Pathogenesis of Gastric Mucosal Injury

During the past two decades considerable insight has been gained into the pathogenesis of gastric mucosal injury and the mechanisms by which the gastric mucosa defends itself against injury. In spite of high concentrations of hydrochloric acid and pepsin, the stomach does not digest itself. In the 19608 Davenport demonstrated the presence of a gastric mucosal barrier to the back-diffusion of acid, which prevents such autodigestion. Certain topi­ cal agents, however, disrupt this barrier and gastric mucosal injury then occurs. Davenport described the sequence of pathophysiological events following such barrier breaking. In the past decade Robert, Whittle, and others showed that the gastric mucosal synthesis of prostaglandins plays an important role in the gastric defensive mechanism. Exogenously adminis­ tered prostaglandin as well as endogenously synthesized prostaglandin can protect the gastric mucosa against a variety of injurious agents even in the presence of acid. Conversely, depletion of endogenous gastric mucosal pros­ taglandin by agents that inhibit prostaglandin synthesis, such as the non­ steroidal anti-inflammatory compounds, is an important pathogenetic factor in gastric mucosal injury induced by such agents. The protection of the gastric mucosa against injury by a mechanism other than inhibition of acid secretion has been called cytoprotection. This article reviews the cur­ rent status of our knowledge concerning the pathogenesis of gastric mucosal injury and how the gastric mucosa defends itself against injury, including both barrier mechanisms and cytoprotection and their relevance to clinical disease.