34 Reflux Esophagitis May Result Primarily from An Immune-Mediated Injury Rather Than from a Caustic, Chemical Injury

Abstract

Esophageal mucosa dilated intercellular spaces (DIS) is involved in the pathogenesis of nonerosive reflux disease (NERD). Patients with NERD have DIS not only in the reflux-exposed distal esophagus but also in the less exposed proximal esophagus. Luminal acid is very important for development of DIS. However, we recently found that In Vitro exposure of rabbit esophageal mucosa to weakly acidic solutions may also induce DIS. It is known that patients with NERD or GERD “on” PPI may still have esophageal exposure to weakly acidic reflux. We assessed, in healthy human subjects, the effect of esophageal acid and weakly acidic perfusions. Our aim was to study changes in mucosal intercellular spaces (ICS) both in the distal “exposed” and in the proximal “non-exposed” esophagus. Methods: 14 healthy volunteers (7 males, 23±1y) underwent upper GI endoscopy with esophageal biopsies at 3 and 13 cm proximal to the esophago-gastric junction (EGJ). Thereafter, subjects received esophageal perfusions with 3 different solutions in random order (separated 3 weeks). Perfusions (2 ml/min) were performed in sitting position, at 5 cm above the EGJ during 30 min. We used: 1) saline (pH 5.5, weakly acidic), 2) saline at pH 2 plus 0.5 mg/mL pepsin (acidic solution) and 3) acid solution plus 2 mM of glycocholic acid (acidic solution +GC). pH was continuously measured at the biopsy sites (3 and 13 cm above ECJ). Biopsies were taken 10 min after end of perfusion. Electron microscopy was used to measure esophageal mucosa ICS. Results: Endoscopy showed no macroscopic erosions after perfusions. pH measurements confirmed distal esophageal mucosa acidification and no changes in nonexposed proximal esophagus in 10 subjects (4 excluded). As expected, distal esophageal perfusion with acid solutions (with pepsin and/or bile acids) provoked DIS. Interestingly; perfusion with saline solution (pH 5.5) provoked DIS. Not only perfusions provoked DIS in the “exposed” distal area. They also induced DIS in the “non-exposed” proximal esophagus (table).Conclusions: The human esophagus is very sensitive to a 30min continuous exposure to acidic and weakly acidic material. Reflux events (acid or weakly acidic), particularly during supine periods, may provoke similar exposure and induce distal and proximal DIS. The mechanism underlying proximal spread of DIS to non-exposed areas requires further investigation.