The innervation of the human upper esophageal sphincter

The neuroanatomy and physiology of the human upper esophageal sphincter (UES) has long been controversial. As a result, there has been little progress in diagnosing and treating dysphagias involving this area. In this study, three specimens of the UES obtained from human autopsies were examined by Sihler's stain. This stain clears soft tissue while counterstaining the nerves, thereby allowing nerve supply to each muscle of the UES to be demonstrated. It was found that the nerve supply to each component of the UES is substantially different. The inferior pharyngeal constrictor (IPC) is supplied by a dense linear plexus which is about 1.0–1.5 cm wide and 10 cm long and located about 1.5 cm lateral to the attachment of the IPC on the thyroid lamina. The cricopharyngeal (CP) muscle receives its innervation from below via the recurrent laryngeal nerve (RLN) and from above via the pharyngeal plexus. Neural connections between the RLN and the pharyngeal plexus were observed. Finally, the upper esophagus (UE) is innervated by the RLN. The innervation pattern of each component of the UES suggests functional differences between these muscles. These observations help clarify the innervation of the UES. Accurate knowledge of the neuroanatomy of the UES is necessary for advances in diagnosis and treatment of pharyngeal dysphagia.     

The hypertensive lower esophageal sphincter

Controversy exists as to whether the hypertensive lower esophageal sphincter (HLES) represents a clinical motility disorder of the esophagus or is merely the right-sided expression of a normal distribution curve. In the present study we describe 16 patients with HLES, defined as a lower esophageal sphincter (LES) pressure of 40 mm Hg (mean +3sd of controls) with normal peristalsis. All of the patients suffered from chest pain and nine from dysphagia. Delayed bolus transit at the gastroesophageal junction was demonstrated in four patients by radiography. Manometric studies showed that during swallowing the LES residual pressures were significantly greater (9.2±5.0 mm Hg) than observed in normal controls (1.8±2.2 mmHg) (mean±1sd). However, the percent LES relaxation in patients did not differ significantly from controls. Clinical improvement was associated with pharmacological or mechanical reduction of resting LES pressure with an accompanying fall in the nadir pressure. These observations suggest that HLES may have clinical and pathophysiological significance and that evidence for the entity should be sought during manometric studies in the clinical laboratory.     

The use of intraluminal manometry to assess upper esophageal sphincter function

The UES is a striated muscular structure that exhibits substantial variation in tone in response to a wide variety of stimuli as well as during deglutition. It is an asymmetric structure subject to substantial axial movement. Hence the findings on UES manometry are highly dependent upon the manometry equipment used, positioning of this equipment in relation to the UES, and external stimuli. There is considerable intrasubject and intersubject variation in some parameters from UES pressure recordings. These factors must be taken into account in the clinical use of UES manometry.     

Repetitive contractions of the upper esophageal body and sphincter in achalasia

This report describes repetitive contractions in the upper esophageal sphincter (UES) and the repetitive upper esophageal spontaneous contractions (RUESCs) of patients with achalasia and relates this activity to repetitive contractile activity (RCA) recorded in the more distal esophageal body, to intraesophageal pressure (IEP), and to lower esophageal sphincter (LES) pressure. Two hundred and sixteen consecutive esophageal motility studies from 156 achalasia patients were retrospectively assessed. RUESCs were found in 105 patients (67%) and 125 of 216 studies (58%). General features of the RUESC were (1) coincidence with simultaneous repetitive increases in pressure throughout the entire esophageal body; (2) amplitude of pressure increases tended to be higher in the proximal esophagus; (3) RUESC frequency was different than respiration, except for 6 cases where continuous, RUESC and RCA were synchronized with inspiration; and (4) RUESCs were positively associated with increased IEP, and with increased LES pressure (>40 mmHg). RCA in the esophageal body was uncommon without RUESC. It is concluded that (1) RUESCs are common in achalasia and appear to be closely linked to contractile activity in the upper esophageal body; (2) the close relationship of RUESC and RCA in the esophageal body to increased IEP and elevated LES pressure suggests that esophageal tone is high in these subjects; and (3) these findings indicate a potential mechanism for localization of some of the clinical symptoms to the retrosternal and suprasternal areas, for the inability to readily belch, and for the development of structural features such as a prominent cricopharyngeal bar.     

Effects of body position and bolus consistency on the manometric parameters and coordination of the upper esophageal sphincter and pharynx

The development of a solid-state intraluminal sphincter transducer has alleviated many of the problems associated with manometric studies of the upper esophageal sphincter (UES) and pharynx (P). We used this technology to study the effect of position (upright vs. supine) on resting UES pressures and the pressure dynamics of the UES/P complex during both wet and dry swallows in 11 normal volunteers and the effects of foods of different consistencies on the UES/P swallow dynamics in 10 normal volunteers. The UES/P coordination parameters were defined as the 15 time intervals that can be measured between any 2 of 6 pertinent points: the beginning, peak, and end of the pharyngeal contraction and the beginning, nadir, and end of the UES relaxation. Data from both the circumferential transducer used to measure sphincter pressures and a standard microtransducer used to measure pharyngeal pressures were collected on-line by an Apple IIe microcomputer and analyzed by programs written in our laboratory. Significant changes in swallow coordination were measured between upright and supine swallows of the same bolus size, between wet and dry swallows in the same position, and among foods of varying consistencies. Resting UES pressure was unchanged by position and pharyngeal contraction pressure was unchanged by bolus size or consistency.     

食管下端括约肌内肠神经系统研究进展

食管下端括约肌(LES)的调控机制是治疗胃食管反流性疾病的关键,而括约肌内参与调控的肠神经系统中各类神经及其递质的关系复杂。随着研究的深入,越来越多的神经被证实具有调节LES的功能。此文从病理组织学、神经生物学、药理学角度介绍各类神经研究情况。     

An update on the physiology of the components of the upper esophageal sphincter

The upper esophageal sphincter is defined as the components of the pharyngoesophageal region which contribute to the opening and closing of the pharyngo-esophageal junction during various physiologic states.     

Effect of head position on the dynamics of the upper esophageal sphincter and pharynx

Due to limitations in available technology it has been difficult to obtain data on upper esophageal sphincter (UES) and pharyngeal (P) function under varying physiologic conditions. We used a manometry system with solid-state intraluminal transducers, including a circumferential sphincter transducer, and computer analysis to measure pressure changes in UES and P during wet (5 ml H₂O) swallows as the head was moved through a 75 degree arc in nine normal volunteers. UES residual pressure increased markedly and duration of UES relaxation decreased with increasing head extension. Similar decreases were also seen with time between P peak and both UES nadir and UES end. There were no changes in either pharyngeal peak pressures or the duration of the pharyngeal contraction. Head extension produces major changes in UES relaxation and UES/P coordination. These effects may be clinically important when feeding neurologically impaired patients.     

In vitro effect of pantoprazole on lower esophageal sphincter tone in rats

AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were used throughout the study.They were anesthetized before decapitation.LES tissues whose mucosal lining were removed were placed in a stan-dard 30-mL organ bath with a modif ied Krebs solution and continuously aerated with 95% oxygen-5% carbon dioxide gas mixture and kept at room temperature.The tissue...     

Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease

The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter （LES） and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction （EGJ） into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease （GERD）.     

Correlation between esophageal contraction amplitude and lower esophageal sphincter pressure in patients with nutcracker esophagus

Nutcracker esophagus (NE) is a primary esophageal motility disorder characterized by high-wave amplitude at the distal esophagus. The aim of this study was to analyze patients with NE and determine the relationship between distal esophageal contraction amplitude and lower esophageal sphincter (LES) pressure. Esophageal manometry tracings of patients with NE, defined as the presence of distal contraction amplitude of more than 182 mmHg after wet swallow, were analyzed. LES pressure was measured as the mean end-expiratory value. Spearman's correlation coefficient analysis was used to compare esophageal contraction amplitude with LES pressure. This comparison was also performed in patients with isolated hypertensive LES (HLES) and in subjects with normal manometry. Forty patients (25 female, 15 male; mean age 54 years) with NE were included in the study. Mean (SD) distal esophageal contraction amplitude was 230 (35.7) mmHg and mean LES pressure was 27.3 (5.7) mmHg. Esophageal contraction amplitude showed a positive correlation with LES pressure (r = 0.49, P < 0.01). In contrast, no correlation was found in patients with HLES (r = 0.21, P > 0.05) and in those with a normal manometric study (r = 0.18, P > 0.05). It is concluded that in patients with nutcracker esophagus a positive correlation exists between distal esophageal contraction amplitude and LES pressure, suggesting a diffuse hypertensive pattern involving smooth muscle at the distal esophagus and adjacent LES.     

Effect of secretin on lower esophageal sphincter pressure in patients with esophageal achalasia

The effect of a bolus intravenous administration of secretin (2.0 U/kg) on resting lower esophageal sphincter pressure (LESP) was investigated in seven patients with esophageal achalasia. Basal LESP before secretin injection in the patients was 60.113.4 mmHg (Mean±SEM), which was significantly higher than 26.9±2.5 mmHg in normal controls consisting of eight healthy volunteers. LESP significantly decreased within 1 min after the injection both in the patients and the controls. The maximum pressure change from each basal LESP was 31.2±5.2 mmHg in the patients, which was significantly greater than 12.1±1.8 mmHg in the controls. The effect of secretin disappeared within 5 min in the controls. The effect in the patients, however, lasted throughout the investigation time of 30 min. It is concluded that secretin has a long-acting effect on muscular relaxation of the lower esophageal sphincter in esophageal achalsia patients.     

Mobility of the upper esophageal sphincter in relation to the cervical spine: A morphologic study

If the posterior part of the upper esophageal sphincter (UES) were to lag behind due to the presence of dense tissue strands between the sphincter and the prevertebral ligament, as suggested in the literature, it would be impossible to use the larynx as a radiographic indicator of the location of the UES at intraluminal pressure measurements. The goal of this investigation was to study UES behavior during induced movements in autopsy specimens and to search for dense fibrous strands between the UES and the prevertebral fascia. Histologic studies of frozen sections and paraffin sections showed a loose fatty tissue in the prevertebral space. There were no dense connective tissue strands. Autopsy specimens were used in experiments mimicking the laryngeal/UES elevation during swallowing. The results of this study indicate that the larynx and the UES move as one entity. When one is attempting to register the UES movement during swallowing, the laryngeal skeleton can therefore serve as a radiographic indicator of the UES movements.     

Effect of aging on the deglutitive oral,pharyngeal, and esophageal motor function

Aging affects some members of the swallowing orchestra and spares the others. It seems that changes in the pharynx of the elderly are more of a positive nature than a negative one and reflect an adaptation to age-induced structural changes of the upper esophageal sphincter. In the esophagus, the positive change in deglutitive peristaltic amplitude and duration seem to revert to a negative one over the age of 90 years. In the upper esophageal sphincter, it appears that aging reduces the resting pressure, but spares its response to various stimuli. Considering the increasing elderly population and their medical needs, further normalcy data about various manometric aspects of deglutition is needed for physiologic studies as well as diagnostic and therapeutic purposes.     

Effects of transdermal nicotine on lower esophageal sphincter and esophageal motility

Cigarette smoking has been shown to decrease lower esophageal sphincter pressure (LESP) by 19–42%. This decrease in LESP may be due to nicotine in the cigarette smoke or substances other than nicotine. The aim of this study was to evaluate the effects of a nicotine patch on esophageal motility since nicotine patches are devoid of all toxins present in the cigarette smoke except the nicotine. Ten healthy nonsmoking volunteers underwent baseline esophageal manometry. Esophageal manometry was repeated after placing a nicotine transdermal patch (Nicotrol) designed to deliver 15 mg of nicotine per day. The parameters that were compared included LESP by rapid pull-through (LESP-RPT) and station pull-through (LESP-SPT), LES relaxation, and velocity, amplitude, and duration of esophageal contractions. Plasma nicotine and cotinine levels were measured prior to baseline manometry and after 12 hr of placing the nicotine patch. the LESP-RPT decreased by 31% from 17.4±6.1 to 12.1±3.3 (P=0.013) and the LESP-SPT by 27% from 13.4±5.4 to 9.8±4.8 (P=0.029) after the nicotine patch. LES relaxation was present in 100% before and after nicotine patch. There were no significant differences in velocity, duration, and amplitude of esophageal contractions after the nicotine patch. Plasma nicotine and cotinine was absent in all subjects at baseline but was significantly elevated after 12 hr of nicotine patch. Transdermal delivery of nicotine results in a significant reduction in LESP in healthy subjects without effecting LES relaxation or esophageal body motility.The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense.This work was published in an abstract form in Gastroenterology 106:A1047, 1994.     

Investigation of cholecystokinin receptors in the human lower esophageal sphincter

AIM:To compare the binding of cholecystokinin(CCK)-8to CCK receptors in sling and clasp fibers of the human lower esophageal sphincter.METHODS:Esophageal sling and clasp fibers were isolated from eight esophagectomy specimens,resected for squamous cell carcinoma in the upper two thirds of the esophagus,which had been maintained in oxygenated Kreb’s solution.Western blot was used to measure CCK-A and CCK-B receptor subtypes in the two muscles.A radioligand binding assay was used to determine the binding parameters of 3H-CCK-8S to the CCK receptor subtypes.The specificity of binding was determined by the addition of proglumide,which blocks the binding of CCK to both receptor subtypes.RESULTS:There was no significant difference between the sling and clasp fibers of the human lower esophageal sphincter in the amount of CCK-A[integratedoptical density(IOD)value:22.65±0.642 vs 22.328±1.042,P=0.806]or CCK-B receptor protein(IOD value:13.20±0.423 vs 12.45±0.294,P=0.224)as measured by Western blot.The maximum binding of radio-labeled CCK-8S was higher in the sling fibers than in the clasp fibers(595.75±3.231 cpm vs 500.000±10.087 cpm,P<0.001)and dissociation constant was lower(Kd:1.437±0.024 nmol/L vs 1.671±0.024nmol/L,P<0.001).The IC50 of the receptor specific antagonists were lower for the CCK-A receptors than for the CCK-B(P<0.01).CONCLUSION:CCK binding modulates the contractile function of the lower esophageal sphincter through differential binding to the CCK-A receptor on the sling and clasp fibers.