Etiology

GERD develops when reflux-promoting factors, such as corrosiveness of the gastric juice, overcome protective mechanisms, such as the gastroesophageal junction and esophageal acid clearance.

• Gastroesophageal junction dysfunction can occur because of the following factors:

  • Increased frequency of transient lower esophageal sphincter relaxations (TLESRs) [4]

    • TLESRs allow venting of accumulated gases to prevent distention of the stomach.

    • In individuals with GERD [5]

      • About two-thirds of TLESRs are also accompanied by reflux of gastric content.

      • The frequency of TLESRs increases.

  • Imbalance between intragastric and lower esophageal sphincter (LES) pressures [5]

    • Reflux occurs when the intragastric pressure is higher than that created by the LES.

    • LES tone can be decreased by substances such as caffeine and nitroglycerin, as well as by conditions that cause denervation of the muscle layer, such as scleroderma (see “Risk factors/associations” below).

    • Intragastric pressure is increased in pregnancy, delayed gastric emptying, and obesity, among other conditions.

  • Anatomic abnormalities of gastroesophageal junction (e.g., hiatal hernia, tumors)

• Impaired esophageal acid clearance [6]

  • Normally, acid reflux is neutralized by salivary bicarbonate and evacuated back to stomach via esophageal peristalsis.

  • Clearance can be disrupted by reduced salivation (e.g., due to smoking) and/or decreased peristalsis (e.g., due to inflammation).

• Smoking, caffeine and alcohol consumption

• Stress

• Obesity

• Pregnancy

• Angle of His enlargement (> 60°)

• Iatrogenic (e.g., after gastrectomy)

• Inadequate esophageal protective factors (i.e., saliva, peristalsis)

• Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric cardiac carcinoma

• Scleroderma

• Sliding hiatal hernia: ≥ 90% of patients with severe GERD [6]

• Asthma

The histopathological findings include the following (may vary depending on the severity of mucosal damage):

• Superficial coagulative necrosis in the nonkeratinized squamous epithelium

• Thickening of the basal cell layer

• Elongation of the papillae in the lamina propria and dilation of the vascular channels at the tip of the papillae (leading to hyperemia)

• Inflammatory cells (granulocytes, lymphocytes, macrophages)

• Transformation of squamous into columnar epithelium leads to Barrett metaplasia