A patient receiving furosemide for heart failure develops hypokalemic metabolic alkalosis. The direct mechanism by which furosemide causes metabolic alkalosis is best explained by:
- A Increased delivery of Na+ to the collecting duct stimulates aldosterone-driven H+ secretion via H+-ATPase ✓
- B Direct inhibition of carbonic anhydrase in the proximal tubule increasing HCO3- reabsorption
- C Furosemide blocks K+ secretion, causing intracellular H+ to shift extracellularly
- D Contraction of extracellular fluid volume reduces GFR, concentrating plasma HCO3-
Correct answer: A. Increased delivery of Na+ to the collecting duct stimulates aldosterone-driven H+ secretion via H+-ATPase
Explanation
Furosemide inhibits NKCC2 in the thick ascending limb, increasing Na+ and Cl- delivery to the collecting duct. In the presence of aldosterone (stimulated by volume contraction), this increases ENaC-mediated Na+ reabsorption, which creates a lumen-negative potential that drives H+ secretion by H+-ATPase on alpha-intercalated cells, generating new bicarbonate — the key mechanism of contraction alkalosis. Additionally, volume contraction itself stimulates aldosterone, amplifying H+ secretion. Contraction alkalosis (option D) is a contributing but secondary mechanism.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.