A 62-year-old man comes to the physician for a follow-up appointment. He experienced acute myocardial infarction 2 years ago and has a long history of hypertension. After physical examination and laboratory testing, the physician decides to increase the dose of his diuretic. Repeat laboratory studies indicate that his serum calcium level increases after this adjustment. The diuretic used in this patient acts predominantly on which of the following nephron segments?

Question

A 62-year-old man comes to the physician for a follow-up appointment.  He experienced acute myocardial infarction 2 years ago and has a long history of hypertension.  After physical examination and laboratory testing, the physician decides to increase the dose of his diuretic.  Repeat laboratory studies indicate that his serum calcium level increases after this adjustment.  The diuretic used in this patient acts predominantly on which of the following nephron segments?

Quizplus · Accepted Answer

11ec160b_3c75_d7ec_9249_e1da87e13800_MD0001_00 Thiazide diuretics work in the distal convoluted tubule, causing enhanced Na⁺, Cl^-, and water excretion. The apical membrane of early distal tubule cells contains the Na⁺/Cl^- symporter while the basolateral side has Na⁺/K⁺ ATPases and Cl^- channels that maintain a NaCl gradient across the apical cell membrane. Thiazides inhibit the apical Na⁺/Cl^- symporter, decreasing luminal NaCl absorption into the distal tubular cell. This can cause hypercalcemia by reducing intracellular Na⁺ concentrations, which in turn increases the activity of the basolateral Na⁺-Ca²⁺ exchanger. The resulting reduction in intracellular Ca²⁺ levels acts to increase luminal Ca²⁺ absorption in the distal tubule. Increased Ca²⁺ absorption in the proximal tubule secondary to volume depletion can also contribute to hypercalcemia in thiazide-treated patients. There are a number of thiazide and thiazide-like diuretics available. Examples include hydrochlorothiazide, chlorothiazide, indapamide, and metolazone. They differ in potency, bioavailability, and half-life. Thiazides are not as efficacious as loop diuretics as only a small amount of filtered Na reaches the distal tubules. They are used to treat edema secondary to heart failure, renal disease, and liver disease. Thiazides are also commonly used to treat hypertension. More common side effects include hypokalemia, hyponatremia, and hypomagnesemia. Less common side effects include hypotension, volume depletion, and hypercalcemia. (Choices A and B) Carbonic anhydrase inhibitors block the reabsorption of NaHCO₃ and work in the convoluted and straight portions of the proximal tubule. (Choice C) Osmotic diuretics such as mannitol function mainly in the proximal tubule and the descending limb of the loop of Henle to reduce Na and water reabsorption. (Choice D) Loop diuretics work in the thick ascending limb and are the most potent diuretics. (Choice F) The collecting duct system includes the connecting tubules and ducts. Here, aldosterone and ADH make final adjustments to electrolytes and water content. Potassium- sparing diuretics and aldosterone antagonists work in the collecting duct. Educational objective: Thiazide diuretics work by blocking Na⁺-Cl^- symporters in the distal convoluted tubules, causing enhanced Na, Cl, and water excretion. Since only a small amount of filtered Na⁺ reaches the distal tubules, thiazides are not as efficacious as loop diuretics. Unlike loop diuretics, thiazides can cause hypercalcemia. __________ References: Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. (http://www.ncbi.nlm.nih.gov/pubmed/12846750)

A 62-Year-Old Man Comes to the Physician for a Follow-Up