In chronic metabolic acidosis, the kidney augments net acid excretion substantially within days. Which process accounts for most of this increase, and where does it occur?

• A Increased bicarbonate reabsorption via NHE3 in the proximal tubule
• B Increased titratable acid formation from phosphate in the distal nephron
• C Increased ammonium production from glutamine in the proximal tubule ✓
• D Increased proton pump insertion in alpha-intercalated cells only

Explanation

Phosphate availability limits titratable acid excretion, so it cannot rise much above baseline. Bicarbonate reabsorption is already near complete in health. The adaptive response is ammoniagenesis: proximal tubular cells metabolize glutamine to produce NH4+ and new bicarbonate, with NH4+ excreted in urine trapping H+. This pathway can increase several fold over days and is induced by acidosis itself and by hypokalemia.

Reference: Vander's Renal Physiology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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