Question
An 9-year-old boy is brought to the physician for evaluation of an excessive bleeding after undergoing a dental procedure. Laboratory studies show a platelet count of 195,000/mm3, a partial thromboplastin time of 44 sec, and a prothrombin time of 12 sec. A one-stage clotting assay shows a decreased factor VIII. Therapy with a drug that acts on endothelial cells is initiated. This drug is most likely to result in which of the following?
| A. |
Decreased cAMP in renal tubular cells
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| B. |
Increased tubular fluid osmolarity in the loop of Henle
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| C. |
Decreased binding of angiotensin II to AT1 receptor
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| D. |
Increased permeability to urea in the collecting duct
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Show Answer
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Correct Answer � D
Explanation
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Ans-D-Increased permeability to urea in the collecting duct
Decreased cAMP in renal tubular cells
Decreased cAMP in renal tubular cells would be observed in patients who were given vasopressin (receptor) antagonists, e.g., conivaptan. Desmopressin, however, increases cAMP via interaction with V2-receptors and subsequent activation of adenylyl cyclase. The effects of high cAMP concentrations include the integration of aquaporins into the plasma membrane of collecting duct cells and an increase in water reabsorption.
Increased tubular fluid osmolarity in the loop of Henle
Increased tubular fluid osmolarity in the loop of Henle would be seen in patients who have received mannitol, which is freely filtered by the kidneys without undergoing reabsorption and thereby creates a strong osmotic gradient with subsequent diuresis. Mannitol is commonly used in patients with elevated intracranial pressure or acute prerenal failure. In contrast, the concentrating effect of desmopressin occurs only in the collecting ducts, thus leaving the osmolarity in the loop of Henle.
Decreased binding of angiotensin II to AT1 receptor
Decreased binding of angiotensin II to AT1 receptors would be observed in a patient taking angiotensin receptor blockers, not desmopressin. ARBs would be of no use in this patient, as they promote diuresis through vasodilation and natriuresis and have no role in the treatment of hemophilia.
Increased permeability to urea in the collecting duct
Increased permeability to urea in the collecting duct is found in patients who are treated with vasopressin analogs. This group of drugs binds to V2-receptors, triggering a cascade of intracellular reactions that ultimately result in increased numbers of UT-A1 proteins in the apical plasma membrane. UT-A1 facilitates urea reabsorption in the inner medullary collecting duct.
