Enteric nervous system

Also known as: ENS, second brain, intrinsic nervous system of the gut

An intrinsic network of hundreds of millions of neurons in the wall of the gut, from oesophagus to anus, that can independently control motility, secretion and local blood flow and is modulated by sympathetic and parasympathetic input.

Overview

Number of enteric neurons≈200–600 million (estimates vary; comparable to the spinal cord)

Gut serotonin≈90–95% of body 5-HT

Slow-wave frequency≈3/min (stomach) to ≈12/min (duodenum)

The ENS is organised in two ganglionated plexuses. The myenteric (Auerbach) plexus, between the longitudinal and circular layers of the muscularis externa, mainly controls motility. The submucosal (Meissner) plexus, in the submucosa of the small and large intestine, mainly controls secretion, absorption and mucosal blood flow. Each plexus contains complete reflex circuits:
• intrinsic primary afferent neurons (IPANs) that sense stretch and luminal chemistry;
• ascending and descending interneurons;
• motor neurons: excitatory to muscle (ACh, substance P), inhibitory to muscle (NO, VIP, ATP) and secretomotor or vasodilator to the epithelium.
Enteric glia, similar to astrocytes, support the neurons.

Isolated segments of bowel still show coordinated peristalsis. In the peristaltic reflex, distension excites contraction behind the bolus (orad) and relaxation ahead of it (aborad), propelling the contents. Extrinsic nerves modulate rather than command this activity. Vagal and pelvic parasympathetic fibres generally enhance motility and secretion; sympathetic fibres inhibit motility, constrict sphincters and reduce blood flow. The interstitial cells of Cajal are not neurons but pacemaker cells that generate slow waves (≈3/min in the stomach, ≈12/min in the duodenum). The ENS is a key part of the gut–brain axis.

Location

Wall of the gastrointestinal tract from the oesophagus to the internal anal sphincter, plus the gallbladder and pancreas.

Parts & subdivisions

Myenteric (Auerbach) plexus

Between the longitudinal and circular muscle layers along the whole tract; controls the tone, rhythm and propagation of contractions.

Submucosal (Meissner) plexus

In the submucosa (mainly small and large intestine); controls epithelial secretion, absorption, local blood flow and muscularis mucosae.

Intrinsic primary afferent neurons

Sense mucosal distortion, stretch and luminal chemicals (often via serotonin released from enterochromaffin cells).

Enteric motor neurons

Excitatory (ACh, tachykinins) and inhibitory (NO, VIP, ATP) neurons to smooth muscle; secretomotor neurons (ACh, VIP) to crypts.

Interstitial cells of Cajal

Mesenchymal pacemaker cells that generate electrical slow waves and transmit neural input to smooth muscle; the cell of origin of GIST.

Function

Generates peristalsis, segmentation and the migrating motor complex

Controls epithelial secretion of water and electrolytes

Regulates local mucosal blood flow

Coordinates sphincter relaxation (e.g. receptive relaxation, LES opening)

Relays gut sensory information to the CNS (gut–brain axis)

Physiology

About 90–95% of the body's serotonin is made by enterochromaffin cells of the gut mucosa and acts on IPANs and vagal afferents. 5-HT3 antagonists such as ondansetron block vagal afferent signalling of nausea. Opioids act on enteric μ-receptors to cause constipation.

Clinical significance

Hirschsprung disease

Failure of neural crest migration leaves a distal aganglionic segment, always involving the rectum, that cannot relax. The result is functional obstruction with proximal megacolon, delayed passage of meconium (>48 h), abdominal distension and a risk of enterocolitis. It is associated with RET mutations and Down syndrome. Rectal suction biopsy shows absent ganglion cells and increased acetylcholinesterase-positive nerve fibres. Treatment is resection of the aganglionic segment (pull-through).

Achalasia

Loss of inhibitory (NO/VIP) myenteric neurons in the distal oesophagus means the lower oesophageal sphincter fails to relax and peristalsis is lost. It causes dysphagia to both solids and liquids, and a barium swallow shows a "bird's beak". Chagas disease (Trypanosoma cruzi) destroys enteric neurons and causes a similar megaoesophagus and megacolon.