Role of gastrin supersensitivity in the pathogenesis of lower esophageal sphincter hypertension in achalasia

Abstract

A B STRA CT Intraluminal manometric studies were carried out in 19 patients with untreated achalasia and in 20 normals. Lower esophageal sphincter (LES) pressure was 50.5 ±4.6 mm Hg in patients with achalasia as compared with 19.4 ±1.3 mm Hg in the normal group.In both groups, the LES pressure was lowered when exogenous 0.1 N HCl was placed into the stomach. Although the nadir of pressure attained with acid suppression was the same, the per cent inhibition was significantly greater in patients with achalasia. Serum gastrin levels were the same in the two groups studied. The patients with achalasia, pre-and postpneumatic dilatation, showed a supersensitivity to exogenous intravenous gastrin I, as compared with normals. These data suggest that high, acid-suppressible levels of LES pressure, in patients with achalasia, are due to supersensitivity to endogenous gastrin. INTRODUCTIONIn patients with achalasia, dysfunction of the lower esophageal sphincter (LES)' plays a major role in the pathogenesis of impaired esophageal emptying. Although this point is well recognized, a clear understanding of the pathophysiology of this dysfunction is not available. The classic concept of a normotensive LES, which fails to relax upon deglutition (1, 2) has been questioned (3). It has been suggested that LES dysfunction consisted of a marked elevation in LES pressure and a limited, but distinct, ability to relax upon deglutition. By this latter concept, LES hypertension would play a major role in the impairment of esophageal emptying. It is the purpose of this study to utilize a method of proven

Differences between idiopathic and chagasic achalasia

“…Consequently lower esophageal sphincter pressure is frequently increased in idiopathic achalasia [14][15][16][17] and frequently decreased in Chagas' disease [16][17][18][19] which may explain the variation in the lower esophageal sphincter pressure [20] , and the heterogeneity seen in these patients [21] .…”

“…Previous studies have reported differences in esophageal response to gastrin [14,15,18] and to atropine [15,22] . These mechanisms have not been completely elucidated in Chagas' disease [11,13] [ Table 1].…”

Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum.

“…If circulating gastrin is not responsible for the genesis of LESP, then an alternative mechanism of inhibitory effect of such hormone must be considered. (b) Defects in gastrin release and gastrin sensitivity have been proposed as the basis of LES incompetence (10,11) and LES hypertension in achalasia (11)(12)(13), respectively. If gastrin is not a major determinant of LESP, then concepts about the pathogenesis of LES disorders need to be revised, and alternative pathogenetic mechanisms must be investigated to provide a basis for rational therapy.…”

“…Some observers have proposed that circulating gastrin (3,4) is the major determinant of LESP. This hypothesis of gastrin closure of lower esophageal sphincter (LES) has been used as a model: (a) to explain the pathogenesis of a variety of disorders of the LES such as sphincter incompetence in reflux esophagitis (9)(10)(11) and sphincter hypertension in achalasia (11,12); (b) to explain the mechanism of inhibitory action of secretin (3) and cholecystokinin (13) on LESP; and (c) to estimate endogenous gastrin activity in vivo (14). On the other hand, others (5-7) have recently questioned some of the evidence which formed the basis of the hypothesis that gastrin has a major role in the physiological regulation of LESP.…”

The Genesis of Lower Esophageal Sphincter Pressure: Its Identification through the Use of Gastrin Antiserum

“…1 Abbreviations used in this paper: CCK-PZ, cholecystocompetence at the gastroesophageal junction in man (1)(2)(3)(4)(5). Recent studies have focused on the neural (6, 7) and humoral (8)(9)(10)(11) factors that augment LES pressure above its resting level. However, the genesis of the resting LES strength itself is not known.…”