Outline the mechanism of HCl secretion by parietal cells.

• A. CO2 diffuses into the cell and forms H2CO3 via carbonic anhydrase; H+/K+-ATPase pumps H+ into the lumen; HCO3- is exchanged for Cl- on the basolateral membrane; Cl- follows into lumen to form HCl
• B. H+ is pumped into lumen by Na+/H+ exchanger; Cl- enters by Cl-/HCO3- exchanger
• C. HCl is produced directly in lumen by proton pumps without bicarbonate involvement
• D. HCO3- is secreted into lumen to form HCl

Answer: (A)

Understanding how parietal cells secrete HCl relies on the coordinated generation of H+ and Cl- inside the cell and their delivery into the stomach lumen. Carbon dioxide diffuses into the parietal cell and, with water, is converted to carbonic acid by carbonic anhydrase, which rapidly dissociates into H+ and bicarbonate. The H+ is pushed into the lumen by the H+/K+-ATPase, the gastric proton pump, while the bicarbonate is transported out of the cell in exchange for chloride on the basolateral membrane. Chloride then enters the cell from the bloodstream and moves into the lumen through apical Cl- pathways, meeting the secreted H+ to form HCl in the stomach lumen. The bicarbonate that leaves to the blood during this process also explains the transient rise in blood bicarbonate after a meal. This sequence accurately reflects how HCl formation depends on carbonic anhydrase activity, the proton pump, and the basolateral Cl-/HCO3- exchange coordinating luminal Cl- delivery.