EoE ToT Module 4 References-Tack et al Gastroenterology 2018 Pathophysiology of GERD

Tack et al Gastroenterology 2018 Pathophysiology of GERD

Pdf Summary

The pathogenesis of Gastroesophageal Reflux Disease (GERD) is multifaceted, implicating reflux exposure, epithelial resistance, and visceral sensitivity. The primary symptom-inducing factor is gastric refluxate, a harmful mixture often consisting of acid, bile, and digestive enzymes, which damages the esophagus. The severity of GERD depends on the extent and duration of esophageal exposure to this refluxate, disrupted epithelial resistance, and visceral sensitivity to reflux events. Physiologically, GERD arises when the balance between the anti-reflux barrier and the esophagus's capability to clear and buffer refluxate is disturbed.<br /><br />A normal anti-reflux barrier entails structures like the lower esophageal sphincter (LES) and the crural diaphragm. Dysfunction in these components, such as transient lower esophageal sphincter relaxations (tLESRs) or low LES pressure, increases reflux events. Additional factors, including hiatal hernia and impaired esophageal motility, exacerbate GERD by prolonging mucosal exposure to gastric contents. The dysfunction of esophageal clearance mechanisms, such as peristalsis and salivation, further contributes to the persistence of refluxate in the esophagus.<br /><br />GERD exhibits diverse symptoms, not only confined to the esophagus (heartburn, regurgitation) but also extra-esophageal manifestations like laryngitis, asthma, and dental erosions. Obesity is notably correlated with GERD due to increased intra-abdominal pressure which impacts the anti-reflux barrier.<br /><br />Symptom perception in GERD individuals varies significantly and can be influenced by visceral sensitivity and central mechanisms, including stress and psychological comorbidities like anxiety and depression. Some individuals with normal esophageal acid exposure still experience symptoms due to increased sensitivity of the esophageal nerves (reflux hypersensitivity). Both peripheral factors, such as mucosal barrier integrity and afferent sensory receptor function, and central factors, affecting signal processing in the nervous system, contribute to the symptomatology of GERD.<br /><br />The ongoing research into GERD focuses on understanding these intricate interactions to develop targeted treatments, considering individual patient pathophysiology.

Keywords

GERD

pathogenesis

gastric refluxate

lower esophageal sphincter

hiatal hernia

esophageal motility

visceral sensitivity

obesity

reflux hypersensitivity

treatment