The effect of Helicobacter pylori infection on gastric acid secretion in man

El-Omar, Emad Munir Abdel-Gabbar (1995) The effect of Helicobacter pylori infection on gastric acid secretion in man. MD thesis, University of Glasgow.

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Abstract

Helicobacter pylori (H pylori) infection is the commonest chronic bacterial infection world-wide. The work carried out in this thesis has sought to explore the effect of the infection on gastric secretory function in man. We developed a new test of gastric acid secretion using the substance gastrin releasing peptide (GRP) as the stimulus. Acid secretion measured in response to intravenous infusion of GRP reflects the combined functional response of the antrum and body of the stomach. It activates both stimulatory and inhibitory controls of acid secretion and in these respects it simulates the response to eating. The reproducibility of the GRP test was assessed and was found to be high for both gastrin and acid secretion. Using this new tool we studied acid secretion in a variety of subjects with and without H pylori infection. We have found that GRP stimulated acid secretion is increased six fold in DU patients with the infection compared to H pylori negative healthy volunteers (true normals). This exaggerated acid response is likely to represent a key pathophysiological defect which underlies DU disease. We have demonstrated for the first time that eradication of H pylori infection leads to normalisation of basal and GRP stimulated acid secretion in DU patients. These novel findings have shed considerable light on the understanding of the pathophysiology of DU disease and the role of H pylori infection in it. We have also shown for the first time that GRP stimulated acid secretion is increased two to three fold in H pylori positive healthy volunteers compared to true normals. This secretory abnormality also fully resolves following eradication of the infection. Since half the world's population is colonised with H pylori, it is essential that all future gastric secretory studies ensure that their control subjects are negative for the infection. The presence of the secretory abnormality in healthy volunteers may also be of relevance to other upper Gl diseases such as reflux disease. We proceeded to investigate the mechanism of the exaggerated acid response to GRP in DU patients and presented evidence compatible with this being due to impaired inhibitory control of acid secretion. We proceeded to examine the effect of the most commonly prescribed medication for dyspepsia, i.e. ranitidine, on acid secretion in healthy volunteers with and without H pylori infection. We showed that a two month course of ranitidine leads to a doubling of basal acid output and a 68% increase in GRP stimulated acid output two days after withdrawing treatment. This rebound acid hypersecretion is not associated with any significant change in gastrin concentrations and fully resolves within ten days of stopping ranitidine. These findings may offer an explanation for the common clinical problem of rapid resurgence of dyspeptic symptoms following discontinuation of acid suppressive therapy. Finally, we used the GRP test to study acid secretion in patients with non ulcer dyspepsia (NUD) and H pylori infection. We showed that a significant proportion of NUD patients had an exaggerated acid response to GRP similar to DU patients i.e. they displayed the DU diathesis. This raises the exciting possibility that this group of NUD patients may also be cured by eradication of their H pylori infection.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Kenneth McColl
Keywords: Microbiology
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-71699
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 17 May 2019 09:31
URI: http://theses.gla.ac.uk/id/eprint/71699

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