In distal renal tubular acidosis (Type 1 RTA), the alpha-intercalated cells of the collecting duct fail to secrete H⁺. This failure is most often due to a defect in which transporter/channel?
- A H⁺-ATPase (V-type proton pump) or AE1 (Cl⁻/HCO₃⁻ exchanger) on the basolateral membrane ✓
- B Na⁺/H⁺ exchanger 3 (NHE3) on the apical membrane
- C NKCC2 in the thick ascending limb, reducing NH₄⁺ trapping
- D Carbonic anhydrase IV deficiency reducing CO₂ availability
Correct answer: A. H⁺-ATPase (V-type proton pump) or AE1 (Cl⁻/HCO₃⁻ exchanger) on the basolateral membrane
Explanation
Type 1 (distal) RTA results from failure of alpha-intercalated cells to acidify urine (urine pH >5.5 despite acidemia). The most common molecular defects are loss-of-function mutations in the V-type H⁺-ATPase (ATP6V1B1 or ATP6V0A4 subunits, associated with sensorineural hearing loss) on the apical membrane, or mutations in AE1 (SLC4A1) basolateral Cl⁻/HCO₃⁻ exchanger needed to export HCO₃⁻. NHE3 is the dominant proximal tubule H⁺ secretor; its dysfunction causes Type 2 (proximal) RTA.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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