Can the relevance of abnormalities of gastric emptying to the pathogenesis of gastroesophageal reflux disease be asserted?
How should the frequently normal or accelerated gastric emptying of solids and liquids in gastroesophageal reflux disease be interpreted?
A. Dubois (Bethesda)
Based on the response given to the question of the correlation between gastric secretory volume and reflux frequency, it is evident that abnormalities of gastric emptying will modify the intragastric volume, available for reflux, and thereby contribute to gastroesophageal reflux disease (GERD). As early as 1976, it was suggested that gastric stasis could facilitate gastroesophageal reflux (GER) [1, 2] which led to numerous publications that reported on gastric emptying in GERD. However, most studies have determined gastric emptying during the postprandial period, which is relevant only to postprandial reflux. In the only study in which gastric emptying was examined during fasting, however, there was no difference between patients with GERD and healthy controls [3].
Gastric emptying of liquids was determined in 14 studies using various methods. Emptying was found to be slower in patients with GERD in 5 of these studies [2, 4-8], while there was no change or emptying was actually increased in some of the subjects included in the remaining 9 studies [3, 9-16].
Gastric emptying of solids (expressed as the percentage of radioisotopic marker remaining in the stomach at two hours) was significantly slower in 57% of the patients evaluated in two early studies [14, 15]. Interestingly, emptying of solids was faster in 5% of the patients. In another study using the same methodology, gastric emptying of solids (expressed as gastric T1/2) was also slower in 44% of patients with GERD [7]. Furthermore, the average percentage of solids remaining in the stomach at 100 min was significantly greater (p < 0.05) in patients with reflux and endoscopic esophagitis than in those without esophagitis, although the overlap was considerable [7]. Finally, epigastric fullness was reported by 84% of the patients, but there was no correlation between this complaint and T1/2 for either solids or liquids [7] A delay of gastric emptying of solids was observed in five other studies [17-21]. In one of those studies, in addition, a direct correlation was observed between T1/2 and esophageal damage (r = 0.830, p < 0.01) [17].
However, these results have not been confirmed in seven other studies [13, 22-27]. For example, emptying of the solid fraction of a meal (chicken liver tagged in vitro with 99mTc sulfur colloid) was not altered in a group of twenty patients with severe GERD disease [13]. In another study, gastric T1/2 of a technetium-tagged solid meal were comparable in 23 patients with GERD and in 9 healthy controls, although 35% of the patients had gastric T1/2 greater than the mean plus 2 SD observed in controls [22]. In a third study, gastric emptying of a chicken liver meal tagged in vivo with 99mTc sulfur colloid was measured in a group of thirty-three refluxers and in fifteen controls [23]. Gastric emptying of solids was not significantly different in those two groups, even when patients with reflux were separated into those with, and those without, erosive esophagitis. In fact, only two patients (6%) had abnormally slow gastric emptying. In one additional study, emptying of oatmeal tagged with 99mTc-sulphur colloid was delayed in a similar number of patients with (19/51; N.S.) and without (11 of 25) reflux [26]. In sharp contrast to the reported association between slow emptying and esophageal damage [7, 17], this study showed that emptying was accelerated in more patients with esophagitis (6/51) than in patients without esophagitis (1/26), although this trend did not reach a level of statistical significance [26].
To investigate whether this variability of the results was related to the heterogeneity of the population of patients with GER, gastric emptying of a scrambled egg meal (tagged with 99mTc-sulfur colloid) was determined in a more homogeneous population of refluxers, i.e. fourteen patients with Barrett's esophagus [24]. In this subgroup of patients, however, mean gastric emptying was not significantly different compared to controls. Values obtained in five patients (35% of the group) fell outside the normal range set as the mean ± 1 SD: two had slower emptying and three had accelerated emptying.
The cause of the altered gastric emptying that is observed in some patients with GERD is probably multifactorial. Smooth muscle fibers forming the lower esophageal sphincter (LES) belong to the third muscular layer of gastric wall [28] and this layer may play an important role in the adaptive relaxation of the proximal stomach. Therefore, the decreased LES pressure observed in patients with reflux esophagitis can be associated to alterations in the contractility of the proximal stomach in those patients. This hypothesis is supported by the decrease in intragastric pressure that was observed in response to gastric distention in patients with GERD [29]. In addition, the motility of the distal stomach was found to be decreased in a group of thirteen patients with reflux esophagitis compared to nine age-matched controls [9]. On the average, the number of antral contractions and cumulative antral activity was reduced in patients with reflux, although 50% of them had values similar to those of controls. This observation suggests that decreased gastric emptying in some patients with GERD could be due to defective contractility of the distal stomach.
Another important aspect of the pathophysiology of GERD that was established by these studies is that some patients with GERD actually have accelerated gastric emptying. This abnormality could promote esophagitis by increasing intragastric pressure and thereby causing transient LES relaxation. Furthermore, rapid emptying could also play a role in esophagitis by shortening the time during which gastric contents are buffered by foods, as suggested by the finding that patients with slow emptying were less likely to develop esophagitis [26]. The mechanism of this accelerated emptying is unclear, although it could be due to defective relaxation of the proximal stomach. This hypothesis is supported by the severe reflux that has been observed in some patients with proximal gastric vagotomy, an operation that is known to cause defective gastric relaxation [26].
In conclusion, published evidence demonstrates that, even in series where gastric emptying was found to be delayed, this abnormality was present in only a fraction of the patients with GERD. It is also important to remember that most patients with gastric retention caused by functional or mechanical outlet obstruction do not have reflux esophagitis. Thus, gastric stasis is only one of the factors that contribute to GERD.
References