Pylori
Learning objectives
1. Describe the regulation of gastric secretion 2. Discuss the pathophysiology of peptic ulcer disease and the role of H. pylori 3. Discuss the pharmacological basis for the treatment of peptic ulcer disease and H. pylori 1. Discuss the epidemiology of peptic ulcer disease
Gastrin stimulates the release of HCl from parietal cells both indirectly and directly
Actions of Gastrin
i. ii. Acts on parietal cells directly Promotes release of histamine from ECL cells
Binding to CCKB receptors on both
iii. iv.
Causes chief cells to secrete pepsinogen Promotes stomach contraction and relaxation of pyloric sphincter
Somatostatin is released from D cells in the gastric antrum in response to increased gastric acidity and suppresses release of gastrin
Increased acidity also reduces secretion of gastrin by negative feedback
These effects may be potentiated by environmental factors e.g. smoking some remain asymptomatic
Gastric cancer
Presents with anorexia, weight loss, anaemia Usually incurable
Vast majority >95% attributable to H.pylori Small minority occurring in subjects never infected due to strong genetic predisposition
E.g. autosomal dominant E-Cadherin germline mutation
H.pylori is a necessary but not sufficient factor for noncardia gastric cancer
Screening of H.pylori
Very complex question Intervention studies not yet shown benefit in reducing cancer incidence All studies so far based on assumptions therefore results uncertain Less controversial Non-invasive H.pylori test and treating dyspeptics Reduce H.pylori prevalence by improving living conditions