Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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

Is acid exposure at all esophageal levels higher in Barrett's esophagus than in common reflux disease?

A.P.M. Smout, E.C. Niemantsverdriet, R. Breumelhof, R. Timmer (Utrecht, Nieuwegein)

Barrett's esophagus is usually defined as the presence of columnar metaplastic epithelium with histologically proven intestinal metaplasia in the distal esophagus over a length of more than 2-3 cm. It is generally accepted that Barrett's esophagus is the consequence of prolonged and severe exposure of the esophageal mucosa to acid and other constituents of gastric and duodenal fluids. The process is thought to occur during the period of esophageal mucosal repair, during which pluripotent stem cells develop into columnar epithelium.

Numerous studies using 24-hour ambulatory esophageal pH monitoring have shown that patients with Barrett's esophagus have an increased esophageal acid exposure when compared to controls or patients with mild forms of gastroesophageal reflux disease (GERD) [1-12]. The difference in esophageal acid exposure between patients with Barrett's esophagus and patients with high-grade esophagitis is less clear [7, 8]. Patients with long columnar-lined segments (classical Barrett's esophagus) have more pronounced esophageal acid exposure than patients with short segments (< 3 cm) of columnar epithelium [13]. Some controversy exists concerning the question whether patients with Barrett's esophagus and complications, such as ulceration or stricture, have esophageal acid exposures which are higher than those found in patients with uncomplicated Barrett's esophagus [5, 14].

The available data suggest that the increase in total reflux time found in Barrett's esophagus patients is not caused by a high incidence of reflux episodes, but rather by an increase in the duration of the reflux episodes [2, 5].

The question whether gastroesophageal reflux has a more proximal extent in patients with Barrett's esophagus than in patients with milder forms of GERD, was not addressed extensively. With the development of the ion-sensitive field effect transistor (ISFET) technique multiple-site pH monitoring with only one small caliber catheter became possible. Using this technique Weusten et al. have shown that not only distal but also proximal acid exposure is increased in patients with low-grade GERD [15].

Using a 5-channel esophageal pH monitoring technique, we studied 119 patients within two weeks after endoscopical evaluation because of symptoms of reflux disease. Only patients who were not treated with acid-inhibiting or prokinetic drugs were included. Fourty-three patients had no mucosal abnormalities during endoscopy. However, a pathological 24-hour pH profile or a strong association between reflux symptoms and reflux episodes was found. In 37 patients, mild esophagitis (Savary Miller grade I or II) was found. In 10 patients severe esophagitis (grade III or IV) was present. In 29 patients Barrett's esophagus (defined as presence of columnar-lined epithelium with intestinal metaplasia over a distance of more than 3 cm) was found. Twenty healthy subjects, ageand sex-matched with the previous groups, were used as controls.

All subjects underwent conventional manometry to measure the position of the lower esophageal sphincter (LES). Thereafter, a five-sensor ISFET transducer with sensors placed at 3 cm intervals (Sentron, Roden, the Netherlands) was positioned in the esophagus. The distal sensor was placed at 3 cm above the upper border of the LES and consequently the other sensors were at 6, 9, 12 en 15 cm above the LES.

Twenty-four hour esophageal pH monitoring was carried out using a portable digital datalogger (Medical Measurement Systems, Enschede, the Netherlands) which sampled and stored pH values at a rate of 1 Hz.

As shown in Figure 1, 24-hour esophageal acid exposure increased with increasing degree of esophageal mucosal damage, the exposure being lowest in the endoscopynegative group and highest in the group of patients with Barrett's esophagus. The differences in esophageal acid exposure between the groups were most pronounced in the distal esophagus. However, at higher esophageal levels differences between Barrett's esophagus and mild or no mucosal damage were still significant. The differences between patients with Barrett's esophagus and patients with milder forms of the disease were much

Figure 1. Median percentage of time (24 hours) with pH below 4 at 5 esophageal levels in patients with negative endoscopy (NERD), patients with grade 1-2 and grade 3-4 esophagitis and in patients with Barrett's esophagus.

greater during the night than during the day. Patients with grade III and grade IV esophagitis had proximal esophageal acid exposure times that were quite similar to those found in Barrett's patients. However, at 3 cm above the LES, the percentage of time with pH < 4 was higher in patients with Barrett's esophagus than in patients with high-grade esophagitis, both during the total 24-hour period as well as during the night and during the day separately. This difference in percentage of time with acid exposure was caused by both a higher number of reflux episodes and a longer mean duration of the reflux episodes at 3 cm. In addition, it was found that the length of the Barrett segment was correlated significantly to the extent of proximal acid exposure in the supine position (r = 0.45, p < 0.05 at 12 cm from the LES and r = 0.58, p < 0.03 at 15 cm) and that the number of reflux episodes showed a strong positive correlation with the length of the Barrett segment (r = 0.81, p < 0.007). Thus, the available evidence strongly suggests that the presence of a segment of classical Barrett's esophagus is associated with increased acid exposure, of both the distal and the proximal esophagus and that the length of the columnar-lined segment is associated with the extent of proximal acid exposure. The question is whether increased proximal acid exposure in patients with Barrett's esophagus and patients with high-grade esophagitis is the consequence of abnormal esophageal peristalsis or of a greater volume of the refluxate. Further studies are needed to shed more light upon this issue.


1. Bremner RM, Crookes PF, DeMeester TR, Peters JH, Stein HJ. Concentration of refluxed acid and esophageal mucosal injury. Am J Surg 1992;164:522-526.

2. Robertson D, Aldersley M, Shepherd H, Smith CL. Patterns of acid reflux in complicated oesophagitis. Gut 1987;28:1484-1488.

3. Champion G, Richter JE, Vaezi MF, Singh S, Alexander R. Duodenogastroesophageal reflux: relationship to pH and importance to Barrett's esophagus. Gastroenteroloy 1994;107:747-754.

4. Vaezi MF, Richter JE. Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology 1996;111:1192-1199.

5. Gillen P, Keeling P, Byrne PJ, Hennessy TP. Barrett's oesophagus: pH profile. Br J Surg 1987;74:774-776.

6. Singh P, Taylor RH, Colin-Jones DG. Esophageal motor dysfunction and acid exposure in reflux esophagitis are more severe if Barrett's metaplasia is present. Am J Gastroenterol 1994;89:349-356.

7. Neumann CS, Cooper BT. 24 hour ambulatory oesophageal pH monitoring in uncomplicated Barrett's oesophagus. Gut 1994;35:1352-1355.

8. Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus. Gut 1990;31:964-967.

9. Niemantsverdriet C, Timmer R, Breumelhof R, Smout AJPM. The roles of excessive gastro-oesophageal reflux, disordered oesophageal motility and decreased mucosal sensitivity in the pathogenesis of Barrett's oesophagus. Eur J Gastroenterol Hepatol 1997;9:515-519.

10. Coenraad M, Masclee AA, Straathof JW, Ganesh S, Griffioen G, Lamers CB. Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis? Am J Gastroenterol 1998;93:1068-1072.

11. Salminen JT, Tuominen JA, Ramo OJ, Farkkila MA, Salo JA. Oesophageal acid exposure: higher in Barrett's oesophagus than in reflux oesophagitis. Ann Med 1999;31:46-50.

12. Loughney T, Maydonovitch CL, Wong RK. Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short and long segment Barrett's esophagus. Am J Gastroenterol 1998;93:916-919.

13. Oberg S, DeMeester TR, Peters JH, Hagen JA, Nigro JJ, DeMeester SR, Theisen J, Campos GM, Crookes PF. The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure. J Thorac Cardiovasc Surg 1999;117:572-580.

14. Vaezi MF, Richter JE. Synergism of acid and duodenogastroesophageal reflux in complicated Barrett's esophagus. Surgery 1995;117:699-704.

15. Weusten BLAM, Akkermans LMA, van Berge Henegouwen GP, Smout AJPM. Dynamic characteristics of gastrooesophageal reflux in ambulatory patients with gastro-oesophageal reflux disease and normal control subjects. Scand J Gastroenterol 1995;30:731-737.

Publication date: August 2003 OESO©2015