The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms

Abstract

Heartburn is the most common and characteristic symptom of gastroesophageal reflux disease. It ultimately results from contact of refluxed gastric acid with nociceptors within the esophageal mucosa and transmission of this peripheral signal to the central nervous system for cognition. Healthy esophageal epithelium provides an effective barrier between refluxed gastric acid and esophageal nociceptors; but this barrier is vulnerable to attack and damage, particularly by acidic gastric contents. How gastric acid is countered by defensive elements within the esophageal mucosa is a major focus of this discussion. When the defense is successful, the subject is asymptomatic and when unsuccessful, the subject experiences heartburn. Those with heartburn commonly fall into one of three endoscopic types: nonerosive reflux disease, erosive esophagitis and Barrett's esophagus. Although what determines endoscopic type remains unknown; it is proposed herein that inflammation plays a key, modulating role.

Figure 1

The diagram depicts a proposed means by which acid injury to esophageal epithelium is perpetuated by inflammation. Inflammation is shown to alter both longitudinal and circular smooth muscle function in distal esophagus, resulting in impairment in both antireflux mechanisms [reduction in lower esophageal sphincter (LES) pressure and creation of a hiatal hernia] and luminal clearance (impaired peristalsis). These defects in turn are shown to create more damage and inflammation by cycling back to induce more acid reflux.

Figure 2

The diagram depicts a proposed means by which acid injury to esophageal epithelium leads to the three common endoscopic types of gastroesophageal reflux disease (GERD): nonerosive reflux disease (NERD), erosive esophagitis, and Barrett's esophagus. Notably, all three have in common the histopathologic lesion of dilated intercellular spaces within esophageal ‘squamous’ epithelium; and inflammation is shown to be the promoter of progression from NERD to erosive esophagitis. Barrett's esophagus is an aberrant form of repair that occurs in some subjects and this is shown to extend from erosive esophagitis.