Physiology of normal esophageal motility

Abstract

The esophagus consists of 2 different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consists of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure because of its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles.

Conflict of interest statement

Conflict of Interest: None

Figures

Figure 1. Simultaneous esophageal manometry and fluoroscopy

Note that, on swallowing, the barium column moves down the esophagus. Such barium movement in the upright position occurs largely due to gravity. The tail of the barium column moves down the esophagus by the esophageal peristaltic contraction. Note that barium moves through the esophagus in its relaxed state. Also note that onset of peristaltic contraction at lowest level of the esophagus occurred at 8.5 sec after a swallow, at which time the entire column of barium passes into the stomach. (Source: Modified from Dodds WJ, Christensen J, Dent J, Arndorfer RC, Wood JD. Pharmacologic investigation of primary peristalsis in smooth muscle portion of opossum esophagus. Am J Physiol 1979;237(6):E561–E566 and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 2. A model of peristalsis in the striated muscle of the esophagus

Note that swallow-induced peristalsis is due to sequential activation of lower motor neurons in the nucleus ambiguus in the brainstem. When the peripheral end of the decentralized vagus nerve is electrically stimulated (VS), all segments of the esophagus contract simultaneously. (Source: Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 3. A model of intramural mechanism of peristalsis in the esophageal smooth muscle

The cholinergic excitatory innervation (open circles) is most marked in the proximal part and decreases gradually in the distal part. On the other hand, the inhibitory innervation (close circles) increases distally along the esophagus. Upon stimulation of the inhibitory nerves alone, the latency of contraction increases gradually distally along the esophagus, resulting in peristaltic sequence of contraction that is entirely located locally in the wall of the esophagus. However, cholinergic nerves further reduce the latency, particularly in upper levels of the esophagus because of their greater influence in the upper esophagus. (Source: Crist J, Gidda JS, Goyal RK. Intramural mechanism of esophageal peristalsis: roles of cholinergic and noncholinergic nerves. Proc Natl Acad Sci USA 1984; 81(11):3595–3599 and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 4. Demonstration of deglutitive inhibition on successive rapid swallowing (as in rapid drinking) in a health volunteer

Note that the subject was making repeated swallows every 1 to 2 seconds. During the swallows, there was no activity in the esophagus. The last swallow was followed by a peristaltic contraction.( Source: Ask P, Tibbling L Effect of time interval between swallows on esophageal peristalsis. Am J Physiol. 1980 Jun;238(6):G485-90 and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 5. A model of neuromuscular organization of smooth muscle of esophageal body and the LES

The innervations of the esophageal body and LES are similar. The excitatory pathway includes vagal preganglionic neurons that are located in the rostral part of the DMN in the brainstem. These fibers project onto the excitatory postganglionic neurons that contain acetylcholine (ACh) and substance P. The inhibitory pathway includes pre-ganglionic vagal fibers that are located in the caudal part of the DMN. These fibers project onto postganglionic inhibitory neurons that contain nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and adenosine triphosphate (ATP). However, as the esophageal body (EB) muscle is phasic in nature, it does not exhibit resting tone and contracts transiently upon nerve stimulation with a certain latency. On the other hand, the lower esophageal sphincter (LES) muscle is tonic in nature; it exhibits basal tone and initially relaxes on intramural nerve stimulation. (Source: Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 6. A model of central control of peristalsis in the smooth muscle esophagus

The inhibitory and excitatory pathway neurons (cell bodies) to the esophageal smooth muscle are segregated in the caudal and rostral parts of the dorsal motor nucleus of the vagus. Upon swallowing, the inhibitory pathway neurons in the caudal DMN (cDMN) are activated first, which causes simultaneous inhibition of all parts of the esophagus. This inhibition lasts longer in the lower than in the upper parts. As the inhibition ends, sequential activation of excitatory (cholinergic) neurons in the rostral DMN (rDMN) elicits a contraction wave that is combined with the rebound peristaltic wave. (Source: Ravinder K. Mittal and Raj K Goyal, Sphincter mechanisms at the lower end of the esophagus. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo14, 2006).

Figure 7. Diagrammatic presentation of the lower esophageal sphincter and the crural diaphragm that constitute the intrinsic and extrinsic sphincters

The two sphincters are anatomically superimposed on each other and are anchored by the phrenoesophageal ligament. (Source: Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med 1997;336:924–932 and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 8. A model of regulation of basal LES tone

Basal LES pressure is dependent on three factors: 1) myogenic tone; 2) inhibitory nitrergic nerves; and 3) excitatory cholinergic nerves. The effect of inhibitory and the excitatory nerves is normally counteracted. The loss of all nerves may not decrease LES pressure, the loss of inhibitory nerves may cause transient LES hypertension and the loss of the cholinergic excitatory nerves may cause transient LES hypotension. EB, esophageal body; LES, lower esophageal sphincter.

Figure 9. Loss of LES relaxation to a swallow in neuronal nitric oxide synthase (nNOS) deficient but not in the wild type mice

These studies established that nNOS is the enzymatic source of nitric oxide involved in the inhibitory neurotransmission (Source: Sivarao, DV, Mashimo, HL, Thatte HS and Goyal RK. Lower esophageal sphincter is achalasic in nNOS−/− and hypotensive in W/Wv mutant mice. Gastroenterology 200l; 121:34–42 and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 10. An example of so-called transient LES relaxation (TLESR)

Note the swallow associated events, including submental EMG activity, pharyngeal contraction, and esophageal peristaltic contraction. Also note TLESR-associated events, including the lack of submental EMG activity and the lack of pharyngeal or esophageal peristalsis. Also note the TLESR that is associated with a brief esophageal contraction and fall in esophageal pH from 5 to 1. The TLESR is of longer duration than swallow-induced LES relaxation. (Source: Mittal RK, McCallum RW. Characteristics of transient lower esophageal sphincter relaxation in humans. Am J Physiol 1987; 252:G636–G641 and Ravinder K. Mittal and Raj K Goyal, Sphincter mechanisms at the lower end of the esophagus. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo14, 2006).

Figure 11. A model of neural pathway for TLESR

The subdiaphragmatic vagal afferents arising from the stomach project on to the nucleus tractus solitarius (NTS). The NTS neurons connect with neurons of the inhibitory pathway in the caudal part of the DMN. The inhibitory pathway neurons in the DMN mediate relaxation via nitrergic neurons. This is in contrast to swallow induced relaxation that is accompanied by slightly delayed activation of the excitatory motor neurons. (Source: Goyal RK, Padmanabhan R, Sang Q. Neural circuits in swallowing and abdominal vagal afferent-mediated lower esophageal sphincter relaxation. Am J Med. 2001; 111 Suppl 8A:95S–105S and Hiroshi Mashimo and Raj K Goyal. Physiology of esophageal motility. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo3, 2006).

Figure 12. Classification of esophageal motility disorders based on pathophysiology

The esophageal smooth muscle motility disorders can be classified based on involvement of one or more of its three components, namely, inhibitory nerves, excitatory nerves and smooth muscle. Note that the loss of inhibitory innervation leads to achalasia involving LES and EB and diffuse esophageal spasm (DES) involving only esophageal body. These and related conditions are characterized by loss of the deglutitive inhibition and latency gradient. Over-activity of the inhibitory TLESR may lead to gastroesophageal reflux disease (GERD). On the other hand, impairment of cholinergic excitatory innervation leads to hypotensive LES leading to GERD, and hypotensive peristalsis. Similarly, impairement of myogenic contractile activity also leads to hypotensive LES and GERD, and hypotensive peristalsis. Severely hypotensive peristalsis also causes dysphagia. Hypertensive LES and hypertensive peristalsis (nutcracker esophagus) may be due to over-activity of the excitatory nerves or myogenic hyper-excitability. (Source: W.G. Patterson, Raj K Goyal and Fortunée Irene Habib, Esophageal motility disorders. GI Motility Online, www.GIMotilityonline.com; doi:10.1038/gimo20, 2006).