Physiology, Esophagus

Article Author:
Suhaib Bajwa
Article Editor:
Anup Kasi
4/3/2019 11:11:29 AM
PubMed Link:
Physiology, Esophagus


The esophagus is a conduit for the passage of a food bolus from the pharynx to the stomach. Typically, the esophagus starts at the cricopharyngeus muscle, forming part of the upper esophageal sphincter (UES), and ends at the lower esophageal sphincter, surrounded by the crural part of the diaphragm at the tenth thoracic vertebra (T10). Following the relaxation of the UES and the passage of the food bolus into the esophagus, peristaltic muscular contractions propel the bolus toward the lower esophageal sphincter (LES). Relaxation of the LES in conjunction with the peristaltic propulsion of the bolus allows the entry of the bolus into the stomach.

Issues of Concern

Problems in the normal physiology of the esophagus and its associated sphincters begin to arise when patients report having difficulty swallowing or dysphagia. Generally, dysphagia can be broken into two groups, obstructive lesions or motor disorders. Obstructive lesions involve a narrowing of the esophagus or an outgrowth resulting in decreased luminal diameter. Motor disorders involve atrophy of muscles, degeneration of nerves, or improper function of nerves associated with the esophageal function. Dysphagia can also be broken down based on location such as pre-esophageal/oropharyngeal dysphagia, esophageal/transport dysphagia, or postesophageal/esophagogastric dysphagia. Oropharyngeal dysphagia is particularly important because it can result in aspiration[1].


The esophagus is composed of a mucosa, a submucosa, a muscularis propria, and an adventitial layer. The mucosa helps to form the lumen and is subdivided into three layers. The three sublayers of the mucosa are a mucous membrane layer comprised of stratified squamous similar to that of skin, a lamina propria layer comprised of a thin layer of connective tissue, and a muscularis propria made primarily of irregularly arranged smooth muscle. The next layer lying beneath the mucosa is the submucosa which is comprised primarily of blood vessels, small mucous glands, and connective tissue. The next layer lying underneath the submucosa is muscularis propria of the esophagus which is more complex than the previous layers. The adult esophagus has several muscle layers which are primarily subdivided into a muscularis mucosae layer and two muscularis externa layers. The muscularis externa includes the longitudinal and circumferential layers which can be variably composed of striated and smooth muscle. The proximal esophagus is comprised of striated muscle while the distal esophagus is comprised of smooth muscle. Additionally, there is a transition zone between the distal and proximal ends which is comprised of a mixture of both smooth and striated muscles. Between the longitudinal and circular layers of muscle are nerve plexuses called the myenteric or Auerbach’s plexus. Nerve plexuses located in the submucosa are called submucous or Meissner’s plexus. The final layer of the esophagus is the adventitia which is an external fibrous layer which connects the esophagus to other external structures[2].


The initial formation of the esophagus happens during the fourth week of gestation with the development of a nascent foregut. At this time, the esophagus is barely a small tube separating the stomach from the pharynx but proceeds to undergo rapid division and differentiation over the next few weeks. The circular muscle fibers, ganglion cells of the myenteric plexus, and blood vessels begin to develop in the sixth week[2]. Around the eighth week of gestation, the epithelium is simple columnar and generally stays this way until about the seventeenth-week of gestation when the number of ciliated cells starts to decrease. By birth, the non-keratinized stratified squamous epithelium is fully formed[3].

Organ Systems Involved

The esophagus serves as a conduit for the transportation of a bolus from the pharynx to the stomach. As such, it is impacted by events that occur upstream, in the mouth, and events that occur downstream, in the stomach. The esophagus is also related to neighboring structures such as the trachea and the diaphragm. The trachea is situated anterior to the esophagus, and it is connected to the esophagus by connective tissue. The crural part of the diaphragm surrounds the LES and plays an important role in helping to mediate the relaxation of the LES high-pressure region which allows for the passage of the food bolus to the stomach.


Upper Esophageal Sphincter (UES)

The UES is the high-pressure area that lies between the esophagus and the pharynx. One-third of the UES is comprised of the cricoid cartilage on the posterior surface, the arytenoid and inter arytenoid muscles in the upper part, and the cricopharyngeus muscle posteriorly and laterally. The remaining two-thirds of the UES is accounted for by the thyropharyngeus muscle. Physiologically, the UES protects against reflux of food into airways and prevents the entry of air into the digestive tract. The opening of the UES involves relaxation of the cricopharyngeus and thyropharyngeus muscles and forward movement of the larynx via contractions of the hyoid muscles[4].

The trigger for the relaxation of the UES begins with the reception of the bolus into the oropharynx which transmits signals along afferent nerves to the swallowing center of the brainstem[5]. The brainstem identifies the incoming signals and produces a response sent along the efferent nerves to the muscles involved in swallowing, the opening of the UES, cessation of breathing, and peristalsis in the esophagus. The efferent signals at the cricopharyngeus muscle trigger relaxation by inhibition of signals that trigger tonic contractions rather than direct inhibitory signals. A similar mechanism of the action happens to trigger the relaxation of the thyropharyngeus muscle[4].

Efferent signals at the hyoid muscle stimulate contraction which elevates the hyoid and happens almost simultaneously with the UES relaxation. The hyoid muscles can also contract without the initiation of a pharyngeal swallow via muscular attachments to the tongue. Relaxation of the cricopharyngeus and thyropharyngeus muscles resulting in decreased UES pressure, movement of the larynx away by the hyoid muscles, and the propulsion force of the bolus allow the bolus to overcome the pressure in the UES region and pass into the esophagus[6].

The volume of the bolus also plays an important role in mediating the physiology of the UES. The bolus volume dictates the duration between the opening of the UES and pharyngeal movement. Increasing the volume of the bolus also results in the faster onset of pharyngeal movement while increasing the thickness of the bolus was also associated with increasing time differential between the opening of the UES and pharyngeal movement[6].


Once the bolus has passed through the UES, it arrives into the esophagus. The upper portion of the esophagus is composed mainly of striated muscle under the control of central control mechanisms. The lower portion of the esophagus is comprised primarily of smooth muscle and is under the control of central and intrinsic control mechanisms[7].

The esophagus is comprised of a muscle layer termed the muscularis mucosa. This muscle layer can be further divided into longitudinal muscle fibers and internal circular muscle fibers. The exact role of longitudinal muscles in esophageal physiology is not known, but recent studies have shown that longitudinal muscle contraction helps to reduce the tension associated with circular muscle contractions which helps to augment peristaltic contraction. On the other hand, the role of circular muscle fibers in esophageal physiology is well known, and they contract radially to provide peristaltic propulsion of the bolus in the aboral direction[8].

Entering of the bolus into the esophagus triggers primary peristalsis. Generally, in peristalsis, the area ahead of the bolus is relaxed, and the area behind the bolus is undergoing peristaltic contraction which allows for the bolus to be propelled forward. A series of nervous inputs accomplish contraction behind the bolus on the oral side and relaxation on the aboral side of the bolus[4].

In striated muscle, upon swallowing, lower motor neurons in the nucleus ambiguous of the brainstem are activated. Each lower motor neuron is activated sequentially to create a peristaltic wave. In smooth muscle, however, upon swallowing, caudal dorsal motor nucleus (cDMN) inhibitory neurons are activated and cause simultaneous inhibition of all parts of the esophagus. This simultaneous inhibition in the smooth muscle of the esophagus is termed “deglutitive inhibition” and is the first step to generating a peristaltic wave. This inhibition lasts longer in the lower portion of the esophagus than the upper portions of the esophagus. As the inhibition ends, sequential activation of excitatory neurons in the rostral dorsal motor nucleus (rDMN) elicit peristaltic contraction. Central control mechanisms mediate the mechanisms described above[7].

The excitatory pathway in smooth muscle for the generation of primary peristalsis includes vagal preganglionic neurons of the rostral part in the DMN of the brainstem. The DMN is a cranial nerve nucleus for the vagus nerve in the medulla that lies ventral to the floor of the fourth ventricle. The rDMN pre-ganglionic neurons attach to the excitatory postganglionic neurons that release acetylcholine (ACh) and substance P. The inhibitory pathway includes preganglionic vagal fibers in the cDMN. These fibers project onto postganglionic inhibitory neurons that contain nitric oxide (NO), vasoactive intestinal peptide (VIP), adenosine triphosphate (ATP), and substance P (SP)[7].

Interestingly, the esophagus can also undergo secondary peristalsis which is initiated by the intrinsic nervous system and vaso-vagal responses if there is residual food in the esophagus. Secondary peristalsis can have the same strength and speed as primary peristalsis but is generated in the absence of a swallow[5]. In skeletal muscle, secondary peristalsis is centrally mediated and occurs in a similar method to primary peristalsis with nerve innervations arising from the nucleus ambiguus. In smooth muscle, secondary peristalsis is due to a peripheral mechanism. The peripheral mechanism involves the activation of sensory neurons by stimulation from distention or the presence of a food bolus in the esophagus. The excited sensory neuron transmits the signal to an interneuron which relays the signal to a motor neuron. Subsequently, the motor neuron then releases acetylcholine orally and NO aborally to create a secondary peristaltic wave. This peristaltic wave in smooth muscle is locally contained and generated by the peripheral mechanism[9].


Once the bolus has arrived at the end of the esophagus, it must pass through the LES to arrive in the stomach. The LES and crural diaphragm constitute the high-pressure zone between the esophagus and stomach. The LES and the crural diaphragm function as anti-reflex barriers to protect the esophagus but also allow for the passage of the bolus into the stomach[10].

The LES is comprised mainly of smooth muscle and has no dilator muscles to help open the LES. The opening of the LES is triggered by direct inhibitory innervation resulting in relaxation of the smooth muscles in the LES in conjunction with the movement of the bolus through the relaxed sphincter[7].

LES pressure is dependent on the myogenic tone, inhibitory nitrergic nerves, and excitatory cholinergic nerves. The myogenic tone is responsible for the tonic contraction of the LES and is due to the specialized properties of the smooth muscle cells at the LES. The LES smooth muscle cells are thought to have more depolarized resting membrane potentials resulting in spontaneous spike-like action potentials and generation of basal tone[10].

Excitatory cholinergic nerves (ACh) and the tonic, myogenic property of the LES favor contraction, whereas the inhibitory nitrergic (NO) pathway favors inhibition. The LES remains contracted due to its myogenic property even when it is entirely denervated as in advanced achalasia[10].

Presence of a bolus in the pharynx triggers receptors which relay signals that eventually induce esophageal peristalsis and LES relaxation. The sensory stimulus travels to the nucleus of tractus solitarius which connects with the DMN. The vagal efferent nerves from the DMN, however, do not innervate the smooth muscle but instead innervate the myenteric plexus which mediates LES relaxation. The myenteric plexus is composed of inhibitory and excitatory motorneurons, and the location of stimulus dictates inhibitory or excitatory actions since the inhibitory pathway neurons arise from the cDMN while the excitatory pathway neurons arise from the rDMN. Important excitatory postganglionic neurotransmitters are ACh and tachykinins while NO is the most important inhibitory postganglionic neurotransmitter[10].

Another important physiological component of the LES other than relaxation during swallowing is transient lower esophageal sphincter relaxation (TLESR). TLESR is a physiological mechanism designed to allow the venting of gas from the stomach[11]. TLESR afferent nerves arise from the pharynx, larynx, and the stomach while the efferent nerves use the same pathway as the swallow reflex to trigger LES relaxation[12].

The other component that constitutes the high-pressure zone between the esophagus and stomach is the crural diaphragm. The crural diaphragm also plays important roles in helping to regulate the rate of reflux into the esophagus and allowing the passage of a food bolus into the stomach. The crural diaphragm is anchored to the LES by the phrenoesophageal ligament which means that the two structures move together on inspiration and expiration but can separate during peristalsis and transient LES relaxation[13]. For the food bolus to pass into the stomach and allow for reflux from the stomach into the esophagus, the crural diaphragm must relax. Although the exact mechanism of relaxation for the crural diaphragm is not known, the crural diaphragm is controlled by the phrenic nerve via nicotinic cholinergic receptors which induce contraction[14].

Related Testing

There are several tests available to assess the function of the esophagus including endoscopy, barium swallow, high-resolution manometry (HRM), pH measurement, and impedance monitoring of the esophagus. Endoscopies, barium swallow studies, and high-resolution manometry are the more frequently used tests to evaluate esophageal function[15]. Endoscopies are used to evaluate the mucosa and submucosa of the esophagus and frequently involve taking biopsies to better evaluate the tissue. A barium swallow study involves the administration of barium followed by sequential usage of x-rays to determine the movement of barium through the upper gastrointestinal (GI) tract. This helps to evaluate the physiology of the UES, the esophagus, LES, or for the presence of any potential anatomical defects. Barium studies, however, are problematic because it is difficult to determine what is the normal luminal diameter of the esophagus[15]. High-resolution manometry involves the use of pressure sensitive catheters to evaluate esophageal motor function and sphincter function. The catheter is moved sequentially down the esophagus and its associated sphincters and when the sphincters open/close or peristalsis occurs, the pressure sensitive catheters pick up the pressure changes[16]. Ultrasound may also be used to test for the function of the esophagus, but it has not gained wide popularity[15].


There are several mechanisms by which dysphagia can occur including physical obstructions or motor issues. The physical obstruction or motor issue can additionally be localized at the level of the UES, esophagus, or LES. Some motor causes of dysphagia include diffuse esophageal spasms, achalasia, scleroderma, or diabetes mellitus. Some physical obstructions in the esophagus causing dysphagia include esophageal carcinoma, reflux esophagitis, peptic strictures, or Schatski’s rings. The UES can also be a cause of motor dysphagia but occurs in the oropharyngeal portion of the GI tract[4].

Esophageal spasms are characterized by uncoordinated contractions of the esophagus resulting in dysphagia. Characteristic x-ray findings are described as “corkscrew” or rosary bead” esophagus and manometry is used to evaluate the motor function of the esophagus[17].

Achalasia, on the other hand, is the failure of the smooth muscle to relax due to inhibition of inhibitory nerve fibers. Achalasia can also affect sphincter muscles and inhibit their relaxation which prevents the ability of the bolus to pass onto the next stage of the GI tract. Generally, achalasia is associated with the absence of peristalsis on diagnostic testing and diagnosis is made based on barium swallow or esophageal manometry testing[18].

Scleroderma is also due to reduced smooth muscle contractions but because the smooth muscle has atrophied and been replaced by collagen fibers. This fibrosis of smooth muscle results in hypomotility. Manometry is the gold standard for diagnosis of this condition[19].

Diabetes mellitus (DM), however, causes dysphagia by inducing mechanic-structural remodeling in the esophagus. Remodeling is triggered because of esophageal sensorimotor abnormalities and symptoms encountered by DM patients. The sensory dysfunction appears to arise due to demyelination and progressive axonal atrophy of parasympathetic nerves in the esophagus. Increased autonomic neuropathy also leads to a decreased LES tone which results in gastroesophageal reflux (GES)[20].

Esophageal carcinomas are usually either squamous cell carcinomas or adenocarcinomas. The exact mechanism for dysphagia in esophageal carcinomas is not known. Endoscopy with a biopsy is used for diagnosis[21].

Peptic strictures are the narrowing of the esophagus due to prolonged inflammation and scarring from stomach acid or exposure to other irritants. These are normally diagnosed based on barium swallow or endoscopy with a biopsy[22].

A Schatzki’s ring is a ring of redundant mucosa over the normal mucosa resulting in a decreased luminal diameter of the esophagus. A Schatzki’s ring is formed due to in-folding of the esophagus during transient shortenings of the esophagus. Diagnosis is normally made based on EGD or barium swallow studies. It is often associated with hernias[23].

Lack of UES relaxation can also trigger dysphagia. For the bolus to pass the UES, normal muscle tension must be overcome. The tension of the UES is reduced by the contraction of the cricopharyngeus and thyropharyngeus muscles. This means that the timing of the muscle contraction and proper force are necessary for the bolus to pass to the esophagus. Any diseases or disorders that disrupt these muscles or increase the baseline tension that must be overcome will prevent the bolus from passing through the UES. One such case is the improper relaxation of the cricopharyngeus muscle resulting in a Zenker’s diverticulum. A Zenker’s diverticulum is a diverticulum occurring just between the cricopharyngeus muscle and the inferior pharyngeal constrictor muscles due to excessive pressure in the lower pharynx causing the weakest portion of the of the pharyngeal wall to balloon out. Barium swallow studies diagnose this. Dysphagia in Zenker’s diverticulum can be due to the incomplete opening of the UES and/or the compression of the esophagus by the diverticulum itself[24].

Clinical Significance

Dysphagia is a condition affecting over 9 million individuals in the United States. Oropharyngeal dysphagia, specifically, happens in as much as 50% of the elderly and 50% of patients with neurological pathologies. Clinically, oropharyngeal dysphagia can present with severe symptoms such as aspiration and death. Esophageal dysphagia, on the other hand, is a rarer condition with less severe symptoms but is easier to recognize due to symptoms arising from diseases of the enteric nervous system or esophageal muscular layers. Advances in the understanding of the pathophysiology of the causes for dysphagia and in imaging techniques have allowed for more rapid identification and treatment of patients with dysphagia[25].


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