The acid pocket - a novel target for the treatment of gastro-esophageal reflux disease

Abstract

Increased acid reflux after meals is a key feature of gastro-esophageal reflux disease (GERD) and is the most important cause for patient symptoms, particularly heartburn and acid regurgitation. Chronic acid exposure also predisposes to associated pathologies including reflux esophagitis, esophageal stricture, Barrett's esophagus, and Barrett's carcinoma (esophageal adenocarcinoma). The severity of esophageal symptoms and mucosal damage is related to two key factors, (i) the acidity of the refluxate, which depends primarily on the gastric secretory output and its distribution within the stomach, and (ii) the frequency and duration of reflux events which depends on the efficacy of the reflux barrier at the gastro-esophageal junction and the esophageal clearance function. The concept of the acid pocket is an attempt to bring these two factors into a unified patho-mechanism.The acid pocket describes an area of unbuffered, highly acidic, gastric secretion in the proximal stomach adjacent to the esophago-gastric junction (GEJ) which forms in the postprandial period and is the source of acid refluxate into the esophagus. It is observed both in healthy individuals as well as in reflux patients. However, the presence of a hiatus hernia and/or a weak lower esophageal sphincter in patients allows the acid pocket to encroach on the gastro-esophageal junction. This results in very high acid exposure of the squamous epithelium of the distal esophagus, leading to mucosal damage and symptoms. Recently, the acid pocket has been proposed as a target for pharmacological and surgical therapies of GERD. Proton pump inhibitors and related medications reduce its acidity; whereas, alginate preparations, prokinetics, and fundoplication displace it away from the gastro-esophageal junction.