Gastro-Esophageal Reflux Disease and Bile Acids

Gastro-esophageal reflux disease (GERD) is commonly thought of as the abnormal passage of acidic gastric contents into the esophagus. The lower esophageal sphincter is supposed to prevent this. However, in patients with GERD the lower esophageal sphincter either has an abnormally low resting pressure or there is transient decrease in lower resting pressure that allows gastro-esophageal reflux to take to place. Typical GERD symptoms are those of heartburn, acid regurgitation, and water brash. If complications occur, other symptoms include hematemesis or dysphagia. Gastro-esophageal reflux can cause non-GI symptoms such as hoarseness, cough, asthma, and aspiration pneumonia. It has recently been suggested that it may even have a role in glue ear (1). In 50% of adults at endoscopy the esophagus is normal. If damage is present, it can vary from mild erosions to frank ulceration, esophageal strictures, columnar lined oesophagus, in which the distal squamous mucosa of the oesophagus is replaced by columnar epithelium (also known as Barrett esophagus), and finally esophageal adenocarcinoma. The role of acid in GERD has been well demonstrated. The ability of acid to cause esophageal damage has been confirmed in animal studies in vivo and also in vitro. The presence of pepsin is also required in the gastroesophageal refluxate to cause esophageal damage. In humans, the degree of esophageal damage correlates reasonably well with the degree of esophageal acid exposure when this is assessed by esophageal 24-hour pH monitoring (2,3). The use of acid suppressant therapy in the form of H2 receptor antagonists and proton pump inhibitors leading to resolution of symptoms and allowing endoscopic healing confirms the importance of acid in GERD. Some papers have shown no difference in esophageal acid exposure between those with severe esophagitis but no complications and those with complications of GERD (i.e., esophageal ulcer, esophageal stricture, and Barrett esophagus). It has therefore been suggested that there may be another factor involved, other than gastric acid and pepsin. Gastric acid is not the only substance that refluxes from the stomach into the esophagus. Trypsin and bile acids may also reflux into the esophagus, the latter both originating in the duodenum. The correct term for this is duodenogastro-esophageal reflux (DGOR). The presence of duodenal contents in the esophagus has been confirmed directly by esophageal aspiration studies and also more recently by Bilitec monitoring (4,5). Bilitec 2000 is a fiber optic probe that detects the presence of bilirubin by its color with the bilirubin acting as a marker for DGOR. In adults, the amount of DGOR increases with the degree of esophageal damage, the highest levels being found in patients with Barrett oesophagus. The results of the study by Orel et al. reported in this journal are in keeping with the findings in adults. Orel et al. have demonstrated that esophageal exposure to acid increases as the severity of endoscopic esophageal damage worsens from none to those patients who have severe oesophagitis. In terms of bile reflux they have demonstrated that the proportion of patients with DGOR increases in a similar fashion in relation to oesophagitis severity. Not only does the proportion of patients with DGOR increase, but the magnitude of DGOR also increases. It is also worth noting they found some patients had pathological DGOR, but no pathological acid reflux. Orel et al. do not state whether DGOR in these patients was taking place in an acidic or an alkaline environment. Studies in adults have shown that most DGOR actually takes place in an acidic environment. Thus, Nehra et al. reported that episodes of DGOR took place at variable pH, but most occurred when the refluxate was acidic (6), though the pH levels are not described in detail. Marshall This editorial accompanies an article. Please see Bile in the Esophagus: A Factor in the Pathogenesis of Reflux Esophagitis in Children. R. Orel, S. Markovic. J Ped Gastroenterol Nutr 2003;36:266–273. Journal of Pediatric Gastroenterology and Nutrition 36:172–174 © February 2003 Lippincott Williams & Wilkins, Inc., Philadelphia