Inflammation MCQ

*The answer is D.* 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 A.* Aspirin (acetylsalicylic acid) blocks the cyclooxygenase pathway of arachidonic acid metabolism, which leads to reduced prostaglandin generation. Prostaglandins promote vasodilation at sites of inflammation. Chemotaxis is a function of various chemokines, and complement C3b may promote phagocytosis, but neither is affected by aspirin. Leukocyte emigration is aided by various adhesion molecules. Leukocyte release from the marrow can be driven by the cytokines interleukin-1 and tumor necrosis factor.

A 10-year-old child developed a sore throat and fever over 24 hours. Physical examination shows pharyngeal erythema and swelling. Laboratory findings include leukocytosis. The child is given acetylsalicylic acid (aspirin). Which of the following features of the inflammatory response is most affected by this drug? (A) Vasodilation (B) Chemotaxis (C) Phagocytosis (D) Emigration of leukocytes (E) Release of leukocytes from bone marrow

*The answer is E.* 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.* 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.* 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 E.* (A) Incorrect. Histamine increases vascular permeability and promotes vasodilation. (B) Incorrect. Prostaglandin is more important as a mediator of inflammation in producing pain, vascular permeability, and vasodilation (C) Incorrect. Hageman factor is Factor XII of the coagulation sequence and is activated by contact with collagen and basement membrane in damaged tissues. (D) Incorrect. Bradykinin, a product of the kinin system and derived from high molecular weight kininogen, causes pain and promotes vasodilation and vascular permeability. (E) CORRECT. The C5a component of complement, along with chemokines, leukotrienes, and bacterial products, is chemotactic for neutrophils.

A 20-year-old man has experienced painful urination for 4 days. A urethritis is suspected, and Neisseria gonorrheae is cultured. Numerous neutrophils are present in a smear of the exudate from the penile urethra. These neutrophils undergo diapedesis to reach the organisms. Release of which of the following chemical mediators is most likely to drive neutrophil exudation? A Histamine B Prostaglandin C Hageman factor D Bradykinin E Complement

*The answer is C.* This patient is experiencing an acute inflammatory response, with edema, erythema, and pain of short duration. Neutrophils form an exudate and release various proteases, which can produce liquefactive necrosis, starting at the mucosa and extending through the wall of the tube. This mechanism results in perforation. Fibroblasts are more likely participants in chronic inflammatory responses and in healing responses, generally appearing more than 1 week after the initial event. Langhans giant cells are a feature of granulomatous inflammation. Mononuclear infiltrates are more typical of chronic inflammation of the fallopian tube, in which rupture is less likely. Epithelial metaplasia is most likely to occur in the setting of chronic irritation with inflammation.

A 20-year-old, sexually active woman experiences lower abdominal pain of 24 hours' duration. She has no previous history of this type of pain. Her temperature is 37.9°C, and on palpation, the left lower abdomen is markedly tender. Laboratory findings include a total WBC count of 29,000/mm3 with 75% segmented neutrophils, 6% bands, 14% lymphocytes, and 5% monocytes. Laparotomy reveals a distended, fluid-filled, reddened left fallopian tube that is about to rupture. A left salpingectomy is performed. Which of the following is most likely to be seen on microscopic examination ofthe excised fallopian tube? (A) Fibroblastic proliferation (B) Langhans giant cells (C) Liquefactive necrosis (D) Mononuclear infiltrates (E) Squamous metaplasia

*The answer is A.* 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. Examination of this breast fluid under the light microscope will most likely reveal an abundance of a particular inflammatory cell. Which of the following mediators of inflammation facilitates chemotaxis, cytolysis, and opsonization at the site of inflammation in the patient? (A) Complement proteins (B) Defensins (C) Kallikrein (D) Kinins (E) Prostaglandins

*The answer is D.* 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.* Purulent 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 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) Purulent inflammation

*The answer is C.* This patient is experiencing an acute inflammatory response, with edema, erythema, and pain of short duration. Neutrophils form an exudate and release various proteases, which can produce liquefactive necrosis, starting at the mucosa and extending through the wall of the tube. This mechanism results in perforation. Fibroblasts are more likely participants in chronic inflammatory responses and in healing responses, generally appearing more than 1 week after the initial event. Langhans giant cells are a feature of granulomatous inflammation. Mononuclear infiltrates are more typical of chronic inflammation of the fallopian tube, in which rupture is less likely. Epithelial metaplasia is most likely to occur in the setting of chronic irritation with inflammation.

A 24-year-old, sexually active woman has experienced lower abdominal pain for the past day. Her temperature is 37.9° C, and on palpation, the left lower abdomen is markedly tender. Laboratory findings include a total WBC count of 29,000/mm3 with 75% segmented neutrophils, 6% bands, 14% lymphocytes, and 5% monocytes. Laparotomy reveals a distended, fluid-filled, reddened left fallopian tube that is about to rupture. A left salpingectomy is performed. Which of the following is most likely to be seen on microscopic examination of the excised fallopian tube? A Fibroblastic proliferation B Langhans giant cells C Liquefactive necrosis D Mononuclear infiltrates E Squamous metaplasia

*The answer is E.* 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 E.* 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 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 A.* 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 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.* 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.* 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.* Deficiency of C1 inhibitor, with excessive cleavage of C4 and C2 by C1s, is 17 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 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 defi ciency (D) Selective IgA defi ciency (E) Wiskott-Aldrich syndrome

*The answer is B.* 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.* This patient has an infective endocarditis with septic embolization, producing a cerebral abscess. The tissue destruction that accompanies abscess formation as part of acute inflammatory processes occurs from lysosomal enzymatic de- struction, aided by release of reactive oxygen species. Nitric oxide generated by macrophages aids in destruction of infectious agents. Immunoglobulin formed by B cells neutralizes and opsonizes infectious agents. Prostaglandins produced by endothelium promote vasodilation. Interferon-γ released from lymphocytes plays a major role in chronic and granulo- matous inflammatory responses.

A 29-year-old woman with a congenital ventricular septal defect has had a persistent temperature of 38.6° C and headache for the past 3 weeks. A head CT scan shows an enhancing 3-cm, ring like lesion in the right parietal lobe of her brain. Which of the following actions by inflammatory cells has most likely produced this CT finding? A Elaboration of nitric oxide by macrophages B Formation of immunoglobulin by B lymphocytes C Generation of prostaglandin by endothelium D Production of interferon-γ by T lymphocytes E Release of lysosomal enzymes from neutrophils

*The answer is D.* 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 C.* Exudation of fluid from venules and capillaries is a key component of the acute inflammatory process. Several mechanisms of increased vascular permeability have been proposed, including formation of interendothelial gaps by contraction of endothelium. This is caused by mediators, such as histamine and leukotrienes. The vessels then become more "leaky," and the fluid leaves the intravascular space to accumulate extravascularly, forming effusions in body cavities or edema in tissues. Arteriolar vasoconstriction is a transient response to injury that diminishes blood loss. After neutrophils reach the site of tissue injury outside of the vascular space, they release lysosomal enzymes. Platelets adhere to damaged endothelium and promote hemostasis. Lymphatic obstruction results in the accumulation of protein-rich lymph and lymphocytes, producing a chylous effusion.

A 35-year-old man has had increasing dyspnea for the past 24 hours. A chest radiograph shows large, bilateral pleural effusions. Thoracentesis yields 500 mL of slightly cloudy yellow fluid from the right pleural cavity. Cytologic examination of the fluid shows many neutrophils, but no lymphocytes or RBCs. Which of the following mechanisms contributes most to the accumulation of the fluid in the pleural space? (A) Arteriolar vasoconstriction (B) Neutrophil release of lysosomes (C) Endothelial contraction (D) Inhibition of platelet adherence (E) Lymphatic obstruction

*The answer is B.* Exudation of fluid from venules and capillaries is a key component of the acute inflammatory process. Several mechanisms of increased vascular permeability have been proposed, including formation of interendothelial gaps by contraction of endothelium. This contraction can be caused by mediators such as histamine and leukotrienes. The vessels then become more "leaky," and the fluid leaves the intravascular space to accumulate extravascularly, forming effusions in body cavities or edema within tissues. Arteriolar vasoconstriction is a transient response to injury that helps diminish blood loss. Platelets adhere to damaged endothelium and promote hemostasis. Lymphatic obstruction results in the accumulation of protein-rich lymph and lymphocytes, producing a chylous effusion within a body cavity. After neutrophils reach the site of tissue injury outside of the vascular space, they release lysosomal enzymes that promote liquefaction.

A 35-year-old man has had increasing dyspnea for the past 24 hours. A chest radiograph shows large, bilateral pleural effusions. Thoracentesis yields 500 mL of slightly cloudy yellow fluid from the right pleural cavity. Cytologic examination of the fluid shows many neutrophils, but no lymphocytes or RBCs. Which of the following mechanisms contributes most to the pleural fluid accumulation? A Arteriolar vasoconstriction B Endothelial contraction C Inhibition of platelet adherence D Lymphatic obstruction E Neutrophil release of lysosomes

*The answer is E.* 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 B.* 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 E.* One outcome of acute inflammation with ulceration is chronic inflammation. This is particularly true when the inflammatory process continues for weeks to months. Chronic inflammation is characterized by tissue destruction, mononuclear cell infiltration, and repair. In acute inflammation, the healing process of fibrosis and angiogenesis has not begun. Serous inflammation is an inflammatory process involving a mesothelial surface (e.g., lining of the pericardial cavity), with an outpouring of fluid having little protein or cellular content. Granulomatous inflammation is a form of chronic inflammation in which epithelioid macrophages form aggregates. In fibrinous inflammation, typically involving a mesothelial surface, there is an outpouring of protein-rich fluid that results in precipitation of fibrin.

A 36-year-old man has had midepigastric abdominal pain for the past 3 months. An upper gastrointestinal endoscopy shows a 2-cm, sharply demarcated, shallow ulceration of the gastric antrum. A biopsy specimen of the ulcer base shows angiogenesis, fibrosis, and mononuclear cell infiltrates with lymphocytes, macrophages, and plasma cells. Which of the following terms best describes this pathologic process? (A) Acute inflammation (B) Serous inflammation (C) Granulomatous inflammation (D) Fibrinous inflammation (E) Chronic inflammation.

*The answer is C.* 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, strawlike 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 B.* One outcome of acute inflammation with ulceration is chronic inflammation. This is particularly true when the inflammatory process continues for weeks to months. Chronic inflammation is characterized by tissue destruc- tion, mononuclear cell infiltration, and repair. In acute inflammation, the healing process of fibrosis and angio- genesis has not begun. In fibrinous inflammation, typically involving a mesothelial surface, there is an outpouring of protein-rich fluid that results in precipitation of fibrin. Granulomatous inflammation is a form of chronic inflammation in which epithelioid macrophages form aggregates. Serous inflammation is an inflammatory process involving a mesothelial surface (e.g., lining of the pericardial cavity), with an outpouring of fluid having little protein or cellular content.

A 37-year-old man has had midepigastric pain for the past 3 months. An upper gastrointestinal endoscopy shows a 2-cm, sharply demarcated, shallow ulceration of the gastric antrum. Microscopic examination of a biopsy from the ulcer base shows angiogenesis, fibrosis, and mononuclear cell infiltrates with lymphocytes, macrophages, and plasma cells. Which of the following terms best describes this pathologic process? A Acute inflammation B Chronic inflammation C Fibrinous inflammation D Granulomatous inflammation E Serous inflammation

*The answer is E.* An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue.

A 37-year-old man has had nausea and vomiting for 5 weeks. He experienced an episode of hematemesis yesterday. On physical examination he has no abnormal findings. Upper GI endoscopy is performed, and there is a 1.5 cm diameter lesion in the gastric antrum with loss of the epithelial surface. These findings are most typical for which of the following pathologic processes? A Abscess B Serositis C Granuloma D Gangrene E Ulcer

*The answer is C.* 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 E.* Nonhuman microbial substances such as double- stranded RNA of viruses, bacterial DNA, and bacterial en- dotoxin, can be recognized by Toll-like receptors (TLRs) on human cells as part of an innate defense mechanism against infection. Caspase-1 is activated by an inflammasome complex of proteins responding to bacterial organisms, and pro- duces biologically active interleukin-1 (IL-1). Complement receptors on inflammatory cells recognize complement components that aid in triggering immune responses through co-stimulatory signals. Lectins found on cell surfaces can bind a variety of substances, such as fungal polysaccharides, that trigger cellular defenses. T cell receptors respond to peptide antigens to trigger a cell-mediated immune response

A 4-year-old child has had a high-volume diarrhea for the past 2 days. On examination she is dehydrated. A stool sample examined by serologic assay is positive for rotavirus. She is treated with intravenous fluids and recovers. Which of the following components is found on intestinal cells and recognizes double-stranded RNA of this virus to signal transcription factors that upregulate interferon production for viral elimination? A Caspase-1 B Complement receptor C Lectin D T cell receptor E Toll-like receptor

*The answer is C.* 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 E.* Fever is produced by various inflammatory mediators, but the major cytokines that produce fever are interleukin-1 (IL-1) and tumor necrosis factor (TNF), which are produced by macrophages and other cell types. IL-1 and TNF can have autocrine, paracrine, and endocrine effects. They mediate the acute phase responses, such as fever, nausea, and neutrophil release from bone marrow. Bradykinin, generated from the kinin system on surface contact of Hageman factor with collagen and basement membrane from vascular injury, promotes vascular permeability, smooth muscle contraction, and pain. Histamine released from mast cells is a potent vasodilator, increasing vascular permeability. Leukotriene B4, generated in the lipoxygenase pathway of arachidonic acid metabolism, is a potent neutrophil chemotactic factor. Nitric oxide generated by macro- phages aids in destruction of microorganisms; nitric oxide released from endothelium mediates vasodilation and inhibits platelet activation.

A 41-year-old man has had a severe headache for the past 2 days. On examination, his temperature is 39.2° C. A lumbar puncture is performed, and the cerebrospinal fluid obtained has a WBC count of 910/mm3 with 94% neutrophils and 6% lymphocytes. Which of the following substances is the most likely mediator for the fever observed in this man? A Bradykinin B Histamine C Leukotriene B4 D Nitric oxide E Tumor necrosis factor (TNF)

*The answer is B.* 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 B.* This acute inflammatory process leads to production of acute-phase reactants, such as C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein. These proteins, particularly fibrinogen, and immunoglobulins increase red blood cell rouleaux formation to increase sedimentation, which is a nonspecific indicator of inflammation. CRP productionis up-regulated by interleukin-6, whereas fibrinogen and SAA are up-regulated mainly by tumor necrosis factor and interleukin-1. Interferon-γ is a potent stimulator of macrophages. Nitric oxide can induce vasodilation or can assist in microbial killing within macrophages. Prostaglandins are vasodilators.

A 43-year-old man has had a cough and fever for the past 2 days. On examination, he has a temperature of 37.6°C. A blood culture grows Streptococcus, viridans group. His erythrocyte sedimentation rate (ESR) is increased. Microbial cells are opsonized and cleared. Which of the following chemical mediators is most important in producing these findings? (A) Bradykinin (B) C-reactive protein (C) Interferon-γ (D) Nitric oxide (E) Prostaglandin (F) Tumor necrosis factor

*The answer is C.* Figure A shows diffuse reticulonodular pulmonary densities, and Figure B shows noncaseating granulomas with many epithelioid cells and two prominent large Langhans giant cells. If special stains and/or cultures for organisms (usually mycobacteria or fungi) are negative, then this is likely sarcoidosis. Macrophage stimulation and transformation to epithelioid cells and giant cells are characteristic of granuloma formation. Interferon-γ promotes the formation of epithelioid cells and giant cells. Bradykinin is released in acute inflammatory responses and results in pain. Complement C5a is chemotactic for neutrophils. Although occasional neutrophils are seen in granulomas, neutrophils do not form a major component of granulomatous inflammation. Macrophages can release nitric oxide to destroy other cells, but nitric oxide does not stimulate macrophages to form a granulomatous response. Prostaglandins are mainly involved in the causation of vasodilation and pain in acute inflammatory responses.

A 43-year-old man has had a cough and fever for the past 2 months. A chest CT scan shows the findings in the figure (A). A transbronchial lung biopsy is performed, yielding a specimen with the microscopic appearance shown in the figure (B). Which of the following chemical mediators is most important in the pathogenesis of this lesion? A Bradykinin B Complement C5a C Interferon-γ D Nitric oxide E Prostaglandins

*The answer is B.* This acute inflammatory process leads to production of acute-phase reactants, such as C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein. These proteins, particularly fibrinogen, and immunoglobulins increase RBC rouleaux formation to increase the erythrocyte sedimentation rate (ESR), which is a nonspecific indicator of inflammation. CRP production is upregulated by interleukin-6 (IL-6), whereas fibrinogen and SAA are upregulated mainly by tumor necrosis factor (TNF) and interleukin-1 (IL-1). Interferon-γ is a potent stimulator of macrophages. Nitric oxide can induce vasodilation or can assist in microbial killing within macro- phages. Prostaglandins are vasodilators.

A 43-year-old man with a ventricular septal defect has had a cough and fever for the past 2 days. On examination, he has a temperature of 37.6° C and a cardiac murmur. A blood culture grows Streptococcus, viridans group. His erythrocyte sedimentation rate (ESR) is increased. Microbial cells are opsonized and cleared. Which of the following chemical mediators is most important in producing these findings? A Bradykinin B C-reactive protein C Interferon-γ D Nitric oxide E Prostaglandin F Tumor necrosis factor (TNF)

*The answer is A.* (A) CORRECT. Epithelioid cells and giant cells are derived from activated macrophages. Tissue macrophages are derived from blood monocytes. These cells are important in the development of granulomatous inflammation in the adaptive immune response to tuberculosis. (B) Incorrect. Although collagen is laid down around a granuloma as part of the response, it is not the major component involved in granuloma formation. (C) Incorrect. Although some neutrophils may be present in a granuloma, they are not the major contributors to granuloma formation (D) Incorrect. Mast cells are few in number. They are involved in release of mediators primarily in acute inflammatory responses. (E) Incorrect. Platelets are mainly involved in coagulation.

A 43-year-old woman has had a chronic cough with fever and weight loss for the past month. A chest radiograph reveals multiple nodules from 1 to 4 cm in size, some of which demonstrate cavitation in the upper lobes. A sputum sample reveals the presence of acid fast bacilli. Which of the following cells is the most important in the development her lung lesions? A Macrophage B Fibroblast C Neutrophil D Mast cell E Platelet

*The answer is C.* 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 C.* 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 B.* 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? (A) Bradykinin (B) Hageman factor (C) Kallikrein (D) Plasmin (E) Thrombin

*The answer is C.* Serous inflammation is the mildest form of acute inflammation. A blister is a good example of serous inflammation. It is associated primarily with exudation of fluid into the subcorneal or subepidermal space. Because the injury is mild, the fluid is relatively protein-poor. A protein-rich exudate results in fibrin accumulation. Acute inflammatory cells, mainly neutrophils, exuded into a body cavity or space form a purulent (suppurative) exudate, typically associated with liquefactive necrosis. Loss of the epithelium leads to ulceration. Granulomatous inflammation is characterized by collections of transformed macrophages called epithelioid cells.

A 5-year-old child reaches up to the stove and touches a pot of boiling soup. Within several hours, there is marked erythema of the skin of the fingers on the child's right hand, and small blisters appear on the finger pads. Which of the following terms best describes this process? (A) Fibrinous inflammation (B) Purulent inflammation (C) Serous inflammation (D) Ulceration (E) Granulomatous inflammation

*The answer is E.* 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.* 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 F.* Inflammation involving an epithelial surface may cause such extensive necrosis that the surface becomes eroded, forming an ulcer. If the inflammation continues, the ulcer can continue to penetrate downward into submucosa and muscularis. Alternatively, the ulcer may heal, or it may remain chronically inflamed. An abscess is a localized collection of neutrophils in tissues. A caseating granuloma is granulomatous inflammation with central necrosis; the necrosis has elements of both liquefaction and coagulative necrosis. Chronic inflammation occurs when there is a preponderance of mononuclear cells, such as lymphocytes, macrophages, and plasma cells, in a process that has gone on for more than a few days—more likely weeks or months—or that accompanies repeated bouts of acute inflammation. Pus, or a purulent exudate, appears semiliquid and yellowish because of the large numbers of granulocytes present. A serous effusion is a watery-appearing transudate that resembles an ultrafiltrate of blood plasma, with a low cell and protein content.

A 53-year-old woman has experienced abdominal pain for 2 weeks. She is afebrile. There is mild upper abdominal tenderness on palpation, and bowel sounds are present. An upper gastrointestinal endoscopy is performed. The figure shows microscopic examination of a biopsy specimen of a duodenal lesion. Which of the following pathologic processes is most likely present? A Abscess B Caseating granuloma C Chronic inflammation D Purulent exudate E Serous effusion F Ulceration

*The answer is D.* These signs and symptoms suggest acute bacterial pneumonia. Such infections induce an acute inflammation dominated by neutrophils that fill alveoli, as shown in the figure, and are coughed up, which gives the sputum its yellowish, purulent appearance. Langhans giant cells are seen with granulomatous inflammatory responses. Macrophages become more numerous after initiation of acute events, cleaning up tissue and bacterial debris through phagocytosis. Mast cells are better known as participants in allergic and anaphylactic responses. Lymphocytes are a feature of chronic inflammation.

A 53-year-old woman has had a high fever and cough productive of yellowish sputum for the past 2 days. Her vital signs include temperature of 37.8° C, pulse 103/min, respirations 25/min, and blood pressure 100/60 mm Hg. On auscultation of the chest, crackles are audible in both lung bases. A chest radiograph shows bilateral patchy pulmonary infiltrates. The microscopic appearance of her lung is shown in the figure. Which of the following inflammatory cell types is most likely to be seen in greatly increased numbers in her sputum specimen? A Langhans giant cells B Macrophages C Mast cells D Neutrophils E T lymphocytes

*The answer is B.* The patient's signs and symptoms suggest acute bacterial pneumonia. Such infections induce an acute inflammation dominated by neutrophils, which gives the sputum its yellowish, purulent appearance. Macrophages become more numerous after acute events, cleaning up tissue and bacterial debris through phagocytosis. Mast cells are better known as participants in allergic and anaphylactic responses. Lymphocytes are a feature of chronic inflammation. Langhans giant cells are seen with granulomatous inflammatory responses.

A 53-year-old woman has had a high fever and cough productive of yellowish sputum for the past 2 days. Her vital signs include temperature of 37.8°C, pulse of 83/min, respirations of 17/min, and blood pressure of 100/60 mm Hg. On auscultation of the chest, crackles are audible in both lung bases. A chest radiograph shows bilateral patchy pulmonary infiltrates and fluid in the right pleural cavity. Thoracentesis yields 500 mL of cloudy yellow fluid. Which of the following inflammatory cell types is most likely to be seen in greatly increased numbers in a sputum specimen? (A) Macrophages (B) Neutrophils (C) Mast cells (D) Small lymphocytes (E) Langhans giant cells

*The answer is C.* 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 D.* 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 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 A.* 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 intraalveolar 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 B.* 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.* 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? (A) Bradykinin (B) Histamine (C) Leukotrienes (D) Nitric oxide (E) Thromboxane A2

*The answer is D.* 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 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.* Exudation of fluid from venules and capillaries is a key component of the acute inflammatory process. Several mechanisms of increased vascular permeability have been proposed, including formation of interendothelial gaps by contraction of endothelium. This contraction can be caused by mediators such as histamine and leukotrienes. The vessels then become more "leaky," and the fluid leaves the intravascular space to accumulate extravascularly, forming effusions in body cavities or edema within tissues. Arteriolar vasocon- striction is a transient response to injury that helps diminish blood loss. Platelets adhere to damaged endothelium and promote hemostasis. Lymphatic obstruction results in the ac-cumulation of protein-rich lymph and lymphocytes, producing a chylous effusion within a body cavity. After neutrophils reach the site of tissue injury outside of the vascular space, they release lysosomal enzymes that promote liquefaction.

A 6-year-old child has a history of recurrent infections with pyogenic bacteria, including Staphylococcus aureus and Streptococcus pneumoniae. The infections are accompanied by a neutrophilic leukocytosis. Microscopic examination of a biopsy specimen obtained from an area of soft tissue necrosis shows microbial organisms, but very few neutrophils. An analysis of neutrophil function shows a defect in rolling. This child's increased susceptibility to infection is most likely caused by a defect involving which of the following molecules? A Complement C3b B Integrins C Leukotriene B4 D NADPH oxidase E Selectins

*The answer is B.* 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.

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 A.* Macrophages, present in such lesions, play a prominent role in the healing process. Activated macrophages can secrete various cytokines that promote angiogenesis and fibrosis, including platelet-derived growth factor, fibroblast growth factor, interleukin-1, and tumor necrosis factor. Plasma cells can secrete immunoglobulins and are not instrumental to healing of an area of tissue injury. Neutrophils are most numerous within the initial 48 hours after infarction, but are not numerous after the first week. Eosinophils are most prominent in allergic inflammations and in parasitic infections. Epithelioid cells, which are aggregations of activated macrophages, are typically seen with granulomatous inflammation. The healing of acute inflammatory processes does not involve granulomatous inflammation.

A 63-year-old man develops worsening congestive heart failure 2 weeks after an acute myocardial infarction. An echocardiogram shows a markedly decreased ejection fraction. He dies 1 day later. At autopsy, a section of the infarct shows that the necrotic myocardium has largely been replaced by capillaries, fibroblasts, and collagen. Various inflammatory cells are present. Which of the following inflammatory cell types in this lesion plays the most important role in the healing process? (A) Macrophages (B) Plasma cells (C) Neutrophils (D) Eosinophils (E) Epithelioid cells

*The answer is C.* Macrophages, present in such lesions, play a prominent role in the healing process. Activated macrophages can secrete various cytokines that promote angiogenesis and fibrosis, including platelet-derived growth factor, fibroblast growth factor, interleukin-1 (IL-1), and tumor necrosis factor (TNF). Eosinophils are most prominent in allergic inflammations and in parasitic infections. Epithelioid cells, which are aggregations of activated macrophages, are typically seen with granulomatous inflammation, and the healing of acute inflammatory processes does not involve granulomatous inflammation. Neutrophils are most numerous within the initial 48 hours after infarction, but are not numerous after the first week. Plasma cells can secrete immunoglobulins and are not instrumental to healing of an area of tissue injury.

A 65-year-old man develops worsening congestive heart failure 2 weeks after an acute myocardial infarction. An echocardiogram shows a markedly decreased ejection fraction. Now, capillaries, fibroblasts, collagen, and inflammatory cells have largely replaced the infarcted myocardium. Which of the following inflammatory cell types in this lesion plays the most important role in the healing process? A Eosinophils B Epithelioid cells C Macrophages D Neutrophils E Plasma cells

*The answer is D.* 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 coal- dust 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-fl ow 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 E.* Bacterial infections often evoke an acute inflammatory response dominated by neutrophils. The extravasated neutrophils attempt to phagocytose and kill the bacteria. In the process, some neutrophils die, and the release of their lysosomal enzymes can cause liquefactive necrosis of the tissue. This liquefied tissue debris and both live and dead neutrophils comprise pus, or purulent exudate. Such an exudate is typical of bacterial infections that involve body cavities. Another term for purulent exudate in the pleural space is empyema. An abscess is a localized collection of neutrophils within tissues. Chronic inflammation occurs when there is a preponderance of mononuclear cells, such as lymphocytes, macrophages, and plasma cells, in a process that has gone on for more than a few days—more likely weeks or months—or that accompanies repeated bouts of acute inflammation. Edema refers to increased cellular and interstitial fluid collection within tissues, leading to tissue swelling. In fibrinous inflammation, exudation of blood proteins (including fibrinogen, which polymerizes to fibrin) gives a grossly shaggy appearance to surfaces overly- ing the inflammation. A serous effusion is a watery-appearing transudate that resembles an ultrafiltrate of blood plasma, with a low cell and protein content.

A 68-year-old man has had worsening shortness of breath for the past week. On physical examination, his temperature is 38.3° C. On percussion, there is dullness over the left lung fields. Thoracentesis performed on the left pleural cavity yields 800 mL of cloudy yellow fluid that has a WBC count of 2500/mm3 with 98% neutrophils and 2% lymphocytes. A Gram stain of the fluid shows gram-positive cocci in clusters. Which of the following terms best describes the process occurring in his left pleural cavity? A Abscess B Chronic inflammation C Edema D Fibrinous inflammation E Purulent exudate F Serous effusion

*The answer is E.* 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

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. Sputum cultures obtained from the patient described 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 B.* 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 E.* 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

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 primarily responsible for secondary injury to alveolar basement membranes and lung parenchyma in the patient described? (A) Complement proteins (B) Fibrin split products (C) Immunoglobulins (D) Interleukin-1 (E) Lysosomal enzymes

*The answer is B.* 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 E.* The formation of an exudate containing a significant amount of protein and cells depends on the "leakiness" of blood vessels, principally venules. When exudation has occurred, the protein content of the extravascular space increases, and extravascular colloid osmotic pressure increases, causing extracellular fluid accumulation. Leukocytosis alone is insufficient for exudation because the leukocytes must be driven to emigrate from the vessels by chemotactic factors. The lymphatics scavenge exuded proteinaceous fluid and reduce the amount of extravascular and extracellular fluid. Sodium and water retention helps drive transudation of fluid.

A 72-year-old man with severe emphysema has had worsening right ventricular failure for the past 5 years. For the past 4 days, he has had fever and increasing dyspnea. A chest radiograph shows an accumulation of fluid in the pleural spaces. Fluid obtained by thoracentesis has a specific gravity of 1.030 and contains degenerating neutrophils. The most likely cause of this fluid accumulation is due to changes in which of the following? A Colloid osmotic pressure B Leukocytic diapedesis C Lymphatic pressure D Renal sodium retention E Vascular permeability

*The answer is C.* 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 B.* Endothelial cells can release nitric oxide to produce vasodilation. Nitric oxide also can be administered to patients to promote vasodilation in areas of ischemic injury. Thromboxane A2, platelet-activating factor, and leukotriene E4 have vasoconstrictive properties.

A 78-year-old woman experiences a sudden loss of consciousness, with loss of movement on the right side of the body. Cerebral angiography shows an occlusion of the left middle cerebral artery. To prevent further ischemic injury to the cerebral cortex, which of the following mediators would be most beneficial? (A) Thromboxane A2 (B) Nitric oxide (C) Leukotriene E4

*The answer is C.* Macrophages in tissues derived from circulating blood monocytes are phagocytic cells that respond to a variety of stimuli, and they represent the janitorial crew of the body. The other cells listed are not phagocytes. B cells can differentiate into plasma cells secreting antibodies to neutralize infectious agents. Fibroblasts form collagen as part of a healing response. Mast cells can release a variety of inflammatory mediators. T cells are a key part of chronic inflammatory processes in cell-mediated immune responses.

An 11-year-old child falls and cuts his hand. The wound becomes infected. Bacteria extend into the extracellular matrix around capillaries. In the inflammatory response to this infection, which of the following cells removes the bacteria? A B lymphocyte B Fibroblast C Macrophage D Mast cell E T lymphocyte

*The answer is D.* Interferon-γ is secreted by activated T cells and is an important mediator of granulomatous inflammation. It causes activation of macrophages and their transformation into epithelioid cells and then giant cells. Tumor necrosis factor can be secreted by activated macrophages and induces activation of lymphocytes and proliferation of fibroblasts, which are other elements of a granuloma. Complement C3b acts as an opsonin in acute inflammatory reactions. Leukotriene B4 induces chemotaxis in acute inflammatory processes. Interleukin-1 can be secreted by macrophages to produce various effects, including fever, leukocyte adherence, fibroblast proliferation, and cytokine secretion.

A 9-year-old boy has had a chronic cough and fever for the past month. A chest radiograph shows enlargement of hilar lymph nodes and bilateral pulmonary nodular interstitial infiltrates. A sputum sample contains acid fast bacilli. A transbronchial biopsy specimen shows granulomatous inflammation within the lung, marked by the presence of Langhans giant cells. Which of the following mediators is most likely to contribute to giant cell formation? (A) Tumor necrosis factor (B) Complement C3b (C) Leukotriene B4 (D) Interferon-γ (E) Interleukin-1

*The answer is B.* Interferon-γ is secreted by activated T cells and is an important mediator of granulomatous inflammation. It causes activation of macrophages and their transformation into epithelioid cells and then giant cells. Complement C3b acts as an opsonin in acute inflammatory reactions. Interleukin-1 (IL-1) can be secreted by macrophages to produce various effects, including fever, leukocyte adherence, fibroblast proliferation, and cytokine secretion. Leukotriene B4 induces chemotaxis in acute inflammatory processes. Tumor necrosis factor (TNF) can be secreted by activated macrophages and induces activation of lymphocytes and proliferation of fibroblasts, which are other elements of a granuloma.

A 9-year-old boy has had a chronic cough and fever for the past month. A chest radiograph shows enlargement of hilar lymph nodes and bilateral pulmonary nodular interstitial infiltrates. A sputum sample contains acid-fast bacilli. A transbronchial biopsy specimen shows granulomatous inflammation with epithelioid macrophages and Langhans giant cells. Which of the following mediators is most likely to contribute to giant cell formation? A Complement C3b B Interferon-γ C Interleukin-1 (IL-1) D Leukotriene B4 E Tumor necrosis factor (TNF)

*The answer is A.* A. CORRECT. The formation of a fluid filled cavity following an infection with S. aureus suggests that liquefactive necrosis has occurred. The cavity is filled with tissue debris and viable and dead neutrophils (pus). Localized, pus filled cavities are called abscesses. The liquified contents seek a level (air-fluid level). B. Incorrect. The inflammation continues, she still has fever and an abnormal chest x-ray C. Incorrect. Neoplasia is not a consequence of acute inflammatory processes. D. Incorrect. Granulomas can become large and cavitate from central caseous necrosis. However, this process takes months. In this case, acute inflammation was complicated by abscess formation with liquefactive necrosis. The most common organism causing pulmonary granulomas is Mycobacterim tuberculosis.

A 94-year-old woman has developed a fever and cough over the past 2 days. Staphylococcus aureus is cultured from her sputum. She receives a course of antibiotic therapy. Two weeks later she no longer has a productive cough, but she still has a fever. A chest radiograph reveals a 3 cm rounded density in the right lower lobe whose liquefied contents form a central air-fluid level. There are no surrounding infiltrates. Which of the following is the best description for this outcome of her pneumonia? A. Abscess formation B. Resolution C. Bronchogenic carcinoma D. Chronic inflammation E. Granulomatous cavitation

*The answer is D.* Serous inflammation is the mildest form of acute in- flammation. A blister is a good example of serous inflammation. It is associated primarily with exudation of fluid into the subcorneal or subepidermal space. Because the injury is mild, the fluid is relatively protein-poor. A protein-rich exudate results in fibrin accumulation. Granulomatous inflammation is characterized by collections of transformed macrophages called epithelioid cells. Acute inflammatory cells, mainly neutrophils, exuded into a body cavity or space form a purulent (suppurative) exudate, typically associated with liquefactive necrosis. Loss of the epithelium leads to ulceration.

A 95-year-old woman touches a pot of boiling water. Within 2 hours, she has marked erythema of the skin of the fingers of her hand, and small blisters appear on the finger pads. This has led to which one of the following inflammatory responses? A Fibrinous inflammation B Granulomatous inflammation C Purulent inflammation D Serous inflammation E Ulceration

*The answer is B.* (A) Incorrect. Granulomatous inflammation typically pursues a course over months to years, and the most important inflammatory cell is an activated macrophage. B) CORRECT. The short course of days and the purulent exudate are typical features of acute inflammation with a neutrophilic response, most often caused by a bacterial organisms such as group A Streptococcus. Lacking evidence for an acute bacterial infection, avoid use of antibiotics. (C) Incorrect. Gangrene refers to extensive inflammation with necrosis involving a whole organ or body part. (D) Incorrect. With complete resolution, the purulent exudate should be removed, and the course to this point would probably be longer. The process may resolve to an abscess, become more chronic, or lead to scarring (E) Incorrect. Chronic inflammation generally pursues a course of weeks. Purulent exudate is not typical for chronic inflammation, where the predominant cell types are mononuclears: lymphocytes, monocyte-macrophages, plasma cells.

A clinical study is performed of patients with pharyngeal infections. The most typical clinical course averages 3 days from the time of onset until the patient sees the physician. Most of these patients experience fever and chills. On physical examination, the most common findings include swelling, erythema, and pharyngeal purulent exudate. Which of the following types of inflammation did these patients most likely have? A Granulomatous B Acute C Gangrenous D Resolving E Chronic

*The answer is A.* 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

A patient 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

*The answer is E.* The findings here are those of strep throat with acute inflammation. Bacterial organisms often lead to fever accompanying infection through release of exogenous pyrogens that induce inflammatory cells to release endogenous pyro- gens such as tumor necrosis factor (TNF) and interleukin-1 (IL-1). The pyrogens stimulate prostaglandin synthesis in the hypothalamus to "reset the thermostat," so that fever occurs as a sign of the acute inflammatory response. Hageman factor initiates the coagulation cascade. Immunoglobulin E is often increased in response to inflammatory responses with allergens and with invasive parasites. Interleukin-12 (IL-12) released by macrophages stimulates T-cell responses. Nitric oxide generated in endothelium leads to vasodilation, where- as nitric oxide produced in macrophages aids in microbial killing.

An 8-year-old girl has had difficulty swallowing for the past day. On examination, her pharynx is swollen and erythematous with an overlying yellow exudate. Laboratory studies show neutrophilia. Streptococcus pyogenes (group A streptococcus) is cultured from her pharynx. Which of the following substances is most likely to increase in response to pyrogens released by this organism? A Hageman factor B Immunoglobulin E C Interleukin-12 (IL-12) D Nitric oxide E Prostaglandins

*The answer is D.* 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.* Septicimia (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 D.* If inflammation is limited and brief, and the involved tissue can regenerate, then resolution is the likely outcome, without significant loss of function. In older persons this may take longer, but can still occur. Multiple bouts of acute inflammation, or ongoing inflammation, can become chronic, and there tends to be loss of some tissue function. If significant tissue destruction occurs, there is likely to be formation of a fibrous scar in the region of the tissue loss. Acute inflammation is not a preneoplastic event. Ulceration refers to loss of an epithelial surface with acute inflammation; if the epithelium regenerates, then there is resolution.

An 87-year-old woman has had a cough productive of yellowish sputum for the past 2 days. On examination her temperature is 37° C. A chest radiograph shows bilateral patchy infiltrates. Her peripheral blood shows leukocytosis. A week later she is afebrile. Which of the following is the most likely outcome of her pulmonary disease? A Chronic inflammation B Fibrous scarring C Neoplasia D Resolution E Ulceration

*The answer is B.* Chemokines include many molecules that are chemotactic for neutrophils, eosinophils, lymphocytes, monocytes,and basophils. Bradykinin causes pain and increased vascular permeability. Histamine causes vascular leakage, and prostaglandins have multiple actions, but do not cause chemotaxis. Complement C3a causes increased vascular permeability by releasing histamine from mast cells.

An experiment introduces bacteria into a perfused tissue preparation. Leukocytes leave the vasculature and migrate to the site of bacterial inoculation. The movement of these leukocytes is most likely to be mediated by which of the following substances? (A) Bradykinin (B) Chemokines (C) Histamine (D) Prostaglandins (E) Complement C3a

*The answer is B.* 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

Endothelial cells ata 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 G.* Fever is produced by various inflammatory mediators, but the major cytokines that produce fever are interleukin-1 (IL-1) and tumor necrosis factor (TNF), which are produced by macrophages and other cell types. They mediate the acute phase responses, such as fever, nausea, and neutrophil release from marrow. Bradykinin, generated from the kinin system on surface contact of Hageman factor with collagen and basement membrane from vascular injury, promotes vascular permeability, smooth muscle contraction, and pain. Leukotriene B4, generated in the lipoxygenase pathway of arachidonic acid metabolism, is a potent neutrophil chemotactic factor. Histamine released from mast cells is a potent vasodilator, increasing vascular permeability. Myeloperoxidase is contained within the azurophilic granules of neutrophils and in the presence of halide converts hydrogen peroxide to HOCl−, which destroys phagocytized organisms by halogenation. Nitric oxide generated by macrophages aids in destruction of microorganisms; nitric oxide released from endothelium mediates vasodilation.

For the past 2 days, a 41-year-old man has had a severe headache, and he now has a temperature of 39.2°C. A lumbar puncture is performed, and the cerebrospinal fluid obtained has a very high WBC count with 94% neutrophils and 6% lymphocytes. Which of the following substances is the most likely mediator for the fever observed in this patient? (A) Bradykinin (B) Leukotriene B4 (C) Histamine (D) Myeloperoxidase (E) Nitric oxide (F) Tumor necrosis factor (G) IL-1 and TNF

*The answer F.* The COX-2 enzyme is inducible with acute inflammatory reactions. The cyclooxygenase pathway of arachidonic acid metabolism generates prostaglandins, which mediate pain, fever, and vasodilation. Ankle swelling is most likely to result from peripheral edema secondary to congestive heart failure. Asthma results from bronchoconstriction mediated by leukotrienes that are generated by the lipoxygenase pathway of arachidonic acid metabolism. Easy bruisability results from prolonged glucocorticoid administration, which also causes leukopenia. Inhibition of histamine released from mast cells helps reduce urticaria. Fever can be mediated by prostaglandin release, not inhibition.

In a 6-month randomized trial of a pharmacologic agent, one group of patients receives a cyclooxygenase-2 (COX-2) inhibitor, and a control group does not. Laboratory measurements during the trial show no significant differences between the groups in WBC count, platelet count, hemoglobin, and creatinine. The group receiving the drug reports subjective findings different from those of the control group, however. Which of the following findings was most likely reported by the group receiving the drug? (A) Ankle swelling (B) Increased bouts of asthma (C) Easy bruisability (D) Reduced urticaria (E) Increased febrile episodes (F) Reduced arthritis pain

*The answer is B.* Chemokines include many molecules that are chemotactic for neutrophils, eosinophils, lymphocytes, monocytes, and basophils. Bradykinin causes pain and increased vascular permeability. Complement C3a causes increased vascular permeability by releasing histamine from mast cells. Histamine causes vascular leakage. Prostaglandins have multiple actions, but they do not cause chemotaxis.

In an experiment, bacteria are introduced into a perfused tissue preparation. Leukocytes leave the vasculature and migrate to the site of bacterial inoculation. The movement of these leukocytes is most likely to be mediated by which of the following substances? A Bradykinin B Chemokines C Complement C3a D Histamine E Prostaglandins

*The answer is E.* The respiratory burst is an essential step for the generation of microbicidal activity.

In an experiment, neutrophils collected from peripheral blood are analyzed for a "burst" of oxygen consumption. This respiratory burst is an essential step for which of the following events in an acute inflammatory response? (A) Increased production in bone marrow (B) Attachment to endothelial cells (C) Opsonization of bacteria (D) Phagocytosis of bacteria (E) Generation of microbicidal activity

*The answer is D.* The polarizable material is the suture, and a multinucleated giant cell reaction, typically with foreign body giant cells, is characteristic of a granulomatous reaction to foreign material. Granulation tissue may form a nodular appearance, and begins to appear 3 to 5 days following injury, but is unlikely to persist for a month. Chronic inflammation alone is unlikely to produce a localized nodule with giant cells. Edema refers to accumulation of fluid in the intersti- tial space. It does not produce a cellular nodule. If a large, gaping wound is not closed by sutures, it can granulate it and myofibroblastic contraction eventually helps close the wound by second intention.

One month after an appendectomy, a 25-year-old woman palpates a small nodule beneath the skin at the site of the healed right lower quadrant sutured incision. The nodule is excised, and microscopic examination shows macrophages, collagen deposition, small lymphocytes, and multinucleated giant cells. Polarizable, refractile material is seen in the nodule. Which of the following complications of the surgery best accounts for these findings? A Abscess formation B Chronic inflammation C Exuberant granulation tissue D Granuloma formation E Healing by second intention

*The answer is C.* 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

Which of the following preformed substances is released from mast cells and platelets, resulting in increased vascular permeability in the lungs? (A) Bradykinin (B) Hageman factor (C) Histamine (D) Leukotrienes (SRS-A) (E) Thromboxane A2

*The answer is D.* 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 fi brinolysis, 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