Non-acid mechanisms of gastric and duodenal ulcer formation

The pathophysiology of gastric and duodenal ulcer disease has two sides: the aggressive attack, principally by the highly corrosive gastric acid; and the defending forces of mucus, mucosal resistance, and other protective substances and functions. This report reviews the roles of both the attacking and defending forces in the pathophysiology of ulcer disease. It also discusses how an early notion of ulcer formation (e.g., the Schwarz dictum of "no acid, no ulcer," first published in 1910) became the slogan by which ulcer disease was understood and from which therapy took its cue. Subsequent work has since found that the Schwarz dictum holds for duodenal ulcer, but not for gastric ulcer. Non-acid mechanisms of ulcer formation--i.e., impairment of at least one of the defending or protective forces--are also described, as are treatment approaches to ulcer disease. Although suppression of acid secretion is a mainstay of treatment, agents that safely and effectively strengthen the defense are being used more frequently. There are signs that the safe limits for acid-suppressing therapy have been reached or passed. On the other hand, the search for therapy that strengthens the defensive factors has only begun.