Nerves #

Classically the autonomic nervous system consists of two components, cholinergic and adrenergic nerves; the former are contained mostly in the parasympathetic, and the latter mostly in the sympathetic division. For the past 4 decades a third component of the autonomic system, which is neither cholinergic nor adrenergic, has been recogized; the principal active substance released from these nerves in the gastrointestinal tract is a purine nucleotide; they have been called purigenic nerves by Burnstock (l972). An increasing number of peptides with a dual localization in endocrine cells and peripheral nerves in the walls of the gastrointestinal tract has now been recognized. This has led to the concept of a three-part autonomic control system consisting of cholinergic, adrenergic and peptidergic nerves (Bishop et al. l977).

Parasympathetic Nerve Supply #

The parasympathetic nerve supply to the stomach is derived from the anterior and posterior vagal trunks and their branches. Afferent fibres are also present in the vagi, which are mixed nerves.

Anterior Vagus #

The anterior vagal trunk, which is derived mainly from the left vagus nerve but which includes fibres from the right vagus and also some sympathetic fibres from the splanchnic nerves, enters the abdominal cavity through the oesophageal hiatus in the diaphragm. It is usually single but may be divided into two or even three trunks. The manner of distribution of its branches is in the main constant (Latarjet et al. l921; McCrea l924).

Having supplied several fine twigs to the lower end of the oesophagus and cardiac part of the stomach, the anterior trunk breaks up into its main branches.

According to Latarjet three main sets of branches are present:

1. The first set, consisting of 4 to 5 direct branches, emanating "one below the other", supplies the upper part of the lesser curvature. These nerves do not form a plexus and can be dissected separately. A few filaments from the sympathetic supply join these direct branches via the coeliac plexus. One of the branches in this group is always bigger than the others and very distinct; Latarjet (l921) called it the principal anterior nerve of the lesser curvature. It innervates the area from the cardia to the pyloric vestibule, and does not proceed beyond the latter (Fig 8.1).

2. Branches emanating from the vagal supply to the liver. These branches, usually 3 to 5 in number, descending in the lesser omentum, "fall like rain" on the superior margin of the pylorus and first part of the duodenum. Latarjet called them the superior pyloric nerves (Fig 8.1).

3. The third set consists of vagal filaments from the hepatic branches, accompanying the sympathetic nerves along the right gastroepiploic artery next to the greater curvature. They provide a few vagal twigs to the inferior margin of the pylorus. Latarjet called these the inferior pyloric nerves (Fig 8.1).

According to Latarjet (l921) the anterior vagus can be divided into two distinct functional divisions. The first division, consisting of the direct branches, supplies the fornix and body, i.e. the "reservoir" part of the stomach. The second division, through the hepatic branches, supplies the pylorus and first part of the duodenum, i.e. the "sphincteric" part of the stomach. (Comment: According to Latarjet, the principal anterior nerve of the lesser curvature does not supply the pylorus; the pylorus and first part of the duodenum are innervated by the superior and inferior pyloric nerves, emanating from the hepatic branches). Latarjet found the innervation in dogs to be similar to that in man.

The papers of McCrea (l924), Mitchell (l940) and Jackson (l948) describe personal investigations and provide an analysis of the literature. The following findings are pertinent to the present discussion.

According to McCrea (l924) the anterior vagal trunk breaks up into 3 to 6 main branches. To the left a group of gastric branches arise, supplying the anterior surface of the cardia, the fornix and proximal portion of the body of the stomach. These may or may not form an anterior gastric plexus.

Fig. 8.1. Diagram of gastric branches of anterior vagus. 1., Direct branches; 2., branches emanating from vagal supply to liver (superior pyloric nerves); 3., branches emanating from vagal supply to liver (inferior pyloric nerves); H., hepatic branch or branches; A.L., anterior nerve of Latarjet (principal anterior nerve of lesser curvature)

On the right there are the following three main groups of branches:

1. The first or hepatic branch proceeds laterally in the lesser omentum towards the porta hepatis; it is frequently duplicated. Its terminal twigs are divided into 2 series, viz. a proximal which supplies the porta hepatis, and a distal, which turns downwards towards the pylorus. From the latter twigs pass (a) to the pylorus and first part of the duodenum; (b) along the right gastric artery to the region of the pyloric canal; (c) to run deep to the pylorus with the gastroduodenal artery towards the head of the pancreas and second part of the duodenum; (d) to run proximally on the wall of the hepatic artery, and (e) to communicate with sympathetic twigs passing to the gall bladder. Communications with sympathetic twigs are common.

2. The second branch on the right, a large nerve, passes downwards between the layers of the lesser omentum, a short distance from, and parallel to, the lesser curvature of the stomach. It is distributed to the anterior surface of the pyloric "antrum" and body of the stomach, but does not reach the pyloric "canal".

3. The third branch lies on and follows the lesser curvature along the attachment of the lesser omentum; it descends as far as the incisura angularis. All these branches may communicate with the coeliac sympathetic plexus, and in the region of the fornix communications are received from the posterior vagal trunk.

McCrea (l924) concludes that the pyloric canal, pyloric "sphincter" and first part of the duodenum are supplied by the hepatic branches of the anterior vagus. The remainder of the stomach is supplied by the gastric, and second and third right branches. It is stated specifically that the second branch supplies the anterior surface of the "antrum" and body, but that it does not reach the pyloric "canal". McCrea found the distribution of the vagi in the abdomen of the cat, dog and rabbit to be essentially similar to that of man.

Mitchell's (l940) findings differ in certain minor respects from those of McCrea (l924). According to Mitchell some of the lowermost gastric branches (which primarily supply the cardia, fornix and upper lesser curvature) reach almost, but not quite, to the pylorus.

The hepatic branches (of which there are two to four), running towards the right to the porta hepatis, divide at the hepatic artery, one branch passing upwards to the liver and the other downwards to the pylorus and coeliac plexus. In one out of 15 specimens the uppermost hepatic branch divided into three: one to the porta hepatis, one to the cystic duct and gall bladder, and the third to the pylorus.

The greater anterior gastric nerve (i.e. McCrea's second branch) supplies two pyloric twigs according to Mitchell (l940). The first arises near the upper end of the lesser curvature, passes almost horizontally between the layers of the lesser omentum as far as the hepatic artery, then turns downwards on the left side of the hepatic artery to reach the pylorus and proximal part of the duodenum. It often bifurcates, sending one branch upwards to the liver and the other downwards to the pylorus, and it is connected to the hepatic plexus. The other pyloric twig usually arises from the greater anterior gastric nerve about halfway along the lesser curvature, and passes obliquely between the layers of the lesser omentum to the pyloric "antrum", some fibres reaching the pyloric "sphincter". This twig arises at a lower level, but supplies the pylorus proximal to the branch first described.

Thus according to McCrea (l924) and Mitchell (1940), the main innervation of the pyloric region from the anterior vagus occurs via its hepatic branches. According to Mitchell (l940) the pylorus is also innervated by twigs arising in the greater anterior gastric vagal branch, running between the layers of the lesser omentum.

Jackson (l948) studied the distribution of the vagus in 50 cadavers. The hepatic branches of the anterior trunk, running to the porta hepatis, were identified in 43 cases. In the first case the hepatic branch was followed to its termination and was found to supply the first few centimeters proximal to the pylorus, the pylorus itself and the first part of the duodenum. In the remainder of the dissections attention was concentrated on the more proximal parts of the branches, and the hepatic branches were followed only to the fissure of the ductus venosus. The principal anterior nerve of the lesser curvature described by Latarjet (l921) was found in 28 instances. From its origin it passed along the lesser curvature, returning to the stomach generally from 2.5-9 cm proximal to the pylorus; the closest any branch of this nerve came to the pyloric "sphincter" was 2.5 cm.

Skandalakis et al. (l986) reiterate that separation of the anterior vagal trunk into anterior gastric and hepatic divisions is usually found on the surface of the distal oesophagus at the gastro-oesophageal junction. Usually a major branch of the anterior gastric division forms the principal anterior nerve of the lesser curvature (nerve of Latarjet). In most instances it can be traced to the level of the incisura; occasionally it may proceed as far as the first part of the duodenum (in these cases the pylorus is still innervated via the hepatic branch). It may also be absent, the "antrum" being supplied by branches arising from the anterior vagal trunk proximal to the origin of the hepatic division. Many variations exist, and Skandalakis et al. (l986) referred to "the vagaries of the vagus nerve". However, these authors point out that the usual supply to the pylorus is a descending branch (or branches) from the hepatic division before it reaches the liver; occasionally the pyloric branch may arise from the anterior gastric division.

Posterior Vagus #

The posterior vagal trunk, which is derived mainly from the right vagus nerve but includes fibres from the left vagus and some sympathetic fibres, enters the abdomen through the oesophageal hiatus in the diaphragm on the posterior surface of the oesophagus. The number and direction of its branches is more constant than that of the anterior vagus (Latarjet l921; Skandalakis et al. l986). Shortly after entering the abdomen it divides into 2 main divisions. The larger or coeliac division proceeds to the coeliac and other abdominal sympathetic plexuses. The smaller or posterior gastric division first gives off fine twigs to the lower oesophagus and fornix. It then continues along the lesser curvature, giving off 4 to 6 posterior gastric branches. Latarjet (l921) called the most inferior and also the largest of these branches the principal posterior nerve of the lesser curvature; this has subsequently become known as the posterior nerve of Latarjet. Together with the other posterior branches it innervates the posterior wall of the stomach, with the exception of the pylorus and immediate prepyloric region. It also anastomoses with sympathetic twigs from the coeliac plexus, as well as with the principal anterior nerve of the lesser curvature.

McCrea's (l924) findings are similar to those of Latarjet, but he terms the branch from which the posterior gastric twigs arise, the "stem". Thus the stem gives off branches to the posterior aspect of the proximal portion of the body of the stomach. It then continues downwards, giving off branches to the posterior surface of the body and pyloric "antrum", the most distal being distributed in the region of the incisura angularis. According to McCrea the posterior vagus does not reach the pyloric canal.

Mitchell's (l940) findings are almost identical. What he calles the posterior gastric nerve (McCrea's "stem") gives off branches at intervals which pass to the stomach, but the terminal branches extend only to the pyloric "antrum", failing to reach the pyloric "sphincter". Slender hepatic twigs may also be given off towards the porta hepatis.

In 50 dissections of the posterior vagal trunk, Jackson (l948) charted the gastric branches and determined the point of origin of the coeliac branch. The principal posterior nerve of the lesser curvature (nerve of Latarjet) was identified in 19 instances. It proceeded along the lesser curvature in the direction of the pylorus, but, before reaching it, turned across the posterior surface of the stomach towards the greater curvature. Jackson concluded that the vagal supply to the pylorus was via the hepatic branches of the anterior vagus.

According to Skandalakis et al. (l986) the posterior gastric division forms the posterior nerve of Latarjet. The posterior gastric division usually terminates higher on the lesser curvature than the anterior gastric division; in a small minority of cases it reaches the pylorus. The most frequent pattern of the posterior gastric division is that described by McCrea (l924), which is a typical, but not universal, pattern.

Parasympathetic Ganglia #

The left vagus supplies efferent preganglionic fibres mainly to the anterior surface, and the right vagus mainly to the posterior surface of the stomach. In addition both vagi send branches to the coeliac plexus. The parasympathetic preganglionic vagal fibres penetrate the layers of the gastric wall, to form synapses in the ganglion cells of the plexus of Auerbach between the longitudinal and circular muscle coats, and in the plexus of Meissner in the submucosa. From the ganglia postganglionic fibres emerge to supply the musculature and mucosa. According to Horton (l928), Auerbach's plexus is continuous from the pyloric region to the duodenum.

In addition to the myenteric (Auerbach's) and submucous (Meissner's) plexuses, Rash and Thomas (l962) described a third group, namely the subserous plexuses; they also mentioned the differentiation of enteric neurones into argyrophilic Dogiel Type I cells with short dendrites, and argyrophobic Dogiel Type II with fewer but longer dendrites. According to Smith (l970) the axons of argyrophilic neurones do not leave the plexuses and do not reach muscle fibres; their function is to coordinate peristalsis. The axons of argyrophobic cells, which are strongly cholinergic, form secondary and tertiary plexuses and supply muscle fibres; they act by initiating contractions. The general effect of myenteric plexus damage is loss of coordinated muscular contractions which serve to propel luminal contents caudally; this may lead to local muscular hypertrophy, e.g. hypertrophic pyloric stenosis (Chap 23).

Discussion #

The investigators quoted, namely Latarjet (l921), McCrea (l924), Mitchell (l940), Jackson (l948) and Skandalakis et al. (l986), found that the main, and in most cases the only, nerve supply from the anterior vagus to the pylorus is via its hepatic branch or branches. The region supplied in this way encompasses the distal "few centimetres" of the stomach, the pylorus and first part of the duodenum. While none of the authors referred to the findings of Cunningham (l906), Forssell (l913) or Torgersen (l942), it is clear that the region of the pylorus innervated in this way, corresponds to the pyloric sphincteric cylinder.

In the vast majority of cases the principal anterior nerve of the lesser curvature (nerve of Latarjet) does not innervate the sphincteric cylinder. A few exceptions were mentioned. Mitchell (l940) stated that in some cases a few fibres from the anterior vagus might reach the pylorus directly from gastric branches higher up. Skandalakis et al. (l986) found that Latarjet's nerve might occasionally proceed as far as the duodenum; in these cases there was still a separate branch from the hepatic division to the pylorus.

The investigators quoted found that the posterior vagus (including the posterior nerve of Latarjet) does not usually innervate the pylorus and prepyloric region, the most distal twigs extending only as far as the incisura angularis or the "commencement of the antrum". It is clear that the region which is not innervated by the posterior vagus, corresponds to the pyloric sphincteric cylinder. One of the few exceptions was mentioned by Skandalakis et al. (l986); in a small minority of cases they found that fibres of the posterior gastric division could reach the pylorus.

It is concluded that the vagal supply to the pyloric sphincteric cylinder (which includes the pyloric ring musculature) and to the first part of the duodenum, occurs via the hepatic branch of the anterior vagus in the vast majority of cases; the hepatic branch (or branches) breaks up into the superior and inferior pyloric nerves, supplying the cylinder. It is of interest to note that, when first describing the pyloric sphincteric cylinder in l906, Cunningham surmized that its powerful musculature was probably under control of a special innervation.

Sympathetic Nerve Supply #

The sympathetic nerve supply to the stomach is almost entirely derived from the coeliac plexus. The gastric branches of the coeliac plexus accompany the vessels supplying the stomach, and the maximum number are found alongside the left gastric, hepatic and phrenic arteries, while others accompany the splenic, right gastric and gastro-epiploic vessels.

According to McCrea (l924) these nerves can be grouped as follows:

1. Fibres from the coeliac plexus accompany the left inferior phrenic artery, wind across the anterior aspect of the lower oesophagus, communicate with branches of the anterior vagus, and are distributed to the cardia and fornix.

2. Fibres from the coeliac plexus pass with the left gastric artery and divide into three groups: (a) Fibres passing with the oesophageal and superior branches of this artery to the cardia and proximal part of the body of the stomach; these twigs communicate with branches of the anterior and posterior vagal trunks. (b) Fibres passing with the main stem of the artery along the lesser curvature to supply the anterior and posterior surfaces of the body of the stomach and pyloric "antrum". (c) Fibres passing between the layers of the lesser omentum towards the porta hepatis, communicating with hepatic branches of the anterior vagal trunk in most instances.

3. Fibres passing from the coeliac plexus along the hepatic artery and distributed with its branches. They reach the pyloric region of the stomach with the right gastric and right gastroepiploic arteries.

In all major respects Mitchell's (l940) description agrees with that of McCrea, although he adds some exceptions. According to Mitchell the terminal twigs accompanying the main branch of the left gastric artery, i.e. group 2b of McCrea, did not reach the pylorus in any of the 15 specimens examined by him, but united with the nerve filaments lying alongside the right gastric artery. The right gastric branches, (group 3 of McCrea) supply the upper parts of the pyloric region.

Sympathetic Ganglia #

Preganglionic sympathetic fibres end in the coeliac ganglia; efferent fibres emerging from the coeliac ganglia to accompany the arteries are postganglionic. Even though they traverse the enteric ganglia they probably have no functional relationship to the enteric plexuses; they are distributed with the postganglionic vagal fibres emerging from the plexuses.

Afferent visceral fibres from the stomach travel the same course in reverse, to ganglion cells in the posterior spinal nerve roots. They do not synapse in, or arise from, sympathetic ganglia. Although the sympathetic nerves are motor, they also carry fibres from sense organs in the viscera.

Discussion #

It seems that the main sympathetic supply to the pyloric region occurs via fibres accompanying the hepatic artery and its branches.

Peptidergic System #

The peptidergic system refers to a widespread group of cells, derived from neuroectoderm embryologically and having certain biochemical features in common. They are also referred to as neuroendocrine cells and belong to the APUD cell line, based on their capacity to synthesize monoamines through a process of amine precursor uptake and decarboxylation. During recent years a large number of biologically active peptides, produced by APUD cells, have been demonstrated in central and peripheral neurogenic tissues as well as in the walls of the gastrointestinal tract (Chap. 9). Some of the peptides, notably gastrin and vasoactive intestinal peptide (VIP), were first detected in the gut and subsequently in the brain; others, such as somatostatin, enkephalin and neurotensin were first identified in brain tissue and subsequently in the walls of the alimentary tract. Substance P has long been known to be present in both locations.

Most of the monoamines have several molecular forms or sizes. Some types are released into the circulation, producing their biological effects in distant target organs; these can be looked upon as true hormones acting in an endocrine way. Others act locally in the vicinity of their site of origin in a paracrine way. A third group functions as neurotransmitters, acting in a neurocrine way. A clearcut separation of endocrine, paracrine and neurocrine functions is not always feasible. Burnstock (l986) pointed out that thinking mainly in terms of antagonistic parasympathetic cholinergic and sympathetic adrenergic control of functions, is no longer tenable. The involvement of a multiplicity of neurotransmitters and of sophisticated peripheral control mechanisms such as neuromodulation and co-transmission, has to be recognized. This is accomplished through non-cholinergic, non-adrenergic nerves of the purigenic system.

APUD cells and regulatory peptides in the pyloric region of the stomach will be discussed in somewhat greater detail in the next chapter.

References #

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