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 between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from the luminal acid to near neutrality at the surface of the epithelial cells, thereby acting as an important mucosal defence mechanism. The regulation of bicarbonate secretion is a complex process related to motility and neural activity. Stimulation is by acid, PGE2, NO, VIP, cAMP, and mucosal protective agents. Bicarbonate secretion is inhibited by atropine, muscarinic antagonists, alpha-adrenoceptor agonists, indomethacin, bile acids, tobacco smoking, and probably also by infection by Helicobacter pylori. Apart from mucus and bicarbonate, the mucosal defence is supported by a hydrophobic epithelial lining, rapid cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question being: why does only a fraction of the infected population develop an ulcer?