Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

Abstract

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.

Keywords: advancement; anti-reflux barrier disruption; dynamic mechanism; esophageal clearance impaired; gastroesophageal reflux disease.

Figure 1

Incidence of GERD symptoms worldwide. Generally, the prevalence rate is relatively high in developed western countries and lower in Asia.

Figure 2

Structural characteristics of the LES. (A) In healthy people, LES contraction can lead to an increased LES pressure that can prevent acidic gastric contents from reflux. However, LES dysfunction in patients with GERD can lead to acidic gastric content regurgitation. (B) Reflux occurs when the resting pressure of LES is abnormally low, resulting in higher gastric pressure than esophageal pressure.

Figure 3

Anti-reflux barrier disruption at the esophageal junction. (A and B) In healthy people, the resting pressure of LES, an anti-reflux barrier at the esophagogastric junction, is approximately 10-30 mmHg. (C) People with obesity, pregnancy, or gastric emptying disorders had significantly higher gastric pressure and average gastroesophageal pressure gradient, which promoted the GERD occurrence. In addition, hypotensive LES, hiatal hernia, and dysmotility are also related to GERD occurrence.

Figure 4

TLESR mechanism of GERD. In the case of gastric distention, the vagal afferent fibers around EGJ are activated, and the nerve impulses after activation are transmitted along the vagal afferent fibers to the solitary tract nucleus. Subsequently, it triggers the signal transmission between the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), and finally nerve impulses are transmitted along the efferent fibers of the vagus to the LES and crural diaphragm, weakening the role of the anti-reflux barrier and causing the onset of GERD.

Figure 5

Classification of HH. (A) Type I is a sliding HH with a small hernia sac. (B) Type II is a para-hiatal hernia in which the fundus of the stomach can enter the thoracic cavity through the hiatus. (C) Type III is a mixed HH. The esophageal hiatus has large defects, but no other organ in the abdominal cavity can enter the thoracic cavity. (D) Type IV is a giant HH in which the stomach and other organs pass through the esophageal hiatus and enter the thoracic cavity due to the defect of the huge esophageal hiatus.