The Urease Activity of Helicobacter pylori and Duodenal Ulcer Disease

Neithercut, William Duncan (1992) The Urease Activity of Helicobacter pylori and Duodenal Ulcer Disease. MD thesis, University of Glasgow.

Abstract

Helicobacter pylori, a spiral shaped bacterium has recently been identified as one of the most important acquired factors in the development of duodenal ulcer disease. This organism colonises the gastric antral mucosa, the body of the stomach and areas of gastric metaplasia in the duodenum. Infection of the gastric mucosa by H pylori is associated with the development of type B gastritis, but also with the development of gastric ulcers, and more strongly with the development of duodenal ulcers. Almost 100% of individuals who have a duodenal ulcer have infection with H pylori. Eradication of H pylori infection of the antral mucosa is associated with a fall in basal plasma gastrin concentration, the meal stimulated gastrin response and gastric acid output suggesting that infection with H pylori could lead to increased gastric acidity and cause the development of duodenal ulcer disease. H pylori possesses unusually high urease enzyme activity. It has been suggested that the organism's urease activity could enable it to survive at low gastric pH by producing a cloud of ammonium which markedly raises the pH of the organism's environment and of the antral mucosal surface. The production of an alkaline microenvironment above the antral gastrin producing G cells could block the normal inhibition of gastrin release by gastric acid. An increased antral pH could also promote the uptake of amines which promote gastrin release. To examine the effects of infection on gastric ammonium concentration, plasma gastrin concentration and the creation of an alkaline microenvironment a series of studies were undertaken. The effect of infection by H pylori on the concentrations of ammonium and urea in gastric juice was investigated. The effect of stimulating and inhibiting urease activity on gastrin release was investigated. The effect of the alkalinisation of the gastric antrum on gastrin release was also investigated. The effect of urease activity on the survival of H pylori was also studied in a series of in vitro environments. Characteristic changes in the concentrations of ammonium and urea in gastric juice samples were demonstrated. In 27 subjects with duodenal ulcer disease the median (range) ammonium concentration was 3.4 mmol/L (1.0-13.0 mmol/L) when H pylori was present compared with 0.64 mmol/L (0.02-1.4 mmol/L) following eradication. In 16 subjects with chronic renal failure the median gastric juice ammonium concentration when infection was present was 20.0 mmol/L (13.9-43.1 mmol/L) compared with 4.8 mmol/L (0.5-12.3 mmol/L) when infection was absent. Gastric juice urea concentrations were lower when infection with the organism was present, median 0.8 mmol/L (0.5-2.9 mmol/L) compared with 2.1 mmol/L (1.0-3.7 mmol/L) after it had been eradicated. In subjects with chronic renal failure with infection the median gastric juice urea concentration was 2.2 mmol/L (0.5-8.7 mmol/L) compared with 13.8 mmol/L (5.4-20.8 mmol/L) when the organism was not present. The concentrations of urea and ammonium in the gastric juice samples did not clearly distinguish between the presence or absence of infection. When the urea/ammonium ratio was calculated all subjects with H pylori had a ratio of less than 0.8 while those free of infection had a ratio greater than 0.9. The urea/ammonium ratio could therefore be used to detect the presence of infection. The effect of stimulating and inhibiting urease activity, on the plasma gastrin concentration was studied. Urease activity was stimulated by the intragastric infusion of dextrose solution containing urea. Subjects with duodenal ulcer disease who had proven infection with H pylori were studied. The same subjects acted as their own controls following eradication of H pylori. The intragastric infusion of 50 mmol/L urea in a dextrose solution increased the median gastric juice ammonium concentration from 2.3 mmol/L (1.3-5.9 mmol/L) to 6.1 mmol/L (4.2-11.9 mmol/L). There was no change in plasma gastrin concentration observed during infusion of urea either before or after eradication of the organism. Inhibition of H pylori urease activity was also attempted. The specific urease inhibitor, acetohydroxamic acid was administered as a single 750 mg oral dose to 6 subjects who had duodenal ulcer disease. Inhibition of enzyme activity was demonstrated by the suppression of a 14C-urea breath test administered shortly after the dose of acetohydroxamic acid and reversion of the urea/ammonium ratio to that of non-infected subjects. No change in the basal plasma gastrin concentration or meal stimulated gastrin response occurred following inhibition of urease activity. Some investigators have failed to observe a rise in plasma gastrin concentration in response to alkalinisation of the gastric antrum. This could explain why stimulating and inhibiting urease activity failed to alter plasma gastrin concentrations. (Abstract shortened by ProQuest.).

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Kenneth McColl
• Keywords: Medicine, Pathology, Microbiology
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-74730
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 13 Nov 2019 15:58
• Last Modified: 13 Nov 2019 15:58
• URI: https://theses.gla.ac.uk/id/eprint/74730