Gastroduodenal defence mechanisms.

In the healthy stomach and duodenum aggressive factors such as luminal acid and pepsin are balanced by defence and repair processes. In recent years components of the mucosal defences which have been identified include the layer of mucus gel adherent to the surface of these mucosae, surface epithelial alkali secretion, mucosal blood flow and the supply of bicarbonate to the surface epithelium as well as the processes involved in rapid mucosal repair. Secretion of alkali maintains the pH within the mucus gel on the epithelial cell surface at neutrality, in spite of luminal pHs as low as 1.5 to 2.0. Alkali secretion is stimulated up to ten-fold by luminal acid. This response is mediated by endogenous production of prostaglandins, humoral factors and, possibly, by nervous mechanisms. Impairment of the response results in mucosal ulceration. The mucus layer (approximately 200 micron deep in man) provides an unstirred zone at the mucosal surface in which diffusing is delayed, allowing time for secreted HCO-3 to neutralize acid diffusing toward the mucosa. In addition mucus is impermeable to pepsin. During secretion of H+ ions, HCO-3 is produced, and secreted by the surface epithelium. Stimulation of acid secretion increases the ability of gastric mucosa to resist acid and pepsin, presumably by providing more HCO-3. Parenteral HCO-3 (but not other buffer species) provides similar protection to both the gastric and duodenal mucosae. The remarkably rapid reconstitution of the surface epithelium, within 30 minutes after acute superficial damage, is clearly an important 'defence' mechanism. Studies of the control of these defence and repair mechanisms should provide a greater understanding of common gastroduodenal diseases.