Is acid the cornerstone factor in gastroesophageal reflux disease and its related complications?

Acid is a key factor, but not the only factor, in the pathogenesis of gastroesophageal reflux disease (GERD). Our understanding of acid's role in this disease has evolved considerably over the past decade, but much remains to be learned. The hydrochloric acid (HCl) in gastric juice alone does not appear to be capable of damaging the esophagus unless it reaches pH levels of 1.3 or less, levels uncommonly observed during reflux episodes in GERD patients. HCl combined with pepsin can cause esophageal damage at higher pH levels (∼2), but recent studies suggest that acid-peptic attack usually does not kill esophageal cells directly, but rather it induces them to secrete pro-inflammatory cytokines that attract inflammatory cells, which ultimately damage the esophageal cells. The precise mechanism whereby esophageal acid exposure elicits the sensation of heartburn also remains unclear. While gastric acid suppression with proton pump inhibitors (PPIs) has been very successful in treating reflux esophagitis and heartburn, PPIs have actions independent of acid suppression that might contribute to their beneficial effects. Thus, response to PPIs does not establish acid as the only important pathogenetic factor in GERD. Recently, it has been appreciated that pathologic acid reflux induces an esophageal dysbiosis that can contribute to esophageal inflammation and heartburn, and that might predispose the esophageal mucosa to further damage from acid reflux. This chapter focuses on what is known and what remains unclear about acid's role in GERD.