Pathophysiology of GERD: Lower Esophageal Sphincter Defects

44 INTRODUCTION T he most common cause of gastroesophageal reflux disease (GERD) is lower esophageal sphincter (LES) dysfunction. The LES is a 3–4 cm high-pressure zone of muscular activity in the distal esophagus. The LES is anatomically and histologically distinct from the esophageal body. Manometric and radiographic studies can be used to identify the LES. Intraluminal manometry can detect the LES as a 2–4 cm high pressure region at the gastroesophageal junction. The basal pressure of the LES is 10–45 mmHg. LES pressures are asymmetric; a higher pressure can be detected at the left side of the LES where it is abutted by the diaphragm and gastric sling fibers (Figure 1). The crural diaphragm and gastric sling fibers provide structural support and contribute to LES pressure and competence. Ultrasound images demonstrate thicker muscle at the middle of the LES compared to the proximal and distal ends (2). The LES can be distinguished from the esophageal body by its propensity to maintain tonic contraction. The ability of the LES to maintain a tone higher than structures proximal and distal is a result of spikes of calcium influx that are mediated by excitatory cholinergic neurons (1). Higher intracellular calcium levels are present in the resting LES compared to nonsphincteric esophageal muscle. The main function of the LES is to serve as a barrier to protect the esophageal mucosa and more proximal structures from potentially damaging substances in the stomach including gastric acid, pepsin, and bile salts. Incompetence in some form of the LES is the predominant determinant of GERD. The aim of this article is to review the three main LES sphincter defects that lead to GERD. These defects include transient LES relaxations, a chronically hypotensive lower esophageal sphincter, and the effects of a hiatal hernia on sphincteric function.