title: Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease.
abstract: Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm(-2)·h(-1)) than in the proximal segment (368 nmol·cm(-2)·h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Froukje B
authors.initials: FB
authors.lastname: van Hoeij
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Pim W
authors.initials: PW
authors.lastname: Weijenborg
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Marius A
authors.initials: MA
authors.lastname: van den Bergh Weerman
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: René M J G J
authors.initials: RM
authors.lastname: van den Wijngaard
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;
authors.forename: André J P M
authors.initials: AJ
authors.lastname: Smout
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; a.j.bredenoord@amc.uva.nl.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bredenoord
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D017097:Electric Impedance; D000071041:Esophageal Mucosa / Q000293:injuries / Q000378:metabolism* / Q000648:ultrastructure; D004945:Esophagoscopy; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D006356:Heartburn / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D058748:Pain Perception; D010539:Permeability; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D006851:Hydrochloric Acid
keywords: acid sensitivity; dilated intercellular spaces; heartburn; mucosal barrier; mucosal integrity; perception