Functional anatomy and physiology of the upper esophageal sphincter

Functional Anatomy and Physiology of the Upper Esophageal Sphincter D.V. Sivarao, PhD, Raj K. Goyal, MD

Upper esophageal sphincter (UES) refers to the highpressure zone located in between the pharynx and the cervical esophagus. The physiological role of this sphincter is to protect against reflux of food into the airways as well as prevent entry of air into the digestive tract. UES is a musculocartilaginous structure with its anterior wall being formed by the full extent of the posterior surface of the cricoid cartilage and arytenoid and interarytenoid muscles in the upper part. Posteriorly and laterally the cricopharyngeus (CP) muscle is a definitive component of the UES. CP has many unique characteristics: it is tonically active, has a high degree of elasticity, does not develop maximal tension at basal length, and is composed of a mixture of slow- and fast-twitch fibers, with the former predominating. These features enable the cricopharyngeus to maintain a resting tone and yet be able to stretch open by distracting forces, such as a swallowed bolus and hyoid and laryngeal excursion. CP, however, constitutes only the lower one third of the entire high-pressure zone. The thyropharyngeus (TP) muscle accounts for the remaining upper two thirds of the UES. The UES pressure is not entirely the result of myogenic activity, as a component of the pressure is the result of passive elasticity of the tissues. The opening of the UES involves relaxation of CP and TP muscles and forward movement of the larynx by the contraction of hyoid muscles. The UES function is controlled by a variety of reflexes that involve afferent inputs to the motorneurons innervating the sphincter. These physiological reflexes elicit either contraction or opening of the UES. Inability of the sphincter to open leads to difficulty in swallowing. Opening of the sphincter without associated CP relaxation leads to the clinical syndrome of cricopharyngeal bar. Am J Med. 2000;108(4A):27S–37S. © 2000 by Excerpta Medica, Inc.

From the Center for Swallowing and Motility Disorders, Brockton/ West Roxbury Veterans Affairs Medical Center and Harvard Medical School, West Roxbury, Massachusetts. Supported in part by research grant DK 31092 from the NIDDK and a Veterans Affairs Merit Review Award from the Medical Research Service, Department of Veterans Affairs. Requests for reprints should be addressed to Raj K. Goyal, MD, Research and Development (151), 1400 VFW Parkway, West Roxbury, Massachusetts 02132. © 2000 by Excerpta Medica, Inc. All rights reserved.

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he upper esophageal sphincter (UES) is functionally defined as the intraluminal high-pressure zone that lies in between the pharynx and the cervical esophagus. The physiological role of the UES is to prevent air from entering the digestive tract during inspiration and to protect the airways from aspiration by preventing esophageal contents refluxing into the hypopharynx. The UES relaxes transiently during swallowing to allow a bolus to enter the esophagus and, during belching and vomiting, to allow the egress of air and vomitus from the esophagus. It is generally believed that the cricopharyngeus (CP) is the main muscle responsible for the UES function. Therefore, the UES is frequently referred to as the cricopharyngeal sphincter.

THE CRICOPHARYNGEUS MUSCLE The CP is the most definitive component of the UES. It arises from the lower part of the dorsolateral aspect of the cricoid cartilage and forms a horizontal loop to attach to the cricoid cartilage on the opposite side. The CP is structurally, biochemically, and mechanically distinct from the surrounding pharyngeal and esophageal muscles. It is composed of striated muscle fibers of small average diameter (25 to 35 ␮m), which are not oriented in a strict parallel fashion.1–3 The CP contains a large mount of endomysial connective tissue (approximately 40%).1,2 Originally considered as abnormal,4 aberrant histological and histochemical features, such as internalized nuclei, ragged red crescents, splits, degenerating fibers, and nemaline rods, are now known to characterize normal CP tissue.5 It has been suggested that unlike most other striated muscles that insert into the skeletal framework, the CP inserts onto the connective tissue framework, thereby forming a muscular network.2 The CP has both slowtwitch (type 1, oxidative) and fast-twitch (type 2, glycolytic) muscle fibers; however, the predominant fiber is of the slow-twitch type.1–3,6 The presence of both slow- and fast-twitch fibers enables the CP to maintain a constant basal tone and yet rapidly relax in response to a swallow or a belch reflex.3 The length at which the CP develops maximum tension is approximately 1.7 times its basal length,7 whereas for most striated muscles, maximum tension develops at in situ or basal length itself. The source of this elasticity may be attributable to the parallel elements comprising the connective tissue, sarcolemma, and the contractile apparatus of the CP.8,9 This elasticity enables the sphinc0002-9343/00/$20.00 27S PII S0002-9343(99)00337-X

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ter to maintain a basal tone even without distension or extraneous neural influence. The tension of the sphincter increases throughout its range of distension by increasing bolus sizes, similar to Starling’s law of the cardiac muscle.7 It is physiologically unlikely that the UES will stretch beyond its optimal length during a swallow of maximal volume. Because the CP is highly elastic and does not develop maximum tension at resting length, the UES can be opened by increased intraluminal pressure, such as exerted by a bolus, or active distraction, such as effected by hyoid excursion, without active relaxation or inhibition of the CP.7 Innervation of the CP is also distinctive. The CP is innervated bilaterally from above by a linear pharyngeal plexus that is formed mainly by the vagus nerve by way of its pharyngeal and superior laryngeal branches and the glossopharyngeal nerve and the sympathetic nerve fibers from the cranial cervical ganglia. The recurrent laryngeal nerve, which is also a branch of the vagus, contributes to the plexus from below.10 –12 Functional evidence using glycogen-depletion studies in the rat has shown that the principal motor innervation is by pharyngeal and superior laryngeal nerves,13 and the recurrent laryngeal nerve may provide partial motor innervation bilaterally to the CP in humans and sheep.14 Although there is no prominent raphe demarking the CP bilaterally, it is bilaterally innervated by the nerves,10 with each half of the CP acting as a distinct motor unit.7 The motor end plates in the CP are scattered throughout the tissue, and they are clustered along the midline in the thyropharyngeus (TP; see below) muscle, which is situated immediately above the CP.15 The cell bodies of the lower motor neurons innervating the CP are located ipsilaterally, in the semicompact and rostral compact portions of the nucleus ambiguus.13,16 –22 Additional motor neurons are located outside the nucleus ambiguus.13,20 The motoneurons of the nucleus ambiguus have extensive dendritic arborization into the adjacent reticular formation23 with both excitatory and inhibitory synaptic contacts.24 This dendritic architecture of the motor neurons innervating the CP may form an anatomic basis for an extensive reflex control of the UES by different afferent inputs (see below). Acetylcholine is the principal neurotransmitter for efferent innervation of the CP, acting via the skeletal muscle nicotinic receptors.25 In addition, many putative neuropeptides have been demonstrated within the nerve terminals innervating the CP.26,27 These include calcitonin gene–related peptide, neuropeptide Y, substance P, vasoactive intestinal polypeptide, and galanin. Their role in regulating CP function is currently unknown, although some of these peptides were associated with nerve terminals innervating the blood vessels supplying the CP and may have a role in regulating regional blood flow.27 The pharyngeal vagal afferents, with their cell bodies in jugular and nodose ganglia,20 terminate on premotor 28S

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neurons in the interstitial and intermediate regions of the nucleus tractus solitarius. These in turn project onto pharyngeal motoneurons in the semicompact region of the nucleus ambiguus.16 The glossopharyngeal nerve fibers innervating the CP may be afferents involved in carrying information to the brain, because transection of this nerve abolished a recently characterized pharyngo-UES contractile reflex.28 The CP is devoid of muscle spindles.1,2 However, a Golgi tendon–like structure has been reported in the human CP that may be involved in monitoring muscle tension and providing feedback to the pharyngeal motoneurons.29 The excitatory amino acid L-glutamate or a similar compound may be involved in afferent neurotransmission to the nucleus tractus solitarius. The functional significance of sympathetic innervation is unknown.20

CP MUSCLE ACCOUNTS FOR ONLY THE LOWER THIRD OF THE UES Although the CP is agreed to be an important part of the UES, it does not account for the entire UES high-pressure zone. The UES high-pressure zone, as defined by intraluminal manometry in humans, extends to approximately 2 to 4 cm below the laryngeal opening.30 Anatomically, this region corresponds to several components of the collapsed segment of lower pharynx that spans from the laryngeal aditus to the lower border of the cricoid cartilage. These include the muscular-cartilaginous hypopharynx, including the cricoid cartilage and arytenoid cartilages ventrally and the inferior pharyngeal constrictor muscle (IPC) posteriorly and laterally (Figure 1).30 –32 The IPC is the thickest of the three pharyngeal constrictor muscles and has two distinct components to it, the pars obliqua and the pars fundiformis, distinguished by both the location of the muscular attachment to the cartliage and the angle at which the muscle fibers extend posteriorly.1 The pars obliqua, also known as TP, arises from the oblique line on the side of the lamina of the thyroid cartilage and spreads dorsally and medially to be inserted with the muscle of the opposite side into the posterior midline raphe of the pharynx. As outlined above, CP fibers, also called pars fundiformis, extend horizontally around the posterior circumference of the hypopharynx to attach to the dorsolateral aspects of the cricoid cartilage on each side, posterior and inferior to the attachment of the pars obliqua.12 The CP muscle, however, is only 1 cm wide and therefore cannot by itself account for the entire high-pressure zone. Anatomically, the CP covers only the caudal third of the entire cricoid cartilage. Therefore, the TP part of the IPC must contribute to the remaining part of the UES. In humans, the area that extends from the laryngeal opening (bottom of the air column on a lateral x-ray of the pharynx) to the lower border of the cricoid cartilage is approximately 3.2 cm. The arytenoid and interarytenoid

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Figure 1. Dorsal view of the pharyngeal musculature. External aspect is illustrated on the left side and internal aspect on the right side. Thyropharyngeus and cricopharyngeus muscles constitute oblique and horizontal components of the inferior pharyngeal constrictor, respectively. The vertical bar represents the anatomic extent of the upper esophageal sphincter (UES) high-pressure zone that corresponds to the posterior surface of the cricoid cartilage and the transverse arytenoid muscles above it. Note that cricopharyngeus muscle is present in the lower and thyropharyngeus muscle in the upper parts of the UES. (Modified from The CIBA Collection of Medical Illustrations.32)

Figure 2. Lateral radiograph of a patient with a prominent cricopharyngeal bar (arrow) observed during a barium swallow. Note that cricopharyngeus muscle is present in the lower part of the cricoid cartilage. The upper esophageal sphincter (UES) extends from the level of the vocal cords to the lower border of the cricoid cartilage. March 6, 2000

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muscles extend vertically down 0.75 cm from the laryngeal opening and the cricoid lamina extends 2.5 cm vertically below that. If the high-pressure zone extends to approximately 3 cm below the air column33 (Figure 2), the posterior surface of the cricoid cartilage, visible on radiographs, will form its anterior boundary. Anatomically, this high-pressure zone is bound by the pyriform sinuses laterally and the IPC posteriorly. Owing to its anatomic features, the UES forms a transverse slit-like structure when closed, the so called “lip of the esophageal mouth.”34 Goyal et al,31 comparing UES manometric data from three different sources, came to the conclusion that the CP muscle corresponds to the declining profile of the bell-shaped high-pressure zone and the peak high-pressure zone corresponds to the maximal dorsal bulge of the posterior surface of the cricoid cartilage (Figure 3). Thus, the CP seems to correspond to the distal third of the sphincteric high-pressure zone, and the zenith of the high-pressure zone lies 0.5 to 1.5 cm proximal to it. It may be noted that the surgical procedure cricopharyngeal myotomy, performed to relieve impaired UES relaxation and oropharyngeal dysphagia, actually involves the division of 4- to 6-cm-long muscle that involves not only the CP and the TP but also the cervical esophagus.31,35,36 The logic for including cervical esophagus in the myotomy is not clear. Interestingly, a recent study documented the UES pressure in patients undergoing sequential surgical myotomy of the CP, using a sleeve sensor.36 They found that the UES pressure was unaffected with a 2-cm division of the cervical esophagus, decreased significantly (P ⬎0.05) with a further 2-cm division of the cricopharyngeal area, and again decreased significantly with a final 2-cm division of the hyopharyngeal musculature.36 A skeletal muscle constituting a sphincter is expected to be tonically active as a result of an ongoing cholinergic neural stimulation.37,38 Indeed, studies employing simultaneous manometric and electromyographic studies in the opossum have demonstrated that both the CP and the TP exhibit continuous spike activity at rest in awake as well as lightly anesthetized animals.39,40 Cessation of the electrical activity in these muscles, by motor nerve section or skeletal muscle nicotinic receptor blockade, causes a marked reduction in the resting UES pressure. Like the CP, the thin inner muscular layer of the TP is composed mainly of oxidative slow-twitch fibers that are well suited for tone maintenance.41 Physiologically, the CP electrical activity ceases during swallowing, vomiting, and belching, preceding and signaling the UES relaxation.39,42 Some investigators have suggested that the circular muscle of the proximal cervical esophagus makes up the reminder of the UES.43,44 Others have found little functional evidence for a sphincter inferior to the CP.39,45 For example, in the opossum, unlike CP and IPC, the esoph30S

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ageal fibers just distal to the CP are electrically quiescent under resting condition.39 Mucosal squeeze alone may explain the small elevation of pressure that extends further into the esophagus. In summary, all the available data suggest that the CP contributes to the lower third of the UES and the TP muscle constitutes the upper two thirds of the sphincter. It is for this reason, although generally referred to as the UES, it is perhaps more anatomically accurate to call the high-pressure zone the inferior pharyngeal sphincter. The anatomical landmarks of UES and their relation to the high-pressure zone is shown in Table 1.

BASAL UES PRESSURE IS THE RESULT OF THE ACTIVE MUSCLE CONTRACTION AND PASSIVE MECHANICAL FACTORS The closing pressure of the UES varies somewhat with the circumstances under which the measurements are made.46 – 49 The pressure profile of the UES shows axial asymmetry with a sharp ascent in its upper part and a more gradual decline in its lower part as well as marked radial asymmetry.39,47,50 Welch et al50 constructed a three-dimensional pressure profile of the UES in humans. The pressures are higher in the anterior-posterior than in the lateral orientation, but there is also a dissociation of peak pressures along the anterior and posterior aspects. In humans, the peak pressure occurs 1 cm below the upper border of the high-pressure zone anteriorly and 2 cm below the upper portion of the high-pressure zone posteriorly. Thus, the sphincteric musculature posteriorly and the rigid cricoid cartilage anteriorly act like slightly offset jaws of a vise enclosing the peak-high-pressure zone.50 The radial and axial asymmetry is not observed after laryngectomy, indicating that the rigid cartilages of the larynx forming the anterior wall of the UES are responsible for the asymmetry.50,51 In the opossum, the posterior rather than the anterior pressure peak is closer to the pharynx.39 Reported resting UES pressures in normal subjects with low compliance recording systems have ranged from 35 to 200 mm Hg.46,49 Pressure recorded with a laterally oriented manometric device is 33% of the magnitude of pressures recorded when the device is oriented in the anterior or posterior direction. By using a circumferentially sensitive solid state pressure transducer that records an average pressure ⬎360 degrees and thus obviates orientation asymmetry, reproducible UES pressures ranging from 30 to 110 mm Hg have been reported.46,47,49,52 The significance of continuous electrical activity in the UES has been a subject of debate.39,53–55 Doty56 concluded that resting UES closure was entirely the result of passive forces caused by elasticity of the tissues and that tonic electrical spike activity is caused by reflex stimulation by the intraluminal manometry tube or other re-

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Figure 3. Compiled data from three different studies of manometric profiles of the upper esophageal sphincter and their relationship to the cartilages in the anterior wall and muscles in the posterior wall. Important anatomic landmarks in this region are the vocal cords, which can be recognized by the air level in the laryngotracheal area. The vocal cords mark the junction of arytenoids and the cricoid cartilage. Notice that the peaks of the three reported profiles of the high-pressure zone (bell-shaped curve) lie above the anatomical extent of the cricopharyngeus muscle (CPM) (horizontal hatched bar). A ⫽ arytenoid; AEF ⫽ aryepiglottic fold; CC ⫽ cricoid cartilage; ESO ⫽ cervical esophagus; IPC ⫽ inferior pharyngeal constrictor (thyropharyngeal part); PE ⫽ pharyngoesophageal; TR ⫽ tracheal ring; VC ⫽ vocal chord. (Adapted from Dysphagia.31) Table 1. Anatomical Boundaries High Pressure Zone Upper third Middle third Lower third

Anterior

Posterior

Side

Arytenoid pyriform sinus Arytenoid pyriform sinus Cricoid

Cricothyropharyngeus

Cricothyropharyngeus

Killian’s triangle

Cricothyropharyngeus

Cricopharyngeus

Cricopharyngeus

flexes.57–59Asoh and Goyal,39 in contrast, suggested that continuous electrical spike activity, combined with passive forces, are responsible for the resting UES pressure. Electromyographic spike activity of the CP and IPC in deeply anesthetized opossums is markedly reduced.39 In humans, most of resting UES pressure is eliminated during sleep and increases sharply at the onset of periods of wakefulness, presumably as a result of a decrease and increase in neurally mediated myoelectrical activity, respectively.60 The residual pressure that remains during sleep may be the result of the elasticity of the UES components that passively compress the passage to the cervical esophagus.39,60 Resting UES pressure may be low in infants and in the elderly.61– 65 Acute stress and other emotional states cause a significant elevation of resting UES pressure

in normal human subjects as well as patients with a history of globus sensation.66,67

UES OPENING REQUIRES RELAXATION OF THE SPHINCTER MUSCLES AND CONTRACTION OF THE SUPRAHYOID MUSCLES The UES opening has two components to it; cricopharyngeal relaxation and laryngeal displacement. The relaxation component is the result of the cessation of tonic activity in the CP and IPC muscles, whereas the opening is the result of contraction of the suprahyoid muscles. In experimental settings, contraction of geniohyoid muscle may obliterate the UES high-pressure zone even when the CP continues to be contracted.39 Under normal circum-

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Figure 4. Temporal relationship between hyoid and laryngeal anterosuperior excursion and upper esophageal sphincter (UES) opening. Horizontal bar indicates duration of UES opening and transphincteric barium flow. Notice that the sphincter relaxation precedes sphincter opening. Also note that UES opening is associated with anterior and superior movement of larynx and the hyoid bow. Data were compiled from concurrent videofluorographic and manometric study from eight human subjects. (Adapted from Am J Physiol.68)

stances, however, the cessation of activity in the CP and contraction of the suprahyoid muscles are coordinated to ensure efficient opening of the UES.68 –70 UES opens during deglutition, rumination, vomiting, regurgitation, and belching.59,71–74 During swallow-induced opening of the UES, the continuous spike activity of the CP muscle ceases.39,75 This may be due to a transient chloride-dependent inhibition of tonically active lower motor neurons in the brain stem innervating the UES.56,76 Corresponding to this inhibition, manometric recordings demonstrate a decrease in UES pressure immediately after the onset of deglutition, approximately 150 msec preceding radiologic opening of the UES (Figure 4).68 A brisk anterior movement of the larynx gener32S

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ated by anterior motion of the hyoid during its superior excursion, and caused by the contraction of suprahyoid muscles, is required to abolish this residual pressure and open the sphincter. Indeed, detailed studies using manometry and fluoroscopic techniques have demonstrated that the UES relaxes and opens during the superior and anterior movement of the larynx and closes during laryngeal descent (Figure 4).72 This initial opening of approximately 0.7 cm in humans is independent of bolus volume and can be effected during dry swallows.68 Pressures at the nadir of relaxation may reach subatmospheric levels but do not usually reach intraesophageal levels.33 The nadir UES pressure may sometimes be briefly interrupted by a brief increase in pressure that

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corresponds to the backward movement of the tongue (T wave).30,40 During anterior displacement of the cricoid, the posterior pharyngeal wall is restricted from moving forward by prevertebral fascia.77 However, the pharyngeal musculature moves freely in the longitudinal direction. During swallowing, shortening of the pharyngeal elevator muscles, such as the stylopharyngeus, also elevates the larynx and widens the transverse UES diameter. During the period of maximal sphincter elevation, the infrahyoid musculature has the mechanical advantage to pull the anterior wall of the sphincter forward.40 Orad excursion of the larynx not only facilitates UES opening but also enlarges the pharynx to receive the bolus, shortens the distance the bolus must travel, and protects the larynx against aspiration. With a 5-mL swallow, the larynx moves superiorly approximately 2.5 cm and approximately 0.75 cm anteriorly.68 The hyoid and larynx elevation achieved during swallowing in adults recapitulates, if only momentarily, the high resting position of these structures in infancy and in nonhuman primates.78,79 Along with hyoid and laryngeal excursion, the high-pressure zone itself moves 2 to 2.5 cm in an orad direction.80 – 82 UES opening duration may be slightly longer in women than men.83 Aging may cause a delayed UES relaxation relative to peak pharyngeal contraction61,62,64 and a slightly higher residual pressure at peak UES relaxation.62 Aged subjects also demonstrate higher hypopharyngeal pressure wave amplitude and duration in response to a swallow, suggesting an adaptation response to pharyngeal outflow compromise, such as a less compliant UES.64 The increased UES outflow resistance in the elderly was shown to decrease with specific exercises that targeted and strengthened the suprahyoid group of muscles,84 presumably the result of enhanced distraction of the UES. Biofeedback techniques, such as Mendelsohn maneuver (volitional prolongation of the superior and anterior displacement of the larynx at midswallow), can prolong swallow-related hyoid and laryngeal excursion, and thus increase UES opening time by maintaining traction on the anterior sphincter wall.85 The most marked effect of this maneuver on the UES opening profile was at the tail end rather than the beginning. Thus the stage of “sphincter collapse” is amenable to delay by this technique and in some cases the normal mechanism of sphincter closure as a result of the propagated pharyngeal wave was entirely absent among trained subjects employing this maneuver.85 On the other hand, by turning the head to either side, it is possible to enhance the degree of UES opening and reduce the sphincter resistance to the incoming bolus, without affecting the period of opening or oropharyngeal transit time.86,87 In individuals with substantial impairment of pharyngeal propulsion, head turning reduces the resistance of the sphincter that must be over-

come by the pharyngeal contraction. For example, in patients with a flaccid hemipharynx, which dissipates pharyngeal pressure, head rotation toward the paretic side excludes these structures from the bolus path and allows pharyngeal pressure to be directed at the UES.86 Increased bolus volume and viscosity can both independently enhance and prolong UES opening.69,88 –91 Although intrabolus pressure is not needed for the initiation of UES opening, larger boluses contribute to the magnitude of sphincter opening by exerting a radial distending force within the sphincter lumen. For bolus volumes ⬎5 mL, modest progressive increases occurred in opening pressure, flow pressure, and maximal UES diameter.69,70 The major effect of increased bolus volume was an earlier onset of anterior tongue base movement, superior palatal movement, anterior laryngeal movement, and UES opening. These events provide receptive adaptation for receiving a larger bolus.69,88 –91 This adaptive response is not affected by pharyngeal mucosal anesthesia or by cold.92,93 Unrelated to bolus volume, the effect of bolus viscosity on UES performance was to prolong and increase the opening, along with an increase in pharyngeal peristaltic wave duration and a delay in pharyngeal transit.88,89 Paralysis of suprahyoid muscles such as geniohyoid significantly impairs UES opening even when the CP functions normally.39 On the other hand, contraction of the suprahyoid muscles may cause considerable opening of the UES despite impaired cricopharyngeal relaxation. Impaired relaxation of the CP muscle or loss of its compliance by fibrosis is responsible for the prominent cricopharyngeal bar or cricopharyngeal achalasia (Figure 2).31,94 –96 The major abnormality in cricopharyngeal bar patients was the sphincter dimension, which did not show any adaptability for increases in swallowed bolus,95 suggesting a rigid CP. In these patients, a normal transphincteric flow rate may still be maintained by abnormal increases in incoming bolus pressure. Decrease in CP compliance leading to a somewhat diminished ability to open seems to be a natural process of aging.94,97,98 This observation correlates well with an overall increase in intrabolus pressure among aged subjects.98 In some patients, impairment of CP relaxation causes outpouching of the relatively thin posterior hypopharyngeal wall (Killian’s triangle/dehiscence) directly above the CP muscle, called Zenker’s diverticulum. Decreased CP compliance resulting from muscle fiber necrosis and its replacement with fibroadipose tissue has been suggested to be the basis for the diverticulum in some Zenker’s patients.94,99 –101 In patients that undergo laryngectomy, CP spasm may cause dysphagia and interference in postlaryngectomy speech.53 This problem may be treated with surgical myotomy of the CP or a neurectomy in which the nerve plexus innervating the CP is disrupted.102–104 Simulta-

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neous electromyographic and manometric studies are useful in investigating dysfunction of the UES.53,54 The relaxed and open UES actively contracts as the deglutitive pharyngeal peristaltic wave reaches the sphincter.105 Asoh and Goyal39 recorded spike bursts in the CP and TP in association with this peristaltic contraction. The magnitude of this contraction is usually twice that of the baseline UES pressure, and it seems to do more than merely restore the sphincter’s resting tone. Pouderoux and Kahrilas106 quantified the axial force elicited within the UES during deglutition by positioning a sphere tethered to a traction-force transducer within the UES. The onset of traction force coincided with the pharyngeal peristaltic wave but lingered on well beyond. On videofluoroscopy, this persistent force was correlated with the aboral motion of the ball trapped within the UES. The force finally abated with the gradual slippage of the UES lip around the ball and was described by the authors as the “grabbing effect.” Thus, the grabbing effect of the UES, attributed to the UES contraction and laryngeal descent, might serve to transfer luminal contents from the level of the laryngeal vestibule to 2 to 3.5 cm below, thereby facilitating hypopharyngeal clearence and facilitating protection against aspiration.106

REFLEXES OF THE UES In addition to the swallowing reflex, a number of other reflexes that affect UES function and illustrate the physiological role of this region, have been documented. Belch-associated UES opening has been well characterized and differs significantly from swallow-induced UES relaxation.71,74 As expected, with the former, there was no accompanying primary peristalsis.71 Furthermore, belchassociated UES relaxation duration was significantly longer than that of swallow–induced relaxation.71 The orbit and direction of hyoid excursion in belching differs significantly with that of swallowing.74 During belching, as evidenced by the direction of the hyoid movement, the vector of the pulling force is mainly directed anteriorly, whereas during swallowing it is directed anterosuperiorly. Lastly, as judged by the magnitude of hyoid motion during videofluoroscopy, the amount of anterior pulling on the UES during belching is significantly less than that of swallowing.74 Experimentally, a belch reflex can be induced by rapid distension of the proximal esophagus with gas or a long cylindrical balloon.71 Reflex increase in UES pressure occurs with pharyngeal stimulation causing gagging,28,107 slow esophageal distension,108 and intraesophageal acid infusion.109 –113 The reflex increase in UES pressure induced by exogenous acid infusion or balloon distension is more marked when the more proximal rather than the distal esophageal segments are stimulated and bilateral vagal cooling abolishes this reflex increase in UES pressure.112,114,115 Esophageal acid-induced augmentation in UES pressure 34S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威

has been reported in infants too.63 However, in patients with gastroesophageal reflux disease, there seems to be no effect on resting UES tone even as respiratory and pharyngolaryngeal manifestations of reflux are being increasingly recognized,116 –118 thus suggesting that resting UES tone alone is an ineffective barrier against acid reflux. Resting UES tone varies with head position82,119 and also increases during phonation, with higher pitch notes being associated with higher resting tone.82,119,120 During restfulness and sleep, the low basal UES tone increases in phase with each inspiration, presumably resulting from excitatory bursts to the UES muscles, providing extra protection to the airways against aspiration.60,121 Distension-sensitive esophageal mechanoceptors that have been reported previously122–124 may be involved in mediating these reflexes. The UES pressure also increases with pressure applied to the pharyngeal mucosa,28 glossopharyngeal breathing, gagging, and during the Valsalva maneuver when it is performed against a closed mouth and nose as opposed to a closed glottis.40

REFERENCES 1. Bonington A, Mahon M, Whitmore I. A histological and histochemical study of the cricopharyngeus muscle in man. J Anat. 1988;156:27–37. 2. Bonington A, Whitmore I, Mahon M. A histological and histochemical study of the cricopharyngeus muscle in the guinea-pig. J Anat. 1987;153:151–161. 3. Brownlow H, Whitmore I, Willan PL. A quantitative study of the histochemical and morphometric characteristics of the human cricopharyngeus muscle. J Anat. 1989;166:67–75. 4. Hanna W, Henderson RD. Nemaline rods in cricopharyngeal dysphagia. Am J Clin Pathol. 1980;74:186 –191. 5. Singer MI, Blom ED. Selective myotomy for voice restoration after total laryngectomy. Arch Otolaryngol. 1981;107: 670 – 673. 6. Aziz Q, Rothwell JC, Hamdy S, Barlow J, Thompson DG. The topographic representation of esophageal motor function on the human cerebral cortex. Gastroenterology. 1996;111:855– 862. 7. Medda BK, Lang IM, Dodds WJ, et al. Correlation of electrical and contractile activities of the cricopharyngeus muscle in the cat. Am J Physiol. 1997;273:G470 –G479. 8. Grimm AF, Whitehorn WV. Characteristics of resting tension of myocardium and localization of its elements. Am J Physiol. 1966;210:1362–1368. 9. Spiro D, Sonenblick EH. Comparison of ultrastructural basis of the contractile process in heart and skeletal muscle. Circ Res. 1964;15(suppl 11):14 –37. 10. Mu L, Sanders I. The innervation of the human upper esophageal sphincter. Dysphagia. 1996;11:234 –238. 11. Mu L, Sanders I. Neuromuscular organization of the human upper esophageal sphincter. Ann Otol Rhinol Laryngol. 1998;107:370 –377. [Published erratum appears in Ann Otol Rhinol Laryngol. 1998;107:734.] 12. Williams P, Warwick R, Dyson M, Bannister LH. Gray’s Anatomy. Edinburgh: Churchill Livingstone, 1989. 13. Kobler JB, Datta S, Goyal RK, Benecchi EJ. Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat. J Comp Neurol. 1994;349:129 –147. 14. Hammond CS, Davenport PW, Hutchison A, Otto RA.

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