Pathogenesis of duodenal ulcer disease: the rest of the story

Although several duodenal ulcer disease-specific abnormalities in gastric function have been described (e.g. exaggerated gastrin releasing peptide-stimulated acid secretion and an abnormal sensitivity of the parietal cells to gastrin), none has withstood careful examination. We describe here the critical nature of the duodenal acid load in precipitating and washing out bile salts, which inhibit the growth of Helicobacter pylori (H. pylori) in the development of duodenal ulcer disease. The risk of duodenal ulcer is enhanced by infection with proinflammatory H. pylori (e.g. with an intact cog pathogenicity island). Progressive damage to the duodenum promotes gastric metaplasia, resulting in sites for H. pylori growth and more inflammation. This cycle results in an increasing inability of the duodenal bulb to neutralize acid entering from the stomach until changes in duodenal bulb structure and function are sufficient for an ulcer to develop. Cure of the H. pylori infection results in a sustained fall in duodenal acid load as well as a marked (and continuing) reduction in inflammation, which results in the cure of chronic ulcer disease.