Pathophysiology of Gastroesophageal Reflux Disease

Recent data support the likelihood that GERD begins in the stomach. Fundic distention occurs because of overeating and delayed gastric emptying secondary to the high-fat Western diet. The distention causes the sphincter to be taken up by the expanding fundus, exposing the squamous epithelium with the high-pressure zone, which is the distal 3 cm of the esophagus, to gastric juice. Repeated exposure causes inflammation of the squamous epithelium, columnarization, and carditis. This is the initial step and explains why in early disease the esophagitis is mild and commonly limited to the very distal esophagus. The patient compensates by increased swallowing, allowing saliva to bathe the injured mucosa and alleviate the discomfort induced by exposure to gastric acid. Increased swallowing results in aerophagia, bloating, and repetitive belching. The distention induced by aerophagia leads to further exposure and repetitive injury to the terminal squamous epithelium and the development of cardiac-type mucosa. This is an inflammatory process, commonly referred to as carditis and explains the complaint of epigastric pain so often registered by patients with early disease. The process can lead to a fibrotic mucosal ring at the squamocolumnar junction and explains the origin of a Schatzki ring. Extension of the inflammatory process into the muscularis propria causes a progressive loss in the length and pressure of the distal esophageal high-pressure zone associated with an increased esophageal exposure to gastric juice and the symptoms of heartburn and regurgitation. The loss of the barrier occurs in a distal to proximal direction and eventually results in the permanent loss of LES resistance and the explosion of the disease into the esophagus with all the clinical manifestations of severe esophagitis. This accounts for the observation that severe esophageal mucosal injury is almost always associated with a permanently defective sphincter. At any time during this process and under specific luminal conditions or stimuli, such as exposure time to a specific pH range, intestinalization of the cardiac-type mucosa can occur and set the stage for malignant degeneration.