esophageal sphincter.
Source: Clouse RE, Diamant NE. Esophageal motor and sensory function and motor disorders of the esophagus. In: Feldman M, Freidman LS, Sleisenger MH, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 8th ed. © 2006, Elsevier.
The longitudinal muscle is not an innocent bystander, as it contracts sequentially in close association with circular muscle peristalsis and is involved in esophageal reflexes [268, 269]. Cholinergic stimulation, substance P, and, in contrast to circular muscle, NO are mediators of longitudinal muscle contraction [246, 270, 271]. Heightened sensitivity to longitudinal muscle stimulation may be a potential mechanism for esophageal shortening and hiatus hernia development in association with esophagitis [272, 273]. It is not known how the sequencing of longitudinal muscle by cholinergic excitation occurs during peristalsis in the absence of an inhibitory NO mechanism. Stimulation of the cut vagus results in simultaneous contraction [224]. Since the central vagal fibers connect to neurons in the enteric nervous system, excitation must finally result from an intramural mechanism, either primarily directed by the sequential vagal firing or from a coordinating intramural network.
Integration of central and peripheral mechanisms
Central control and peripheral neural and myogenic mechanisms must integrate effectively to direct peristalsis in the smooth muscle segment. Which mechanism is dominant under normal circumstances is not established. The esophagus ordinarily is both mechanically and electrically silent, and for a contraction to occur, some form of stimulus is required. With a swallow, the central mechanism controls and initiates contractions in the striated muscles of the oropharyngeal stage and in the upper striated muscle portion of the esophagus. For initiation of a contraction in the smooth muscle portion, the excitatory cholinergic neuron must be adequately stimulated by central and/or peripheral neural input. The threshold for muscle contraction, timing in the peristaltic sequence, and contraction amplitude are determined by the balance between excitatory and inhibitory influences at the muscle level.
Deglutitive inhibition
Deglutitive inhibition is primarily mediated centrally by the SPG. Activation of the SPG at any level is associated with inhibition of neurons and motor neurons distal to this level, with the inhibition increasing more distally (see Figure 5.2). When a swallow has reached the upper esophagus, a second swallow will inhibit progression of the first swallow after a short period of time, with a delay until the second swallow appears [208, 274, 275]. Centrally, the second swallow shuts down the firing of the motor neurons to the esophagus, with these neurons again active later for the second swallow. The inhibitory neurons in the esophagus may also be activated by separate vagal inputs from the SPG that could normally occur with the second swallow. An experiment suggesting this activation of local inhibitory neurons first produced a zone of high pressure with mild intraluminal balloon distention, likely in large part due to reflex vasovagal activation of the SPG and excitatory output to the esophagus [125]. A second swallow caused a decrease in pressure in the artificial high‐pressure zone but would also inhibit the central activation. When a sequence of many rapid repetitive swallows occurs, not only is the first swallow wave inhibited and not present, but all subsequent swallow waves are prevented until after the last swallow, which is then followed by an augmented peristaltic contraction [276]. This physiologic phenomenon is the basis for esophageal provocative testing using multiple rapid swallows (MRS) during esophageal manometry, where augmentation of contraction following the final swallow of the sequence demonstrates contraction reserve in the esophageal smooth muscle, indicating intact neuromuscular function [277, 278]. Both circular and longitudinal esophageal smooth muscle participate in deglutitive inhibition [279].
Secondary peristalsis is also inhibited by a swallow [208, 211]. However, secondary peristalsis initiated in the smooth muscle esophagus may not consistently or effectively inhibit a primary swallow when the stimulus arrives later in the SPG program.
A previous swallow or the presence of a swallow‐induced contraction in the esophagus can alter the nature of a subsequent swallow that occurs within 20–30 s. Amplitude can decrease, and velocity can decrease or increase, even to the point of the wave being non‐peristaltic [274, 276]. Therefore, routine manometry studies need to space swallows by at least 20–30 s [280].
Lower esophageal sphincter
There is a closed 3–4 cm long high‐pressure zone at the distal end of the esophagus that functions as an antireflux barrier and separates negative intrathoracic pressure in the esophagus from positive intra‐abdominal pressure in the stomach. This high‐pressure zone is considered to normally have two components: an intrinsic smooth muscle sphincter known as the LES, and the surrounding diaphragmatic crura that functions as an external sphincter [281]. When normally positioned, the LES is therefore part of a more complex structural arrangement called the esophagogastric junction (EGJ) that includes the phrenoesophageal membrane and the hiatal portion of the diaphragm. 3D high‐resolution manometry studies have demonstrated that the LES is asymmetric, and both the intrinsic LES and the crural diaphragm contribute to the basal tone of the EGJ [282].
Anatomy and innervation
Phrenoesophageal membrane
The phrenoesophageal membrane or “ligament” has a thin lower leaf that runs caudally and attaches to the adventitia of the esophageal wall just above the angle of His. A thicker upper leaf arising from the endothoracic fascia of the diaphragm runs cranially to attach firmly to the esophagus with collagenous extensions that penetrate to the submucosa, at about the level of the squamocolumnar junction [283–285]. This tough ligament serves to limit displacement of the esophagus into the thorax and to draw it back into position while minimizing circumferential traction on the LES. Attenuation of the ligament with age would facilitate the development of hiatus hernia [286].
Diaphragm
The diaphragm, commonly the right crus, surrounds the LES at approximately the mid‐level of the sphincter [287]. The crura arise from a lumbar vertebra and encircle the distal esophagus in a scissor‐like fashion to form a 2 cm long hiatal canal (Figure 5.14). The diaphragm receives its motor innervation from second‐order neurons in the phrenic motor nucleus of the spinal cord [288]. However, afferent signaling from both the crural diaphragm and the phrenoesophageal ligament passes via the vagus nerve to the SPG and, through efferent vagal pathways from the DMNV, takes part in inhibition of both the LES and crural diaphragm [289, 290]. This inhibition is present with swallow‐induced relaxation and with spontaneous transient LES relaxations (TLESR).
Intrinsic lower esophageal sphincter
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].