytoskeletal proteins. Car· cinomas uniformly express cytokeratins, which are intermedjate filaments. Alpha-fetoprotein (choice A) is a marker for yolk sac carcinoma and hepalocellular carcinoma. Calretinin (choice B) provides a marker for mesothelioma. Carcinoembryonic antigen (choice C) is a marker for colon carcinoma and many other malignancies. Synaptophysin (choice E) is a marker for neuroendocrine tumors, including small cell carcinoma of the lung. ***Diagnosis: Squamous cell carcinoma of lung
9 vVl1ich of the fo llowing potent carcinogens was most likely involved in the pathogenesis of lung cancer in the patient desCJibed in Question 8? ***(A) Aflawxin B1 ***(B) Asbestos ***(C) Azo dyes ***(D) Polycyclic aromatic hydrocarbons ***(E) Vinyl chloride
9 The answer is D: Polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbons, originally derived from coal tar, are among Lhe most extensively studied carcinogens. These compounds produce cancers at tl1e site of application. Since polycyclic hydrocarbons have been identified in cigareue smoke, it has been suggested (bm not proved) that they are involved in the pathogenesis of lung cancer. Aflatoxin B1 (choice A), a natural product of the fungus Aspergillus flavus, is among the most potent liver carcinogens. Asbestos (choice B), a mineral , is associated with mesothelioma and adenocarcinoma of lung. Industrial workers exposed to high levels of vinyl chloride (choice E) in the ambient atmosphere developed angiosarcomas of the liver. ***Diagnosis: Squamous cell carcinoma of lung
10 A 33-year-old woman discovers a lump in her left breast on self-examination. Her mother and sister bOlh had breast cancer. A mammogram demonstrates an ill-defined density in the omer quad rant of th e left breast, \Vith microcalcifications. Needle aspiration reveals the presence of malignant, ductal epithelial cells. Genetic screening identifies a mutation in BRCAl. In addition to cell cycle control, BRCAl protein p romotes which of the following cellular functions? ***(A) Apoptosis ***(B) Cell adhesion (C} DNA repair ***(D) Gene transcription ***(E) Transmembrane signaling
10 The answer is C: DNA repair. Breast (BR) cancer (CA) suscepLibility genes (BRCAl and BRCA2) encode tumor suppressor proteins involved in checkpoint functions related to progression of the cell cycle into S phase. BRCAl and BRCA2 proteins also promote DNA repair by binding to RAD51, a molecule that mediates DNA double-strand repajr breaks. The other choices may be abnormal in neoplasia, bm they are not primarily affected by BRCAl. ***Diagnosis: Breast cancer
11 A 60-year-old man who worked for 30 years in a chemical facto ry complains of blood in his urine. Urine cytology discloses dysplastic cells. A bladder biopsy demonstrates transitional ceU carcinoma. Which of the fo llowing carcinogens was most likely involved in the pathogenesis of bladder cancer in this patiem? ***(A) Aniline dyes ***(B) Arsenic ***(C) Benzene ***(D) Ci.splatinum ***(E) Vinyl ch loride
11 The answer is A: Aniline dyes. Transitional cell carcinoma is the most common malignant tumor of the urinary bladder, and the incidence of bladder cancer is increased in aniline dye workeTs. These azo dyes are converted to water-soluble carcinogens in the liver. They are excreted in the urine, where they pnmarily affect the transitional epithelium of the bladder. Benzene exposure (choice C) is associated with leukemia. Vinyl chloride exposure (choice E) has been associated with hepatic angiosarcomas. ***Diagnosis: Transitional celJ carcinoma of bladder
12A 60-year-old man presems with an ulcerated, encrusted, and tnfilnating lesion on the sun-exposed dorsal aspect of a finger (shown in the image). A biopsy reveals squamous cell carcinoma. The metast:acic potential of this neoplasm would be enhanced by upregulation of the gene for which of the following proteins? ***(A) Collagen type N ***(B) Desmin ***(C) E-cadherin ***(D) Glmathione peroxidase ***(E) Plasminogen activator
12 The answer is E: Plasminogen activator. Malignam cells and stromal cells associated with cancers elaborate a variety of proteases that degrade basemem membrane components. Such enzymes include the urokinase-type plasminogen activator (u-PA) and matrix metalloproreinases. u-PA converts serum plasminogen to plasmin, a serine p rotease that degrades laminin and activates type IV procotlagenase. Changes in the expression of u-PA, the u-PA receptor, and PA inhibi tors have been reported in differenl cancers. Metastatic cells would be e>q)ected to show reduced expression of collagens (choice A) and cadherins (choice C). Desmin (choice B) is found in cells of mesenchymal origin. ***Diagnosis: Squamous cell carcinoma of skin
13 A 45-year-old man presems wi th a 9-momh history of a reddish nodule on his foot. Biopsy of the nodule d1scloses a poorly demarcated lesion composed of fibroblasts and endothelial-Like cells lining vascular spaces. Funher work-up identifies similar lesions in the lymph nodes and liver. The tumor cells comain sequences of human h erpesvirus-8 (HHV-8). This patiem most likely has which of the following diseases? ***(A) Acquired inununodeficiency ***(B) Ataxia telangiectasia ***(C) Li-f raumeni syndrome ***(D) Neuronbromatosis t)•pe l ***(E) Xerodenna pigmemosum
13 The answer is A: Acquired immunodeficiency. Kaposi sarcoma is the mosL conunon neoplasm associaLed with acquired immunodeficiency syndrome (AID$). The neoplastic celJs contain sequences of a novel virus, HHV-8, which is also known as Kaposi sarcoma-associated herpesvirus. ln addition w infecting the spindle cells of Kaposi sarcoma, HHV-8 is lymphotropic and has been implicaLed in two uncommon B-cell lymphoid malignancies, namely, primary effusion lymphoma and mullicentric Castleman disease. Like other DNA viruses, Lhe HHY-8 genome encodes proteins thm imerfere wiLh the p53 and pRb tumor suppressor pathways. The oth er choices are hereditary conditions associated with can cer; however, these parient.c; do not Lypically acquire Kaposi sarcoma. The predominant malignancy seen in patiems with ataxia telangiectasia (choice B) is lymphoma/ leukemia. ***Diagnosis: Kaposi sarcoma, AIDS
14 Dming a routine checkup, a 50-year-old man is found to have blood in h ls urine. He is otherwise in excellent health. An abdominal CT scan reveals a 2-cm right renal mass. You inform the patient that staging of this tumor is key to selecting treatment and evaluating prognosis. Which of the following ls the most imponam staging factor for this patient? ***(A) Histologic grade of the rumor ***(B) Metastases to regional lymph nodes ***(C) Proliferative capacity of the tumor cells ***(D) Somatic mutations in the p53 tumor suppressor gene ***(E) Tumor cell karyotype (aneuploidy)
14 The answer is B: Metastases to regional lymph nodes. The choice of surgical approach or treatment modabties is influenced more by the stage of a cancer than by its cytologic grade. The significant criteria used for sLaging vary with differem organs. Commonly used criteria include (l) tumor size, (2) extent of local growth, (3) presence of lymph node metastases, and (4) presence of distam metastases. The mher choices reflect grade of the tumor. ***Diagnosis: Renal cell carcinoma
15 A 68-year-old man who has worked in a shipyard and manufacturing plam all his adult life con1plains of a 4-momh history of chest discomfort, malaise, fever, night sweats, and weight loss. A ch est X-ray reveals a large pteural eiTc1sion. The patiem dies 5 months later of cardiorespiralory failure. The lung at auwpsy is shown in the image. This malignant neoplasm is associaLed ·wilh environmemal e>q)osure Lo which o[ the following carcinogens? ***(A) Mlawxin B 1 ***(B) Asbesws ***(C) Beryllium ***(D) Ionizing radiation ***(E) Silica
15 The answe-r is B: Asbestos. The characteristic tumor associated \vith asbestos e>q)osure is mesothelioma of the pleural and petiwneal cavities. This cancer has been reponed to occur in 2% to 3% of heavily exposed workers. The pipe fitters ln shipyards were the most exposed workers. Many of these workers developed mesotheliomas 20 to 40 years after e}..rposure. lt is reasonable to sum1ise that mesotheliomas of both the pleura and the peritoneum reflect the close contact of these membranes with asbestos fibe rs transponed w them by l)mphatic channels. Like the polycyclic aromatic hydrocarbons, aflawxin B1 (choice A) can bind covalemly w DNA and is among the most potem liver carcinogens recognized. Betyllium (choice C) and silica (choice E) cause lung disease, bU[ they are not carcinogenic. ***Diagnosis: MesotheHoma
16 A 58-year-old woman with colon cancer presents with 3 months of increasing shortness of breath. A chest X-ray reveals numerous, bilateml, round masses in both lungs. Histologic examination of an open-lung biopsy discloses malignant gland-like strucrures, which are near!)' identical to the colon primary. Which of the following changes in cell behavior was the first step in the process leading to tumor metastasis fTom the colon to the lung in this patient? ***(A) AlTest within the circulating blood or lymph ***(B) Exit from the circulation into a new tissue ***(C) Invasion of the underlying basement membrane ***(D) Penetration of vascular or lymphatic channels ***(E) Stimulation of angiogenesis ·within the pulmonary metastases
16 The answer is C: Invasion of the underlying basement membrane. The 6rsr event in tumor cell invasion is breach of the basement membrane that separates an epithelium from the underlying mesenchyme. Afu:r invading the imerstidal tissue, malignant cells penen·are lymphatlc or vascular channels (choice D). ln the lymph nodes, communications between the lymphatics and venous tributaries allow malignant cells access to the systemic circulation. The other choices are imponam f OT tumor metastases, but the}' OCCur JateT than basement membrane invasion. ***Diagnosis: Adenocarcinoma of colon
17 A 68-year-old man complains of recem changes in bowel habits and blood-tinged stools. Colonoscopy reveals a 3-cm mass in the sigmoid colon. Biopsy of the mass shows infiltrating malignant glands. These neoplasdc cells have most likely acquired a set of mutations that cause whkh of the following changes in cell behavior? ***(A) Decreased cellular motility ***(B) Enhanced stem cell differentiation ***(C) Increased cell-cell adhesion ***(D) lncreased susceptibility to apoptosis ***(E) Loss of cell cycle resuiction point control
17 The answer is E: Loss of cell cycle restriction point con· trot. Cancer ce lls often d isplay loss of cell cycle restriction point control through mechanisms such as overe>..'Pression of cyclin Dl, loss of Cdk inhibitors, or inactivation of the pRb or p53 proteins. The p53 gene is deleted or mutated in 75% of cases of colorectal cancer and frequently mutated in numerous other tumors. The p53 protein is a negative regulator of cell division. Inactivating mutations of p53 cause loss of ceU cycle restriction point control and allow cells ,:vilh damaged DNA to progress through the cell cycle. Malignant cells have increased cellular motility (see choice A), reduced stem cell differenriation (see choice B), decreased cell adhesion (see choice C), and decreased susceptibility to apoptosis (see choice D). ***Diagnosis: Adenocarcinoma of colon
18 A35-year-old woman complains of nipple disd1arge and iiTegular menses of 5 months duration. Physical eo'Xamination reveals a milky discharge from both nipples. MRl shows an enlargement of the anterior pituiLalY Which of the following is the most likely hismlogic diagnosis of Lhis patient's pimi Lary tumor? ***(A) Adenoma ***(B) Choristoma ***(C) Hamartoma ***(D) Papilloma ***(E) Teramma
18 The answer is A: Adenoma. Benign tumors mising from a glandular epithelium are termed adenomas. Patients with a prolactin-secreting pituitary adenoma present with amenorrhea and galactonhea. Ectopic islands of nom1al tissue are called choristomas (choke B). Localized, disordered differentiation during development results in a hamartoma (choice C). Papillomas (choice D) do not occur in the pituitary Benign tumors that arise from germ cells and contain all three germ layers are termed teratomas (choice E). ***Diagnosis: Pituitary adenoma, prolactinoma
19 A 52-year-old woman presents with a 1-year histOt)' of upper truncal obesity and moderate depression. Physical examination shows hirsutism and moon facies. A CT scan of the thorax displays a hJiar mass. A transbronchial lung biopsy discloses small ceO carcinoma. Electron microscopy of this patiems lung tumor will most likely reveal which of the following cytologic features? ***(A) Councilman bodies ***(B) Hyperplasia of endoplasmic reticulum ***(C) Miwchondrial calcification ***(D) Myelin figures in lysosomes ***(E) Neuroendoc1ine granules
19 The answer is E: Neuroendocrine granules. Neuroendocrine tumors may synthesize a number of hormones. The presence of small, membrane-bound granules with a dense core is a feature of these neoplasms. Dense granules are visible by electron microscopy. ln this way; electron microscopy may aid in the diagnosis of poorly differentiated cancers, whose classification is problematic by light microscopy. Carcinomas often exhibit desmosomes and specialized junctional complexes, which are structures that are not typical of sarcomas or lymphomas. Myelin figures (choice D) are seen in patients with inherited lysosomal swrage disease. Councilman bodies {choice A) arc apoptotic hepatocytes (acidophilic bodies). ***Diagnosis: SmalJ cell carcinoma of lung, paraneoplastic syndrome
20 Cytogenetic s tudies in a 40-year-old woman with follicular lymphoma clemonslrate a t(l4;18) chromosomal translocation involving the bd-2 gene. Consmurive expression of the protein encoded by the bcl-2 gene inhibits which of the follo\ving processes in this patiem5 transformed lymphocytes? ***(A) Apoptosis ***(B) DNA excision repair ***(C) Gl-to-5 cell cycle p rogression ***(D) Oxidative phosphorylaLion ***(E) Protein (N-linked) glycosylation
20 The answer is A: Apoptosis. Many human cancers show abnormalities in the comrol of apoptosis. For example, follicular B-ceU lymphomas display a charaCLeristic chromosomal translocation in wh.ich the bcl-2 gene is brought under the transctiptional control of the immunoglobulin light-cl1ain gene prommer, thereby causing overexpression of bcl-2. As a result of Lhe antiapopwtic properties of bd-2, the neoplastic clone accumulates in lymph nodes. Since its demonsu·arion in follicular tymphomas, bc1-2 expression has been observed in a variety of other human cancers. None of the other choices describes the fcmction of bcl-2. ***Diagnosis: Follicular ly"D1phoma
21 A 60-year-old man presems with a 6-month history ofincreasing weight loss and fatigue. Physical examination reveals conspicuous hepatomegaly. An abdominal CT scan reveals multiple canon baiJ nodules in the liver (shown in the image). A CTguided biopsy revea1s a mucous-secreting adenocarcinoma. This patients metastatic liver cancer most hkely originated in which of the following anatomic locations? ***(A) Adrenal medulla ***(B) Bone marrow ***(C) Brain ***(D) Pancreas ***(E) Urinary bladder
21 The answer is D: Pancreas. Radiologic evidence of "canon ball" lesions in the liver or lung suggests metastatic cancer. The liver is involved in a thi rd of all metastatic cancers, including halr of those of the gastrointestinal tract, breast, and lung. Other tumors that characteristically metastasize to the liver are pancreatic carcinoma and malignant melanoma. Liver metastases are the most common cause of massive hepatomegaly. Vlsible secre tions of tumor cells, such as mucin or serous Quid, provide important clues for tumor diagnosis. Mucin-secreting glandular epithelium and mucin-secreting adenocarcinoma are e::\.-pected in the pancreas. None of the OLh.er organs are composed of glandular epithelial cells or produce mucin. ***Diagnosis: Metastatic cancer
22 A 59-year-old woman presents with increasing pigmemation of the skin. PhysicaJ examination shows hyperkeratosis and hyperpigmemation of the axilla, neck. flexures, and anogenital region. Endocrinologic studies reveal nonnal semm levels of adrenal conkosteroids and glucoconicoids. If this patients skin pigmemation represents a paraneoplastic syndrome, the primary tumor would most likely be found in which of the following anatomic locations? ***(A) Bladder ***(B) Ce rvi..~ ***(C) Esophagus ***(D) Pleura ***(E) Stomach
22 The answe.r is E: Stomach. Acamhosis mgncans is a cutaneous disorder marked by hyperkeratosis and pigmentation of the axilla, neck, flexures, and anogenital region. lt is of particular imerest because more than half of patients with acanthosis nigricans have cancer. Over 90% of cases occur in association with gastrointestinal carcinomas (primarily stomach cancer). The other mmors are uncommon causes of acanth osis nigricans. ***Diagnosis: Paraneoplastic syndrome, acanthosis nigricans
23 A 65-year-old man dies after a protracted baule with metastatic colon carcinoma. At autopsy, the liver is filled 'Nith multiple nodules of cancer, many of which display central necrosis (umbilication). Which of the following best ex:plains the pathogenesis of rumor umbilication in this patient? ***(A) Biphasic tumor ***(B) Chronic inflammation ***(C) Granulomatous inflammation ***(D) Ischemia and infarcdo11 ***(E) Snmulauon of angiogenesis
23 The answer is D: Ischemia and infarction. Angiogenesis is a requirement for the continued growth of cancers, whether plimary or metastatlc. ln the absence of new vessels to supply the nutrients and remove waste products, malignant tumors do not grow larger than llo 2 mm in diameter. ln general, causes of tumor cell death in situ include (l) programmed cell death (apoptosis); (2.) inadequate blood supply, >vith consequent ischemi.a; (3) a paucity o[ nutrients; and (4) vulnerability to specific and nonspecific host defenses. The CT scan provided [or Question 2.1 shows central necrosis (umbtlicatlon) in most of the metastatic rumor nodules. None of the other choices are likely causes of tumor necrosis. ***Diagnosis: Metastatic cancer
24 A 59-year-old man complains of progressive weakness. He reports that his stools are very dark. Physical examination demonstrates fullness in the right lower quadrant. Labo ratory studies show iron deficiency anemia, with a serum hemoglobin level of 7.4 gldl. Stool specimens are positive for occult blood. Colonoscopy discloses an ulcerating lesion of the cecum. Which of the following serum mmor tnarkers is most likely to be useful for following this patient after surgery? ***(A) Alpha-fetopmtein ***(B) Carcinoembryonic antigen (C} Chorlonic gonadotropin ***(D) Chromogranin ***(E) Coagula non factOr VIII
24 The answer is 8: Carcinoemhryonic antigen {CEA) . Colorectal cancer is asymptomatic in its initial stages. As the mmor grows, the most common sign is occult blood in feces, especially when the tumor is in the proximal ponion of the colon. Chronic, asymptomatic bleeding typically cau ses iron-deficiency anemia. Adenocarcinomas of the colon usually e":press CEA, a glycoprotein that is released mto the circulation and serves as a serologic marker for these tumors. CEA is also found in association with malignant rumors of the pancreas, lung, and ova1y AFP (choice A) is expressed by hepatocellular carcmoma and yolk sac tumors. Chromogranin (choice D) is e."<pressed by neuroendoaine rumors. Chmionic gonadmropin (choice C) is secreted by chmiocarcinoma. ***Diagnosis: Colon cancer
25 l aboratory studies of Lhe surgical specimen obtained from the patient described in Question 24 demonstrate hypem1ethylation of the p53 gene. Which of the following best charactelizes this biochemical change in Lhe neoplastic cells? ***(A) Epigenetic modification ***(B) Gene amplificaLion ***(C) Insertional mutagenesis ***(D) Nonreciprocal translocation ***(E) Protooncogene mutation
25 The answer is A: Epigenetic modification. Hypermethylation of many rumor suppressor and DNA repair genes has been demonso·ared in human rumors. The pa1:hways controlled by these genes are, therefore, suppressed. For example, the normal p53 gene can be inactivated by hypennethylation. Thus, aberrant methylation of tumor suppressor genes may be an epigenetic mechanism for a "second hit," leading to loss of he1:erozygosi1:y. Unlike genetic ch<mges in cancer, ep1genetic changes are reversible, and a search for drugs that influence DNA methylation is under way. The other choices are unrelal: cd to DNA methylation. ***Diagnosis: Colon cancer
26 A 20-year-old woman has an ovarian tumor removed. The surgical specimen is 10 em in diameter and cystic. The cystic cavity is found to contain black h air and sebaceous material. Histologic examination of the cyst wall reveals a variety of benign differentiated tissues, including skin, cartilage. brain, and mucinous glandular epithelium. Wh at is the diagnosis? ***(A) Adenoma ***(B) Chondroma ***(C) Hamartoma ***(D) Teratocarcinoma ***(E) Teratoma
26 The answer is E: Teratoma. Teratomas are benign tumors composed of tissues derived from all three primary gem1 layers: ectoderm, mesoderm, and endodem1. They are most common in the ovary but also occur in the testis and extragonadal sites. Teratocartlnomas (choice D) are malignant tumors that harbor emb ryonal carcinoma stem cells. Adenoma (choice A) is a benign tumor of epithelial origin. Chondroma (choice B) is a benign cartilaginous tumor. Hamartoma (choice C) is disorganjzed normal tissue. ***Diagnosis: Mature teratoma
27 A +2-year-old man preseniS with upper gastroimestinal bleeding. Upper endoscopy and biopsy reveal gastric adenocarcinoma. Which country of the world has the highest incidence of this malignant neoplasm' ***(A) Argentina ***(B) Canada ***(C) Japan ***(D) Mexico ***(E) United States
27 The answer is C: Japan. The highest incidence of stomad1 cancer occurs in Japan, where the disease is almost ten times as frequent as it is among American whites. A study of Japanese residents o [ Hawaii found that emigrants from Japanese regions with the highest risk of stomach cancer continued to exhibit an excess risk in Hawaii. By contrast , their offspring who were born in Hawaii had the same incidence of this cancer as American whites. The highest incidence of colorectaJ cancer is found in the United States (choice E). ***Diagnosis: Gastric cancer
28 An 8-year-old girl with numerous hypopigmcnted, ulcerated, and crusted patches on her face and forearms develops an indurated, crater-like, skin nodule on the back of her left hand. Biopsy of this skin nodule discloses a squamous cell carcinoma. Molecular biology sn1dies reveal that this patient has gennline mutations in the gene encoding a nucleotide excision repair enzyme. What is the appropriate diagnosis? ***(A) Ataxia relangieClasia ***(B) Hereditary albinism ***(C) Li -Fraumeni syndrome ***(D) Neurofibromawsis. type 1 ***(E) Xerodenna pigmemosum
28 The answer is E: Xeroderma pigmentosum. Xeroderma pigmentosum is an aULosomal recessive disease in which increased sensitivity Lo sunlight is accompanied by a high incidence of skin cancers, including basal ceU carcinoma, squamous cell carcinoma, and malignant melanoma. Several xeroderma pigmemosum genes arc involved in nucleodde excision of ultraviolet-damaged DNA. Li-Fraumcni syndrome (choice C) refe rs to an inherited predisposition to develop cancers in many organs due to gerrnline mutations of p5.3 Ataxia telangiectasia (choice A) fe.arures cerebellar degeneration, immunologic abnormalities, and a predisposition to cancer. The mULated gene codes for a nuclear phosphoprotein involved in regulation of the cell cycle and DNA repair. Patients with hereditary albinism (choice B) are also at high risk for development of squamous cell carcinoma of the skin, but they do not have a defect in DNA excision repair. Patients with neurofibromatosis (choice D) develop benign cutaneous neu rofibromas. ***Diagnosis: Xeroderma pigmemosum
29 A 59-year-old woman complah1S of"feeling light-headed" and losing 5 kg (11 lb) in the last month. A CBC Teveals a normocytic, nom1ochromic anemia. The patient subsequently dies of metastatic cancer. Based on current epidemiologic data for cancer-assoctated monality in women. which of the following ts the most lD<ely primaty sire for this patiems malignant neoplasm? ***(A) Brain ***(B) Breast ***(C) Colon ***(D) Lung ***(E) Urinary bladder
29 The answer is D: Lung. lung carcinoma is Lhe caLLSe of most cancer-related deaths in the United States and \>\!estern Europ-e in men and women. The second most common cause of death from cancer in women is breast cancer (choice B) One of the most conm1on findings in patients with cancer is anemia, but the mechanism for this paraneoplastic syndrome is nor dear. The anemia is usually normocydc and normochromic, although iron deficiency anemia is common in cancers 1.hat bleed imo the gastrointestin al tract. ***Diagnosis: lung cancer
30 The parents of a 6-month-old girl palpate a mass on the left side of the childs abdomen. Urinalysis shows high levels of vanillylmandelic acid. A CT scan reveals an abdominal tumor and bony metastases The primary tumor is surgically resected. Histologic examination of the surgical specimen disdoses neuroblastoma. Evaluation of the N-myc prowoncogene in this childs tumor will most hkely demonstrate which of the following genetic changes? ***(A) Chromosomal translocation ***(B) Exon deletion ***(C) Expansion of a trinucleotide repeat ***(D) Frameshift mutation ***(E) Gene amplification
30 The answer is E: Gene amplification. Chromosomal alterations that result in an increased number of copies of a gene have been found p1imarily in solid tumors. Such aben adons are recognized as (l ) homogeneous sLaining regions (HSRs); (2) abnonnal banding regions on chromosomes; or {3) double minutes, which are visualized as small, paired cytoplasmic bodies. In some cases, gene amplification has been shown to involve prmooncogenes. f or example, HSRs may be seen in neuroblastomas and are all de1ived from the N-myc protooncogen e. The presence of N-myc H$Rs is associated with up to 700-fold ampli.ficanon of this gene and is a marker of advanced disease with a poor prognosis. Although Lhe other choices are mechanisms for protooncogene activation, they do nor cause up regulation of N -myc in patients with neuroblastoma. ***Diagnosis: Neuroblastoma
31 An 8-year-old African boy presents with swelling in his jaw and massive facial disfiguration. Biopsy reveals a tumor invading u1e bone marrow of the jaw. The pathogenesis of this malignant neoplasm is associated with a virus that exhibits a lTopism for which of the follo\ving cells? ***(A) Chondrocytes ***(B) Fibroblast5 ***(C) Lymphocytes ***(D) Macrophages ***(E) Osteocyt.es
31 The answer is C: Lymphocytes. Four DNA viruses Omman papillomavirus, Epstein-Barr vi rus I EBVI , hepatitis 13 virus, and herpesvirus-B) are incriminated in the development of human cancers. EBV was Lhe first v1ms to be uneguivocally lin ked to the development of a human tumor. ln 1958, Burkiu described a fonn of childhood lymphoma in a geogTaphicaJ belt across eguatorial Africa, which he suggesled might have a viral etiology A few years later, EpsLein and Barr discovered viral particles in cell lines cultured from patients wi th Burkitt lymphoma. African Burkitt lymphoma is a B-cell mmor, in \'.'hich the neoplastic lymphocytes invariably contain EBV in theiT DNA and manifest EBV-related antigens. EBV does not infect the other choices. ***Diagnosis: Burkitt lymphoma, EBV
32 A 58-year-old woman undergoes rou tine colonoscopy. A 2-cm submucosal nodule is idemified in the appendix. Biopsy of the nodule shows nests of cells with round, urn form nuclei. El ectron microscopy reveals numerous n euroendocrine granules in the cywplasm. This patients neoplastic disease is associated \vith which of the following clinical fea tures? ***(A) Congestive heart failure ***(B) Flushing and wheezing ***(C) Muscular dystrophy ***(D) Progressive systemic sclerosis ***(E) Pulmonary embolism
32 The an:swer is B: Flushing and wheezing. Carcinoid synd rome is a systemk paraneoplastic disease caused by the release of hom10nes fTom carcinoid tumors (via neuroendoctine granules) into venous blood. Sympwms of Oushing, bronchial wheez]ng, watery diarrhea, and abdominal colic are caused by the release of serotonin, b radykinin , and histamine. Carcin aids are neuroendocrine tumors of low malignancy that are most commonly located in the submucosa of the intestines (e.g., appendix, tem1inal ileum, and rectum). The other choices are not associated with this paraneoplastic syndrome. ***Diagnosis: Carcinoid tumor, paraneoplastic syndrome
33 A 55-year-old woman presents with increasing weight loss and fatigue and su bsequently dies of metastatic cancer. The vertebral column at autopsy is shown in the image. \.Vhat is the diagnosis? ***(A) Chondrosarcoma ***(B) Melanoma ***(C) Multiple myeloma ***(D) Qs[eosarcoma ***(E) Rhabdomyosarcoma
33 The answer is B: Melanoma. The photograph shows pigmented cells in the vertebral bodies of a person who died of malignant melanoma. This autopsy finding illusmues the point that accurate mmor identification depends on morphologk resemblance to nom1al tissue. Tumor emboli in this case probably reached bone after surviving passage through the pulmonary microcirculation. Non e of the other tumors show pigmentation. ***Diagnosis: Melanoma
34 A 45~year-old woman presents with abdominal pain and vaginal bleeding. A hysterectomy is performed and shows a benign tumor of the uterus derived from a smooth muscle celL What is the appropriate diagnosis' ***(A) Angiomyolipoma ***(B) Leiomyoma ***(C) Leiomyosarcoma ***(D) Myxoma ***(E) Rhabdomyoma
34 The answer is B: leiomyoma. Leiomyoma is the most common benign tumor of the uterus, usually arising in women of reproductive age. lt originates from smooth muscle cells of the myometrium. None of the other choices are benign tumors of smooth muscle. ***Diagnosis: Leiomyoma of uterus
35 Cytogenetic studies in a 70-year-old woman v•.rith chronic myelogenous leukemia {CML) demonstrate a L(9;22) chromosomal translocation. Which of the following best explains the role of this u·anslocation in the pathogenesis of leukemia in this patient? ***(A) Altered DNA methylation status ***(B) Enhanced expression of telomerase gene ***(C) Expansion of a trinucleotide repeat ***(D) Inactivation o[ mmor suppressor protein ***(E) Protooncogene activation
35 The answer is E: Protooncogene activation. The best-known example of an acquired chromosomal nanslocadon in a human cancer is the Philadelphia chromosome, which is found in 95% of patients with CML. The c-abl prowoncogene on chromosome 9 is translocated w chromosome 22, it is placed in juxtaposition w the breakpoint cluster region (ho} The c-ab[ gene and bcr region unite to produce a hybrid oncogene that codes for an aberrant protein \vi th very high levels of tyrosine kinase activity, which generates nliLOgenic and amiapopLOtic signals. ***Diagnosis: Chronic myelogenous leukemia, Philadelphia chromosome
36 A 33-year-old woman presents with a diff·use scaly skin rash of 4 weeks duration. Biopsy of lesional skin reveals a cutaneous T-cell lymphoma (mycosis fungoides). Which or t.he following immunohistochemical markers would be most useful for identifying malignant cells in the skin of this patient? ***(A) Calcitonin ***(B) CD4 ***(C) Desmin ***(D) HMB-45 ***(E) S-100
36 The answer is B: CD4. CD4 is a cluster-differentiation antigen of helper T lymphocytes. ffivtB-45 and S-100 (choices D and E) are markers for malignanr melanoma, among other mmors. Calcitonin (choice A) is a peptide hom1one. Desmin (choice C) is an intermediate filament protein found in cells of mesenchymal mi gin. ***Diagnosis: Mycosis fungoides
37 A 63-year-old woman ·with chronic bronchitis presents with shortness of breath. A chest X-ray reveals a 2-cm "coin lesion" in the upper lobe of the left lung. A CT-guided lung biopsy is obtained. Which of the followmg describes the histologic features of this lesion if the diagnosis is hamartoma? ***(A) Benign neoplasm of epithelial origin ***(B) Disorganized nom1al tissue ***(C) Ectopic islands of normal tissue ***(D) Granulation tissue ***(E) Granulomawus inflammation
37 The answer is 8: Disorganized normal tissue. Localized, disordered differentiation during embryonic development resul lS in a hamartoma, a disorganized caricature of normal tLc;sue components. Such tumors, which are not strictly neoplasms, contain varying combinations of cartilage, ducts or bronchi, cmmecrive tlSSue, blood vessels, and lymphoid tissue. Ectopic islands of normal tissue (choice C), called chorisroma, may also be mistaken for true neoplasms. These small lesions are represemed by pancreatic tissue in the wall of the stomach or intestine, adrenal rests under the renal capsule, and nodules of splenic tissue in the periwneal cavity ***Diagnosis: Hamartoma
38 A 67 -year-old woman presents with a massively swollen abdomen. The patient was diagnosed with papillary, serous cystadenocarcinoma of the ovary 3 years ago. She dies in a hospice 1 month later. At auwpsy, the pe1iwneum is studded wilh smallmmors (shown in the image), and there are 4 L of ascites. Which of the following routes of tumor metastasis accounts for these auwpsy findings? ***(A) Direct tumor extension ***(B) Hematogenous spread ***(C) Lymphatic spread ***(D) Seeding of body cavity ***(E) Venous spread
38 The answer is D: Seeding of body cavity. The photograph shows a loop of small bowel and mesentery studded with small nodules of metastatic cancer. Malignant tumors that arise in organs adjacem to body cavities (e.g., ovaries, gastrointestinal tract, or lung) may shed malignant cells into these spaces. Such body cavities include principally the petitoneal and pleural cavities, although occasional seeding o[ the pericardia! cavity, joint space, and subarachnoid space are observed. Tumor cells in these si tes grow in masses and often produce fluid (e.g., ascites or pleural Ouid), sometimes in massive quantities. Although the other choices provide routes for rumor metastasis, they do not lead to peritoneal carcinomatosis in patienlS with ovatian cancer. ***Diagnosis: Ovarian cancer, carcinomatosis
39 A 2-year-old boy is found to have bilateral retinal tumors. Molecular studies demonstrate a germline mutation tn one allde of the Rb gene. Which of the follmvinggenetic events best explains the mechanism of carcinogenesis in this patient? ***(A) Balanced translocation ***(B) Expansion of trinucleotide repeat ***(C) Gene amplification ***(D) Loss of heterozygosity ***(E) Maternal nondisjunction
39 The answer is D: Loss of heterozygosity. Retinoblastomas are 1nalignam ocular tumors of young children. In cases of hereditmy retinoblastoma, an affected child inherits one defective Rb aUele mgether wi£h one nom1al gene. This heterozygous state is not associated with any observable changes in t.he retina because 50% of the Rb gene product. is sufficient. to prevent the development of retinoblastoma. However, if the remaining nmmal Rb allele is inactivated by deletion or mutation, l11e loss of its suppressor function leads to the appearance of a neoplasm. This genetic process is referred to as loss of heterozygosicy: The other choices have not been associated 'Nilh the loss of £Umor suppressor genes in somatic cells. ***Diagnosis: Retinoblastoma
40 A 48-year-old nulliparous woman complains that her menstrual blood fiow is more abundant Lhan usual. An ultrasound examination reveals a polypoid mass in the ute1ine fundus. The patient subsequemly, undergoes a hysterectomy, which reveals a poorly differentiated endometrial adenocarcinoma_ The development o [this neoplasm was preceded by which of the following histopathologic changes in the glandular epithelium? ***(A) Atrophy ***(B) Hydropic swelling ***(C) Hyperplasia ***(D) Hypemophy ***(E) Metaplasia
40 The answer is C: Hyperplasia. The cellular and molecular mechanisms of hyperplasia are related to the control of eel] proliferation and provide a basis for further genetic changes that can lead to neoplasia. Endometrial hyperplasia refers to a spectrum that ranges from simple glandular crowding to conspicuous proliferation of atypical glands. These changes are often difficult to distinguish from carcinoma. The risk of developing endometrial cancer increases with higher degrees of endometrial hyperplasia. Estrogen exposure is thought to be a risk factor for both endometrial hyperplasia and endometrial carcinoma. Neoplas tic transfonnation may occur in the se tting of a metaplastic epithelium (e.g., cancers of the lung, cervix, stomach, and bladder); however, metapLasia (choice E) does not precede Lhe development of merine adenocarcinoma. The other cholces do not represem risk factors for cancer. ***Diagnosis: Endometrial adenocarcinoma
41 A 53-year-old womru1 with a longstanding history of ulcerative colitis presents with increasing chest pain and shortness oJ breath of 2 mom.hs duration. She reports four recent episodes of hemoptysis_ The patiem subsequently develops overwhelming sepsis and expires. A section through the tight lung is examined at autopsy (shown m the image) What is the appmpriate diagnosis? ***(A) Carcinoid tumor of lhe lung ***(B) P1imary adenocarcinoma of the lung ***(C) Metastatic carcinoma of the lung ***(D) tvHJiary tuberculosis ***(E) Sarcoidosis
41 The answer is C: Metastatic carcinoma of the lung. This patient's lung shows numerous nodules of metastatic carcinoma conesponding to "cannon ball" meLastases seen radiologically Pulmonary metastases are more common than primary lung rumors, and the histologic appearance of most metastases resembles that of the prima1y tumor. Persons with ulcerative colitis (such as this patient) have a higher risk of colorectal cancer than the general population. The risk is related to the extent of colorectal involvement and the duradon of the inflammatory disease. Carcinoid rumor of the lung (choice A) and primmy lung cancer (choke B) would not typically show multiple, circumscribed nodules. Milia1y tuberculosis (choice D) and sarcoidosis (choice E) feamre 111m-sized inl1ammawry nodules (minute granulomas). ***Diagnosis: Metastatic cancer, metastatic carcinoma of the lung
42 A 50-year-old woman presents with a 2-year histOI)' of upper truncal obesity and depression. Serum levels of glucose and cortisol are elevated. ACT scan of the abdomen reveals a 2-cm suprarenal mass. The surgical specimen is shown in the image. If this neoplasm is benign, which of the following is the most appropriate diagnosis? ***(A) Adenoma ***(B) Chondroma ***(C) Upoma ***(D) Papilloma ***(E) Teratoma
42 The answer is A: Adenoma. The patient shows signs and sympwms of Cushing syndrome (upper truncal obesity and hyperconisolism). The surgical specimen reveals a circumscribed tumor of the adrenal cortex that produces cortisol. Hismlogic examination of this tumor reveals nests of clear, lipid-laden epithelial cells. None of the other choices desCiibe a benign rumor of glandular epithelial origin. ***Diagnosis: Adrenal adenoma, Cushing syndrome
43 A 65-year-old man presents with a pearly papule on his upper lip (pa tient shown in the image). A biopsy reveals buds of atypical, deeply basophilic kerannocytes extending from the overlying epidermis into the papillary dermis. Which of the following carcinogenic stimuli was the most imponant risk factor for developmem of this patients skin cancer? ***(A) Aflatoxin B1 ***(B) Divalem metal cations ***(C) Aromatic ammes and azo dyes ***(D) Vinyl chloride ***(E) Sunlight
43 The answer is E: Sunlight. Basal cell carcinoma {BCC} is the most common malignam rumor in persons with pale skin. 13CC usually develops on the sun-damaged skin of people with fair skin and freckles. There is a direct correlation betwee11 total exposure lO sunlight and t.h.e incidence of 13CC, as well as squamous cell carcinoma and melanoma. The deleterious effects of sunlight (l)V radiation) include enzyme inactivation, mutagenesis, and cell death. Divalent metal cations such as nickel, lead, cadmhtm, cobalt, and beryllium (choice 13) can react v.rith biomolecules and induce cancer. Most metalinduced cancers occur in an occupational setting; however the carcinogenic mechanis1ns are unknown. ***Diagnosis: Basal cell carcinoma
44 A 28-year-old man with a familial disease affecting the gastrointestinal tract undergoes a colectomy. The surgical specimen is shown in the image. Molecular studies demonstrate a germline mutation in the APC gene. The normal product of this gene (protaoncogene) primatil y regulates which of the following cell behaviors? ***(A) Apoptosis ***(B) Autophagy ***(C) Ce 11 cycle ***(D) Differemiation ***(E) Motility
44 The ait.swer is C: Cell cycle. The surgical specimen reveals thousands of small adenomatous polyps on the mucosal surface of the colon. Patients with adenomatous polyposis coU have mutations in the APC rumor suppressor gene. Most cases are familial, bm 30% to '50% represem new mutations. The mean age for occurrence of symptoms is 36 years. 'Without the APC protooncogene, cells are unable to downregulate signals from E-cadherin to f3-catenin to nuclear transcription facwrs (myc and cyclin D) LhaL regulate cell cycle progression. Autophagy (choice B) is a normal catabolic process in which cellular components and organelles are degraded in lysosomes. Autophagy is often a response to cell injury It is also believed lO protect cells from intracellular pathogens and slow the p rogression of valious chronic diseases, including cancer. ***Diagnosis: Ade11omawus polyposis coli
1 A 4-year-old gi rJ presents for a preschool physical examination. The child has a small head circumference, thin upper Hp, and low-bridge nose. She shows evidence of mild mental retardation. Her paren ts slate that sl1e is often "emotional." Which of the following maternal causes of birth defects most likely accounts for these clinicopathologic findings? ***(A) Alcohol abuse ***(B) Cigarette smoking ***(C) Congenital syphilis ***(D) Inadequate nmrition ***(E) Poorly controlled diabetes mellitus
1 The answer is A: Alcohol abuse. Fetal alcohol syndrome refers to a complex of abnormalities induced by the maternal consumption of alcoholic beverages while pregnant that includes (l) growth retardation, (2) dysfunction of the cemral nervous system, and (3) characteristic facial dysmorphology (e.g., small head circumference and thin upper lip). One fifth of children with fetal alcohol syndrome have IQs below 70, and 40% have lQs between 70 and 85. Even with a nom1al JQ, these children tend to have short memory spans, impulsiveness, and emotional instability. The children of mothers who smoke (choice B) or who have inadequate nutrition (choice D) may also exhibit deficiencies in physical growth and intellectual development; however, Lhere is no associaLion with the pattern of facial dysmorphology and emotional instability seen in this case. Congenital syphilis (choice C) may also cause mental retardation, but it would show protean manifestations not illustrated in Lhis case. Gestational diabetes (choice E) does noL cause mental retardation. ***Diagnosis: Fetal alcohol syndrome
2 A 12-month-old boy is brought LO the emergency room for examination of his right arm following a rumble at home. Radiologic examination of the Umb reveals a recent fracrure of the right ulna and evidence of additional healing fTactures. The child is noted to have blue sclerae. This patient most likely carries a mmation in a gene that encodes which of the follO\ving proteins? ***(A) Collagen ***(B) fibrillin ***(C) Keratin ***(D) Myosin ***(E) Tubulin
2 The answer is A: Collagen. Osteogenesis imperfecta (01), or briLtle bone disease, is a group of inherited disorders expressed principally as fragility of bone. The genetic defects in the four types of OI are heterogeneous, but all affect the synthesis of type I collagen. Type l Ol is characterized by a nonnal appearance at birth, bm fractures of many bones occur during infancy and at the time the child leams to walk. Such patients have been desCJibed as being as "fragile as a China doll." Children with type I 0 1 typically have blue sclerae as a result of the deficiency in collagen fibers, which imparts translucence to the sclera. A high incidence of healing loss occurs because fractures and fusion of bones of the middle ear restr icL their mobility. Fibrillin gene mutations (choice B) are found in patients with Marfan syndrome. Ke ratin gene mutations (choice C) are found in patients with epidermolytic hyperkeratosis. ***Diagnosis: Osteogenesis imperfecta
_3_ A 28-year-old woman gives binh to a stillborn with a severe neural tube defect (neonate shown in the image). This birth defect was caused by an error of morphogenesis that occurred at \Vhich of the following slages of development after fertilization? ***(A) lto 10 days ***(B) 20 to 40 days ***(C) 90 to 120 days ***(D) 6w 9 momhs ***(E) Birth trauma
3 The answer is B: 20 to 40 days. Anencephaly refers to the congenital absence of the cranial vault, with cerebral hemispheres either missing or reduced w small masses. It is a dysraphlc anomaly of neural mbe closure that results from an injury to the fetus be tween the 23rd and 26th day of gestation. Dming feLal developmem, the neural plate is transformed into the neural tube by fusion of the posterior surfaces. Failure of the neural tube to close results in the lack of closure of the overlying bony so·ucrures of the cranium and an absence of the calvarium, skin, and subcutaneous tissues of this region. The exposed brain is incompletely formed or absem. Blastocyst fonnation and implantation occur on days 1 to 10 after fertilization (cholce A). ***Diagnosis: Acrania, neural LUbe defect
4 A 20·year-old man is examined by a new family physician who discovers numerous pigmemed patches and pedunculated skin tumors on his chest. Biopsy of a tumor discloses a berugn neoplasm detived from Schwann cells. Neither the patients father nor mot.her shows signs of this djsease. This patient most likely carries a mutation in a gene that encodes which of the fo llowing proteins? ***(A) Epidennal growth factor receptor ***(B) GTPase activating prQ[ein ***(C) NF·KB transcripLion fanor ***(D) Protein kinase C ***(E) Ras protein p21
4 The answer is 8: GTPase activating protein. Neurofibroma· . ..__ tosis type l (NFl) is characterized by (l) disfigming neurofibromas , (2) areas or dark pigmentation of the skin (cafe au lait spots), and (3) pigmented lesions of the iris (Lisch nodules). lt is one of the more common autosomal dominam disorders. The NFl gene has a high rate of mutation, and half of cases are sporadk rather than familial. The protein product, tem1ed neurofibromin, is expressed in many tissues and belongs to a family of GTPase-act.ivating proteins (GAPs), which inactivate ras protein (choice E). Thus, NFl is a classic tumor suppressor gene. Loss of GAP activity (in cells acquiring a second hit mutation) pennits uncomrolled ras p21 activation, an effect that p redisposes ro the formation of benign neurofibromas. None of the other choices (A, C, and D) are associated with the pathogenesis of neurofibromatosis. ***Diagnosis: Neurofibromatosis, type 1
5 The patient described in Question 4 is at increased risk of developing which of the following malignant neoplasms? ***(A) Ganglioneuroma ***(B) Glioblastoma multifom1e ***(C) Neurofibrosarcoma ***(D) Serous cystadenocarcinoma ***(E) Squamous cell carcinoma
5 The answer is C: Neurofibrosarcoma. One of the major compll cations of neuro6bromawsis type 1 (NF1), occurring in 3% w 5% of patients, is the appearance of a neuro6brosarcoma in a neurofibroma. Nfl is also associated with an increased incidence of other neurogenic tumors, including meningioma, optic glioma, and pheoch romocytoma. The other tumors listed are not associated with NFl. ***Diagnosis: Nemofibromatosis, type 1
6 A 25-ye.ar-old pregnant woman, at 16 weeks of gestation, visits her obstetrician. A screening test suggests the possibility of a neural rube defect iJ1 her ferus. An uJr rasound e.:xamination shows a 3--em neural tube defect m the thoracic spine. The screening test that was administered to Lhe mother measured serum levels of which of the follo\ving proteins? ***(A) Albumin ***(B) Alpha.fetoprotein ***(C) Bilirubin ***(D) Chromogranln ***(E) Human chorlonic gonadotropin
6 The answer is 8: Alpha·fetoprotein (AFP) . Scree11ing of preg· nam women for serum AFP and examination by ulnasonography allow detection of virtually all anencephalic fetuses. Levels of the mher prmeins are nor significamly affected by a neural mbe defect in the fetus. ***Diagnosis: Neural tube defect, spina bifida
7 A 25-year-old man presems for a routine physical examination. TI1e paliem is 1.all (6 fl, 5 in) and has long fingers (shown in the image). One year later, he suiTe rs a dissecting aonic aneurysm. This patient most likely cani es a mutation in a gene that encodes which of the following proteins? ***(A) Collagen ***(B) Dystrophin ***(C) Elasdn ***(D) Fibrillin ***(E) Myosin
7 The answer is D: Fibrillin. The cause ofMarfan syndrome has been established as missense mUlations in the gene coding for fiblillin-1 (FBNl). Fibrillin is a famUy of connective tissue proteins analogous m the collagens. It is widely disuibmed in many tissues in the fom1 of a fiber system H~Imed microfib1ils. For example, the deposition of elastin on microfibnllar fibers produces the concentric rings of elastin in the aonic walL Collagen gene mutations (choice A) are found in patien ts with Ehlers-Danlos syndrome and osteogenesis imperfecta. Dystrophin gene mutations (choice B) are found in patient.<; ''lith muscular dystrophy. ***Diagnosis: Marfan syndrome
8 The genetic disease encountered in the patient described in Question 7 follows which of the following patterns of inheritance? ***(A) Autosomal dominam ***(B) Autosomal recessive ***(C) Multifactorial ***(D) X-linked dominant ***(E) X-linked recessive
8 The answer is A: Autosomal dominant. Mar fan syndrome is an autosomal dominant, inherited diso rder of connective tissue characterized by a variety of abnormalities in many organs, including the heart, aona, skeleton, eyes, and skin. One third of cases represent sporadic mmations. The incidence in the United States is l per 10,000. ***Diagnosis: Marfan syndrome
9 A 12-momh-old boy shmvs progressive weakness, mental deterioration, and loss of vision. Laboratory smdies demonsnate decreased activity ofhexosaminidase A. The child evemually becomes blind and dies at 3 years of age. Which of the fo llowing best describes the pathogenesis of neuronal degeneration in this patient? ***(A) Accumulation of unmetabolized substrate ***(B) Decreased utilization of metabolic end-product ***(C) Fonnauon of an abnormal metabolic end-product ***(D) Opening of mitochondr ial membrane pore ***(E) Synthesis o[ a novel glycosphingolipid
9 The answer is A: Accumulation of unmetabolized substrate. Tay-Sachs disease is the catastrophic infantile variant of a class of lysosomal storage diseases known as Gtv~ gangliosidoses. This ganglioside is deposited in neurons of the central nervous system due to a failure oflysosomal degradaLion and accumulation of an unmetabolized substrate. Gangliosides are glycosphingolipids that are presenL in the outer leaflet of the plasma membrane, particularly in neurons. The lysosomal catabolism of ganglioside GM2 is accomplished through the activit)' of the ~-hexosarninidases (A and B), which are composed of a and p subunits and require the participation of the GM2-activator protein. A deficiency in any of these components results in clinical disease. None of the other choices e~rplains the pathogenesis of tlus disease. ***Diagnosis: Tay-Sacbs disease
10 lf the parenl5 of the child described in Question 9 have a total of four sotlS and t\VO daughters, then, on average, how many of their children may be expected to be asymptomaLlc (ie., silent) carriers of tl1is gene mmation? ***(A) One child ***(B) Two children ***(C) Three children ***(D) Four children ***(E) Five children
10 The answer is C: Three <hildren. Tay-Sachs disease is inherited as an amosomal recessive trait and is predominantly a disorder of Ashkenazi jews, in whom the carrier rate is lin 30, and the natural incidence of homozygotes is l in 4,000 live newborns. In amosomal recessive diseases, on average, half of the o(fspring are expected to be heterozygmes and silem carriers of the gene mmation. ***Diagnosis: Tay-Sachs disease
11 A 4-year-old boy is admitted to the hospital with pneumon ia and respiratory distress. The nurses repon that the childs bowel movements are greasy and have a pungent odor. A sweatchiOJide test is posi tive. Which of the following mechanisms of disease is the most likely cause of steatorrhea in this child? ***(A) Abnmmal dietary intake ***(B) Bacterial overgrowth ***(C) Hyperbilirubinemia with kernlcterus ***(D) L1ck of pancreatic enzyme secretion ***(E) Obstruction caused by meconium ileus
11 The answer is D: Lack of pancreatic enzyme secretion. Cystic fibrosis (CF) is an autosomal recessive disorder affecting children, which is characterized by (l) chronic pulmonary disease, (2) deficient exocrine pancreatic function , and (3) mher complications of inspissated mucus in a number of organs, including the small intestine, the liver, and the reproductive n·act. The diagnosis of CF is most reliably made by the dem- 011Stration of increased concentrations o[ electrolytes in the sweat. The decreased chloride conductance characteristic of CF resulls in a failure of chloride reabsorption by the cells of the sweat gland ducts and, hence, w the accumulation of sodium chloride in !.he sweat. AU of the pathologic consequences of CF can be amibULed to the presence of abnormal ly thick mucus. Lack of pancreatic enzyme secretion in patients ''lith CF causes malabsorption and foul-smelling fatty stools (steawrrhea). The other choices do not address the underlying cause of malabsorption in patients with CF. ***Diagnosis: Cystic fibrosis
12 The patiem described in Question 11 carries mutations in the gene that encodes which of the following types of protein? ***(A) Membrane ion channel ***(B) Mitochondrial transport protein ***(C) NaT/K' A:rPase ***(D) Nuclear transport protein ***(E) Recepwr tyrosine kinase
1 Z The answer is A: Membrane ion channel. The gene responsible for cystic fibrosis (CF) encodes a large protein termed the cystic fibrosis transmembrane conductance regulator (CfTR). CFTR is a member of the AIP-binding family of membrane transporter proteins that constitutes a chloride chmmel in most epithelia. The secretion of chloride anions by mucoussecreting epithelial cells controls the parallel secretion of fluid and, consequently, the viscosity of the mucus. h is estimated th at 1 in 25 whiLes is a heterozygous car rier of the CF gene, and the incidence is lin 2,500 newborns. The most common cause of morbidity and mortality in patients with CF is pulmonary disease, secondary to chronic infections. Receptor tyrosine kinase gene mutations often lead to uncontrolled cell growth. ***Diagnosis: Cystic fibrosis
13 A lO~year· ol d child presents with xanthomas on the ex'tensor surfaces of his forearms. laboratory studies demonstrate a total serum cholesterol of 820 mgldl. The childs mother and maternal gran dfather also have elevated serum cholesterol. This patient most likely has murations in the gene that encodes which of the following proteins involved in lipid metabolism? ***(A) ApoE4 ***(B) Cholesterol hydroxylase ***(C) Chylomicron transport protein ***(D) High-density lipoprotein receptor ***(E) Low-density lipoprotein recepLOr
13 The answer is E: Low-density lipoprotein (LDL) receptor. Familial hypercholesterolem1a is an autosomal dominant disorder characterized by high levels of LDLs in the blood, accompanied by the deposition of cholesterol in arteries, tendons, and skin. It is one of the most common autosomal dominant disorders, and in its heterozygous form, it affects at least l in 500 adults in the United States. Only l in I million persons is homozygous for the disease. Familial hypercholesterolemia results from abnormalities in the gene that encodes the cell su rface receptor that removes LDLs fmm the b lood. Mutations in the other genes do not cause hypercholesterolemia. ***Diagnosis: Familial hypercholeste rolemia
14 A 10-momh-old boy \~.rho was adop ted from an orphanage in Eastern Europe p resents for a physical examination. His paren i:S believe that he is failing to meet developmental mHestones. The child is fair skinned and has blond hair. On physical examination, the patient is noted to have a "mousy" odor. Laboratory studies demonstrate an inborn error of amino acid metabolism. To prevent mental retardation, this patient should be placed on a special diet that lacks which of the following essential amino acids? ***(A) Isoleucine ***(B) Methionine ***(C) Phenylalanine ***(D) TI1reonine ***(E) Tryptophan
14 The answer is C: Phenylalanine. Phenylketonuria (PKU, hyperphenylalaninemia) is an autosomal recessive disorder characterized by progressive mental deterioration Ln the first few years of life due to high levels of circulating phenylalanine, secondary to a deficiency of phenylalanine hydroxylase. The disorder is based on a genetic defect, but its expression depends on the provision of a dietary consdment. The affected infant appears normal at birth, but mental retardation is evident willun a few months. lnfams with PKU tend to have fair skin, blond hair, and blue eyes because the inability to convert phenylalanine to tyrosine leads to reduced melanin synthesis. These patients exude a umousy" odor due to the formation of phenylacetic acid. The o·eatment of PKU involves the restriction of phenylalanine in the diet. None of the other essemial amino acids accumulates in patiems with PKU. ***Diagnosis: Phenylketonuria
15 Which of the following best describes the pathogenesis of mental retardation in Lhe patient described in Question 14' ***(A) Accumulation of unmetabolized substrate ***(B) Decreased utilization of metabolic end-product ***(C) Formation of an abnormal metabolic end-product ***(D) Increased utilization of metabolic end-product ***(E) Opening of miwchondrial membrane pore
15 The answer is A: Accumulation of unmetabolized substrate. Phenylalanine is an essendal amino acid that is de1ived e..'iclusively from the diet and is oxidized in the liver to tyrosine by phenylalanine hydroxylase (PAH). A deficiency in PAH results in both hyperphenylalaninemia and the fonnadon of phenylkewnes from rhe rransamination of phenylalanine. The excretion in the urine of phenylpymvic acid and its deJivatlves accoums for the original name of phenylkeLOnuria. However, it is now established that phenylalanine itself, rather than its metabolites, is responsible for the neurologic damage cemral to th]s disease. Thus, the term hyperphenylalaninemia is actually a more approptiate designation than PKU. None of the other choices e>q>lains the accumulation of phenylalanine in these patients. ***Diagnosis: Phenylketonuria
16 A 4-year-old boy is found to have extremely pliable skin. His parents note that he bruises easily. His joints can be hyperextended. Biochemical studies demonstrate a deficiency of lysyl hydro:>..)llase. Ultrastructural examination of a skin biopsy of this patiem would most likely reveaJ abnormalities associated with which of the following cell/ tissue components? ***(A) Actin-myosin filaments ***(B) Collagen fibers ***(C) Glycocalyx ***(D) lmermediate filaments ***(E) Mitochondria
16 The answer is B: Collagen fibers. Ehlers-Danlos syndromes (EDS) are a group of rare, autosomal dominam, inherited disorders o[ connective tissue that feature remarkable hyperelasticity and fragility of the skin, joint hypermobility, and often a bleeding diathesis. The common feamre of most types of ED$ is a generalized defect in collagen, including abnormalities in irs molecular stmctttre, synthests, secretion, and degradation. Patients typically can stretch the skin many centimeters, and uivial injuries can Lead lO serious wounds. Because sutures do not hold well, dehiscence of surgical incisions is common. Hypermobility of the joints allows unusual ex1ension and flex]on. Abnormalities would not be e>q)ected in the other cell/tissue components listed. ***Diagnosis: Ehlers-Danlos syndrome
17 A 25-year-olcl woman complains of recunent bone pain and increasing abdominal ginh. Physical examination reveals massive hepatosplenomegaly. Radiologic studies reveal several radiolucent bone defects. A bone marrow biopsy discloses enlarged cells with a fibrillar appearance reminiscent of "wrinkled tissue paper." Microscopic examination of a splenectomy specimen is shown. This paoem most Likely carries mutations in the gene that encodes which or the following rypes of hydro lyric enzymes? ***(A) Galactosidase ***(B) Glucosidase ***(C) Hexokinase ***(D) N-acetylgalactosaminidase ***(E) Neuraminidase
17 The answer is B: Glucosidase. Gaucher disease is characte1ized by the accumulation of glucosylceramidc, primati ly in the 1ysosomes of macrophages. The underlying abnom1ality in Gaucher disease is a deficiency in glucocerebrosidase, a type of lysosomal acid P-gtucosidase. The hallmark of this disorder is the presence of Gaucher cells, which are lipidladen macrophages that are characteristically present in the red pulp of the spleen, liver sinusoids, lymph nodes, lungs, and bone marrow. These cells are derived from the residem macrophages in the respective organs (e.g., KupiTer cells in the liver and aJveolar macrophages in the lung). Galactosidase gene mutations (choice A) are found in patients with Fabry disease. N-acetylgalactosaminidase gene mutations (choice D) are found in patients with Tay-Sachs disease. ***Diagnosis: Gaucher disease
18 Which of the following besL describes the pathogenesis of hepatosplenomegaly and bone pain in the patiem described in Question 1 7? ***(A) Accumulation of unmetabolized substrate ***(B) Decreased utilization of metabolic end-product ***(C) Formation of an abnonnal metabolic end-product ***(D) Increased utilization of metabolic end-product ***(E) Opening of mitochondrial membrane pore
18 The answer is A: Accumulation of unmetaboli:ted substrate. Glucosylceramide is a conunon core structure for membrane glycosphingolipids. The glucosylceramide that accumulates in Gaucher cells in the spleen, liver, bone marrow, and lymph nodes derives principally from the catabolism of senescent leukocytes. The membranes of these cells are rich in the cerebrosides, and when t11eir degradation is blocked by the deficiency of glucocerebrosidase, the intermediate metabolite, glucosylceramide, accumulates. The other biochemical pathways listed do not cause sphingolipid accumulation in patients with lysosomal storage diseases. ***Diagnosis: Gaucher disease
19 A neonate is born with severe motor dysfunction involving the lower extremities. Radiologic sntdies show that vertebral bodies in the lumbar region lack posterior arches. The vertebral defects are covered by a thin membrane. The space underneath the membrane contains a mass of tissue that is composed of meninges and spinal cord. The pa rents ask for info rmation regarding risks for similar birth defects in their future offspring. You mention that dieta ry supplememat:ion of the maternal diet has been shown to reduce the incidence of neural mbe defects. What is this substance? ***(A) Folk acid ***(B) Niacin ***(C) Thiamine ***(D) Vitamin 8 0 ***(E) Vitamin B12
19 The answer is A: Folic acid. Spina bifida is a congertital defect in the closure o[ Lhe spinal canal. Like other dysraphic disorders (anencephaly, meningocele, and menmgomyelocele), spina bifida is of polygenic otigin. Folic acid supplied in Lhe peli conceplional period lowers Lhe incidence of neural rube clefecls. ln 1998, the United States Food and Dmg Administration began requiling manufacturers of emiched flour, bread, and some OLher products LO supplement these foods with folate This mandate has been associated with a significant decrease in the incidence of neural tube defects. Folk acid deficiency can resulL in elevated serum Levels of homocysteine, a maternal risk factor for neural rube defects. Thiamine deficiency (choice C) causes beri-beti (polyneuropathy, edema, and heart failure). Vitamin B12 deficiency (choice E) causes megaloblastic anemia bm not neural tube defects. ***Diagnosis: Spina bifida
20 The paren ts of an infam with cleft lip and palate (iniam shown in rhe image) visit a genetic counselor to discuss the chance t.hat a similar birth defect will occur in their future offspring. ln addition LO teratogen exposure and multifactorial inher itance, whkh of the following is an imponam cause of this error of morphogenesis? ***(A) Down syTtdrome ***(B) First pregnancy before 25 years of age ***(C) Maternal-fetal Rh incompatibility ***(D) Structural chromosomal abnom1ality ***(E) Turner syndrome
20 The answer is D: Structural chromosomal abnormality. Cleft lip and cleft palate exemplify multifactorial inheritance in which multiple genes interact with various environmemaJ factors lO p roduce disease. On the 35th day of gestation, the frontal prominence fuses with the ma;...'illary process to form t.he upper lip. Disturbances in gene expression at this time (hereditary or environmemal) lead to interfe rence wilh p roper fusion and result in cleft lip, with or wi thout cleft palate ln addition to multifactorial inheritance, this developmemal anomaly may be part of a malfom1ation syndrome caused by teratogens (e.g., rubella and anticonvulsants). It is also often encountered in children \:vith chromosomal abnonnalities (conect answer). The incidence of cleft lip, with or without ddt palate, is 1 in 1,000, and the incidence of deft palate alone is 1 in 2,500_ lf one child is bom with a deft lip, the chances are 4% dmt the second child will exhibit the same defect. lf the first two children are affected , the risk of cleft lip increases to 9% for the third child. The more severe the anatomical defect, the greater the probability of tTansnutdng cleft lip will be. Whereas 75% of cases of deft Lip occur m boys, the sons of women with cleft lip have a four times higher 1isk of acquiting ll1e defect than the sons of affected fathe rs. None of the other choices are associated with a significantly increased risk of cleft lip. ***Diagnosis: deft Lip, multifactOrial inheritance
21 A 4-year-old boy is brought to the physician by his parents because he tires easily. Physical examination reveals weakness in the pelvic and shoulder girdles and enlargement of the child's calf muscle. Semm levels of creatine kinase are elevated. A biopsy of calf muscle shows marked variation in size and shape of muscle fib ers. There are foci of muscle fiber necrosis, with myophagocytosis, regenerating fibers, and fibrosis. Molecular diagnostic assays would most likely show alterations in the length of the primary transcript for which of the following muscle-associated proteins? ***(A) Actin ***(B) Desmin ***(C) Dystrophin ***(D) Glycogen phosphorylase ***(E) Myosin
21 The answer is C: Dystrophin. Duchenne muscular dystrophy (DMD) is a severe, X-linked condition characterized by progressive degeneration of muscles, particularly those of the pelvic and shoulder gi rdles. A milder form of the disease is known as Becker muscular dystrophy (BMD). Both DMD and BMD are caused by a deficiency of dystrophin, a member of lhe family of membrane cytoskeletal prmeins, which includes cx-acttnin and specnin. The protein is located on the cytoplasmic face of the plasma membrane of muscle cells and is linked to it by imegral membrane glycoprOleins (dystrophiD-associated glycoprotein complex), wh.ich in turn, are bound to extracellular laminln. lt has been proposed that the absence of dystrophin leads lO a defective membrane that is damaged dming contraction, an effect that predisposes to death of the myocyte. Serum levels of creatine kinase are increased. Glycogen phosphorylase gene mutations (choice D) are found in patients with McArdle disease. ***Diagnosis: Duchenne muscular dystrophy
22 What will be the lil<ely cause of death in the patiem described in Question 21? ***(A) Cardiomyopathy ***(B) Cerebrovascular disease ***(C) End-stage renal disease ***(D) Pulmonary saddle embolism ***(E) Res pi 1-ato ry i nsu £ficiency
22 The answer is A: Cardiomyopathy. The symptoms of Duchenne muscular dystrophy (DMD) progress with age. During the first year of Ilfe, the infanlS appear nonnal, but more than half failw walk by 18 months of age. More than 90% of afflicted boys are wheelchair bound by the age of ll years. In advanced disease. cardiac sympwms are almost universal, and cardiomyopathy is a common cause of dearJ1. The mean age at death m boys with DMD is 17 years. The other choices are unrelated tO DMD. ***Diagnosis: Duchenne muscular dysu·ophy
23 A 2.2-year-old man complains about his inability to conceive a child. On physical examination, the patient is noted to be tall (6 ft, 5 in} and exhibits gynecomastLa and testicular anophy. Laborawry srudies demonstrate increased serum levels of folU cle-stimuladng hormone. Cytogenetic studies reveal a chromosomal abnom1ality. What is the most common cause of this patiem's chromosomal abnormality? ***(A) Expansion of a trinucleotide repeat ***(B) Isochromosome fmmation ***(C) Meiotic nondisjunctLon ***(D) Nonreciprocal translocation ***(E) Rlng chromosome fom1adon
23 The answer is C: Meiotic nondisjunction. Klinefelter syndrome, or testicular dysgenesis, is related to the presence of one or more X chromosomes in excess of the nonnal male XY complement. Most persons with Klinefelter syndrome (80%) have one extra X chromosome (47 ,XXY karyotype). The additional X chromosome(s) arises as a result of n ondisjunction during gametogenesis. ln half o[ cases, nondisjunction occurs during patemal meiosis l, leading to a spenn containing both an X and a Y chromosom.e. FertiJizadon of a nmmal oocyte by such a spenn gives a zygote with a 4 7 ,Xt'\Y complement of chromosomes. Klinefelter syndrome occurs in l per 1,000 male newboms, which is roughly comparable to the incidence of Down syndrome. None of the other choices are associated with trisomy. ***Diagnosis: Klinefelter syndrome
24 A 35-year-old pregnant woman delivers a baby prematurely at 28 weeks of gestation. Shonly after binh, the neonate becomes short of breath , with intercostal retraction and nasal flati ng during respiration. The neonate is placed on a ventilator, but d.ies of respiratory insufficiency and intraventticular hemonhage. Microscopic examination of the lungs at autopsy is shown. The eosinophilic material lining the air spaces represents an accumulation of which of the fo llow1ng proteins? ·- - - ~ -· ***(A) Collagen ***(B) Dystrophin ***(C) Fibnn ***(D) Fibronectin ***(E) Laminin
24 The answer is C: Fibrin. The pathogenesis of respiratory disuess syndrome (RD$) of the newbom is innmately linked LOa deficiency of surfactant. Collapse of the alveoli (atelectasis) secondary to surfactant deficiency results in perfused but not ventilated alveoli, a situmion that leads to hypo>.:ia and acidosis. The leak of fib rin-rich Ouid into the alveoli from th e injured vascular bed cont1ibmes to the typical clinical and pathologic features of RDS. On gross examination, the lungs are dark red and airless. The alveolar ducts are lined by conspicuous, eosinophilic, fi.brin-ti ch, amorphous structures, tenned hyaljne membranes. Although collagen (choice A) , fibronectin (choice D), and laminin (choice E) are found in most tissues, they do not represent the major protein found in hyaline membranes. ***Diagnosis: Respiratory distress syndrome of the neonate
25 If the neonate described in Question 24 had survived, which of the following would be the most l ikely complication related to anO)(ia and acidosis? ***(A) Bilirubin encephalopathy (kernicterus) ***(B) Erythroblastosis fetalis ***(C) Necrotizing enterocolitis ***(D) Pulmonary embolism ***(E) Ventricular sepual defect
25 The answer is C: Necrotizing enterocolitis. The first symptom of RDS (usually appealing within an hour of birth) is increased respirato ry effort, ·with forceful intercostal retraction and the use of accessmy neck muscles. Despite advances in neonatal intensive care, tlle overall mortality of RDS ts about 15%. Necrotizing enterocolitis is the most common acquired gastrointestinal emergency in newborns and is thought to be related to ischemia of the intestinal mucosa. This injury is followed by bacterial colonization, usuaUy with Clo.sl1idium difficile. The lesions vary from those of typical pseudomembranous enterocolitis to gangrene and perforation of the boweL None of the other choices are related to respiratory insufficiency. ***Diagnosis: Respiratory distress syndrome of the neonate, enterocolitis
26 A 16-year-old girl complains that she has not started menstmating like other girls her age. The patient is short (4 ft, 11 in) and has a duck-webbed neck. Physical exammation reveals widely spaced nipples and poor breast developmem. If this patient's genetic disease was caused by nondisjunction during mitosis of a somatic cell in the early stages of embryogenesis, which of the following is the patients most likely kmyotype? ***(A) 45,X ***(B) 45 ,X/-t6 ,X-\: ***(C) 45,X/46,XY ***(D) 47,XX,+21 ***(E) 47)CXY
26 The answer is B: 45,X/46,XX. Mitotic nondisjunction may involve embryonic cells during early stages of development and result in chromosomal aberrations. This condition in which the body contains two or more karyotypically different cell lines is called mosaicism. Mosaicism involving sex chromosomes is found in patients with Turner and Klinefelter syndromes. Turner syndrome re fers to the spectrum o[ abnormalities that resuh from the presence of complete or partial monosomy of the X chromosome in a phenotypic female. rlalf of women vvi1h Turner syndrome lack an entire X chromosome (monosomy X, choice A). The remainder of women with Turner syndrome are mosaics or display s tructural aberrations of th e X chromosome. Mosaics characterized by a 45,X/46,XX karyotype (15%; choice B) tend to have milder phenQ[ypic manifes tations. b1 about 5% of patien ts, the mosaic karyotype is 45,X/46,)CY (choice C). A patient wi th the 47,XX.+21 karyotype (choice D) is a female with Do'\\rn syndrome. The 4 7 .~'\'Y ka1yotype (choice E) is a feature of Klinefelter syndrome. ***Diagnosis: Turner syndrome
27 A34-year-old woman in her second pregnancy delivers a female neonate with severe generalized edema and jaundice A CBC of the neonate shows hemolytic an.emia. Subsequent workup of the mOlher and the newborn reveal an Rh-incompadbility Transplacental passage of which of the following proteins is the ptincipal cause of anasarca and jaundice in this neonate? ***(A) Complemem C3 ***(B) Complement C4 ***(C) IgG ***(D) lgM ***(E) Interferon-a.
27 The answer is C: lgG. E1ythroblastosis fetalis is an antibodymediated hemolyric disease dmt affects the ferus in utero. It is usually caused by transplacenr.al passage of maternal an tibodies w antigens v:pressed on fetal RBCs. The introduction of Rh-posidve fetal eryth rocytes (>1 ml) into the circulation of an Rh-negative mQ[her at the time of delivery sensitizes her to the D antigen. vVhen the antigen-sensitized mother again bears an Rh -posidve fetus, much smaller quanti ties of fetal D antigen elicit an increase in antibody titer. ln contrast to IgM (choice D), IgG antibodies are small enough to cross the placenta and thus produce hemolysis in the fetus. This cycle is exaggerated in multiparous women , and the severity of erythroblastosis tends to increase progressively with each succeeding pregnancy ***Diagnosis: Hemolytic anem1a of the neonate, erythroblastosis fetalis
28 The parents of a 2-year-old boy with hyposadias (urethra opens on the vemral aspect of the penis) visit a genetic counselor to discuss the chances that a similar binh defect \Viii occur in their future offspring. This birth defect shmvs which of the following patterns of inheritance? ***(A) Autosomal recessive ***(B) Autosomal dominant ***(C) Mulrifacroria1 ***(D) X-linked dominant ***(E) X-linked recessive
28 The answer is C: Multifactorial. The inheri tance of a number of binh deJects is multifactorial. Most normal human Lraits are inhetited neither as dominant nor as recessive mendeUan attributes, but rather in a more complex manner. For example, multifactorial inheritance determines imelligence, height, skin color, body habitus, and even emotional disposition. Similarly, most of the common chronic disorders of adults represent multifactorial genetic diseases and are well known to "run in families ." Such maladies include diabetes, atherosclerosis, and many forms of cancer and arthritis, and hypertension. The inheritance of a number of birth defects is also multifactOJial (e.g., cleft Up and palate, pyloric stenosis, hypospadias, and congenital heart disease). The concept of multi factOJia l inheritance is based on the notion that multiple genes interact with various environmental facto rs to produce disease in an individual patient. Such inheritance leads to familial aggregation that does not obey simple mendelian rules (see choices A, B, D, and E). As a consequence, the inheritance of polygenic diseases is smdied by the methods of population genetics, rather than by the analysis of individual family pedigrees. ***Diagnosis: Hypospadias, multifacwrial inheritance
29 A 42-year-old woman gives birth to a neonate with multiple congenital abnonnalities. Physical findings included a flat facial profile, slanted eyes, epicantha1 folds, Brushfield spots, short nose, short neck, dysplastic ears, clinodactyly, a large prottuding tongue, and a pronounced hearr murmur. \oVhat is the most common cause of this developmental birth disease? ***(A) Chromosomal deletion ***(B) Chromosomal translocation ***(C) Expansion of trinucleotide repeat ***(D) Frameshift point mutation ***(E) Nondisjunction
29 The answer is E: Nondisjunction. Nondisjunction during the firsL meiotic division of gametogenesis accoums for most (92% to 95%) paLiems vvith Down syndrome who have trisomy 21. The e..xtra chromosome 21 is of maternal origin in about 95% of Down syndrome children. Translocation of an e"-'tra long am1 of chromosome 21 to another acrocemric chromosome (choice B) causes abom 5% of cases of Down syndrome. The other choices are unrelared to trisomy 21. ***Diagnosis: Down syndrome, trisomy 21
30 As an adult, the brain of the patient described in Question 29 will show histopathologic changes that are seen in patients \Vith which of the following neurologic diseases? ***(A) Alzheimer disease ***(B) Huntington disease ***(C) Krabbe disease ***(D) Multiple sclerosis ***(E) Parkinson disease
30 The answer is A: Alzheimer disease. One of the mosrintriguing neurologic featmes o[ Down syndrome is its association with Alzheimer disease. The morphologic lesions characteristic o[ Alzheimer disease progress in aU patients with DO\vn syndrome and are universally demonstrable by age 35 years. These changes in the brain include (1) granulovacuolar degeneration, (2) neurofibrillary tangles, (3) senile plaques, and (4) loss of neurons. The senile plaques and cerebral blood vessels of both Alzheimer disease and Dovm syndrome always contain an amyloid composed of the same fibrillar protem (I)-amyloid protein). The other chokes are unrelated to Down syndrome. ***Diagnosis: Down syndrome
31 A 50-year-old man wi th a history of type 2 diabetes mellirus asks about the chances that his children v.rill inherit this metabolic disorder. The patient is told that he has a genetic disease that shows which of the following patterns of inheritance? ***(A) Autosomal dominant ***(B) Autosomal recessive ***(C) Multifactorial ***(D) X-linked dominant ***(E) X-linked recessive
31 The answer is C: Multifactorial. Most of the common chronic disorders of adults represent multifactorial genetic diseases that tend to "run in families.·· Such maladies include djabetes, atherosclerosis, and many forms of cancer, anhritis, and hypertension. Fragile X syndrome and Duchenne-Becker muscular dystrophy are examples of X-linked recessive genetic diseases. ***Diagnosis: Diabetes mellims
32 A 2.5-year-old man with a history of autism and mental retardation is seen by a genetic counselor. The man has coarse facial fearures , an increased head circumference, and macro-orchidism. His maternal uncle is similarly affected. After funher evaluation, a diagnosis of fragile X syndrome is rendered. What is the most likely underlying cause of this patients genetic disease? ***(A) Chromosomal nondicsjunction ***(B) Chromosome inversion ***(C) Expansion of trinucleotide repeat ***(D) Frame-shift mutation ***(E) Nonreciprocal translocation
32 The answer is C: Expansion of trinucleotide repeat. FragLle X syndrome, the most common cause of inherited mental retardation, is caused by expansion of a CGG trinucleotide repeat in a noncoding region immediately adjacent to the FMRJ gene on the X chromosome. Ln a poorly understood manner, the e>..rpanded CGG repeat silences the FMRl gene by methylation of its promoter. The abnormal repeat is associated with an inducib le "fragile sire·· on the X chromosome, which appea rs in cytogenetic studies as a nonstaining gap or chromosomal break. The male newborn afflicted with the Cragile X syndrome appears nom1al, but dtning childhood, characteristic features appear, including an increased head circumference, facial coarsening, joint hyperextensibUity, enlarged testes, and abnormalities of the cardiac valves. Mental retardation is profound, '"'ith IQ scores varying From 20 to 60. A significant proportion of autistic male children carry a fragile X chromosome. The other choices do not cause fragile X syndrome. ***Diagnosis: fragile X syndrome
33 A 2.8-year-old man presents to the emergency room l h our after experiencing crushing substernal chest pain. U:lboratory studies and ECG confirm the diagnosis of acute myocardial infarction. The patient dies 24 hours later of cardJac arrhythmia. Thts patient most likely had which of the following genetic diseases? ***(A) Adult-onset (type 2) diabetes ***(B) a 1-Antitrypsin deficiency ***(C) Familial hypercholesterolemia ***(D) Marfan syndrome ***(E) Niemann-Pick disease
33 The answer is C: Familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder caused by mutations of the gene encoding the LDL receptor. lt is one o[ the most common autosomal dominant disorders , affecting 1 in 500 adults in the United States. The gene defect affects the uptake of LDL in the liver, causing hypercholesterolemia. Clinically, the disease presents as severe atherosclerosis, which usually becomes symptomatic at an early age. Diabetes mellitus (choice A) also causes accelerated atherosclerosis bm rarely at this age. Marfan syndrome (choice D) is associated with dissecting aortic aneurysm. Niemann-Pick disease (choice E) is a hereditary lysosomal storage disease. ***Diagnosis: Familial hypercholesterolemia
34 A 5-year-old boy presents with a maculopapular rash. On physical examination, the rash affects the palms and soles. Cracks and fissures are noted around the mouth and anus. There is funduscopic evidence of interstitia] keratitis. Mild hepatosplenomegaly is present. The anterior tibial bones exhibit an outward curvature. What is the mostli.kely etiology of these clinicopathologic findin gs? ***(A) AlDS ***(B) Cytomega1ovims ***(C) Herpes ***(D) Syphilis ***(E) Toxoplasmosis
34 The answer is D: Syphilis. The acronym TORCH refers to a complex of similar signs and symptoms produced by fetal or neonatal infection with a variety of microorganisms, including Toxoplasma (T), Rubella {R), Cytomegalov irus (C), and Herpes {H). The letter "0" represents "mhers" including congenital syphilis The acronym was coined to alert pediatricians w the faCl that infections in the fetus and newborn by TORCH agents are usually indistinguishable from each other and that testing for one of the four major TORCH agents should include testing [or the other three and others as well. The organism that causes syphilis, Treponema pallidum, is transmitted to the fetus by a mother who has acquired syphilis during pregnancy. A maculopapular rash is a common early finding in congenital syphilis. The most common osseous lesion in congenital syphilis is periostitis and outward curving of the anterior tibia (saber shins). Flat raised plaques (condylomata lata) around the anus and female genitalia may develop early or after a few years. The diagnosis of congenital syphilis is suggested by clinical findings and a history of maternal infection. None of the other pathogens cause these clinicopathologic findings. D.iagnosis: TORCH syndrome, syphilis 35 The answer is A: Aplasia . Aplasia is the absence of an organ coupled with perslstence or the organ anlage or a mdiment. Thus, aplasia of the lung refers to a condition in which the main bronchus ends blindly in nondescript tissue composed of rudimentary ducts and connective tissue. Dysraphic anomalies (choice C) are defects caused by the failure of apposed structures to fuse. Hypoplasia (cho ice D) refers to reduced size owing to the incomplete development or all or part of an organ. Examples include microphthalmia and microcephaly Involution failures (chmce E) reOect the persistence of embryonic or fetal strucmres that should involute at cen.ain stages of development A persistent th)'t'oglossal duct is the result of incomplete involution of the tract that connects the base of the tongue witb the thyroid ***Diagnosis: Pulmonary aplasia
35 A 3-year-old boy djes in an automobiJe accident. At autopsy, the right lung is markedly shrunken. Dissection shows that the right main stem bronchus ends blindly in nondescript tissue composed of rudimentary ducts and connective tissue. This finding represents an example of which of the following errors of morphogenesis? ***(A) Aplasia ***(B) Attesia ***(C) Dysraphic anomaly ***(D) Hypoplasia ***(E) Involution failure
36 The answer is 8: Atresia. Atresia refers to defects caused by the incomplete formation of a lumen. Many hollow organs originate as strands and cords of cells whose centers are progranm1ed to die, thus forming a central cavity or lumen. Atresia of the esophagus is characterized by partial ocdusion of the lumen, which was not fully established in embryogenesis. Dysplasia (choice C) is caused by abnormal organization of cells into tissues, which is a situation that results in abnonnal hlc;togenesis. Tuberous sclerosis is a striking example of dysplasia, in which the brain contains aggregates of nonnally developed cells ananged into grossly visible "mbers." Ectopia (choice E) is an anomaly in which an organ is outside its normal anatomic site. ***Diagnosis: Esophageal atresia
36 The mother o[ a newborn boy is alanm:d that her baby regurgicaLes at every feediJl g. An endoscopic examination reveals that the child's esophagus is almost completely occluded. This finding represents an example of which of the following errors of morphogenesis? ***(A) Aplasia ***(B) Atresia ***(C) Dysplasia ***(D) Dysraphic anomaly ***(E) Ectopia
37 The answer is A: Choristoma. Chorlstomas are minute or microscopic aggregates of normal tissue in aberrant locations. Choristomas are represented by rests of pancreatic tissue in the wall of the gastrointestinal tract or of ad renal tissue in the renal conex. By contrast, hamartomas (choice B) represent focal, benign overgrowths of one or more of the mature cellular elements of a normal tissue, often with one element predominating. Hemangiomas (chmce C) are the most frequently encountered tumors in childhood. ***Diagnosis: Choristoma
37 An 87 -year-old woman dies peacefctlly in her sleep. At autopsy, a rest of pancreatic tissue is identified in the wall of the lower esophagus. This finding represents an example of which oflhe following congenitalmmor-llke conditions? ***(A) Choristoma ***(B) Hamartoma ***(C) Hemangioma ***(D) Papilloma ***(E) Teratoma
38 The answer is D: Lecithin. Inmlaturity of the lungs poses one of the most. common and immediate threats to t.he viability of the low birth weight. infam because the lining cells o[ the feral alveoli do noL difTerentiate until ian~ pregnancy. Alveoll are maintained in the e~,.:panded stare, in pan, by d1e presence of pulmonary surfactam. This material, which is produced by type 1 L pneumocytes, is a complex mixture of several phospholipids, 75% phosphatidykholine (lecithin) and 10% phosphatidylglycerol. The concemration of lecithin increases rapidly at the beginning of the third utmester and, thereafter, Jises rapid1y to reach a peak near term. Maturity of the fetal lung can be assessed by measuring pulmonary surfactam released imo the amniotic fluid. A lecithin-to-sphingomyelin ratio above 2:1 implies t.hat the fetus will survive \Vit.hom developing respiratory distress syndrome. Alpha-retoprotein (choice B) is used to monitor for anencephaly. ***Diagnosis: Ery1hroblasLOsis fetalis
38 A 3D-year-old pregnam woman visits her obstetrician for prenatal care and eventual delivery The patiem volunteers that two of her three children had "yellow jatmdice" at birth. Her youngest girl had been severely jaundiced and had been given two blood transfusions. Prenatal laboratory tests indicate that the mother is blood type 0, Rh negative, whereas her husband is blood rype A, Rh positive. The obstetrician samples amniotic fluid aL 36 weeks of gestation to ascertain whether the fetus is rnamre enough for pretem1 delivery Quantitative analysis of which of the fo llowing was most likely used as an indicawr of fetal lung maturity? ***(A) Absorbance aL 450 nm ***(B) AJpha-ferop rmein ***(C) Creatinine ***(D) l ecithin ***(E) Total protein
39 The answer is B: Congestive heart failure. Erythroblastosis fetalis is a hemolytic disease of the newborn caused by maternal antibodies against fetal erythrocytes. Erythroblastosis fetalis does not ordmarily occur dUJing the first pregnanC)', because the quamity of fetal blood necessary to sensitize the mmher is imroduced imo her circulation only at the dme of delivery. too late lO affect the ferus. However, when the sensitized mother again bears an Rh-positive fetus, much smaller quantities of fetal D antigen can elicit an increase in lgG antibody titer. This cycle is exaggerated in multiparous women, and the sevetity of erythroblastosis tends to increase progressively with each succeeding pregnancy. However, even after multiple pregnancies, only 5% of Rh-negative women are ever delivered of infants with ef)'lhroblastosis fetalis. The severily of etythroblastosis fetalis varies from a mild hemolysis to fatal anemia, and the pathological findings are det.ennined by the extem or the hemolytic disease. Hydrops fe taHs refe rs to the most serious form of etythroblastosis fetalis, and is characterized by severe edema secondary to congestive heart failure caused by severe anemia. The od1er choices do not cause of anasarca in erythroblastosis fetal is. ***Diagnosis: Erythroblastosis fetalis, hydrops fetalis
39 The patient described in Question 38 delivers a female at 37 weeks of gestation with evidence of severe generalized edema (neonate shown in the image)_ The baby is given exchange transfusions with Rh-negmive cells but subsequently dies. vVhich of the follov.l}.ng best describes the pathogenesis of anasarca in thi.s baby? ***(A) BiJirubin encephalopathy ***(B) Congestive heart failure ***(C) Nephrotic syndrome ***(D) Respiratmy distress syndrome ***(E) Rupture of the liver
40 The answer is D: Spontaneou.s resolution. Birth injury spans the spectmm from mechanical trauma to anoxic damage. Some birth injuries relate to poor obstetric manipulation, whereas many are unavoidable sequelae of routine delivery. Binh inj uries occur Ln about 5 per 1,000 live births. Factors that precUspose to birth injury include cephalopelvic disproportion, dystocia (dLfficultlabor), prematurity, and breech presentation. Cephalohemmoma is defined as a subperiosteal hemorrhage that is confined to a single cranial bone and becomes apparem \vithin the first few hours after binh. It may or may not be assodated wilh a linear fracture of the underlying bone. Most cephalohemawmas resolve without complicmion and require no Lreatmem. ***Diagnosis: Cephalohemawma
40 An H)-year-old woman delivers a male neonate following a difficult labor and delivery (dystocia). The baby appears vigorous at binh (Apgar score = 9), but a cephalohematoma is apparent 2 hours later. ACT scan of the baby's head shows subperiosteal hemonhage over one of the calvarial bones. What is the most likely outcome of this complication of labor and delivery? ***(A) Facial nerve palsy ***(B) Kernkterius ***(C) Respiratory distress syndrome ***(D) Sponlaneous resolution ***(E) Subaraclmoid hemorrhage
41 The answer is C: Encephalopathy. Kemicte:rus, also termed bilirubin encephalopathy, is defined as a neurological condition associated with severe jaundice and characterized bv bile . ' staining of the brain, particularly o[ the basal ganglia, pontine nuclei, and dentate nuclei in the cerebellum. Kernicterus (German: kem , nucleus) is essentially confined to newborns with severe unconjugated hyperbilirubinemia, usually related to erythroblastosis fetalis. The bilirubin derived from the desuuction of erythrocytes and the cambolism of the released heme is not easily conjugated by the immamre liver, which is deficient in glucuronyl transferase. The developmem of kemictems is directly related w the level of unconjugaLed bilirubin and is rare in tem1 infants when serum bilirubin levels are below 20 mg/ dL Premamre infants are more vulnerable w hyperbilimbinemia and may develop kernictems at levels as low as 12 mgldL Bilimbin is thought w injure the cells of the brain by imerfe1ing with mitochondrial function. Severe kernicterus leads initialJy w loss of the stanle reflex and athetoid movements, which in 75% progresses to letl1argy and death. Most su1viving infants have severe choreoathetosis and mental retardation~ a minority have varying degrees of intellectual and motor retardation. Exchange transfusions may keep the maximum serum bilimbi11 at an acceptable level. However, phototherapy. which converts the to;.dc unconjugated bilirubin into isomers that are nontoxic and ~xcreted in the urine, has greatly reduced the need for exchange LTansfusions. The other chokes are not complications of untreated hyperbilimbinemia in newborns. ***Diagnosis: Kernic terus, physiological jaundice
41 A 42-year-old woman in her third pregnancy delivers a female neonate at 30 weeks of gestation. The baby develops jaundice within 2 days. The unconjugated serum bilirubin is 15 mgldL Which of the following is the most serious complication of untreated hyperbilirubinemia in this neonate? ***(A) Acme pancreatitis ***(B) Bronchopulmonal)' dysp lasia ***(C) Encephalopathy ***(D) Gallstones ***(E) Hemolytic anemia
42 The answer is B: Embryonic lethality. lf a conceptus is exposed to harmful exogenous lnnuences, the noxious agent exerts the same effect on all blastomeres and also causes death . Thus, either a conceptus dies or development proceeds unintenupted, since the interchangeable blastomeres replace lhe loss. As a rule, exogenous toxins acting on preimplantationstage embryos do not produce errors of morphogenesis and do not cause malformations. The most common consequence of toxic exposure at the preimplantation stage is death of lhe embryo, which often passes unnoticed or is perceived as heavy, albeit delayed, mensm1al bleeding. Approximately 30% of fenilized ova are aboned spontaneously, without the woman being aware that pregnancy had occurred. Placenta accreta (choice C) is an abnormal adherence of the placenta to the underlying uterine walL The other choices are errors of morphogenesis that rnanifesr at later stages of development. ***Diagnosis: Spontaneous abortion
42 A 27-year-old woman presents for a pregnancy test. She Tecalls drinking heavily during the week in v,rhich she may have conceived. What is the most likely consequence of toxic exposure to the conceptus during early (preimplantation) development? ***(A) Conjoined £wins ***(B) Embryonic lelhalily ***(C) Placenta accreta ***(D) Neural tube defect ***(E) Vemricular-septal defect
"42 The answer is B: Embryonic lethality. If a conceptus is exposed to harmful exogenous influences, the noxious agent exerts the same effect on all blastomeres and also causes death. Thus, either a conceptus dies or development proceeds uninterrupted, since the interchangeable blastomeres replace the loss. As a rule, exogenous toxins acting on preimplantation- stage embryos do not produce errors of morphogenesis and do not cause malformations. The most common consequence of toxic exposure at the preimplantation stage is death of the embryo, which often passes unnoticed or is perceived as heavy, albeit delayed, menstrual bleeding. Approximately 30% of fertilized ova are aborted spontaneously, without the woman being aware that pregnancy had occurred. Placenta accreta (choice C) is an abnormal adherence of the placenta to the underlying uterine wall. The other choices are errors of morphogenesis that manifest at later stages of development. ***Diagnosis: Spontaneous abortion
1 A 60-year-old man with a histmy o f multiple myocardial L...- infarcts is hospi talized for shortness of breath. Physical examination reveals marked j ugular distension, hepatomegaly, ascites, and pitting edema. A chest X- ray reveals cardiomegaly. The patient subsequently dies of cardiorespiratory failure . Examination of the lungs at autopsy would most likely disclose which of the following pathologic changes? ***(A) Diffuse alveolar damage with hyaline membranes ***(B) Intra-alveolar pumlem exudate ***(C) Lymphocytic interstitial pneumonitis ***(D) Pulmonary aneriopathy with plexifmm lesions ***(E) Vascular congestion and hemosiderin-laden macrophages
1 The answer is E: Vascular con.gestion and hemosiderin-laden ......_ manophages. Left ventricular failure leads Lo chronic passive congestion of the lungs. Blooclleaks from the congested pulmonary capillaries imo the alveoli. Alveolar macrophages degrade RBCs and accumulate hemosiderin. These hemosidetin-laden macrophages are called heart failure cells. Diffuse alveolar damage with hyaline membranes (choice A) is a feature of adult respiratmy distress syndrome. Pumlent exudate (choice B) is observed in bacte1ial pneumonia. Lymphocytic interstitial pneumonitis (choice C) is characteristic of viral pneumonitis. Plexiform lesions (choice D) are typically seen in patien ts with pulmonary hypenension. ***Diagnosis: Congestive hean failure, pulmonary edema
2A 92-year-old woman is brought unconscious to the emergency room from a nursing home. Her blood pressure is 70/30 mm Hg. She is febrile (38°C/l00.5°F) and tachypneic. Laboratory studies demonstrate a WBC count of 22,000/)..tl with 92% neun·ophils. U1inalysis reveals numerous Gram-negative organisms. Which of the folJowing most likely accounts for this patient's signs and symptoms? ***(A) Anaphylactic shock ***(B) Cardiogenic shock ***(C) Hypovolemic shock ***(D) Neurogenic shock ***(E) Septic shock
2 The answer is E: Septic shock. Septic shock results from a systemic inflammatory response syndrome that leads to multiple organ dysfunction and hypotension. Clinical features include two or more signs of systemic inflammation (e.g., fever, tachycardia, tachypnea, leukocytosis, or leukopenia) in the setting of a known cause of inflammation. These processes often p rogress to multiple organ dysfunction syndrome in critically Lll patients. Septicemia with Gram-negati.ve organisms is the most common cause of septic shock Anaphylactic shock (choice A) occurs as a consequence of a systemic type I hypersensitivity reaction. Neurogenic shock (choice D) can follow acme injury to the brain or spinal cord , which impairs Lhe neural control of vasomotor wne, leading to generalized vasodilation. Cardiogenic shock (choice B) is a feamre of advanced hcan fai.lure. Hypovolemic shock (choice C) occurs fo llmving blood loss. ***Diagnosis: Septic shock
3 A 21-year-old pregnam woman expe1iences abruptio placentae at 37 weeks o[ gestation and develops severe vaginal bleeding that is difficult to control. Five momh.o:; later. the patient presents with pro[ound lethargy. pallor, muscle weakness, failure of lactation, and amenonhea. Which of the following best o..'Plains the pathogenesis of pituitary insufficiency in this patient? ***(A) Abscess ***(B) Embolism ***(C) In[arction ***(D) Passive hyperemia ***(E) Thrombosis
3 The answer is C: Infarction. Hypotension caused by postpartum bleeding can , in rare cases, lead to infarction of the #NAME? because its enlargement during pregnancy renders it vulnerable to a reduction in blood !1ow. None of the other choices cause clinical featu res of pan-hypop ituitaJism. ***Diagnosis: Sheeh an syndrome, pituitary infarction
4 A 62-year-old man with a h]story of hypertension is rushed .....__ LO the emergency room with severe "tearing pain" of the anterior chest. His blood pressure is 80/50 mm Hg. Physical examination shows pallor, diaphoresis, and a murmur of aonic regurgitation. Laboratory studies and ECG show no evidence of acute myocardial infarction. Four hours later, the patient goes into cardiac arrest. An ECG reveals dectromechanicaJ dissociation. Which of the foUowing best explains the pathogenesis of cardiac tamponade in this patient? ***(A) Disseminated intravascular coagulation ***(B) Embolism ***(C) Hemorrhage ***(D) Passive hyperemia ***(E) Thrombosis
4 The answer is C: Hemorrhage. Pericardia] J1uid may accu- .__ mulate rapiclly, panicularly •.vith. hemorrhage caused b>• a n.tptured myocardial infarct, dissecting aonic aneurysm (seen in this patient), or trauma. In these circumstances, the pressure in the pericardia] cavity exceeds the filling pressure of the he an, a condition tetmed cardiac tamponade. The term e lectromechanical dissociation refers to a heart rhythm that should produce a pulse, bUL does not. The most common cause of this condiuon is hypovolemia The resulting precipitous decline in cardiac ompur is often fa tal. The pathogenesis of dissecring aortic aneurysm in most instances can be tTaced w a weakening of the aonic media (cystic media] necrosis). Most patients have a history of hypertension. Disseminated intravascular coagulation (choice A) refers to widespread ischemic changes seconda1y to microvascular thrombi. Passive hyperemia (choice D) refers Lo the engorgement of an organ vvith venous blood. ***Diagnosis: Dissecting aonic aneurysm
5 A 58-year-old woman is brought to the emergency department 4 hours after vomiting blood and expe1iencing bloody stools. The pariem was diagnosed with alcoholic cin·hosis 2 years ago. Endoscopy reveals large esophageal varices, one of which is actively bleeding Which of the following best explains the pathogenesis of dilated esophageal veins m this patient? ***(A) Decreased intravascular oncotic pressure ***(B) Increased capilla~y pem1eability ***(C) Increased intravascular hydrostatic pressure ***(D) Vasoconstriction of arterioles ***(E) Vasodilatation of capillaries
5 The answer is C: Increased intravascular hydrostatic pressure. This patient wilh alcoholic cirrhosis has ponal hypenension (increased hydrostatic pressure) and bleeding esophageal valices. Massive hematemesis is a fTequent cause of death in patients with esophageal va1ices. Decreased intravascular oncotic pressure (choice A) contributes to the development of ascites in patients with cirrhosis but not to the development of esophageal valices. ***Diagnosis: Esophageal varices, hematemesis
6 A 69-year-old retired man is brought to the emergency department because of the sudden onset of left-sided chest pain, which is exacerbated upon inspiration. Physical examination reveals dyspnea and hemoptysis. His temperamre is 38°C (101 °f), pulse 110 per minute, respirations 35 per minute, and blood pressure 158/100 mm Hg. A lateral chest wall friction rub is p resent on auscultation. The left leg is markedly edematous with a positive Homans' sign. A chest X-ray reveals a left pleural effusion. What is the most likel)' cause of this patiems pulmonary condition? ***(A) Congesdve heart failure ***(B) Cor pulmonale ***(C) Mitral stenosis ***(D) Subacute endocarditis ***(E) Thromboembolism
6 The answer is E: Thromboembolism. This patiem with mild congestive hean faLlure developed pulmonary embolism . Small pulmonary emboli rarely cause infarctions because of the dual blood supply 1.0 the lungs and because oxygen can diffuse from the alveoli into lung tissue. Symptoms depend upon the extent of blockage of the pulmonaxy anerial tree , whether there is already cardiopulmonary disease, and whether pulmonary infarction occurs. The othe r choices do not induce these pleural signs and sympwms. ***Diagnosis: Pulmonmy thromboembolism
7 A 22-year-old cotL.c;truction worker falls 30 ft and fracmres .__ several bones, including his femoral shafts. Six hours later, the patiem develops shortness of bream and cyanosis. Which of me following hemodynamic disorders best explains the pathogenesis of shock in this patient? ***(A) Acute myocardial infarction ***(B) Deep venous thrombosis ***(C) Fat embolism ***(D) Paradmacal embolism ***(E) Septic shock
7 The an.swer is C: Fat embolism. Fat emboli origmate from adipose tissue in the medulla of fTacrnred long bones. Fat carried by venous blood reaches the lungs, filters through 1.he pulmonary circulation, enters anerial blood, and is disseminated throughout the body. The occlusion of cerebral capillaries is accompanied by petechial hemorrhages in the brain and is the most important complication of fat embolism. Acme myocardial infarction (choice A) would be unlikely in a 22-year-old patient. Deep venous thrombosis (choice B) and septic shock (choice E) would be unlikely within this time frame. Paradoxical embolism (choke D) refers w emboll that mise in the venous circulation and bypass the lungs by rraveling through a11 incompletely closed foramen ovale, suhsequemly entering the arterial ci rculation. ***Diagnosis: Fat embolism
8 A 20-year-old woman presents to the emergency room complaining of having had a severe headache for 4 hours. Physical examination reveals numerous small red spots on Lhe e..'<LremiLies and a stiiT neck. Her temperamre is 38. 7°C (103°F). Lmnbar puncture returns purulent ftuid, with segmented neutmphiJs and Gram-negative organisms resembling meningococci. A few hours later, me patient goes into shock and becomes comatose. Severe endothelial injury in thls patient ts primarily mediated by which or Lhe following proteins? ***(A) 0.-Fetoprotein ***(B) lgG ***(C) Imerferon-y ***(D) Transfonning growth factor-~ ***(E) Tumor necrosis facwr-a
8 The answer is E: Tumor ne<rosis factor-a (TNF·a ). Septicemia with Gram-negative organisms is the most common cause of septic shock. The invading bacteria are responsible for the release of endotoxin, a lipopolysaccharide (l.PS). On entry into the circulation, LPS binds to the surface of monocyt.es/ macrophages. The CD 14 recognition comple.x mediates signaling through activation of nuclear transcliption factorkappa B (NF-KB) and upregulates the expression of TNF-a. In septic shock, this protein is released in great excess, resulting in effects that are often LethaL None of the other mediators cause severe injury to vascular endothelium in patients with septic shock. ***Diagnosis: Meningitis, septic shock
9 A 69-year-old man is brought to the emergency room complaining of visual difficulty and weakness. On physical examination, the patient is aphasic wi th a right-sided henliplegia. Retinal hemonhages are seen bilaterally. You suspect that a thromboembolus coursed to the left middle cerebral artery and smaller emboli traveled w the rednal arteries. Which of the follO\ving anatomic sites is the most likely source [or these emboli in this patient? ***(A) Adrenals ***(B) Deep leg veins ***(C) Heart ***(D) Uver ***(E) Lungs
9 The answer is C: Heart. The hean is the most common source of anetial thromboemboli, which usually arise from mural thrombi or diseased valves. These emboli tend to lodge at points where the vessel lumen narrows abmptly (e.g., at bifurcations or in the area of an aLherosclermic plaque). The viability of the tissue supplied by tl1e vessel depends on the availability of collateral circulation and on the fate of the embolus itself. Paradoxical emboli from the right side of the circuladon are exceedingly rare. ***Diagnosis: Cerebral embolism, stroke
10 The body of a 78-year-old homeless man is broughl to the coroners office. Histologic examination of the lungs under polmized light is shown. Which of l.he following is the most likely cause of the birefringence observed in this pulmonary lesion? ***(A) Alcoholism ***(B) Asptradon of mmeral oil ***(C) Baclcrial pneumonLa ***(D) Cocame abuse ***(E) Imravenous dmg use
10 The answer is E: Intravenous drug use. Embolism is the passage Lhrough the venous or anerlal circulations of any material capable of lodging in a blood vessel and, thereby, obstructing Its lumen. Intravenous drug abusers who use calc as a camer ror illicil drugs may introduce it into lhe lung via the bloodstream (i.e .. venous embolism). None of the other choices exhibit biref1ingence under polalizecllighL ***Diagnosis: Pulmonary embolism, talc embolism
11 A 25-year-old woman dellvers a healthy baby aL 39 weeks of gestation. Six hours later, the mother develops severe shortness of bre<uh and appeal'S cyanotic. Despite resuscitation, she dies 2 hours later. A section of lung at autopsy is shown in the image. These pathologic findings are associated with which of the following mechanisms of disease? ***(A) Amniotic Ouid embolism ***(B) Cardiogenic shock ***(C) Mal.emal-fetal histoincompatibility ***(D) Metastatic squamous cell carcinoma ***(E) Pulmonary thromboembolism
11 The answer is A: Amniotic fluid embolism. Amniotic fluid embolism refers to the entry of amniotic fluid containing fetal cells and debris imo the maternal ci rculaLion through open uterine and cervical veins. lt is a rare maternal complication of childbirth, but when it occurs, it is often catastrophic. This disorder usually occurs at the end of labor when the pulmonary emboli are composed of the epithelial consti.tuents (squamae) contained in the a1m1iotic iluid . None of the mher choices show these pathologic findings. ***Diagnosis: Amniotic fluid embolism
12 Lf the patient dese1ibed in Quesu on 11 had Sltrvived the acme episode of cyanosis and shock, she would have been at risk for developing which of the follov.ring life-threatening complications? ***(A) Bacterial endocarditis ***(B) Disseminated intr avascular coagulation ***(C) Fat embolism ***(D) Neurogenic shock ***(E) Septic shock
12 The answer is 8: Disseminated intravascular coagulation (DIC) . The clinical presentation of amniotic fluid embolism can be dramatic, with the sudden onset of cyanosis and shock, followed by coma and death. lf the mother survives the acute episode, she may cUe of DIC. Should she overcome this compli cation , she is at risk of developing acute respiratory disrress syndrome. DIC is a thrombotic microangiopathy. Fibrin thrombi form in small blood vessels because of uncontrollable coagulopathy, which consumes fibrin and other coagulation facwrs. Once coagulation factors are depleted, uncomrollable hemorrhage ensues. None of the OLher choices are complications of amniotic iluid embolism. ***Diagnosis: Amniotic fluid embolism
13 A 68-year-old man with ischemic heart disease and a history of smoking complains of increasing shormess of breath. On physical examination , the patient has swollen legs. an enlarged liver. and fluid m the pleural spaces (bubbly rales are heard on oscultation). Which of the following hemodynamic disorders explains the pathogenesis of heparomegaly in this patient? ***(A) Arterialthromboembolism ***(B) Chronic passive congestion ***(C) Deep venous thrombosis ***(D) Multiple hepatic infarcts ***(E) Thrombosis of the hepauc vein
13 The answer is B: Chronic passive congestion. A generalized increase in venous pressure, typically fTom chronic hean failure, results in an increase in the volume of blood in many organs (e .g., llver, spleen, and kidneys). The liver i.s panicular1y vulnerable to chrome passive conge.o:;oon because the hepatic veins empty into the vena cava immediately inferior ro the heart. Budd-Chi.ari syndrome (thmmbosis of the hepatic vein; choice E) may cause hepawmegaly. but it is nola complication of congestive heart failure. ***Diagnosis: Congestive hean failure, nuoneg liver
14 The pauem described in Question 13 suffers a massive heart auack and expires. ~1icroscopic examination of the liver at auwpsy would most likely reveal which of Lhe following histopathologic changes? ***(A) Diiiuse hydropic degeneration ***(B) Large iron deposits witl1in hepatocytes ***(C) Massive hepatic necrosis ***(D) Regenerating hepatic nodules surrounded by fibrous bands ***(E) Sinusoids dilated with blood
14 The answer is E: Sinusoids dilated with blood. In patients with chronic passtve congestion of the liver, the cemral veins of tbe hepatic lobule become dilated. The increased venous pressure leads to dilation of the sinusoids and pressure atrophy of the centrilobular hepatocytes. Grossly, the cm surface of the chronically congested liver exJ1ibits dark foci of cennilobular congestion surrounded by paler zones of unaffected peripheral ponions of the lobules. The result resembles a cross section of a nutmeg and is appropriately called nutmeg liver. Longstanding passive congestion leads to bridging fibrosis; however, only in the most extreme cases is the fib rosis sufficiently severe to justify the label cardiac cirrhosis (choice D). None of the other choices are associated v..'ith congestive heart failure. ***Diagnosis: Congestive hean failure, nurmeg liver
15 A 33-year-old woman presents with black stools. Laborawry sLUdies demonstrate a hypochromic, microcyLic anemia. Upper Gl endoscopy reveals a duodenal ulcer. Which of the following best describes the stools in this patient with peptic ulcer disease? ***(A) Hematemesis ***(B) Hematobilia ***(C) Hematochezia ***(D) Melena ***(E) Steatorrhea
15 The answe-r is D: Melena. Melena (black stool) is a sympwm of upper gastroime.slinal bleeding. Blood from ruptured esophageal va1ices or a peptic ulcer is partially digested by hydrochloric acid. Hemoglobin is transfom1ed into a black pigmem (hematin), which imparts a typical "coffee-grounds" color lO the stool. Hemalemesi.s (choice A) is vomiting of blood. Hematobilia (choice B) is bleeding into the billary passages, as a complication of trauma or neoplasia. Hematochezia (choice C) is passage of bloody stools caused by lower gasnointeslinal hemorrhage. Steatorrhea (choice E) is passage of fatty stools caused by pancreatic disease and malabsorption. ***Diagnosis: Peptic ulcer disease
16 A 53-year-old man is hospitalized after injuring his neck in an automobile accident. He is placed in cervical traction . One week later, the patiem develops painful swelUng and erythema of his left calf. Doppler imaging discloses deep venous thrombosis. Wh ich of the following is the most likely cause for the developmem of thrombosis in this patient? ***(A) Age ***(B) Endothelial damage ***(C) Hypercoagulability ***(D) Infection ***(E) Stasis
16 The answer is E: Stasis. Venous thrombosis is caused by the same factors that predispose to arterial tlu·ombosis, namely endothelial injUJy, stasis, and a h)'percoagulable state. Although all of the choices are 1isk factors for deep venous thrombosis, the most likely choice, given the patients' immobilization, is stasis. Most venous thromboses occur in the deep veins of the legs. ***Diagnosis: Deep venous thrombosis
17 A 23-year-old man with hemophilia is recently wheelchair bound. Which of the following best accoums for this development? ***(A) Hemarthrosis ***(B) Hematemesis ***(C) Hematocephalus ***(D) Hematochezia ***(E) Hemoptysis
17 The answer is A: Hemarthrosis. Hemarthrosis refers to bleed· ing into the joint cavity. It is associated with joint swelling and is a crippling complication of hemophilia. Repeated bleeding may cause deformities and may bmit the mobility of the joints. Hematemesis (choice B) is vomiting blood. Hemawcephalus (choice C) is an intTacranial infusion of blood. Hematochezia (choice D) is passage o[blood caused by lower gastrointestinal hemonhage. Hemoptysis (choice E) is coughing up blood. ***Diagnosis: Hemophllia, hemarthrosis
18 A 50-year-old fi re fighter emerges from a burning house with third-degree bums over 70% of his body The patient expires 24 hours later. Whkh of the following was the most likely cause of death? ***(A) Congestive hean failure ***(B) Disseminated inrravascular coagulation ***(C) Hypovolemic shock ***(D) Pulmonary saddle embolism ***(E) Toxic shock syndrome
18 The answer is C: Hypovolemi( shock. Hypovolemic shock m.ay be caused by hemorrhage, fluid loss [rom severe burns, diarrhea, excessive mine formalion, perspiration, or Lrauma. In the case of burns or trauma, direct damage to the microcirculation increases vascular pem1eabilit:y. Persons with third-degree burns weep large amounts of plasma. The oilier choices are unlikely causes o£ death in an acme bum VIC[im. ***Diagnosis: Hyperthermia, hypovolemic shock
19 A 23-year-old woman complains of a recent 011Sel of yellowing of her skin and increasing abdominal girth. Physical examination reveals jaundice and ascites. Ultrasound examination of her abdomen demonstrates thrombosis of the hepatic veins. A liver biopsy discloses severe sinusoidal dilation ·within the cemril obular regions. This patholOgiC finding is caused by which of the following hemodynamic disorders? ***(A) Active hyperemia ***(B) Arterial embolism ***(C) Hematoma ***(D) Hemonhage ***(E) PassiVe hyperemia
19 The answer is E: Passive hyperemia. Passive hyperemia (chronic passive congestion) may be confined to a limb or an organ as a result of locaJ ized obsuuction w venous drainage. E-xamples include deep venous thrombosis of the leg veins, with resulting edema of the lower extremity, and thrombosis of the hepatic veins (Budd-Chiari syndrome, this patient) with secondary chronic passive congestion of the liver. AcLive hyperemia (choice A) is an augmemed supply of blood loan organ, usually as a physiologJc response to an increased functional demand. The most striking active hyperernia occurs in association with inflammation. Arterial embolism (choice B) typically causes infarction. Hematoma (choice C) and hemorrhage (choice D) represent extravascular accumulation of blood. ***Diagnosis: Budd-Chiari syndrome
ZO A 42-year-old woman undergoes a face lift. Two days later, she presents for follow-up care with confluent bluish hemorrhages in the skin around her eyes ("black eyes"). ·which of the following best describes this pattern of superficial skin hemorrhage? ***(A) Ecchymosis ***(B) Hematocephalus ***(C) Maculopapular rash ***(D) Peted:tiae ***(E) Purpura
20 The answer is A: Ecchymosis. Ecchymosis is a larger superficial hemorrhage in the skin. Following hemorrhage, the initially purple discoloralion of the skin tunlS green and then yellow before resolving. This sequence of events reflects Lhe progressive m.::idation of biJimbin released from lhe hemoglobin of degraded erythrocytes. A ''black eye·· is a good example of an ecchymosis. Petechiae (choice D) are pinpoint hemorrhages, usually in tJ1e skin or conjunctiva. Purpura (choice E) is a diffuse superficial hemorrhage in the skin up to 1 em in diameter. ***Diagnosis: Ecch>rmosis
21 A 19-year-old woman complains of swelling of her eyelids, abdomen, and ankles. At bedtime, there are depressions in her legs at the location of the elastic in her socks. A chest X-ray shows bil ateral pleural effusions. U1ine protein electrophoresis demonsu·ates 4+ proteinuria. A percutaneous needle biopsy of the kidney establishes the diagnosis of minimal change nephrotic sy11drome. Soft tissue edema in this patient is most likely caused by which of the following mechanisms of disease? ***(A) Active hyperemia ***(B) Chron ic passive congestion ***(C) Decreased imravascular oncotic pressure ***(D) Hyperalbuminemia ***(E) Increased capillary permeability
21 The answer is C: Decreased intravascular oncotic pressure. The pressure differential bei:Ween the intravascular and the lmersddal compartments is largely determined by the concemration of plasma proteins, especially albumin. Any condition that lowers plasma albumin levels, whether from albuminuria in nephrotk syndrome or reduced albumin synthesis in chronic hver disease, tends to promote generalized edema. ***Diagnosis: Minimal change neplu-otic syndrome
22 A 50-year-old alcoholic is rushed to the hospital wiLh bleeding esophageal varices and expires. At auwpsy, the patients protruding abdomen is [ound w contain a large volume of serous fluid. What is the appropriate term used to desctibe this fluid? ***(A) Ascites ***(B) Exudate ***(C) HemotThage ***(D) Hydrothorax ***(E) lymphedema
22 The answer is A: Ascites. A protruding belly and fluid accumulation in palients with cirrhosis represents ascites (i.e., accumulation of serous O.uid in the abdominal cavity). lt is primarily a consequence of portal hypertension and hypoalbuminernia. None of the other choices describe serous Ouid accumulation in the abdomen. ***Diagnosis: Cirrhosis, portal hypertension
23 A 1-year-old girl is brought to the emergency room by her parenLS who report she has had a fever and diarrhea for 3 days. Her temperature is 38°C (101 "f). The CBC shows a nom1al WBC count and increased hematocrit ( 48 gtdL). Which of the following is Lhe most likely cause of tncreased hematocrit in this patiem7 ***(A) Acute phase response ***(B) Dehydration ***(C) Diabetes insipidus ***(D) Malabsorption ***(E) Septic shock
23 The answer is B: Dehydration. lncreased hematocrit in this patient reflects hemoconcentration caused by dehydration, secondary to diarrhea. This hematologic condiLion, termed relative polycythemia, is charactetized by decreased plasma volume with a nonnal red cell mass. When patiems suffer from bums, vomiting, excessive sweating, or diarrhea, they not only lose Ouid but also suffer electrolyte disturbances. Systemic blood pressure falls with continuous dehydration, and declining perfusion eventually leads to death. Diabetes insipidus (choice C) may cause dehydration bm is an unlikely chmce because the patient has a hiswry of diarrhea. None of th e other choices cause relative polycythemia. ***Diagnosis: Dehydration, relative polyc}rt.hemia
24 A 40-year-old man with a history of bac£erial endocarditis notices numerous pinpoint hemorrhages around the orbit of his eyes (shown in the image; see arrows). 'vVhat is the approprime term used to describe this fo rm of superficial hemorrhage? ***(A) Ecchymosis ***(B) Erythema ***(C) Hyperemia ***(D) Petechia ***(E) Purpura
24 The answer is D: Petechia. Petechiae are pinpoint hemorrhages, usually in the skin or conjunctiva. TWs lesion represems the rupture of a capillary or aneri ole and occurs in conjunction with vasculitis and coagu lopath)~ Petechiae may also be produced by microemboli from infected heart valves (bacte1ial endocarditis). Hyperemia (choice C) refers to increased blood in a tissue or organ. Erythema (choice B) is inAammatory redness of the skin. Ecchymosis (choice A) is a larger superficial hemorrhage in Lhe skin. Purpura (choice E) is a diffuse superficial hemorrhage in the skin up to l em m diameter. ***Diagnosis: Endocarditis, petechia
25 A 67-year-old man presents \IVith sudden left leg pain, absence of pulses, and a cold limb. His past medical history is significant for coronary anery disease and a small aonic aneurysm. Which of the folto\IVing is most likely responsible for development of a cold limb in this patient? ***(A) Acute myocardial infarction ***(B) Aaerialthromboembolism ***(C) Cardiogenic shock ***(D) Deep venous thrombosis ***(E) Ruptured aonic aneurysm
25 The answer is 8: Arterial thromboembolism. Embolism of an artery of the leg leads to sudden pain, absence of pulses, and a cold limb. ln some cases, the limb must be amputated. None of the other choices would cause Lhis clinical presemation. Rupmred aonic aneurysm (choice E) presents with pain, shock, and a pulsatile mass in the abdomen. ***Diagnosis: Arterial thromboembolism
26 A 78-year-old woman dies in her sleep. A Prussian blue stain of the lungs at autopsy is shown in the image. Which of the following is the most likely cause or these histopathologic findings? ***(A) AcULe myocardial infarction ***(B) Congestive hean failure ***(C) Diffuse alveolar damage ***(D) Hereditaty hemochromatosis ***(E) Pulmonary infarction
26 The answer is 8: Congestive heart failure. Chronic failure of the left ventricle constitutes an impediment to the exit or blood from the lungs and leads to chron ic passive congestion of the lungs. The pressure in the alveolar capHlaries increases, and Lhe vessels become engorged with blood . Microhemorrhages release erythrocytes into the alveolar spaces, where they are degraded by alveolar macrophages. The released iron, in the form ofhemosiderin, remains in Lhe macrophages, which are then labeled "heart failure cells." None of the other choices are consistent with chronic microhemorrhages in the lung. ***Diagnosis: Congestive hean failure
27 A 60-year-old man who is recovering from surge1y w conect an abdominal aneurysm suddenly develops acme chest pain and dies. A thromboembolus at the bifurcation of the left and 1ighr pulmonary ane1ies is nmed at autopsy (shown in the image). Which of the following is the most likely cause of this patients pulmonary embolus? ***(A) Bacterial endocarditis ***(B) Complkated atherosclerotic plaque ***(C) Deep venous thrombosis ***(D) Parado:>:ical embolizalion ***(E) Right ventJicular mural thrombus
27 The answer is C: Deep venous thrombosis. One of the most tragic calamities complicating hospilalization is the sudden death or a patienl who appeared to be on the way to recovery. The cause of this catastrophe is often massive pulmomny embolism. A Large pulmonary embolus may lodge at the bifurcation of the main pulmonaty artery (saddle embolus), obstruning blood flow to both lungs. With acute obstruction of more than half or the pulmonary arterial tree, the patient e>..'Periences severe hypotension and may die \vithin minutes. The other choices are causes of anerial embolism. ***Diagnosis: Pulmonary thromboembolism
28 A 20-year-old man is brought to the emergency room after mpturing his spleen in a motorcycle accidem. His blood pressure on admission is 80/60 mm Hg. Analysis of arterial blood gasses demonsrrates metabolic acidosis. This padem is most likely suffering from which of the following conditions? ***(A) Acme pancreatitis ***(B) Cardiogenic shock ***(C) Hypersplemsrn ***(D) Hypovolemic shock ***(E) Sepdc shock
28 The answer is D: Hypovolemic shock. Hypovolemic shock is secondary w a pronounced decrease in blood or plasma volume, caused by the loss of Ouid from the vascular compartment. Hemonhage, fluid loss from severe burns, diarrhea, excessive urine fom1ation, perspiration , and trauma are major mechanisms of fluid loss that can lead to hypovolemic shock. Cardiogenic shock {choice B) is caused by myocardial pump failure. Septic shock (choice E) is improbable in thjs seui.ng. ***Diagnosis: Hypovolemic shock
29 A 72-year-old man is dead on arrival after collapsing at home. Rena] cortical infarcts are noted ar autopsy. A section through the arcuate anery is shown. Which of the following is the most likely source of the atheroembolus occluding this anery? ***(A) Abdominal aorta ***(B) Common carotid anery ***(C) lnferior vena cava ***(D) Left vennicle ***(E) Mesenteric artery
29 The answer is A: Abdominal aorta. ln patients \'lith severe aortic atherosclerosis, embolization of atheromatous debris into the renal aneries and vascular tree may cause acme renal failure. Cholesterol clefts are observed in the photomicrograph shown. None of the other choices are sources of renal atheroemboli. ***Diagnosis: Renal infarct, anerial embolism
30 A 72-year-old woman complains of shormess of breath on exenion . She states that she also becomes shon of breath at night unless she uses three pillows (orthopnea). Phys1cal examination reveals mild obesity. bilateral pitting leg edema, an enlarged liver and spleen, and fine crackling sounds on inspiration (rales). A chest X-ray shows cardiomegaly. What is the most likely cause of orthopnea in this patient? ***(A) Asthma ***(B) Cardiac tamponade ***(C) Emphysema ***(D) Hypovolemic shock ***(E) Pulmonary edema
30 The answer is E: Pulmonary edema. Patients in left~sided congestive heart failure complain of shormess of breath (dyspnea) on exertion and when recumbent (orthopnea). They may be awakened from sleep by sudden eptsodes of shortness of breath (paroxysmal nocturnal dyspnea). Physical examination usually reveals distended jugular veins. Persons with right-sided fallure have pining edema of the lower extremities and an enlarged and tender Liver. Patients in congestive heart failure with pulmona1y edema have crackling breath sounds (rales) caused by the expansion of fluid-filled alveoli. Cardiac tamponade (choke B) occurs when the pressure in the pericardia] cavity rises to exceed the filling pressure of the hean. Orthopnea is nOLa feature of the other choices. ***Diagnosis: Congestive heart failure
31 A 63-year-old man suffers a massive s troke and expires. At autopsy, the pathologist finds a laminated thrombus adherent to the wall of Lhe left ventr icle (shown in the image). Which of the following is the most likely cause of this autopsy finding? ***(A) Atrial fib1illation ***(B) Bacterial endocarditis ***(C) Marantic endocarditis ***(D) Myocardial infarction ***(E) Viral myocarditis
31 The answer is D: Myocardial infarction. Myocardial infarction is the most common cause of mural thrombi in the left ven~ tricle. These mural thrombi are a common source of arterial thromboemboli. Such emboli may occlude cerebral arteries and cause cerebral infarcts, known clinically as strokes. Atrial fibrillation (choice A) predisposes to the formation of mural thrombi in that location. ***Diagnosis: Mural thrombus
32 Histologic examination of the heart in the patient described in Question 31 shows extensive growth of fibroblasts and deposition of collagen in Lhe mural thrombus. Which of the following terms describes this outcome of thrombosis? ***(A) Can alization ***(B) Hyaltnizalion ***(C) Organization ***(D) Propagation ***(E) Regeneration
32 The answer is C: Organization. Once fo rmed, arterial thrombl may undergo (1) lysis, (2) propagation, (3) organization, (4) canalization, or (5) embolization. Organization refers to the invasion of connective tissue elements, which causes a Lhrombus to become firm and appear grayish white. Canalization (choice A) is the process by which new lumina lined by endothelial cells fonn within an orgarLized thrombus. Propa~ galion (choice D) implies an increase in size. ***Diagnosis: Mural thrombus
33 A 50-year-old woman presents with fatigue and shortness of breath. Physical examination shows evidence of pulmonaty edema, enlargement of the left atrium, and calc.ification of the mitral valve. ACT scan demonsmues a large obstructing mass in the left atrium. Before open heart surgery can be perfom1ed to remove the mmor, the patient suffers a stroke and expires. Which of the foiiO\~ng hemodynamic disorders best expla ins the pathogenesis of stroke in this patient? ***(A) Arterial embohsm ***(B) Atherosclerosis ***(C) Card10genic shock ***(D) Hypertensive hemorrhage ***(E) Septic shock
33 The answer is A: Arterial embolism. Cardiac myxoma is the most common p1imary tumor of the heart. One third or patients vlith a left atrial or left ventricular myxoma die from tumor embolization to the brain. Less likely causes of stroke in this patient with a cardiac myxoma include atherosclerosis (choice B) and hypertensive hemonhage (choice D). ***Diagnosis: Cardiac myxoma
34 A 50-year-old woman appears at your office. She was subjected to radical mastectomy and axillary node dissection for breast cancer a year ago. $he now notices that her arm becomes 5\Vollen by the end of the day. What is the appropti· ate name for this rruid accumulation? ***(A) Chylothorax ***(B) Hydrothorax ***(C) Lymphedema ***(D) Pumlem e.>..'1.ldate ***(E) Fibrinous exudate
34 The answer is C: Lymphedema. Obsuuction o£ lymphatic now may occur in a number of clinical settings, but is most common because o£ surgical removal of lymph nodes or rumor obsnuction. For example, the lymphatic system may be obstructed after axillary lymph node dissection for breast cancer. Prolonged lymphatic obstruction in the patient's shoulder causes edema, progressive dilation of lymphatic vessels (lymphangiectasia), <mel overgrowth of fibrous tissue. Lymp· hangiosarcoma has also been described. Chylothorax (choice A) represents an accumulation of lymphedema in the pleura] space. Exudates (choices D and E) are associated witJ1 acute innammation. ***Diagnosis: Lymphedema, breast cancer
35 A 68-year-old man develops sudden, severe substernal chest pain. Laboratory smdies and ECG corlfinn an acute myocardial infarct. Despite vigorous rherapy, the palient cannot maintain his blood pressure and expires 24 hours later. A cross section of £he lefL vemricle is examined at amopsy (shown in the image). The arrows point w a soft, yellow area of necrosis. Which of the following was the most likely cause of death? ***(A) Cardiogenic shock ***(B) Hypovolemlc shock ***(C) Neurogenic shock ***(D) Septic shock ***(E) Pulmonary edema
35 The answer is A: Cardiogenic shock. Cardiogenic shock is caused by myocardial pump failure. This condition usual ly arises as a result of a large myocardial infarction, but myocarditis may also be responsible. Conditions that prevent left or right hean 61Ung reduce cardiac output, resulling in obstructive shock. Such conditions include pulmonary embolism, cardiac tamponade, and (rarely) aLrial myxoma. The other choices do not reflect a loss of cardiac output secondary w the loss of myocardial tissue owing LO ischemia. ***Diagnosis: Acute myocardial infarction
36 An 80-year-old woman with a history of hypertension is rushed to Lhe emergency room complaining of chest pain of 1-hour duration. Physical examination discloses bilateral pirLing leg edema, hepatosplenomegaly, and rates at 1.he bases of bOLh lungs. The pariem is apprehensive and sweating The patient loses consciousness and dies of a cardiac arrhyrlm1ia. Microscopic examination o[ the lungs at auropsy is shown. Which of the following hemodynamic processes best explains this pathologic finding? ***(A) Decreased capillary permeability ***(B) Decreased intravascular oncolic pressure ***(C) Increased intravascular hydrostatic pressure ***(D) Increased inu·avascular oncolic pressure ***(E) Vasoconstriction of precapillary arterioles
36 The answer is C: Increased intravascular hydrostatic pressure. In patients with congestive heart failure , venous engorgement of the lung leads to accumulation of a transudate in the alveoli. Chronic left venuicle failure impedes blood flow out of the lungs and leads to passive pulmonary congestion. As a result, pressure in the alveolar capillaries increase (increased hydrostatic pressure) and these vessels become engorged with blood. Increased pressure forces fluid from d1e blood into the alveolar spaces, resulting in pulmonary edema, which interferes with gas exchange. The photomicrograph shows pink staining fluid in the alveoli. None of the other choices cause pulmonary edema in patients with congestive hean railure. ***Diagnosis: Pulmonary edema, congestive heart failure
37 A 9-momh-old infant is brought to the emergency room with a 3-hour history of intense abdominal pain and bloody diarrhea. Physical examination reveals a tender abdomen without ascites. The child dies 24 hours later, and torsion (volvulus) of the small bowel is discovered at autopsy. The small bowel appears dilated and hemorrhagk (shown in the image). Wl1ich of the following best describes these pathologic findings? ***(A) Ecchymosis ***(B) Infarct ***(C) Petechia ***(D) Purpura ***(E) Ulcer
37 The answer is B: Infarct. Volvulus is an example of intestinal obsu·uction in which a segment of gut twists on its mesentery, thereby kinking the bowel and usually interrupting the blood supply. lschemia leads to infarction and intestinal gangrene (this case). Volvulus is vinuaL\y always a consequence of an underlying congenital abnom1ality. Defective intestinal rotation in fetal life leads w abnom1al positions of the small intestine and colon, anomalous auachments, and bands. The clinical impon ance of such rotational anomalies lies in their propensity to cause catastrophic volvulus of the small and large intestine and incarceration of the bowel in an internal hernia. Malrotation of the bowel permits undue mobility of the bowel loops and predisposes to midgut volvulus. When the cecum or right colon is invested with a mesente1y rather than bei:ng retroperitoneal, the resulL may be cecal volvulus. An unusually long sigmoid colon, which occurs sometimes in patients wi Lh idiopathic constipation, permits the development of sigmoid volvulus. Meconium ileus in babies with cystic fibrosis may be complicated by volvulus and intestinal atresia. Ecchymosis (choice A), petechia (choice C), and purpura (choice D) represent hemorrhages of various sizes in the skin. ***Diagnosis: Volvulus, ischemic colitis
38 An autopsy of a 70-year-old woman reveals a subendocardial, circumferential infarct of the left ventricle. This type of infarct is most commonly associated with which of the following? ***(A) Deep venous thrombosis ***(B) Hypotensive shock ***(C) Pelicardial tamponade ***(D) Tl1rombotic occlusion of the right coronary artery ***(E) Il1rombotic occlusion of the circumflex anery
38 The answer is B: Hypotensive shock. Myocardial infarcts ;ue described as transmural (through the entire wall) or subendocardiaL A transmural infarct results from complete occlusion of a major extramural coronary artery Subendocardial infarction reflects prolonged ischemia caused by partially occluding lesions of the coronary aneries when lhe requirement for oxygen exceeds the supply. Such a siruation prevails in disorders such as shock, anoA'ia, or severe tachycardia. Thrombotic occlusion (choices D and E) is more likely to cause transmural myocardial infarcts. ***Diagnosis: Myocardial infarction
39 A 76-year-old woman is brought to the emergency departmem because of the sudden onset of two episodes of hemoptysis and left-sided chest pain, wh ich is exacerbated upon inspiration. Her temperamre is 38°C (101 °F), pulse 110 per minute, respirations 35 per minme, and blood pressure 158/100 mm Hg. The pariem is admitted, bur suffers a massive stroke and e>rpires 48 hours later. Auwpsy reveals a pulmonmy infarct in upper segments of the lower lobe (shown in the image). Which of the following best explains the color of this patients pulmonary infaTct? ***(A) Accumulation of hemosiderin-laden rnacrophages ***(B) Development of bronchopneumonia ***(C) Hernonhage from bronchtal anenes ***(D) Orgamzauon of a pulmonary thromboernbolus ***(E) Passi,•e congestion of bronchopulmonary segments
39 The answer is C: Hemorrhage from bronchial arteries. The gross and microscopic appearance of an infarct depends on its location and age. Pale infarcts are cypically seen in the hean, kidneys, and spleen. Red infarcts may result from either arterial or venous occlusion. They are distinguished from pale infarcts by bleeding into the necrotic area from adjacent arteries and veins. Red infarcts occur principally in organs with a dual blood supply, such as the lung, or those \Vilh extensive collateral circulation, such as the small intestine and brain. ln the heart, a red in fa rct occurs when the infarcted area is reperfused, as may occur following spontaneous or therapeutically induced lysis of the occluding thrombus . Grossly, red infarcts are sharply circumscribed, finn, and dark red to purple. Over a petiod of several days, acute in fiammatory cells infiltrate the necrotic area from the vi able border. The cellular debris is phagocytosed and digested by polymorphonuclear leukocytes and later by macrophages. Granulation tissue eventually fo rms, to be rep laced ultimately by a scar. None of the other choices would cause hemorrhage into an infarcL ***Diagnosis: Pulmona1y infarction, pulmonary thromboembolism
40 A 22-year-old woman delivers a baby at 29 weeks of gestaLion. Shortly after binh, the neonate becomes short of breath. The neonate is placed on a ventilator, buL dies of respirato ry msufficicncy. The brain at autopsy is shown. Which of the following mechanisms of disease best explams this complication of rcsptratory distress syndrome (RDS) of the neonate? ***(A) Anoxic injury ***(B) Birth trauma ***(C) Chronic passive congesLion ***(D) Hemolytic anemia ***(E) Hypertension
40 The answer is A: Anoxic injury. The pathogenesis of RDS of the newborn is intimately linked to a deficiency of surfaclant. This material lowers the surface tension of the alveoli at low lung volumes and thereby prevents collapse (atelectasis) of the alveoli during expiration. Atelectasis secondary to surfactant deficiency results in perfused but not ventilated alveoli, a situation that leads to hypoxia and acidosis. Intraventricular cerebral hemorrhage is a major complication of RDS. The perivenLricular germinal matrix in the newborn brain is particularly vulnerable to hemorrhage because the dilated, thin-walled veins in this area rupture easil)' (see photograph). The pathogenesis of Lhis complication is believed LO reflect anoxic injury to the perivemricular capillaries, venous sludging and thrombosis, and impaired vascular autoregulation. Despite advances in neonatal intensive care, the overall mortality ofRDS is about 15%, and one third or infams born before 30 weeks of gestational age die of this disorder. Although the other choices are associated with bleeding. they are unlikely causes of perivemricular hemorrhage in a baby with RDS. ***Diagnosis: Respiratory distress syndrome of the neonate
1 A 65-year-old woman \.Vilh a history of smoking presents L...- with a 3-week history of chest pain and bloody sputurn. An X-ray film of the chest reveals a hilar lung mass. The surgical specimen reveals a squamous cell carcinoma growing within the lumen of a bronchus (shov.'tl in the image). Which of the fo llowing chemical agents may be associated with the pathogenesis of the cancer in this patient? ***(A) Allaw:-.ins ***(B) Aromatic hydrocarbons ***(C) Benzene ***(D) Branched chain amino acids ***(E) Carbohydrate polymers
1 The answer is B: Aromatic hydrocarbons. These compounds (e.g., benzopyrene, methyl cholanthrene) are potent expelimental carcinogens. Aflatoxins (choice A) produce experimental liver cancer. The mmor in this patient is a squamous cell carcinoma, which bears a strong resemblance to nom1al squamous cells and synthesizes keratin, as evidenced by epithelial pearls. ***Diagnosis: Squamous cell carcinoma of the lung
2A 75-year-old man who had worked in a shipyard for 25 years dies of a thoracic mmor. Autopsy reveals a pleural rumor !hat encases the lung. lmerstitial pulmonary fibrosis and multiple pleural plaques are noted. Numerous, brown, beaded ferrugtnol. l':; bodies are also found in the lungs (shown in the image). Which of the following agents is most Likely assodated with the pathogenesis of the cancer in this patient? ***(A) AsbesLos ***(B) Beryllium ***(C) Carbon ***(D) Silica ***(E) Tobacco
2 The answer is A: Asbestos. Occupational exposure to asbestos poses a risk for the development of a pleural mmor termed malignam mesothelioma. \ltalignam disease may become evident 20 to 30 years following exposure. The inhalation of asbestos fibers also causes interstitial fibrosis of the lungs and pleural plaques consisting of dense connenive tissue. Asbestos fibers coated with protein and iron are tem1ed asbesws (femlginous) bodies. The mher choices do nor produce ferruginous bodies or cause mesmhdioma. ***Diagnosis: MesOlhelioma, asbestosis
3 A 4 7 -year-old man presems with a 6-week his wry of increasing fatigue and dark-colored swols. Complete blood count shows hemoglobin of 8.6 gldl and microcytic, hypochromic RBCs. Upper gastrointestinal endoscopy reveals a peptic ulcer along the lesser curvature of the stomach. This patient's anemia is most likely caused by deficiency of which of Lhe follovving? ***(A) Folic acid ***(B) lron ***(C) Thiamine ***(D) Vitamin B 12 ***(E) Zinc
3 The answer is B: Iron. Gastrointestinal hemonhage leads to the loss of heme iron at a rate faster than it is replaced from dieta1y sources. The result is microcytic hypochromic anemia. The anemias associated with deficiencies of folic acid (choice A) and vitamin B12 (choice D) are macrocytic. ***Diagnosis: Iron-deficiency anemia
4 A 49-year-old woman presents with a 2-month history of yellow discoloration of her eyes, abdominal pain, weight loss, and low-grade fever (38.4°C, 101 °f). Physical examination shows a distended abdomen, right upper qua dram tenderness, and a palpable liver 2 em below Lhe costal margin. A liver biopsy reveals alcoholic hepatitis. The patiem recovers and is strongly advised to abstain from alcohol. However, she subsequently imbibes some antifreeze containing ethylene glycol and develops acme failure of which organ? ***(A) Brain ***(B) Heart ***(C) Kidney ***(D) Liver ***(E) Pancreas
4 The answer is C: Kidney. The major toxicity of ethylene glycol is acute tubular necrosis of the kidney, which resulLS in renal failure. The compound has li ttle effect on the other organs. ***Diagnosis: Acute renal failure
5 A neonate was noted to have mild growth retardation and facial dysmorphology. The mOLher was a known abuser of several subsmnces. This infants problem most likely resuhed from maternal intake o r which of the following? ***(A) Alcoh ol ***(B) Cocaine ***(C) Ethylene glycol ***(D) Heroin ***(E) lvlarijuana
5 The answer is A: Alcohol. Fetal alcohol syndrome is the most common acquired cause of mental retardation in the United States. The common features of the syndrome include intrauterine growth retardation, facial dysmorphology, neurologic impairment, and other congenital anomalies. ln cases with lesser manifestat]ons, tenned fetal alcohol effect, chJldren later suffer from mental retardation and minor dysmorphic features. Cocaine {choice B) may cause neonatal dirficulties and heroin {choice D) intake may result in neonates that arc addicted to that opiate, but they are not associated with characteristic facial dysmorphology. ***Diagnosis: Fetal alcohol syndrome
6 A 10-ye<n-old boy presents with irritability and ataxia. He is subsequently found to have anemia, basophilic stippling of erythrocytes, and dark-gray pigmentation of the gums. Exposure to which of the following chemical agenlS is most likely associated with this disease? ***(A) Arsenic ***(B) Copper ***(C) Lead ***(D) Mercury ***(E) Nickel
6 The answer is C: Lead. Chronic lead poisoning inhibi!:s deltaarninolevuUnic acid dehydratase and ferrochelatase (enzymes essential for heme synthesis), thereby causing microcytic hypochromic anemia. The inhibition of heme symhesis leads to basophilic stippling of erythrocytes, which is due w residual ribosome cluslers in the cytoplasm. Chronic e)q>osure of children to lead also leads lO cognitive loss. Mercmy (choice D) poisoning has neurologic sequelae, bm nm these hemawlogic characteristics. ***Diagnosis: Lead poisoning
7 A 50-year-old man presems for a routine physical examination, which demonstrates an enlarged liver. During the visit, he describes memos from hjs supervisor at work regarding chronic e:xposure [ 0 vinyl chloride. The patiem has an elevated risk for which of the fo llowing rumors? ***(A) Angiosarcoma of lh e liver ***(B) Carcinoid tumor ***(C) Hepatic adenoma ***(D) Lymphoma ***(E) Metastatic colon cancer
7 The answer is A: Angiosarcoma of the liver. Occupational e".'posme co vinyl chloride (used in the production of plastics) is associated with the developmem of this malignam tumor of endothelial cells in the liver_ Angiosarcoma is also associated with exposure w arsenic (a component of pesticides) and Thorouast (a radioactive contrast medium used by radiologists prior LO 1950). None of the other tumors have been associated \Vilh occupational exposure w vinylchlmide. Hepatic adenoma (choice C) is associated with the use of oral contraceptives. ***Diagnosis: Angiosarcoma of the liver
8 A severely depressed 32-year-old man commits suicide by running his car motor in his closed garage for several hours. The mechanism of death in this case of carbon monoxide (CO) poisoning is through which of the following mechanisms? ***(A) Displacement of oxygen on hemoglobin by CO ***(B) Hepawcellular necrosis ***(C) Inhibition of protein synthesis ***(D) Inhibition of the respiratory chain enzymes ***(E) Myocardial infarction
8 The answer is A: Displacement of oxygen on hemoglobin by CO. CO combines with hemoglobin with an affinity 240 times greater than that of OX')'gen to form carboxyhemoglobin. At concentrations above 50% carboxyhemoglobin, cerebral anoxia, coma, convulsions, and death ensue. The other choices do not reflect the su·ong binding affinity of CO for hemoglobin. ***Diagnosis: Carbon monoxide poisorung
A japanese fisherman who lives in the vicinity of a plastics factory develops severe neurologic symptoms, including constriction of visual fields, paresthesias, ataxia, dysanhria, and hearing loss. Public health authorities find a number of similar cases in the local village. Exposure to which of the follovling chemical agems is most likely associated with the pathogenesis of this man:S neurologic disease? ***(A) Arsenic ***(B) Copper ***(C) Lead ***(D) Mercmy ***(E) Nickel
9 The answer is D: Mercury. Mercmy released imo the environment may be bioconcemrated and enter the food chain, particularly predatory fish. Organic mercurials principally damage the brain, whereas inorganic mercury is wxjc to the kidneys. Large outbreaks attributed to metbyl mercury poisoning have been reponed in Japan (fish) and Iraq (fungicides). Poisonings by the other choices do not elicit these neurologic symptoms ***Diagnosis: Mercmy poisoning
10 A 12-year-old boy is rescued 2 days afrer becoming lost in the Canadian woods in february. Physical examination shows he has gangrene of his fingers and roes. Which of the following mechanisms of cell injury played the most important role in mediating necrosis in the fingers and toes of this patient? ***(A) Activation of proapoptotic proteins ***(B) Generation of activated oxygen species ***(C) Lipid peroxidation ***(D) Membrane disruption by water crystals ***(E) PrO[ein and DNA crossli11king
10 The answer is D: Membrane disruption by water crystals. Exposure of the extremi ties to severe cold resuhs in the CiystallJzation of tissue water, which causes cellular disiUption and vascular changes, resulting in frostbite . Locallzed thrombosis often leads to focal ischemia and gangrene of toes and fingers. Mechanical disruption of cellular membranes by ice crystals occurs during both freezing and thawing. The other choices are associated with cell death, but they are not early events in frostbite-induced necrosis. ***Diagnosis: frostbite
11 A 35-year-old man is hospitalized with third-degree burns after being rescued from a house fire. Initially, he suffers from shock and oligmia, but his renal function retun1S to normal within a few days. Which of the following would be the most likely cause of death i [complications were w arise? ***(A) Ascites ***(B) Curling ulcers with hemonhage ***(C) Cushing ulcers ***(D) Pseudomembranous colitis ***(E) Sepsis
11 The answer is E: Sepsis. The most common cause of death in seriously burned patients is sepsis after infection of the burned skin. Gastric ulcers (stress or Curling ulcers, choice B) are occasionally encountered in burn patients, bmthey do not represem a common cause of death. Cushing ulcers of the stomach (choice C) are associated with trauma LO the central nervous system. ***Diagnosis: Sepsis, thermal injury
12 A healthy adult runs a marathon in the surruner and develops hot d1y skin, cessation of sweating, lactic acidosis, hypocalcemia, and muscle necrosis (rhabdomyolysis). Whlch of the following is the appropriate diagnosis? ***(A) Dysautonomia ***(B) Heat stroke ***(C) Malignant hyperthermia ***(D) Myotonic dystrophy ***(E) Polymyositis
12 The answer is B: Heat stroke. :Exenional heat stroke occurs in healthy men dming unusually vigorous exercise, particularly when the an1bient temperature is high. Lactic acidosis, hypocalcemia, and rhabdomyolysis may be severe problems. Myoglobinuric acute renal failure is not uncommon. Malignam l1ypenhermia (choice C) occurs in surgical parienlS after anesLhesia. ***Diagnosis: Heat stroke
13 A 26-year-old electrician is found unconscious in his backyard beside a metal ladder and an e}.lJOSed elecui cal wire, suffeting from a deep bum on his right hand. ResuscitaUon attempts are unsuccess ful. Whkh of the follm.ving was the most likely cause of death? ***(A) Cardiac arrhythmia ***(B) Disseminated intravascular coagulation ***(C) Myocardial infarction ***(D) Rupture of Lhe ascending aorta ***(E) Uncoupling of oxidative phosphorylation
13 The answer is A: Cardiac arrhythmia. Electrical ene rgy disrupts the electrical system wi thin the bean and frequemly causes death through ventricular fibrillation. The force produced by high-voltage cunents vaporizes tissue water and produces extensive damage. The other choices are nol consequences of powerful electrical currents. Allhough myocardial infarction (choice C) can cause an immediate anhythmia, it reflects obstmction of the coronary circulation. ***Diagnosis: Eleclrical injury, cardiac anhythmia
14 A sailor on a nuclear-powered submarine is seen by a physician after a breach in the reactor comainmem system. Physical examination is unremarkable, but the patiem subsequently develops profound pancytopenia. Hemoglobin is 7.8 gtdl, WBC coum is 900/f.l l , and platelets are 20,000/IJL. How many rads of acute total-body radiation djd this patient most likely receive? ***(A) 1 ***(B) 3 ***(C) 30 ***(D) 300 ***(E) .3,000
14 The answer is D: 300. Acute total-body irradiation o[ abour 300 rads causes depression of the bone marrow, and symptoms related Lo granulocytopenia and thrombocytopenia develop wilhin 2 weeks. Anemia follows more slowl)' because red blood cells have a longer lifespan than leukocytes and pla1.elets. EJ..'Posure w 3,000 rads (choice E) is rapidly fatal owing to ceno·al nervous system damage. ***Diagnosis: Radiation sickness
15 Another sailor on the submarine (see Question 14) dies 10 days after the accident as a result of severe dianhea and dehydration. Which of the fo llowing doses (in rads) of acute tmal-body radiation did this sai lor most like!)' receive? ***(A) 1 ***(B) 3 ***(C) 100 ***(D) 300 ***(E) 1,000
15 The answer is E: 1,000. A radiation dose of 1,000 rads causes destruction of tissues composed of proliferating cells. Damage m the gastrointestinal tract is the most serious consequence and ensues within days of exposure. Death resulLs from massive flu id loss from the denuded intestinal mucosa and superimposed passage of bacteria through the damaged imestine. The lower doses listed in the question do nol destroy 1.he gasLroimestinal epithelium. ***Diagnosis: Radiation sickness
16 A 66-year-old woman presents with a 6-month history of scaling and abnom1al pigmentation of the skin. Her past medical hiswry is significant for the treatment of thyroid cancer I year ago. Biopsy of lesional skin shows atrophy of the epidermis and dense fibrosis of the dennis, which clisplays dl1ated superficial blood vessels. These pathologic findi ngs are most Jjkely caused by previous exposure to which of the following? ***(A) Chemotherapy ***(B) Corticosteroids ***(C) Organic iodine ***(D) Radiation therapy ***(E) Tumor necrosis factor-a.
16 The answer is D: Radiation therapy. Ionizing radiation administered for the treatmem of cancer must firsl traverse the skin, leading to radiation dermatitis. Skin biopsy shows atrophy of 1.h e epidermis and dense fibrosis of the dermis, wl1ich displays dilated superficial blood vessc Is. ln some cases, persistem ulcers require skin grafts. The other choices do not cause these dermal findings. ***Diagnosis: Radiation injury
17 A 28 -year~o ld radar technician aboard an aircraft carrier has been subjected to intense microwave radiation for 7 years. He has an elevated 1isk for developing which of the following? ***(A) Aplastic anemia ***(B) Hodgkln disease ***(C) Lymphocytic leukemia ***(D) Myelogenous leukemia ***(E) None of the above
17 The answer is E: None of the above. The absorption of microwave energy produces only heat and is not associated wi th any knovm health risks. ***Diagnosis: Radiarion injury
18 A 15-year-old African boy has a history of tooth loss, gingiviLis, skin hemorrhages, mnldple infections, and poor wound healing. Physical examination shows Lhat the child is m the 20th percentile for height and lOth percentile for weight. TI1is patient most likely has which of the following underlying conditions? ***(A) Beri-beri ***(B) Irnpetigo ((:) Kwashiorkor ***(D) Pellagra ***(E) Scurvy
18 The answer is E: Scurvy. Vitamin Cis essential for collagen synthesis, and its defidency results in poor wound healing. Pe rifollicular hemorrhages arise from capUlaries £hat have weak walls and are easily damaged by minor trauma. Impai red collagen synthesis leads to gingivitis and alveolar bone resorption. resulting in loss of teed1. Wound healing requires collagen synthesis and is impaired in patients with vitamin C deficiency (scurvy). ***Diagnosis: Scurvy, vitamin C deficiency
19 A 24-year-old woman, who is a food faddist, eats only combased foods. She p resents with dermatitis, diarrhea, and dementia. This patient most like!)' suffers from whkh of the following conditions? ***(A) Be1i-beri ***(B) Impetigo ***(C) KVv·ashiorkor ***(D) Marasmus ***(E) Pellagra
19 The answer is E: Pellagra. Niacin deficiency leads to the 3 Ds: dennatitis, diarrhea, and dementia. A swollen, fissured tongue and chron.i.c watery diarrhea are also characteristic. Dementia reflects degeneration of ganglion cells in the cerebral cortex. ***Diagnosis: Pellagra, niacin deficiency
20 A 45-year-old woman with longstanding Crohn disease and severe Cat malabsorption e.\.'Peliences a fracture of the femoral neck after a minor comusion. This woman most llkely has a dellciency or which of the fo llowing vitamins7 ***(A) Vitamin B1 (thiamlne) ***(B) Vitamin C ***(C) Vitamin D ***(D) Vitamin K ***(E) Niacin
20 The answer is C: Vitamin D. Lipid malabsorption interferes with the absorption of vi tamin D, thereby leading to a deficiency state. ln adults, vitamin D deficiency results in osteomalacia, a disorder characterized by inadequate mineralization of newly formed bone marri.x. The consequent weakness of bone is associated with a vulnerability to spontaneous fractures. Vitanun D deficiency i.n children is termed rickets_ Deficiencies Ln the other choices are not associated with these bone abnormalities. ***Diagnosis: Osteomalacia, vitamin D deficiency
21 A homeless man, who is a chronic aJcohohc, is brought to the hospital in a wasted staLe. He is noted to have a peripheral neuropathy, difficulty balancing, and dememia. He dies suddenly of an arrhythmia, and at autopsy; lesions are found m the mami11ary bodies and the viciniry of the third vetmicle. The vi tamin deficiency associated with these signs and syruproms is which of the following? ***(A) Vitamin B1 (thiamine) ***(B) Vitamin B11 ***(C) Vitamin D ***(D) Niacin ***(E) Pytidoxine
21 The answer is A: Vitamin 81 (thiamine} . This man suffers from b eri-beri (heart) and Wernicke-Korsakoff syndrome (brain). Thiamine deficiency in deteriorated alcoholics results in encephalopathy, peripheral neuropathy. and other disorders. Atrophy of the mammillary bodies, with loss of ganglion cells and mpture of small blood vessels, is characteristic. Deficiencies of the other vitami ns are not related tO these disorders. ***Diagnosis: Beri-ber i, Wernicke encephalopathy
22 A -+0-year-old, malnourished woman presents with a 6-month history of night blindness. Physical examination reveals keratoma! acia and corneal ulceration. \-Vhich of the following viLamin deficiencies would be suspected in this patient? ***(A) Vitamin A ***(B) Vitamin B2 (riboflavin) ***(C) Vitamin C ***(D) Vitamin E ***(E) Folk acid
22 The answer is A: Vitamin A. Vitamin A deficiency causes squamous metaplasia at a number of sites. In the cornea, it leads to xerophthalmia (dry eye), which rnay progress to softening of the tissue (keratomalacia) and corneal ulceration. Deficiencies of the other vitamins are not related to these dimcal and pathologic findings. ***Diagnosis: Vitamin A deficiency, keratomalacia
23 A 26-year-old woman presents to the emergency room with fever and shaking chms. Her temperature is 38PC (l03°F), pulse 120 per minute, and blood pressure 140/80 mm Hg. Ph)'sical examination reveals a harsh systolic murmur. The patient develops a headache. slips into a coma and e:>..'})ircs. The aortic valve is examined at autopsy (shown in the image). Vl/hich of the fo llowing is the most important risk factor for this pathologic finding? ***(A) Alcoholism ***(B) Autoimmune disease ***(C) Cigarette smoking ***(D) lntravenous dmg abuse ***(E) OraJ contraceptive use
23 The answer is D: Intravenous drug abuse. The introduction of bacteria by intravenous drug abuse may lead to septic complications in many organs. Bacterial endocarditis, often involving Staphylococcus aureus , may occur on both sides of the heart. Infected emboli can occlude vessels leading to gangrene. Infected emboli in the b rain can cause cerebral abscess. The photograph shows ad herent vegetations on the aortic valve. These vegetations are comp osed of platelets, fibrin, cell debris, and masses of organisms. In addition to intravenous drug abuse , risk fac tors for bacte1ial endoca rditis include congenital heart disease (children), rheumatic heart disease, prosthetic heart valves, transient bactere!1Ua, and diabetes. Although certain autoimmune diseases (cl1oice B) are associated endocarditis (e g , Libman-Sacks), the verrucous vegetations are sterile (nonbactenal). The other choices are not associated with a significantly increased risk of bacterial endocarditis. ***Diagnosis: Bacterial endocarditis
24 A 50-year-old woman presents with easy fatigability, a smooth sore tongue, numbness and tingling o[ the feet, and weakness of the legs. A complete blood count shows a megaloblastic anemia that is not reversed by folate therapy: Hemoglobin is 5.6 gldL, vVBC count is 5 ,100/!lL, and platelets are 240,000/ JlL This patient most Ukely has a deficiency of which of the following vitamins'? ***(A) Vitamin B1 (thiamine) ***(B) Vitamin B1 (riboaavin) ***(C) Vitamin B 12 ***(D) Vitamin K ***(E) Niacin
24 The answer is C: Vitamin B12 • Except for a few rare situations, vitam]n B11 (cyanocobalamin) deficiency is usually a result of pernicious anemia, an autoimmune disease of the stomach. Vitamin B12 is required for DNA symhesis, and its deficiency results in large (megaloblastic) nuclei. ***Diagnosis: Vitamin B12 deficiency, pernicious anemia
25 A starving, 4-year-old, African boy presents \vim apathy, generalized edema, and an enlarged fatty liver. The physician notes that, despite generalized growth failure, subcutaneous fat is preserved. What is the appropriate cliagnosis? ***(A) Beri·beri ***(B) Kwashiorkor ***(C) Marasmus ***(D) Pellagra ***(E) $curvy
25 The answer is B: Kwashiorkor. Kwashiorkor is a syndrome that results from a deficiency of protein in a diet relatively high in carbohydrates. 1l is one of the most common diseases of infancy and childhood in the nonindustrialized world. It usually occurs after an infant is weaned, when a protein -poor diet, consisting principaUy of staple carbohydrates, replaces mothers milk. Unlike marasmus (choice C), the diso rder fea rures edema, large farcy liver, and depigmemation of the skin. Extreme apathy is notable, dian-hea is common, and anemia is the mle. These changes are reversible if and when sufficient protein is made available. ***Diagnosis: Kwashiorkor
26 Petechial hemorrhages were n oticed on the upper and lower extremities of a 5-day-old infant. Hemorrhagic disease of the neonate was most likely caused by a deficiency of "vhich of the following vitamins? ***(A) Vitamin B2 (riboflavin) ***(B) Vitamin D ***(C) Folic acid ***(D) Vitamin K ***(E) Pyridoxine
26 The answer is D: Vitamin K. Hemon-hagic disease of Lhe newborn may be caused by a deficiency of vitamin K. ViLatnin K Lc; an lmponant coagulation factor, which is necessary for the carboxylation and activation of prothrombin, as well as of clotting facwrs VII, IX, and X. Newborn i.nfams frequent ly exhibit vitamm K deficiency because the vitamin is not transported well across the placenta, and the sterile gm of the newborn does not have bacteria to produce it. The mher viLamin deficiencies do noL impair coagulation. ***Diagnosis: Vitamin K deficiency, hemolytic disease of Lhe newborn
27 A 6-year-old girl is examined at a clinic in central Af1ica. Physical examination reveals wasdJ1g of muscle and fat, and a protuberant abdomen. Her pulse, blood pressure, and temperature are low. The face appears wrinkled. There is no evidence of generalized edema. Wl1at is the appropriate diagnosis? ***(A) Beri-beri ***(B) Kwashiorko r ***(C) Marasmus ***(D) Pellagra ***(E) Scurvy
27 The answer is C: Marasmus. Defictency of all elements of Lhe dieLleads lO marasmus. The condition is common throughout the nonindustrialized world, particularly when breasL feeding is stopped, and a child must subsist on a caloncally inadequate diet. TI1e pathological changes are similar w Lhose in starving adulLs and consist of decreased body weighL, diminished subcutaneous fa t, a protuberant abdomen, muscle wasting, and a \Winkled face. In general , the child appears as a "shrunken old person." Wasting and increased li pofuscin pigmem are seen in most visceral organs. especially the hean and t:he Uver. No edema is present. The pulse, blood pressure, and temperamre are low, and diarrhea is common. Because immune responses are impaired, the child suffers from numerous infections. An important consequence of marasmus ls growth failure. If these children a re not p rovided w1th an adequate diet during ch ildhood, they will not reach their full potential stature as adults. Kwashiorkor (choice B) resulrs from deficiency of protein in the diet. Choices A, D, and E result fTom deficiencies of vitamin B1 , nicacin, and vitamin C. respectively. ***Diagnosis: Marasmus
28 A 40-year-old , chronicalJy Ul man from a Vietnamese village presents with painful sores around his mouth. Physical examination reveals prominem fissures at the angles o£ his mouth. Cheilosis in this patient is most likely caused by a deficiency of which of the following vitamins? ***(A) Vitamin A ***(B) Vitamin B1 {thiamine) ***(C) Vitamin B2 (riboflavin) ***(D) Vitamin B12 ***(E) Vitamin C
28 The answer is C: Vitamin 82 (riboflavin). Cheilosis refers to fissures at the angles of the mouth and is a common finding in patients with vitamin B2 (riboflavin) deficiency. RlboOavin participates in the synthesis of flavin mononucleolides. Seborrheic keratosis and interstitial keratitis of the comea also occur in pmiems wi.th vitamin B1 (riboflavin) deficiency. Except for viLamin A deficiency (which does not cause cheilosis), the other choices (B, D, and E) do nm affect Lhe skin. ***Diagnosis: Cheilosis, vi tamin B2 (ribo flavin) deficiency
29 A 32-year-old woman is a vegan (i.e., a srrict vegetarian who eats no animal products of any kind). She is weak and pale, and laboratory studies show a macrocytic, normochromic anemia (hemoglobin= 6.2 gldl). This patient most likely has whkh ol the following vitamin deficiencies? ***(A) Yilamin A ***(B) Vitamin B 12 ***(C) Vitamin D ***(D) Vitamin E ***(E) Niacin
29 The answer is B: Vitamin 812• Vitamin B1 P which is necessary for DNA synthesis, is contained only m animal products, including eggs. Extreme vegetarians may suffer vitamin B12 deficiency after many years of a restricted dieL. The result is a macrocytlc anemia similar to that seen in pemicious anemia. Macrocytic anemia is not a consequence of the other choices. ***Diagnosis: Vitamin B12 deficiency, megaloblastic anemia
30 A 46-year-old man complains of weakness, dyspnea on exertion, and palpitations. His temperature is 3JOC (98 6°F), pulse 95 per minute, respirations 24 per minme, and blood pressure 120/80 mm Hg. Physical examination reveals pulmonary rales and peripheral edema. Laboratory studies show nom1al serum cholesterol (180 mgldl ) and elevated fasting blood sugar (160 mgldL). An echocardiogram discloses significant cardiomegaly bm no valvular abnormalities or evidence of old myocardial infarcts. An angiogram shows nonnal corona1y arteries. What is the most likely cause o[ his disease? ***(A) Chronic alcoholism ***(B) Cigarette smoking ***(C) Diabetes mellirus ***(D) Diffuse alveolar damage ***(E) Rheumatic heart disease
30 The answer is A: Chronic alcoholism. Alcoholic cardiomyopa· thy correlates \Vith the total lifetime dose of alcohol and leads lO dilation and hypertrophy of the heart. As in this case, the disorder may cause congestive heart failure. Cigarette smoking (choice B) and diabetes mellitus (choice C) are associated with coronary anety disease, and rheumatic heart disease (choice E) features valvular abnormalities. ***Diagnosis: Alcoholic cardiomyopalhy
31 A 28-year-old pregnant woman weighs 86.4 kg (190 lb) and gives birth after 39 ·weeks of gestation to a small baby weighing 2,300 g (5 lb. l oz). The baby has no congenital anomalies. Which of the following maternal factors in this case may be associated with the infants low birth weight? ***(A) Folic acid deficiency ***(B) Obesity ***(C) Premature delivery ***(D) Previous oral contraceptive use ***(E) Smoking
31 The answer is E: Smoking . Fetal tobacco syndrome refers to the deleterious effects of maternal cigarette smoking on the development of the ferus_ Infants born w women who smoke during pregnancy are, on average, 200 g lighter than infants born to women who do nm smoke. These infants are nm bom preterrn, but rather, are small for gestational age. The noxious effect of smoking on t:he ferns is mirrored by its effen on the uteroplacemal unit. The incidences of abruptio placentae, placenta previa. uterine bleeding, and premature mpmre of t:he membranes are all increased in women who smoke. Evidence indicates that the injurious effects of maternal cigarette smoking are nm limited w the fetus but extend to the physical, cognitive, and emotional development o [ children at older ages. Choices A, B, and D are not associated with low birth weight infants. ***Diagnosis: Fetal tobacco syndrome
32 A 52-year-old man pTesents with sudden crushing chest pain and tachycardia He admits Lo cigarette smoking, consumption of alcohol, and abuse of illicit dmgs. An ECG is consistent with ischemic change in the anrerosepLal region of the heart. Laboratory studies show elevated semm levels o£ CK-MB and tmponin I. Semm cholesterol is 240 mgldL Which of the following most llkely contributed to this patients condition'? ***(A) Alcohol consumption ***(B) Cigarette smoking ***(C) Heroin addiction ***(D) Inadequate calcium intake ***(E) Marijuana use
32 The answer is 8: Cigarette smoking. Cigarette smoking is recognized as a major independent risk factor for myocardial infarction and acts synergistically \vith olher risk factors such as high blood pressure and elevated blood cholesterol levels. 1t not only serves to precipitate initial myocardial infarction but also increases the risk for second heart attacks and diminishes survival after a heart attack among those who continue to smoke. Smoking also increases the incidence of sudden cardiac death, possibly by exacerbating regional ischemia. Atherosclerosis of the coronary arteries and the aon a is more severe and extensive among cigarette smokers than among nonsmokers, and the dfect is dose related. Chronic alcohol consumption (choice A) actually protects against coronary aneTy disease, although dilated cardiomyopathy may develop. The other choices are not related to hean disease. ***Diagnosis: Myocardial infarction
33 A 52-year-old man presenrs with a chronic cough and shortness of breath. He admits lO smoking two packs of cigareues a day for 30 years Pulmonary function tests reveal chronic obstructive pulmonary disease. In counseling this patient, you advise him w swp smoking immediately. You also mention Lhat, in addition to emphysema, which of the following organs carries a significantly increased risk of smoking-related cancer7 ***(A) Brain ***(B) Uver ***(C) Pancreas ***(D) Skin ***(E) Small bowel
33 The answer is C: Pancreas. Cancer of the pancreas has shown a steady increase in inctdence, which is panty related LO cigarene smoking. The risk for adenocarcinoma of the pancreas in male smokers is elevated two- lO threefold, and a clear doseresponse relat]onship exists. ln fact, men who smoke more than rwo packs a day have a five Limes greater risk of developing pancreatic cancer than nonsmokers. Smoking does not 1ncrease the risl< of cancer for the other choices. ***Diagnosis: Chronic obstructive pulmonary disease
34 A homeless, poorly nourished man collapses on the street and cannot be revived by the emergency medical technicians. A social service agency notes that he had a long history of abusing many illicit drugs. An autopsy is petfonned and reveals a moderately enlarged heart, with patent coronary arte1ies and no vah'\Ilar abnonnalities. Microscopic examination shows patchy fibrosis of the myocardium. Which of the fol lowing substances most likely caused thjs cardiomyopathy? ***(A) Cocaine ***(B) Heroin ***(C) Lysergic acid diethylamide (LSD) ***(D) Matijuana ***(E) Methamphetamine
34 The answer is A: Cocaine. Cocaine overdose leads to anxiety, delirium, and occasion ally seizures. Cardiac arrhythmias and other effects on the heart may cause sudden death in other\ Vise healthy persons. Chronic abuse of cocaine is associated with the occasional development of a charactensti.c dilated cardiomyopathy, probably because of its effects in small, imramyocarcltat, coronary arteries. The other choices do nol cause cardiomegaly. ***Diagnosis: Cocaine cardiomyopathy
35 A 52-year-old, obese man (BMI = 34 kglm2) presents to his physician with complain£5 of hoarseness for 2 months. He has worked in a chemical factory for 25 years and gives a history of smoking, consumption of one or two beers a day, and occasional use of illicit dmgs. Physical examination reveals enlarged and firm cervical lymph nodes. Direct laryngoscopy reveals a fixed and enlarged left vocal cord, which appears ulcerated. A biopsy of the lesion is interpreted by the pathologist as squamous cell carcinoma. vYhat is the most likely cause of this mans disease? ***(A) Alcohol ***(B) Benzene inhalation ***(C) Cigarette smoking ***(D) Cocaine use ***(E) High-fat diet
35 The answer is C: Cigarette smoking. Cancers of the hp, wngue, and buccal mucosa occur principally (>90%) in wbacco users. Cancer of the la1ynx and esophagus also result fTom smoking (>80% of cases) In some large studies, aU deaths fmm cancer of the la1ynx occurred in smokers. There is no epidemiologic evidence that the other choices are 1isk factors for la ryngeal cancer, although chronic alcoholism may be associated with a slightly increased risk. ***Diagnosis: Laryngeal carcinoma
36 A 48-year~old man complains of weakness and easy fatigability for 6 weeks. He has worked for 20 years in a chemical factory that produces a variety of plastics and other synthetic compOLmds. A complete blood count shows a hemoglobin level of 8.2 g!dL, WBC count of 45,000/~L , and a platelet coum of 40,000/~L Examination of a bone marrow aspirate reveals numerous malignant myeloblasts, and a diagnosis of acme myeloid leukemia is made. Exposure to which of the following agents is the most likely cause of this patient's hematologic disease? ***(A) Benzene ***(B) Benzopyrene ***(C) Carbon tetrachloride ***(D) Glycerin ***(E) Ttichloroethylene
36 The answer i.s A: Benzene. Vinually all cases of acute and chronic benzene toxicity have occurred against the background of industrial exposure. Acute benzene poisoning pnmarily affects the cenu·al nervous system, and death results from respiratOl)' fai lu re. However, the long-term effects of benzene exposure have attracted the most attention. The bone marrow is the principal target in chronic benzene intoxication. Patients who develop hematologic abnonnalities characreristically ex.hibit hypoplasia or aplasia of the bone marrow and pancytopenia. Aplastic anemia usually is seen while the workers are still exposed to high concemmtions of benzene. In a substantial proportion of cases of benzene-induced anemias, acme myeloblastic leukemia develops. Overall, the risk of leukemia is increased 60-fold in workers eA.'Posed to t.he highest atmosphetic concentrations of benzene. The other choices are not linked to t.he development of leukemia. ***Diagnosis: Acute myelogenous leukemia
37 A 48-year-old woman complains she has had weakness, fatigue, and easy bmis.ability for 2 months. She had worked as a technician in a nuclear energy plant for 15 years and was involved in an accident during which she was exposed to considerable radtation. PhysicaJ examination reveals an enlarged liver and spleen. What disease should you suspect as a likely cause of her condition? ***(A) Chronic myelogenous leukemia ***(B) Hairy cell leukemia ***(C) Metastatic carcinoma of the breast ***(D) Metastatic carcinoma of the stomach ***(E) Osteogenic sarcoma
37 The answer is A: Chronic myelogenous leukemia. The evidence that. whole-body radiation can lead to cancer is mcontmverdble and comes from animal experiments and studies of the effects of occuparional eA.1Josurc, radiation therapy for nonneoplastic conditions, the diagnostic use of certain radioisotopes, and the atom bomb explosions. Some survivors of the atom bomb explosions and patien ts subjected to spinal radiation later developed chronic myelogenm..1s leukemia. Although the other choices may lead to hepatosplenomegaly, they are not linked to acute radiation exposure. ***Diagnosis: Chronic myelogenous leukemia
38 A 16-year-old girl has suffered from severe celiac disease for years and reports continued stearorrhea. She suddenly develops abdominaJ pain in the 1ight lower quadrant. A complete blood count shows a hemoglobin level of 14 gldL, WBC of 18,000/!Jl , with 84% neutrophils, and a platelet coum of 280,000/!JL. A diagnosis of appendicitis ts made, and tests before surgery reveal a prolonged prothrombin time of 17 seconds (control = 2). What is the most likely cause of her coagulation problem? ***(A) Hemophilia A ***(B) Hemophilia B ***(C) Hypolipidemia ***(D) Lymphoblastic leukemia ***(E) Vitamin K deficiency
38 The answer is E: Vitamin K deficiency. Vitamin K deficiency is common in severe fat malabsorption, as seen in ce Hac sprue and biliary tract obsuuction. The destruction of intestinal flora by antibiotics may also result in vitamin K deficiency. Vitamin K, whkh conJers calcium-binding properties to certain proteins, is imponant for the activicy of four clmting factors: prothrombin, factor Vll, factor lX, and facto r X. Deficiency of vitamin K can be serious because it can lead to catastrophic bleeding ***Diagnosis: Vitamin K deficiency
39 A 24-year-old beating victim is brought to the emergency room \.Vith a -1--cm linear tear of the skin caused by blum trauma. Which of the following terms best describes this patients skin 1e st.o n_1 ***(A) Abrasion ***(B) Avulston ***(C) Blast injury ***(D) Comusion ***(E) Laceration
39 The answer is E: Laceration. A laceration is a linear tear of the skin produced by a fo rce that causes unidirectional displacement. A surgical incision is a comrolled laceration. Internal organs may also be lacerated by trauma or by the surgeon. An abrasion (choice A) is a skin defect caused by crushes or scrapes. Avulsion (choice B) is a tearing away or forcible separation. A contusion (choice D) is a localized mechanical injury with [ocal hemorrhage. ***Diagnosis: Laceration
· 1 A 2.3-year-old man presenlS \Vilh a 6-day history of fever, sore tJ1roat, swollen lymph nodes, weight loss, and fatigue. Physical examination shows generalized lymphadenopathy, most prominent in the cervical lymph nodes, and mild h epatosple- 11omegaly The pe1ipheral blood smear shows 65% atypical lymphocyJes. A Paul-Bunnell antigen test (heterophile an tibody test) is positive. The semm ALT, AST, and bilintbin are slightly elevated. The atypical lymphocytes in this patients peripheral blood are described as which of the foltmving? ***(A) Activated T cells ***(B) lmmamre B cells ***(C) Mature B ce lls ***(D) Natural killer cells ***(E) Plasma cells
1 The answer is A: Adivated T cells. Infectious mononucleosis is characterized by fever, pharyngitis, lymphadenopathy, and circulming atypical lymphocytes. This systemic viral infection is caused by EpsLein-Barr virus (EBV), a herpesvirus chat is n·m15n)jued through respiratory droplets and saliva and binds w nasopharyngeal cells and B lymphocytes. T cells proliferate in response w activated B lymphocytes and appear in the petipheral blood as atypical lymphocytes. Anemia and thrombocytopenia are conunon. Ln developed countries, mfecrious mononucleosis commonly affects teenagers and young adults and is often referred was the "kissing disease." In underdeveloped commies, EBV infections are typically seen as subclinka] infections in chUdhood and are associated \".:ith an increased risk of Burkitt lymphoma and nasopharyngeal carcinoma. Although EBV infects B ce!Js, the circulating atypical lymphocytes seen in patien ts with infectious mononucleosl'> are not immature B cells (choice B), but rather indirectly activated T cells. ***Diagnosis: Infectious mononucleosis
2Which of the following is the most likely compUcarion for the patient described in Question 1? ***(A) Burkitt lymphoma ***(B) Cirrhosis ***(C) Encephaluis ***(D) Laryngeal stricture ***(E) Rupmre o[ the spleen
2 The answer is E: Rupture of the spleen. Splenomegaly often develops in patients with mfectious mononucleosis due w lymphoid infilo·ation, hyperplasia, and edema. The enlarged spleen may rupture after minor trauma. Burkitt lymphoma (choice A) is associated wiLh Epstein-Barr virus infection in certain parts of the world but is uncommon in Nonh Ametica. ***Diagnosis: Infectious mononucleosis
3 A 19-year-old woman presents with vague lower abdominal pain and a swollen , painful right knee. She denies any tTauma to the knee or history of arthritic disorders. Physical examination reveals an enlarged joint that is red, warm, and painful. Pelvic examination is exquisitely painful and reveals an illdefined thickening in both adnexae. A green-yello'.v purulent vaginal discharge is noted. The patiem is febrile and has an devated 'NBC count of 15,000/).1L Which of the following e£iologic agems is most likely responsible for this patiems condi Lion? ***(A) Escherichia coli ***(B) Neisseria gmwrdweae ***(C) Streptococws pyogenes ***(D) 1h~p011ei1W pallidum ***(E) Yersinia pestis
3 The answer is 8: Neisseria gonorrhoeae. N. gonorrfweae causes an acute suppurative infection of the genital tract. wruch presents as urethrltis in men and endocervicitis in women. lt is 011e of the most commonse>.'Ually transmiued diseases_ Gonorrhea may involve the throat, anus, rectwn, epicUdymis, cervix, fallopian rubes, prostate gland, or joims. Septic arthritis due to N. gonon1weae, a suppurative inflammadon most commonly caused by hemawgenous spread, is usually monoarticular, most commonly affecting hips and knees. The other choices do not typically exhibit arthritis and acute pelvic disease. Primary syphilis (choice D) presents \vith chancre. ***Diagnosis: Gon orrhea
4 A 54-year-old man presents with a worsening skin rash of 10 days in durmion. Physical examination shows an extensive, desquamative maculopapular rash of the palms and soles (shown in Lhe image). The VDRL and FT-ABS tcsLs are both positlve. Which of the following lesions is also expected in this patient at this stage of his disease? ***(A) Chancre ***(B) Dementia ***(C) Endarteritis obliLerans ***(D) Gummas ***(E) Tabes dorsalis
4 The answer is C: Endarteritis obliterans. Seconda1y syphilis represents systemic dissemination and proliferation of the spirochete. Treponema pallidum. This stage is charaCLerized pathologically by lesions in skin, mucous membranes, lymph nodes, meninges, sLOmach, and liver. The lesions show a petivascular lymphocytic infiltration and endaneritis obliterans. In most cases, the rash appears 2 weeks to 3 momhs after 1.he primary lesion (chancre) heals. Other lesions a.ssociated with secondary syphilis include condylomata lata, follicular syphilis, and nummular syphUis. Chancre (choice A) is a characteristic lesion of primary syphilis. Choices B, D, ru1d E are encoumered ln patiems wilh tertimy syphilis. ***Diagnosis: Syphilis
5 A 35-year-old man presems with multiple skin lesions on his left forearm. He had worked in a garment factmy, where he sorted wool imported from Iran. Physical examination shows an elevated cutaneous papule with blood)' pumlem eA'Udate. An adjacem lesion displays a black scab. There is prominent axillary lymphadenopathy This patients necrotizing skin lesions are most likely caused by which of the following pathogens? ***(A) Bacillus anthracis ***(B) Clostridium pe1jringens ***(C) Escherichia coli ***(D) Streptococcus pyogene.s ***(E) Tn~ponema pallidum
5 The answer is A: Bacillus anthracis. Amh rax is a necrmizing disease caused by B. anthracis. The clinical presentation of anthrax depends on the si te of inoculation and includes malignant pusLUle, pulmonary amhrax, septicemic amhrax, and gastroimest.inal amhrax. B. anthacis typically produces extensive tissue necrosis at the site or infection, with a mild neutrophilic infiltration Malignant pusmle is seen in over 95% of all cases of anthrax and represems the cutaneous form of this infectious disease. The infected person presents with an elevated cutaneous papulae that enlarges and erodes into an uker. Local hemorrhagic pustules may progress to carbuncles. Cutaneous lesions comain numerous organisms that rel.ease a potent necrotizing to:>..'in. The other choices do not typically present with these necrotizing cutaneous manifestations. ***Diagnosis: A.nrhrax, malignam pusrule
6 A 24-year-old man, who has just returned from a lrip to India, complains of fatigue and severe, unremitting, watery diauhca. l aboratory studies show severe hypernatremia and hypokalemia. Which of the following metabolic changes in enterocytes is chiefly responsible for lh e pathogenesis of this patients acute gastrointestinal disorder? ***(A) Decreased intracellular calcium ***(B) Decreased plasma membrane biosynthesis ***(C) Decreased ..,.vater secretion ***(D) lncreased inu·acellular cAMP ***(E) Increased intracellular water
6 The answer is D: Increased intratellular tAMP. Cholera is a severe diarrheal illness caused by the enterotoxin or Vibrio cltoleraE an anaerobic Gram-nega tive rod . The organism proliferates in the lumen of the small intestme and causes profuse watery diarrhea and rapid dehydration. Shock and death can ensue within 24 hours from the onset or symptoms. The AB toxin secreted by the organism binds to ganglioside GMl on intestinal epithelial cells and stimulates an increase in innacellular levels of cAMP, thereby leadmg to water secretion. The mucosa does not show significant pathologic changes The other choices directly injure the intestinal mucosa and cause hemorrhage. ***Diagnosis: Cholera, acute gastroenteritis
7_ A 12-year-old girl develops feve r, abdominal pam, and bloody dianhea l to 2 days after eating a hamburger at a fast food restaurant. Physical examill ation reveals an extensive purpuric skin rash. The patient develops oligu ria, and laboratory studles show elevated serum Levels o[ BUN and creati11ine. Which of the foUov.ring is the most likely etiolog~c agem responsible for this patient's condition? ***(A) Campylobacterjejuni ***(B) Escherichia coli 0157-H7 ***(C) Salmonella typhi ***(D) Sl1igella dysenteriae ***(E) Yersinia pestis
1 The answer is 8: Escherichia coli 0151·H1. Emerohemorrhagic E. coli (serotype 0157-H7), which may contaminate meat or mHk, causes bloody diarrhea, which can be fol1owed by the hemolytic-uremic synd rome. The organism adheres to the colonic mucosa and releases an enterowx'in that destroys epithel]al cells. Patients present with abdominal pain, 10\vgrade fever, and bloody diarrhea. Stool examination shows leukocytes and erythrocytes. Hemolytic-uremic syndrome is manifested by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal fai lure. Although they may be associated with bloody diarrhea, the other choices do not present with hemolytic-uremic syndrome. ***Diagnosis: Hemolytic-uremic syndrome, enterohemorrhagic E. coli
8 A 65-year-old man undergoes cardiac bypass surgery and is placed on postoperative, broad-spectmm, an tibiotic prophylaxis. Several days later, he develops feve r, abdominal pain, and bloody diarrhea. Colonoscopic bio psy demonstrates a thick mucopuntlent exudale. Which of the following is the most likely etiology of this patiems gastrointestinal disorder? ***(A) Clostridium botulinum ***(B) Clostriditm1 difficile ***(C) Clost ridium pe•f ringens ***(D) Clost ridiwn tetani ***(E) Escltericl1ia coli 0157-H?
8 The answer is 8: Clostridium ditficile. C. diffic ile is the most common cause of diarrhea in patients on antibiotic therapy (e.g., clindamycin or cephalosporlns) v.tho are has· pilali.zed for more than 3 days. Necrotizing enterocolitis (pseudomembranous colitis) is a disease t11at may affect the colon in segments or in its entirety. The mucosa is covered by yellow-green, necrotic exudates (pseudomembranes). f ood poisoning and necrotizing entercoliris are caused by the emerotoxit15 of C. pe1jringens (choice C). Abom 48 hours after the ingestion of contaminated meal, patiems p resent with abdominal pain and distemion, vomiting, and passage of bloody stools. C. pe1jringens is also the most common cause of gas gan grene foUowing wound infection or septic abortion. C. tetal'li (choice D) produces a potent neurowxin that causes tetany and generalized muscle spasms. Clostridium botulinum (choice A) produces a neurowxin that causes paralysis. ***Diagnosis: Pseudomembranous colitis, Clostridittm difficile
9 A 24-year-old woman develops an expanding erythematous .___ skin lesion after hiking th rough the woods in Connecticut. The rash disappears, buLl year later. the patiem develops anhralgias and right facial nerve palsy Vv'hich of the following is the most likely etiologic agent responsible for this patiem's symptoms? ***(A) Chlamydia ***(B) Mycobacterium ***(C) Prowzoa ***(D) Rkkettsia ***(E) Spirochete
9 The answer is E: Spirochete. Lyme disease is a chronic infection that begins with a characteristic skin lesion and later vatiably manifests cardiac, neurologic, and joinr dismrbances. The causative a gem is Bon-elia br~rgdorferi , a large spirochete rhat is rransmitted from its animal reservoir to huma115 by the bite of the deer tick (Lxodes). 13. burgda~fe ri reproduces althe site of inoculation, spreads to regional lymph nodes, and is eventually dtsseminated throughomthe body. Untreated Lyme disease is chronic, with petiods of remission and exacerbation. Stage 1 is charactetized by erythema chronicum migrans, a skin lesion that appears at the site of the tick bile. Stage 2 features migratory musculoskeletal pain and the development of cardiac or neurologic abnormalities (meningitis and facial nerve palsy). Stage 3 begins months to years after infection and involves joint, skin , and neurologic abnonn alities. Over half of these patients develop a severe arthritis of the hips and knees, which is indistinguishable h·om the symptoms of rheumatoid arthritis. ***Diagnosis: Lyn1e disease
10 A 3-year-old child attending a daycare center develops fever, chills, generalized rash, and a stiff neck. The chUd becomes hypotensive and expires the next day Postmortem examination demonstrates bilateral adrenal hemonhages {shown on light). Which of the following etiologic agents is the most likely cause of this childs disease? ***(A) Haemophiltts injl.ttenzae ***(B) Klebsiella 1meumoniae ***(C) Neisseria meningitides ***(D) Strepto cocctiS pnewnoniae ***(E) Tr·el'onenta pallidum
10 The answer is (: Neisseria meningitides. Acme meningococcal meningitis may develop rapidly and is often fatal. Meningococcal sepsis is marked by profound endotoxemic shock and disseminated imravascular coagulation, knowt1 as Waterhouse-Friderichsen syndrome. Airborne transmission in crowded places (e.g., schools or barracks) can cause "epidemic meningitis.- Fever, malaise, petechial rash, and adrenal hemorrhages are common. Although they may cause meningitis, choices A, B, and D are nor typically associated \vith Waterhouse-Friderichsen syndrome. Diagnods: Meningococcal meningitis, Waterhouse-Friderichsen syndrome
11 A 45-year-old woman from lndia develops paroxysms of feve r, chills, and severe h eadache while vis iting her brmher in the United States. Physical examination demonstrates hepawsplenomegaly and general pallor. Laboratory studies show anemia and hyperbilirubinemia. Her utine appears dark on visual inspection, and a urin e dipstick is positive for hemoglobin. The patient develops tonic-clonic seizures and becomes comatose. Which of the followi ng pathogens is most likely responsible for this patient's symptoms? ***(A) Naegleria Jowleri ***(B) Pla.~modium falciparum ***(C) P/a.-;modium vivax ***(D) Schistosoma 1taematobiLtm ***(E) Trypanosoma bmceii
11 The answer is B: Plasmodium falclparum . Malaria is a mos- L...- quito-borne illness that infects over 200 million persons per year world\vide. There are four species of Plasmodium: P Jalciparum , P. vivax, P. a vale, and P. ma lariae. All of these organisms infect erythrocytes, but P. Jalc i parum causes the most severe disease. ln malignant"" malaria caused by P. falciparum ," ischemic injm)' to the b rain causes a range of symptoms, including somnolence, hallucinations, behavioral changes, seizures, and even coma. The liver, spleen, and lymph nodes are darkened by macrophages chat are filled with hemosiderin and malmia pigmems. Naegleria fowleri (choice A) is associated with a fatal rype of meningitis. Schistosoma l!aematobiwn (choice D) is associated with bladder infections but does not cause the hematologic symptoms seen in this patiem. ***Diagnosis: Malaria
12 A '56-year-old woman undergoes multidrug chemotherapy for breast cancer. After 10 days, she develops cough , feve r, and respirawry distress. An X-ray film of the chest shows multiple areas of consolidation, with a large cavity in the right upper lobe. Despite vigorous therap y. the patiem dies. Examination of the lungs at auwpsy discloses multiple, sharply delineated, gray foci with hemonhagic borders. A section of lung impregnated \vilh silver is shown in the image. Which of the following mechanisms of disease best accounts for these pathologic findings? ***(A) Allergic inOammation ***(B) Necrosis of type 1 pneumocytes and formation of hyaline membranes ***(C) Pe1ivascular plasma cell infiltrate with obliterative endarteritis ***(D) Production of toxins d1at inhibit protein synthesis ***(E) Thrombosis of blood vessels invaded by hyphae
12 The answer is E: Thrombosis of blood vessels invaded by hyphae. The photomicrograph displays mvasive aspergillosis. This is the most serious manifestation of Aspergillus infection, occunmg almost exclusively as an oppommisLic infection in persons wiLh compromised immunity. Aspergillus readily invades blood vessels and causes thrombosis and local infarction. Branching hyphae (visualized by silver stain) are found in the walls and lumens of pulmonary vessels. ***Diagnosis: Invasive aspergillosis
13 A 30-year-old woman presems with persistent dry cough, fatigue, and low-grade fever. Physical examinaLion shows marked pallor, respiratory distress, nasal flaring, and intercostal retractions. A chest X-ray reveals diffuse, bilateral interstitial infiltrates. A photomicrograph of bronchoalveolar lavage is shown. Which of the following etiologic agents is most likely responsible for this patiem's pulmonary disease? ***(A) As11ergillus fumigatlt5 ***(B) Legionella tmeumoniae ***(C) Mycoplasma pneumoniae ***(D) Pneumocystis jiroveci ***(E) Respiratory syncytial virus
13 The answer is D: Pneumocystis jiroveci. P. jiroveci (formerly P. carinii) was identified in malnourished infants at the end of 'vVorld War ll. lt causes progressive, often fatal pneumorua in persons with impaired cell-mediated immunil:)' and is one of the most common opportunistic pathogens in persons with AIDS. The organism is now classified with the fungi. The infection begins with the attachment of trophozoites to Lhe alveolar lining. Trophozoites feed, enlarge, and transform into cysts within the host cells. Eventually, the cysts burst, releasing new trophozoites. Progressive consolidation of the lung ensues. Although the other choices cause pneumonia, they do not exhibit these charactetistic cysts. ***Diagnosis: Pneumocystis pneumonia
14 A 28-year-old man presents with sudden onset of fever, chills, and a productive cough with blood-tinged sputum. His past medical history is significant for a splenectomy following a motor vehicle accident 3 years ago. An X-ray of the chest demonstrates consolidation of the right middle lobe. Sputum culture shows Gram-positive diplococci. ¥Vhich of the following is the most likely cause of thi.s patients respiratory infection? ***(A) Klebsiella 1me~tmo niae ***(B) Legionella pneumophila ***(C) Mycoplasma pneumoniae ***(D) Staphylococcus m~reus ***(E) Streptococws pneumoniae
14 The answer is E: Streptococcus pneumoniae. S. pneumoniae (pneumococcus) causes pyogeruc infections involving the lungs (pneumonia), middle ear (otitis media) , sinuses (sinusitis), and meninges (meningitis) It is one ofthe most common causes of community-acquired pneumonia. Consolidation of lung parenchyma typically produces lobar pneumonia, whid1 passes through four stages: (l) congestion and edema, {2) red hepatization, (3) gray hepatization, and (4) resolution. During the acme phase, the alveoli are packed with neutrophils, fibrin, and debris. Pneumonia is caused by the other organisms with much lower frequency. ***Diagnosis: Pneumococcal pneumonia
15 An 11-year-old boy presents with tea-colored urine and reduced urine output. He was seen for acute pharyngitis 3 weeks previously: Physical examination shows puniness around the eyes and pining edema of the lower extremities. Temperature and blood pressure are normaL Utinalysis reveals 2.+ hematuria and 3+ protein uria. Blood analysis discloses reduced semm levels of C3 and an elevated titer of antistreptolysin 0 andbodies. This patient's renal disease is most likely mediated by which of the following mechanisms? ***(A) Antineurrophil cytoplasmic amoamibodies ***(B) Deposition of circulating immune complexes ***(C) Directly cytotoxic lgG and lgM amibodies ***(D) IgE- mediated mast cell degranulation ***(E) T cell-mediated delayed hypersensitivity reaction
15 The answer is B: Deposition of circulating immune complexes. Infection with Streptococcus pyogenes causes tvvo major nonsuppurative complications, namely rheumatic fever and acute postsu-eptococcal glomeruloneph1itis. Postsu-eptococcaJ glomerulonephritis is a classic immune complex-mediated disease that is associated with nephritic syndrome. Posrsrrepwcoccal illnesses are not mediated by any of the other choices. ***Diagnosis: Poststreptococcal glomerulonephritis
16 A 59-year-old man with colon cancer is treated with chemotherapy. Two months later, he develops increasing cough and respiratory distress. A chest X-ray shows diffuse bilateral interstitial infiltrates. Spun.lm cultures are negative, and the patient does not respond to antibiotic therapy. A lung biopsy reveals acute and chronic interstitial pneumonitis. There are enlarged cells with prominent, dark-blue nuclear inclusions (shown in the image). Which of the following is most likely responsible for this patient's pulmonary condition? ***(A) Cytomegalovirus ***(B) Epstein-Barr virus ***(C) Herpes simplex virus ***(D) Mycoplasma ***(E) Pneumocystis jiroveci
16 The answer is A: Cytomegalovirus (CMV) . CMV infection induces interstitial pneumortia in infants and immunocompromised persons. InJected alveolar ceUs show cytomegaly and display a single, dark basophilic nucleaT inclusion surrounded by a halo. The virus may be Lransmirted from mother to child in mero or acquired during delivery. In adullS, CMV is transmitLed through sexual encoumers, blood transfusions, rransplamarion, and even duough the inhalation of infectious viral panicles. Central nervous symptonls predominare in symptomatic infants and children. In adults, the virus produces mostly respiratory and gastrointestinal symptoms but does not cause encephalitis. Herpes simplex virus {ch oice C) also feamres intranuclear inclusions (also surrounded by a clear halo) but does not cause ch ronic imersddal pneumonia. ***Diagnosis: lnLerstilial pneumoo.iLis, cytomegalovirus pneumonitis
17 A 6-month-old female infam is brought to Lhe physician with a 2.-day history of severe cough, wheezing, and respiratory distress. Physical examination shows rhinitis, mild cyanosis, and fever. Which of the following is the most likely etiology of d1is child's pulmonary infection? ***(A) Adenovirus ***(B) Cywmegalovi rus ***(C) Parainfl uenza virus ***(D) Respirawry syncytial vims ***(E) Rhinovirus
17 The answer is D: Respiratory syncytial virus (RSV). R5V is an RNA vints, which i.s the m~jor cause of bronchiolitis and pneumonia in infams. RSV bronchiolitis or pneumonitis presems with e.:-:p iracory and inspiratory wheezing, cough , and hypere;...'}Jansion of both lung fields. Hyperinflation, imerstidal infiltrates, and segmented atelectasis are expected findings on chest X-ray. The illne.c;s is usually self-limited and typically resolves within 1 to 2 weeks. Monality ls low in healthy babies. The oLher viruses cause pn eumonia much less frequently. ***Diagnosis: Respirawry syncytial virus, bronchiolitis
18 A 75-year-old woman died in February o[ respiratOl)' failure after a febrile disease of 1 week in duration. An au topsy shows necrotizing bronchitis and diffuse , hemonhagic necrotizing pneumonia. Which o[ Lhe following pathogens was most likely responsible for this patients fatal pulmonary infection? ***(A) lnfluenza vims ***(B) Norwalk-like viruses ***(C) Respiratmy syncytial vims ***(D) Rhinovirus ***(E) Rotavirus
18 The answer is A: Influenza virus. In fluenza A and B arc RNA vi1uses. Influenza infections are common in the >vin te rtime, wirh the severity of the illness depending on the immune status of the individual. Patients typically presem with fever, tachypnea, conjunctivitis, and pharyngeal inflammation. In severe cases, they may develop extreme respirat01y distress and prostration Influenza affects all segments of the populati on, bm severe cases are more commonly seen among the very young and the elderly Rhinoviru..c; (choice D) i.s the most f1-equem cause of the .. common cold." Notwatk-like virus (choice B) and rmavin.LS (choice E) cause diarrhea in children. Infection with respiratmy syncytial virus (choice C) is commonly seen. in duldren Lmder 2 years of age. ***Diagnosis: In fluenza vi rus, pneumonitis
19 A 4-year-old girl, whose parents recenlly immigrated from Ecuador, presents with high fever, cough, and skln rash of 3 days in duration . Her parents report that her rash began in the form of pink papules behind the ears and spread around her body Physical examimuion shows an extensive maculopapular rash over the childs face, neck, mmk, and limbs. She displays smal1 white spots on buccal surfaces. Tllis patients skin rash is most likely caused by infection \1./ith which of the following agents7 ***(A) Candida albicans ***(B) Epstein-Barr virus ***(C) Measles virus ***(D) Mumps virus ***(E) Rotavirus
19 The answer is C: Measles virus. Measles virus is an RNA vims Lhat causes an acme, highly contagious, self-limited iUness Lhat is characterized by upper respiraLory tract symptoms, fever, and rash . The measles virus, which is transmitted in respirawry droplets and secretions, is primarily a disease of children, bm its dfects may be particularly severe in adults. The skin rash results from 1.he reaction ofT cells with infected cells of Lhe vascular endothelium. "Koplik spots" appear on the postetior buccal mucosa and consist of minute gray-white dots on an erythematous base. Although measles is usually a selflimited disease, measles pneumonia (particularly in adults) is a serious malady that may be fatal. Epstein-Ban virus infection and mumps (choices Band D) do not present with gen eralized rash. Rotavirus infection (choice E) is the most common cause of severe diarrhea worldwide. The yeast, Candida albicans (choice A), usually causes localized infection. ***Diagnosis: Measles
20 A 50-year-old woman presents whh increasing dry cough and shortness of breath that has lasLed for 3 weeks. She is a bird fancier, and her house is filled Virlth parrots. An X-ray film of the chest shows diffuse lung infiltrates. Spurum cultures are negative, and the patiem does rrot respond to antibiotic therapy. A transbronchial aspirate reveals chronic interstitia] pneumonia. The patient responds well to tetracycline. vVhkh of the following is the most likely etiologic agenl responsible for this patients symptoms? ***(A) Chlamydia ***(B) Fungus ***(C) Gram-positive bactetium ***(D) Mycobacterium ***(E) Rickettsia
20 The answer is A: Chlamydia. Psittacosis is a self-limited pneumonia transmitLed to humans from birds. The etiologic agent, Chlamydia psittaci, is present in blood, feces, and feathers of infected birds. The organism first infects alveolar macrophages, which carry it to the liver and spleen, where it reproduces. The organism is then distributed hematogenously to produce a systemic infection. C. psittaci reproduces in alveolar lining cells, whose destmction elicits an inflammatory response and interstitial pneumonia. Type 11 pneumocy1es are hyperplastic and may show charactetistic chlamydial cytoplasmic inclusions. Clinically, the disease presents with persistent dry cough, fever, headache, malaise, myalgias, and anhralglas. The ocher agents listed do nor cause chronic mterstitial pneu- . moma. ***Diagnosis: PsiLtacosis
21 A 5-year-old boy dies of respiratory insufficiency and complications of pneumonia. Histologic examination of the lungs at autopsy shows giant cells with up to 100 nuclei (shown in the image). Which of the following viruses most likely caused this childs fatal respiratory u act infection? ***(A) Aden ovi rus ***(B) Cytomegal OVl rus ***(C) Measles virus ***(D) Mumps nrus ***(E) Rube1la\1rus
21 The answer is C: Measles virus. Measles virus can cause f·usion of infected cells, producing multinucleated cells termed "Wanhin-Finke1dey giant cells." These multinucleated giam cells are pathognomonic of measles infections. Cywmegalovirus-infected cells (choice B) are very large and contain nuclear and cytoplasmic viral inclusions, but they are not multinucleated. Adeno•"lrus (cholcc A) also feawrcs intranuclear inclusions but not multinucleation. Mumps and rubella viruses (choices D and E) induce a mononuclear infiltrate composed of lymphocytes, macrophages, and plasma cells (no giant cells). ***Diagnosis: Measles
22 A 4'5-year-old man who IS a hem-y smoker complams of sudden onset of h1gh fever and ch1lls. nonproductive cough, and chest pam. An X-ray film of the chest shows bilateral, diffuse, patchy infiltrates. The patient repor ts that a number of similar cases have occurred recently in the building where he works. He responds w antibiotics and recovers. Which of the following is the most likely a reservmr for the microorganism mar is responsible for this patient's respi ratory traer infection? ***(A) Cooling towers ***(B) Elevawr shafts ***(C) Floor cleaners ***(D) Heat pumps ***(E) Industrial solvents
22 The answer is A: Cooling towers. Legionella pneumophila causes a pneumonia that ranges from mild lO a severe lifethreatening, necroti~ing pneumonia refetTed to as "legionnaire disease." The bacterium is found in natural bodies of fresh water and survives chlorination, atl01.ving it to proliferate ln cooling towers, water heaters , humidifie rs, and ventilation systems. l egionella pneumonia begins when microorganisms enter alveoll, where they are phagocytized by resident macrophages. Bacteria multiply within macrophages and are released to infect ne\v macrophages. The disease presents as an acme bronchopneumonia, with a diff·use and pau:hy pattern of infiltration. None o[ the Olher situations creales suitable conditions for bacter ia to multiply. ***Diagnosis: Legionnaire disease
23 A 37-year-old man is admitted to the hospital with a productive cough, fever, and night sweats. An X-ray film of the chest shows an ill-defined area of consolidation at the periphety of the right middle lobe and mediastinal lymphadenopathy. Sputum culture grows acid-fast bacilli. Lymph node biopsy in this patient would most likely show which of the following pathologic findings? ***(A) Caseating granulomas ***(B) Follicular hyperplasia ***(C) Nodular amyloidosis ***(D) Noncaseating granulomas ***(E) Pumlem abscess
23 The answer is A: Caseating granulomas. Tuberculosis is a chronic, communicable disease in which the lungs are the prime Larger. The disease is caused principaUy by Mycobacterium tuberculosis Jwminis (Koch baciJlus), bur infection with other species occu rs, nmably M. tttb ercu losis bovis (bovine tuberculosis) Primary tuberculosis consists of lesions in the lower lobes and subpleural space, rderred to as the Ghon focus. The infection then dnnns to hilar lymph nodes. The combinarion of Chon focus and hilar lymphadenopathy is known as "Ghon complex." The t)1)ica! lesion of tuberculosis is a caseous granuloma, wilh a soft core surrounded by epilh el]oid macrophages, Langhans giant cellc:;, lymphocytes, and pe1ipheral fibrosis. Noncaseating granulomas (choice D) are a feature of sarcoidosis, among other causes. ***Diagnosis: Primary tuberculosis
24 A 24-year-old woman with insulin-dependem (type 1) diabetes mellitus presents to the emergency room with severe respiratory distress and pleuritic chest pain. The pmiem has a history of antibiotic-resistant sinusitis. Physical examhuuion reveals pe1iorbital edema and a mucopmulent postnasal discharge. Despite therapy, the patient dies of acute respiratmy failure. Cross secnon of the lu11g at autopsy shows hemorrhagic infarction. The vessel in the center of the field is occluded by a septic thrombus (sl1own in the image). These clinicopathologic featu res are typical of which of the fo ll O\\rlng pulmonary diseases? ***(A) Haemophi/Lts injl uenzae pneumonia ***(B) Mucormycosis ***(C) Parainfluenza vims pneumonia ***(D) Pneumocystis jiroveci pneumonia ***(E) Psittacosi.s
24 The answer is B: Mucormycosis. Environmental fungi, such as Rhi zopt-ts, Muco r, Rhizomucor, and Absidia species, can produce necrotizing opportunistic infections that begin in the nasaJ sinuses or lungs. Mucor is ubiquitous in the nasal sinuses and invades sun ounding tissues. The hard palate or nasal cavity is typically covered by a black crust, and the underlying tissues become friable and hemorrhagic. The fungal hyphae grow imo arte ries, causing devasLating and rapidly progressive septic embolic infarctions. There are Ll1ree principal fom1s of mucormycosis, namely rhinocerebral, pulmonary, and subcutaneous. Pulmonary mucom1ycosi.s is usually fatal. Microscopic examination shows a p urulem ane1itis \vi.th thrombi composed of hyph ae. Mucormycosis should be suspected in patients who present with a paranasal sinusitis unrespon sive lO antibiotic treatmem, particularly those who also have an underlying chronic disease (e.g., diabetes or leukemja). The other choices do not show rapidly progressive, septic, embohc infarctions of the lungs. Parainfluenza vintS (choice C) does not cause thrombosis or infarction. Pneumocystis j iroveci pneumonja (choice D) is noninvasive and causes interstitial pneumonitis. ***Diagnosis: Pulmona1y rnuconnycosis
25 A 3-year-old boy is brought to the emergency room by his parents with a high fever, sore throat, hoarse voice, and acute respiratory distress. On physical examination, the child is observed to be leaning forward with a hyperextended neck The epiglottis appears swollen and erythematous. Which of 1.he following is the most likely cause of this child's upper respiratory tract infection? ***(A) Bordetella pertussis ***(B) Haemophiltis injlue11zae ***(C) Klebsiella 1mmmoniae ***(D) ParainDuenza vlms ***(E) Resp1rarmy syncytial vims
25 The answer is B: Haemophilus influenzae. H. in.fluenzae is a Gram-negative coccobacillus that is the leading cause of meningitis and epiglotritis in children world\vi.de. Infections may also hwolve the middle ear, sinuses, facial skin, lungs, and joints. H. influenzae spreads from person to person in respiratory droplets and secretions. Inflammation of the epiglottis, aryepiglottis sinus, and pyriform recess produces signHicant ai rway obstruction, which can be fatal. Since the widespread use of the HiB vaccine in the United States, invasive disease due to H. irif7uenzac type B in pediatric patients has been reduced by 80% to 90%. Other agents, such as Streptococcus pyogenes , S. pneumoniac, and Staphy lococcu_s aureus, now represent a larger proponion of pediatric cases of epiglottitis in the United States. ***Diagnosis: Acute epiglottitis, Haemophiltt.~ mfluerzzae
26 A 31-year-old man with AlD$ complams of painful swallowing. Physical examination of his oral cavi ty demonstrates a whitish membrane cove1ing much o[ his tongue and pala1.e. Endoscopic e:xamination reveals the same whitish membrane covering his esophageal mucosa. An endoscopic biopsy is shown in the image. Which of the following is the most Ukely etiologic agem responsible for this patient's symptoms? ***(A) Chlamydia ***(B) Fungus ***(C) Protozoon ***(D) Rickettsia ***(E) Spirochete
26 The answer is B: Fungus. The genus Candida comprises over 20 species of fungi, which i.nclude the most common opportunistic pathogens. Many Car1dida species are endogenous human flora. When the no1mal bacte1ial flora that limit f1.mgal growth a re suppressed, the yeast converts to an invasive form, eliciting an inflammatory reaction. Thrush signilies candida] infection of the tongue and mucous membranes of the mom h. It consists of friable, white , curd-like membranes adherent to the affected area. Removal of this membrane leaves a painful bleeding surface. The other choices do not fonn thrush. ***Diagnosis: Tlu·ush, Candida esophagitis
27 A 35-year-old man with AIDS presents to the emergency room vvith a 2-week history of progressive weight loss and productive cough with bloody sputum. An X-ray film of Lhe chest shows a cavitaty lesion in the right middle lobe. A smear of the spurum reveals many acid-fast rods. Which of the following is Lhe most likely diagnosis? ***(A) Ghon complex ***(B) Miliary tuberculosLs ***(C) Plimary tub erculosis ***(D) Secondaty tuberculosis ***(E) Tuberculous pleuritis
27 The answer is 0: Secondary tuberculosis. Secondary tuberculosis results from the proliferation of M. Luberculosi.s in a person who has been previously infected and has mounted an immunologic response_ The source of infection is usually dormanr bacteria from old granulomas bm may also represem a newly acquired infection. Various conditions may predispose lO the reemergence of endogenous microorganisms, including immunosuppressive states such as cancer, chemmherapy, immunosuppressive therapy, AIDS, and old age. The lungs are the most common sires of reinfection. The bacilli elicit an acute inOammatory response that leads to extensive tissue necrosis and the production of tuberculous cavities. Clinically, patients present with cough, low-grade fever, malaise, fatigue, anorexia, weight loss, and night sweats. The other conditions are not associated with pulmonary cavitation. ***Diagnosis: Secondary mberculosis
28 A 1-year-old girl is brought to the clinic in January by her parents because of a fever, runny nose, congestion, "barking" cough, and difficulty breathing. Physical examination shows a red throaL Parainfluenza virus is Lr;olated . Which of the follmving is chief1y responsible for the barking cough and inspiratory stridor seen in this patient? ***(A) Lmyngeal fibrosing strictures ***(B) La1yngorracheal papillomatosis ***(C) Latyngotracheitis ***(D) Tonsillar hyperplasia ***(E) Vocal cord paralysis
Zl The answer is C: Laryngotracheitis. Parainfluenza vi ruses cause acute upper and lower respiratory tract infections particularly in young children. These RNA viruses are the most conm1on cause of laryngotracheobronchitis, which is referred to as "croup." The infection is charaClerized by a subglouic swelUng and airway obstruction, which lead to acme respiratory distress. The infection spreads fTom person to person thmugh contaminated respiratOJy aerosols and secretions. The parainfluenza virus infects and kllls ciliated respiratmy epithelial cells and elicits an inflaJru11awry response. When lary11gotracheitis occurs, localized edema compresses the upper ai rway enough to obstruct breathing. Symptoms associated with croup include fever, hoarseness. barking cough, and inspiratory snidor. The other conditions are not features of parainfluenza infection. ***Diagnosis: Croup, parainfluenza vims
29 A 7-year-old black girl with sickle cell anemia presents witl1 sudden onset of fauguc and joint pain. Physical examination shows marked pallor of the skm and mucous membranes and anhralgias of the lower limbs. The mmher mdicated that the child had recemly recovered from a minor "flu.·· The CBC shows pancytopema. Wh1ch of the followmg agents JS responsible for thiS paucms symplOITJS? ***(A) Adenovuus ***(B) Norwalk \irus ***(C) Paramfluenza \1TUS ***(D) Parvovmts 819 ***(E) RubellavmJS
29 The answer is D: Parvovirus 819. Human parvovirus Bl9 is a DNA virus that causes systemic infections characte1ized by rash, anhralgias, and a transient defect in e1ytluopoiesis. The virus is spread from person Lo person through respiratmy secretions. Infections are common in children. The virus is cytopathic for erythroid precursor cells in the bone marrow. The nuclei of infected cells are enlarged, and the chromatin is displaced to the periphery. MosL patients suffer a mild exanthem known as erythema infectiosum. However, in patients with chronic l1emolytic anemia (e.g. , sickle cell disease), this transient interruption in erythropoiesis causes a potenLially fatal condition kno\'\'11 as "aplastic c1isis." The other choices are not associated with anemia. ***Diagnosis: Aplastic crisis
30 A 2-day-old prcmalUrc infant develops tonic-donie seizures m the nursery. ACT scan of the head shows microcalcifications. Three days late r, the neonate dies. The brain at auwpsy reveals large areas of subcpcndymal necrosts with calcification (shown in the image, see arrows). Which of the following pathogens is the most li kely cause of death in this neonate? ***(A) Cytomegalovirus ***(B) Herpes simplex type 1 ***(C) Human immunodeficiency virus ***(D) Toxoplasma gondii ***(E) Trel'onema pallidmn
30 The answer is D: Toxopla_~ma gondii. Toxoplasmosis is a worldwide disease caused by the prowzoan T. gondii. Most infections are asympwmatic, but a devastating necrotizing disease may occur when they involve the fetus or an immunocompromised adltlt. Infection of the central nervous system produces a necrotizing meningoencephalitis, which, in the most severe cases, results in destruction of brain parencJl }'l11a, cerebral calcHication, and hyd rocephalus. Ocular infections cause chorioretinitis. None of the other pathogens induce th ese ch aracteristic pathologic findings . ***Diagnosis: Congenital wxoplasmosis, TORCH syndrome
31 A 2-month-old infant presems with fever to 38.6°C (103¢F) and neck tigidity. Cerebrospinal fluid shows numerous neuLrophils, decreased glucose, and increased protein Gramposidve cocci are presem. Which of the following is the most likely cause of meningitis in this neonaLe7 ***(A) Group B streptococcus ***(B) Haemophilus injluenzae ***(C) Neisseria gonorrhoeae ***(D) Neisselia meningitidis ***(E) Staphylococcus aw'eus
31 The answer is A: Group B streptococcus. Several thousand neonatal infections with group B streptococci occur in the Uni ted States every year. About 30% of infected infams die. The mher choices are much less common causes of meningitis in this age group. Meningococci are Gram-negative organisms. ***Diagnosis: Neonatal bacterial meningitis
32 A 40-year-old man, who works in a grain silo in the Amelican Southwest, preseniS with skin rash , headache, and feve r. As pan of his duties, he is requ.ired to uap rodeniS. Physical examination shows bilateral swelling or the parotid glands and a purpuric, maculopapular rash that spares the palms , face , and soles. Biopsy of lesional skin discloses intrace]]ular microorganisms up to l J.tm in length within capillary endothelial cells. Which of the following pathogens is responsible for this patient's d i.sease? ***(A) Bonelia burgdmferi ***(B) C/1/amydia ps itlac i ***(C) Coxiel la hurnetii ***(D) Richettsia tytJiti ***(E) Toxoplasma gondii
32 The answer is D: Rickettsia typhi. Endemic typhus is a severe vasculitis transmitted by R. typhi through the bite of infected lice. The disease begins with localized infection of capillary endothelium. which progresses w systemic vasculitis. Mononuclear cell infi ltrates are found in multiple organs and are typically arranged in typhus nodules. Louse-borne typhus is characterized clinically by fever, severe headache, and myalgias, followed by the appearance of a maculopapular rash on the upper trunk and axillary folds, spreading centrifugally to the extremities. The other choices do not infect endothelial cells or produce a vasculitis. ***Diagnosis: Endemk ryphus
33 A 40-year-old immigram from Brazil presems with a 2-month history of fever, weight loss, and prominent muscle pain. She repons a "suange feeling around her hean." Physical examination shows tachycardia and an irregular heart beat. Laboratory studies reveal marked peripheral eosinophilia. The patient dies 2 days later of an arrhythmia. A photomicrograph of the heart at autopsy is shown. Which of the following pathogens is the most likely cause of ca r· diac arrest? . .- ***(A) Pneumocystis jiroveci ***(B) Schistosoma mansoni ***(C) Treponema pallidttm ***(D) 1hchwis trichiura ***(E) 1iypanosoma cruzi
33 The answer is E: Trypanosoma cruzi. Chagas disease is an lnsect-bome systemic infection in humans caused by t.h e protozoan T auz i. Acute manifestations and long-term sequelae of infection occur p1imarily in the hean and gastrointestinal uact.. The infections are endemic in Central and South America, where they are transmitted by the Reduviid ("kissing") bug, which hides w1tbin the cracks and straw roofs of older homes. The parasite reproduces within the myocardium and causes myocarditis. The other pathogens do not cause myocarditis. ***Diagnosis: Chagas disease
34 A 45-year-old man presents with chesl pain, fever, productive cough, and rust-colored spurum. The patient was diagnosed with mberculosis in his early 20s. A chest X-ray shows multiple, nodular infiltrates and cavitary lesions. A lung biopsy reveals necrotizing inflammation and vascular thrombi with branching fungal hyphae. Which of the following is the most likely diagnosis? ***(A) Actinomycosis ***(B) Aspergillosis ***(C) Candidiasis ***(D) Cryptococcosis ***(E) Histoplasmosis
34 The answer is 8: Aspergillosis. Fungus balls (aspergillomas) consist of rounded, lobulated masses of h yphae and occur in patients with a previous hiswry of cavitating pulmonary disease (e.g., pulmona1y tuberculosis). Aspergi llus is a common environmental fungus that causes opportunistic infections in U1e lungs. Inhaled spores germinate in the warm humid atmosphere provided by cavitary lung lesions, filling them with masses of hyphae. The organisms generally do not. invade the lung parenchyma. There are three different types of pulmonary aspergillosis, namely allergic bronchopulmonary aspergillosis, aspergillomas, and invasive aspergillosis. Candidiasis (choice C) is incorrect because Candida infections an~ not typicaUy angioinvasive. The other choices do not show characteristic branching fungal hyphae. ***Diagnosis: Pulmonary aspergillosis, aspergilloma
35 A 25-year-old man, who recently rerurned from a trip 1.0 Central America, presents with right upper quadrant pain and fever of 3 weeks in duration. A CT scan of the abdomen shows a large cystic cavity of the liver, after which a 12.-cm abscess is excised (shown in the image). Histologic examination of the lesion reveals chocolate-colored, odorless debris, surrounded by a shaggy fibrin lining, scant inOammatory reaction, and organisms auached to adjacem cells. Which of the following pathogens is responsible fo r this patients liver abscess? ***(A) Clonorchis sinensis ***(B) Entamoeba histolytica ***(C) Giardia lmnblia ***(D) Schistosoma mansoni ***(E) Streptococcus pyogene.s
35 The answer is 8: Entamoeba histolytica. E. lti.stolytica resides in the colon of in fected pe rsons and is transmitted by fecaloral cont:acL The trophozoiles invade submucosal veins of the colon, enter the ponal circulation, and gain access to the liver. The amebae kill hepatocytes, producing a slowly expanding, necrotic cavity. The abscess is filled with a dark brown material that resembles anchovy paste. An amebic liver abscess can mpture and extend into the peritoneal cavity Although the oth er choices may involve the liver, they do not cause hepatic abscess. ***Diagnosis: Amebic liver abscess
36 A 24-year-old \Moman presents with severe vomiting, abdominal cramps, and diatThea 2 hours after dining at a local restaurant. Many of 1.he customers that night reponed similar symptoms. Which of the fo llowing mecharusms of disease is chiefly responsible for the development of gastroimesdnal sympLOms in !his patle.nr? ***(A) Activation of membrane-associated tyrosine kinase ***(B) Exposure to preformed enterotoxin ***(C) IgE-mediated mast cell degranulaLion ***(D) Immune-complex deposition and complemem activation ***(E) Receptor-mediated stimulation of intracellular cAMP
36 The answer is B: Exposure to preformed enterotoxin. Stal'ltyJococcus attreus food poisoning is caused by the ingestion of food comaminated with preformed, heaL-stable enterotoxin B. Ombreaks occur when food handlers inoculate foods such as meat or dairy products (salad dressings, cream sauces, and custard-fi1led pasnies) wilh contaminated wounds or infected nasal droplets. Staphylococcal food poisoning typically begins less than 6 hours after a meal. Nausea and vomiting usually resolve with in 12 hours. The other choices do not initiaLe rapid gastrointestinal symptoms. ***Diagnosis: Staphylococcal food poisoning
37 A 48-year-old man with AIDS is admjtted to the hospital with a fever of 38°C (l03°F), night sweats, persistent cough, and prolonged diarrhea. His CD4 celJ count is less than 300/).JL Stool culture reveals the presence of acid-fast bacilli. 'vVhich of the following pathogens is responsible for this patients respiralOry and gastrointestinal disease? ***(A) Campylobacterjejuni ***(B) Cryptosporidit@ ***(C) Clostridium peifringens ***(D) Mycobacterium avium-i ntracellttlare ***(E) Slreptococws pyogenes
37 The answer is D: Mycobacterium avium-intracellulare. M. avit~m and M. intrace llulare are similar mycobacte1ial species that cause idemical cliseases and are, therefore, classified wgether as M. avium-intracellulare complex (MAC). MAC is a rare , granulomatous, pulmonary disease in lmmunocompetem persons, but it is a progressive systemic disorder in patients with AIDS. One third of all AlDS patients develop oven MAC infections. The proliferation of organisms and the recruitment of macrophages produce expanding lesions, ranging fTom epithelioid granulomas comaining few organisms lO loose aggregates with foamy macrophages. Symptoms associated with MAC resemble those of tuberculosis; however, progressive involvemem of the small bowel produces malabsorption and diarrhea. Camplyobacter jejuni (choice A) produces a self-limited bacterial diarrhea. Clyptosporiditm1 (choice B) is a protozoan that causes diarrhea iJ1 immunocompromised patients but is not associated with respiratmy in rections. ***Diagnosis: Atypical mycobacterial infection mAIDS
38 A 14-year-old gul presenlS with yellow and red crusted lesions around her mouth and arms (shown ln the image). She bas a recent hiswry of imem1iltent low-grade fever. This patients skin lesions are most likely caused by which of the fo ll ov.l]ng microorganisms? ***(A) Staphylococcus epidennidis ***(B) Streptococcus pneumoniae ***(C) Streptococc t~s pyogenes ***(D) Streptococcus viridam ***(E) Treponema pallidum
38 The answer is C: Streptococcus pyogenes. lmpetigo in this patienL represents a localized, Lmraepidermal infection wuh 5. pyogenes. lt spreads by dose comaCL and most commonly affects children. Minor trauma allows inoculation of the bacteria, forming an imraepithelial pusmle that eventually ruptures and leaks a purulent e".'udare. 5. pneumoniae (choice B) is a major cause of lobar pneumonia, otitis media, sinusitis and meningitis 5. viridans (choiCe D) is a major cause of bacterial endocarditis. Treponema pallidtvn (choice E) produces a maculopapular rash of the palms and soles in secondary syphilis. ***Diagnosis: Impetigo
39 A 28-year-old dntg abuser presents with high fever, chUls, productive cough, hemoptysis, and right-sided chest pain. Physical examination shows the stigmata of intravenous drug abuse, as well as splenomegaly and pleuritis. Auscultation reveals a sysLolic ejection murmur over the tricuspid area. Which of the following is the most likely etiology of this parems valvular heart disease' ***(A) Candida albicans ***(B) Legionella pneumophiLa ***(C) Mycobacterium tuberculosis ***(D) Mycoplasma pnewnoniae ***(E) Stapllyl ococcus aureus
39 The answer is E: Staphylococcus aureus. 5. aureus is a Gram-positive coccus that is tile most common cause of suppurative infections involving the skin, joints, and bones. lL is also one of the most common causes of acute bacterial endocardi tis. This infection features colonization of heart valves or mural endocardium, leading to the formation of friable vegetations composed of thrombotic debris and microorganisms. Bacterial growth is often associated with dest.ruction of the underlying valve tissue. Tricuspid insufficiency sec· ondary to bacterial endocarditis is one of tbe most common complications of IV drug abuse. The most common source of bacteria in these patients is the skin_ The tricuspid valve is infected m half of the cases. The other choices do not cause endocarditis_ ***Diagnosis: Bacte rial endocarditis
40 A 50-year-old woman presents ·...vi th sudden-onset, crampy abdominal pain and watery diarrhea. She also complains of low-grade fever with chtlls, nausea, and vomiting. She ate partially cooked eggs 24 hours prior to the onset of these symptoms. Which of the following pathogens is most likely responsible for this patient's gastrointestinal disorder? ***(A) Clostridium pe1jringens ***(B) Escherichia coli ***(C) Hepatitis A virus ***(D) Salmonella sp. ***(E) Stapllylococcus aureus
40 The an.swer is 0: Salmonella. Nomyphoidal species of Salmonella contaminate a va1iety of foods, including poultry. eggs, meat, and daily products. Salmonella infections are characterized clinically by djanhea, which begins 12 £O 24 hours after ingestion of the contaminated food. Salmonella rood poisoning is self-llnuted, lasting from l to 3 days. The bacte1ia pro· liferate in the small intestine and invade enterocytes, where they produce several toxins that contTibute to the dysfunction of the intestinal epithelium. The mucosal surface of the ileum and colon become acutely inOamed and occasionally ulcerated. Pathogenic Esd1erichia coli (choice B) does not typicaJly inJect eggs. Stap!tylococcus autetts (choice E) characteristically causes diarrhea 1 to 6 hours after ingestion. ***Diagnosis: Salmonella enterocolitis
41 A 30-year-old man presents with inguinal swelling and pain· less penile and perianal ulcers. He admits to having unpro· tected sexual intercourse with multiple partners. A silver slain of a biopsy from a skin lesion (sho\'.rn in the image) reveals organisms clustered in large macrophages. Which of the following is the most likely diagnosis? ***(A) Chancroid ***(B) Gemtal herpes ***(C) Gonorrhea ***(D) Granuloma ingumale ***(E) Syphtlis
41 The answer is D: Granuloma inguinale. Granuloma inguinale is a sexually transmitted, chronic, superficial ulceration of the genital, inguinal, and perianal region. It is caused by Calymmatobacte rium granulomatis , a small Gram-negative bacilltts. The characteristic lesion is a beefy-red superficial ulcer. Microscopically, the dermis and subcutis are infiltrated by macrophages and plasma cells. Skin lesions show microorganisms, termed "Donovan bodies," clustered \\'ithin enlarged macrophages. The other choices do not display visible lnnacellular microorganisms. ***Diagnosis: Granuloma inguinale
42 A 42-year-old man presents with a 1-week history of myalgia, low-grade fever, and swelling o( the left calL The patiem repons recently attencUng a fireman:S pig-roasL Laboratmy data show elevated serum levels of creatine kinase. Examination of a muscle biopsy in this patiem would most likely reveal an infiltrate of which of the following cell types? ***(A) Eosinophils ***(B) Mast cells ***(C) Plasma cells ***(D) Segmented neutrophils ***(E) Smooth muscle cells
42 The answer is A: Eosinophils. Trichinosis is p roduced by the roundworm Tr ichinella spiralis. After mating, the females liberate larvae imo the circulation. The larvae can invade almost any tissue but survive only in skeletal muscle i.n an encapsulated form. Elevated serum levels of creatine kinase indicate muscle cell necrosis. Early muscle involvement elicits an intense inflammatory infiltrate rich in eosinophils. The other cells do not typically respond to acute parasitic infestations. ***Diagnosis: Trichinosis
43 A 32-year-old immigram from Viernam presents with a 4-year hi.swry of progressive loss of eyebrows; patchy hypopigmentation of skin; coarse facial features; and multiple, firm subcutaneous nodules. Acid-fast organisms are seen on skin biopsy. Which of the following is the most likely etiology of this patients condition? ***(A) BacillLLS anthracis ***(B) Mycobacterium lcprae ***(C) Mycobacterium tuberculosis ***(D) 1i·e1)011ema pallidwn ***(E) 1iypanosoma cntzi
43 The answer is B: Mycobacterium leprae. Leprosy (Hansen disease) is caused by M. leprae and appears in two fom1s, namely tuberculoid and lepromawus. The tuberculoid type occurs in patiems who moum an immunologic response, whereas those with the lepromatous form are anergic. Leprornawus leprosy is a chronic, slowly progressive, destructive p rocess involving peripheral nerves, skin, and mucous membranes. Patiems exhibit multiple nodular lesions of the skin, eyes, testes, nerves, lymph nodes, and spleen. The skin infiinates o -.. pand slowly lO distort and disfigure the face, ears, and upper airvvays. There is also Lnvolvemenl of the eyes, eyebrows, eyelashes, nerves, and testes. M_ tuberculosis (choice C) is acid-fast, but does not cause Lhe symptoms listed for this case. Amhrax (choice A), syphilis (choice D), and u·ypanosomLasis (choke E) manifest diffe rentlYDiagnosis: Leprosy
44 A 16-year-old girl presen i:S >vith fever and swollen lymph nodes. Physical examination reveals painful lymphadenopathy in her left axill a. The gl rl remembers that she was scratched by her cat 3 weeks ago. A sllver stain of a lymph node biopsy is shown in the image. Which of the following is the most likely cause oflymphadenopathy in this patient? --- - ***(A) Bartonella henselae ***(B) Eih ene/Ja cormdens ***(C) Pastwrella multocida ***(D) Staphylococcus attretLS ***(E) Streptococcus l'Yogenes
44 The answer is A: Bartonella henselae. Cat-scratch disease is a self-Limited infection caused by B. 1-Jenselae or (more rarely) B. qt~i~ltarw. These bacteria are small, Gram-negative rods that are difficult to culture bm easlly seen in a lymph node biopsy when s tained with silver. B. llenselae multiplies in the walls of small vessels and extracellular collagen fibers at the site of inoculation. Tl1e organisms are carried w rJ1e lymph nodes, where they produce suppurative lymphadenitis. The lymph nodes enlarge and drain through the skin. About half of infected patients present with systemic symptoms such as fever, malaise, rash, and erythema nodosum. Pasteurella multocida {choice C) is associated with wound infection after animal bites. Eihenella conodens (choice B) produces wound infections after human bites. ***Diagnosis: Cat-scratch disease
45 A 12-year-old farm boy from Mexico complains of generalized weakness and abdominal pain. Physical examination shows pallor and pitting edema of the lower extremities. A CBC reveals severe microcytic, hypochromjc anemia (hemoglobin = 8.2 gldL). Whkh of the following pathogens is the most likely cause of anemia in this patient? ***(A) Ascaris lumbricoides ***(B) Giardia Iamblia ***(C) Hookw01m (Ancy lostoma duode r1ale) ***(D) Pinworm (Enterobius vennicrt laris) ***(E) Whipworm (1i-ich11ris trichiura)
45 The answer is C: Hookworm (Ancylostoma duodena/e) . Hookworms are intestinal nematodes that inJect the small boweL A duodenale molts within the duodenum and attaches to the mucosa. With extensive Infections, particularly with A duodenale, considerable blood loss results in iron-deficiency anemia. The other choices do not cause intestinal bleeding and iron-deficiency anemia. ***Diagnosis: Hookwonn, ancylostomiasis
46 A 65-year-old man with a hisLOry of Hodgkin lymphoma develops a painful erythematous rash with a band-like distribmion over 1.he left side of his chest, which becomes vesicular over the next several days. Biopsy of lesional skin is shown in the image. Which of the following is the most likely etiology of this patient's rash7 • ***(A) Cytomegalovirus ***(B) Epstein-Barr virus ***(C) Human herpesvirus-6 ***(D) Human herpesvims-8 ***(E) Varicella-zoster virus
46 The answer is E: Varicella-zoster virus. Varicella-zoster virus initially infects cells of the respirat01y tract or conjunctival epithelium. It then reproduces and spreads via the bloodstream and lymphatic system. First exposure ro the virus produces chickenpox, an acute systemic illness whose dominant feature is a generalized vesicular skin eruption. Reactivation of la tent virus in adults causes herpes zoster. Microscopically, intraepithelial vesicles contain multinucleated giam cells and nuclear in clusions. Human herpesvirus-8 (choice D) is associated with Kaposi sarcoma in pmiems with AlDS. The other choices do not produce vesicular eruptions. ***Diagnosis: Herpes zoster
47 A 23-year-old woman presems with low-grade fever and multiple. painful, vesicular lesions on the vulva. A Pap smear shows multinucleated giam cells with intranuclear inclusions. Which of the following pathogens is the mosL likely cause of this pmient's genital lesions? ***(A) Calymmatobacterium grant4lomalis ***(B) Epstein-Barr virus ***(C) Herpes simplex virus cype 2 ***(D) Human papillomavirus ***(E) 1i·eponema paUidum
47 The answer is C: Herpes simplex virus type 2. Herpes simplex vi ruses are common human pathogens, which most frequent!)' produce recurrent painful vesicular eruptions of the skin and mucous membranes. The other choices do not show grouped vesicles. CaTymmatobacte1·ium granttlomatis (choice A) is associated with a painful genital ulcer (chancroid). Human papillomavi rus (choice D) relates to genital warts. Trepor1ema pallidum (choice E) causes syphilis. ***Diagnosis: Genital herpes
48 TI1e patiem described in Question 47 asks you about the possibi. lity of future outbreaks and the risks of se.lfual transmission. ln addressing her concerns, you might consider that the vi rus is harbored in a latent fonn in which of the fol lowing anatomic locations? ***(A) Germ cells of the ovary ***(B) Glandular epithelium of the endocervix ***(C) Mucosa of the external genitalia ***(D) Sensory neurons of sacral ganglia ***(E) Squamous mucosa of the exocervix
48 TheanswerisD: Sensory neurons of sacral ganglia. He1pesvirus ascends from genital lesions along sensory neurons and survives in a latent fom1 in the sacral ganglia. Nonspecific stimuli (including sexual intercourse and menses) can reactivate the virus, which then descends along axons to the genital mucosa, causing recurrent b listers on the external and internal genitalia. ***Diagnosis: Gen ital herpes
49 A 6-year-old girl presents \"'ith intense perianal itching, especially at nighL Physical examination reveals perianal excor iad. on. An adhesive tape test is positive for worms. vVhich of the following is the most likely parasite m this patient? ***(A) Ancy lostoma duodenale ***(B) Asca1is lwnbricoides ***(C) Enterobi tiS vennicularis ***(D) Necator wnericam1s ***(E) Toxocara cani..~
49 The answer is C: Enterobius vermicularis. E. vennicularis ("pinworm") is an imestinal nematOde Lhat is encountered worldwide btu is more common in temperate zones. Individuals can be infected at any age, but parasilism is more common in children. Most people complain of pruritus caused by migrating worms. Ancylostoma duodenale and Necator americanus (choices A and D) are hookworms associated with intestinal bleeding and iron-deficiency anemia. ***Diagnosis: Enterobiasis
50 An Egyptian fishetman develops lower abdominal pain and pain on urination, and repons seeing blood in rus mine. Which of the following parasites is the most lU<ely cause of urinary symptoms in this patient? ***(A) Clonorchis sinensis ***(B) Dipltyllobothrium latum ***(C) Fasciola hepatica ***(D) Schistosoma haematobiLtm ***(E) Schistosoma mansoni
50 The answer is D: Schistosoma baematobium. Schiswsomiasis is the most imponam helmmthic disease of humans. It is characterized by intense inflammatory and immunologic respon ses that damage the liver, intestine, and urinmy bladder. In this case, the patient presents \\lith urogeniwl schiswsomiasis. 5. haematobiwn causes urogenital infections and increases the risk for developing squamous cell carcinoma of the bladder. 5. mansoni (choice E) affects the liver. ***Diagnosis: Schistosomiasis
51 A 34~year-old man with history of diabetes mellitus presents 'Nith a fever of 3 days duration and a painful , swnllen finger (shown in the image). Physical examination reveals erythema and edema affecting the fourth digiL Which of the following is the most likely etiology of this lesion? ***(A) Pseudomonas aeruginosa ***(B) Sporotllrix sciJenchii ***(C) Staphylococcus attreLL~ ***(D) Staphylococcus epidermidis ***(E) StTeptococcus l'yogenes
51 The answer is E: Streptococcus pyogenes. Erysipelas is an erythematous swelling of the skin caused chiefly by 5. pyogenes infection. 5. pyogenes, also known as group A streptococcus, is one of the most frequent bacterial pathogens of humans, producing various diseases ranging from acute self-limited pharyngitis to rheumatic fever. The rash usually begins on the face but can affect any part of the body. Cutaneous microabscesses and foci of necrosis are common. The other choices are noL typically associated with erysipelas. ***Diagnosis: Erysipelas
52 A 22-year-old student living in a college dormitmy presents with a 4-week history of a nonproduc tive cough and previous low-grade fever. An X- ray film of Lhe chest shows patchy consolidation of the right lower lobe, with evidence of interstitia] involvement. Which of the following is the most likely etiology of this paliems pulmonary infection? ***(A) Klebsiella 1meumoniae ***(B) Mycobacterium t11bercu/osis ***(C) Mycoplasma pneumoniae ***(D) Staphylococcus mmms ***(E) Streptococcus pneumoniae
52 The answer is C: Mycoplasma pneumoniae. M. pneumoniae produces an acme self-hmiLed lower respirmory tracl infecdon, primarily in children and young adults. Most infections occur in groups of persons living in close contact. M. pneumoniae tends to be milder Lhan oLher baclerial pneumonias and has , therefore, eamed the appellmion "walking pneumonia." Fever usually persisrs for no more Lhan 2 weeks, although a cough may linger for 6 weeks or more. Chest X-ray commonly shows patchy consolidation of a single segment of a lower lung lobe. M. pneumoniae is responsible for abom 20% of all pneumonias in developed commies. The other chokes do not cause imerstitial pneumonia. ***Diagnosis: Mycoplasma pneumoniac
53 A 47-year-old woman receiving chemotherapy for leukemia complains of headache, cough , and dyspnea. An X-ray film of the chest shows nodular pulmonary infiltrates and thin -walled cavities. A mucicarn~ne stain of a lung biopsy discloses budding yeast surrounded by a mucin-1ich capsule. vVhich of the following is the most likely pathogen? ***(A) Aspergillus Jlavus ***(B) Candida albicam ***(C) Coccidioides immitis ***(D) C1yptococcus neojom1ans ***(E) Histoplasma capsulatum
53 The answer is D: (ryptococcus neoformans. Clyptococcosis is a mycosis thaL primarily affects the meninges and lungs. C. neofomwns is unique among pathogenic fungi because il has a proteoglycan capsule, which is essential for pathogenicity The main reservoir for this fungus is pigeon droppings. The organisms appear as faintly stained, basophilic yeast with a clear, 3- LO 5-f..Lm thick mucinous capsule. Cryptococcus almosl exclusively a(fects persons with impaired cell-mediated immunity. The other choices do not stain with mucicannine. ***Diagnosis: Cryptococcosis
54 A JO~year~old man presents with abrupl onsel of (ever, chUls, myalgia, nausea, and vomiting. He had just returned from a month-long nip Lo the jungles of South America. lf this patient has yellow feve r, pathologic changes would most Ukely be observed in which of the following organs? ***(A) Brain ***(B) Kidney ***(C) Liver ***(D) Lung ***(E) Stomach
54 The answer is C: Uver. Yellow fever is an acute hemorrhagic fever, which is associated ·wiLh hepatic necrosis and jaundice. The illness is caused by a mosquito-borne Oavivirus. Extensive injury to vascular endothelial cells may cause hemorrhage and shock. This virus l1as a tropism for liver cells, where it causes extensive hepatocellular injury CounciJm.an bodies (apoptotic bodies) and miCrovesicular fa tty change are evident. In severe cases, the entire liver lobule may become necrotic. The other choices are incorrect, because the yellow fever vims is hepatorropic. ***Diagnosis: Yellow fever
55 A SO~ye~n·~old man, who recently returned from a trip to Africa, complains of darkening o[ his skin, weight loss, a11d an increased tendency to bleed. His Lemperature is 38°C (lOl °F), pulse raLe 22 per minute, and blood pressure 90/80 mm Hg Physical examination reveals a pale cachectic man wi.lh massive splenomegaly. CBC shows anemia, thrombocytopenia, and leukopenia. A bone marrow biopsy (silver srain) displays macrophages filled with proliferating organisms. Which of the following infectious diseases is mosLiikdy responsible for this patient's condition? ***(A) BiJharzi asis ***(B) Chagas disease ***(C) Cysticercosis ***(D) fascioliasis ***(E) Leishmaniasis
55 The answer is E: Leishmaniasis. Leishmaniae are protozoans that are uan..smiued w humans through insect bites. They cause a spectrum of clinical syndromes, ranging from indolent self-resolving cutaneous ulcers w fatal disseminated disease. Leishman iasis is transmiued by the bite of phlebowmus sandflies, which acquire infections from feeding on infected animals. The infestation is prb11arily a disease of less developed commies, where over 20 million people are believed lO be infected. Three distinct clinical entities are recognized: (l) localized cutaneous leislunaniasis, (2) mucocutaneous leishmaniasis, and (3) visceral leishmaniasis. Patients with visceral leishmaniasis suffer persistent fever, progressive weight loss , hepatosplenomegaly, anemia, thrombocytopenia, and leukopenia. Light-skinned persons develop darkening of the skin. lf untreated, the disease is fatal. Aside from clinical differences, the other choices do not represent infection of macrophages and do not lead to massive splenomegaly. ***Diagnosis: Leishmaniasis
56 A 6-year-old boy presents with a 10-month history of diarrhea, crampy abdominal pain, and progressive weight loss. He recently imnugrated to the United $rates from Mexico. Physical examination shows mild abdominal distension and evidence of malabsorption. The stool guaiac test is negative. Which of !he following is the most likely etiology of this child's gastrointestinal disease? ***(A) Campylobacterjejuni ***(B) Escherichia coli ***(C) Giardia Iamblia ***(D) Shigella dy senteriae ***(E) Staphylococcus attrnts
56 The answer is C: Giardia Iambiia. Gia rdiasis is an infestation of the smaU intestine by the flagellated protozoan G. lmnblia . The organisms can be acquired from contaminated water or food, and the in fection is characterized by abdominal cramping and nonbloody diarrhea. The gastrointestinal symptoms usually resolve in 1 w 4 weeks, but chronic giardiasis may lead to malabsorption, weight loss, and growth re tardation. The organisms are recovered from stool specimens, duodenal aspirates, or imestinal biopsies. The O£her choices do noL lead lO chronic infection. ***Diagnosis: Giardiasis, Gtardta Iamblia
57 A 52.-year-old man presents with a 3-day history of sore throat, cough, fever, and runny nose. The symptoms of this patients common u pper respiratory tract infection are primarily caused by which of the following infectious agents? ***(A) Aden ovirus ***(B) Epstein-Barr virus ***(C) Herpes simplex virus ***(D) Lentivirus ***(E) Rhinovirus
57 The answer is E: Rhinovirus. The common cold is an acute , self-limited disorder of the upper respiratory tract caused by infection with a variety o[ RNA viruses, inclucllng over 100 distinct rhinoviruses and several coronavimses. These viruses infect nasal respiratory epithelial cells, causing edema and increased mucus production. Clinically, Lhe common cold is characterized by rhinorrhea, pharyngitis, cough, and lowgrade feve r. Sympwms last about a week. HlV ts a lemivhus (choice D) ***Diagnosis: Common cold
58 A 29-year-old woman (gravida Ill, para 11) delivers a premature infant at 28 weeks of gestation. At birth, the neonate shows signs of profound anemia and generalized edema (hydrops fetalis). The disease is most likely caused by an intrauterine infection with which of the following TORCH agents? ***(A) Cytomegalovirus ***(B) Herpes simplex virus ***(C) Parvovirus Bl9 ***(D) Rubellavims ***(E) Toxoplasma gondii
58 The answer is C: Parvovirus 819. Human parvovirus Bl9 is a DNA vims that causes systemk infections characterized b}' rash, anhralgias, and transient interruption i11 etythropoiesis. The vims produces characterLstic cytopathic effects in erythroid precursor cells. The nucleus of an affected cell is enlarged, and the chromatin is displaced peripherally by central, glassy, eosinophilic ma terial. When the fetus is infected with parvovirus Bl9, a transient cessation of erythrocyte production leacls to severe anemia, hydrops feLalis, and often death in utero. The other choices do not interfere with erythropoiesis ***Diagnosis: Hydrops fetalis, TORCH syndrome
59 A 36-year-old woman presents witl1 a 2-day history of feve r, myalgias, headache, and watery diarrhea (5 to 10 per day) tl1at contains some blood. A stool smear shows leukocytes and Gram-negative curved bacilli. The patiem reports drink· ing raw milk 7 days ago. Which of the follO\ving microorganisms is the most likely cause of this womans gastrointestinal disorder? ***(A) CatntJylobacterjejuni ***(B) Escltericltia coli ***(C) Salmonella typlJi ***(D) Shigella dysent.eriae ***(E) Staphylococcus attreus
59 The answer is A: Campylobacter jejuni. C. jejuni causes an acute, self-limited, inGammatory diarrheal illness. The organism is distributed worldwide and is acquired through contaminaLed food or waLer. It is a major cause of childhood mortality in developing counnies and is responsible for many cases of travelers' diarrhea. C. jejuni causes a superficial enterocolitis primarily involving the terminal ileum and colon. Focal necrosis of d1e intestinal epithelium is accompanied by an acute inflammatory infiltrate. ln severe cases, focal disease progresses w small ulcers and patchy inflammatory exudates (pseudomembranes). The symptoms typically Tesolve in 5 Lo 7 days. A few patients develop a severe, protracted ilJness resembling acute ulcerative colitis. The mher choices are characterized by a more rapid onset of symptoms after infection. ***Diagnosis: Campylobacrer emeritis
60 A 45-year-old construction worl<er sLtrfers a penetrating wound of the left leg, which is cleaned and sutured. Three days later, the patient presents \vith sudden onset of severe pain at the site of injury. Physical examination shows darkening of the surrounding skin , hemorrhage, and cutaneous necrosis. The wound shows a thick serosanguinous discharge with gas bubbles and a fragrant odor. Which of the following is the most likely etiology of this patient's wound infeclion? ***(A) Clostridiwn botulimw1 ***(B) Clostridium pelfringens ***(C) Staphylococcus aureus ***(D) StC1phy lococcus epidermidis ***(E) St reptococcus pyogenes
60 The answer is B: Clostridium perfringens. Gas gangrene (clostridial myonecrosis) is a necrotizing, gas-forming infection that begins in contaminated wounds and spreads rapidly to adjacent tissues. The disease can be fatal within hours of onset. Gas gangTene follows the deposition of C. pe1jringens into tissues under anaerobic conditions. Such conditions occur in areas of extensive necrosis (e.g., severe trauma, wartime injuries , and septic abortions). Clostridial myonecrosis is rare when the wound is subjected to prompt and thorough debridement of dead tissue. Damage to previously heal thy muscle is mediated by a myotoxin. C. botulinum (choice A) secretes a preformed neurotoxin. ***Diagnosis: Gas gangrene, closnidial myonecrosis
61 A 32-ye.ar-old man presents with the sudden onset of tonicdonie seizures and dies the next day The brain at autopsy is shmvn in the image. This patient most likely contracted which of the following infectious diseases? ***(A) Aspergillosis ***(B) Clonorchiasis ***(C) Cysticercosis ***(D) Fascioliasis ***(E) Paragonimiasis
61 The answer is C: Cysticercosis. Pigs acquire cysticerci by ingesting eggs of Taenia solium shed in human feces. However, when humans accidentally ingest the eggs from human reces and become infeCLed with cysticerci, the consequences may be catastrophic. The eggs release oncospheres, which penetrate the wall of the gut, enter the bloodstream, lodge in tissues, and differentiate to cysticerci. The cysticercus is a sphe1ical milky white cyst of about 1 em in diameter that contains fiuid and an invaginated scolex (head of the worm) Viable cysts can be shelled out from the infected tissue. Multiple cysticerci in the brain may impan a "Swiss cheese" appearance and manifest cJinically as headaches and seizures. The other worms (choices B, D, and E) do not infect the brain. Aspergillosis of the brain {choice A) is distinctly uncommon. ***Diagnosis: Cysticercosis
62 A 5-year-old boy is brought to the emergency room with a fever of 103"F (38 7°C), chest pain, and productive cough The patient has a history of recurrent pulmonary disease and respiratory distress. What microorganism recovered from the lungs of this child is virtually diagnostic of cystic fibrosis? ***(A) Klebsiella sp. ***(B) Legiorwe/la sp. ***(C) Pneumocystis sp. ***(D) Pseudomonas sp ***(E) Streptococcus sp.
62 The answer is D: Pseudomonas sp. Cystic fibrosis is the most conunon lethal amosomal recessive disorder m the white population. The disease is characterized by (1) chronic pulmonary disease, (2) deficient exocrine pancreatic function, and (3) other complications of inspissated mucus in a number of organs, including the small intestine, the Liver, and the reproductive tract. It results from abnonual electrolyte transport caused by impaired function of the chloride channel of epithelial cells. The pulmonary symptoms of Cf begin with cough, which eventually becomes productive of large amoums of tenacious and purulem spu rum. Episodes of infectious bronchitis and bronchopneumonia become progressively more frequent, and eventually shormess of breath develops. Respiratory failu re and the cardiac complications of pulmonary hypeltension (cor pulmonale) are late sequelae. The most common organisms that infect the respiratory tract in CF are Staphy lococcus and Pseudomonas species. As the disease advances, Pseudomonas may be the only organism culntred from the lung. ln fact, the recovery of Pseudomonas sp., particularly the mucoid variety. from the lungs of a child with chronic pulmonary disease is vinually diagnostic of CF ***Diagnosis: Cystic fibrosis
1 An 80-year-old man with long-standing diabetes and systemic hypertension dies of congestive heart failure. The luminal sur· face of the abdominal aona is shown in the image. Which of the following pathologic changes would you expect to see on microscopic examination! ***(A) Acute inflammation of Lhe vessel wall ***(B) BaClerial colonies in the vessel wall ***(C) Cystic medial necrosis ***(D) Lipid deposition and smooth muscle cell hyperplasia ***(E) Obliterative endarteritis of the vasa vasomm
1 The answer is D: Lipid deposition and smooth muscle cell .____ hyperplasia . Atherosclerosis is a disease of large- and medium- sized elastic and muscular aneries that results in the progressive accumulation wi Lhin the intima of inflammatory cells, hyperplastic smooth muscle cells, lipids, and connective tissue. The resulting characLeJisdc lesion, the lipid plaque (atheroma), contains pools of extracellular lipid and numerous lipid-laden macrophages (foam cells). lt is not an acULe inflammatory or infectious process (choices A and B). Obliterative endanelitis (choice E) is a syphilitic lesion. ***Diagnosis: Atherosclerosis
2 A 60-year-old mildly obese woman is admiued w the hospital '-Vith a chief complaim or recurrem chest pain on exenion. The patient repons several episodes of chest pain over the past several years and painful leg cramps when walking. Fasting blood glucose (160 m&'dl) and total serum cholesterol (3 70 mgl dl) are high. The ECG is normal and blood tests for ca rdiac· specifi c proteins are negative. Chest pain in this patient is most likely due to which of the following u nderlying conditions? ***(A) Atherosclerosis of coronary artery ***(B) Congenital anomalous origin of coronary artery ***(C) Coronary arteritis ***(D) Imramural course of the LAD coronary artery ***(E) Thrombosis of coronary artery
2 The answer is A: Atherosclerosis of coronary artery. Patients \viLh severe atherosclerosis present with organ-specific vascular disorders, including intermittent claudicanon, abdominal aortic aneurysms, coronary anery disease (chest pain), cerebrovascular disease, and pe1ipheral vascular disease. Angina pecwris is the pain of myocardial ischemia. It typically occurs in the substernal portion of Lhe chesL and may radiate 1.0 the left arm, jaw, and epigasuium. lL is lhe most common symptom of ischemic heart disease. Laboratory findings in Lhis patiem show evidence of diabetes mellitus and hyperlipidemia, which are 1isk factors for atherosclerosis. Thrombosis of a ruptured atheromatous plaque (choice E) usually p recipitates acute myocardial infarction. The other conditions (choices C. D, and E) may limit coronary blood flow and present with chest pain on exertion, but they are less conunon than coronmy atherosclerosis. ***Diagnosis: Ischemic hean disease, atherosclerosis
3 A 69-year-old woman presems with crushing substernal chest pain and nausea. Laboratory studies show elevated serum levels of cardiac proteins (CK-MB = 8.5 nglml; noponin-1 = 3.2 nglml). A diagnosis or myocardial infarction is confirmed by ECG. Despite treatment, the patient becomes hypotensive, and resuscitation attempts are unsuccessful. A cross section of lhe patient's 1ight coronary anery at autopsy is shown in the image. Which of the following pathologic changes are evident in this aulOpsy specimen? ***(A) Arteritis and atherosclerosis ***(B) Atherosclerosis and thrombosis ***(C) Microaneurysm and canalization ***(D) Thrombosis and calcification ***(E) Vasodilation and aneJitis
3 The answer is B: Atherosclerosis and thrombosis. The photomicrograph shows severe atherosclerosis and a recem thrombus in the narrowed tumen. The mamre atheroma is highly Lhrombogemc, and Lhrombosis of an atherosclerotic p laque can abmpLly occlude Lhe lumen of med1um-sized muscular arteries causing ischemic necrosis of dependent tissues. Thrombotic occlusion may manifest as myocardial infarction, stroke, or gangrene of intestinal loops or lower exLremities. Aneritis (choice A) would exhibit i11 Oammatory cells. Calcification (choice D) would appear as inegular blue material with H&E stain. ***Diagnosis: Myocardial infarcLion
4 Upids sequestered by foam cells within the coronary arteries of the patient described in Question 3 were derived primari ly from which of the following sources? ***(A) Apoptotic bodies of smooth muscle cells ***(B) Upids found in platelet granules ***(C) Membranes of dead cells at the sile of vascular injllly ***(D) Secretory product of activated macrophages ***(E) Serum lipoproteins
4 The answer is E: Serum lipoproteins. Hyperlipidemia is cor- #NAME? disease. Cholesterol carried by serum lipoproLeins is deposited in the aLheroma, where it is endocytosed by macrophages (lipid-laden foam cells}. ***Diagnosis: Myocardial infarcLion, atherosclerosis
5 A 55-year-old man with a history of hypertension and type 2 diabetes is rushed to Lhe emergency room after collapsing He describes "tearing chest pain" radiating to the back. His blood pressure is 90/50 mm Hg, and pulse is diminished. Cardiac auscul tation reveals a dlastohc murmur, consistem with aortic regurgitation. The ECG is nonnal, and blood tests for cardiacspecific proteins and enzymes are negadve. TI1e patient dies within 24 hours of admission. The thoracic aona at amopsy is shown in the image The pathogenesis of this lesion is most closely related to which of the following underlymg conditions? ***(A) Connective tissue weakness of the aortic wall ***(B) fibrinoid necrosis and smooth muscle hyperplasia ***(C) Inunune complex-mecUated vasculitis ***(D) Neovascularization of a complicated atheromatous plaque ***(E) Subintimal lipid deposition and smooth muscle necrosis
5 The answer is A: (onnedive tissue weakness of the aortic wall. Dissecting aneurysm refers to the emry or blood into the anerial wall and its extension along the length of the vessel, which is associated with a degeneration and weakening of the aortic media. Some cases are seen in patients with Marfan syndrome, a systemic connective tissue disorder associated with mutations in the gene encoding the extraceullar matrix glycoprotein, 6brillin. Although the other choices may lead to saccular or fusifonn aneurysms in other locations, they do not cause an aortic dissection. ***Diagnosis: Dissecting aortic aneurysm
6 A previously healthy 67-year-old man presents to the emergency room with numbness of his left leg. Temperature and blood pressure are nmma1. Physical examination shows pallor and a cool left leg with absence of distal pulse. An ECG reveals no abnormalities. An arteriogram demonstrates a markedly dilated abdominal aorta and occlusion of the left popliteal anety The blockage is removed surgically, and the patient recm-ers. Which of the following is the most likely source of the anerialthromboembolus in this patient? ***(A) Deep venous thrombosis ***(B) Left vennicular mural1.hrombus ***(C) Nonbacterial endocarditis ***(D) Paradmdcal emboli ***(E) Thrombus from an aLheromatous aorta
6 The answer is E: Thrombus from an atheromatous aorta. This patient has an abdominal aortic aneurysm. A thrombus that forms over the aneurysm may embolize and lodge in a distal vesseL ln this case, a thmmboembolus occluded the popliteal artery, causing ischemia of the patient's left leg. Although a mural thrombus of the left ventricle (choice B) can embolize, there is no evidence of underlying myocardial infarction in this case. Choices B, C, and D are much rarer causes of thromboembolism. ***Diagnosis: Anerial thromboembolism
7 A 28-year-old man develops the "worst headache of his life" and then becomes comatose. A CT scan of the head reveals subarachnoid hemorrhage. The patient eventually dies, and autopsy reveals an aneurysm al the base of the brain (shown in the image; see arrow). The pathogenesis of this abnormalily is most closely linked to which of the £ollm:ving condi tions? ***(A) Arterial waU defect due to diabetes ***(B) Atherosclerotic plaque deposition ***(C) Muscle weakness of the arterial wall ***(D) Cystic medial necrosis ***(E) EndarteriTis of the vasa vasorum
7 The answer is C: Musde weakness of the arterial wall. The most conunon tJl)e of cerebral aneurysm is a saccular aneuI)' Sm, also referred to as a berry aneurysm. The lesion results from a congenital defect in smooth muscle distribmion at a branch poim of the arterial wall. The most common site of berry aneurysm formation is between the anterior communicaling and the anterior cerebral aneries in the circle of ·willis. In this case, the berry aneurysm arose from the posterior cerebral an ery (see photograph). Diabetes (choice A) and atherosclerosis (choice B) do not cause berry aneur)•sms. Cystic medial necrosis (choice D) is associated \vith dissecting aortic aneurysm. Endaneritis of the vasa vasorum (choice E) is associated with syphilitic aneurysm of the ascending aona. ***Diagnosis: Berry aneurysm, subarachnoid hemon-hage
8 A 45-year-old man presents with pain in the legs upon exerc1se and destmnion of the tips of his fingers. He has an SO-packyear history of smoking. Laboratory values include hemoglobin of 16gldl, WBC of 8,500/jll, serum cholesterol of 22 0 mgldL, fasting blood sugar of 90 mgldl, and negative tests for antinuclear antibodies. Biopsy of the affected area (shown in the image) reveals intraluminal thrombi in medium-sized anenes and inflammation extending from arteries to neighboring veins and nerves. What is the appropriate diagnosis? . ..,.. ***(A) Buerger disease ***(B) Churg-Strauss disease ***(C) Kawasaki disease ***(D) Polyaneritis nodosa ***(E) Takayasu arteritis
8 The answer is A: Buerger disease. Buerger disease (thromboangiitis obliterans) is an occlusive inflammatory disease of medium and small aneries of the distal arms and legs. The etiologic role of smoking has been emphasized by the observation that cessation of smoking can be followed by remission. Microscopic examination of affected vessels shows polymorphonuclear infiltrates extending ro neighboring veins and nerves. Inflammation of the endOlhelium is associated with thrombosis and obliteration of the affected vessels. The other choices are not associated with smoking and do not exhibit these characteristic histologic findings. ***Diagnosis: Buerger disease
9 A 45-year-old man is brought to the emergency room with rapid pulse and cold and clammy skin. Blood pressure is 90/50 mm Hg. An X-ray film of the chest demonstrares dilation of the ascending aona. Cardiac auscultation reveals a diastolic murmur in the aortic region. Laboratory studies show that serum cholesterol is 160 mgldl , hematocrit is 35%, and hemoglobin is 13.6 gldL The fluorescent Treponema amibody rest is positive The patiem suddenly becomes hypotensive and dies. The luminal surface of rhe ascend ing aona at amopsy is shown in the image. Which of the following was most likely involved in the pathogenesis of this aon ic lesion? ***(A) Arterial wail defect due to diabetes ***(B) Atherosclerosis ***(C) Congenital defect of the arterial wall ***(D) C)'Stk medial necrosis ***(E) Endaneritis of the vasa vasorum
9 The answer is E: Endart.eritis of the vasa vasorum. The results of laboratory tests indicate that the patient has syphilis. Syphilitic anemysm typicalJy a!Tects the ascending aona. Microscopk examination shows obliterative endarteritis and periarteritis of the vasa vasomm. The vasa vasomm ramify in 1.he adventitia and penen·are the outer and middle third of the aorta. ln syphilitic disease, they become encircled by lymphocytes, plasma cells, and macrophages Obliteration oflhe vasa vasomm causes focal necrosis and scaning of the media, with dismption and disorganization of the elastic lamellae. The inner surface of the affected aona shows a typical utree bark" appearance. The other choices are not involved in the pathogenesis of syphilitic anemysm. ***Diagnosis: Syphilitic aneurysm
10 A 38-ye.a r-old woman with a history of ischemic heart disease presents with disfiguring skin lesions. Physical examination shows xanthomas on the dorsal surface of both hands (shown in the image) and xanrhelasmas of the eyelids. Laboratory studies reveal serum cholesterol of 820 mgldL and significantly elevated serum ttiglycerides and LDL Which of the following histopathologic findings would be expected in a biopsy of this patients skin lesions7 ***(A) Detmal calcium deposits ***(B) Foamy macrophages ***(C) Hypertrophic scar tissue ***(D) Multinuclealed giant cells ***(E) Smooth muscle hyperplasia
10 The answer is 8: Foamy macrophages. This patiem has familial hypercholesterolemia and has inherited mutations in the LDL receptOr gene. The LDL receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocyLOsis and recycling of apolipoprotein (apo)E. Lacking LDL receptor function , high levels of LDL circulate, are taken up by dssue macrophages, and accumulate to form occlusive arterial plaques (atheromas) and papules or nodules of Lipid-laden, foamy macrophages (xanthomas). The other choices are not expected findings in xamhomas. ***Diagnosis: Familial hypercholesterolemia, xanthoma
11 A 55-year-old man suffers from an acme myocardial infarction after occlusion of the Left anterior descending cororuuy artery. The patient undergoes coronary bypass surgery 3 days later. Wl1ich of the follm:ving is the most frequent cause of saphenous vein graft failure seveml years fo llowing coronary bypass surgery? ***(A) Acme inOammalion ***(B) Atherosclerosis ***(C) Graft-versus-host disease ***(D) MetasLatic calcification ***(E) Microaneurysm
11 The answer is 8: Atherosclerosis. Saphenous veins are used as aurografts in coronary anery bypass surgety These grafts usually undergo a se ries of adapdve and reparative changes. Venous grafts in place for 5 to lO years typically show athcrosderotic plaques th at arc indistinguishable from those found in native coronal)' arteries, a process referred LO as atherosclerotic restenosis. ***Diagnosis: Atherosclerosis
12 A 45-year-old black man undergoes renal biopsy for evaluation of chronic renal faUure. The patient has a 60-pack-year hiswry of smoking. Physical examination reveals a blood pressure of 190/120mm Hg. A renal biopsy shows thickening of small arteries and anerioles, as well as edemawus intimal expansion and fibrinoid necrosis. The Congo red stain is negative. Labomtory studies show hemoglobin is 10.2 gldl and serum cholesterol is 250mgldl. BUN and serum crearinine are 42 and 5.5 mgldl, respectively. Which or the fo llowing is the most likely cause of renal failure in this padem7 ***(A) Amytoid nephropathy ***(B) Chronic pyelonephritis ***(C) Malignam hype rtension ***(D) Polya1teritis nodosa ***(E) Proliferative glomerulonephr itis
12 The answer is C: Malignant hypertension. Malignant hyperLension refers to an elevated blood pressure that may result in rapidly progressive vascular disease affecting the brain, heart, and kidney. The disease injures endothelial cells, causing increased vasculax permeability, which leads to the insudation of plasma proteins imo the vessel wall and morphologk eVIdence of fibrinoid necrosis. Polyanerilis nodosa (choice D) is an inDammaLOry process. 1n this patiem, acme vascular injury is followed by smooth muscle proliferation with an increase in concentric layers of smooth muscle cells that yield the socalled uonion skin" appearance. Poor perf·usion of the kidneys stimulates the release of renin, which serves to elevate systemic blood pressure even further (renovascular hypertension). ***Diagnosis: Hypertensive nephTosclerosis
13 A 32-year-old woman from Africa presents with a 4-momh hiswry of swelling of her tighr leg (patient shown in the image). Laboratory studies demonstrate a parasitic infestation. Soft nssue swelling of this lJatiems leg was most likely caused by which of the following conditions' ***(A) Congesuve hean failure ***(B) Deep venous thrombosis ***(C) Kidney disease ***(D) Uver disease ***(E) Lymphauc obstrucuon
13 The answer is E: Lymphatic obstruction. The patient has lilar ial worm infestation of an inguinal lymph node which has caused elephantiasis. Vnder normal circumstances, more nuid is fillered into the intersti tial spaces than is reabsorbed in to the vascular bed . This excess interstitial nuid is removed by the lymphatics. Thus, obstruction to the lymphatic now leads to localized edema fonnalion. Lymphattc channels can be obstructed by (l ) malignant neoplasms, (2) fibrosis resulting from innammation or in-adiation, and (3) surgical ablation_ The m nammatory response to filarial worms (Bancroftian and Malayan filariasis) can result in lymphatic obstruction that produces massive lymphedema of the scrotum or extremity (elephantiasis). Lymphatic edema diffe rs from other forms of edema in its high protem content, since lymph is the vehicle by which proteins and interstitial cells are returned w the circulation. This increased protein concentration may be a fibrogenic stimulus in the formation of dermal fibrosis in chronic edema (indurated edema). Congestive hean failure (choice A), kidney d isease (choice C), and ]jver disease (choice D) can cause generalized noninnammatory edema, but the swelling is bilateral. Although deep venous thrombosis can cause tenderness and swelling, it does not cause elephantiasis. ***Diagnosis: Elephamiasis, lymphedema
14 A 60-year-old man presems with dizziness , nausea, and severe shonness of breath of several months' duration. Physical examination shows hepatomegaly, ascixes, and anasarca. His blood pressure is 2001115 mm Hg An X-ray film of the chest demonstrates cardiomegaly and mild pulmonary edema. Although different mechanisms may have comTibmed to the pathogenesis ofhypenension in this patient, the common end result for all of them is which of the following? ***(A) Arterial cystic medial necrosis ***(B) Decreased plasma oncotic pressure ***(C) Gene ralized vasodilation ***(D) lncreased peripheral vascular resistance ***(E) Increased vascular pem1eabihry
14 The answer is D: Increased peripheral vascular resistance. In patients with systemic hypertension, the end result of autoregulation is al1..vays iJlcreased peripheral resistance. Most cases of hypertension represent an imbalance between renal function and sodium homeostasis. ln this context, the renjn-angiotensin system increases blood pressure, whereas this axis is antagolljzed by atrial nauiuretic factor. Cystic medial necrosis (choice A) is a factor in aortic dissecting aneurysm. Vasodilation (choice C) decreases blood pressure. Choices Band E may be a consequence of uncontrolled hypertension, but do not cause it. ***Diagnosis: Hypenensive heart disease
15 A 40-ye.ar-old woman presents with an 8-momh history of severe headaches, weakness, and dizziness. Blood pressure is 180/110 mm Hg. Physical e.:mmin.ation shows diminished tendon reflexes. An abdominal CT scan reveals a 4-cm mass in the light adrenal gland. The results of laboratory studies include serum potassium of 2. 3 mEq/L, semm sodium of 155 mEq/L, plasma cortisol of 25Jlgfdl (8AM) and 20J.1gfdl (4PM), and low plasma renin. These clinical and laboratory findings are consistent with an adrenal mmor that secretes which of the following honnones? ***(A) Aldosterone ***(B) Conisol ***(C) Epinephrine ***(D) Renin ***(E) Testosterone
15 The answer is A: Aldosterone. Th is patient has Conn syndrome, an endocrine disorder most commonly caused by an adrenal cortical adenoma. Aldosterone secreted by Lhe adrenal conical tumor causes hypertension, hypematremia, and hypokalemia. Epinephrine, renin, and testosterone (choices C, D, and E) are nm produced by adrenal conical rumors. Cordsol (choice B) may be produced by adrenal con ical mmors but does not significantly alter eleCLmlyte homeostasis. ***Diagnosis: Conn syndrome, hyperaldosteronism
16 A 25-year-old woman with a recent histOt)' of acute hepatitis B infection presems with reddish-blue lesions on her ]ower extremities, fever, muscle pain, and mild weight loss. Physical e.xamination reveals numerous regions of red-purple discoloration a([ecting the skin of both legs. Laboratory tests demonstrate positive P-ANG'\ and an elevated erythrocyte sedimemation rate. Urinalysis shows 2+ proteinuria. Biopsy of lesional s!Cn is shown in me image. Which of the following is the most Hkely diagnosis? ***(A) Benign arteriosclerosis ***(B) Ftbromuscular dysplasta ***(C) Henoch-Schonlcm purpura ***(D) Monckcberg mcdtal sclerosis ***(E) Polyaneritis nodosa
16 The answer is E: Polyarteritis nodosa (PAN) . PAN is an acute necrotizing vasculitis that affects medium-sized and smaller muscular arter ies. On occasion, PAN extcnds into larger arteries , such as the renal , splenic, or coronary artelies. The most common morphologic feature of affected arteries is fibrinoid necrosis, in which the medial muscle and adjacent tissue are fused imo an eosinophilic mass that stains for fibrin. PAN affecting small vessels is frequently associated with the presence of P-ANCA. Approximately 15% of patients vvith PAN demonstrate either HBsAg or anti-HCV antibodies. Choices A, B, and D are not characterized b)' necrosis of the arterial wall. The immune complexes seen in Henoch-$chonlein purpura (choice C) are unrelated to hepatitis B. ***Diagnosis: Polyarteritis nodosa
17 A 33-year-old man with AIDS presems with multiple, purplecolored skin nodules on his hands and feet. The lesions vary in size from 1 mm to 1 em in diameter. Biopsy of lesional skin is shown in lhe image. Which of d1e following vimses is implicated in the pathogenesis of this patients skin neoplasm? ***(A) Cywmegalovirus ***(B) Human herpesvirus-6 ***(C) Human herpesvirus-8 ***(D) Human immunodeficiency vims ***(E) Human papillomavirus
17 The answer is C: Human herpesvirus-8 (HHV-8). Patiems with AIDS may develop Kaposi sarcoma. Microscopic examination of a skin lesion shows numerous poorly dilferemiated spindleshaped neoplastic cells and vascular lesions filled with red blood cells, characteristic of Kaposi sarcoma. HHV-8 is implicated in the paLhogenesis of this tumor in HIV-infected patients. HIV (choice D) by itself is not a cause of Kaposi sarcoma. ***Diagnosis: Kaposi sarcoma, AtD$
18 A 30-yeaT-old woman presents with a widespread skin rash that she has had for 5 days. She is taking sulfa medication fo r recurrent cystitis. A skin biopsy shows leukocyLOclastic vasculitis involving dermal venules. What is the appropriate diagnosis? ***(A) Buerger disease ***(B) Giam cell granulomatous arteritis ***(C) Henoch-Schonlein purpura ***(D) Hypersensitivity angiitis ***(E) Polyarter itis nodosa
18 The answer is 0: Hypersensitivity angiitis. Hypersensitivity angiitis refers to a broacl spectnnn of inflammatory lesions that represem a reaction to foreign matetials (e.g., bacterial products or more commonly drugs). When the vascular lesions are confined to Lhe skin, the Lerms leukocytoclaslic vasculitis, cutaneous vasculltis, or cutaneous necrotizing venulilis are applied. The Q[her choices are not caused by sulfa drugs. ***Diagnosis: Hypersensitivity angiitis
19 A 70-year-old woman complains of a throbbing unilateral headache and vision problems. She repons weight loss and mandibular pain while eating. The patient also has a history of recurrem bouts of fever accompanied by malaise and muscle aches. Physical examination reveals nodular enlargement o[ the temporal artery with pain on palpation. A biopsy is obtained (shown in the image). What is the approptiate diagnosis? ***(A) Giam cell arteritis ***(B) Hypersensitivily angiitis ***(C) Kawasaki disease ***(D) Polyarteritis nodosa ***(E) Wegener granulomatosis
19 The answer is A: Giant cell arteritis. Giam cell (temporal) anerius is the most common vasculitis. The disease is a local, chronic granulomawus inflammation of the temporal aneties. The average age at onset is 70 years. Hiswlogic examination shows gjam cell granulomawus inflammation. whtch destroys the media of the temporal anety and predisposes to thrombosis (see photomicrograph). Headaches, cypically in the form or throbbing temporal pain and visual problems, may appear. A palpable, wnuous, and s'vollen temporal anery may be the only finding on physical examlnation. \¥egener granulomatosis (choice E) causes granulomatous inflammation, but not in the temporal artery. The other choices are not associated with multinucleated giant cells. ***Diagnosis: Giam cell granulomatous aneritis, temporal aneritis
ZO A 48-year-old man presents with an exquisitely painful. raised, red lesion on the dorsal surface o f his left hand. Hiswlogic examination of a skin biopsy reveals nests of round regular cells within cormective tissue associated 'Nilh branching vascular spaces. \Vhich of the following is the most likely diagnosis? ***(A) Angiosarcoma ***(B) Dermatofibroma ***(C) Glomus LUmor ***(D) Hemangioma ***(E) Upoma
20 The answer is C: Glomus tumor. A glomus tumor is a benign tumor of the glomus body, which is often extremely painful. Glomus bodies are normal neu romyoarteJial recepto rs that are sensitive to temperature and regulate arte1iolar blood flow. The lesions are small, usually smaller than l em in diameter. The two main histologic components are branching vascular chann els in connective tissue stroma and aggregates of specialized glomus cells. The mher choices tend nm LO be painful. ***Diagnosis: Glomus tumor
Z1 A 60-ye~u·~old man has his left forearm amputated because he has invasive rhabdomyosarcoma. The pathologist notes calcification in the wall of the radial anery, which otherwise appears w1remarkable. Which of the following is the appropriate diagnosis? ***(A) Churg~Strauss disease ***(B) Complicated atherosclerotic plaque ***(C) Fibromuscular dysplasia ***(D) Monckeberg medial sclerosis ***(E) Polyarteritis nodosa
21 The answer is D: Monckeberg medial sclerosis. Moncl<eberg medial sclerosis is charactelized by calcification or the media of large· and medium·sized arteries of older persons who are not othenvise affected by atherosclerosis (choice B). On gross examination, the involved aneries are hard .and dilated. These arterial changes are usually asymptomatic. None of the other choices display calciGcation. ***Diagnosis: Monckeberg medial sclerosis
22 A 20-year-old woman complains of double vision, fainting spells, tingling of the fingers of her left hand, and numbness of the fingers of her tight hand. Physical examination reveals absence of pulse in her right arm. LaboraLory tests sho\v elevated erythrocyte sedimentation rate and thrombocytosis. An aonogram demonstrates narrowing and occlusion of branching aneries, including the right subclavian artery. The patient subsequently develops hean failure and dies of massive pulmonary edema. At amopsy, the aorta has a thickened wall and shows vasculitis and fragmentation of elastic fibers. Which of the follo\ving is the most likely diagnosis? ***(A) Buerger disease ***(B) Churg-Strauss disease ***(C) Kawasaki disease ***(D) Polyartelitis nodosa ***(E) Takayasu arteritis
22 The answer is E: Takayasu arteritis. Takayasu aneritis is an inflammawry disorder of large arteries, classicaUy !he aortic arch and its major branches. On gross examination. the aona is thickened, and the intima exhibits focal, raised plaques. The branches of 1.he aorta often display localized sl.enosis or occlusion, which interferes with blood flow and accounts for the symptoms of ''pulse less" disease. Ischemic cerebrovascular episodes in a young woman and a differential between the blood pressure in the left and the right ann suggesL the diagnosis of Takayasu disease. More than 90% of patients aTe women under 30 )'ears of age. The o!her chokes are diseases of arteries that have di£ferem clinical and pathologic manifestations. ***Diagnosis: Takayasu arteritis
23 A 19-year-old man with a history of recent-onset asthma presents with chest pain, intermittent claudication, and respiratory distress that is unresponsive to bronchodilators and anlibiolics. Physical examination reveals mild hypertension (blood pressure = 150/100 mm Hg), bilateral wheezing, and numerous purpuric skin lesions on the feeL Laboratory studies demonstrate that leukocytes are increased to 14,000/ J..LL with increased eosinophils and platelets are increased to 450 ,000/J..LL. BUN is elevated to 30 mgldL, and semm creatinine is elevated to 3.5mgldL The serum antineutrophil cytoplasmic antibody test is positive Urinalysis discloses 3+ proteinmia and RBCs. A renal biopsy demonstrates vasculitis of medium-sized aneries, accompanied by eosinophilia. Which of the follo\ving is the most likely diagnosis? ***(A) Churg-So·auss disease ***(B) Henoch-Schonlein purpura ***(C) Loeffler syndrome ***(D) Polyarter itis nodosa ***(E) Wegener granulomatosis
23 The answer is A: Churg-Strauss disease. Churg·Strauss disease is an idiopathic, sys1.emic, granulomatous disease of small- and medium-size arteries characterized by vasculitis of many organs, fluctuating eosinophilia, and late-onset asthma. The majority o[ patiems display anlineurrophil cytoplasnuc ami bodies. The disease is also known as allergic granulomatosis and angiitis. Transbronchiallung biopsy shows granulomarous lesions in vascular and extravascular sites, accompanied by intense eosinophilia. The vasculitis hiswlogicaUy resembles the lesions of polyaneritis nodosa (choice D) and Wegener granulomawsis (choice E), bm these diseases do not cypically present wil.h an asthmatic syndrome. ***Diagnosis: Churg-$rrauss disease
24 A 40-yea l~old man presenlS with a :Z-week history of recurren t oral ulcers, gen]tal ulcers, inteJmittent arthritic pain of the knees, and abdominal pain. Physical examination reveals shallow ulcerations of the mucosa of the glans penis, as well as oral aphthous ulcers and conjunclivids. Which of the following is the most Likely diagnosis? ***(A) Behc;et disease ***(B) Genital he11)es ***(C) Gonon hea ***(D) Polyane1itis nodosa ***(E) Syphilis
24 The answer is A: Beh~et disease. Behc;et disease is a systemic vasculitis characterized by oral aphthous ulcers, genital ulceration, and ocular inflammation, with occasional involvement of the nervous, gastrointestinal, and cardiovascular systems. The mucocutaneous lesions show a nonspecific vasculitis of arterioles, capillaries, and venules. The cause of the necrotizing inflammaLion of small blood vessels is not known, but an association with specific HLA subtypes suggests an immune basis. Herpes (choice B) does not presem with arthritis. ***Diagnosis: Be h c;;et disease
25 A neonate has a well-demarcated lesion in the upper eyelid and forehead resembling a tumor (shown in the image) A biopsy shows large vascular channels imerspersed with small, capillary type vessels. What is the appropriate diagnosis? ***(A) Angiosarcoma ***(B) Capillary lymphangioma (C} Cavernous hemangioma ***(D) Hemangioendothelioma ***(E) Hemangiopericytoma
25 The answer is C: Cavernous hemangioma. Congenital cavernous hemangioma is a benign lesion consisting of large vascular channels, frequently interspersed wtth small capillary- type vessels. These lesions occur ptimarily in the skm, where they are te rmed pon-wine stains. Cavernous hemangiomas may also be fow1d in the brain. where, after a long quiescem period, they may slowly enlaTge and cause neurologic symptorns. Cavemous hemangiomas can w1dergo a vatiety of changes, in cluding thrombosis and fibrosis, cystic cavitations, and intracystic h emorrhage. Capillary lymphangioma (ch oice B) is a rumor of the lymphatic system and is not discolored. The other ch oices are not characteristically encoumered as congenital lesions of the face. ***Diagnosis: Congenital cavernous hemangioma
26 A 48-year-old man wilh diabetes presents with a history of progressive pain in both legs for several years. The pain is severe after walking two blocks or climbing one flight of stairs. Blood pressure is 145/90 mm Hg. Laborawry studies show a serum cholesterol of 320 mgldL. He neither smokes nor drinks. Bruits are evident upon auscultation of both femoral aneries. The pathogenesis of intermittent claudication ln this patient is most closely associated with which of the following risk factors? ***(A) Hyperglycemia ***(B) Hyperlipidemia ***(C) Obesity ***(D) Sedentary lifestyle ***(E) Systemic' hype rtension
Z6 The answer is 8: Hyperlipidemia. The pathogenesis of atherosclerosis is believed to involve in,imy to the imb11a, insudation of cholesterol, activation or platel ets, and growth factor-mediated recruitment of fibroblasts, macrophages, and smooth muscle ce lls. The principal risk factors for atherosclerosis are age, male sex, heredity, lipid metabolism (hypercholesterolemia), obesity, h )'Penension, diabetes mellitus, smok· ing, and sedentary lifestyle. Although several of these lisl< factors apply to this patient (choices A, 0, and E), h yperli pidemia is considered to be the major fac tor in the pathogenesis of atherosclerosis. Chronic ischemia of the lower limbs due to atherosclerosis causes hypoperfusion of the leg muscles. When the blood supply becomes inadequate, usually upon exertion , the muscles develop cramps (imermittent cJaudication). ***Diagnosis: Atherosclerosis
27 A 70-year-old, previously healthy man presents \Vi.th right upper quadrant pain. Physical examination demonstrates hepatomegaly. A llver biopsy reveals a vascular lesion composed of pleomorphic endothelial cells ''lith hyperchromatic nuclei and numerous mitoses. Laboratory tests ror HIV infection are negative. Vv'hich of the following is the most likely diagnosis? ***(A) Angiosarcoma ***(B) Dem1atofibroma ***(C) Glomus tumor ***(D) Hemangioma ***(E) Kaposi sa rcoma
Z7 The answer is A; Angiosarcoma. Angiosarcoma is a highly malignant tumor composed of masses of malignant endothelial cells, The most common locations are the skin, breast, bone, liver, and spleen. Angiosarcoma exhibits varying degrees of di[[erentiarion, ranging from mmors composed of distinct vascular elements to undifferentiated wmors with nuclear pleomorphism, and frequent mitosis. Kaposi sarcoma (choice E) is most commonly associated with AIDS pariems who are inJected by HHV-8_ ***Diagnosis: Angiosarcoma
28 A 60-year-old man with a history of recurrent headaches and blurred vision presents to the emergency room with excruciating pain radiating to his back, beginning 2 hours prior tO admission. Blood pressure on admission is 110/70 mm Hg. He appears pale and sweaty. Echocardiogram shows an enlargemem of the left vermicular wall. ECG is normal. and blood tesrs for cardiac proteins are negative. One hour after admission, the patient experiences pain radiating to his left flank and right side of his neck. The patient suddenly becomes hypotensive and expires. Microscopic examination of the thoracic aona at autopsy is shown in the Image (aldehyde fuchsin stain). Which of the following best characterizes these pathologic findings? ***(A) Acute inflammation ***(B) Atherosclerosis ***(C) Chronic inflammation ***(D) Cystic medial necrosis ***(E) Fibrinoid n ecrosis
28 The answer is D: Cystic medial ne<rosis. Dissecting aneurysms typically affect the thoracic aorta, but may extend to other vessels. The morphologic findings are characteri sLic of a degenerative process known as cystic medial necrosis (of Erdheim). Focal loss of etastic and muscle fibers in the aortic media leads to "cystic" spaces filled with pools of metachromatic myxoid material (see photomicrograph). Neither inflammation (choices A and C), atherosclerosis (choice B), nor fib rinoid necrosis (choice E) are presenL ***Diagnosis: Dissecting aortic aneurysnc, cystic medial necrosis
29 A 65-year-old man presen lS with a 2-week history of abdomi· nal discomfort. Physical examination reveals a pulsatile, abdominal mass in the periumbilical region. ACT scan shows a segment of abdominal aorta proximal to the bifu rcation that is dilated (5 em) and calcified. The patient is scheduled for corrective surgery but suffers a massive stroke and e.:-.:pires. The abdominal aorta is examined at autopsy (shown in the image). Which or the follovving is the most likely underlying cause of this patient's abdominal mass? ***(A) Angiosarcoma ***(B) Atherosclerosis ***(C) Cystic medial necrosis ***(D) Hypercalcemia ***(E) Thromboembolism
29 The answer is B: Atherosclerosis. Aneurysms are localized dilations of blood vessels caused by either congenital or acquired weakness. An aneurysm is defined as an increase in the vessels diameter by at least 50%. Fonns of aneur}'Sm include saccular, fusiform , and dissecting (tear in the media) The large majority of aneurysms of the abdommal aona in elderly patients are related to atherosclerosis. The aneurysm in this patient was opened longimdinally to reveal a large mural thrombus within the lumen (see photograph). The tisk of rupture of an abdominal aortic aneurysm is a funcdon of its size. Aneurysms under 4cm in diameter rarely rupmre, whereas up to 40% of (hose larger than S em mpture within 5 years. Cystic medial necrosis (choice C) is associated with dissecting aortic aneurysm. The other choices do nm cause abdominal aneurysm. ***Diagnosis: Aneurysm, atherosclerotic
30 A 48-year-old woman with familial hypercholesterolemia complains of severe, crushin g, substernal chest pain. The pain is relieved by administration of sublingual nitroglycerin or bed resL The patient subsequendy goes into cardiorespiratory arrest and expires. The left coronary anery at autopsy is shown in the image. The material that has acutely occluded the lumen of this blood vessel is largely composed of which of Lhe following cellular components? ***(A) Activated endothelial cells ***(B) Lipid-laden (foamy) macrophages ***(C) Multinucleated giant cells ***(D) Platelets and red blood cells ***(E) Segmemed neutrophils
30 The answer is D: Platelets and red blood cells. Patiems '.vilh familial hyperlipidemia develop complications of aLherosderosis at an early age, including coronary artery thrombosis. A thrombus is a collection of fibrin and retained blood elements (e.g., platelets and RBCs) that adhere to the vascular \valL Thrombi may result in complete ane1ial occlusion, followed by ischemia and infarction. The mher choices do not represem cellular components of a thrombus. ***Diagnosis: Myocardial infarction
31 A 30-year-old woman with Sjogren syndrome presents with a 24-hour history of a purpuric skin rash_ Which of the following is the most likely diagnosis? ***(A) Buerger disease ***(B) Giant cell granulomatous aneritis ***(C) Hypersensitivity vasculitis ***(D) Thrombotic thrombocytopenic purpura ***(E) Wegener granulomatosis
31 The answer is C: Hypersensitivity vasculitis. Purpura or skll1 rash in a patient with a known amoimmune disease, such as Sjogren syndrome or systemic lupus erythematosus, is usually amibuted to hypersensitivity vasculitis. This vasculitis is caused by the deposition of immune complexes in dem1al venulcs. The other choices are not p1imarily immune complex diseases. ***Diagnosis: Hypersensitivity vasculitis
32 A 62-year-old man is discovered to have hyperlipidemia on screening tests after a routine physical examination_ Laboratory studies show total serum cholesterol of 285 mgldL, LDL of 215mgldl, HDL of 38mg!dL, and triglycerides of 300mgl dL This patient is most at risk of developing an aneurysm in which o[ the followmg anammic locations? ***(A) Abdominal aorta ***(B) Ascending aorta ***(C) Circle of Willis ***(D) Coronmy artery ***(E) Renal ane1y
32 The answer is A: Abdominal aorta. Abdominal aortic aneurysms, which are defined as an increase in aortic ruamerer of 50% or more, are rhe most frequent aneurysms, usually developing after the age of 50 years. The most common cause of these abdominal aonic aneurysms is atherosclerosis. Aneul)' Sms secondary to atherosclerosts are tess common in the other anatomic locations listed. ***Diagnosis: Atherosclerosi.s
33 A 3-year-old gtrl presents wnh htgh fever, extensive skin rash, and conjunctival congestion. Physical examination reveals cervical lymphadenopathy, erythematous palms and soles, and a dry and red oral mucosa. A throat culture is negative. Rouune CBC ts normal, and the monospot test for infectious mononucleosts IS ncgauvc. Addmona] laboratory tests rule om C)'l.OmegaloVlrus mfccuon and toxoplasmosis. Two months later, the chtld develops stgns and symproms of hean fatlure and C\'Cntually goes mto cardtac arrest. The hean at autopsy is shown m the tmage. What 1s the appropnate dtagnosis? ***(A) Buerger disease ***(B) Churg-Strauss disease ***(C) G1am cell granulomawus ancnus ***(D) Kawasaki dtsease ***(E) Takayasu anentis
33 The answer is D: Kawasaki disease. Kawasaki disease, or mucocutaneous lymph node syndrome, is a vasculitis of unknown etiology that presen ts with fever, skin rash, mucosal innammation, and lymph node enlargemem. The disease usuaUy has a self. [imited course but may involve the coronary arteries and lead to aneurysm formation. Heart failure occu rs in l% to 2% of cases. The other choices are not associated with aneurysms of coronary arteries. ***Diagnosis: Kawasaki disease
34 A 45-year-old woman presents with a 4-momh history of severe headaches and pain, and blanching of the hands upon c>rposu re to cold. She is a nonsmoker. Over the past6 months, she has noticed progressive difficulty in swallowing solid food. Phys•cal examination reveals smooth and uglu ski11 over the face and fingers. The serolog.c test for ami-Scl-70 (amitopo•somcrasc) IS positive. Painful hands m this patient arc best descnbed usmg \Vh1ch of the followmg terms? ***(A) Chilblains ***(B) Homans' sign ***(C) lmermittem claudication ***(D) Raynaud phenomenon ***(E) Trousseau phenomenon
34 The answer is 0: Raynaud phenomenon. This patient suffers from scleroderma complicated by Raynaud phenomenon. The latter refers to intermittent, bilaLeral attacks or vasospasm of the fingers or wes (sometimes affecting the ears or nose), resulting in pallor, pa resthesias, and pain from ischemia. The symptoms are precipitated by cold or emotional stimuli and relieved by heat. Raynaud phenomenon may occur as an isolated disorder or as a feature of a number of systemic diseases, including systemic lupus e1ythematosus and sclerodenml. Intermittent claud[cation (choice C) is associated with peripheral vascular disease (atherosclerosis). Chilblains (choice A) represem iLchy or tender red or purple bumps that occur as a reaction to cold. ***Diagnosis: Scleroderma
35 A 6-year-old gi rl presems with a 2-week history of a skin rash over her buttocks and legs and joint pain. The parents report seeing blood in the mine. Physical examination reveals palpable purpuric skin lesions and markedly swollen knees. The resltlts of laboratory studies reveal abnormally high erythrocyte sedimentation rate (30mmlh), BUN of 25 mgtdl , and serum creatinine of 3 mgldL Urinalysis demonstrates RBCs and RBC casts. The stool guaiac test is positive. Biopsy of lesional skin reveals deposits of lgA in the walls of small blood vessels. Which of the following is the most likely diagnosis? ***(A) Henoch-SchonJein purpura ***(B) Hypersensitivity vasculitis ***(C) Kawasaki disease ***(D) Polyaneritis nodosa ***(E) Poststreptococcal glomerulonephritis
35 The answer is A: Henoch-Schonlein purpura. HenochSchtmlein purpura is the most common type of childhood vasculitis and is caused by vascular localization of immune complexes. comaining predominantly lgA. Purpuric skin lesions and glomerulonephritis in a child suggest the diagnosis of Henoch-Schonlein purpura. The other choices do nor include deposits of IgA in tl1e blood vessels. ***Diagnosis: Henoch-SchonJein purpura
36 A 504 year-old woman with type 2 diabetes and hypenension undergoes renal biopsy for evaluation of chronic renal disease. The biopsy is shown in the image. What is the appropriate diagnosis? ***(A) H)'aline aneriolosclerosis ***(B) Kimmelstiel-Wilson disease ***(C) Monckeberg medial sclerosis ***(D) Papillary necrosiS ***(E) Polyarteritis nodosa
36 The answer is A: Hyaline arteriolosclerosis. Hyaline aneriolosclerosis is demonstrated by vessels (smallest aneries and arte1ioles) that are markedly thickened by the deposition of basement membrane material and accumulation of plasma proteins. HyaliJ1e arteriolosclerosis is often seen in the elderly. but more advanced lesions are observed in persons 'Nith diabetes or long-standing hypertension. The other choices are incorrect because they are not diseases of artelioles. Kimmelstiel- Wilson disease (choice B) affects glomeruli in patients with diabetes mellin1s. ***Diagnosis: Hyaline arteriolosclerosis
37 A 79-year-old man presents with a history or extensive ulce rs on both legs for 4 years. A photograph or the patients legs is show·n in the image. What is the appropriate diagnosis? ***(A) Deep venous thrombosis ***(B) Lymphangitis ***(C) Mil roy disease ***(D) Severe aneriolosclerosis ***(E) Varicose veins
37 The answer is E: Varicose veins. The principle diseases affecting the veins are tl1rombophlebitis (tbrombosis-induced local inflammation) and vaticosities. A varicose vein is an enlarged and tortuous blood vessel. Superficial vaticosities of the leg veins, usually in the saphenous system, are among the most common ailments of humans due w our upright posture. Blood How becomes mrbulent and slow. and leaks from the engorged capillaries imo the surrounding tissue cause stasis dermatitis (as shown here). Varicose veins predispose w deep venous thrombosis (choice A). bmthere is no specific evidence [or this condition ln the patients clinical histoty Lymphangitis and Milroy disease (choices Band C) represent diseases of lhe lymphatic syslem. ***Diagnosis: Varicose veins
38 A 76-year-old woman presents whh a 1-hour histmy of substernal chest pain. Shortly after admission the patient expires. At autopsy. extensive calcium deposilS are noted in the cora· nary and otl1er arteries aiTected by severe atherosclerosis. Which of the following tenns best describes these autopsy findings? ***(A) Dystrophic calcification ***(B) Hyperplastic calcification ***(C) Hypemophic caldficalion ***(D) Metastatic calcification ***(E) Physiologic calcification
38 The answer is A: Dystrophic calcification. Dystrophic calcification is a response to cell injury. Serum levels of calcium are normal, and the calcium deposits are located in previously damaged tissue. This patient suffered from coronaty ane1y atherosclerosis. The pathogenesis of the atherosclerotic plaque is a dynamic process that usually occurs over decades, leading to erosion, ulceration or fissuring of the surface of the plaque; plaque hemorrhage; mural thrombosis; and calciFication. Calcification is thought to depend on a balance of mineral deposition and resorption in areas of vascular necrosis. These apposing metabolic processes are regulated by osteoblast-like and osteoclast-like cells in the vessel wall. Metastatic calcification (choice D) is associated with hypercalcemia. Physiologic cakificadon (choice E) occurs in normal bone. ***Diagnosis: Atherosclerosis, dystrophic calcification
39 A 48-year-old man with a longscanding hiswry of chronic constipation complains of anal itching and cliscomfon toward the end of the day. He desCJibes a perianal pain when sitting and finds himself sitting sideways to avoid discomfort. Physical examination reveals painful varicose dilations in the anal region, associated with edema. \IVhich of the following is the most lil<ely diagnosis? ***(A) Anal cancer ***(B) Anal fissure ***(C) Hemorrhoids ***(D) Ischiorectal abscess ***(E) Rectal cancer
39 The answer is C: Hemorrhoids. Hemorrhoids are dilations of veins of the rectum and anal canal, which may occur inside or outside the anal sphincter. This condition may be aggravated by constipation and pregnancy and can also result from venous obstruction by rectal mmors. Thrombosis of hemorrhoids is exquisitely painful. or interest, internal hemorrhoids typically bleed without pain, whereas external hemorrhoids typically hurt but do not bleed. The other choices do not feature dilaled veins. ***Diagnosis: Hemorrhoids, varicose veins
40 A 45-year-old woman complains that her fingers [eel stiff. On physical examination the skin of the patiem's face appears tense and radial funows are evident around the mouth. Laboratmy stucUes establish a diagnosis of scleroderma. Several years later, the patiem subsequently develops renal insufficiency. A renal biopsy is shown in the image. Which of the following best describes the pathogenesis of renal vascular involvement in this patient wi!.h progressive systemic sclerosis? ***(A) Accelerated atherosc1erosis ***(B) Cystic medical necrosis ***(C) Organization of microthrombl ***(D) Perivascular arteritis ***(E) Subintimal fibromuscular thickening
40 The answer is E: Subintimal fibromuscular thickening. Scleroderma is charaClerized by vasculopalhy and excessive collagen deposition in the skin and a variety of imemal organs. The disease occurs four times as often m women as in men, mosdy in persons between 25 and 50 years of age. Lesions in the arteries, arterioles, and capilJaries are typical, and m some cases may be the first demonstrable pathological finding in the disease. The kidneys are involved in more than half of patients \'lilh scleroderma. They show marked vascular changes, often with focal hemorrhage and cortical infarcts. Among the most severely affected vessels are the interlobular aneries and afferent arterioles. Early fibromuscular thickening of the subimLma causes luminal narrowing, followed by fibrosis. The other pathologic lesions may occur, but they are not the principal cause of vasculopathy in patiems with scleroderma. ***Diagnosis: Scleroderma
41 An 80-year-old woman with a history of smoking experiences acme chest pain and is rushed to the emergency room. Laboratory studies and ECG confirm a diagnosis of myocardial in[arction; however, coronary artery angiography 2 hours later does not demonstrate evidence of vessel occlusion. 'vVhich of d1e following proteins mediated fib rinolysis at d1e site of temporary blockage in this patiem:S coronary anery? ***(A) Bradykinin ***(B) Collagenase ***(C) Kallikrein ***(D) Plasmin ***(E) Thrombin
41 The answer is D: Plasmin. A thrombus may undergo several fates including (l) lysis, (2) growth and propagation, (3) detachment and embolization, or (4) organization and canalization . The combination of aggregated platelets and clotted blood is made unstable by the activation or plasmin. Plasmin is a fibrinolytic enzyme that is fom1ed from plasminogen by tissue plasminogen activator (tPA). tPA is a serine protease that catalyzes the conversion of plasminogen to plasmin. Once formed, plasmin lyses fibrin and dissolves the thrombus. Occlusive thrombi can also be dissolved by enzymes, such as streptokinase, that activate plasma fibrinolytic activity The conversion of plasminogen to plasmin, and the activity of plasmin, are regulated by specific inhibitors. None of the other choices are involved in fibrinolysis. ***Diagnosis: Myocardial infarction, thrombolysis
1 A heart murmur is noted during the preschool physical examination of a 4-year-old girl. An echocardiogram reveals a defect between the right and left atrium involving the limbus of the toramen ovale. What is the most likely diagnosis? ***(A) Aerial septal detect (ASD), ostium primum ***(B) ASD, ostium secundum ***(C) Tetralogy ofFallOl ***(D) Tmncus arteriosus ***(E) Ventricular septal defect
1 The answer is B: ASD, ostium secundum. Ostium secundumtype ASD accoums for 90% of all ASDs. It reflects a true deficiency of the atrial sepLum and should nm be confused with patem foramen ovale. OsLium secundum defects commonly occur in lhe middle ponion of the septum and vary in size from a trivial opening to a large defect of the entire fossa ovalis. A small ASD is unlikely Lobe functional, but LefL-to-rtght shunting may occur in Large defects, causing dilation and hypertrophy of lhe right atrium and ventricle. The ostium pnmum anomaly occurs adjacent LO the AV valves and is usually associated with a cleft ame1ior mitral leaflet. Ventricular septal defect (choice E) occurs in the imervemncular septum The diagnoses in choices C and D are characterized by multiple congenital abnormalities and early cyanosis. ***Diagnosis: Ao·ial septal defect
2A 15-year-old girl is brought to the emergency room with heart palpitations and dyspnea. Her past medical history is significant for an unrepaired atrial septal defect (.ASD). Physical examination reveals cyanosis, cUstended JUgular veins, hepatosplenomegaly, and a sysmlic ejection murmur. This patient has most likely developed which of the following complications of congenital heart disease? ***(A) Aortic anelll)'Sm ***(B) Myocardial infarction ***(C) Parado:Aical embolism ***(D) Pneumonia ***(E) Pulmonary hypertension
2 The answer is E: Pulmonary hypertension. Patieni.S with uncorrected ASDs may develop narrowing of the pulmonary vasculature, in which case the (low of blood through the defect may be reversed, thereby creating a Ti gh t-to- left shunt. The increase in pulmonary capillary pressure is transmitted to the pulmonary arte1ies, a condition termed pulmonary hypertension, ultimately resulting in right-sided hean failure. Complications of ASDs include cyanosis, atrial arrhythmias, right ventricular hypertrophy, tight heart failure, bacterial endocarditis, and paradoxical emboli. None of the other cholces are associated wi rh a right-to-left shunt. ***Diagnosis: Eisenmenger syndrome, atrial septal defect
3 A 5-year-old boy is found to have a harsh holosystolic murmur heard at the left 4th intercostal space. The child has a history of recurrent pneumonias and respiratoty tract infections. An echocardiogram reveals a hean defect and biventricular cardiac hypertrophy. Cardiac catheterization discloses pulmona.y hypertension. This patient likely has which of the fol lowing congenital heart diseases? ***(A) Coarctation of aorta ***(B) Hypoplastic left ventricle ***(C) Patent ducLus aneriosus ***(D) Pulmonic stenosis ***(E) Ventricular septal defect
3 The answer is E: Ventricular septal defect {VSD) . VSD is the ..__ most common congenital heart lesion. Such anomalies occur as isolated lesions or in combination with other malformations. VSDs vary in size, occuni.ng as a small hole in the membranous septum, a large defect involving more than the membranous portion, defects in the muscular portion, or a complete absence of septum. Small VSDs may have little functional signlficance and often close spontaneously. Large VSDs are initially characterized by a left-to-tight shunt, with left ventricular dilation and congestive hean failure. If the patient survives long enough, pulmonary hypenension may cause reversal of the direction of the shunt and Lead to cyanosis. Coarctation of aorta (choice A) presents only with left ventricular hypertrophy and does not typically cause pulmonary hypertension. Pulmonic stenosis (choice D) presems \vith right ,·emricular hypertrophy. ***Diagnosis: Vennicular septal defect
4 An 8-month-old girl with Turner syndrome is brought to the emergency room by her parents, who complain that their daughter is breathing rapidly and not eating. Physical examill ation reveals tachypnea, pallor, absent femoral pulses, and a munmn heard at the left axilla. There is hypertension in the upper extremities and low blood pressure in both legs. A chest X-ray shows notchi.ng or scalloping of the ribs. WhaL is the appropriate diagnosis? ***(A) Aortic valve stenosis ***(B) Atrial septal defect ***(C) Coarctation of aorta ***(D) Patent ductus aneriosus ***(E) Tetralogy ofFalloL
4 The answer is C: Coardation of aorta. Aortic coarctation is common, accounting for 6% of all cases of congenital heart disease. Coarctation usuaUy occurs in the thoracic portion of the descending aorta, distal to the takeoff of the left subclavian artety at the site of the ductus arteriosus. The incidence of a bicuspid aonic valve in association with coarctation is 80% to -85%. The cardinal physical finding is dimmution or absence of femoral pulses and hypenension in the upper extremities. Notching or scalloping of the tibs caused by marked enlargement of the intercostal collaterals can be seen on X-ray. None of the other choices exhibit these charactetistics. Aortic valve stenosis {choice A) does not present with hypertension in the upper extremities. ***Diagnosis: Coarctation of aorta
5 A 2.-week-old boy is i tTitable and feeding poorly On physical ....__ examination, the infant is irritable, diaphoretic, tachypneic, and lachycardic. There is circumoral cyanosis, which is not alleviated by nasal oxygen. A systolic thrill and holosysLolic murmur are heard along the left sternal border. An echocardiogram reveals a hean defect in which the aorta and pulmonaty artery form a single vessel that overrides a ventticular septal defect. What is the approptiate diagnosis? ***(A) Atrial septal de feet ***(B) Coarctation of aorta , preductal ***(C) Patem ductus aneriosus ***(D) Tetralogy ofFallot ***(E) Truncus aneriosus
5 The answer is E: Truncus arteriosus. Truncus arteriosus refe rs to a common trunk for the origin of the aorta, pulmonary aneries, and coronary aneries.lt results from absenL or incomplete partitioning of the truncus arteriosus by the spiral septum during development. Most infants with persistent u1.mcus anen osus have wrrenual pulmonary blood flow, whtch leads w heart failure. None of the other choices are chsLi.nguished by a single vessel that carries blood from the heart. ***Diagnosis: Truncus arteriosus
6 A 2-week-old girl is found to have a harsh munnur along the left sternal border. The parents report that the baby gets "bluish" when she cries or drinks fTom her bottle. Echocardiogram reveals a congenital hean defect associated v.rith pulmonaty stenosis, ventricular septal defect, dextropositjon of the aona, and ligh t ven tricular hypertrophy. What is the appropriate diagnosis? ***(A) Ao·ial septal de feeL ***(B) Coarctation of aorta, postductal ***(C) Coarctation of aorta, preductal ***(D) Tetralogy of Fal1ot ***(E) Tmncus aneriosus
6 The answer is D: Tetralogy of Fallot. Tetralogy of Fallot is defined by four anatomic changes: pulmonary stenosis, ventTicular septal defect, dextroposilion of the aorta, and right ventricular hypertrophy. lt is the most cotrunon cyanotic congenital heart disease, accounting for 10% of all con genital bean defects. Cyanosis appears shortly after birth or in early infancy due wright- to-left shunting of venous blood from the 1ight venui cle into Lhe de.-..moposed aorta. The aorta overrides the ventricular septal defect and receives blood from both ventricles. Narrowing of the pulmonary an ery impedes the entry of blood lnro the lung, thereby increasing the pressure in the 1ight ventricle. None of the other choices exhibit this particular constellation of congenital h eart defects. ***Diagnosis: Tetralogy of Fallot
._7_ A 2-momh-old boy is admitted to the pediatric ward in acme respiratory distress. Physical ex:ammation shows pallor, peripheral cyanosis, tachypnea, intercostal retractions, and nasal flaring with gruming. Cardiac auscultation reveals third heart sounds. An X-ray film of the chest shows severe cardiomegaly and bilateral pleural effusion. The patient expires 2 days after admission. The heart at autopsy is shO\vn in the linage. Which of the following is the most likely diagnosis? ***(A) Cardiac amyloidosis ***(B) Endocardial fibroelastosis ***(C) Hypoplastic left hcan syndrome ***(D) Patent ductus anenosus ***(E) Tetralogy of Fallot
7 The answer is B: Endocardial fibroelastosis (EF) . EF is characterized by fibroelasmric thickening of the endocardium of the left ventricle, which may also affect the valves. The endocardium and valves of the left ventricle show im~gular gray-white patd1es of fibroelastotic thickening usually accompanied by degeneration of sub endocardial myocytes. EF occurs in association witl1 underlying cardiovascular anomalies that lead to left vennicular hypenrophy in rhe face of an inability to meet the increased oxygen demands of the myocardium (e.g., aortic stenosis and coarctation of the aona). Endocardial thickening observed m the photograph is nola feature of the other choices. ***Diagnosis: Endocardial fibroelastosis
8 A 29-year-olcl woman complains of a 3-momh history of nervousness and weakness. $he feels hot and sweaty and has experienced a 9-kg (20-lb) weight los_<; over the past 2 months, despile increased caloric intake. She frequently finds her heart racing and can feel it pounding in her chesl. Physical examination reveals an enlarged thyroid , warm hands , and bulging eyes. This patient is at risk of developing which of the following cardiovascular complications? ***(A) Cardiac tamponade ***(B) Cor pulmonale ***(C) High-output heart failure ***(D) Pericardia! effusion ***(E) Ventricular aneurysm
8 The answer is ( : High-output heart failure. The patient suffers from hypenhyroidism (Graves disease). This autoimmune condjtion causes decreased periph eral resistance, which in time requires increased cardiac omput. Hypen byroidism may lead to high-outpm heart failure None of the other choices are characterized by increased cardiac output. ***Diagnosis: Graves disease , hyperthyroidism
9 A 56-year-old man presems to the emergency room Virith 1 hour of chest pain. Laboratory studies show an increased leukocyte count and increased serum levels of cardiac enzymes. ECG confirms a massive transmural myocardial infarction of the left ventride. The patient dies 2 days later. Histologic examination of the left main corona1y artery at autopsy is shO\.vn in the image. Examination of injured heart muscle would be expected to show which of the following pathologic changes by Hght microscopy? ***(A) CoUagen-rich scar tissue ***(B) Extensive infiltration of myocardium with mononuclear cells ***(C) Necrosis of cardiac myocytes and infiltrates of neutrophils ***(D) No obvious changes evident by light microscopy ***(E) Proliferation of fibroblasts and capillary endothelial cells
9 The answer is (: Necrosis of cardiac myocytes and infiltrates of neutrophils. Two days after myocardial infarction, the affected hean muscle will show myofiber necrosis, edema, and focal hemorrhage Polymorphonuclear leukocytes accumulate at the border of the zone of infarction and infiltrate the necrotic tissue. Lack of changes evident by light microscopy (choice D) is expected during the first 24 hours but not at 2 days. The other changes (choices A, B, and E) occur after longer periods of Lime. ***Diagnosis: Acute myocardial infarction
10 A ++-year-old man presents to the emergency room "vith acute chest pain_ The ECG is normaL Analysis of which pair of serum markers given below would be most helpful in excluding a diagnosis of acme myocardial infarction in this patiem? ***(A) Cardiac troponin-1 and myoglobin ***(B) CK-BB and myoglobin ***(C) CK-MB and cardiac troponin-l ***(D) CK-MM and lactate dehydrogenase (LDH)-1 ***(E) Myoglobin and CK-BB
10 The answer is C: CK-MB and cardiac troponin·l. Laboratory evaluation of myocardial infarction is based on measuring blood levels of intracellular macromolecules that leak out of necrotic myocardial cells. These proteins include myoglobin, cardiac troponin-T and -1, creatine kinase (CK), and LDH. The preferred biomarkers for myocardial damage are cardiac-specific proteins, panicularly troponin-1 and troponin- T. The MB isofom1 of creatine kinase (CK-MB; ch oice C) is also cardiac specific. CK-BB (choice B) is elevated ptimarlly in patients with infarction of brain tissue. CK-MM (choice D) and myoglobin are usually elevated following necrosis of skeletal muscle. ***Diagnosis: Ischemic hean disease
11 A 35-year-old man presents with acute chest pain and nausea_ ECG and laboratory studies confirm the diagnosi5 of myocardial infarction_ The patient expires .2 days later_ A phowmicrograph of hi5 left main coronary anery is shown in Lhe image. This patient most likely suffered from which of the following hereditary diseases? ***(A) Ehlers-Danlos syndrome ***(B) Familial hypercholesterolemia ***(C) Kawasaki disease ***(D) Marfan syndrome ***(E) Systemic hypertension
11 The answer is 8: Familial hypercholesterolemia. Patients with familial hypercholesterolemia have a defective LDL receptor, whkh inhibits cholesterol uptake by the liver. They develop complications of atheroscl erosis ar an early age. Cholesterol and serum Lipoproteins are deposited in the atheroma, where they are continuously endocytosed by macrophages (lipidladen foam cells) The mamre atheroma is highly thrombogenic Although systemic hypertension (choice E) may accelerate atherosclerosis, it is nol a common cause of early myocardial infarction. The other choices (choices A, C, and D) do not accelerate the development of atherosclerosis. ***Diagnosis: Myocardial infarction, familial h)rpercholesterolemia
12 A 60-year-old man with a history of emphysema remrns home from the hospital after su ffering a myocardial infarction involving the apex of the left vetmicle. $b{ months later, an echocardiogram reveals the development of a ventticular bulge that does not contract during syswle. The padem subsequently suffers a massive stroke and suddenly e>.'Pires. Which of the following is an expected pathologic finding ar autopsy"? ***(A) Calcific aortic stenosis ***(B) Dilated cardiomyopathy ***(C) Milral valve prolapse ***(D) Mural thrombus ***(E) Ventricular rupture
12The answer is D: Mural thrombus. Mural thrombi Conn on the endocardium, over Lhe affected myocardium, early after infarction and are found in half of all patients who die after myocardial infarction. Mural thrombi also form over ventricular an eurysms, as in this case, which are found at the site of a h ealed, transmural myocardial infarct. Such thrombi are a source of systemic emboli. Mural thrombi may fonn in cases of dilated cardiomyopathy (ch oice B), but there is no clinical evidence for Lhat disease in th is vignette. ***Diagnosis: Mural lhrombus, venmcular aneurysm
13 A 50-year-old man with familial hyperlipidemia undergoes resection of an abdominal aneurysm. Signs of congcslive hean failu~ develop shortly after surgery. Despite treatment, the patient becomes hypotensive and expires 2 days Later. Autopsy reveals marked narrowing of coronary ane1ies, v.Tithomthrombosis. Multiple foci of necrosis a rc found circumferemially around the inner walls of borh ventricles. Which of the following is the most likely cause of congestive heart failure in this patient? ***(A) Calcific aortic stenosis ***(B) Dilated cardiomyopathy ***(C) Rupmre of papiUary muscle ***(D) Subendocardial myocardial infarction ***(E) Transmural myocardial infarction
13 The answer is D: Subendocardial myocardial infarction. Subendocardial circumferential infarcts generally occur as a consequence of hypoperfusion of the heart secondaty to poor coronaty blood flow, often in the setting of hypotension. Coronary artery narrowing is common, but total occlusion is usualiy not seen. $ubendocarcUal myocardial infarcts aiTectthe inner one third ro one half of the ventricle. They may arise within the terrirory of one of the major coronary arteries or may involve the subendocardial distribution of all coronary aneties. Transmural myocardial infarction (choice E) generally follows occlusion of a major coronary anery. ***Diagnosis: Subendocardial myocardial infarction
14 A 68-year-old obese woman (BMI = 32 kglm1 ) presents witl1 substem al chest pain and a histmy of recurrent angina pecwris and imermittent claudication. The following day, she develops a fever of 38°C (101 °f). Results of laboratmy studies include an elevated WBC count (13,000/J.t L), CK-MB of 6 .6nglmL, and troponin-1 of 2.5ngtml. ECG confirms a myocardial infarction of the left ventricular walL \ .Vhich of the following mechanisms is most likely responsible for the m>'ocardial infarction in this palicnt? ***(A) Coromuy artery tllrombosis ***(B) Corona1y artery vasospasm ***(C) Decreased collateral blood fiow ***(D) Deep venous thrombosis ***(E) Paradox'ical embolism
14 The answer is A; Coronary artery thrombosis. Coronary artery thrombosis is the most common cause of acute myocardial infarction and is often secondary to rupture of an atherosclerotic plaque. Coronary artery vasospasm (choice B) would be unlikely in this clinical setting. ***Diagnosis: Myocardial infarction
15 Two months later, the patient described in Question 14 expeliences several days of severe, sharp, re trosternal chesL pain radiating to Lhe neck and shoulders. The pain is worse when she is in the supine position and less imense when she is sitdng upright and leaning fon.vard. Which of the following is the most likely cause of the patients symptoms? ***(A) Congestive hean failure ***(B) Dressler syndrome ***(C) Left vennicular aneurysm ***(D) Mural thrombi ***(E) Ruptured papillary muscle
15 The answer is 8: Dressler syndrome. Postmyocardial infarction syndrome (Dressler syndrome) refers to a delayed form of pericarditis that develops 2 to 10 weeks after myocardial infarction. The pain associated with pericarditis may be confused with that resulting from postinfarction angina or recurrem infarction. The other choices would nm present whh a prolonged history of chest pain or the clinical fearures seen in this case. ***Diagnosis: Dressler syndrome
16 A 65-year-old man with a 2-year history of angina pecwris is admiued w the h ospital with excmciating substernal chest pain that is not reli.eved by rest or medication. Physical examination shows diaphoresis and dyspnea. Results of laborawry studjes include Vv'BC of 13,000/jlL, CK-MB of 6.8nglmL, and troponin-l of 3.0 nglmL. An ECG shows ST segment elevation. The patient expires 1 hour after admjssion. At auwpsy, the hean is found to be enlarged bm otherwise anatomically normal. Which of the following is the most likely cause of death? ***(A) Cardiac tamponade ***(B) Postmyocardial infarction syndrome ***(C) Ruptured myocardial infarct ***(D) Septal perforation ***(E) Ventricular fib1illation
16 The answer is E: Ventricular fibrillation. Arrhythmias account for half of all deaths within the first 2.4 hours after an acute myocardial infarction. Acute infarction is often associated \vith pre rna Lure ventricular beats, vemricular tachycardia, com plele heart block, and venLricular fib tillation. The cause of arrhyth· mias is multifacrorial but acute ischemia may promote conduction dismrbances and myocardial i rritabilil y. The other choices occur after longer time pe1iods. ***Diagnosis: Myocardial infarction
17 After suffering an acute myocardial infarction , a 54-year-old man presents to the emergency room 3 ·weeks later, complaining of sharp pain on the left side of his chest. On physical examination, the patient is apprehensive and sweating His blood pressure is 80/40mmHg and the pulse rate is 100 per minme. The patient dies within minutes. The ventricular wall at autopsy is shovvn in Lhe image. What is Lhe most Hkely cause of death? ***(A) Cardiac tamponade ***(B) Dissecting aortic aneurysm (C} Pulmonary edema ***(D) Pulmonary thromboembolism ***(E) Septic shock
17 The answer is A: Cardiac tamponade. The gross specimen shows a ruprured myocardial wa1l, which causes cardiac tamponade. This catastrophe reflects the accumulation of pericardia] nuid (blood in this case), which restricts the mmion of the hean. Pulsus paradoxus (>lOmmHg fall in anerial blood pressure with inspiration) is commonly observed in such cases. Although aortic dissection (choice B) can break through to the pericardium. it does not cause rupture of the myocardium. The other choices do not cause cardiac tamponade. ***Diagnosis: Hemopericardium
18 A 48-year-old man complains of chest pain upon exertion. He had been well umil 4 months previously. when he first developed a chest discomfort while jogging. His symptoms have progressed to the point that he now develops chest pain after climbing a single flight of stairs. He has a history of diabetes controlled by diet and of 25 pack-years of cigarette smokin g. His father and maternal grandfather both died of hea1t disease before the age of 60. On the 5th hospital day, the patient develops chest pain dming periods of mild activity, which is minimally responsive to sublingual nitroglycerin. Results of laboratory studies include WBC of 8,100/J.ll, CK-MB of 4.5 nglmL, and troponin-1 of 0.5nglmL Which of the following is the most likely diagnosis? ***(A) Acute myocardial infarction ***(B) Cardiac arrhythmia (C} Dressler syndrome ***(D) Pulmonary thromboembolism ***(E) Unstable angina
18 The answer is E: Unstable angina. Unstable angina refers to a pattern of pain that occurs progressively and wid1 increasing frequency. It often occurs at rest and tends to be of more prolonged duration. Unstable angina is often a prodrome of myocardial infarction. Acme myocardial infarction (choice A) is ruled out 111 this case because blood ana1vsis does not show ' evidence of infarction. ***Diagnosis: Ischemic heart disease
19 On the morning of the sixth day. the patient described in Quesdon 18 experiences acute , substernal chest pain and nausea. He is rreated with plasminogen activator and O),.'ygen but expires several hours later. A cross section of the heart at autopsy is shown in the image. This infarct was most likely caused by thrombotic occlusion of which of the follo\ving coronary arteries? ***(A) Left anterior descending ***(B) Left meum ncx ***(C) Main right ***(D) Postenor descendmg ***(E) Sinoamal nodal
19 The answer is A: Left anterior descending. The left amenor descending coronary ane1y supplies the anterior and part of the lateral portions of the left ventricle. Acme blockage of this ane1y produces an infarct of the apical. ame1ior, and ameroseptal walls of the left ventricle. Sinoatrial (SA) nodal anery (choice E) primarily supplies the right atrium and the SA node. The distribudon of choices C and D largely encompass the poste1ior wall of the heart. ***Diagnosis: Myocardial infarction
ZO A 69-year-old woman presents w1th cruslung substernal chest pain and nausea. She ts treated w1th plasminogen acth•awr, o.>.:ygen, and morphme sulfate. Laborarmy studies show a WBC count of 13 ,000/J.l l , CK-MB of 6.6nglml, and troponin- 1 of 2.5 n?fmL. An ECG shows ST segment elevation. Cardiac catheterizauon reveals diffuse atherosclerosis of all major coronary anencs. The panent subsequently becomes acutely hypotensive and undergoes cardiac arrest. The surface of the hean aL autopsy ts shown m the image. At what point in dme following acuLc myocardial infarction did this pathologic condition most likely occur? ***(A) 0 lO 6 hours ***(B) 6 w 12 hours ***(C) l2 to 24 hours ***(D) 1 to 4 days ***(E) 6 momhs to 1 year
20 The answer is D: 1 to 4 days. The autopsy reveals hemopelicarclium {see photograph). Myocardial rupture and hemorrhage imo the pericardia! sac may occur at almost any time during the first 3 weeks following infarction, but is most commonly seen between the 1st and 4th days. During this critical interval, the infarcted wall is weak, being composed of soft necrotic tissue. The extracellular matrLx within the infarct is degraded by prOleases released by inflammatory cells. Choices A, B, and C are incorrect because the strength of the ventricular wall is maintained during the first 24 hours. Choice E is incorrect because the scar tissue that has formed by this nme provides mechanical stability w the site of injury. ***Diagnosis: Hemopericardium, cardiac tamponade
21 A 66-year-old woman collapses while shopping and expires suddenly of cardiac arrest. Her past medical history is signifi· cant for long-standing type 2 diabetes mellitus. Her relatives note that she had complained of chest heaviness and shor tness of breath for the past 2 weeks. Sterile fibrinous peri· carditis and pericardia! effusion are observed at autopsy. ·wh at additional finding would be expected during autops)' of this patient? ***(A) Endocardial fibroelastosis ***(B) Marantic endocarcUtis ***(C) Mitral valve prolapse ***(D) Myocardial infarct ***(E) Right ventlicular hypertrophy
21 The answer is D: Myocardial infarct. Fibrinous pericarditis may develop 2 to 10 weeks after a nansmural myocardial infarction. Patients with long-standing diabetes mellitus are particularly susceptible to coronary atherosclerosis and myocardial infarction. One fourd1 w one half of all nonfatal myocardial infarctions arc asympLOmatic. ln such patients, sudden dead1 usually reGects a cardiac arrhydunia. Right ventricular hypertrophy (choice E) may be encountered but is not related w the development of pericarditis. ***Diagnosis: Myocardial infarction
22 A 68-year-old woman with a history of diabetes mellitus expires suddenly of cardiac arrest The padent suffered a massive anterior myocardial infarction l year earlier. The heart at autopsy is shown in the image. 'vVhich of the following is the most likely complication of this condition7 ***(A) Aonic stenosis ***(B) Coronary artery aneurysm ***(C) Hypertrophic cardiomyopathy ***(D) Pulmonary embolism ***(E) Stroke
22 The answer is E: Stroke. As myocardial infarcts heal, newly deposited collagenous matrix is susceptible to stretching and may become dilated. Mural thrombosis in the aneurysm is common and may lead LO the release of emboli to the brain (stroke). Pulmonary embolism (choice D) involves the venous system and the right-sided circulation of the hean. ***Diagnosis: Ventlicular aneurysm, mural thrombus
23 A 60-year-old woman with a 30-pack-year history of smokJng and a 10-year history of emphysema expires of congestive heart failure. There is no evidence of coronary artery disease or valvular heart disease. The heart at autopsy is shown in the image. Which of the following is the most likely cause of right vcnuicular hypertrophy? ***(A) Endocardial fibroelastosis ***(B) Essential hypertension ***(C) Pulmonary hyperten.':;ion ***(D) Pulmonary sLenosis ***(E) Systemic hypertension
23 The answer is C: Pulmonary hypertension. Cor pulmonale is defined as right ventricular hypemophy and dilation secondary to pulmonary hypenension. The most common cause of cor pulmonale is chronic obstructive pulmonary disease usually as a result of smoking. Pulmonary stenosis (choice D) is a rare cause of cor puJmonale. ***Diagnosis: Cor pulmonale, pulmonary hypertension
24 A 72-year-old man presenl5 with difficulty breathing He says that he becomes shan of breath at night unless he uses three pillows to prop himself up. Measuremems of VItal signs reveal normal temperature, mild tachypnea, and a blood pressure of 180/100 mm Hg Physical e..xamination discloses obesity, bilateral 2+ pitting leg edema, hepatosplenomegaly, and rales at the bases of both lungs. An X-ray film of the chest shows mild enlargement of the hean and a mild pleural effusion. Echocardiography reveals left ventricular hypenrophy withom valvular hean defects. Which of the following is the most likely diagnosis? ***(A) Acute cor pulmonale ***(B) Consnktive pericarditis ***(C) Dilated cardiomyopathy ***(D) Hypertensive heart disease ***(E) R£nal failure
24 The answer is D: Hypertensive heart disease. Systemic hypertension is one of the most prevalen t and serious causes of corona1y artery and myocardial disease in the United States. lt is defined as a persistem increase in systemic blood pressure Lo levels above 140mm Hg systolic or 90 mm Hg diastolic, or both. Chronic hypertension causes compensatory hypertrophy of the left venttide as a result of the increased workload imposed on the heart muscle. The left ventricular wall and interventricular septum become uniformly thickened. Congestive heart failure is the most common cause of death in untreated hypertensive patients. lnn·acerebral hemorrhage is also a frequent fatal complication. ln addition, death may result from coronary atherosclerosis and myocardial infarction, dissecdng aneurysm of the aorta, or ruptured beny anemysm of the cerebral circulation. Renal failure may supervene \Vhen nephrosclerosis induced by hypertension becomes severe. Although dilated cardiomyopathy (choice C) may present with similar clinical findings, it does not feamre hypertension. The other choices do not exhibit left ventricular hypertrophy ***Diagnosis: Hypertensive hean disease
25 A 62-year-old man with a lustory or hypertension is brought to the emergency room with severe left chest and back pain. His blood pressure is 80/50 nm1 Hg. Physical examination shows pallo r, diaphoresis, and a murmur of aortic regurgitation. An ECG does not show myocardial infarction. An X-ray fih11 of the chest reveals mediastinal widening. Which of the following is the most likely diagnosis' ***(A) Bacterial endocarditis ***(B) Dissecting aneurysm ***(C) PeJicarditis ***(D) Pulmonary thromboembolism ***(E) Ruptured myocardial wall
25 The answer is 8: Dissecting aneurysm. Aortic dissection re n.ects hemorrhage between and along the laminar planes of the media, \vith the fonnalion of a blood-filled channel withln the aortic wall. lf it begins in the ascending aorta, it may extend backward toward the aortic valve or distally to involve the thoracic and abdominal aona. More than 90% of dissections occur in men between the ages of 40 and ()0 with amecedent hypertension. The second major group of patients, usually younger, has a systemic or localized abnonnality o[ connective tissue that affects the aon:a (e.g. , Marfan syndrome). Although bacterial endocarditis (choice A) can result in aortic regurgitation, it does not lead to acme chest pain. The other choices are not associated \Vith aortic regurgitation ***Diagnosis: Aortic dissection
26 A 30-year-old woman presents with a heart murmur. There is a history of recunent episodes of arthtitis, skin rash, and glomerulonephtili. s. Blood cultures are negative. Laboratory tesl5 for antinuclear antibodies (ANA) and anti-double-stranded DNA are positive. Which of the following is the most likely cause of heart munnur jn this patiem? ***(A) Libman·Sacks endocarditis ***(B) Mitral valve prolapse ***(C) Myocardial infarct ***(D) Mitral valve prolapse ***(E) RJ1eumatic fever
26 The answer is A: Libman-Sacks endocarditis. In patients with systemic lupus erythematosLLS , endocarditis is the most suiking cardtac lesion, termed Libman-Sacks endocardins. Nonbacterial vegetations are seen on the undersurface of the mitral valve close to the origin of the leaGets from the valve ring (Ubman-Sacks endocarditis). There is fib1inoid necrosis of small vessels with focal degeneration of imerstiLial tissue. Rheumatic (ever (choice E) is not commonly associated with AN As seen in this case. ***Diagnosis: Systemic lupus erythematosis
27 A 50-year-old man wi.th adenocarcinoma of the pancreas is brought to the emergency room in a comatose state. A CT scan of the brain is consistent wi.th a recent infarct in the left temporal lobe. Blood cultures are negative. The patiem n ever regains consciousness and expires 2 days later. The heart at autopsy is shown in the image. Which of the follmving is the most likely underlying cause of s troke in this patient? ***(A) Calcine aonic stenosis ***(B) Carcinoid heart disease ***(C) Cardiac metastases ***(D) Nonbacterial thrombotic endocarditis ***(E) Subacute bacterial endocarditis