The LES provides a pressure barrier between the esophagus and stomach. Although an anatomically distinct LES has been difficult to identify, microdissection studies show that, in humans, the sphincterlike function is related to the architecture of the muscle fibers at the junction of the esophageal tube with the gastric pouch. The sphincter actively remains closed to prevent reflux of gastric contents into the esophagus and opens by a relaxation that coincides with a pharyngeal swallow . The LES pressure returns to its resting level after the peristaltic wave has passed through the esophagus. Consequently, reflux of gastric juice that may occur through the open valve during a swallow is cleared back into the stomach.
If the pharyngeal swallow does not initiate a peristaltic contraction, then the coincident relaxation of the LES is unguarded and reflux of gastric juice can occur. This may be an explanation for the observation of spontaneous LES relaxation, thought by some to be a causative factor in gastroesophageal reflux disease (GERD). The power of the esophageal body is insufficient to force open a valve that does not relax. The relaxation of the LES that occurs with pharyngeal swallowing or distention of the esophagus is mediated by parasympathetic activity. Consequently, vagal function appears to be important in coordinating the relaxation of the LES with esophageal contraction.
The LES has intrinsic myogenic tone, which is modulated by neural and hormonal mechanisms. Alpha-adrenergic neurotransmitters or beta-blockers stimulate the LES, and alpha blockers and beta stimulants decrease its pressure. It is not clear to what extent cholinergic nerve activity controls LES pressure. The vagus nerve carries both excitatory and inhibitory fibers to the esophagus and sphincter. The hormones gastrin and motilin have been shown to increase LES pressure; and cholecystokinin, estrogen, glucagon, progesterone, somatostatin, and secretin decrease LES pressure. The peptides bombesin, B-enkephalin, and substance P increase LES pressure; and calcitonin gene-related peptide, gastric inhibitory peptide, neuropeptide Y, and vasoactive intestinal polypeptide decrease LES pressure. Some pharmacologic agents such as antacids, cholinergics, domperidone, metoclopramide, and prostaglandin F2 are known to increase LES pressure; and anticholinergics, barbiturates, calcium channel blockers, caffeine, diazepam, dopamine, meperidine, prostaglandin E1 and E2, and theophylline decrease LES pressure. Peppermint, chocolate, coffee, ethanol, and fat are all associated with decreased LES pressure and may be responsible for esophageal symptoms after a sumptuous meal.
During 24-hour esophageal pH monitoring, healthy individuals have occasional episodes of GE reflux. This physiologic reflux is more common when a person is awake and in the upright position than during sleep in the supine position. When reflux of gastric juice occurs, normal subjects rapidly clear the acid gastric juice from the esophagus regardless of their position.