Esophagus-full.doc

THE ESOPHAGUS
W.G. Paterson and S. Mayrand

1. Introduction
(We would like to acknowledge and thank Dr. I. T. Beck for his contribution of several of the figures for the chapter and valuable editorial advice.)
The esophagus is a hollow muscular organ whose primary function is to propel into the stomach the food or fluid bolus that it receives from the pharynx. Symptoms of esophageal disease are among the most commonly encountered in gastroenterology. Fortunately, most symptoms are due to benign disease that can be easily remedied. The physician must be on the lookout, however, for the more serious disorders, which can present with a similar spectrum of symptoms. This chapter will focus on the pathophysiology, diagnosis and management of the more common esophageal disorders. Rare diseases involving the esophagus will be dealt with only briefly. 

2. Anatomy
2.1 Muscular Anatomy
The esophagus is a hollow muscular tube closed proximally by the upper esophageal sphincter (UES) and distally by the lower esophageal sphincter (LES). The UES consists predominantly of the cricopharyngeus and the caudal fibers of the inferior pharyngeal constrictor muscles. The UES forms a transverse slit at the C5-C6 vertebral level due to surrounding bony structures and cartilage. In the proximal one-quarter to one-third of the esophagus, the muscle is striated. There is then a transition zone of variable length where there is a mixture of both smooth and striated muscle. The distal one-half to one-third of the esophageal body and LES are composed of smooth muscle. The LES is located at the junction between the esophagus and stomach, usually localized at or just below the diaphragmatic hiatus. Despite its distinct physiological function, it is not easily distinguished anatomically.

2.2 Innervation
page 89
The motor innervation of the esophagus is via the vagus nerves. The cell bodies of the vagal efferent fibers innervating the UES and the proximal striated-muscle esophagus arise in the nucleus ambiguus, whereas fibers destined for the distal smooth-muscle segment and the LES originate in the dorsal motor nucleus. The esophagus and LES also receive sympathetic nerve supply (both motor and sensory) arising from spinal segments T1-T10. Sensory innervation is also carried via the vagus and consists of bipolar nerves that have their cell bodies in the nodose ganglion and project from there to the brainstem.

2.3 Blood Supply
page 89
Arterial blood supply to the UES and cervical esophagus is via branches of the inferior thyroid artery. Most of the thoracic esophagus is supplied by paired aortic esophageal arteries or terminal branches of bronchial arteries. The LES and the most distal segment of the esophagus are supplied by the left gastric artery and by a branch of the left phrenic artery. Venous drainage is via an extensive submucosal plexus that drains into the superior vena cava from the proximal esophagus and into the azygous system from the mid-esophagus. In the distal esophagus, collaterals from the left gastric vein (a branch of the portal vein) and the azygos interconnect in the submucosa. This connection between the portal and systemic venous systems is clinically important; when there is hypertension, variceal dilation can occur in this area. These submucosal esophageal varices can be the source of major gastrointestinal hemorrhage.

2.4 Lymphatic Drainage
page 89
In the proximal third of the esophagus, lymphatics drain into the deep cervical lymph nodes, whereas in the middle third, drainage is into the superior and posterior mediastinal nodes. The distal-third lymphatics follow the left gastric artery to the gastric and celiac lymph nodes. There is considerable interconnection among these three drainage regions.

2.5 Histology
page 89
The wall of the esophagus consists of mucosa, submucosa and muscularis propria. Unlike other areas of the gut, it does not have a distinct serosal covering, but is covered by a thin layer of loose connective tissue. The mucosa consists of stratified squamous epithelium in all regions of the esophagus except the LES, where both squamous and columnar epithelium may coexist. Beneath the epithelium are the lamina propria and the longitudinally oriented muscularis mucosa. The submucosa contains connective tissue as well as lymphocytes, plasma cells and nerve cells (Meissner's plexus). The muscularis propria consists of an inner circular and an outer longitudinal muscle layer. The circular muscle layer provides the sequential peristaltic contraction that propels the food bolus toward the stomach. Between the circular and longitudinal muscle layers lies another nerve plexus called the myenteric or Auerbach's plexus, which mediates much of the intrinsic nervous control of esophageal motor function.    

3. Physiology
The major function of the esophagus is to propel swallowed food or fluid into the stomach. This is carried out by sequential or "peristaltic" contraction of the esophageal body in concert with appropriately timed relaxation of the upper and lower esophageal sphincters. The esophagus also clears any refluxed gastric contents back into the stomach and takes part in such reflex activities as vomiting and belching.

3.1 Deglutition: Primary Peristalsis

The act of deglutition is a complex reflex activity. The initial phase is under voluntary control. Food is chewed, mixed with saliva and formed into an appropriately sized bolus before being thrust to the posterior pharynx by the tongue. Once the bolus reaches the posterior pharynx, receptors are activated that initiate the involuntary phase of deglutition. This involves the carefully sequenced contraction of myriad head and neck muscles. The food bolus is rapidly engulfed and pushed toward the esophagus by the pharyngeal constrictor muscles. Simultaneously there is activation of muscles that lift the palate and close off and elevate the larynx in order to prevent misdirection of the bolus. Almost immediately upon activation of this reflex, the UES opens just long enough to allow the food bolus to pass through; it then rapidly shuts to prevent retrograde passage of the bolus. The oropharyngeal phase is thus completed and the esophageal phase takes over. This involves two major phenomena: (1) the sequential contraction of the circular muscle of the esophageal body, which results in a contractile wave that migrates toward the stomach; and (2) the relaxation and opening of the LES, which allows the bolus to pass. The peristaltic sequence and associated UES and LES relaxation induced by swallowing are termed primary peristalsis. These can be assessed manometrically using an intraluminal tube to measure pressures. The typical sequence seen during primary peristalsis is depicted in Figure 1. Secondary peristalsis refers to a peristaltic sequence that occurs in response to distention of the esophagus. This is a localized peristaltic wave that usually begins just above the area of distention. It is associated with LES relaxation, but not with UES relaxation or deglutition.

3.2 Upper Esophageal Sphincter Function

The UES serves as a pressure barrier to prevent retrograde flow of esophageal contents and the entry of air into the esophagus during inspiration. This high-pressure zone is created by tonic contraction of the UES muscles, which is produced by tonic neuronal discharge of vagal lower motor neurons. With deglutition this neuronal discharge ceases temporarily and permits relaxation of the UES. UES opening will not occur with relaxation of the muscles alone; it requires elevation and anterior displacement of the larynx, which is mediated by contraction of the suprahyoid muscles. Relaxation lasts for only one second and is followed by a postrelaxation contraction (Figure 1).

3.3 Esophageal Body Peristalsis

There is a fundamental difference in the control mechanisms of peristalsis between the upper (striated-muscle) esophagus and the lower (smooth-muscle) esophagus. In the striated-muscle segment, peristalsis is produced by sequential firing of vagal lower motor neurons so that upper segments contract first and more aboral segments subsequently. In the smooth-muscle segment, the vagal preganglionic efferent fibers have some role in the aboral sequencing of contraction, but intrinsic neurons are also capable of evoking peristalsis independently of the extrinsic nervous system. Transection of vagal motor fibers to the esophagus in experimental animals will abolish primary peristalsis throughout the esophagus; however, in this setting, distention-induced or secondary peristalsis will be maintained in the smooth-muscle but not in the striated-muscle segment. Furthermore, if vagal efferent fibers are stimulated electrically (Figure 2), a simultaneous contraction will be produced in the striated-muscle esophagus that begins with the onset of the electrical stimulus, lasts throughout the stimulus, and ends abruptly when the stimulus is terminated. In the smooth-muscle esophagus, however, the response to vagal efferent nerve stimulation is quite different, in that the onset of contractions is delayed relative to the onset of the stimulus. The latency to onset of the contraction increases in the more distal segments of the esophagus (i.e., the evoked contractions are peristaltic).
This experimental observation indicates that intrinsic neuromuscular mechanisms exist and can mediate peristalsis on their own. Further evidence for this mechanism is found in studies where strips of esophageal circular smooth muscle are stimulated electrically in vitro. The latency to contraction after stimulation is shortest in the strips taken from the proximal smooth-muscle segment and increases progressively in the more distal strips.
This latency gradient of contraction is clearly important in the production of esophageal peristalsis. Although the exact mechanisms are unclear, initial or deglutitive inhibition is important. With primary or secondary peristalsis, a wave of neurally mediated inhibition initially spreads rapidly down the esophagus. This is caused by the release of a nonadrenergic, noncholinergic inhibitory neurotransmitter (most likely nitric oxide) that produces hyperpolarization (inhibition) of the circular smooth muscle. It is only after recovery from the initial hyperpolarization that esophageal muscle contraction (which is mediated primarily by cholinergic neurons) can occur. Thus, the duration of this initial inhibition is important with respect to the differential timing of the subsequent contraction. Derangements of the mechanisms behind this latency gradient lead to nonperistaltic contractions and dysphagia. Such derangements could result from problems with either the intrinsic neural mechanisms (enteric nervous system) or the central neuronal sequencing.

3.4 Lower Esophageal Sphincter Function
page 94
The LES is an intraluminal high-pressure zone caused by tonic contraction of a region of physiologically distinct circular smooth muscle at the junction of the esophagus and stomach. This results in a pressure barrier that separates the esophagus from the stomach and serves to prevent reflux of gastric contents up into the esophagus. In normal individuals, resting LES pressure averages between 10 and 30 mm Hg above intragastric pressure. Patients with very feeble resting LES pressure are prone to develop gastroesophageal reflux disease (GERD). Unlike that of the UES, the resting tone of the LES is primarily due to myogenic factors that result in tonic contraction of the sphincter. Extrinsic innervation as well as circulating hormones can modify the resting tone; however, the muscle fibers themselves have inherent properties that result in their being tonically contracted.
At the time of deglutition or when the esophagus is distended, the LES promptly relaxes. Swallow-induced LES relaxation is mediated by vagal efferent fibers that synapse on nonadrenergic, noncholinergic inhibitory neurons of the myenteric plexus. The inhibitory neurotransmitter released from these intrinsic neurons is probably nitric oxide. LES relaxation usually lasts about five to seven seconds, and is sufficient to abolish the gastroesophageal pressure barrier. This permits the food bolus to pass unimpeded from the esophagus to the stomach. The LES also relaxes to permit belching or vomiting. Inadequate LES relaxation is seen in achalasia and results in dysphagia.    

4. Symptoms and Signs of Esophageal Diseases
4.1 Symptoms
4.1.1 DYSPHAGIA
This sensation of food sticking during swallowing is a manifestation of impaired transit of food through the mouth, pharynx or esophagus. It is important to differentiate oropharyngeal ("transfer") dysphagia from esophageal dysphagia. If the patient has problems getting the bolus out of the mouth, then one can be certain of an oropharyngeal cause; if the food sticks retrosternally, an esophageal cause is indicated. Some patients, however, will sense food sticking at the level of the suprasternal notch when the actual obstruction is the distal esophagus. Thus, it can be difficult to determine the site of the problem when patients refer their dysphagia to the suprasternal notch or throat area. With these patients it is important to elicit any ancillary symptoms of oropharyngeal-type dysphagia, such as choking or nasal regurgitation. It may also be helpful to observe the patient swallowing in an attempt to determine the timing of the symptom; with esophageal dysphagia referred to the suprasternal notch, the sensation of dysphagia onsets several seconds after swallowing begins.
The history can also be used to help differentiate structural from functional (i.e., motility disorders) causes of dysphagia. Dysphagia that is episodic and occurs with both liquids and solids from the outset suggests a motor disorder, whereas when the dysphagia is initially for solids such as meat and bread, and then progresses with time to semisolids and liquids, one should suspect a structural cause (e.g., stricture). If such a progression is rapid and associated with significant weight loss, a malignant stricture is suspected.
Associated symptoms help determine the etiology of dysphagia. For instance, a reflux-induced stricture should be suspected if the dysphagia is associated with heartburn or regurgitation, esophageal cancer if there is associated mid-back pain and weight loss, a motor disorder such as diffuse esophageal spasm if there is angina-like chest pain, and a "scleroderma esophagus" if there is arthralgia, skin changes or Raynaud's phenomenon.

4.1.2 ODYNOPHAGIA
page 95
This refers to the sensation of pain on swallowing. Local inflammation or neoplasia in the mouth and pharynx can produce such pain. When the pain is retrosternal, one should suspect nonreflux-induced forms of esophagitis, such as infection, radiation or pill-induced (chemical) injury. Less commonly it occurs with esophag