Regulation of intracellular pH: role in gastric mucosal defence

The gastric mucosa is constantly exposed to conditions that would normally be damaging to living cells. A complex defensive system has evolved that involves multiple mechanisms arranged in a laminar fashion, that as a whole constitute the gastric mucosal barrier to acid. As antisecretory therapy becomes perfected, more attention has been focused on these defensive components of the gastric mucosal barrier in disease. Recently, our laboratory has developed a means of measuring intracellular pH (pHi), mucosal blood flow, acid secretion, surface cell acidification rate, and acid secretion simultaneously in vivo. This system has enabled our laboratory to explore how the different components of the gastric mucosal barrier interact so as to protect the pHi of the surface cells under a variety of conditions. Analysis of these studies has revealed a significant inverse correlation between the initial fall in pHi of surface cells during luminal acid exposure and the thickness of the mucus gel, suggestive of a role of adherent gastric mucus in retarding the permeation of luminal protons into the epithelial cells. Another correlation has been between recovery of pHi and the presence of a hyperemic response to luminal acid, which suggests that the hyperemic response is an important defense mechanism in the intact mucosa. Our data is consistent with the hypothesis that gastric mucosal defense mechanisms, like gastric acid secretion, are dynamically regulated according to need. Disturbance of the regulation of these mechanisms, for example by cirrhosis, might be one of the major factors underlying clinical ulcer disease.