GIT Motility

The motility of the gastrointestinal (GI) tract is a highly integrated process, essential for the efficient digestion and absorption of nutrients, as well as the propulsion of undigested material. This integration is mediated by complex regulatory systems, including peptides and the nervous system.

I. Types of Intestinal Contractions

Contractions in the small intestine serve at least three primary functions: mixing ingested foodstuffs with digestive secretions and enzymes, circulating intestinal contents to facilitate contact with the mucosa, and propelling contents in an aboral (downstream) direction. The GI tract's contractile tissue is primarily smooth muscle, with distinct patterns of contraction.

• Segmentation Contractions:

    ◦ These are the most common pattern of contraction in the small intestine during digestion.

    ◦ They serve to mix and locally circulate the intestinal contents (chyme).

    ◦ During segmentation, a section of the small intestine contracts, displacing contents in both orad (upstream) and caudad (downstream) directions. The section then relaxes, allowing contents to move back into the segment, resulting in mixing without significant net forward movement.

    ◦ In the large intestine, most contractions are also of the segmenting type, aiding in water and electrolyte absorption.

• Peristaltic Contractions:

    ◦ These are highly coordinated contractions that primarily serve to propel the chyme through the small intestine towards the large intestine.

    ◦ They involve contraction behind a food bolus and simultaneous relaxation in front of it, causing aboral propulsion.

    ◦ While often invoked to explain normal material movement, peristalsis involving long segments of the intestine is seldom seen in healthy individuals, though short-segment peristaltic contractions (1 to 4 cm) do occur.

    ◦ In the large intestine, aboral movement is slow, usually taking days, with most movement occurring during infrequent, powerful peristaltic contractions called mass movements [72, 69f]. These typically occur three to four times a day, often during or immediately after a meal, driving colonic contents into the rectum.

• Migrating Motor Complex (MMC):

    ◦ This is a distinct pattern of contractions observed in fasting humans.

    ◦ It consists of cycles where phases of minimal or no contractions are followed by a phase of intense contractions (Phase 3) that ends abruptly.

    ◦ This phase of intense contractions appears to migrate aborally, sweeping from the stomach through the small intestine to the ileum, taking approximately 1.5 hours.

    ◦ The functions of the MMC include sweeping undigested contents from the stomach and small intestine into the colon, and maintaining low bacterial counts in the upper intestine.

    ◦ In non-fasting individuals, the MMC disappears, and contractions are spread more uniformly over time.

II. Mechanisms and Essential Features of Contraction

Intestinal contractions are fundamentally governed by the properties of smooth muscle cells and specialized pacemakers.

• Smooth Muscle Anatomy:

    ◦ The small intestine's contractile activity is carried out by two layers of smooth muscle cells: an outer longitudinal layer and an inner circular layer.

    ◦ The circular layer is generally thicker, and both layers are more abundant proximally, decreasing in thickness towards the ileocecal junction.

    ◦ Unlike skeletal muscle, smooth muscle cells are non-striated; their contractile elements are not arranged in orderly sarcomeres.

    ◦ In the digestive tract, circular smooth muscle contraction decreases the lumen's diameter, while longitudinal muscle contraction shortens the segment.

• Interstitial Cells of Cajal (ICCs):

    ◦ ICCs are prominent in and adjacent to the enteric nerves and muscular layers of the intestine.

    ◦ They serve as the pacemaker cells for GI smooth muscle.

    ◦ At least two major classes of ICCs are identified: those generating slow waves and those mediating neural input to smooth muscle cells.

• Slow Waves (Basic Electrical Rhythm):

    ◦ Smooth muscle cells in the small intestine exhibit a membrane potential that fluctuates rhythmically with cyclic depolarizations and repolarizations (5 to 15 millivolts). These are called slow waves or basic electrical rhythm.

    ◦ Slow waves are always present, regardless of whether contractions are occurring.

    ◦ Their frequency is constant at any one site but decreases along the length of the bowel. In humans, the frequency decreases from approximately 12 cycles/minute (cpm) in the duodenum to about 8 cpm in the terminal ileum.

    ◦ Slow waves determine the pattern of action potentials and, therefore, the pattern and maximal frequency of contraction.

• Spike Potentials (Action Potentials):

    ◦ These are rapid fluctuations in membrane potential superimposed on the depolarization phase of the slow wave.

    ◦ Spike potentials, not slow waves themselves, initiate contractions of the muscle.

    ◦ Their presence and pattern depend on the digestive state and on neural and humoral activities. When the plateau potential of a slow wave exceeds a threshold, spike potentials fire, leading to contraction.

• Role of Calcium (Ca2+):

    ◦ In smooth muscle, stimulation induces a rise in intracellular Ca2+, which in turn triggers phosphorylation of the myosin light chain, leading to muscle contraction. This mechanism is crucial for both phasic and tonic contractions.

III. Regulation of Intestinal Motility

Intestinal motility is under sophisticated neural and hormonal control, integrating various inputs to ensure optimal digestive function.

• Intrinsic (Enteric) Nervous System (ENS):

    ◦ Often called the "brain of the gut," the ENS is contained entirely within the wall of the GI tract.

    ◦ It consists of prominent nerve plexuses: the myenteric (Auerbach's) plexus (primarily controls motility) and the submucosal (Meissner's) plexus (primarily controls secretion and blood flow).

    ◦ The ENS receives input from receptors within the GI tract and extrinsic nerves, allowing for coordinated activities and local reflexes even in the absence of extrinsic innervation.

    ◦ The peristaltic reflex (also known as the "law of the intestines") is coordinated by the enteric nervous system.

• Extrinsic Nervous System (Autonomic Nervous System - ANS):

    ◦ Innervates the GI tract and modulates the intrinsic activity of the effector cells.

    ◦ Parasympathetic System: Primarily supplied by the vagus and pelvic nerves.

        ▪ Usually excitatory on GI functions.

        ▪ Preganglionic vagal fibers synapse mainly with cells of the enteric nervous system.

        ▪ Vagal stimulation generally increases contractions.

        ▪ Vagovagal (long) reflexes play important roles in regulating GI functions, relaying information between the gut and the brainstem.

    ◦ Sympathetic System: Postganglionic efferent fibers from sympathetic ganglia innervate elements of the enteric system, smooth muscle, blood vessels, and secretory cells directly.

        ▪ Usually depresses contractions.

    ◦ Intestino-intestinal Reflex: If an area of the bowel is grossly distended, contractile activity in the rest of the bowel is inhibited. This reflex depends on extrinsic neural connections.

• Hormonal and Neurocrine Control:

    ◦ Motilin: Released cyclically during fasting, it stimulates upper GI motility and accounts for the interdigestive migrating myoelectric complex (MMC). It can initiate premature MMC bursts.

    ◦ Gastrin and Cholecystokinin (CCK): May play a role in converting the MMC pattern to the digestive pattern. CCK decreases contractions and increases gastric distensibility.

    ◦ Vasoactive Intestinal Peptide (VIP) and Nitric Oxide (NO): Important neurocrines that physiologically mediate the relaxation of GI smooth muscle. VIP stimulates NO synthesis. They are proposed to mediate transient relaxation of the lower esophageal sphincter during swallowing.

    ◦ Enkephalins: Neurocrines that increase smooth muscle tone.

    ◦ Somatostatin: An important paracrine agent that inhibits the release of all GI hormones and inhibits gastric H+ secretion.

    ◦ Gastrin-releasing peptide (GRP) / Bombesin: A neurocrine found in nerves of the gastric mucosa, potent releaser of gastrin.

IV. Applied Clinical Aspects

Disorders of intestinal motility can lead to a variety of clinical conditions, often presenting with symptoms related to altered transit and digestion.

• Impaired Gastric Emptying:

    ◦ Can manifest as a rate of gastric emptying that is either too slow or too fast.

    ◦ Causes include gastric cancer, peptic ulcer disease (occlusion from inflammation/scarring), diabetes mellitus, and potassium depletion.

    ◦ Gastroparesis (delayed gastric emptying) can be treated with drugs like erythromycin, which activate motilin receptors.

• Vomiting (Emesis):

    ◦ A complex reflex coordinated in the medulla.

    ◦ Usually involves nausea and retching, which collectively overcome the antireflux mechanisms of the GI tract.

    ◦ Involves reverse peristalsis, where contents from the small intestine are propelled back into the stomach and then expelled.

• Diarrhea:

    ◦ Results from abnormal (often increased) transit of material through the colon.

    ◦ Osmotic Diarrhea: Caused by the presence of non-absorbable, osmotically active solutes in the lumen, drawing water into the intestine.

    ◦ Secretory Diarrhea: Occurs due to increased secretion of fluid and electrolytes into the lumen. For example, cholera toxin activates adenylate cyclase, increasing cAMP in intestinal crypt cells, which in turn activates Cl- secretory channels, leading to primary Cl- secretion followed by Na+ and water.

• Constipation:

    ◦ Results from abnormally delayed transit of material through the colon.

    ◦ Often dietary in origin, with a direct correlation between increased dietary fiber and enhanced transit.

    ◦ Laxatives work either through osmotic effects (e.g., polyethylene glycol) or by increasing colonic propulsion (e.g., bisacodyl).

• Hirschsprung's Disease (Aganglionic Colon):

    ◦ A condition where neuronal ganglion cells of the colon fail to develop.

    ◦ Leads to intestinal obstruction, absence of defecation, and massive distention of the colon (megacolon) early in infancy.

• Esophageal Motility Disorders:

    ◦ Achalasia: A condition affecting the esophagus.

    ◦ Gastroesophageal Reflux Disease (GERD): May occur if the tone of the lower esophageal sphincter (LES) is decreased, allowing gastric contents to reflux into the esophagus, causing heartburn.

    ◦ Diffuse Esophageal Spasm.

• Idiopathic Pseudo-obstruction:

    ◦ A motility disorder characterized by symptoms of intestinal obstruction without any physical blockage.

• Irritable Bowel Syndrome:

    ◦ A common condition where alterations in colonic motility and transit are frequently caused by emotional factors, indicating a strong influence of higher CNS centers.