Do the results of biochemical studies help to define the exact site of the circular muscle of the sphincter ?
C. G. Bremner (Johannesburg)
Lower esophageal sphincter pressure is related to its smooth muscle structure and responses, nerve innervation and endogenous hormonal effects. There are species differences in which myogenic contributions predominate in the control of lower esophageal sphincter (LES) pressure (opposum, cat), but in man LES tone is thought to be maintained by cholinergic vagal nerves. The evidence presented indicates that structuraly and biochemically the LES has different properties to that of the esophageal body.
Muscle structure and responses
Contrary to most observations, Liebermann el al.[\] have identified an area of muscular thickening and a specific fibre arrangement in the distal esophagus. Christensen et al. [2] have described differences in the muscle structure and density of nerve innervation in the lower sphincter which explain its functional differences. They showed that the ganglia and perikarya had the lowest density at the LES level when compared to tissues 2 and 3 cm above the LES. Furthermore, a greater mitochondrial profile area was seen in the LES muscle. The isoenzyme LDH-1 is found in the LES but not in the body of the esophagus, and this is related to aerobic metabolism. Isometric tone of the LES is almost totally aerobic as opposed to other parts of the esophagus which can be sustained anaerobically [3]. The LES has three patterns of relaxation as described by Dent et al. [4]. The first is the response to primary peristalsis, the second is related to esophageal distension and the third is a transient LES relaxation. These functions are all distinct from the peristaltic contraction of the esophagus.
Nerve innervation
In the human, LES tone is dependant on muscarinic stimulation which is vagally driven and therefore blocked by atropine [5]. A sensory vagal mechano-receptor feedback system located in the LES transmits signals via the vagus to the midbrain [6]. Vagal section at the gastroesophageal junction has no effect on LES function because the vagal supply to the LES leaves the main truncks at a higher level. These vagal efferents to the LES pass intramurally through the distal esophagus [7]. The intrinsic nerve plexuses of Auerbach and Meissner receive axons from the vagus. Destruction of Meissner's plexus in the dog model has little effect
on LES function, but resection of Auerbach's plexus results in an increase in LES pressure and a disturbance of relaxation of the LES [8].
Hormonal effects
There is no proven role of hormonal control of the LES, but many hormones have been shown to exert an increase or decrease in basal LES tone, and therefore identify it as being separate from the body of the esophagus. Because fat ingestion inhibits and protein increases LES tone, some feedback system seems likely. The response to intragastric alkali and glycine is inhibited by somatostatin [9], apparently by a hormonally mediated mechanism. Gastrin, motilin, bombesin, vasopressin, substance P and angiotensin all stimulate LES contraction. Secretin, glucagon, progesterone, cholecystokinin, Gastric Inhibitory Peptide, VIP and Neurotensin decrease lower esophageal sphincter pressure.
In summary, therefore, muscle responses, nerve innervation and hormonal effects on the sphincter zone do help to define the exact site of the circular muscle of the sphincter. The site of the sphincter responses correlate well with the area of the sphincter zone which has differences in nerve density and mitochondrial profile.
References