The role of gastrin in ulcer pathogenesis.

Duodenal ulcer patients are characterized by an antrum-predominant, body-sparing, nonatrophic Helicobacter pylori (H. pylori) gastritis, which results in increased gastrin release and increased acid secretion. The increased gastrin release is caused by the infection impairing the acid-mediated inhibitory control of gastrin release. The elevated levels of the gastrin stimulate the healthy uninflamed, non-atrophic acid-secreting region of the stomach to secrete excess amounts of acid. The increased gastrin also exerts trophic effects on the oxyntic mucosa, causing hyperplasia of both the enterochromaffin-like cells and the parietal cells. These trophic changes in the mucosa further enhance its ability to secrete acid. The increased acid secretion results in an increased duodenal acid load, causing gastric metaplasia of the duodenal bulb and eventually the development of ulceration. In H. pylori-infected subjects without duodenal ulceration, a different pattern of gastritis is seen. This includes atrophy of the antrum, which reduces the number of G-cells and thus the degree of hypergastrinaemia induced by the antral infection. There are usually also varying degrees of inflammation and atrophy of the acid-secreting mucosa, which impair its ability to secrete acid in response to gastrin stimulation. The combined effects of the atrophy of the antrum and the inflammation of the antrum of the body mucosa therefore prevent H. pylori-induced acid hypersecretion and may result in varying degrees of hypochlorhydria. The particular pattern of gastritis that a subject develops in response to H. pylori infection and their likelihood of developing a duodenal ulcer is likely to be determinded by host genetic factors plus dietary factors.