The pathophysiology of GERD involves contact of the esophageal epithelium with acid/pepsin in the refluxate. For this contact to occur with sufficient duration, there must be a combination of defects in antireflux and luminal clearance mechanisms for acid/pepsin to overwhelm an intact epithelium, or defects within the epithelium develop that subsequently enable normal acid contact times to become damaging to the epithelium. In either case, the final common pathway is damage to the esophageal epithelium--damage that is reflected in the development of heartburn, esophageal necrosis and inflammation, or both.