Introduction GERD is one of the most prevalent gastrointestinal disorders. Population-based studies show that up to 15% of individuals have heartburn and/or regurgitation at least once a week, and 7% have symptoms daily. Symptoms are caused by backflow of gastric acid and other gastric contents into the esophagus due to incompetent barriers at the gastroesophageal junction. Pathophysiology The normal antireflux mechanisms consist of the LES, the crural diaphragm, and the anatomical location of the gastroesophageal junction below the diaphragmatic hiatus. Reflux occurs only when the gradient of pressure between the LES and the stomach is lost. It can be caused by a sustained or transient decrease in LES tone. A sustained hypotension of the LES may be due to muscle weakness that is often without apparent cause. Secondary causes of sustained LES incompetence include scleroderma-like diseases, myopathy associated with chronic intestinal pseudo-obstruction, pregnancy, smoking, anticholinergic drugs, smooth-muscle relaxants (-adrenergic agents, aminophylline, nitrates, calcium channel blockers, and phosphodiesterase inhibitors), surgical damage to the LES, and esophagitis. tLESR without associated esophageal contraction is due to a vagovagal reflex in which LES relaxation is elicited by gastric distention. Increased episodes of tLESR are associated with GERD. A similar reflex operates during belching. Apart from incompetent barriers, gastric contents are most likely to reflux (1) when gastric volume is increased (after meals, in pyloric obstruction, in gastric stasis, during acid hypersecretion states), (2) when gastric contents are near the gastroesophageal junction (in recumbency, bending down, hiatal hernia), and (3) when gastric pressure is increased (obesity, pregnancy, ascites, tight clothes). Incompetence of the diaphragmatic crural muscle, which surrounds the esophageal hiatus in the diaphragm and functions as an external LES, also predisposes to GERD. Obesity is a risk factor for GERD. Reflux esophagitis is a complication of reflux. It develops when mucosal defenses are unable to counteract the damage caused by acid, pepsin, and bile. Mild esophagitis involves microscopic changes of mucosal infiltration with granulocytes or small numbers of eosinophils, hyperplasia of basal cells, and elongation of dermal pegs. In nonerosive reflux disease (NERD), the mucosa may be normal or mildly erythematous. Erosive esophagitis reveals clear mucosal damage with redness, friability, superficial linear ulcers, and exudates. Histology shows polymorphonuclear or mild eosinophilic infiltrates and granulation tissue. Peptic stricture results from fibrosis that causes luminal constriction. These strictures occur in ~10% of patients with untreated GERD. Short strictures caused by spontaneous reflux are usually 1–3 cm long and are present in the distal esophagus near the squamocolumnar junction (Fig. 286-2, panel 6). Long, tubular peptic strictures can result from persistent vomiting or prolonged nasogastric intubation. Erosive esophagitis may heal by intestinal metaplasia (Barretts esophagus), a risk factor for adenocarcinoma.