Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos II, Madrid, Spain.
Neurogastroenterol Motil. 2013 Oct;25(10):783-99. doi: 10.1111/nmo.12201. Epub 2013 Aug 12.
Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role.
This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed.
胃食管反流病（GERD）非常普遍，对医疗保障系统的成本负担很大。然而，其病理生理学机制非常复杂，目前还没有被完全理解。目前已经提出了几种机制：唾液分泌减少、食管清除能力下降、食管下括约肌静息压力降低、食管裂孔疝、一过性食管下括约肌松弛（TLESR）次数增加、胃酸和胃蛋白酶分泌增加、幽门功能不全导致胆汁酸和胰蛋白酶反流入十二指肠-胃。无论每种机制的相关性如何，最终的现象都是黏膜上皮暴露于酸和胃蛋白酶等物质的时间更长，或者与胃反流物中通常不存在的腔内物质（如胰蛋白酶或胆汁酸）接触，这会导致上皮出现明显损伤（糜烂性食管炎 -EE）或损害黏膜完整性，而没有任何宏观改变，如非糜烂性反流病（NERD）中那样。腔内因素并不是导致这种损伤的唯一原因；最近的数据表明，内源性因素也可能发挥作用。
本文将更新关于胃食管反流病潜在病理生理学机制的最新发现，特别是将重点关注食管黏膜完整性在 GERD 中的作用。本文将讨论用于评估黏膜完整性的方法、其在 EE 和 NERD 中的相关性、其在症状感知中的作用以及腔内和内源性因素的影响。
