Rapid epithelial restitution of the superficially-damaged gastric mucosa

Abstract

Studies begun in the 1950s and 1960s1-5 elucidated some of the mechanisms by which extremely steep ionic gradients could be maintained across the gastric mucosa. The concept of the ‘gastric mucosal barrier’ was developed during this time from physiological experiments which showed that luminally-applied agents such as bile acids, various alcohols, hypertonic solutions and salicylates increased gastric mucosal permeability but also often resulted in frank bleeding into the gastric lumen6-8. Under these conditions which broke the barrier, there was a rapid back diffusion of hydrogen ions from the gastric lumen into the tissue and a concomitant loss of tissue sodium ions. From these studies, a feed forward loop was hypothesized which suggested that acid back diffusion not only resulted in tissue damage but indirectly stimulated parietal cells to secrete more acid into the lumen which initiated additional cycles of this loop9. While there is substantial experimental evidence to verify each component of this model, the cause and effect relationship between breaks in the gastric mucosal barrier and the development of gastric erosions is not understood6. Until recently there has not been sufficient data from which to postulate a mechanism by which this feed forward cycle (acid back diffusion, tissue damage, parietal cell stimulation, acid secretion) could be terminated. This in turn has put emphasis on the prophylactic aspects of gastric mucosal defence while little attention has been focused on the reparative aspects of the damaged barrier.