Primary Motility  Disorders of the  Esophagus
 The Esophageal
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 Barrett's
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OESO©2015
 
Volume: The Esophagogastric Junction
Chapter: GER and gastric motility factors
 

What is the correlation between gastric secretory volume and reflux frequency?

A. Dubois (Bethesda)

Before answering this question, it is important to remember that gastric secretory volume can have two different meanings. It can represent gastric fluid output, that is the amount of fluid secreted by the stomach, expressed in mL.min-1 or mL.hour-1. It can also represent intragastric volume, which is often confused with gastric fluid output, and is the volume (in mL) of fluids (or mixed solids and liquids) present in the stomach at a given time. Intragastric volume depends not only on the volume of fluid output, but also on the volume of food/fluids swallowed, on gastric emptying and on duodenogastric reflux (DGR).

To fully understand the possible role of gastric secretory volume in gastroesophageal reflux disease (GERD), one has to first review the kinetics of gastric fluid output and emptying, as well as the digestive state under consideration. In the fasting state, the volume of the intragastric contents reflects the balance between gastric fluid output and gastric emptying. In normal subjects, the steady state intragastric volume is approximately 10 mL, which results from equal rates of fluid output and of emptying at 1 mL.min-1 (Figure 1, left panel) [1]. In order to analyze emptying independently from gastric fluid output, one should divide the emptying rate by the intragastric volume, thus calculating the fractional rate of gastric emptying (FER). In this example, FER is 10%.min-1. After a meal, intragastric volume increases by the amount of food and liquids swallowed, which can be 250 mL or more. During the early postprandial period, therefore, the contribution of gastric fluid output to intragastric volume is negligible (Figure 1, right panel). While emptying of the meal proceeds, however, the fraction of intragastric volume that depends on gastric fluid output progressively increases to eventually represent the total intragastric volume. Thus, the role of fluid output in GERD is probably very minimal during the postprandial period, while it could theoretically play an important role during fasting, especially nightime. Examples of how increased fluid output can result in increased intragastric volume are illustrated in Figures 2 and 3, which also demonstrate the concurrent importance of gastric emptying, as will be discussed later.

Figure 1. Kinetics of gastric function in healthy volunteers during fasting and immediately after intragastric administration of a liquid meal. In contrast to the fasting situation (left panel), there is no steady state during the immediate postprandial period (right panel), and intragastric volume changes rapidly. At that time, the largest portion of the gastric contents reflects the volume of the meal, and the contribution of gastric fluid output is minimal.
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Figure 2. Kinetics of gastric function during fasting in healthy volunteers and the Zollinger-Ellison. Although ZES patients have a 10-fold increase of fluid output, intragastric volume increases only four-fold due to the concurrent 2.5-fold increase of fractional emptying rate.
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Figure 3. Kinetics of gastric function during fasting in patients with delayed gastric emptying and either normal or increased fluid output. Note that for a similar delay in fractional emptying rate, intragastric volume increases two-fold if fluid output increases from 1 mL.min-1 to 2 mL.min-1.
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Now, what does the literature say about the relation between gastric fluid output (gastric secretory volume) and GERD. To my knowledge, only one study specifically addressed this question. This study demonstrated that fasting basal gastric secretory volume was directly correlated with reflux frequency (r = 0.308; p < 0.02), and also with the duration of exposure of the esophagus to pH ¾3 (r = 0.301; p < 0.01), pH ¾ 4 (r = 0.336; p < 0.01), and ¾ 5 (r = 0.378; p < 0.01) [2]. However, the same study also demonstrated a significant direct correlation between basal acid output and gastroesophageal reflux (GER) with similar correlation coefficients. Since acid and fluid output were also significantly correlated, it is possible that one of these relations was spurious.

One can also attempt to answer the question of the existence of a correlation between gastric secretory volume and reflux frequency by using data from the literature that indicate that GERD is more frequently observed in subjects with fluid hypersecretion. First, fluid output was increased 10-fold in patients with the Zollinger-Ellison syndrome [1] a condition frequently associated with GERD [3]. However, acid output was concurrently increased 27-fold in those patients compared to controls, resulting in a 3-fold increase in acid concentration from 34 to 101 meq/l. [1]. Secondly, gastric fluid output was increased 1.5-fold in a subgroup of patients with GERD who did not respond to standard doses of histamine H2 antagonists (p < 0.02) [4]. However, the rate of acid output was concurrently increased 2.6-fold (p < 0.001), resulting in an increase of intragastric concentration from 51.2 to 86.4 meq/l. Thus, aggressive GERD was found to be associated with increased fluid output in one study. However, the effect of acid and fluid output on GERD has not been analyzed separately, and the suggested association between fluid output and esophagitis may be spurious. Furthermore, another study that used rigorously matched controls did not confirm the presence of a difference in acid or fluid output between responders and non-responders [5].

Finally, one can ask the question: is fluid output increased in patients with GERD, and is the grade of esophagitis related to gastric fluid output? In one study, basal and pentagastrin-stimulated fluid output were significantly increased in patients with GERD and esophagitis compared to controls, although these patients also had increased basal acid secretion [6]. In five other studies, however, no difference in either fluid or acid output was observed between controls and GERD patients [7-10]. The same conclusion was reached in two other studies that used carefully matched controls, demonstrating that acid output and fluid output were not significantly different in patients with GERD and in controls, and that neither parameter was correlated with the severity of esophagitis [11, 12]. Thus, although fluid hypersecretion may be present in some patients with GERD or Barrett's metaplasia, these conditions are not consistently associated with increased fluid output when compared to well matched controls.

Before concluding, just a few words about the role of intragastric volume in the pathophysiology of GERD and of its complications. Early experiments have shown that GER can be induced by intragastric injection of fluids in most subjects. However, as shown in Figure 4, reflux occurred with volumes >= 140 ml 0.1 N HCl in symptomatic refluxers (LES pressure = 7.5 mmHg), whereas volumes > 308 ml were necessary to produce GER in asymptomatic refluxers (LES pressure =13.8 mmHg) [13].

Figure 4. Relation between volume of acid introduced into the stomach and the cumulative percentage of patients with reflux (from [13]). Note that an intragastric volume of 200 mL is associated with reflux in only 10% of asymptomatic subjects compared to 80% of symptomatic patients.
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Increased intragastric volume may also play a role by causing gastric distention. In dogs and cats, low level balloon distention of the stomach was accompanied by increased LES pressure while further increase of distention produced a decreased LES pressure [14, 15]. In man, distention of an intragastric balloon producing epigastric fullness but no pain resulted in a non significant increase in LES pressure [16], whereas rapid distention of the stomach producing epigastric pain was accompanied by a decrease in LES pressure [17]. In addition, gastric distention produced transient LES relaxations which were similar in patients with GER and in healthy controls, although these relaxations were more frequently complete in those patients than in controls (87% vs 73%; p < 0.01) [16]. These observations suggest that rapid gastric distention impairs the protective response of the LES following meals, and that it may be useful to advise patients with GERD to eat slowly.

In conclusion, gastric hypersecretion of fluid, per se, is not consistently increased in GERD. When present, however, it may facilitate reflux, especially if associated with decreased gastric emptying. The resulting increase in intragastric volume, available for reflux, is therefore a non-negligible contributing factor in GERD. As a corollary, antisecretory treatments that decrease fluid output can decrease intragastric volume, and this effect may contribute to their beneficial effects.

References

1. Dubois A, Van Eerdewegh P, Gardner JD. Gastric emptying and secretion in Zollinger-Ellison syndrome. J Clin Invest 1977;59:255-263.

2. Boesby S. Relationship between gastro-oesophageal acid reflux, basal gastro-oesophageal sphincter pressure, and gastric acid secretion. Scand J Gastroenterol 1977;12:547-551.

3. Miller LS, Vinayek R, Frucht H, Gardner JD, Jensen RT, Maton PN. Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology 1990;98:341-346.

4. Collen MJ, Lewis JH, Benjamin SB. Gastric acid hypersecretion in refractory gastroesophageal reflux disease. Gastroenterology 1990;98:654-661.

5. Hirschowitz BI. Acid and pepsin secretion in patients with esophagitis refractory to treatment with H2 antagonists. Scand J Gastroenterol 1992;27:449-452.

6. Baldi F, Corinaldesi R, Ferrarini F, Stanghellini V, Miglioli M, Barbara L. Gastric secretion and emptying of liquids in reflux esophagitis. Dig Dis Sci 1981;26:886-889.

7. Kaye MD, Showalter JP. Pyloric incompetence in patients with symptomatic gastroesophageal reflux. J Lab Clin Med 1974;83:198-206.

8. Dubois A. Clinical relevance of gastroduodenal dysfunction in reflux esophagitis. J Clin Gastroenterol 1986;8:17-25.

9. Bruley des Varannes S, Touchais JY, Weber J, Deschalliers JP, Sauger F, Denis P, Galmiche JP. Œsophagite de reflux: Rôles respectifs des facteurs pathogéniques œsophagiens et gastriques. Gastroenterol Clin Biol 1986;10:662-668.

10. Sekera E, Cadiot G, Poitevin C, Vallot T, Vatier, Mignon M. Gastric proteolytic content in gastro-oesophageal reflux and peptic oesophagitis. Gastroenterol Clin Biol 1992;16:141-147.

11. Hirschowitz BI. A critical analysis, with appropriate controls, of gastric acid and pepsin secretion in clinical esophagitis. Gastroenterology 1991;101:1149-1158.

12. Hirschowitz BI. Gastric acid and pepsin secretion in patients with Barrett's esophagus and appropriate controls. Dig Dis Sci 1996;41:1384-1391.

13. Ahtaridis G, Snape WJ Jr, Cohen S. Lower esophageal sphincter pressure as an index of gastroesophageal acid reflux. Dig Dis Sci 1981;26:993-998.

14. Clark CG, Vane JR. The cardiac sphincter in the cat. Gut 1961;2:252-262.

15. Jennewein HM, Hummelt H, Siewert JR, Weiser F, Waldeck F. The effect of pressure changes inside the antrum on lower esophageal sphincter (LES) pressure in man and dog. Acta Hepatogastroenterol 1976;23:449-454.

16. Holloway RH, Hongo M, Berger K, McCallum RW. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 1985;89:779-784.

17. Muller-Lissner SA, Blum AL. Fundic pressure rise lowers lower esophageal sphincter pressure in man. Hepatogastroenterology 1982;29:151-152.


Publication date: May 1998 OESO©2015