The pathophysiology of gastro-oesophageal reflux disease: an overview.

Gastro-oesophageal reflux disease (GORD) is a multifactorial disease. Although it is primarily a motility disorder, several other disturbances can interfere and contribute to determine the severity of symptoms and the degree of lesions. In normal subjects, as in patients with pathological reflux, nearly all the episodes of reflux obey one of the following three mechanisms: (a) a transient complete relaxation of the lower oesophageal sphincter (TLOSR), (b) a transient increase in intra-abdominal pressure which overcomes the resistance of the antireflux barrier ('stress reflux') and, (c) a spontaneous reflux through a permanently hypotonic sphincter. Gastric distension is the major factor that can induce TLOSRs. Whereas, at rest, the diaphragm probably plays little role in cardial competence, diaphragmatic contraction may help prevent reflux in conditions resulting in increased abdominal pressure such as during physical activity and abdominal staining. The presence of a hiatal hernia increases susceptibility to reflux. A delayed gastric emptying may also facilitate reflux and represents a factor of resistance to antireflux therapy. Most studies in humans have shown that motor abnormalities remain unchanged after healing of oesophagitis. Acid and pepsin are the most noxious agents of the upper gastrointestinal secretions that can participate in the pathogenesis of oesophagitis. However, there is no evidence that patients with reflux have greater acid secretion than subjects without reflux. The clearance function is a two-stage phenomenon requiring first a reduction in volume by peristalsis and then chemical neutralization by saliva. Primary peristalsis is mainly responsible for the clearance of acid in both the upright and the supine positions. It takes longer to clear acid in patients with non-reducing hiatal hernia. The layer of mucus which carpets the mucosa comes from the saliva and also from the submucosal glands of the oesophagus. The paracellular pathway is the major route by which mucosal HCl enters and then damages the oesophageal epithelium. Only a minority of acid reflux episodes are accompanied by symptoms. The acid exposure during the time period that precedes a reflux episode (i.e. the acid burden) is a key factor determining whether that reflux episode will be symptomatic or asymptomatic.