Rubin's Gen Path Flashcards
Review
QUESTION
ANSWER AND RATIONALE
- Bone marrow cells from an organ donor are cultured in vitro at 37°C in the presence of recombinant erythropoietin. A photomicrograph of a typical “burst-forming unit” is shown in the image. This colony, committed to the erythrocyte pathway of differentiation, represents an example of which of the following physiologic adaptations to transmembrane signaling?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
C: Hyperplasia. Hyperplasia is defined as an increase in the number of cells in an organ or tissue. Like hypertrophy (choice D), it is often a response to trophic signals or increased functional demand and is commonly a normal process. Erythroid hyperplasia is typically seen in people living at high altitude. Low oxygen tension evokes the production of erythropoietin, which promotes the survival and proliferation of erythroid precursors in the bone marrow. The cellular and molecular mechanisms that are responsible for hyperplasia clearly relate to the control of cell proliferation (i.e., cell cycle). None of the other choices describe increased numbers of cells. Diagnosis: Erythropoiesis, hyperplasia
- A 50-year-old chronic alcoholic presents to the emergency room with 12 hours of severe abdominal pain. The pain radiates to the back and is associated with an urge to vomit. Physical examination discloses exquisite abdominal tenderness. Laboratory studies show elevated serum amylase. Which of the following morphologic changes would be expected in the peripancreatic tissue of this patient?
a. Coagulative necrosis
b. Caseous necrosis
c. Fat necrosis
d. Fibrinoid necrosis
e. Liquefactive necrosis
C: Fat necrosis. Saponification of fat derived 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 to form soaps, which is a process known as saponification. Entry of calcium ions into the injured tissue reduces the level of calcium in blood. Hypocalcemia is, therefore, a typical finding in patients who had a recent bout of acute pancreatitis. Patients with acute pancreatitis experience sudden-onset abdominal pain,
- A 68-year-old man with a history of gastroesophageal reflux disease suffers a massive stroke and expires. The esophagus at autopsy is shown in the image. Histologic examination of the abnormal tissue shows intestine-like epithelium composed of goblet cells and surface cells similar to those of incompletely intestinalized gastric mucosa. There is no evidence of nuclear atypia. Which of the following terms best describes this morphologic response to persistent injury in the esophagus of this patient?
a. Atypical hyperplasia
b. Complex hyperplasia
c. Glandular metaplasia
d. Simple hyperplasia
e. Squamous metaplasia
C: Glandular metaplasia. The major adaptive responses of cells to sublethal injury are atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, and intracellular storage. Metaplasia is defined as the conversion of one differentiated cell pathway to another. In this case, the esophageal squamous epithelium is replaced by columnar epithelium as a result of chronic gastroesophageal reflux. The lesion is characterized histologically by intestine-like epithelium composed of goblet cells and cells similar to those of incompletely intestinalized gastric mucosa. Squamous metaplasia (choice E) occurs in the 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
- A CT scan of a 43-year-old woman with a parathyroid adenoma and hyperparathyroidism reveals extensive calcium deposits in the lungs and kidney parenchyma. These radiologic findings are best explained by which of the following mechanisms of disease?
a. Arteriosclerosis
b. Dystrophic calcification
c. Granulomatous inflammation
d. Metastatic calcification
e. Tumor embolism
D: Metastatic calcification. Metastatic calcification is associated with an increased serum calcium concentration (hypercalcemia). Almost any disorder that increases serum calcium levels can lead to calcification in the alveolar septa
of the lung, renal tubules, and blood vessels. The patient in this case had a parathyroid adenoma that produced large quantities of parathyroid hormone. Other examples of metastatic calcification include multiple opacities in the cornea of a child given large amounts of vitamin D and partially calcified alveolar septa in the lungs of a patient with breast cancer metastatic to bone. Breast cancer metastases to bone are often osteolytic and, therefore, accompanied by hypercalcemia. Dystrophic calcification (choice B) has its origin in direct cell injury. Arteriosclerosis (choice A) is an example of dystrophic calcification.
Diagnosis: Hyperparathyroidism, metastatic calcification
- A 75-year-old woman with Alzheimer disease dies of congestive heart failure. The brain at autopsy is shown in the image. This patient’s brain exemplifies which of the following responses to chronic injury?
a. Anaplasia
b. Atrophy
c. Dysplasia
d. Hyperplasia
e. Hypertrophy
B: Atrophy. Clinically, atrophy is recognized as diminution in the size or function of an organ. It is often seen in areas of vascular insufficiency or chronic inflammation and may result from disuse. Atrophy may be thought of as an adaptive response to stress, in which the cell shuts down its differentiated functions. Reduction in the size of an organ may reflect reversible cell atrophy or may be caused by irreversible loss of cells. For example, atrophy of the brain in this patient with Alzheimer disease is secondary to extensive cell death, and the size of the organ cannot be restored. This patient’s brain shows marked atrophy of the frontal lobe. The gyri is thinned, and the sulci are widened. Anaplasia (choice A) represents lack of differentiated features in a neoplasm.
Diagnosis: Alzheimer disease, atrophy
- A 68-year-old woman with a history of heavy smoking and repeated bouts of pneumonia presents with a 2-week history of fever and productive cough. A chest X-ray reveals a right lower lobe infiltrates. 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 pattern of cellular maturation
b. Increased numbers of otherwise normal cells c. Invasiveness through the basement
membrane
d. Transformation of one differentiated cell type to another
e. Ulceration and necrosis of epithelial cells
A: Abnormal pattern of cellular 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 that this regular appearance is disturbed by (1) variations in the size and shape of the cells; (2) enlargement, irregularity, and hyperchromatism of the nuclei; and (3) disorderly arrangement of the cells within the epithelium. Dysplasia of the bronchial epithelium is a reaction of respiratory epithelium to carcinogens in tobacco smoke.It is potentially reversible if the patient stops smoking but is considered preneoplastic and may progress to carcinoma. Choices B, D, and E are not preneoplastic changes. Invasiveness (choice C) connotes malignant behavior.
Diagnosis: Pneumonia, dysplasia
- 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 left ventricle measures 2.8 cm on the cross section (shown in the image). This adaptation to chronic injury was mediated primarily by changes in the intracellular concentration of which of the following components?
a. DNA
b. Glycogen
c. Lipid
d. mRNA
e. Water
D: mRNA. Hypertrophic cardiac myocytes have more cytoplasm and larger nuclei than normal cells. Although the elucidation of the cellular 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. Hypertrophy results from transcriptional regulation. Aneuploidy (choice A) is not a feature of myofiber hypertrophy. Water influx (choice E), which is typical of hydropic swelling in acute injury, is not a common feature of hypertrophy.
Diagnosis: Hypertrophic heart disease, hypertrophy
- A 24-year-old woman contracts toxoplasmosis during her pregnancy and delivers a neonate at 37 weeks of gestation with a severe malformation of the central nervous system. MRI studies of the neonate reveal porencephaly and hydrocephalus. An X-ray film of the head shows irregular densities in the basal ganglia. These X-ray findings are best explained by which of the following mechanisms of disease?
a. Amniotic fluid embolism
b. Dystrophic calcification
c. Granulomatous inflammation
d. Metastatic calcification
e. Organ immaturity
B: Dystrophic calcification. Dystrophic calcification reflects underlying cell injury. Serum levels of calcium are normal, and the calcium deposits are located in previously damaged tissue. Intrauterine 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 intrauterine infections. Metastatic calcification (choice D) reflects an underlying disorder in calcium metabolism.
Diagnosis: Dystrophic calcification
- A 30-year-old man with an AIDS-dementia complex develops acute pneumonia and dies of respiratory insufficiency. At autopsy, many central nervous system neurons display hydropic degeneration. This manifestation of sublethal neuronal injury was most likely mediated by impairment of which of the following cellular processes?
a. DNA synthesis
b. Lipid peroxidation
c. Mitotic spindle assembly
d. Plasma membrane sodium transport
e. Ribosome biosynthesis
D: Plasma membrane sodium transport. Hydropic swelling reflects acute, reversible (sublethal) cell injury. It results from 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 plasma membrane sodium pump, and (3) the supply of ATP. Injurious agents may interfere with these membrane-regulated processes. Accumulation of sodium in the cell leads to an increase in water content to maintain isosmotic conditions, and the cell then swells. Lipid peroxidation (choice B) is often a feature of irreversible cell injury. The other choices are unrelated to volume control.
Diagnosis: Acute reversible injury
- A 62-year-old man is brought to the emergency room in a disoriented state. Physical examination reveals jaundice, splenomegaly, and ascites. Serum levels of ALT, AST, alkaline phosphatase, and bilirubin 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 proteins?
a. α1-Antitrypsin
b. β-Amyloid (Aβ)
c. Intermediate filaments
d. Prion protein (PrP)
e. α-Synuclein
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 terminology includes hyaline arteriolosclerosis, alcoholic hyaline in the liver, hyaline membranes in the lung, and hyaline droplets in various cells. Alcoholic (Mal lory) hyaline is composed of cytoskeleton intermediate filaments (cytokeratins), whereas pulmonary hyaline membranes consist of plasma proteins deposited in alveoli. Structurally abnormal α1-antitrypsin molecules (choice A) accumulate in
substantia nigra of patients with Parkinson disease. Diagnosis: Alcoholic liver disease
- A 65-year-old man suffers a heart attack and expires. Examination of the lungs at autopsy reveals numerous pigmented nodules scattered throughout the parenchyma (shown in the image). What is the appropriate diagnosis?
a. Anthracosis
b. Asbestosis
c. Hemosiderosis
d. Sarcoidosis
e. Silicosis
A: Anthracosis. Anthracosis refers to the storage of carbon particles in the lung and regional lymph nodes. These particles accumulate in alveolar macrophages and are also transported to hilar and mediastinal lymph nodes, where the indigestible material is stored indefinitely within tissue macrophages. Although the gross appearance of the lungs of persons with anthracosis may be alarming, the condition is innocuous. Workers who mine hard coal (anthracite) develop pulmonary fibrosis, owing to the presence of toxic/fi brogenic dusts such as silica. This type of pneumoconiosis is more prop
erly classified as anthracosilicosis. Hemosiderosis (choice C) represents intracellular storage of iron (hemosiderin). The other choices are not associated with dark pigmentation in the lung.
Diagnosis: Pneumoconiosis, anthracosis
- A 32-year-old woman with poorly controlled diabetes mellitus delivers a healthy boy at 38 weeks of gestation. As a result of maternal hyperglycemia during pregnancy, pancreatic islets in the neonate would be expected to show which of the following morphologic responses to injury?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Metaplasia
e. Necrosis
C: Hyperplasia. Infants of diabetic mothers show a 5% to 10% incidence of major developmental 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. During fetal development, the islet cells of the pancreas have proliferative capacity and respond to increased demand for insulin by undergoing physiologic hyperplasia. Fetuses exposed to hyperglycemia in utero may develop hyperplasia of the pancreatic β cells, which may secrete insulin autonomously and cause hypoglycemia at birth. Metaplasia (choice D) is defined as the conversion of one differentiated cell pathway to another.
Diagnosis: Diabetes mellitus
- A 59-year-old female alcoholic is brought to the emergency room with a fever (38.7°C/103°F) and foul-smelling breath. The patient subsequently develops acute broncho pneumonia and dies of respiratory insufficiency. A pulmonary abscess is identified at autopsy (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. Liquefactive necrosis
E: Liquefactive necrosis. When the rate of dissolution of the necrotic cells is faster than the rate of repair, the resulting morphologic appearance is termed liquefactive necrosis. The polymorphonuclear leukocytes of the acute inflammatory reaction are endowed with potent hydrolases that are capable of digesting dead cells. A sharply localized collection of these acute inflammatory cells in response to a bacterial infection produces rapid death and dissolution of tissue. The result 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 (choice D) is seen in patients with necrotizing vasculitis.
Diagnosis: Pulmonary abscess, liquefactive necrosis
14. A 20-year-old man from China is evaluated for persistent cough, night sweats, low-grade fever, and general malaise. A chest X-ray reveals findings “consistent with a Ghon complex.” Sputum cultures grow acid-fast bacilli. Examination of hilar lymph nodes in this patient would most likely demonstrate which of the following pathologic changes? (A) Caseous necrosis (B) Coagulative necrosis (C) Fat necrosis (D) Fibrinoid necrosis (E) Liquefactive necrosis
A: Caseous necrosis. Caseous necrosis is a characteristic of primary tuberculosis, in which the necrotic cells fail to retain their cellular outlines. They do not disappear by lysis, as in liquefactive necrosis (choice E), but persist indefi - nitely as amorphous, coarsely granular, eosinophilic debris. Grossly, this debris resembles clumpy cheese, hence the name caseous necrosis. Primary tuberculosis is often asymptomatic or presents with nonspecific symptoms, such as low-grade fever, loss of appetite, and occasional spells of coughing. The Ghon complex includes parenchymal consolidation and ipsi lateral enlargement of hilar lymph nodes and is often accompanied by a pleural effusion. Fibrinoid necrosis (choice D) is seen in patients with necrotizing vasculitis.
Diagnosis: Tuberculosis, Mycobacterium tuberculosis
- 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 with arrows. When compared to cells from the deeper intermediate layer (top), the nuclei of these superficial cells
exhibit which of the following cytologic features?
a. Karyolysis
b. Karyorrhexis
c. Pyknosis
d. Segmentation
e. Viral inclusion bodies
C: Pyknosis. Coagulative necrosis refers to light microscopic alterations in dying cells. When stained with the usual combination of hematoxylin and eosin, the cytoplasm of a necrotic cell is eosinophilic. The nucleus displays an initial clumping 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.
- A 30-year-old woman suffers a tonic-clonic seizure and presents with delirium and hydrophobia. The patient states that she was bitten on the hand by a bat about 1 month ago. The patient subsequently dies of respiratory failure. Viral particles are found throughout the brainstem and cerebellum at autopsy. In addition to direct viral cytotoxicity, the necrosis of virally infected neurons in this patient was mediated primarily 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 ischemia
B: Humoral and cellular immunity. Both humoral and cellular arms of the immune system protect against the harmful 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 arms of the immune system eliminate virus-infected cells by either inducing apoptosis or directing complement-mediated cytolysis. In this patient, the rabies virus entered a peripheral nerve and was transported by retrograde axoplasmic flow to the spinal cord and brain. The inflammation is centered in the brainstem and spills into the cerebellum and hypothalamus. The other choices are seen in acute inflammation, but they do not represent antigen-specific responses to viral infections.
Diagnosis: Rabies
- A 52-year-old woman loses her right kidney following an automobile accident. A CT scan of the abdomen 2 years later shows marked enlargement of the left kidney. The renal enlargement is an example of which of the following adaptations?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
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 hypertrophies to accommodate increased demand. The molecular basis of hypertrophy reflects increased expression of growth-promoting genes (protooncogenes) such as myc, fos, and ras. Hyperplasia (choice C) of renal tubular cells may occur, but enlargement of the kidney in this patient is best referred to as hypertrophy (i.e., increased organ size and function).
Diagnosis: Hypertrophy
- An 82-year-old man has profound bleeding from a peptic ulcer and dies of hypovolemic shock. The liver at autopsy displays centrilobular necrosis. Compared to viable hepatocytes, the necrotic cells contain higher intracellular concentrations of which of the following?
a. Calcium
b. Cobalt
c. Copper
d. Iron
e. Selenium
A: Calcium. Coagulative necrosis is characterized by a massive influx of calcium into the cell. Under normal circumstances, the plasma membrane maintains a steep gradient of calcium ions, whose concentration in interstitial fluids is 10,000 times higher than that inside the cell. Irreversible cell injury damages the plasma membrane, which then fails to maintain this gradient, allowing the influx of calcium into the cell. The other choices would most likely be released upon cell death.
Diagnosis: Coagulative necrosis
- A 28-year-old woman is pinned by falling debris during a hurricane. An X-ray film of the leg reveals a compound fracture of the right tibia. The leg is immobilized in a cast for 6 weeks. When the cast is removed, the patient notices that her right leg is weak and visibly smaller in circumference than the left leg. Which of the following terms best describes this change in the patient’s leg muscle?
a. Atrophy
b. Hyperplasia
c. Metaplasia
d. Ischemic necrosis
e. Irreversible cell injury
A: Atrophy. The most common form of atrophy follows reduced functional demand. For example, after immobilization of a limb in a cast as treatment for a bone fracture, muscle cells atrophy, and muscular strength is reduced. The expression of differentiation genes is repressed. On restoration of normal conditions, atrophic cells are fully capable of resuming their differentiated functions; size increases to normal, and specialized functions, such as protein synthesis or contractile force, return to their original levels. Ischemic necrosis (choice D) is typically a complication of vascular insufficiency. Irreversible injury to skeletal muscle (choice E) would be an unlikely complication of bone fracture. Diagnosis: Atrophy, bone fracture
- 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 confirm a diagnosis of acute myocardial infarction. The patient subsequently develops an arrhythmia and expires. A cross section of the left ventricle at autopsy is shown in the image. Histologic examination of the affected heart muscle
would demonstrate which of the following morphologic changes?
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 heart decreases the delivery of O2 and glucose. Lack of O2 impairs mitochondrial 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 cell dies. The morphologic appearance of the necrotic cell has traditionally been termed coagulative necrosis because of its similarity to the coagulation of proteins that occurs upon heating.
Diagnosis: Myocardial infarction, coagulative necrosis
- Which of the following histologic features would provide definitive evidence of necrosis in the myocardium of the patient described in Question 20?
a. Disaggregation of polyribosomes
b. Increased intracellular volume
c. Influx of lymphocytes
d. Mitochondrial swelling and calcification
e. Nuclear fragmentation
E: Nuclear fragmentation. Nuclear fragmentation (karyorrhexis and karyolysis) is a hallmark of coagulative necrosis. Choices A, B, and D are incorrect because they are features of both reversibly and irreversibly injured cells. Lymphocytes (choice C) are a hallmark of chronic inflammation.
Diagnosis: Myocardial infarction
- A 90-year-old woman with mild diabetes and Alzheimer disease 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 failure
d. Diabetic ketoacidosis
e. Hereditary hemochromatosis
A: Advanced age. Substances that cannot be metabolized accumulate in cells. Examples include (1) 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 particulates (silica and carbon). Lipofuscin is a “wear and tear” pigment of aging that accumulates in organs such as the brain, heart, and liver. None of the other choices are associated with lipofuscin accumulation.
Diagnosis: Aging, lipofuscin
23 Which of the following mechanisms of disease 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
D: Peroxidation of membrane lipids. Lipofuscin is found in lysosomes and contains peroxidation products of unsaturated fatty acids. The presence of this pigment is thought to reflect continuing lipid peroxidation of cellular membranes as a result of inadequate defenses against activated oxygen radicals. None of the other mechanisms of disease leads to the
membrane lipids
(E) Progressive oxidation of bilirubin
formation and accumulation of lipofuscin granules.
Diagnosis: Lipofuscin, intracellular storage disorder
- 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 Prussian blue stain of a liver biopsy is shown in the image. What is the major intracellular iron storage protein in this patient’s hepatocytes?
a. Bilirubin
b. Haptoglobin
c. Hemoglobin
d. Hemosiderin
e. Transferrin
D: Hemosiderin. Hemosiderin is a partially denatured form of ferritin that aggregates easily and is recognized microscopically as yellow-brown 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 stored mostly in the form of hemosiderin, primarily in the liver. Hemoglobin (choice C) is the iron-containing pigment of RBCs. Bilirubin (choice A) is a product of heme catabolism that may accumulate in liver cells but does not stain with Prussian blue. Transferrin (choice E) binds serum iron.
Diagnosis: Hereditary hemochromatosis
- A 60-year-old man with chronic cystitis complains of urinary frequency and pelvic discomfort. Digital rectal examination is unremarkable. Biopsy of the bladder mucosa reveals foci of glandular epithelium and chronic inflammatory cells. No cytologic signs of atypia or malignancy are observed. Which of the following terms best describes the morphologic response to chronic injury in this patient?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
E: Metaplasia. Metaplasia of transitional epithelium to glandular epithelium is seen in patients with chronic inflammation of the bladder (cystitis glandularis). Metaplasia is considered to be a protective mechanism, but it is not necessarily a harmless process. For example, squamous metaplasia in a bronchus may protect against injury produced by tobacco smoke, but it also impairs the production of mucus and ciliary clearance of debris. Furthermore, neoplastic transformation may occur in metaplastic epithelium. Lack of cytologic evidence for atypia and neoplasia rules out dysplasia (choice B). Diagnosis: Chronic cystitis, metaplasia
- A 60-year-old man is rushed to the hospital with acute liver failure. He undergoes successful orthotopic liver transplantation; however, the transplanted liver does not produce much bile for the first 3 days. Poor graft function in this patient is thought to be the result of
“reperfusion injury.” Which of the following substances was the most likely cause of reperfusion injury in this patient’s transplanted liver?
a. Cationic proteins
b. Free ferric iron
c. Hydrochlorous acid
d. Lysosomal acid hydrolases
e. Reactive oxygen species
E: Reactive oxygen species. Ischemia/reperfusion (I/R) injury is a common clinical problem that arises in the setting of occlusive cardiovascular disease, infection, transplantation, shock, and many other circumstances. The genesis of I/R injury relates to the interplay between transient ischemia and the re-establishment of blood flow (reperfusion). Initially, ischemia produces a type of cellular damage that leads to the generation of free radical species. Subsequently, reperfusion provides abundant molecular oxygen (O2) to combine with free radicals to form reactive oxygen species. Oxygen radicals are formed inside cells through the xanthine oxidase pathway and released from activated neutrophils.
Diagnosis: Myocardial infarction
- A 68-year-old woman with a history of hyperlipidemia dies of cardiac arrhythmia following a massive heart attack. Per oxidation of which of the following molecules was primarily responsible for causing the loss of membrane integrity in cardiac myocytes in this patient?
a. Cholesterol
b. Glucose transport proteins
c. Glycosphingolipids
d. Phospholipids
e. Sodium-potassium ATPase
D: Phospholipids. During lipid peroxidation, hydroxyl radicals remove a hydrogen atom from the unsaturated fatty acids of membrane phospholipids. The lipid radicals so formed react with molecular oxygen and form a lipid peroxide radical. A chain reaction is initiated. Lipid peroxides are unstable and break down into smaller molecules. The destruction 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 in patients with myocardial infarction. Diagnosis: Myocardial infarction
- 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 material. This skin wound illustrates which of the following morphologic types of necrosis?
a. Caseous necrosis
b. Coagulative necrosis
c. Fat necrosis
d. Fibrinoid necrosis
e. Liquefactive necrosis
E: Liquefactive necrosis. Polymorphonuclear leukocytes (segmented neutrophils) rapidly accumulate at sites of injury. They are loaded with acid hydrolases and are capable of digesting dead cells. A localized collection of these inflammatory cells may create an abscess with central lique
faction (pus). Liquefactive 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, acute inflammation
- A 42-year-old man undergoes liver biopsy for evaluation of the grade and stage of his hepatitis C virus infection. The biopsy reveals swollen (ballooned) hepatocytes and moderate lobular inflammatory activity (shown in the image). The arrow identifies an acidophilic (Councilman) body. Which of the following cellular processes best accounts for the presence of scattered acidophilic bodies in this liver biopsy?
a. Aggregation of intermediate filament proteins
b. Apoptotic cell death
c. Coagulative necrosis
d. Collagen deposition
e. Intracellular viral inclusions
B: Apoptotic cell death. Apoptosis is a programmed pathway of cell death that is triggered by a variety of extracellular and intracellular signals. It is often a self defense mechanism, destroying cells that have been infected with pathogens or those in which genomic alterations have occurred. After staining with hematoxylin and eosin, apoptotic cells are visible under the light microscope as acidophilic (Councilman) bodies. These deeply eosinophilic structures represent membrane-bound cellular remnants that are extruded into the hepatic sinusoids. The other choices do not appear as acidophilic bodies. Diagnosis: Viral hepatitis
- Which of the following biochemical changes characterizes the formation of acidophilic bodies in the patient described in Question 29?
a. Fragmentation of DNA
b. Loss of tumor suppressor protein p53
c. Mitochondrial swelling
d. Synthesis of arachidonic acid
e. Triglyceride accumulation
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 “laddering.” This pattern of DNA degradation is characteristic of apoptotic cell death. It results from the cleavage of chromosomal DNA at nucleosomes by endonucleases. Since nucleosomes are regularly spaced along the genome, a pattern of regular bands can be seen when fragments of cellular DNA are separated by electrophoresis. The other choices are associated with cell injury, but they do not serve as distinctive markers of programmed cell death.
Diagnosis: Viral hepatitis
- A 56-year-old woman with a history of hyperlipidemia and hypertension develops progressive, right renal artery stenosis. Over time, this patient’s right kidney is likely to demonstrate which of the following morphologic adaptations to partial ischemia?
a. (A) Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Neoplasia
A: Atrophy. Interference with blood supply to tissues is known as ischemia. Total ischemia results in cell death. Partial 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 condition is often compatible with continued cell viability. Under such circumstances, cell atrophy is common. For example, it is frequently seen around the inadequately perfused margins of infarcts in the heart, brain, and kidneys. None of the other choices describe decreased organ size and function.
Diagnosis: Renal artery stenosis
32. A 5-year-old boy suffers blunt trauma to the leg in an automobile accident. Six months later, bone trabeculae have formed within the striated skeletal muscle at the site of tissue injury. This pathologic condition is an example of which of the following morphologic adaptations to injury? (A) Atrophy (B) Dysplasia (C) Metaplasia (D) Metastatic calcification (E) Dystrophic calcification
C: Metaplasia. Myositis ossifi cans is a disease characterized by formation of bony trabeculae within striated muscle. It represents a form of osseous metaplasia (i.e., replacement of one differentiated tissue with another type of normal differentiated tissue). Although dystrophic calcification (choice E) frequently occurs at sites of prior injury, it does not lead to the formation of bone trabeculae.
Diagnosis: Myositis ossifi cans, metaplasia
- A 43-year-old man presents with a scaly, erythematous lesion on the dorsal surface of his left hand. A skin biopsy reveals atypical keratinocytes filling the entire thickness of the epidermis (shown in the image). The arrows point to apoptotic bodies. Which of the following proteins plays the most important role in mediating programmed cell death in this patient’s skin cancer?
a. Catalase
b. Cytochrome c
c. Cytokeratins
d. Myeloperoxidase
e. Superoxide dismutase
B: Cytochrome c. The mitochondrial membrane is a key regulator of apoptosis. When mitochondrial pores open, cytochrome c leaks out and activates Apaf-1, which converts procaspase-9 to caspase-9, resulting in the activation of downstream caspases (cysteine proteases). These effector caspases cleave target proteins, including endonucleases nuclear proteins, and cytoskeletal proteins to mediate the varied morphological and biochemical changes that accompany apoptosis. Reactive oxygen species (related to choices A, D, and E) are triggers of apoptosis, but they do not mediate programmed cell death.
Diagnosis: Apoptosis, squamous cell carcinoma of skin
- A 16-year-old girl with a history of suicidal depression swallows a commercial solvent. A liver biopsy is performed to assess the degree of damage to the hepatic parenchyma. Histologic examination demonstrates severe swelling of the centrilobular hepatocytes (shown in the image). Which of the following mechanisms of disease best accounts for the reversible changes noted in this liver biopsy?
a. Decreased stores of intracellular ATP
b. Increased storage of triglycerides and free fatty acids
c. Intracytoplasmic rupture of lysosomes
d. Mitochondrial membrane permeability transition
e. Protein aggregation due to increased cytosolic pH
A: Decreased stores of intracellular ATP. Hydropic swelling may result from many causes, including chemical and biological toxins, infections, and ischemia. Injurious agents cause hydropic swelling by (1) increasing the permeability of the plasma membrane to 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 other choices are incorrect because they do not regulate the concentration of intracellular sodium.
Diagnosis: Hydropic swelling, hepatotoxicity
- A 40-year-old man is pulled from the ocean after a boating accident and resuscitated. Six hours later, the patient develops acute renal failure. Kidney biopsy reveals evidence of karyorrhexis and karyolysis in renal tubular epithelial cells. Which of the following biochemical events preceded these pathologic changes?
a. (A) Activation of Na+/K+ ATPase
b. Decrease in intracellular calcium
c. Decrease in intracellular pH
d. Increase in ATP production
e. Increase in intracellular pH
C: Decrease in intracellular pH. During periods of ischemia, anaerobic glycolysis leads to the overproduction of lactate and a decrease in intracellular pH. Lack of O2 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 tubular necrosis
- A 58-year-old man presents with symptoms of acute renal failure. His blood pressure is 220/130 mm Hg (malignant hypertension). While in the emergency room, the patient suffers a stroke and expires. Microscopic examination of the kidney at autopsy is shown in the image. Which of the following morphologic changes accounts for the red material in the wall of the artery?
D: Fibrinoid necrosis. Fibrinoid necrosis is an alteration of injured blood vessels, in which the insudation and accumulation of plasma proteins cause the wall to stain intensely with eosin. The other choices are not typically associated directly with vascular injury.
Diagnosis: Malignant hypertension, fi brinoid necrosis
- 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. Lamin
c. Oxidase
d. Polymerase
e. Topoisomerase
B: Lamin. Hutchinson-Gilford progeria is a rare genetic disease characterized by early cataracts, hair loss, atrophy of the skin, osteoporosis, and atherosclerosis. This phenotype gives the impression of premature aging in children. Progeria is one of many diseases caused by mutations in the human lamin A gene (LMNA). Lamins are intermediate filament proteins that form 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
- A 32-year-old woman develops an Addisonian crisis (acute adrenal insufficiency) 3 months after suffering massive 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 accounts for adrenal atrophy in this patient?
a. Chronic inflammation
b. Chronic ischemia
c. Hemorrhagic necrosis
d. Lack of trophic signals
e. Tuberculosis
D: Lack of trophic signals. Atrophy of an organ may be caused by interruption of key trophic signals. Postpartum infarction of the anterior pituitary in this patient resulted in decreased production of adrenocorticotropic hor
mone (ACTH, also termed corticotropin). Lack of corticotropin results in atrophy of the adrenal cortex, which leads to adrenal insufficiency. Symptoms of acute adrenal insufficiency (Addisonian crisis) include hypotension and shock, as well as weakness, vomiting, abdominal pain, and lethargy. The other choices are unlikely causes of postpartum adrenal insuf fi ciency.
Diagnosis: Sheehan syndrome, adrenal insufficiency
- A 47-year-old man with 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 fail to identify a mass, but the bronchial mucosa displays squamous metaplasia. What is the most likely outcome of this morphological adaptation if the patient stops smoking?
a. Atrophy
b. Malignant transformation
c. Necrosis and scarring
d. Persistence throughout life
e. Reversion to normal
E: Reversion to normal. Metaplasia is almost invariably a response to persistent injury and can be thought of as an adaptive mechanism. Prolonged exposure of the bronchi to tobacco smoke leads to squamous metaplasia of the bronchial epithelium. Unlike malignancy (choice B) and necrosis with scarring (choice C), metaplasia is usually fully reversible. If the source of injury in this patient is removed
(the patient stops smoking), then the metaplastic epithelium will eventually return to normal.
Diagnosis: Chronic bronchitis, metaplasia
- A 60-year-old farmer presents with multiple patches of discoloration on his face. Biopsy of lesional skin reveals actinic keratosis. Which of the following terms best describes this response of the skin to chronic sunlight exposure?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
B: Dysplasia. Actinic keratosis is a form of dysplasia in sun-exposed skin. Histologically, 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. Dysplasia is a preneoplastic lesion, in the sense that it is a necessary stage in the multistep evolution to cancer. However, unlike cancer cells, dysplastic cells are not entirely autonomous, and the histologic appearance of the tissue may still revert to normal. None of the other choices represent preneo
plastic changes in sun-exposed skin.
Diagnosis: Actinic keratosis, dysplasia
- A 59-year-old woman smoker complains of intermittent blood in her urine. Urinalysis confirms 4+ hematuria. A CBC reveals increased red cell mass (hematocrit). A CT scan demonstrates a 3-cm renal mass, and a CT-guided biopsy displays renal cell carcinoma. Which of the following cellular adaptations in the bone marrow best explains the increased hematocrit in this patient?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
C: Hyperplasia. Renal cell carcinomas often secrete erythropoietin. This hormone stimulates the growth of erythrocyte precursors in the bone marrow 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 represent physiologic responses to erythropoietin.
Diagnosis: Renal cell carcinoma, hyperplasia
- A 33-year-old woman has an abnormal cervical Pap smear. A cervical biopsy reveals that the epithelium lacks normal polarity (shown in the image). Individual cells display hyper chromatic nuclei, a larger nucleus-to-cytoplasm ratio, and disorderly tissue arrangement. Which of the following adaptations to chronic injury best describes these changes in the patient’s cervical epithelium?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
B: Dysplasia. The distinction between severe dysplasia and early cancer of the cervix is a common diagnostic problem for the pathologist. Both are associated with disordered growth and maturation of the tissue. Similar to the development of cancer, dysplasia is believed to result from mutations in a proliferating cell population. When a particular mutation 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 further mutations. The accumulation of such mutations progressively distances the cell from normal regulatory constraints and may lead to neoplasia. None of the other choices are associated with lack of normal tissue polarity. Diagnosis: Cervical intraepithelial neoplasia, dysplasia
- A 24-year-old woman accidentally ingests carbon tetrachloride (CCl4) in the laboratory and develops acute liver failure. Which of the following cellular proteins was directly involved in the development of hepatotoxicity in this patient?
a. Acetaldehyde dehydrogenase
b. Alcohol dehydrogenase
D: Mixed function oxygenase. The metabolism of CCl4 is a model system for toxicologic studies. CCl4 is first metabolized via the mixed function oxygenase system (P450) of the liver to a chloride ion and a highly reactive trichlo
methyl 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
c. Glucose-6-phosphate
dehydrogenase
d. Mixed function oxygenase
e. Superoxide dismutase
choices are not involved in the formation of the trichloromethyl free radical in liver cells.
Diagnosis: Hepatic failure, hepatotoxicity
- A 30-year-old woman presents with a 2-month history of fatigue, mild fever, and an erythematous scaling rash. She also notes joint pain and swelling, primarily involving the small bones of her fingers. Physical examination reveals erythematous plaques with adherent silvery scales that induce punctate bleeding points when removed. Biopsy of lesional skin reveals markedly increased thickness of the epidermis (shown in the image). Which of the following terms best describes this adaptation to chronic injury in this patient with psoriasis?
a. Atrophy
b. Dysplasia
c. Hyperplasia
d. Hypertrophy
e. Metaplasia
Hyperplasia. Psoriasis is a disease of the dermis and epidermis that is characterized by persistent epidermal hyperplasia. It is a chronic, frequently familial disorder that features large, erythematous, scaly plaques, commonly on the dorsal extensor cutaneous surfaces. There is evidence to suggest that deregulation of epidermal proliferation and an abnormality in the microcirculation of the dermis are responsible for the development of psoriatic lesions. Abnormal proliferation of keratinocytes is thought to be related to defective epidermal cell surface receptors and altered intracellular signaling. The other choices do not describe increased numbers of otherwise normal epidermal cells.
Diagnosis: Psoriasis, hyperplasia
45 A 24-year-old woman with chronic depression ingests a bottle of acetaminophen tablets. Two days later, she is jaundiced (elevated serum bilirubin) and displays symptoms of encephalopathy, including impairment in spatial perception. In 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
E: Smooth endoplasmic reticulum. Carbon tetrachloride and acetaminophen are well studied hepatotoxins. Each is metabolized by cytochrome P450 of the mixed function oxidase system, located in the smooth endoplasmic reticulum. These hepatotoxins are metabolized differently, and it is possible to relate the subsequent evolution of lethal cell injury to 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 toxic to 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: Hepatotoxicity, necrosis
- A 45-year-old woman presents with a 2-month history of fatigue and recurrent fever. She also complains of tenderness below the right costal margin and dark urine. Physical examination reveals jaundice and mild hepatomegaly. The serum is positive for hepatitis B virus antigen. Which of the following best describes the mechanism 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+/K+
ATPase activity
e. Interference with cellular energy
generation
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 enzymes and depleting the cell’s nutri
ents, thereby disrupting the normal homeostatic mechanisms. Some viruses also encode proteins that induce apoptosis once daughter virions are mature. Viruses may also injure cells indirectly through activation of the immune system. Both humoral and cellular arms of the immune system protect against the harmful effects of viral infections by eliminating infected cells. In brief, the presentation of viral proteins to the immune system in the context of a self major histocompatibility complex on the cell surface immunizes the body against the invader and elicits both killer cells and antiviral antibodies. These arms of the immune system eliminate virus-infected cells by inducing apoptosis or by lysing the virally infected target cell with complement. None of the other choices describe mechanisms of indirect viral cytotoxicity.
Diagnosis: Hepatitis, viral
- You are asked to present a grand rounds seminar on the role of abnormal proteins in disease. In this connection, intracellular accumulation of an abnormally folded protein
plays a role in the pathogenesis of which of the following diseases?
a. AA amyloidosis
b. AL amyloidosis
c. α1-Antitrypsin deficiency
d. Gaucher disease
e. Tay-Sachs disease
C: α1-Antitrypsin deficiency. Several acquired and inherited diseases are characterized by intracellular accumulation of abnormal proteins. The deviant tertiary structure of the protein may result from an inherited mutation that alters the normal primary amino acid sequence, or may reflect an acquired defect in protein folding. α1-Antitrypsin deficiency is a heritable disorder in which mutations in the gene for α1-antitrypsin yield an insoluble protein. The mutant protein is not easily exported. It accumulates in liver cells, causing cell injury and cirrhosis. Pulmonary emphysema is another complication of α1-antitrypsin deficiency. Choices A and B are amyloidoses that represent extracellular deposits of fi brillar proteins arranged in β-pleated sheets. Choices D and E are lysosomal storage diseases that represent intracellular deposits of unmetabolized sphingolipids.
Diagnosis: α1-Antitrypsin deficiency
- 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 alleles of a gene that encodes which of the following types of intracellular proteins? a. Deaminase
b. Helicase
c. Oxidase
d. Polymerase
e. Topoisomerase
B: Helicase. Werner syndrome is a rare auto somal recessive disease characterized 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, patients 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 with ATPase, helicase, and exonuclease activity. Hutchinson-Gilford progeria is caused by mutations in the human lamin A gene, which encodes an intermediate filament protein that forms a fibrous meshwork beneath the nuclear envelope. Mutations in the other choices are not associated with Werner syndrome.
Diagnosis: Werner syndrome
49 A 28-year-old man with a history of radiation/bone marrow transplantation for leukemia presents with severe diarrhea. He subsequently develops septic shock and expires. Microscopic examination of the colon epithelium at autopsy reveals numerous acidophilic bodies and small cells with pyknotic nuclei. Which of the following proteins most likely played a key role in triggering radiation induced cell death in this patient’s colonic mucosa?
a. Cytochrome P450
b. β-Catenin
c. E-Cadherin
d. P-Selectin
e. p53
E: p53. Apoptosis detects and destroys cells that harbor dangerous mutations, thereby maintaining genetic consistency and preventing the development of cancer. There are several means, the most important of which is probably p53, by which the cell recognizes genomic abnormalities and “assesses’’ whether they can be repaired. If the damage to DNA is so severe that it cannot be repaired, the cascade of events leading to apoptosis is activated, and the cell dies. This process protects an organism from the consequences of a non
functional cell or one that cannot control its own proliferation (e.g., a cancer cell). After it binds to areas of DNA damage, p53 activates proteins that arrest the cell in G1 of the cell cycle, allowing time for DNA repair to proceed. It also directs DNA repair enzymes to the site of injury. If the DNA damage cannot be repaired, p53 activates mechanisms that terminate in apoptosis. There are several pathways by which p53 induces apoptosis. This molecule downregulates transcription of the antiapoptotic protein Bcl-2, while it upregulates transcription of the proapoptotic genes bax and bak. Cytochrome P450 (choice A) is a member of the mixed function oxidase system. β-Catenin (choice B) is a membrane protein associated with cell adhesion molecules. Selectins (choices C and D) are cell adhesion molecules involved in leukocyte recirculation.
Diagnosis: Apoptosis
- A 22-year-old woman nursing her newborn develops a tender erythematous area around the nipple of her left breast. A thick, yellow fluid 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. Neutrophils
e. Plasma cells
D: Neutrophils. The thick, yellow fluid draining from the breast fissure in this patient represents a purulent exudate. Purulent exudates and effusions are associated with pathologic conditions such as pyogenic bacterial infections, in which the predominant cell type is the segmented neutrophil (polymorphonuclear leukocyte). Mast cells (choice C) are granulated cells that contain receptors for IgE on their cell surface. They are additional cellular sources of vasoactive mediators, particularly in response to allergens. B lymphocytes (choice A) and plasma cells (choice E) are mediators of chronic inflammation and provide antigen-specific immunity to infectious diseases.
Diagnosis: Acute mastitis
- Which of the following mediators of inflammation facilitates chemotaxis, cytolysis, and opsonization at the site of inflammation in the patient described in Question 1?
a. Complement proteins
b. Defensins
c. Kallikrein
d. Kinins
e. Prostaglandins
A: Complement proteins. Complement proteins act upon one another in a cascade, generating biologically active fragments (e.g., C5a, C3b) or complexes (e.g., C567). These products of complement activation cause local edema by increasing the permeability of blood vessels. They also promote chemotaxis of leukocytes and lyse cells (membrane attack complex) and act as opsonins by coating bacteria. Although the other choices are mediators of inflammation, they have a more restricted set of functions. Kinins (choice D) are formed following tissue trauma and mediate pain transmission. None of the other choices are involved in opsonization or cytolysis.
Diagnosis: Acute mastitis
- A 63-year-old man becomes febrile and begins expectorating large amounts of mucopurulent sputum. Sputum cultures are positive for Gram-positive diplococci. Which of the following mediators of inflammation provides potent chemotactic factors for the directed migration of inflammatory cells into the alveolar air spaces of this patient?
a. Bradykinin
b. Histamine
c. Myeloperoxidase
d. N-formylated peptides
e. Plasmin
D: N-formylated peptides. The most potent chemotactic factors for leukocytes at the site of injury are (1) complement proteins (e.g., C5a); (2) bacterial and mitochondrial products, particularly low molecular weight N
formylated peptides; (3) products of arachidonic acid metabolism (especially LTB4); and (4) chemokines (e.g., interleukin-1 and interferon-γ). Plasmin (choice E) is a fibrinolytic enzyme generated by activated Hageman factor (clotting factor XII). Histamine (choice B) is one of the primary mediators of increased vascular permeability. None of the other choices are chemotactic agents.
Diagnosis: Pneumonia
- A 59-year-old man suffers a massive heart attack and expires 24 hours later due to ventricular arrhythmia. Histologic examination of the affected heart muscle at autopsy would show an abundance of which of the following inflammatory cells?
a. Fibroblasts
b. Lymphocytes
c. Macrophages
d. Neutrophils
e. Plasma cells
D: Neutrophils. During acute inflammation, neutrophils (PMNs) adhere to the vascular endothelium. They flatten and migrate from the vasculature, through the endothelial cell layer, and into the surrounding tissue. About 24 hours after the onset of infarction, PMNs are
observed to infiltrate necrotic tissue at the periphery of the infarct. 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 inflammation and provide antigen specific immunity to infectious diseases. Fibroblasts (choice A) and macrophages (choice C) regulate scar tissue formation at the site of infarction.
Diagnosis: Acute myocardial infarction
- A 5-year-old boy punctures his thumb with a rusty nail. Four hours later, the thumb appears red and swollen. Initial swelling of the boy’s thumb is primarily due to which of the following mechanisms?
a. Decreased intravascular hydrostatic pressure
b. Decreased intravascular oncotic pressure
c. Increased capillary permeability
d. Increased intravascular oncotic pressure
e. Vasoconstriction of arterioles
C: Increased capillary permeability. Forces that regulate the balance of vascular and tissue fluids include (1) hydrostatic pressure, (2) oncotic pressure, (3) osmotic pressure, and (4) lymph flow. During inflammation, 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 pressure in the capillary bed (thus, not choice A), potentiating the formation of edema. Vasodilation of venules decreases capillary hydrostatic pressure and inhibits the movement of fluid into the extravascular spaces. Acute inflammation is not associated with changes in plasma oncotic pressure (choices B and D).
Diagnosis: Inflammatory edema
- Which of the following serum proteins activates the complement, coagulation, and fi brinolytic systems at the site of injury in the patient described in Question 5?
a. Bradykinin
b. Hageman factor
c. Kallikrein
d. Plasmin
e. Thrombin
B: Hageman factor. Hageman factor (clotting factor XII) provides a key source of vasoactive mediators. Activation of this plasma protein at the site of tissue injury stimulates (1) conversion of plasminogen to plasmin, which induces fibrinolysis; (2) conversion of prekallikrein to kallikrein, which generates vasoactive peptides of low molecular weight referred to as kinins; (3) activation of the alternative complement pathway; and (4) activation of the
- An 80-year-old woman presents 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 Gram-negative organisms. Which of the following cytokines is primarily involved in the pathogenesis of direct vascular injury in this patient with septic shock?
a. Interferon-γ
b. Interleukin-1
c. Platelet-derived growth factor
d. Transforming growth factor-β
e. Tumor necrosis factor-α
E: Tumor necrosis factor-α (TNF-α). Septicemia (bacteremia) denotes the clinical condition in which bacteria are found in the circulation. It can be suspected clinically, but the final diagnosis is made by culturing the organisms from the blood. In patients with endotoxic shock, lipopolysaccharide released from Gram-negative bacteria stimulates monocytes/ macrophages to secrete large quantities of TNF-α. This glycoprotein causes direct cytotoxic damage to capillary endothelial cells. The other choices do not cause direct vascular injury.
Diagnosis: Septic shock
- A 24-year-old intravenous drug abuser develops a 2-day history of severe headache and fever. His temperature is 38.7°C (103°F). Blood cultures are positive for Gram-positive cocci. The patient is given intravenous antibiotics, but he deteriorates rapidly and dies. A cross section of the brain at autopsy (shown in the image) reveals two encapsulated cavities. Which of the following terms best characterizes this pathologic finding?
a. Chronic inflammation
b. Fibrinoid necrosis
c. Granulomatous inflammation
d. Reactive gliosis
e. Suppurative inflammation
E: Suppurative inflammation. Suppurative inflammation describes a condition in which a purulent exudate is accompanied by significant liquefactive necrosis. It is the equivalent of pus. The photograph shows two encapsulated cavities 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 (choice D) is a normal response of the brain to injury and infection but is not visible on the cut surface of the brain at autopsy.
Diagnosis: Cerebral abscess
- 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 characterizes this pleural effusion?
a. Fibrinous exudate
b. Lymphedema
c. Purulent exudate
d. Serosanguineous exudate
e. Transudate
C: Purulent exudate. The pleural effusion encountered in this patient represents excess fluid in a body cavity. A transudate denotes edema fluid with low protein content, whereas an exudate denotes edema fluid with high protein content. A purulent exudate or effusion contains a prominent cellular component (PMNs). A serous exudate or effusion is characterized by the absence of a prominent cellular response and has a yellow, straw-like color. Fibrinous exudate (choice A) does not contain leukocytes. Serosanguineous exudate (choice D) contains RBCs and has a red tinge.
Diagnosis: Bacterial pneumonia, pleural effusion
- 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 is the most likely etiology of this patient’s myalgia?
a. Autoimmune disease
b. Bacterial infection
c. Muscular dystrophy
d. Parasitic infection
e. Viral infection
D: Parasitic infection. Eosinophils are particularly evident during allergic-type reactions and parasitic infestations. Infections with Trichinella 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 with B and T lymphocytes. Polymyositis, an autoimmune disease (choice A), does not feature eosinophils.
Diagnosis: Trichinosis
- A 10-year-old boy with a history of recurrent bacterial infections presents with fever and a productive cough. Biochemical analysis of his neutrophils demonstrates that he has an impaired ability to generate reactive 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
D: NADPH oxidase. The importance of oxygen dependent mechanisms in the bacterial killing by phagocytic cells is exemplified in chronic granulomatous disease 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 to recurrent bacterial infections. Patients deficient in myeloperoxidase (choice C) cannot produce hypochlorous acid (HOCl) and experience an increased susceptibility to infections with the fungal pathogen Candida. Catalase (choice A) converts hydrogen peroxide to water and molecular oxygen.
Diagnosis: Chronic granulomatous disease
- A 25-year-old woman presents with a history of recurrent shortness of breath and severe wheezing. Laboratory studies demonstrate that she has a deficiency of C1 inhibitor, an
B: Hereditary angioedema. Deficiency of C1 inhibitor, with excessive cleavage of C4 and C2
esterase inhibitor that regulates the activation of the classical complement pathway. What is the diagnosis?
a. Chronic granulomatous disease
b. Hereditary angioedema
c. Myeloperoxidase deficiency
d. Selective IgA deficiency
e. Wiskott-Aldrich syndrome
by C1s, is associated with the syndrome of hereditary angioedema. This disease is characterized by episodic, painless, nonpitting edema of soft tissues. It is the result of chronic complement activation, with the generation of a vasoactive peptide from C2, and may be life threatening because 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 Candida. Selective IgA deficiency (choice D) and Wiskott Aldrich syndrome (choice E) are congenital immunodeficiency disorders associated with defects in lymphocyte function.
Diagnosis: Hereditary angioedema
- A 40-year-old man complains of a 2-week history of increasing abdominal pain and yellow discoloration of his sclera. Physical examination reveals right upper quadrant pain. Laboratory studies show elevated serum levels of alkaline phosphatase (520 U/dL) and bilirubin (3.0 mg/dL). A liver biopsy shows portal fibrosis, with scattered foreign bodies consistent with schistosome eggs. Which of the following inflammatory cells is most likely to predominate in the portal tracts in the liver of this patient?
a. Basophils
b. Eosinophils
c. Macrophages
d. Monocytes
e. Plasma cells
B: Eosinophils. Eosinophils are recruited in parasitic infestations and would be expected to predominate in the portal tracts of the liver in patients with schistosomiasis. Eosinophils contain leukotrienes and platelet-activating factors, as well as acid phosphatase and eosinophil major basic protein. Plasma cells (choice E) are differentiated B lymphocytes that secrete large amounts of monospecifi c immunoglobulin.
Diagnosis: Schistosomiasis, eosinophils
- A 41-year-old woman complains of excessive menstrual bleeding and pelvic pain of 4 months. She 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 following conditions?
B: Chronic inflammation. Inflammation has historically been referred to as either acute or chronic, depending on the persistence of the injury, clinical symptoms, and the nature of the inflammatory response. The cellular components of chronic inflammation are lymphocytes, antibody producing plasma cells (see arrows on photomicrograph), and macrophages. The chronic inflammatory response is often prolonged and may be associated with aberrant repair (i.e., fibrosis). Neutrophils 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
- 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 ejection fraction with normal coronary blood flow. A myocardial biopsy is obtained, and a PCR test for coxsackievirus is positive. Histologic examination of this patient’s myocardium will most likely reveal an abundance of which of the following inflammatory cells?
a. Eosinophils
b. Lymphocytes
c. Macrophages
d. Mast cells
e. Neutrophils
B: Lymphocytes. This patient with viral myocarditis will show an accumulation of lymphocytes in the affected heart muscle. Naïve lymphocytes encounter antigen
presenting cells (macrophages and dendritic cells) in the secondary lymphoid organs. In response to this cell-cell interaction, they become activated, circulate in the vascular system, and are recruited to peripheral tissues (e.g., heart). The other choices are not characteristic responders to viral infections, although acute inflammation may be observed in lytic infections.
Diagnosis: Viral myocarditis
- A 58-year-old woman with long-standing diabetes and hypertension develops end-stage renal disease and dies in uremia. A shaggy fibrin-rich exudate is noted on the visceral pericardium at autopsy (shown in the image). Which of the following best explains the pathogenesis of this fibrinous exudate?
a. Antibody binding and complement activation
b. Chronic passive congestion
c. Injury and increased vascular permeability
d. Margination of segmented neutrophils
e. Thrombosis of penetrating coronary arteries
C: Injury and increased vascular permeability. Binding of vasoactive mediators to specific receptors on endothelial cells results in contraction and gap formation. This break in the endothelial barrier leads to the leakage of intravascular fluid into the extravascular space. Direct injury to endothelial cells also leads to leakage of intravascular fluid. A fibrinous exudate contains large amounts of fibrin as a result of activation of the coagulation system. When a fibrinous exudate occurs on a serosal surface, such as the pleura or pericardium, it is referred to as fibrinous pleuritis or fibrinous pericarditis. Although the other choices describe aspects of inflammation, they do not address the pathogenesis of edema formation with activation of the coagulation system.
Diagnosis: End-stage kidney disease, fibrinous pericarditis
- A 68-year-old man presents with fever, shaking chills, and shortness of breath. Physical examination shows rales and decreased breath sounds over both lung fields. The patient exhibits grunting respirations, 30 to 35 breaths per minute, with flaring of the nares. The sputum is rusty yellow and displays numerous polymorphonuclear leukocytes. Which of the following mediators of inflammation is chiefly responsible for the development of fever in this patient?
a. Arachidonic acid
b. Interleukin-1
c. Leukotriene B4
d. Prostacyclin (PGI2)
e. Thromboxane A2
B: Interleukin-1. Release of exogenous pyrogens by bacteria, viruses, or injured cells stimulates the production of endogenous pyrogens such as IL 1α, IL-1β, and TNF-α. IL-1 is a 15-kDa protein that stimulates prostaglandin synthesis in the hypothalamic thermoregulatory centers, thereby altering the “thermostat” that controls body temperature. Inhibitors of cyclooxygenase (e.g., aspirin) block the fever response by inhibiting PGE2 synthesis in the hypothalamus. Chills, rigor (profound chills with shivering and piloerection), and sweats (to allow heat dissipation) are symptoms associated with fever. The other choices are mediators of inflammation, but they do not directly control body temperature.
Diagnosis: Bacterial pneumonia
- Sputum cultures obtained from the patient described in Question 17 are positive for Streptococcus pneumoniae. Removal of bacteria from the alveolar air spaces in this patient involves opsonization by complement,
an important step in mediating which of the following leukocyte functions?
a. Chemotaxis
b. Diapedesis
c. Haptotaxis
d. Margination
e. Phagocytosis
E: Phagocytosis. Many inflammatory cells are able to recognize, internalize, and digest foreign materials, microorganisms, and cellular debris. This process is termed phagocytosis, and the effector cells are known as phagocytes. Phagocytosis of most biologic agents is enhanced by their coating with specific plasma components (opsonins), particularly immunoglobulins or the C3b fragment of complement. The other functions are not enhanced by opsonization.
Diagnosis: Bacterial pneumonia
- Which of the following mediators of inflammation is primarily responsible for secondary injury to alveolar basement membranes and lung parenchyma in the patient described in Questions 17 and 18?
a. Complement proteins
b. Fibrin split products
c. Immunoglobulins
d. Interleukin-1
e. Lysosomal enzymes
E: Lysosomal enzymes. The primary role of neutrophils in inflammation is host defense and débridement of damaged tissue. However, when the response is extensive or unregulated, the chemical mediators of inflammation may prolong tissue damage. Thus, the same neutrophil-derived lysosomal enzymes that are beneficial when active intracellularly can be harmful when released to the extracellular environment. The other choices are less likely to cause direct injury to the lung in a patient with pneumonia.
Diagnosis: Bacterial pneumonia
- Which of the following proteins inhibits fibrinolysis, activation of the complement system, and protease-mediated damage in the lungs of the patient described in the previous questions?
a. Acid phosphatase
b. Lactoferrin
c. Lysozyme
d. α2-Macroglobulin
e. Myeloperoxidase
D: α2-Macroglobulin. Proteolytic enzymes that are released by phagocytic cells during inflammation are regulated by a family of protease inhibitors, including α1-antitrypsin and α2-macroglobulin. These plasma-derived proteins inhibit plasmin-activated fibrinolysis and activation of the complement system and help protect against nonspecific tissue injury during acute inflammation. Lysozyme (choice C) is a glycosidase that degrades the peptidoglycans of Gram positive bacterial cell walls. Myeloperoxidase (choice E) is contained within neutrophil granules.
Diagnosis: Bacterial pneumonia
- A 35-year-old woman presents with a 5-day history of a painful sore on her back. Physical examination reveals a 1-cm abscess over her left shoulder. Biopsy of the lesion shows vasodilation and leukocyte margination
(shown in the image). What glycoprotein mediates initial tethering of segmented neutrophils to endothelial cells in this skin lesion?
a. Cadherin
b. Entactin
c. Integrin
d. Laminin
e. Selectin
E: Selectin. Selectins are sugar-binding glycoproteins that mediate the initial adhesion of leukocytes to endothelial cells at sites of inflammation. E-selectins are found on endothelial cells, P-selectins are found on platelets, and L-selectins are found on leukocytes. E-selectins are stored in Weibel
Palade bodies of resting endothelial cells. Upon activation, E-selectins are redistributed along the luminal surface of the endothelial cells, where they mediate the initial adhesion (tethering) and rolling of leukocytes. After leukocytes have come to a rest, integrins (choice C) mediate transendothelial cell migration and chemotaxis. Cadherins (choice A) mediate cell-cell adhesion, but they are not involved in neutrophil adhesion to vascular endothelium. Entactin (choice B) and laminin (choice D) are basement membrane proteins.\
Diagnosis: Carbuncle
- A 14-year-old boy receives a laceration on his forehead during an ice hockey game. When he is first attended to by the medic, there is blanching of the skin around the wound. Which of the following mechanisms accounts for this transient reaction to neurogenic and chemical stimuli at the site of injury?
a. Constriction of postcapillary venules
b. Constriction of precapillary arterioles
c. Dilation of postcapillary venules
d. Dilation of precapillary arterioles
e. Ischemic necrosis
B: Constriction of precapillary arterioles. The initial response of arterioles to neurogenic and chemical stimuli is transient vasoconstriction. However, shortly thereafter, vasodilation (choice D) occurs, with an increase in blood flow to the inflamed area. This process is referred to as active hyperemia. None of the other choices cause transient skin blanching.
Diagnosis: Laceration
- An 8-year-old girl with asthma presents with respiratory distress. She has a history of allergies and upper respiratory tract infections. She also has a history of wheezes associated with exercise. Which of the following mediators of inflammation is the most powerful stimulator of bronchoconstriction and vasoconstriction in this patient?
a. Bradykinin
b. Complement proteins
c. Interleukin-1
d. Leukotrienes
e. Tumor necrosis factor-α
D: Leukotrienes. Asthma is a chronic lung disease caused by increased responsiveness of the airways to a variety of stimuli. Chemical mediators released by chronic inflammatory cells in the lungs of these patients stimulate bronchial mucus production and bronchoconstriction. Among these mediators are leukotrienes, also known as slow-reacting substances of anaphylaxis. They are derived from arachidonic acid through the lipoxygenase pathway. Leukotrienes 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 important mediators of inflammation, they do not play a leading role in the development of bronchoconstriction in patients with bronchial asthma.
Diagnosis: Asthma
- Which of the following preformed substances is released from mast cells and platelets, resulting in increased vascular permeability in the lungs of the patient described in Question 23?
a. Bradykinin
b. Hageman factor
c. Histamine
d. Leukotrienes (SRS-A)
e. Thromboxane A2
C: Histamine. When IgE-sensitized mast cells are stimulated by antigen, preformed mediators of inflammation are secreted into the extracellular tissues. Histamine binds to specific H1 receptors in the vascular wall, inducing endothelial cell contraction, gap formation, and edema. Massive release of histamine may cause circulatory collapse (anaphylactic shock). Bradykinin (choice A) and Hageman factor (choice B) are plasma-derived mediators. The other choices are not performed molecules but are synthesized de
- A 75-year-old woman complains of recent onset of chest pain, fever, and productive cough with rust-colored sputum. A chest X-ray reveals an infiltrate in the right middle lobe. Sputum cultures are positive for Streptococcus pneumoniae. Phagocytic cells in this patient’s affected lung tissue generate bacteriocidal hypochlorous acid using which of the following enzymes?
a. Catalase
b. Cyclooxygenase
c. Myeloperoxidase
d. NADPH oxidase
e. Superoxide dismutase
C: Myeloperoxidase. Myeloperoxidase catalyzes the conversion of H2O2, in the presence of a halide (e.g., chloride 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) catabolizes H2O2. Cyclooxygenase (choice B) mediates the conversion of
arachidonic acid to prostaglandins. NADPH oxidase (choice D) is involved in oxygen-free radical formation during the neutrophil respiratory burst. Superoxide dismutase (choice E) reduces the superoxide radical to H2O2.
Diagnosis: Bacterial pneumonia
- A 28-year-old woman cuts her hand while dicing vegetables in the kitchen. The wound is cleaned and sutured. Five days later, the site of injury contains an abundance of chronic inflammatory cells that actively secrete interleukin-1, tumor necrosis factor-α, interferon-α, numerous arachidonic acid derivatives, and various enzymes. Name these cells.
a. B lymphocytes
b. Macrophages
c. Plasma cells
d. Smooth muscle cells
e. T lymphocytes
B. Macrophages. The macrophage is the pivotal cell in regulating chronic inflammation. Macrophages, which are derived from circulating monocytes, regulate lymphocyte responses to antigens and secrete a variety of mediators that modulate the proliferation and function of fibroblasts and endothelial cells. None of the other cells have this wide spectrum of regulatory functions.
Diagnosis: Laceration, wound healing
- A 68-year-old man with prostate cancer and bone metastases presents with shaking chills and fever. The peripheral WBC count is 1,000/µL (normal = 4,000 to 11,000/µL). Which of the following terms best describes this hematologic finding?
a. Leukocytosis
b. Leukopenia
c. Neutrophilia
d. Pancytopenia
e. Leukemoid reaction
B: Leukopenia. Leukopenia is defined as an absolute decrease in the circulating WBC count. It is occasionally encountered under conditions of chronic inflammation, especially in patients who are malnourished or who suffer from a chronic debilitating disease. Leukopenia may also be caused by typhoid fever and certain viral and rickettsial infections. Leukocytosis (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 count. Pancytopenia (choice D) refers to decreased circulating levels of all formed elements in the blood.
Diagnosis: Prostate cancer
- A 25-year-old machinist is injured by a metal sliver in his left hand. Over the next few days, the wounded area becomes reddened, tender, swollen, and feels warm to the touch. Redness at the site of injury in this patient is caused primarily by which of the following mechanisms?
a. Hemorrhage
b. Hemostasis
c. Neutrophil margination
d. Vasoconstriction
e. Vasodilation
E: Vasodilation. Vasodilation of precapillary arterioles increases blood flow at the site of tissue injury. This condition (active hyperemia) is caused by the release of specific mediators. Vasodilation and hyperemia are primarily responsible for the redness and warmth (rubor and calor) at sites of injury. The other choices do not regulate active hyperemia.
Diagnosis: Acute inflammation
- The patient described in Question 28 goes to the emergency room to have the sliver removed. Which of the following mediators of inflammation plays the most important role in stimulating platelet aggregation at the site of injury following this minor surgical procedure?
a. Leukotriene C4
b. Leukotriene D4
c. Prostaglandin E2
d. Prostaglandin I2
e. Thromboxane A2
E. Thromboxane A2. Platelet adherence, aggregation, and degranulation occur when platelets come in contact with fi brillar collagen or thrombin (after activation of the coagulation system). Platelet degranulation is associated with the release of serotonin, which directly increases vascular permeability. In addition, the arachidonic acid metabolite thromboxane A2 plays a key role in the second wave of platelet aggregation and mediates smooth muscle constriction. Prostaglandins E2 and I2 (choices C and D) inhibit inflammatory cell functions. Leukotrienes C4 and D4 (choices A and B) induce smooth muscle contraction.
Diagnosis: Acute inflammation
- Twenty-four hours later, endothelial cells at the site of injury in the patient described in Questions 28 and 29 release a chemical mediator that inhibits further platelet aggregation. Name this mediator of inflammation.
a. Plasmin
b. Prostaglandin (PGI2)
c. Serotonin
d. Thrombin
e. Thromboxane A2
B: Prostaglandin (PGI2). PGI2 is a derivative of arachidonic acid that is formed in the cyclooxygenase enzyme pathway. It promotes vasodilation and bronchodilation and also inhibits platelet aggregation. It activates adenylyl cyclase and increases intracellular levels of cAMP. Its action is diametrically opposite to that of thromboxane A2 (choice E), which 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 conversion of fibrinogen to fibrin.
Diagnosis: Acute inflammation
- A 37-year-old man with AIDS is admitted to the hospital with a 3-week history 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 following inflammatory cells?
C: Macrophages. Granulomas are collections of epithelioid cells and multinucleated giant cells that are formed by cytoplasmic fusion of macrophages. When the nuclei are arranged around the periphery of the cell in a horseshoe pattern (see photomicrograph), the cell is
termed a Langhans giant cell. Frequently, a foreign pathogenic agent is identified within
