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Intrinsic lower esophageal sphincter

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In the human, the LES is composed of at least two main smooth muscle elements: the circular muscle usually forms only a partial ring (or semicircular “clasp”) but can form a complete ring; and the gastric sling muscle runs on the left lateral aspect to interdigitate with the circular muscle and structurally complete this portion of the sphincter (Figure 5.15) [128, 291, 292]. A more recent manometric and ultrasound study has suggested the presence of another smooth muscle component [293, 294], but this finding is yet to be confirmed [295] as different from either the sling or clasp muscles. It is not clear if the very distal circular smooth muscle of the esophageal body contributes to the proximal end of the LES. In many other species such as the cat, dog, and guinea pig, the LES circular muscle forms a complete ring, but with the sling similarly positioned as in the human [296–301].


Figure 5.14 Anatomy of the diaphragmatic hiatus: the right crus encircling the distal esophagus. The right crus arises from the anterior longitudinal ligament overlying the lumbar vertebrae. Two muscular elements cross each other in a scissor‐like fashion, form the walls of the hiatus, and decussate with each other anteriorly as they encircle the distal esophagus.

Source:Kahrilas PJ, Pandolfino JE. Esophageal motor function. In: Yamada T, ed. Textbook of Gastroenterology, 5th ed.Hoboken, NJ: Wiley‐Blackwell; 2008.


Figure 5.15 Lower esophageal sphincter (LES) radial muscle thickness and 3D manometric pressure image. Radial thickness shown in millimeters is on the left, and the 3D pressure image in mmHg is plotted on the right around an axis representing atmospheric pressure. The thickest portion of the LES and highest pressure are seen on the left lateral side. GC, greater curve; LC, lesser curve; PW, posterior wall; AW, anterior wall.

Source: Stein et al. [312] with permissions of Elsevier.

The sling contraction and the normal position of the stomach, with its fundus projecting upward under the left diaphragm, act to form an acute angle where the left lateral wall of the esophagus meets the medial aspect of the dome of the stomach, the angle of His. The LES portion of the distal esophagus tends to angle obliquely and to the left to meet the stomach wall. Viewed from the gastric lumen, this region can be seen as a fold or ridge that has been considered as a flap valve if compressed against the LES opening [302]. As one contributing factor, if the angle of His is less acute, such as with a hiatus hernia or after distal gastrectomy, gastroesophageal reflux is more likely to occur [303–306]. A longitudinal smooth muscle layer covers the sphincter region.

As in the esophageal body, LES circular muscle is formed into bundles separated by connective tissue. The LES cells are somewhat larger and the connective tissue lamina more numerous than in the esophageal body [307]. ICCs are present in both circular and longitudinal muscle layers [158, 159, 308, 309]. Their role as either mechanical receptors and/or transducers of neural input to the smooth muscle cells remains uncertain [308, 310, 311].

The LES receives preganglionic vagal fibers from the DMNV in the brainstem SPG. These fibers enter the esophagus up to 9 cm or more proximal to the LES [313, 314] and synapse on excitatory and inhibitory neurons [30, 32]. Central SPG preganglionic fibers to the LES are also linked to sensory information from the fundus [30]. As in the esophageal body, the neurons have a number of peptides and potential neurotransmitters [315]. However, normal muscle excitation is primarily cholinergic, and inhibition is nitrergic, although the neurons also contain VIP. A VIP or other peptide‐mediated component of inhibition may be present under certain circumstances [248, 308, 310,316–319]. Nitrergic innervation and its effect are greatest in the circular clasp muscle [320, 321]. The inhibitory neurons receive input from the vagus, esophageal body, and gastric fundus, and the clasp and sling are separately innervated [30, 322]. Sympathetic innervation to the LES arrives from the stellate ganglion and from the sympathetic chain via the splanchnic nerve after passing through the celiac ganglion. This innervation excites the muscle directly and through stimulation of acetylcholine release from cholinergic postganglionic nerves while inhibiting the inhibitory innervation, all by alpha‐receptor activation [152, 323, 324]. There is some beta‐receptor–mediated inhibition of the muscle, with its effect species‐dependent and of uncertain importance [151, 323, 325].

Activation of the excitatory and inhibitory neurons in the myenteric plexus is primarily through cholinergic nicotinic receptors, and the inhibitory neuron to a lesser extent by a muscarinic M1 receptor. Both may be activated directly or indirectly by other neurotransmitters, and these activations can have clinical implications. The inhibitory neuron can be activated directly by serotonin [326], but the importance of this is uncertain and by cholecystokinin (CCK) [327–329]. CCK excitation of the excitatory neuron can occur by stimulation of preganglionic nerve structures [329].

There appear to be two vagal pathways to the LES. The first pathway is tonically active and likely excitatory to help maintain resting tone; this discontinues with a swallow. The other pathway is quiescent at rest and activates with a swallow, presumably to stimulate inhibitory neurons for LES relaxation [330, 331]. The inhibitory pathway within the esophageal body to the LES is paucisynaptic and can extend over long sections of the esophageal body [175].

The Esophagus

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