The pathogenesis of gastroesophageal reflux disease: the relationship between epithelial defense, dysmotility, and acid exposure

Abstract

Gastroesophageal reflux disease (GERD) is a complex, multifactorial disease for which the initiating factors are unknown. Acid in contact with the esophageal epithelium, however, is a central event in the development of the disease--the disease developing when acid overwhelms the intrinsic esophageal epithelial defenses. Acid breakdown of the tissue defenses is what ultimately leads to symptom production, ulceration, and other complications of GERD. Patients with GERD generally, although not always, have more episodes of reflux than healthy subjects; this is due to more frequent transient lower esophageal sphincter relaxations in the disease group. GERD patients may also have some impairment in peristaltic frequency on swallowing and/or weakness in the strength of peristaltic contractility. Contributions from other components of the acid clearance and tissue-defensive mechanisms are possible but remain to be adequately established as contributing to GERD. It is likely that one reason for the wide clinical spectrum observed with GERD results from differences in types and degrees of defects within the tripartite esophageal defensive system against damage from the phenomenon of gastroesophageal reflux.