Ultrastructural effects of ulcerogens.
Agents such as ethanol, aspirin, bile acids, and hypertonic urea and glucose, are capable of breaking the physiological gastric mucosal barrier and may cause ultrastructural injury to the epithelial cells within several minutes of exposure. Ethanol at any pH, and aspirin and bile acids at acid pH, are lipid soluble and diffuse rapidly into surface epithelial cells where a sequence of injury can be documented by electron microscopy. First, the nuclear chromatin becomes clumped and the density of the cytoplasmic ground substance decreases. Second, mitochondria become swollen and the apical cell membrane is distorted. Finally, the apical cell membrane ruptures and the cell disintegrates. Throughout this sequence, the tight junctions between cells appear morphologically intact. In contrast to lipid soluble agents, hypertonic urea and glucose do not diffuse well into surface epithelial cells. Although these agents also cause rapid changes in transmucosal potential difference and ion fluxes, their ultrastructural effects are quite different. Hypertonic urea and glucose initially cause small blebs within the tight junctions and larger vacuoles within the cytoplasm of surface epithelial cells, while the remainder of the cell structure appears normal. More severe injury is characterized by more vacuolization and eventual disruption of epithelial cells. These changes presumably are secondary to osmotic shifts of fluid and electrolytes. Although the 'cytoprotective' effects of prostaglandins have been well described, there is virtually no information at the ultrastructural level concerning the protective effects of prostaglandins with regard to these ulcerogenic agents.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000648:ultrastructure*; D006982:Hypertonic Solutions; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D014508:Urea / Q000494:pharmacology
D001647:Bile Acids and Salts; D006982:Hypertonic Solutions; D000431:Ethanol; D014508:Urea