Castell D O, Murray J A, Tutuian R, Orlando R C, Arnold R
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Aliment Pharmacol Ther. 2004 Dec;20 Suppl 9:14-25. doi: 10.1111/j.1365-2036.2004.02238.x.
The pathogenesis of gastro-oesophageal reflux disease (GERD) is multifactorial, involving transient lower oesophageal sphincter relaxations (TLESRs) as well as other lower oesophageal sphincter (LES) pressure abnormalities. GERD is associated with a decrease in LES pressure, which can be provoked by factors such as foods (fat, chocolate, etc.), alcohol, smoking and medications. These factors have also been shown to increase TLESRs. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury, which can potentially progress to oesophageal adenocarcinoma in a minority of patients with Barrett's metaplasia. In addition, duodenogastric contents can also contribute to oesophageal injury. Other factors contributing to the pathophysiology of GERD include hiatal hernia, poor oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia has a permissive role in the pathogenesis of reflux oesophagitis by promoting LES dysfunction. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of TLESRs, contributing to postprandial GER. The mucosal defensive factors have an important role in GERD. When excessive acid causes a breakdown in oesophageal epithelial defenses, epithelial resistance may be reduced. Nocturnal GERD is associated with prolonged acid exposure and proximal extent of acid contact, which elevates the risk for oesophageal damage and GERD-related complications. In sum, GERD is a complex problem caused by many factors that are exacerbated when the patient is in the supine position.
胃食管反流病(GERD)的发病机制是多因素的,涉及一过性下食管括约肌松弛(TLESRs)以及其他下食管括约肌(LES)压力异常。GERD与LES压力降低有关,食物(脂肪、巧克力等)、酒精、吸烟和药物等因素可诱发LES压力降低。这些因素也已被证明会增加TLESRs。结果,胃酸、胆汁、胃蛋白酶和胰酶发生反流,导致食管黏膜损伤,在少数患有巴雷特化生的患者中,这种损伤可能会进展为食管腺癌。此外,十二指肠胃内容物也可导致食管损伤。导致GERD病理生理的其他因素包括食管裂孔疝、食管清除能力差、胃排空延迟和黏膜防御因子受损。食管裂孔疝通过促进LES功能障碍在反流性食管炎的发病机制中起促进作用。胃排空延迟导致胃扩张,可显著增加TLESRs的发生率,导致餐后GER。黏膜防御因子在GERD中起重要作用。当过多的胃酸导致食管上皮防御功能破坏时,上皮抵抗力可能会降低。夜间GERD与酸暴露时间延长和酸接触的近端范围有关,这增加了食管损伤和GERD相关并发症的风险。总之,GERD是一个由多种因素引起的复杂问题,当患者处于仰卧位时会加剧。