Читать книгу The Esophagus - Группа авторов - Страница 147

Independent of swallowing, the LES relaxes spontaneously (TLESR) and with retching and vomiting. In both patients and normal subjects, the TLESR in the face of a normal LES pressure is the most common mechanism of gastroesophageal reflux [373, 374]. Transient LES relaxation occurs largely during daytime post‐prandial periods [375] attributed to a vagal reflex initiated by gastric distention [376, 377]. Belching occurs with a TLESR in response to gastric distention [378]. TLESRs are accompanied by crural diaphragm inhibition except when initiated by laryngeal or pharyngeal stimulation [379–381] and last longer than 10 s (average 21 s), which is longer than swallow‐related relaxations [375, 377, 382]. TLESRs are mediated centrally in the brainstem SPG in response to afferent input from the stomach, esophagus, pharynx or larynx, and crural diaphragm. The efferent signal is then carried in the vagus to produce relaxation of the LES and via the phrenic nerve to the crural diaphragm [290]. The reflex pathways, neurotransmitters, and chemical mediators involved are shown in Figure 5.16. NO may also be released at the diaphragm as a mediator of inhibition. Knowledge of these pathways had led to the potential for therapies directed at reducing TLESRs in GERD [383] by inhibiting cholinergic (M₁ receptor), and CCK‐A receptor effects and enhancing GABA‐B receptor effects [384–386]. Longitudinal muscle contraction participates in LES relaxation and crural diaphragm inhibition that occur concurrent with TLESRs [387], resulting in proximal migration of the EGJ. The rapid return of the EGJ to its resting location following TLESRs is thought to be partly due to elastic recoil of the phrenoesophageal ligament, which is stretched during TLESRs [388].

Figure 5.16 Reflex arc underlying transient lower esophageal sphincter relaxations (TLESRs), and potential sites of actions of different agents. CCK, cholecystokinin; ACh, acetylcholine; GABA, gamma butyric acid; NO, nitric oxide; CD, crural diaphragm; ENS, enteric nervous system; GN, nodose ganglion. NO may also act at the level of the crural diaphragm.

Source: Hirsch [383] with permissions of John Wiley & Sons.