The studies reviewed suggest that the presence of luminal acid is essential for acute gastric stress ulceration to occur and that acid promotes ulceration by diffusing into the mucosa in an ulcerogenic situation. Disruption of the mucosal barrier by the presence of e.g. intragastric bile salts, aspirin, or ethanol increases the hydrogen ion back diffusion, thereby increasing the susceptibility of the mucosa to ulceration. Such a disruption is presumably needed for development of ulcerations in species with a “tight” gastric mucosa, such as the dog, the pig and man, whereas in species with a “leaky” mucosa, such as the rabbit or rat, ulceration occurs even without these agents. However, the response of the mucosa to hydrogen ions is not uniform. Luminal acidities and rates of hydrogen ion back diffusion that are normally harmless may in certain situations cause severe damage to the mucosa.

Thus, the ability of the mucosa to withstand the influxing hydrogen ions is as important as the absolute amount of hydrogen ions diffusing into the mucosa. If the rate of hydrogen ion back diffusion exceeds the ability of the mucosa to dispose of hydrogen ions, acidification of the mucosa occurs, with resultant breakdown of the tissue. The main factors modulating the response of the mucosa to hydrogen ions are availability of bicarbonate in the mucosa and the mucosal blood flow. Bicarbonate contributes to mucosal protection through secretion by the epithelium to form an “alkaline” buffer layer at the epithelial surface, which seems to act as a “firstline” defence mechanism against the influxing hydrogen ions.

In addition, bicarbonate seems to act as an intracellular buffer to neutralise hydrogen ions. Factors that impair the supply of bicarbonate to the mucosa, such as metabolic “low bicarbonate” acidosis, mucosal ischaemia or low hydrogen ion secretion with a decreased attendant “alkaline tide” of bicarbonate, increase the sus-pectibility of the mucosa to ulceration. In addition to delivering bicarbonate to the mucosa, an adequate mucosal blood flow is needed to wash out the influxing hydrogen ions and metabolic waste products from the mucosa and to supply oxygen and other nutrients to the mucosa for maintenance of a normal metabolic state.