Intercellular Space Diameter Research Articles

Dilated Intercellular Spaces of Esophageal Epithelium in Nonerosive Reflux Disease Patients with Physiological Esophageal Acid Exposure

It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time. Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol. Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients. Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.

Dilated intercellular spaces: A morphological feature of acid reflux-- damaged human esophageal epithelium

BACKGROUND & AIMS: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium. METHODS: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal- appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient. RESULTS: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls. CONCLUSIONS: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn. (Gastroenterology 1996 Nov;111(5):1200-5)