Experimental pathogenesis: drugs and chemical lesions in the gastric mucosa.
The goals of this article are to review the similarities and differences in the pathogenesis of acute gastric mucosal injury induced by alcohol, exemplified mostly by ethanol, and aspirin, as a representative of nonsteroidal anti-inflammatory drugs, and to deduce implications from pathogenetic studies for a better understanding of the concept of gastric cytoprotection. The main similarity between the hemorrhagic erosions caused by ethanol and aspirin is their localization in the acid-producing glandular stomach, the rate-limiting step in their pathogenesis being the extent of microvascular injury in the gastric mucosa. The major differences include the fast healing and low probability of transition into chronic gastritis after a single exposure to aspirin. On the other hand, perforated ulcer may develop, especially in the elderly, after chronic aspirin but not ethanol consumption. The main implications of pathogenetic investigations include the relative nature of gastroprotection: that is, initially, the superficial epithelial layer is not protected against concentrated luminal solutions, but it is rapidly replaced by migrating, adjacent, surviving cells if blood flow is maintained and the basement membrane is relatively intact. Vascular changes thus seem to be the rate-limiting step both in the pathogenesis and prevention of chemically induced acute gastric mucosal injury. The ultimate biochemical mechanisms of gastroprotection seem to include an effect on structural and enzymic proteins, and vascular mediators which influence vascular permeability and, indirectly, the extent of tissue injury.
Szabo
S
S
Dept. of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Goldberg
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity*; D004381:Duodenal Ulcer / Q000139:chemically induced; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013276:Stomach Ulcer / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000431:Ethanol; D001241:Aspirin