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Chapter 11: Transplantation

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Hyperacute rejection is caused by

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A. Preformed antibodies

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B. B-cell–generated antidonor antibodies

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C. T-cell–mediated allorejection

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D. Nonimmune mechanism

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Answer: A

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Hyperacute rejection, a very rapid type of rejection, results in irreversible damage and graft loss within minutes to hours after organ reperfusion. It is triggered by preformed antibodies against the donor’s human leukocyte antigen (HLA) or ABO blood group antigens. These antibodies activate a series of events that result in diffuse intravascular coagulation, causing ischemic necrosis of the graft. Fortunately, pretransplant blood group typing and cross-matching (in which the donor’s cells are mixed with the recipient’s serum, and then destruction of the cells is observed) have virtually eliminated the incidence of hyperacute rejection. (See Schwartz 10th ed., p. 324.)

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The mechanism of action of azathioprine (AZA) is

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A. Inhibition of calcineurin

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B. Interference with DNA synthesis

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C. Binding of FK-506 binding proteins

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D. Inhibition of P7056 kinase

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Answer: B

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An antimetabolite, azathioprine (AZA) is converted to 6-mercaptopurine and inhibits both the de novo purine synthesis and salvage purine synthesis. AZA decreases T-lymphocyte activity and decreases antibody production. It has been used in transplant recipients for more than 40 years, but became an adjunctive agent after the introduction of cyclosporine. With the development of newer agents such as mycophenolate mofetil (MMF), the use of AZA has decreased significantly. However, it is preferred in recipients who are considering conceiving a child, because MMF is teratogenic in females and can cause birth defects. AZA might be an option for recipients who cannot tolerate the gastrointestinal (GI) side effects of MMF.

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The most significant side effect of AZA, often dose-related, is bone marrow suppression. Leukopenia is often reversible with dose reduction or temporary cessation of the drug. Other significant side effects include hepatotoxicity, pancreatitis, neoplasia, anemia, and pulmonary fibrosis. Its most significant drug interaction is with allopurinol, which blocks AZA’s metabolism, increasing the risk of pancytopenia. Recommendations are to not use AZA and allopurinol together, or if doing so is unavoidable, to decrease the dose of AZA by 75%. (See Schwartz 10th ed., p. 326.)

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Which of the following is NOT a side effect of cyclosporine?

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A. Interstitial fibrosis of the renal parenchyma

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B. Gingival hyperplasia

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C. Hirsutism

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D. Pancreatitis

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