Prostaglandins and histological changes in the gastric mucosa.
Gastric 'cytoprotection' was originally defined as the prostaglandin (PG)-mediated absence of grossly visible necrotic lesions produced by any of several necrotizing agents. It was assumed that the absence of necrotic lesions was synonymous with an undamaged mucosa. Subsequent microscopic analysis showed that PG did not protect the superficial gastric epithelium against damage by a necrotizing agent and absolute ethanol. Necrotizing agents such as absolute ethanol appear to produce two major types of damage in vivo: (i) superficial damage, which is confined to the interfoveolar, gastric pit and sometimes upper gastric glands and is not accompanied by significant hemorrhage; (ii) necrotic lesions, which are focal regions of vascular stasis, hemorrhage and associated cellular necrosis extending deep within the mucosa. PG pretreatment largely prevents the formation of necrotic lesions (but does lessen the severity of) the superficial damage. Necrotic lesions heal slowly over a period of days to months whereas superficial damage in vivo heals within approximately 60 minutes by the rapid migration of mucous cells from the gastric pit and isthmus of the oxyntic gland. Exogenous PG elicits a thicker mucus gel which has been implicated in cytoprotection. Experimental evidence now suggests that mucus may have an important role in preventing further damage, after the initial insult, by forming a cap or gelatinous layer over the injured regions. In toto these studies demonstrate three additional protective mechanisms of the superficially injured gastric mucosa: (i) a shielding gelatinous layer formed of mucus and exfoliated surface epithelial cells which forms a barrier to substances in the lumen and traps an alkaline fluid next to the healing surface; (ii) a flow of alkaline mucosal fluid into the lumen which dilutes noxious agents there and helps provide an optimum healing environment at the injured surface; (iii) a rapidly healing superficial mucosal layer which quickly reinstates the physical barrier between the gastric lumen and lamina propria. It is concluded that although PGs do not protect the superficial gastric epithelium against damage by a necrotizing agent, PGs markedly lessen the severity of damage primarily by preventing hemorrhagic lesions.
D000222:Adaptation, Physiological; D000818:Animals; D000431:Ethanol / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009093:Mucus / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology*
D011453:Prostaglandins; D000431:Ethanol