What are the different types of lower esophageal sphincter abnormalities responsible for gastro-esophageal reflux?
M. Anselmino, M. Costantini, C. Boccù,
D. Molena, G. Zaninotto (Padova)
Gastro-esophageal reflux disease (GERD) is a common condition in which a lower esophageal sphincter (LES) dysfunction represents the most important aetiological factor. The LES is a physiological entity represented by an asymmetrical muscular thickening at the gastroesophageal junction and manometrically identified as a high pressure zone . This pressure is exerted during resting conditions and is generated by an inward calcium leak with partial depolarization of the LES smooth muscle, which is in a state of tonic contraction. This situation reflects the strength of the anti-reflux barrier. The reflux of gastric content into the esophagus occurs: 1) when the intrinsic LES pressure is primarily and permanently low [2-4]; 2) when the LES pressure is normal but exerted on a limited area, i.e. when the sphincter is too short to offer sufficient resistance to counter the difference between the positive intra-abdominal pressure and the negative thoracic pressure or variations in intra-abdominal pressure ; 3) during spontaneous LES openings unrelated to peristaltic contractions of the esophageal body - the so-called transient LES relaxations [6-8]; 4) during respiratory fluctuations in LES pressure when the sphincter function of the crural diaphragm is of little effect, as in the case of patients with delayed gastric emptying [9, 10].
Physiologically, the LES is a 3-5 cm long segment of tonically contracted smooth muscle, 1-2 cm of which are situated below the diaphragm, and the resting pressure of which varies from 7 to 25 mmHg in relation to intragastric pressure. LES competence, as evaluated by stationary manometry, results from the combined mechanical effect of sphincter pressure, overall length and the length exposed to the positive pressure of the abdomen, i.e. the intra-abdominal length . The normal values of these three parameters, obtained in a population consisting of 17 healthy volunteers and representing the standard reference in our lab, are shown in Table I. These values are comparable with those obtained in a larger population of 50 American healthy subjects . When any of these mechanical components fails, the LES is usually considered as defective. LES deficiency was identified in as many as 60% of patients with reflux symptoms and positive 24-hour pH monitoring . The most mechanical cause of incompetence is represented by a primarily inadequate LES pressure, though the efficiency of a sphincter with a normal pressure may be hindered by an inadequate abdominal length or an abnormally short overall length . This means that patients with a low LES pressure - like those with a normal pressure but a short abdominal length - are unable to prevent the reflux caused by variations in intra-abdominal pressure that commonly occur with daily activities and changes in body position [3, 4]. Similarly, patients with a low LES pressure - or those with a normal LES pressure but a short overall length - are unable to avoid the reflux caused by increases in intragastric pressure beyond the intra-abdominal pressure, as in the case of gastric distention. In this latter case, gastric dilation makes the situation worse because it causes a further shortening of the sphincter (just as the neck of a balloon becomes shorter as it is inflated), the overall length of which decreases to less than the length needed to maintain competence . LES pressure can be directly affected by intra-abdominal pressure, gastric distention, peptides, hormones, foods and many drugs , whereas the shortening or nullifying of the intra-abdominal segment can be found in patients with hiatus hernia .
The LES usually opens in response to swallowing and its intrinsic tone decreases as far as to reach the value of the intragastric pressure. Gastro-esophageal reflux rarely occurs during this LES swallow-induced relaxation because of the protective effect of the oncoming peristaltic wave . Prolonged monitoring of the LES pressure using a sleeve-device has shown that spontaneous LES relaxations may occur in the absence of swallowing, not only in patients with reflux esophagitis, but also in normal LES and in healthy subjects [7, 8]. A combination of the sleeve method with simultaneous esophageal pH monitoring has demonstrated that this mechanism of "transient" LES relaxation (TLESR) is responsible for gastroesophageal reflux (GER) episodes as a result of a balance being created between the intra-esophageal and the intragastric pressure (the so-called "common cavity" phenomenon) and has accounted for 98% of acid-reflux episodes in normal subjects [5, 7]. The complex phenomenon of TLESRs is not completely understood and seems to represent a physiological response triggered by gastric distention [14, 15]. It is not clear as yet whether TLESRs alone can genuinely be responsible for pathological GER. It may be, however, that physiological reflux episodes recorded during TLESRs may become pathological in the event of a defective esophageal peristalsis due to prolonged exposure of the esophageal mucosa to the refluxed material.
The LES pressure measured by side-hole manometry shows respiration-induced pressure oscillations [16, 17]. These pressure oscillations vary and are due to the influence of abdominal and thoracic pressures on the LES , but they are also caused by the combined movements of the point pressure sensor and the LES during breathing . However, the observation that the amplitude of the pressure oscillations is directly proportional to the depth of inspiration, and that these oscillations are abolished by a skeletal muscle paralyzing agent , suggests that there must be an active contraction of the crural diaphragm during inspiration, since the increase in crural diaphragm EMG activity has been demonstrated . It seems that in the event of symptoms typical of delayed gastric emptying (such as vomiting or eructation), but also during esophageal distention, the electrical activity of the crural fibers fades and the strength of the anti-reflux barrier consequently decreases, favoring GER.
Despite GERD being a disease with a multifactorial etiology, LES competence remains the primary factor in its prevention. A knowledge of the factors contributing to LES competence is not only important for the diagnosis of GERD, it also establishes correct indications for surgery and helps guide the making of effective anti-reflux repairs.
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