Pathogenesis of peptic ulcer disease and gastritis: importance of aggressive and cytoprotective factors.

Acid production is a major gastric function. Second messengers (cyclic AMP and calcium) are released when parietal cell membrane receptors (H2, muscarinic and gastrin) are stimulated. The second messengers then stimulate the 'gastric proton pump' to produce hydrogen ions. New evidence suggests that there is a unidirectional flux of hydrogen ions into the lumen induced by unique physical properties of mucus and a sodium gradient from lumen to serosa. Luminal hydrogen ions, bile salts, ingested drugs, and ingested alcohol are potential gastric epithelial toxins. The stomach's protective mechanism includes a well-defined mucus layer, an epithelial bicarbonate secretion, a tight epithelium, and a good nutrient blood supply. Endogenous prostaglandins partly control these mechanisms. Modern therapeutics are increasingly directed towards improving gastric cytoprotection.