Why is the high grade inhibition of gastric acid secretion afforded by proton pump inhibitors often required for healing of reflux esophagitis? An epithelial perspective.

The effectiveness of proton pump inhibitors in the treatment of reflux esophagitis is undisputed. The same is true for the mechanism by which their beneficial effects are achieved and, that is, by potent suppression of gastric acid secretion. The underappreciated side of the story is not that potent acid suppression controls the disease but why in fact such potent acid suppression is often required for control of reflux esophagitis when experience dictates that much lesser reductions in gastric acid secretion are effective for control of peptic ulcer disease of stomach and duodenum. The present discussion, which views this issue from the perspective of the epithelium, concludes that specific differences between the nature of gastroduodenal and esophageal epithelial defenses could explain the apparent need for greater suppression of gastric acid secretion to control acid-peptic injury to esophagus as opposed to that of stomach and duodenum. Among the differences cited that may account for the reduced acid-resistance of the esophageal epithelium are: 1) a lack of mucus and bicarbonate secretion by surface epithelial cells, 2) a lack of defensive enhancement by prostaglandin release, 3) a lack of an effective mucus cap after injury, and 4) an apparent lack of capacity to rapidly heal erosions by the process of epithelial restitution.