Reflux perception and the esophageal mucosal barrier in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common disorders of the gastrointestinal tract. Heartburn, regurgitation and chest pain are the key symptoms. Patients with reflux symptoms often have more than average reflux of acidic contents in the esophagus. However, frequently there is a discrepancy between the severity of esophageal exposure to gastric content and the severity of symptoms. Esophageal sensitivity seems to be an important factor in symptom generation. This thesis aimed to address the perception of reflux and its modulation, with a specific focus on the role of esophageal mucosal barrier function within this spectrum.
In the first part of the thesis we demonstrate that an enhanced esophageal sensitivity of the esophagus is associated with impaired barrier function of the esophageal epithelium, irrespective of the presence of erosions. Mucosal barrier function can be determined in vivo by measuring an impedance spectrum of the esophageal mucosa using a new endoscopic probe. We investigated the role of stress and the transient receptor potential vanilloid 1 in the development of barrier dysfunction in an animal model. Furthermore, we describe the effectivity of proton-pump inhibitor therapy for non-erosive reflux disease and the effectivity of anti-depressant therapy for functional esophageal disorders.
The second part of the thesis comprises several studies regarding esophageal high-resolution manometry (HRM). We provide normal values for esophageal HRM for healthy subjects and after successful anti-reflux surgery. We also demonstrate that HRM can accurately identify the presence and size of a sliding hiatal hernia.