Rubin's Chapter 2

Question 1

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 fl uid under the light microscope will most likely reveal an abundance of which of the following inflammatory cells?

Answer 1

Neutrophils: thick, yellow fluid draining
from the breast fi ssure 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 infl ammation and provide antigen-specific immunity to infectious diseases

Question 2

Which of the following mediators of infl
ammation facilitates
chemotaxis, cytolysis, and opsonization at the site of inflammation in the patient described in Question 1? (Question 1: 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.)

Answer 2

Complement proteins.
Complement proteins act upon one another in a cascade, generating biologically active fragments (e.g., C5a, C3b) or complexes (e.g., C567). These products of complement activation cause local edema by increasing the permeability of blood vessels. They also
promote chemotaxis of leukocytes and lyse cells (membrane attack complex) and act as opsonins by coating bacteria. Although the other choices are mediators of inflammation,
they have a more restricted set of functions. Kinins (choice D) are formed following tissue trauma and mediate pain
transmission. None of the other choices are involved in opsonization or cytolysis

Question 3

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 infl ammation provides potent chemotactic factors for the directed migration of inflammatory cells into the alveolar air spaces of this patient?

Answer 3

N-formylated peptides. The most potent
chemotactic factors for leukocytes at the site of injury are (1) complement proteins (e.g., C5a); (2) bacterial and mitochondrial products, particularly low molecular weight N-formylated peptides; (3) products of arachidonic acid
metabolism (especially LTB4); and (4) chemokines (e.g., interleukin-1 and interferon-γ). Plasmin (choice E) is a fibrinolytic enzyme generated by activated Hageman factor
(clotting factor XII). Histamine (choice B) is one of the primary mediators of increased vascular permeability. None of the other choices are chemotactic agent

Question 4

A 59-year-old man suffers a massive heart attack and expires 24 hours later due to ventricular arrhythmia. Histologic exam-
ination of the affected heart muscle at autopsy would show an abundance of which of the following inflammatory cells?

Answer 4

Neutrophils: during acute inflammation,
neutrophils (PMNs) adhere to the vascular endothelium. They flatten and migrate from the vasculature, through the endothelial cell layer, and into the surrounding tissue. About
24 hours after the onset of infarction, PMNs are observed to infiltrate necrotic tissue at the periphery of the infarct. Their function is to clear debris and begin the process of wound
healing. Lymphocytes (choice B) and plasma cells (choice E) are mediators of chronic infl ammation and provide antigen-specific immunity to infectious diseases. Fibroblasts (choice A) and macrophages (choice C) regulate scar tissue formation at the site of infarction

Question 5

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 follow-
ing mechanisms?

Answer 5

Increased capillary permeability of the endothelial cell layer causes local edema

Question 6

Which of the following serum proteins activates the complement, coagulation, and fibrinolytic systems at the site of injury
in a patient with swelling due to puncture with a rusty nail?

Answer 6

Hageman factor.
Hageman factor (clotting factor XII) provides a key source of vasoactive mediators. Activation of this plasma protein at the site of tissue injury
stimulates (1) conversion of plasminogen to plasmin, which induces fi brinolysis; (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 infl ammation, they have a more restricted set of functions.

Question 7

80 yo F, 4 hr history of fever, chills, disorientation. Physical: diffuse purpura on upper arms and chest. Positive culture for gram - organisms. Which cytokine is involved in the pathogenesis of direct vascular injury in this patient w/ septic shock?

Answer 7

TNF-a. Septicemia/bacteremia denotes the clinical condition in which bacteria are found in the circulation. It can be suspected clinically but the final diagnosis is made by blood culture. LPS is released from gram - bacteria stimulating macrophages to secrete large quantities of TNF-a, which causes direct cytotoxic damage to capillary endothelial cells.

Question 8

24 yo IV drug abuser develops a 2 day history of headache and fever. Blood culture shows for gram + cocci. Given IV antibiotics but he quickly deteriorates and dies. Brain at autopsy shows 2 encapsulated cavities. What is this pathological finding?

Answer 8

Suppartive inflammation: condition in which a purulent exudate is accompanied by significant liquefactive necrosis, it is the equivalent of pus.

Question 9

41 yo F complains of excessive menstrual bleeding and pelvic pain and 4 months. She has an IUD. Endometrial biopsy reveals an excess of plasma cells and macrophages within the stroma. The presence of these cells and scattered lymphoid follicles within the endometrial stroma is evidence of what condition?

Answer 9

Chronic inflammation. Inflammation can be either chronic or acute, depending on its persistence, symptoms and the nature of the inflammatory response. The cellular components of inflammation are lymphocytes, antibody-producing plasma cells and macrophages. The chronic inflammatory process is often prolonged and may be associated w/ aberrant repair like fibrosis.

Question 10

36 yo F w/ pneumoccocal pneumonia develops a R pleural effusion. The pleural fluid displays a high specific gravity and contains lots of polymorphonuclear leukocytes. What describes this pleural effusion?

Answer 10

Purulent exudate. The pleural effusion encountered in this patient represents excess fluid in a body cavity. A purulent exudate or effusion contains a prominent cellular component, like PMNs.

Question 11

A 33 yo M presents w/ 5 week history of calf pain and swelling and low-grade fever. Serum levels of CK are elevated. A muscle biopsy reveals numerous eosinophils. What is the etiology of this myalgia?

Answer 11

Parasitic infection. Eosinophils are particularly evident during allergic reactions and parasitic infection, which often cause eosinophils to infiltrate skeletal muscle.

Question 12

10 yo M w/ ho recurrent bacterial infections presents w/ fever and productive cough. Biochemical analysis of his neutrophils demonstrates that he has an impaired ability to generate ROS. This patient has inherited mutations in the gene that encodes which protein?

Answer 12

NADPH oxidase. The importance of oxygen dependent mechanisms in bacterial killing by phagocytic cells is exemplified in chronic granulomatous disease of childhood. They can’t produce hydrogen peroxide during phagocytosis so they’re susceptible to recurrent bacterial infections.

Question 13

A 25 yo W presents w/ ho recurrent SOB and severe wheezing. Lab studies show deficiency in C1 inhibitor, an esterase inhibitor that regulates the activation of the classical complement pathway. What is the diagnosis?

Answer 13

Hereditary anigoedema. Deficiency of C1 inhibitor with excessive cleavage of C4 adn C2 by C1s, is associated w/ the syndrome of hereditary angioedema. The disease is characterized by episodic, painless, nonpitting edema of soft tissues, resulting in chronic complement activation. May be life threatening with laryngeal edema.

Question 14

40 yo M complains of 2 week history of increasing abdominal pain and yellow discomfort of his sclera. Physical: right upper quadrant pain. Labs: elevated serum alkaline phosphatase and bilirubin. Liver biopsy shows portal fibrosis w/ scattered foreign bodies consistent w/ schistosome eggs. Which inflammatory cell is most likely in the portal tracts of this patient’s liver?

Answer 14

Eosinophils - recruited in parasitic infections and would be expected to predominate in the portal tracts of the liver in patients with schisosmiasis.

Question 15

62 yo F undergoing chemo for breast cancer presents w/ 3 day ho fever and chest pain. Cardiac cath shows reduced ejection fraction w/ normal coronary blood flow. A myocardial biopsy is obtained and a PCR test for coxsakievirus is +. Histo exam of the myocardium will reveal an abundance of which type of inflammatory cell?

Answer 15

Lymphocytes. This patient w/ viral myocarditis will show an accumulation of lymphocytes in the affected heart muscle.

Question 16

58 yo F w/ 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. What explains the pathogenesis of this fibrinous exudate?

Answer 16

Injury and increased vascular permeability. Binding of vasoactive mediators to specific receptors on endothelial cells results in contraction and gap formation. This hole in the endothelial barrier allows intravascular fluid to leak into the extravascular space. Direct injury to the endothelial cells also leads to this leakage. A fibrous exudate contains fibrin, resulting from activation of the coagulation cascade.

Question 17

68 yo M presents w/ fever, shaking chills and SOB. Physical: rales and decreased breath sounds over both lung fields. Grunting respirations and flaring of the nares. Sputum is rusty yellow and has PMN leukocytes. Which mediator of inflammation is chiefly responsible for this patient’s fever?

Answer 17

Interleukin-1. Release of exogenous pyrogens by bacteria, viruses, or injured cells stimulates the production of endogenous pyrogens: IL-1a, IL1-b, TNF-a. IL-1 stimulates prostaglandin synthesis in hypothalamic thermoregulatory centers, altering the body’s thermostat.

Question 18

Sputum culture is + for streptococus pneumoniae. Removing bacteria from the alveolar air spaces in this patient involves opsonization by complement, an important step in mediating which leukocyte function?

Answer 18

Phagocytosis. Complement/opsonins enhance phagocytosis.

Question 19

Which mediator of inflammation is responsible for secondary injury to the alveolar basement membrane and lung parenchyma in strep pneumoniae?

Answer 19

Lysosomal enzymes. The primary role of neutrophils in inflammation is host defense and debridement of damaged tissue. The same neutrophil- derived lysosomal enzymes that are beneficial when active intracellularly, may be harmful and cause tissue damage when released to the extracellular environment.

Question 20

Which protein inhibits fibrinolysis, activation of the complement system, and protease-mediated damage in the lungs of a patient w/ strep pneumoniae?

Answer 20

Alpha-2-macroglobulin. Proteolytic enzymes that are released by phagocytic cells during inflammation are regulated by a family of protease inhibitors, like a1 antitrypsin and a2 macroglobulin. These proteins inhibit plasma-activated fibrinolysis and activation of the complement system, and help protect against non-specific tissue injury during inflammation.

Question 21

A 35 yo F presents w/ 5 day history of a painful sore on her back. Physical: 1 cm abscess on left shoulder. Biopsy: vasodilation and leukocyte margination. What glycoprotein mediates initial tethering of segmented neutrophils to endothelial cells in this skin lesion?

Answer 21

Selectin. Selectins are sugar-binding glycoproteins that mediate the initial of adhesion of leukocytes to endothelial cells at sites of inflammation. E-selectins are on on endothelial cells. P selectins are on platelets, L and leukocytes.

Question 22

14 yo M receives laceration on forehead by hockey puck. There is immediately blanching of the skin around the wound. What mechanism accounts for this transient reaction to neurogenic and chemical stimuli at the site of injury?

Answer 22

Constriction of precapillary arterioles. The initial response of arterioles to neurogeneic and chemical stimuli is transient vasoconstriction, later dilation occurs increasing blood flow to the inflamed area.

Question 23

8 yo F w/ asthma presents in respiratory distress. She has ho allergies and upper resp tract infections, as well as wheezing with exercise. Which mediator of inflammation is the most powerful stimulator of bronchoconstriction and vasoconstriction in this girl?

Answer 23

Leukotrienes. Asthma = chronic lung disease caused by increased responsiveness of the airways to stimuli. Chemical mediators like leukotrienes released by chronic inflammatory cells in the lungs of these patients stimulate bronchial mucus production and bronchoconstriction. Leukotrienes are responsible for many of the clinical symptoms of asthma and allergic reactions.

Question 24

What preformed substance is released from mast cells and platelets, resulting in increased vascular permeability in the lungs of a patient w/ asthma in respiratory distress?

Answer 24

Histamine. When IgE-sensitized mast cells are stimulated by antigen, preformed mediators of inflammation are secreted into the extracellular tissues. Histamine binds to H2 receptors in the vascular wall, inducing endothelial cell contraction, gap formation and edema.

Question 25

A 75 yo F complains of recent onset chest pain, fever, and productive cough w/ rust-colored sputum. CXR shows infiltrate in right middle lobe. Sputum culture + for strep pneumoniae. Phagocytic cells in this patient’s affected lung tissue generate bacteriocidal hypochlorous acid using which enzyme?

Answer 25

Myeloperoxidase. Myeloperoxidase catalyzes the conversion of H2O2 in the presence of a halide to form hypochlorous acid. This powerful oxidant is a major bacteriocidal agent produced by phagocytic cells. Patients w/ myeloperoxidase deficiency can’t produce hypochlorous acid and are susceptible to recurrent infections.

Question 26

28 yo F cuts her hand w/ kitchen knife. Wound is cleaned and sutured. 5 days later the site has a bunch of chronic inflammatory cells that actively secrete interleukin-1, tumor necrosis factor-a, interferon-a, numerous arachidonic acid derivatives and various enzymes. What are these inflammatory cells?

Answer 26

Macrophages. The macrophage is the pivotal cell in chronic inflammation.They regulate lymphocyte response to antigens and secrete a variety of mediators that modulate the proliferation and function of fibroblasts and endothelial cells.

Question 27

68 yo M w/ prostate cancer and bone metastases presents w/ shaking chills and fever. The peripheral WBC count is low. What is this hematolgic finding called?

Answer 27

Leukopenia: absolute decrease in circulating WBC count.

Question 28

25 yo M injured by metal sliver in left hand. Over a few days, the wounded area gets red, tender, swollen and warm. Redness at the site of injury is caused primary by what mechanism?

Answer 28

Vasodilation. Vasodilation of precapillary arterioles increases blood flow to the site of tissue injury in acute hyperemia.

Question 29

25 yo M injured by metal sliver in left hand. Over a few days, the wounded area gets red, tender, swollen and warm. Patient goes to ED to get sliver removed. Which mediator of inflammation is most important in stimulating platelet aggregation at the site of injury following the removal?

Answer 29

Thromboxane A2. Platelet adherence, aggregation and degranulation occur when platelets come in contact w/ fibrillar collagen or thrombin - after activation of the coagulation system. Thromboxane A2 - key in 2nd wave of platelet aggregation and smooth muscle constriction. Platelet degranulation is due to serotonin, which increases vascular perm.

Question 30

25 yo M injured by metal sliver in left hand. Over a few days, the wounded area gets red, tender, swollen and warm. Patient goes to ED to get sliver removed. 24 hrs later, endothelial cells at the site of injury WHAT chemical mediator that inhibits further platelet aggregation?

Answer 30

Prostaglandin, PGI2. PGI2 is a derivative of arachidonic acid that is formed in the cyclooxygenase pathway. It promotes vasodilation and bronchodilation, as well as inhibits platelet aggregation. Its action is exactly opposite to thromboxin A.

Question 31

37 yo M w/ AIDS is admitted to hosptial w/ 3 week ho of chest pain and SOB. CXR: bilateral nodularities of the lungs. Lung biopsy shows multinucleated cells derived from which inflammatory cell?

Answer 31

Macrophages. Granulomas are collections of epithelioid cells and multinucleate 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, this is a Langerhans giant cell.

Question 32

45 yo F w/ autoimmune hemolytic anemia presents w/ increasing fatigue. Which mediator on inflammation is responsible for this antibody-mediated hemolysis?

Answer 32

Complement proteins. Activation of the complement cascade leads to cleavage of complement fragments and formation of biologically active complexes. Fragments combine to form MAC - membrane attack complex, which lyses cells.

Question 33

59 yo alcoholic brought to ED w/ fever and bad breath. CXR: pulmonary abscess in right lower lobe. Pt develops acute bronchopneumonia and dies. Activation of phospholipase A in intra-alveolar cells, results in formation of which mediator of inflammation?

Answer 33

Arachidonic acid. Cellular sources of vasoactive mediators are (1) derived from the metabolism of arachidonic acid (prostaglandins, thromboxanes, leukotrienes, and platelet-activating factor),
(2) preformed and stored in
cytoplasmic granules (histamine, serotonin, and lysosomal
hydrolases),
or (3) generated as normal regulators of vascular function (nitric oxide and neurokinins). The photomicrograph
shows polymorphonuclear leukocytes responding to a
bacterial pneumonia. Free arachidonic acid in these acute
inflammatory cells is derived from membrane phospholipids
(primarily phosphatidylcholine) by stimulus-induced activation of phospholipase A2.

Question 34

10 yo F presents w/ 2 week ho puffiness around eyes and swelling of legs and ankles, Labs: hypoalbuminemia and proteinuria. Urinary sediment contains no inflammatory cells or RBCs. Which term describes the patient’s peripheral edema?

Answer 34

Transudate = noninflammatory edema.

Question 35

25 yo F develops 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 joints was mediated by which family of proteins?

Answer 35

Integrins. Chemokines and other pro-inflammatory molecules activate a family of cell adhesion molecules called integrins. Molecules in this family do cell-cell and cell-substrate adhesions and cell-signaling. They are involved in leukocyte recruitment to site of injury in acute inflammation.

Question 36

Aspirin is effective in relieving symptoms of acute inflammation bc it inhibits which enzyme?

Answer 36

Cyclooxygenase.
Cyclooxygenases metabolize arachidonic acid to generate prostanoids. The 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.

Question 37

A 50 yo F is discovered to have metastatic breast cancer. One week after her first chemo dose she gets bacterial pneumonia. What explains her susceptibility to bacterial infection?

Answer 37

Neutropenia. Chemo causes defective phagocytic cells/ iatrogenic neutropenia which increases severity and frequency of infections due to lack of protection by acute inflammatory cells.

Question 38

53 to M develops weakness, malaise, cough w/ bloody sputum and night sweats. CXR shows apical densities bilaterally. Exposure to TB was documented 20 yrs ago and TB is found in sputum. Describe the histology of the pulmonary lesions?

Answer 38

Granulomatous inflammatin.

Question 39

59 y M experiences acute chest pain. Labs and ECG show acute MI, but coronary angiography 2 hrs later does not show evidence of thrombosis. Intravascular thrombolysis that occurred was mediated by plasminogen activators released by what cells?

Answer 39

Endothelial cells. Vascular endothelium has the ability to produce or inhibit tissue and perfusion inflammatory cell influx through multiple mechanisms. They make plasminogen activators which activate plasmin and initiate thrombolysis.

Question 40

Which mediator of inflammation causes relaxation of vascular smooth muscle cells and vasodilation of arterioles at the site of MI?

Answer 40

Nitric oxide – relaxation of vascular smooth muscle cells and vasodilation of arterioles.

Question 41

68 yo coal miner w/ ho smoking and emphysema develops severe air-flow obstruction and dies. Autopsy: black lung, coal-dust nodules scattered throughout the parenchyma and an area of dense fibrosis. Which cells sequestered the coal dust trapped in the lungs?

Answer 41

Macrophages. Coal miners pneumoconiosis reflects inhaling carbon particles. He is expected to have non-palpable coal dust macules and palpable coal-dust nodules. Nodules consist of dust laden macrophages, associated with a fibrotic stroma.

Question 42

40 yo M presents w/ 5 day ho productive cough and fever. Pseudomonas aeruginosa is isolatated from pulmonary abscess. CBC shows inc WBC and numerous immature cells - bands. What describes this hematologic finding?

Answer 42

Leukemoid reaction - when circulating levels of leukocytes and their precursors reach very high levels, ~ 50,000.

Question 43

19 yo F w/ 5 days of fever and sore throat. Fatigue for past week and difficulty swallowing. Physical: generalized lymphadenopathy. What hematologic findings will CBC show if she has a viral infection?

Answer 43

Lymphocytosis. Peripheral blood lymphocytosis = increase in absolute peripheral blood lymphocyte count. This is caused by acute viral infections or chronic bacterial.

Question 44

40 yo F w/ 8 mo ho itching, weight loss, fatigue and yellow sclera. Physical: jaundice. Anti-mitochondrial antibody test +. Liver biopsy shows periductal inflammation and bile duct injury. Which inflammatory cell is the principle mediator of destructive cholangitis?

Answer 44

T-lymphocytes. Principle biliary cirrhosis is a chronic progressive cholestatic liver disease characterized by destruction of intrahepatic bile ducts. Usually affects middle-aged women and they have circulating anti-mitochondrial antibodies. Cells surrounding sites of bile duct damage - T lymphocytes - mediate destruction of ductal epithelium.

Question 45

25 yo F presents w/ 2 week ho febrile illness and chest pain. She has errythematous, macular facial rash and tender joints, esp wrist and elbow. CBC shows mild anemia and thrombocytopenia. Cortiosteroids are prescribed. This medication induces synthesis of an inhibitor to which inflammatory cell enzyme.

Answer 45

Phospholipase A2. Corticosteroids are widely used to suppress the tissue destruction associated with many chronic infl ammatory 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.

Question 46

Increased serum levels of ceruloplasmin, fibrinogen, a2-macroglobulin, serum amyloid A protein and C-reactive protein. These markers belong to which family of proteins?

Answer 46

Acute phase proteins: sythesized by the liver and released into circulation in response to an acute inflammatory chalange.