Defense mechanisms of the gastric mucosa.

The chemical and physical architecture of the apical membranes of the surface epithelial cells and of the tight junctions which bind the cells together, are such that water and water soluble substances are very slowly admitted. This impermeability is the most important factor in the defense of the gastric mucosa against damaging agents. The barrier provided by this impermeability can be measured by determining the rate of passage of substances from gastric contents to blood. Damage to the barrier will be reflected in an increase in this rate. The common ions, H+, Na+, K+, Cl- and HCO3- and water provide suitable yardsticks for the estimate. The rate of entry of H+ is the most important for it is the common agent producing serious damage to mucosal cells. The state of the barrier is not static. It can be lowered or raised. Barrier breakers are fat soluble, e.g. ethanol, bile, aspirin. They enter the apical membranes of the surface epithelial cells and in doing so permit H+ and other ions to penetrate at accelerated rates. Exposure to a damaging agent can, however, produce an increase in the resistance of the mucosa to subsequent exposures. Increased resistance of the mucosa can be accomplished also by pretreatment with prostaglandins or epidermal growth factor. Both inhibit acid secretion and this is an important element in limiting mucosal damage. Prostaglandins and some barrier breakers also increase the production of HCO3- and of mucus by the mucosa. Both may aid in disposal of damaging agents. Increases in mucosal circulation can also contribute by ridding the submucosa of damaging substances. Protective factors can also increase the impermeability of the membrane but how this is accomplished is unknown.