Pathophysiology of gastroesophageal reflux disease.

The pathophysiology of gastroesophageal reflux disease remains incompletely understood. Its hallmark symptom is "heartburn" and, on the basis of endoscopy, those with heartburn are subdivided into nonerosive reflux disease and erosive esophagitis. Although subjects with nonerosive reflux disease have no gross damage on endoscopy, a characteristic histopathologic feature of this disease is present on endoscopic biopsy. This lesion is known as "dilated intercellular spaces," a finding present within squamous epithelium. This report details how acid in contact with a damaged esophageal epithelium leads to heartburn and to the progression of nonerosive reflux disease to erosive esophagitis. It also addresses the fact that esophageal pH monitoring may be normal in a significant number of subjects with heartburn, particularly with nonerosive reflux disease, and details how this observation suggests that in addition to defects in the antireflux barrier, for example, transient lower esophageal sphincter relaxations and low lower esophageal sphincter pressure, defects in tissue resistance created by contact with ingested products may also be etiologic in some subjects with gastroesophageal reflux disease.