What Causes Barrett's Esophagus
Barrett's esophagus is caused by chronic gastroesophageal reflux disease (GERD), where prolonged acid exposure damages the normal squamous epithelium of the distal esophagus, triggering a metaplastic change to columnar epithelium as a protective response. 1
Primary Pathophysiologic Mechanism
The development of Barrett's esophagus follows a specific sequence of injury and repair:
- Destruction of the normal squamous mucosa is the necessary prerequisite, allowing for reepithelialization of the lower esophagus with metaplastic columnar epithelium 1
- Acid exposure is the primary destructive agent, though the exact contributions of acid, pepsin, and duodenal refluxate remain incompletely defined 1
- The healing environment determines the epithelial type: Animal studies demonstrate that damaged esophageal tissue regenerates columnar epithelium when exposed to acid, but regenerates squamous epithelium when exposed to neutral pH 1
Role of Bile and Duodenal Contents
While acid is the primary driver, bile may play a synergistic role:
- Bile reflux appears more common in patients with Barrett's esophagus compared to those with uncomplicated GERD or control subjects 1
- Bile reflux parallels increased acid reflux in Barrett's patients, suggesting a combined injurious effect rather than bile acting alone 1
- The relative contribution of duodenal contents versus acid remains controversial, but evidence suggests they work together 1
Clinical Risk Factors
The following factors increase risk for developing Barrett's esophagus:
- Chronic GERD symptoms, particularly long-standing (>20 years) and severe reflux 1, 2
- Male gender (significantly higher prevalence) 2, 3
- Caucasian race 3
- Age over 50 years 2, 3
- Obesity and high body mass index 2, 3
- Tobacco use 2, 4, 3
- Hiatal hernia size 2
- Family history 4
Cellular Origin and Metaplastic Process
The exact cellular origin remains incompletely understood:
- Columnar cells differ histologically from gastric cardia cells, ruling out simple upward migration of gastric epithelium 1
- A pluripotential basal cell at the border between squamous and Barrett's mucosa, with features of both columnar and squamous tissue, may be the progenitor of Barrett's epithelium 1
- The metaplastic change represents an adaptive response to chronic injury, where the more acid-resistant columnar epithelium replaces damaged squamous epithelium 1
Important Clinical Considerations
Most patients with Barrett's esophagus are undiagnosed during life, as autopsy studies reveal far more cases than are clinically detected 4
The severity of reflux symptoms does not reliably predict Barrett's development, as there is only moderate correlation between symptoms and actual esophageal acid exposure 1
Barrett's esophagus patients often have decreased sensitivity to reflux symptoms due to the columnar epithelium being less sensitive than squamous epithelium, leading to underdiagnosis 5