A patient with prolonged nasogastric suction develops metabolic alkalosis. The urine chloride is 8 mEq/L. Which mechanism best explains why this alkalosis is chloride-responsive (saline-responsive)?

• A HCl loss via the NG tube contracts effective circulating volume; low luminal Cl⁻ impairs HCO3⁻ secretion by the alpha-intercalated cells (pendrin exchanger) in the cortical collecting duct, maintaining alkalosis ✓
• B Cl⁻ depletion activates ROMK channels in the thick ascending limb, increasing K⁺ secretion and indirectly stimulating H⁺ retention
• C Low Cl⁻ prevents proximal tubular Na-Cl cotransporter activity, causing sodium wasting that secondarily activates aldosterone and H⁺ secretion
• D The kidney cannot excrete bicarbonate without an adequate Cl⁻ supply because bicarbonaturia requires obligate Cl⁻ reabsorption in exchange in the proximal tubule

Explanation

In chloride-responsive metabolic alkalosis (urine Cl⁻ <20 mEq/L), two mechanisms maintain HCO3⁻ elevation: (1) volume contraction stimulates proximal HCO3⁻ reabsorption and reduces filtered load reaching distal nephron; (2) luminal Cl⁻ deficiency impairs pendrin (Cl⁻/HCO3⁻ exchanger) in alpha-intercalated cells of the cortical collecting duct—pendrin normally secretes HCO3⁻ in exchange for Cl⁻, so without luminal Cl⁻, HCO3⁻ secretion (correction) cannot occur. Saline restores Cl⁻, volume, and enables pendrin-mediated HCO3⁻ secretion. Option D incorrectly implies proximal Cl/HCO3 exchange; the dominant proximal HCO3⁻ reabsorption is via H⁺ secretion, not direct exchange.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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