The gastrointestinal (GI) tract is the body’s organ system responsible for digestion, absorption, and excretion of matter vital for energy expenditure and compatibility with life. It utilizes a multitude of organs to achieve this including the mouth, esophagus, stomach, small and large intestines, rectum, liver, biliary tract, pancreas, and glands that work together via complex mechanisms. It can do this using three distinct centers of control[1]:
These processes all work together to achieve four major actions required for a proper functioning GI tract: motility, secretion, digestion, and absorption. This activity will primarily focus on neural control, specifically the physiologic function of the enteric nervous system and autonomic nervous system, and their associated pathology.
The GI tract is organized in distinct cellular layers, each containing unique properties integral to the physiological activity of the system as a whole. The layers include:
Lastly, one specialized group of cells instrumental to GI function include Intramuscular interstitial cells of Cajal (ICC). These cells are interposed between nerve terminals and smooth muscle cells, coupling with the smooth muscle cells to produce the pacemaker activity of the GI tract.
The GI tract consists mainly of the esophagus, stomach, small intestine, and large intestine, with each containing all of, or a combination of four functions mentioned previously.
As mentioned previously, mediation of the innervation of the GI system is via the enteric nervous system and the autonomic nervous system. Enteric nervous system- is the intrinsic nervous system of the GI tract, containing a mesh-like system of neurons. This system coordinates digestion, secretion, and motility to achieve adequate nutrient absorption. It does this through information stimulating the CNS such as sight and smell, and by local mechanical and chemical receptors found within the GI tract. Included in the enteric nervous system is the ICC. These cells positioned between the two muscular layers create the intrinsic pacemaker activity and are primarily responsible for slow-wave propagation found throughout the GI tract. Included in the enteric nervous system is the myenteric plexus, which exhibits control over the longitudinal and circular muscle layers. Additionally, it is estimated that 30% of the neurons in this plexus are sensory neurons.
The second aspect included in the neural control of the GI tract is the autonomic system. This system is comprised of the sympathetic and parasympathetic systems. In the case of the GI tract, the parasympathetic tract is typically excitatory. The parasympathetic system exerts its effects primarily via the vagus (innervates the esophagus, stomach, pancreas, upper large intestine) and pelvic nerves (innervates the lower large intestine, rectum, and anus.) The vagus nerve regulates tone and volume by activating the enteric motor neurons. They do this by synapsing on the myenteric motor neurons and either exhibiting inhibitory action via nitric oxide, or excitatory action via acetylcholine and neurokinins. The enteric motor neurons, including the myenteric plexus, then synapse on the ICC’s found within muscle bundles. These cells then communicate via gap junctions to the smooth muscles cells.
Sympathetic activity in the GI tract is fundamentally inhibitory. These fibers originate from spinal cord levels T-8 through L-2. These fibers then synapse on the pre-vertebral ganglia and continue onward to finally synapse on the myenteric and submucosal plexuses, which respond to manipulate smooth muscle cells, secretory cells, and endocrine cells.
The salivary glands are mainly under sympathetic control, specifically with cranial nerves VII and IX. These stimulate the secretion of serous, low viscous saliva. This saliva secreted relative to to parasympathetic activation is copious in amount and contains large amounts of potassium and bicarbonate, and scant amounts of protein. These glands are under sympathetic control as well but to a lesser extent. Sympathetic fibers extend through the superior cervical ganglion and stimulate the secretion of a highly viscous, thick saliva. The saliva produced is minimal in amount, is rich in protein, and low in potassium and bicarbonate.[11]
Gastric secretions are various and originate from parietal cells, chief cells, as well as mucous neck cells. Parietal cells secrete primarily hydrochloric acid (HCl), and intrinsic factor. There are three mechanisms for release of parietal cell contents, one of which is of neural influence. The first phase of gastric secretion is the cephalic phase. In this phase, a person sees, smells, or thinks about food, activating an area in the medulla oblongata. This then activates the Vagus nerve which secretes acetylcholine, which synapses at the muscarinic receptor allowing for the release of gastric contents. The gastric phase then begins as a bolus enters the stomach. Distension of the stomach activates stretch receptors in the wall of the stomach as well as chemoreceptors in the mucosa of the stomach, stimulating short reflexes which then stimulate the submucosal and myenteric plexuses, leading to parasympathetic activation and gastric secretion.[12]
Intestinal secretions are similar to that of gastric secretions. Intestinal distenison activates mechanoreceptors, and intestinal contents activate chemoreceptors both leading to parasympathetic activation and intestinal secretions.
Ileus often presents in postoperative patients characteristically present with obstipation and the intolerance of oral consumption. Ileus primary results from an active slow wave but the absence of spike-wave activity. While slow waves get produced by the pacemaker cells of the GI tract, they don’t cause contractions by themselves. An action potential, as seen by a spike-wave on top of the slow-wave, is needed for the slow-wave to reach a threshold low enough for the propagation of a full action potential, and consequent stimulation of various GI tissue. In this condition, there is continuous inhibitory neural activity and potential peritoneal irritation from the stasis of food.[13]
Infectious diarrhea, which can be caused by many organisms, has a general theme of rapid, powerful peristalsis that results in a reduced transport time leading to an increased number of bowel movements, as well as a lack of time for absorption and water extraction to occur, leading to bulky and watery stools.
Achalasia, characterized by a perpetually contracted lower esophageal sphincter (LES), is due to the absence or disruption of the ganglionic cells in the myenteric plexus. As these nerves are responsible for esophageal sphincter relaxation and esophageal propulsion, the LES is unable to relax, and food cannot pass through to the stomach.[14]
Hirschsprung disease is a failure of neural crest cells, the precursors to the myenteric plexus, to migrate to the intestines; this leads to constriction of the affected segment, as well as the failure of the intestines to propel food forward. This failure causes a buildup of food in the affected area as well as intestinal distension, and the inability to produce a bowel movement, often seen as a failure to pass meconium.[15]
Diffuse esophageal spasm which can present as dysphagia, heartburn, and regurgitation, is primarily caused by an aberrant response to esophageal distension. Instead of relaxing in response to swallowing and consequent esophageal distension, the esophagus is unable to do so and remains in the contracted state, preventing proper peristaltic movement.
Gastroesophageal reflux disease (GERD), is a chronic problem resulting in the contents of the stomach to reflux back into the esophagus due to an incompetent LES that fails to stay in its contracted state leading to damage of the esophageal epithelium. This condition can have many complications, the most severe of which is disruption of the normal mucosa, and the development of esophageal adenocarcinoma. GERD is commonly exacerbated by specific foods and drinks such as certain proteins, alcohol, and caffeine, as they enhance gastric secretion significantly by stimulating chemoreceptors in the mucosa of the stomach, leading to increased release of HCl by the parietal cells, and an increase of the acidity of gastric contents.[16]
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