Levi, Sassoon; (1991) Studies of the mechanisms of peptic ulceration. Doctoral thesis (M.D), University of London, Royal Free Hospital School of Medicine.

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Abstract

The pathologic mechanisms behind two risk factors for peptic ulceration have been considered: 1. Non-steroidal anti-inflammatory drugs (NSAIDs), which are associated with gastric as well as duodenal damage, and 2. Infection of the gastric antrum with Helicobacter pylori (HP), which is strongly associated with duodenal ulcer (DU). NSAIDs and the gastroduodenal mucosa: At low doses, the normal gastric and duodenal epithelia in man and the rat adapt to NSAID administration by increasing the rate of cell turnover. In man this is accompanied by an increase in gland and crypt duplication by fission. However, indomethacin exacerbates and reduces the rate of healing of experimentally induced gastric ulcers in the rat by specifically inhibiting the regenerative response at the ulcer edge. Likewise patients on NSAIDs with gastric and duodenal ulcers showed markedly lower rates of regeneration at the ulcer edge than patients with ulcers at the same locations not taking NSAIDs. This may explain the greater prevalence of ulcers in patients taking NSAIDs. Large doses (300 μg/kg/d) of misoprostol, a prostaglandin El analogue, reversed the indomethacin-induced inhibition of regeneration at the ulcer edge in the rat. However, in usual therapeutic doses (approx. 10 μg/kg/d) misoprostol failed to influence gastroduodenal proliferation in rat or man. Helicobacter pylori, duodenal ulcers and gastrin: We have also considered the relationship between antral HP colonisation, antral gastrin release and gastric acid secretion. I show that pentagastrin stimulated gastric acid secretion and postprandial plasma gastrin concentrations are significantly higher in HP+ve compared with HP-ve patients with DUs. Furthermore, eradication of antral HP significantly reduces postprandial plasma gastrin responses. These findings may explain the strong association of DUs with antral HP infection, and the lower relapse rates of DU following treatments which eradicate this organism from the antrum.

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