Schiessel R

Ulceration of Isolated Amphibian Gastric Mucosa

Protective mechanisms in gastric mucosa were investigated with the use of closed sacs and open sheets of isolated frog gastric mucosa. Closed sacs ulcerated at a high rate (80%) in a phosphate-buffered serosal medium devoid of HCO3- and gassed with 100% O2. In a nutrient solution buffered with CO2-HCO3-, the incidence of ulceration was significantly lower (10%). The protection afforded by HCO3- in the serosal solution was the same regardless of the presence or absence of CO2. Alkalinization of the serosal medium per se did not protect the mucosa, whereas buffering the luminal contents of the sacs to pH 7 completely abolished ulceration. Acetazolamide, and, to a lesser degree, SITS, increased the susceptibility of the sacs to ulceration. Open sheets of frog gastric mucosa exposed to an acidic mucosal solution (pH 2) gassed with N2 on the mucosal surface to simulate the hypoxic conditions prevailing inside the sacs showed significantly lesser decreases in PD and Isc when the serosal solution contained HCO3- than when phosphate buffer was used. Gross ulceration did not occur, however, unless the concentration of pepsin in the acidic mucosal solution was elevated to the level encountered within closed sacs. Ulceration could be induced in open sheets gassed on both sides with 100% O2 in the absence of nutrient HCO3- only upon the addition of luminal pepsin with a mucosal pH of 2.0. The data indicate that both luminal H+ and pepsin are needed for ulceration to occur in the present model. The presence of nutrient HCO3- significantly protects the mucosa, possibly by providing an intracellular buffer to neutralize the in fluxing luminal H+ and/or by maintaining a higher rate of alkali (HCO3-) secretion by the surface cells of the mucosa.

The gastric mucosal barrier and ulceration

The gastric mucosal barrier is that property which defends against acid and which impedes diffusion of acid from the lumen into the mucosa. The disappearance of luminal H+ is linearly related to luminal (H+) both in the normal stomach and in stomachs exposed to barrier breakers. The latter invaribaly produce anatomic evidence of surface cellular injury. Strong direct evidence for back diffusion of luminal H+ derives from the recent demonstration of a highly significant correlation between the disappearance of luminal H+ and the pH of the lamina propria measured by an implanted microelectrode. The permeabilities of the antrum and fundus to H+ differ from each other in the same species and in different species. Gastric ulceration does not occur in the absence of luminal acid and is not dependent upon the absolute loss of H+ from the luminal solution. Mucosal ischemia induced by hemorrhage reduces tolerance against ulceration as does inhibition of acid secretion, acidification of the tissue caused by absence of nutrient bicarbonate, inhibition of carbonic anhydrase, and blockade of anion exchange by SITS. A tentative schema is proposed by which defense against luminal acid is accomplished in gastric mucosa.