ROLE OF LUMINAL H+ IN THE PATHOGENESIS OF EXPERIMENTAL ESOPHAGITIS

Abstract

The pathogenesis of acidic reflux esophagitis was investigated in an experimental model with special emphasis on the role of lumen-to-mucosa diffusion of H+ in the pathogenetic mechanism. Esophageal damage was produced by perfusing an isolated segment of rabbit esophagus in situ with 3 injurious endogenous secretions of the upper gastrointestinal tract (taurocholate, 10 mM; pepsin, 2500 U/ml; lysolecithin, 2 mg/ml) with and without acid (HCl, 10-150 mM). The severity of mucosal damage was assessed using as indicators of mucosal integrity transmucosal potential difference, net flux of Na+ and mucosal permeability to 2 neutral molecules of different sizes-3H-H2O and 14C-erythritol. Although the presence of luminal acid is needed for mucosal damage to develop, there is no relationship between the severity of the damage and the magnitude of the lumen-to-mucosa diffusion of H+. Even markedly increased diffusion of H+ alone, induced by an unphysiologically high concentration of luminal acid (300 mM HCl), had only a minor influence on mucosal integrity, whereas all 3 test agents were able to cause severe mucosal damage in association with much lower rates of H+ diffusion. The severity of the mucosal damage caused by an individual test agent was not dependent on the HCl concentration used (and hence on the magnitude of lumen-to-mucosa diffusion of H+). Esophageal mucosal damage caused by taurocholate, pepsin or lysolecithin in the presence of luminal acid may be due to the direct action of the agent itself rather than to excessive accumulation of luminal H+ into the mucosal tissue.