Pathophysiology and management of gastroesophageal reflux disease.

Gastroesophageal reflux is a physiological phenomenon but becomes pathological if troublesome symptoms and/or complications occur. Gastroesophageal reflux disease (GERD) has different phenotypes ranging from non-erosive reflux disease (NERD), through reflux esophagitis and Barrett's esophagus, and can present with either typical symptoms such as regurgitation and heartburn, or extra-esophageal symptoms such as cough and laryngitis. In the diagnosis of GERD endoscopy, empirical PPI test, and pH impedance testing all have their own position. Although proton pump inhibitors (PPIs) are very effective in the treatment of esophagitis, a significant proportion of patients have persistent symptoms even during high dosing of PPIs. Therefore, insight into the multifactorial pathophysiology of GERD is needed to develop new anti-reflux therapies. The predominant mechanism underlying reflux is the transient lower esophageal sphincter relaxation (TLESR). Hiatal hernia, impaired esophageal clearance and reduced lower esophageal sphincter pressure play a significant role in patients with moderate to severe reflux disease. Refluxate containing acid, pepsin and bile can cause epithelial injury when epithelial barrier of the esophagus fails to defend. In the majority of patients there is histopathological evidence of epithelial injury, even with NERD where there are more dilated intercellular spaces. The perception of heartburn can be enhanced due to visceral hypersensitivity, leading to more and more severe symptoms. Anti-reflux surgery is as effective as PPI therapy, but has higher morbidity and results decline in the long term. Therefore, new pharmacological, endoscopic and surgical interventions are being developed for these patients.