Furosemide causes hypokalemia and metabolic alkalosis. The mechanism by which furosemide produces metabolic alkalosis is:

• A Volume contraction stimulates aldosterone; increased distal Na+ delivery enhances K+ and H+ secretion by the collecting duct, generating and maintaining metabolic alkalosis ✓
• B Direct inhibition of carbonic anhydrase in the proximal tubule, reducing HCO3- reabsorption
• C Furosemide activates H+/K+-ATPase in the collecting duct, directly excreting protons
• D Inhibition of the NKCC2 transporter causes bicarbonate to substitute for chloride in proximal tubular reabsorption

Explanation

Furosemide inhibits the NKCC2 transporter in the thick ascending limb, causing natriuresis with volume contraction. Volume contraction triggers secondary hyperaldosteronism; aldosterone acts on principal cells of the collecting duct to increase Na+ reabsorption via ENaC, which drives K+ and H+ secretion from alpha-intercalated cells via H+/K+-ATPase and vacuolar H+-ATPase. The net H+ loss generates metabolic alkalosis. Increased distal Na+ delivery from loop blockade also directly drives H+ secretion. This 'contraction alkalosis' combined with increased aldosterone maintains the alkalosis.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.