Can Too Much Acid Sour Your Pancreas?

Simplified model of acinar cell pH regulation and trypsinogen activation. The basolateral membrane adjacent to capillaries is on the left and the luminal or secretory membrane is on the right. The basolateral Na⁺-K⁺ ATPase is responsible for maintaining a low intracellular Na⁺, high K⁺ and a negative intracellular potential. Thus both Na⁺ and H⁺ are diffusing into the cell down their electrochemical gradient and the energy stored in the Na+ gradient is used to pump H⁺ out by the Na⁺-H⁺ exchanger or HCO3⁻ in by the Na⁺-HCO3⁻ cotransporter. Cl- is close to electrochemical equilibrium and at rest the Cl⁻-HCO3⁻ exchanger serves to move HCO₃⁻ out of the cell. Note when cells are incubated in HEPES Ringer medium not all of these mechanisms are activated. Lysosomes maintain an acid pH by virtue of a vacuolar(v)-type H⁺-ATPase. The low pH environment is necessary for activation of trypsinogen by cathepsins.