Mechanisms of Mucosal Injury in the Stomach and Duodenum: Time-sequence Analysis of Morphologic, Functional, Biochemical and Histochemical Studies

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Abstract
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 he 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 andlor indirectly (e.g., release of vasoactive products) endothelial damage in superficial and deep capillaries and venules. The vascular damage results in increased vascular permeability aiid decrease in blood flow leading to complete circulatory standstill in superficial capillareis 1-2 min after intragastric administration of concentrated ethanol. The direct chemical damage to surface mucosal epithelium is theu 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 preceeded by excess acid in the proximal duodenum. This could he due to increaed 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 ahsortive cells in duoceual 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 ohtained 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.