Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

  Browse by Author
  Browse by Movies
Volume: Barrett's Esophagus
Chapter: Pathophysiology

What is the relationship between bile and alkaline reflux?

J.E. Richter (Cleveland)

Until recently, the most popular method for detecting duodenogastroesophageal reflux (i.e. bile reflux) was ambulatory 24-hr pH monitoring. Using this technique, Pellegrini et al. [1] were the first to introduce the term "alkaline" reflux suggesting that pH > 7 could be used as an indirect marker of bile reflux. This group suggested that alkaline refluxers had less heartburn but more frequent and severe regurgitation than patients with classic acid reflux. Furthermore, they suggested that alkaline reflux may be the sole cause of esophagitis, Barrett's esophagus and even esophageal adenocarcinoma [2] However, the measurement of esophageal pH > 7 as a marker of bile reflux is confounded by several problems. Precautions must be taken to use only glass electrodes, dietary restrictions of food with pH < 7, inspection of patients for dental disease, and dilation of strictures to avoid pooling of saliva. Subsequently, studies by Singh et al. [3] and DeVault et al. [4] found that increased saliva production or bicarbonate production by the esophageal submucosal glands were the most common causes of esophageal pH > 7, whereas bile reflux was rare in patients with an intact stomach.

The poorly named syndrome "alkaline reflux" was finally scientifically discredited by the development of the ambulatory bilirubin monitoring system. Using this technique to measure bilirubin as a pH independent surrogate of bile combined with pH monitoring, Richter et al. found no difference in the degree of percent total time pH > 7 across the spectrum of gastroesophageal reflux disease (Figure 1) and no correlation between alkaline reflux and bile reflux into the esophageal lumen (Figure 2). They suggested that the term alkaline reflux was a misnomer and should not be used when referring to duodenogastroesophageal reflux.

Figure 1. Alkaline reflux (percentage total time pH was > 7) for the five study populations. The quantity of alkaline reflux was similar across the groups and did not distinguish them [5].

Figure 2. Relationship between percent of time bilirubin absorbance was = 0.14 as a direct marker of DGER and esophageal pH (both percent of total time pH was > 7 and pH was < 4) in the group of healthy controls and GERD and Barrett's esophagus patients. Patients with partial gastrectomy were excluded from this analysis because most did not have acid reflux. Data presented as logarithmic transformation of raw values to correct for deviation from normality. Linear regression analysis found a poor relationship between percent of time pH was > 7 and bilirubin absorbance but a strong correlation between percent of time pH was < 4 and bilirubin absorbance [6].

Additionally, Just et al. [7] found a poor correlation (r = 0.26) between intragastric pH ("alkaline shiff") and intragastric bilirubin absorbance, concluding that the measurement of alkaline reflux in the esophagus or stomach with an ambulatory pH monitoring alone is "an outdated technique".


1. Pellegrini CA, DeMeester TR, Wernly JA, et al. Alkaline gastroesophageal reflux. Am J Surg 1978;75:177-184.

2. Attwood SEA, DeMeester TR, Bremner CG, et al. Alkaline gastroesophageal reflux:implications in the development of complications of Barrett's esophagus. Surgery 1989;106:764-776.

3. Singh S, Bradley LA, Richter JE. Determinacy of esophageal "alkaline" pH environment and controls in-patients with GERD. Gut 1993;34:309-316.

4. DeVault KR, Georgeson S, Castell DO. Salivary stimulation mimics esophageal exposure to reflux duodenal contents. Am J Gastroenterol 1993;88:1040-1043.

5. Vaezi MF, Richter JE. Role of acid and duodenal gastroesophageal reflux in GERD. Gastroenterology 1996;111:11921199.

6. Champion G, Richter JE, Vaezi MF, et al. Duodenal gastroesophageal reflux:relationship to pH and importance in Barrett's esophagus. Gastroenterology 1994;107:747-754.

7. Just RJ, Leite LP, Castell DO. Changes in overnight fasting intragastric pH show poor correlation with duodenal gastric bile reflux in normal subjects. Am J Gastroenterol 1996;91:1567-1570.

Publication date: August 2003 OESO©2015