A 57-year-old man comes to the office for a follow-up appointment. He has a history of systolic heart failure, which has been managed with appropriate medical therapy. The patient experiences significant functional impairment at baseline and is able to walk only short distances. His most recent echocardiogram revealed a left ventricular ejection fraction of 30% (normal ≥55%). The physician decides to add spironolactone to the treatment regimen. The addition of this medication is most likely to cause a decrease in which of the following?

Question

A 57-year-old man comes to the office for a follow-up appointment.  He has a history of systolic heart failure, which has been managed with appropriate medical therapy.  The patient experiences significant functional impairment at baseline and is able to walk only short distances.  His most recent echocardiogram revealed a left ventricular ejection fraction of 30% (normal ≥55%).  The physician decides to add spironolactone to the treatment regimen.  The addition of this medication is most likely to cause a decrease in which of the following?

Quizplus · Accepted Answer

11ec160b_3c67_f521_9249_ef471b980955_MD0001_00 Aldosterone is a mineralocorticoid produced by the adrenal zona glomerulosa in response to hypotension and reduced renal blood flow (renin-angiotensin-aldosterone system). Hyperkalemia can also stimulate aldosterone secretion. Aldosterone acts primarily in the collecting duct, where it increases the number of basolateral Na⁺/K⁺-ATPase pumps and apical sodium channels on principal cells, increasing sodium and water reabsorption. It also promotes potassium and hydrogen ion secretion from the principal and intercalated cells, respectively. Aldosterone receptor antagonists (eg, spironolactone, eplerenone) inhibit the effects of aldosterone and reduce sodium reabsorption and potassium and hydrogen ion secretion in the collecting duct. Benefits include enhanced diuresis and lower blood pressure. Adverse effects of these medications include hyperkalemia, hyponatremia, metabolic acidosis, and gynecomastia (with spironolactone, which also inhibits the testosterone receptor). (Choice A) Intracellular carbonic anhydrase in the proximal tubule generates H⁺, which is secreted into tubular fluid and used by brush border carbonic anhydrase to help resorb filtered HCO₃⁻. Carbonic anhydrase inhibitors (eg, acetazolamide) suppress both membrane-bound and cytoplasmic forms. (Choice C) The Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb is the target of loop diuretics (eg, furosemide), which cause brisk diuresis by inhibiting solute reabsorption. (Choice D) The microvilli-covered epithelial cells (brush border) of the proximal convoluted tubule have a high capacity for reabsorption of electrolytes, glucose, and amino acids. Isosmotic water reabsorption follows passively. Reabsorption in this segment of the nephron is not affected by aldosterone, but is enhanced by angiotensin II. (Choice E) In addition to increasing the water permeability of the collecting duct, vasopressin (antidiuretic hormone) raises urea reabsorption by increasing the number of cell surface urea transporters. This strengthens the corticomedullary interstitial osmotic gradient, facilitating water reabsorption and increasing urine concentration. Educational objective: Aldosterone acts on the principal and intercalated cells of the renal collecting tubules to increase resorption of sodium and water and increase excretion of potassium and hydrogen ions. Aldosterone receptor antagonists (eg, spironolactone, eplerenone) inhibit these effects.

A 57-Year-Old Man Comes to the Office for a Follow-Up