Roles of gastric acid and pH in the pathogenesis of gastro-oesophageal reflux disease.

In recent years, gastric acid has been shown to play a major role in the pathogenesis of reflux oesophagitis, though it remains possible that defective oesophageal mucosal resistance may also play some part. Abnormally prolonged and/or frequent exposure of the distal oesophagus to a pH of less than 4 is the major defect; this results from frequent gastro-oesophageal reflux, the impact of which is magnified in about half of the patients by slow oesophageal acid clearance. Abnormal oesophageal acid exposure increases in severity from endoscopy-negative reflux disease through worsening grades of reflux oesophagitis. Pepsin activity has been shown to be a major determinant of the aggressiveness of refluxate and, in turn, the full activity of gastric pepsin requires a pH below 3. Thus, gastric acid probably exerts a predominantly indirect effect on the pathogenesis of reflux oesophagitis by determining peptic activity. Although bile and other components of small intestinal juice can injure the oesophageal mucosa, these factors are apparently important only in the exceptional patient with very severe reflux disease. Gastric acid hypersecretion is probably also unimportant in the majority of patients. Peptic activity, and hence the aggressiveness of refluxate, are reduced markedly between pH 3 and 4. Achievement of this threshold, pH 3-4, in the daytime is important as, contrary to traditional beliefs, daytime reflux, triggered by food intake, is of the greatest importance in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)