2. Acute & Chronic Inflammation Flashcards
- 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
(F) Reduced Arthiritis Pain.
The COX-2 enzyme is inducible with acute inflammatory reactions, particularly in neutrophils, in synovium, and in the central nervous system. 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.
- 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
- (B) Chemokines
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 they do not cause chemotaxis. Complement C3a causes increased vascular permeability by releasing histamine from mast cells.
- 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
- (B) Neutrophils
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 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
- (A) Macrophages
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 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
5 (A) Vasodilation
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
- A woman who is allergic to cats visits a neighbor who has several cats. During the visit, she inhales cat dander, and within minutes, she develops nasal congestion with abundant nasal secretions. Which of the following substances is most likely to produce these findings?
□ (A) Bradykinin □ (B) Complement C5a □ (C) Histamine □ (D) Interleukin-1 □ (E) Phospholipase C □ (F) Platelet-activating factor □ (G) Tumor necrosis factor
- (C) Histamine.
Histamine is found in abundance in mast cells, which are normally present in connective tissues next to blood vessels beneath mucosal surfaces in airways. Binding of an antigen (allergen) to IgE antibodies that have previously attached to the mast cells by the Fc receptor triggers mast cell degranulation, with release of histamine. This response causes increased vascular permeability and mucous secretions. 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. Complement C5a is a potent chemotactic factor for neutrophils. Interleukin-1 and tumor necrosis factor, both produced by activated macrophages, mediate many systemic effects, including fever, metabolic wasting, and hypotension. Phospholipase C, which catalyzes the release of arachidonic acid, is generated from platelet activation. Platelet-activating factor (PAF) can be released by neutrophils, mast cells, monocytes, macrophages, endothelial cells, and platelets. PAF promotes vascular permeability, neutrophil aggregation, and platelet activation.
- A 32-year-old woman has had a chronic cough with fever for the past month. On physical examination, she has a temperature of 37.5°C, and on auscultation of the chest, crackles are heard in all lung fields. A chest radiograph shows many small, ill-defined nodular opacities in all lung fields. A transbronchial biopsy specimen shows interstitial infiltrates with lymphocytes, plasma cells, and epithelioid macrophages. Which of the following infectious agents is the most likely cause of this appearance?
□ (A) Staphylococcus aureus □ (B) Plasmodium falciparum □ (C) Candida albicans □ (D) Mycobacterium tuberculosis □ (E) Klebsiella pneumoniae □ (F) Cytomegalovirus
- (D) Myobacterium Tuberculosis
These findings suggest a granulomatous inflammation, and tuberculosis is a common cause. Bacteria such as Staphylococcus and Klebsiella are more likely to produce acute inflammation. Plasmodium produces malaria, a parasitic infection without a significant degree of lung involvement. Candida is often a commensal organism in the oropharyngeal region and rarely causes pneumonia in healthy (non-immunosuppressed) individuals. Viral infections tend to produce a mononuclear interstitial inflammatory cell response.
- 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
- (E) Chronic Inflammation
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 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
- (C) Serous Inflammation
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.
- 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 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 patient?
□ (A) Bradykinin □ (B) Leukotriene B4 □ (C) Histamine □ (D) Myeloperoxidase □ (E) Nitric oxide □ (F) Phospholipase C □ (G) Tumor necrosis factor
10 (G) Tumor Necrosis Factor
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 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 and inhibits platelet activation. Phospholipase C, which catalyzes the release of arachidonic acid, is generated from platelet activation.
- 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 in which of the following molecules?
□ (A) Selectins □ (B) Integrins □ (C) Leukotriene B4 □ (D) Complement C3b □ (E) NADPH oxidase
- (A) Selectins
The patient has a defect in leukocyte rolling, the first step in transmigration of neutrophils from the vasculature to the tissues. Rolling depends on interaction between selectins (P-selectin and E-selectin on endothelial cells, and L-selectin on neutrophils) and their sialylated ligand molecules (e.g., sialylated Lewis X). Integrins are involved in the next step of transmigration, during which there is firm adhesion between neutrophils and endothelial cells. Leukotriene B4 is a chemotactic agent, complement C3b facilitates phagocytosis, and NADPH oxidase is involved in microbicidal activity.
- 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 incision. The nodule is excised, and microscopic examination shows macrophages, collagen, a few 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) Chronic inflammation □ (B) Abscess formation □ (C) Suture granuloma □ (D) Ulceration □ (E) Edema
12 (C) Suture Granuloma
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. Chronic inflammation alone is unlikely to produce a localized nodule with giant cells. An abscess, typically from a wound infection, would have liquefactive necrosis and numerous neutrophils. An ulceration involves loss of epidermis or other epithelial layer. Edema refers to accumulation of fluid in the interstitial space. It does not produce a cellular nodule.
- A 3-year-old boy and other male relatives have a history of multiple recurrent infections, including Aspergillus, Staphylococcus, Serratia, Nocardia, andPseudomonas species. Physical examination shows generalized tender lymphadenopathy. Laboratory findings show normal numbers of morphologically normal circulating WBCs. This child’s increased susceptibility to infection is most likely caused by a defect in which of the following steps of the inflammatory response?
□ (A) Activation of macrophages by interferon-γ
□ (B) Oxygen-dependent killing of bacteria by neutrophils
□ (C) Firm adhesion between leukocytes and endothelial cells
□ (D) Synthesis of lysozyme in neutrophil granules
□ (E) Opsonization of bacteria by immunoglobulins
- (B) Oxygen-dependent killing of bacteria by neutrophils
Chronic granulomatous disease is characterized by reduced killing of ingested microbes because of inherited defects in the NADPH oxidase system. Two thirds of cases are X-linked, and one third are autosomal recessive. This system generates superoxide anions (O2−), essential for the subsequent production of microbicidal products such as H2O2, OH, and HOCl−. Macrophage activation by interferon-γ is a key feature of granulomatous inflammation, which is typical of mycobacterial infections. Firm adhesions between leukocytes and endothelium are impaired in leukocyte adhesion deficiency type 1, in which there is a mutation in the β chain of integrins. Lysozyme contained in neutrophil granules is responsible for oxygen-independent killing of bacteria. Impaired opsonization can lead to infections in states of immunoglobulin deficiency.
- 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
- (E) Generation of microbicidal activity
The respiratory, or oxidative, burst generates reactive oxygen species (i.e., superoxide anion) that are important in destruction of engulfed bacteria. Myelopoiesis does not depend on generation of superoxide. Endothelial attachment of neutrophils is aided by adhesion molecules on the endothelium and the neutrophil surface. These molecules include selectins and integrins. Bacteria are opsonized by complement C3b and IgG, allowing the bacteria to be more readily phagocytosed.
- 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 of the excised fallopian tube?
□ (A) Fibroblastic proliferation □ (B) Langhans giant cells □ (C) Liquefactive necrosis □ (D) Mononuclear infiltrates □ (E) Squamous metaplasia
- (C) Liquefactive necrosis
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.
