Pathophysiology of Gastroesophageal Reflux Disease: Epithelial Factors

This chapter focuses primarily on esophageal tissue resistance as a defense mechanism against gastroesophageal reflux disease and how this tissue resistance is overcome during the pathogenesis of reflux esophagitis. Among the most common noxious agents are the components of gastric refluxate, including acid, pepsin, and bile acids. Acid is made by the gastric parietal cells, and gastric juice typically has a pH of 2 in the fasting state. Concentrated acid can kill epithelial cells by denaturing their vital proteins, activating phospholipases and endonucleases, interfering with cell respiration, and impairing cell volume regulation. To understand how the esophagus generates its defense mechanisms, it is important to first understand esophageal development. An indicator of the functional integrity of the esophageal epithelial barrier is the finding of increased epithelial intercellular space width, termed dilated intercellular spaces.