Mechanisms of mucosal injury in the stomach and duodenum: time-sequence analysis of morphologic, functional, biochemical and histochemical studies.
This review is based on results from our laboratory and those published by others, and is focused on the early stages of pathogenesis that can be studied mostly in animals. Gastric mucosal injury is analysed on the examples of ethanol- and aspirin-induced lesions. Ethanol (50-100%) rapidly penetrates the mucosa, causes directly and/or indirectly (e.g., release of vasoactive products) endothelial damage in superficial and deep capillaries and venules. The vascular damage results in increased vascular permeability and decrease in blood flow leading to complete circulatory standstill in superficial capillaries 1-2 min after intragastric administration of concentrated ethanol. The direct chemical damage to surface mucosal epithelium is then followed by hypoxia and deep hemorrhagic necrosis in 1-5 min (erosion or ulcer). Unionized aspirin initiates a similar and complex yet slower progressing and less extensive erosion than alcohol. Duodenal erosion and ulcer produced by cysteamine, mepirizole or MPTP are preceded by excess acid in the proximal duodenum. This could be due to increased gastric acid output (1-4 hr), decreased bicarbonate secretion or duodenal dysmotility (0.5-8 hr) preventing the proper mix of acid and base in duodenal bulb. Necrosis and desquamation of absorptive cells in duodenal villi are evident 2-4 hr, followed by villus amputation (4-8 hr), erosion and ulcer (8-24 hr). The pathogenesis of gastroduodenal mucosal injury can thus be reconstructed from results obtained with animal models and from human studies. The results should serve as a basis to design protective drugs that are active on the basis of pathogenetic events.
Szabo
S
S
D000818:Animals; D001241:Aspirin; D004381:Duodenal Ulcer / Q000209:etiology; D004386:Duodenum / Q000503:physiopathology*; D000431:Ethanol; D005753:Gastric Mucosa / Q000503:physiopathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000503:physiopathology*; D051381:Rats; D013997:Time Factors
D000431:Ethanol; D001241:Aspirin