PEPTIC-ULCER PATHOPHYSIOLOGY - ACID, BICARBONATE, AND MUCOSAL FUNCTION

The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation betw een acid output and clinical outcome of ulcer disease, or between ulce r recurrence rate after vagotomy and preoperative acid secretion. Ar t he same time, studies have been unable to demonstrate increased acidit y in the duodenal bulb in patients with duodenal ulcer, and consequent ly more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate se cretion creates a pH gradient from the luminal acid to near neutrality at the surface of the epithelial cells, thereby acting as an importan t mucosal defence mechanism. The regulation of bicarbonate secretion i s a complex process related to motility and neural activity. Stimulati on is by acid, PGE(2), NO, VIP, cAMP, and mucosal protective agents. B icarbonate secretion is inhibited by atropine, muscarinic antagonists, alpha-adrenoceptor agonists, indomethacin, bile acids, tobacco smokin g, and probably also by infection by Helicobacter pylori. Apart from m ucus and bicarbonate, the mucosal defence is supported by a hydrophobi c epithelial lining, rapid cell removal and repair regulated by epider mal growth factor. Sufficient mucosal blood flow, including a normal a cid/base balance, is important for subepithelial protection. In today' s model of ulcer pathogenesis, gastric acid and H. pylori work in conc ert as aggressive factors, with the open question being: why does only a fraction of the infected population develop an ulcer?