How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.