Lippincott's Illustrated Q&A Pathology Inflammation
The answer is 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 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
The answer is 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 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 (the guy had bacterial pneumonia from S. Pneumoniae)? (A) Complement proteins (B) Fibrin split products (C) Immunoglobulins (D) Interleukin-1 (E) Lysosomal enzymes
The answer is D: a2-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
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 (the guy had bacterial pneumonia from S. pneumoniae)? (A) Acid phosphatase (B) Lactoferrin (C) Lysozyme (D) α2-Macroglobulin (E) Myeloperoxidase
The answer is D: NAPDH 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 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
The answer is E: Transudate. According to the Starling principle, the interchange of fluid between vascular and extravascular compartments results from a balance of forces that draw fluid into the vascular space or out into tissues. These forces include (1) hydrostatic pressure, (2) oncotic pressure (reflects plasma protein concentration), (3) osmotic pressure, and (4) lymph flow. When the balance of these forces is altered, the net result is fluid accumulation in the interstitial spaces (i.e., edema). Although edema accompanies acute inflammation, a variety of noninflammatory conditions also lead to the formation of edema. For example, obstruction of venous outflow or decreased right ventricular function results in a back pressure in the vasculature, thereby increasing hydrostatic pressure. Loss of albumin (kidney disorders, this case) or decreased synthesis of plasma proteins (liver disease, malnutrition) reduces plasma oncotic pressure. Noninflammatory edema is referred to as a transudate. A transudate is edema fluid with a low protein content. An exudate (choice B) is edema fluid with a high protein and lipid concentration that frequently contains inflammatory cells. An effusion (choice A) represents excess fluid in a body cavity such as the peritoneum or pleura. Lymphedema (choice D) is usually associated with obstruction of lymphatic flow (e.g., surgery or infection). Diagnosis: Nephrotic syndrome, noninflammatory edema
A 10-year-old girl presents with a 2-week history of puffiness around her eyes and swelling of the legs and ankles. Laboratory studies show hypoalbuminemia and proteinuria. The urinary sediment contains no inflammatory cells or red blood cells. Which of the following terms describes this patient's peripheral edema? (A) Effusion (B) Exudate (C) Hydropic change (D) Lymphedema (E) Transudate
The answer is 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
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
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/μL in children and 9,000/μL in infants). The principal causes of absolute peripheral blood lymphocytosis are (1) acute viral infections (infectious mononucleosis, whooping cough, and acute infection lymphocytosis), (2) chronic bacterial infections (tuberculosis, brucellosis), and (3) lymphoproliferative diseases. The other choices are not features of acute viral infections. Diagnosis: Infectious mononucleosis
A 19-year-old woman presents with 5 days of fever (38°C/101°F) and sore throat. She reports that she has felt fatigued for the past week and has difficulty swallowing. A physical examination reveals generalized lymphadenopathy. If this patient has a viral infection, a CBC will most likely show which of the following hematologic findings? (A) Eosinophilia (B) Leukopenia (C) Lymphocytosis (D) Neutrophilia (E) Thrombocythemia
The answer is 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 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. Which of the following mediators of inflammation facilitates chemotaxis, cytolysis, and opsonization at the site of inflammation in the patient described above? (A) Complement proteins (B) Defensins (C) Kallikrein (D) Kinins (E) Prostaglandins
The answer is 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
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
The answer is E: Thromboxane A2. Platelet adherence, aggregation, and degranulation occur when platelets come in contact with fibrillar 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
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. The patient described above 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
The answer is 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 non-suppurative. 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 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 inflmmation (D) Reactive gliosis (E) Suppurative inflammation
The answer is 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 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. He goes to the emergency room to have the sliver removed. Twenty-four hours later, endothelial cells at the site of injury 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
The answer is 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
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
The answer is A: Cyclooxygenase. Arachidonic acid is metabolized by cyclooxygenases (COX-1, COX-2) and lipoxygenases (5-LOX) to generate prostanoids and leukotrienes, respectively. The early inflammatory prostanoid response is COX-1 dependent. COX-2 becomes the major source of prostanoids as inflammation progresses. Inhibition of COX is one mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, indomethacin, and ibuprofen, exert their potent analgesic and anti-inflammatory effects. NSAIDs block COX-2-induced formation of prostaglandins, thereby mitigating pain and inflammation. Myeloperoxidase (choice B) 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. Superoxide dismutase (choice E) reduces the superoxide radical to H2O2. Diagnosis: Gonococcal arthritis
A 25-year-old woman develops a sore, red, hot, swollen left knee. She has no history of trauma and no familial history of joint disease. Fluid aspirated from the joint space shows an abundance of segmented neutrophils. Aspirin is effective in relieving symptoms of acute inflammation in the patient described above because it inhibits which of the following enzymes? (A) Cyclooxygenase (B) Myeloperoxidase (C) Phospholipase A2 (D) Protein kinase C (E) Superoxide dismutase
The answer is D: Integrins. Chemokines and other proinflammatory molecules activate a family of cell adhesion molecules, namely the integrins. Molecules in this family participate in cell-cell and cell-substrate adhesions and cell signaling. Integrins are involved in leukocyte recruitment to sites of injury in acute inflammation. The other choices are extracellular matrix molecules that maintain tissue architecture and facilitate wound healing. Diagnosis: Gonococcal arthritis
A 25-year-old woman develops a sore, red, hot, swollen left knee. She has no history of trauma and no familial history of joint disease. Fluid aspirated from the joint space shows an abundance of segmented neutrophils. Transendothelial migration of acute inflammatory cells into this patient's joint space was mediated primarily by which of the following families of proteins? (A) Entactins (B) Fibrillins (C) Fibronectins (D) Integrins (E) Laminins
The answer is C: Phospholipase A2. Corticosteroids are widely used to suppress the tissue destruction associated with many chronic inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. Corticosteroids induce the synthesis of an inhibitor of phospholipase A2 and block the release of arachidonic acid from the plasma membranes of inflammatory cells. Although corticosteroids are widely used to suppress inflammatory responses, the prolonged administration of these compounds can have deleterious effects, including atrophy of the adrenal glands. Myeloperoxidase (choice B) 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. Superoxide dismutase (choice E) reduces the superoxide radical to H2O2. Diagnosis: Systemic lupus erythematosus
A 25-year-old woman presents with a 2-week history of febrile illness and chest pain. She has an erythematous, macular facial rash and tender joints, particularly in her left wrist and elbow. A CBC shows mild anemia and thrombocytopenia. Corticosteroids are prescribed for the patient. This medication induces the synthesis of an inhibitor of which of the following enzymes in inflammatory cells? (A) Lipoxygenase (B) Myeloperoxidase (C) Phospholipase A2 (D) Phospholipase C (E) Superoxide dismutase
The answer is B: Hereditary angioedema. Deficiency of C1 inhibitor, with excessive cleavage of C4 and C2 by C1s, is associated with the syndrome of hereditary angioedema. This disease is characterized by episodic, painless, non-pitting 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 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 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
The answer is 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 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
The answer is 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 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
The answer is 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 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
The answer is 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 the cytoplasm of a multinucleated giant cell, in which case the label foreign body giant cell is used. The other cells do not form multinucleated giant cells in granulomas. Diagnosis: AIDS, granulomatous 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 fi lm 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? (A) Basophils (B) Capillary endothelial cells (C) Macrophages (D) Myofibroblasts (E) Smooth muscle cells
The answer is 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 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, eosinophils
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
The answer is A: Leukemoid reaction. Circulating levels of leukocytes and their precursors may occasionally reach very high levels (>50,000 WBC/μL). Such a situation, referred to as a leukemoid reaction, is sometimes difficult to differentiate from leukemia. In contrast to bacterial infections, 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 eosinophils. Leukopenia is defined as an absolute decrease in the circulating WBC count. Myloid metaplasia (choice C) and myeloproliferative disease (choice D) are chronic disorders of the hematopoietic system. Although technically correct, neutrophilia (choice E) by itself does not demonstrate immature cells (band forms) and usually refers to lower levels of increased neutrophils. Diagnosis: Pulmonary abscess
A 40-year-old man presents with 5 days of productive cough and fever. Pseudomonas aeruginosa is isolated from a pulmonary abscess. The CBC shows an acute effect characterized by marked leukocytosis (50,000 WBC/μL), and the differential count reveals numerous immature cells (band forms). Which of the following terms best describes these hematologic findings? (A) Leukemoid reaction (B) Leukopenia (C) Myeloid metaplasia (D) Myeloproliferative disease (E) Neutrophilia
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 destructive cholangitis). PBC occurs principally in middle-aged women and is an autoimmune disease. Most patients with PBC have at least one other disease usually classed as autoimmune (e.g., thyroiditis, rheumatoid arthritis, scleroderma, Sjögren syndrome, or systemic lupus erythematosus). More than 95% of patients with PBC have circulating antimitochondrial antibodies. The cells surrounding and infiltrating the sites of bile duct damage are predominantly suppressor/cytotoxic (CD8+) T lymphocytes, suggesting that they mediate the destruction of the ductal epithelium. Macrophages and B lymphocytes (choice B) are associated with periductal inflammation but do not mediate epithelial cytotoxicity. Eosinophils (choice A) have no role in primary immune-related mechanisms. The other inflammatory cells (choices D and E) do not participate in the pathogenesis of PBC. Diagnosis: Primary biliary cirrhosis, chronic inflammation
A 40-year-old woman presents with an 8-month history of progressive generalized itching, weight loss, fatigue, and yellow sclerae. Physical examination reveals mild jaundice. The antimitochondrial antibody test is positive. A liver biopsy discloses periductal inflammation and bile duct injury (shown in the image). Which of the following inflammatory cells is the principal mediator of destructive cholangitis in this patient? (A) Eosinophils (B) B lymphocytes (C) T lymphocytes (D) Mast cells (E) Neutrophils
The answer is 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 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? (A) Acute inflammation (B) Chronic inflammation (C) Granulation tissue (D) Granulomatous inflammation (E) Menstruation
The answer is C: Complement proteins. Activation of the complement cascade by the classical or alternative pathway leads to the cleavage of complement fragments and the formation of biologically active complexes. The C5b fragment aggregates with complement proteins C6, C7, C8, and C9, resulting in the polymerization of the membrane attack complex (MAC). MAC lyses cells by inserting into the lipid bilayer, forming a pore, and destroying the permeability 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, autoimmune disease
A 45-year-old woman with autoimmune hemolytic anemia presents with increasing fatigue. Which of the following mediators of inflammation is primarily responsible for antibody-mediated hemolysis in this patient? (A) Arachidonic acid metabolites (B) Coagulation proteins (C) Complement proteins (D) Kallikrein and kinins (E) Lysophospholipids
The answer is 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 coagulation system. Although the other choices are mediators of inflammation, they have a more restricted set of functions. Diagnosis: Inflammation
A 5-year-old boy punctures his thumb with a rusty nail. Four hours later, the thumb appears red and swollen. Which of the following serum proteins activates the complement, coagulation, and fibrinolytic systems at the site of injury in the patient described above? (A) Bradykinin (B) Hageman factor (C) Kallikrein (D) Plasmin (E) Thrombin
The answer is 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
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
The answer is E: Neutropenia. The importance of protection afforded by acute inflammatory cells is emphasized by the frequency and severity of infections in persons with defective phagocytic cells. The most common defect is iatrogenic neutropenia secondary to cancer chemotherapy. Chemotherapy would not be expected to deplete serum levels of complement (choice A) or alter the respiratory burst within activated neutrophils (choice B). Diagnosis: Bacterial pneumonia
A 50-year-old woman is discovered to have metastatic breast cancer. One week after receiving her first dose of chemotherapy, she develops bacterial pneumonia. Which of the following best explains this patient's susceptibility to bacterial infection? (A) Depletion of serum complement (B) Impaired neutrophil respiratory burst (C) Inhibition of clotting factor activation (D) Lymphocytosis (E) Neutropenia
The answer is E: Granulomatous inflammation. The photograph shows a necrotizing granuloma due to M. tuberculosis. The necrotic center is surrounded by histiocytes, giant cells, and fibrous tissue. Granulomatous inflammation is elicited by fungal infections, tuberculosis, leprosy, schistosomiasis, and the presence of foreign material. It is characteristically associated with caseous necrosis produced by M. tuberculosis. The other choices may be seen as secondary features in granulomatous inflammation. Diagnosis: Pulmonary tuberculosis
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 Mycobacterium tuberculosis was documented 20 years ago, and M. tuberculosis is identified in the sputum. The patient subsequently dies of respiratory insufficiency. The lungs are examined at autopsy (shown in the image). Which of the following best characterizes the histopathologic features of this pulmonary lesion? (A) Acute suppurative inflammation (B) Chronic inflammation (C) Fat necrosis (D) Fibrinoid necrosis (E) Granulomatous inflammation
The answer is 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 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
The answer is A: Arachidonic acid. Cellular sources of vasoactive mediators are (1) derived from the metabolism of arachidonic acid (prostaglandins, thromboxanes, leukotrienes, and platelet-activating factor), (2) preformed and stored in cytoplasmic granules (histamine, serotonin, and lysosomal hydrolases), or (3) generated as normal regulators of vascular function (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 (primarily phosphatidylcholine) by stimulus-induced activation of phospholipase A2. Phospholipase A2 activation does not generate the other inflammatory mediators listed. Diagnosis: Bacterial pneumonia
A 59-year-old alcoholic man is brought to the emergency room with a fever (38.7°C/103°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 the lungs at autopsy is shown in the image. Activation of phospholipase A2 in these intra-alveolar cells resulted in the formation of which of the following mediators of inflammation? (A) Arachidonic acid (B) cAMP (C) cGMP (D) Diacylglycerol (E) Inositol trisphosphate
The answer is D: Nitric oxide. Nitric oxide (NO), which was previously known as endothelium-derived relaxing factor, leads to relaxation of vascular smooth muscle cells and vasodilation of arterioles. NO also inhibits platelet aggregation and mediates the killing of bacteria and tumor cells by macrophages. Histamine (choice B), leukotrienes (choice C), and thromboxane A2 (choice E) stimulate the contraction of smooth muscle cells. Diagnosis: Acute myocardial infarction
A 59-year-old man experiences acute chest pain and is rushed to the emergency room. Laboratory studies and ECG demonstrate an acute myocardial infarction; however, coronary artery angiography performed 2 hours later does not show evidence of thrombosis. Which of the following mediators of inflammation causes relaxation of vascular smooth muscle cells and vasodilation of arterioles at the site of myocardial infarction in the patient described in Question 39? (A) Bradykinin (B) Histamine (C) Leukotrienes (D) Nitric oxide (E) Thromboxane A2
The answer is B: Endothelial cells. The vascular endothelium has the ability to promote or inhibit tissue perfusion and inflammatory cell influx through multiple mechanisms. For example, endothelial cells in the vicinity of the thrombus produce tissue-type plasminogen activators, which activate plasmin and initiate thrombolysis (fibrinolysis). None of the other cells produce significant quantities of plasminogen activators. Diagnosis: Myocardial infarction, hemostasis
A 59-year-old man experiences acute chest pain and is rushed to the emergency room. Laboratory studies and ECG demonstrate an acute myocardial infarction; however, coronary artery angiography performed 2 hours later does not show evidence of thrombosis. Intravascular thrombolysis that occurred in this patient was mediated by plasminogen activators that were released by which of the following cells? (A) Cardiac myocytes (B) Endothelial cells (C) Macrophages (D) Segmented neutrophils (E) Vascular smooth muscle cells
The answer is 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 antigenspecific 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 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
The answer is 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 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
The answer is 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 fi brinolytic 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 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
The answer is D: Macrophages. Coal workers' pneumoconiosis reflects the inhalation of carbon particles. The characteristic pulmonary lesions of simple coal worker's pneumoconiosis include nonpalpable coal-dust macules and palpable coaldust nodules, both of which are typically multiple and scattered throughout the lung as 1- to 4-mm black foci. Nodules consist of dust-laden macrophages associated with a fibrotic stroma. Nodules occur when coal is admixed with fibrogenic dusts 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: Anthracosilicosis, coal workers' pneumoconiosis
A 68-year-old coal miner with a history of smoking and emphysema develops severe air-flow obstruction and expires. Autopsy reveals a "black lung," with coal-dust nodules scattered throughout the parenchyma and a central area of dense fibrosis. The coal dust entrapped within this miner's lung was sequestered primarily by which of the following cells? (A) Endothelial cells (B) Fibroblasts (C) Lymphocytes (D) Macrophages (E) Plasma cells
The answer is 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
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
The answer is 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 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
The answer is 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 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
The answer is 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 preformed molecules but are synthesized de novo following cell activation. Diagnosis: Asthma
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 history of wheezes associated with exercise. 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 above? (A) Bradykinin (B) Hageman factor (C) Histamine (D) Leukotrienes (SRS-A) (E) Thromboxane A2
The answer is 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
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 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
The answer is E: Tumor necrosis factor-a (TNF-a). 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
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
The answer is 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
Sputum cultures obtained from the patient described in Question 17 (the guy had bacterial pneumonia) 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
The answer is A: Acute phase proteins. These proteins are synthesized primarily by the liver and are released into the circulation in response to an acute inflammatory challenge. Changes in the plasma levels of acute phase proteins are mediated primarily by cytokines (IL-1, IL-6, and TNF-α). Increased plasma levels of some acute phase proteins are reflected in an accelerated erythrocyte sedimentation rate, which is an index used clinically to monitor the activity of many inflammatory diseases. None of the other choices describe the set of serum markers listed in this question. Diagnosis: Systemic lupus erythematosus
The patient described in Question 45 is noted to have increased serum levels of ceruloplasmin, fibrinogen, α2-macroglobulin, 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) Anaphylatoxins (C) Inhibitors of platelet activation (D) Protease inhibitors (E) Regulators of coagulation