L5 Smooth Muscle and Motility Notes

Smooth Muscle and Motility

Types of Muscle in GIT

  • Smooth (involuntary) muscle:
    • Found in most regions of the GIT.
    • Responsible for motility.
    • Usually has two layers: inner (circular) and outer (longitudinal).
  • Skeletal (voluntary) muscle:
    • Found in the pharynx, the top third of the esophagus, and the external anal sphincter.

Smooth Muscle Motility

  • Phasic Contractions (rapid contractions):
    • Occur in the body of the esophagus, stomach antrum, and small and large intestines.
  • Tonic Contractions (sustained contractions):
    • Occur in sphincters and the upper stomach.

Gastrointestinal Motility

  • Definition: The movements of the digestive system and how its contents transit within it.
  • Involves coordinated contractions and relaxations of the GIT to move contents from mouth to anus.
  • Three main patterns of motility:
    • Peristalsis
    • Segmentation
    • Tonic contraction

Contraction Types

  • Phasic:
    • Rapid contraction and relaxation.
    • Examples: peristalsis in the body of the esophagus, stomach antrum, small and large intestines.
  • Tonic:
    • Sustained contractions.
    • Examples: sphincters (lower esophageal, ileocecal, internal anal), orad (upper) stomach.

Muscle Contraction Mechanism

  1. Membrane Depolarization

  2. Calcium Influx: Calcium (Ca2+Ca^{2+}) enters the cell.

  3. Calmodulin Activation: Calcium binds to Calmodulin.

  4. Myosin Light Chain Kinase (MLCK) Activation: The calcium-calmodulin complex activates MLCK.

  5. Myosin Phosphorylation: MLCK phosphorylates myosin, using ATP, which allows it to bind to actin.

  6. Contraction: Actin and myosin interact, causing muscle contraction.

    • Receptors such as muscarinic receptors (stimulated by Acetylcholine (ACH)) can initiate this pathway via Phospholipase C (PLC) and IP3.
  • Relaxation:
    • Myosin Light Chain Phosphatase (MLCP) dephosphorylates myosin, leading to relaxation.
    • Protein Kinase A (PKA), when active, can inhibit contraction by promoting dephosphorylation. Beta-adrenergic receptors and Vasoactive Intestinal Peptide (VIP) activate Adenylate cyclase, increasing cAMP, activating PKA, and leading to relaxation.

Innervation of the GIT

  • Extrinsic Innervation:
    • Autonomic Nervous System:
      • Parasympathetic
      • Sympathetic
  • Intrinsic Innervation:
    • Enteric Nervous System (ENS)

Parasympathetic Innervation

  • Vagus Nerve (CN X):
    • Innervates the esophagus, stomach, small intestine, large intestine (up to the splenic flexure).
    • Preganglionic fibers.
  • Pelvic Nerves:
    • Innervate the rectum and anus.
    • Originate from the sacral spinal cord (S1-S3).
    • Preganglionic fibers.

Enteric Nervous System (ENS)

  • Myenteric Plexus Activation:
    • Increases tonic contraction.
    • Increases the intensity and rate of rhythmic contractions.
    • Increases the velocity of conduction.
  • Submucosal Plexus Activation:
    • Increases secretory activity.
    • Modulates intestinal absorption.

Communication Through the Enteric Nervous System

  1. Sensory neuron in the submucosal plexus.
  2. To interneuron (e.g., in myenteric plexus).
  3. To motor neuron in myenteric plexus.
  4. Signal to longitudinal muscle, circular muscle, and mucosa.

Enteric Sensory Neurons (Intrinsic Primary Afferent Neurons - IPANs)

  • Chemoreception:
    • Detect acid (low pH).
    • Detect short-chain fatty acids.
    • Detect 5-HT (serotonin) released by enterochromaffin cells.
  • Mechanoreception:
    • Detect distension.
    • Stretch in muscle cells activates a reflex contractile response.

Long-Range Intestinal Reflexes

  • Activatory (Excitatory):
    • Gastro-Enteric
    • Gastro-Ileal
    • Gastro-Colic
    • Duodeno-Colic
  • Inhibitory:
    • Ileo-Gastric
    • Intestino-Intestinal

Pathology of ENS

  • Hirschsprung Disease:
    • Congenital lack of neuronal ganglionic cells in the ENS.
  • Chagas Disease:
    • Infectious disease caused by the parasite Trypanosoma cruzi, leading to a reduction in ganglionic cells in the ENS.
  • Achalasia:
    • Dramatic reduction in neuronal cells in the lower esophageal segment.

Hirschsprung Disease

  • Aganglionic, aperistaltic bowel segment prevents propulsion of the fecal stream.
  • Results in megacolon above the point where nerves are missing and hypertrophy of the normal proximal colon.

Chagas Disease

  • Caused by infection with the protozoan parasite Trypanosoma cruzi, transmitted by Triatoma infestans.
  • Cardiologic and gastrointestinal manifestations.
  • Can affect the esophagus and cause megacolon or the entire gut.
  • Involvement of the ENS is pivotal in the pathogenesis.
  • Leads to degeneration and decreased number of intrinsic myenteric neurons, deficiency of interstitial cells of Cajal (ICC), and ganglion cell damage by T lymphocytes.

Achalasia

  • Disease of the esophagus.
  • Due to a lack of inhibitory motor neurons in the lower part of the esophagus and in the LES (lower esophageal sphincter).
  • Results in a characteristic “bird’s beak” image.

Gastric Motility

  • Gastric Functions:
    • General
    • Food storage
    • Mixing
    • Emptying/release (and pyloric function)
  • Control of Gastric Activity:
    • Cephalic phase
    • Gastric phase
    • Intestinal phase

Gastric Emptying

  • Contents of the stomach are discharged into the duodenum.
  • Primarily regulated by the autonomic nervous system (vagus nerve) and gastrointestinal hormones.
    • Pyloric sphincter regulates the emptying of gastric contents and prevents regurgitation of duodenal contents into the stomach; innervated by vagus (relaxation) and sympathetics (constriction).

Storage Function of Stomach

  • Empty stomach volume approximately 50ml.
  • Highly folded, allowing the folds to flatten out upon filling, with only slight changes in wall tension and intraluminal pressure.
  • Relaxation in the fundus is regulated by the vago-vagal reflex termed ‘receptive relaxation.’
  • Interruption of vagal innervation increases intragastric pressure.

Retropulsion of Large Particles

  • Liquids and small particles leave the stomach more rapidly than large particles (= sieving function).
  • Large particles are retained in the bulge of the terminal antrum and subject to grinding.

Control of Gastric Emptying

  • Cephalic:
    • Approach of food or food in the mouth.
  • Gastric:
    • Food in the stomach.
  • Intestinal:
    • Food in the duodenum, ileum, or colon.

Motility of the Stomach

  • Regulated by neural and hormonal factors.
  • Influences gastric emptying.
  • Increased Gastric Emptying:
    • Increased food volume, pressure, peristaltic waves, hypoglycaemia
  • Decreased Gastric Emptying:
    • Solids, fats, non-isotonic solution and hyperglycaemia
Neural and Hormonal Factors
  • Neural factors:
    • Increased Parasympathetic input (vagus nerve)
    • Decreased Sympathetic activity
  • Hormonal factors
    • Increased Gastrin, motilin
    • Decreased Secretin, cholecystokinin

Gastroparesis

  • A disorder characterized by a delay in gastric emptying in the absence of mechanical obstruction of the stomach; its pathogenesis is unclear.
  • Diabetes is the most frequently identified disease linked to gastroparesis.
  • Underdiagnosed due to similar presentation as GORD.
  • Symptoms: postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain.
  • Treatment/management: dietary changes (several small meals/day), pro-motility agents.

Intestinal Phase

  • Controlled through hormonal and paracrine mechanisms.
  • Activated by duodenal chemoreception.
  • Overview:
    • Low pH activates secretion of Secretin.
    • High fats/lipids increase secretion of CCK.
    • High levels of amino acids increase secretion of Gastrin.
    • High levels of carbohydrates increase secretion of GIP.
  • Motor Reflexes:
    • Ileogastric reflex: Chyme entering the ileum activates pressure receptors, which delays gastric emptying via nerves in plexi.

Functions of Motor Activity of the GI Tract

  • Segmental Contractions:
    • Non-propulsive movement of luminal contents.
    • Increased mixing/churning enhances digestion and absorption of dietary nutrients.
  • Peristaltic Contractions:
    • Propulsion/propagated movement in the caudal direction.
    • Elimination of nondigested, non-absorbed material.
  • Reservoir Formation:
    • Hollow organs (e.g., stomach and large intestine) hold the luminal content.
    • Tonic and phasic muscle are essential for these properties.

Small Intestine

  • 9 ft long, 1.5 in diameter, extending from the stomach to the colon.
  • Location for almost all digestion and absorption.

Small Intestine Motility in Fed (Absorptive) State

  • Segmentation:
    • Rings of circular muscle at intervals contract and then relax; adjacent rings then contract and relax.
    • Overall result: mixing mainly.
  • Peristalsis:
    • Overall result: propels chyme along.

Small Intestine Motility in Fasted (Non-Absorptive) State

  • Migrating Motor Complex (MMC):
    • Small bowel is relatively quiescent.
    • Synchronized, long-range, rhythmic changes in both electrical and motor activity.
    • Decreasing power of contractions towards caudal small intestines.

MMC Functions

  • Propels particles greater than 2 mm in diameter from the stomach into the duodenum.
  • Clears the small intestine of its residual content, including undigested food, desquamated cells, and intestinal and pancreatic biliary secretions.
  • Stops colonic bacteria from migrating into the terminal ileum.
  • Regulation:
    • ENS, humoral factors, and extrinsic innervations regulate MMCs and transition to the fed state.
    • Major determinant of the MMC pattern is the hormone motilin (22 amino acids).
    • Synthesized in the duodenal mucosa and released just before the initiation of phase 3 of the MMC cycle.

The Colon

  • 2.5 in diameter, last 4 ft of GIT.
  • Parts: Cecum, Ascending, Transverse, Descending, Sigmoid, Rectum, Anus

Functions of the Colon

  • Absorb large quantities of fluid and electrolytes, converting liquid content of ileocecal material to solid.
  • Absorb SCFA (product of carbohydrate fermentation).
  • Storage/reservoir function.
  • Regulated release of fecal material.
  • Provides an environment for beneficial bacteria to synthesize vitamins (K, B complex).
  • Secretes mucus and ions (K+K^+, Cl−Cl^-, HCO3−HCO_3^-).
  • Proximal colon: site of absorption and bacterial fermentation.
  • Distal colon: reservoir/storage function.

Colonic Rhythmic Phasic Contractions

  • Fluid contents of the ascending colon become semi-solid to solid in the sigmoid colon as water is absorbed.
    • Short-duration RPCs (2-3s):
      • No propagation
      • Amplitudes vary considerably
    • Long-duration RPCs (15-20s):
      • Propagate over short distances
      • Turn over and propel semi-solid to solid contents more effectively

Colonic Giant Migrating Contractions (GMCs)

  • Large-amplitude, lumen-occluding contractions that propagate very rapidly (approximately 1 cm/sec) in the distal direction over appreciable distances to produce mass movements.
  • Spontaneous GMCs occur randomly about 2 to 10 times a day in the proximal, middle, or descending segments of the colon.
  • Colonic GMCs occur in both the fasting and the postprandial state.

Colon Motility

  • Rhythmic Phasic Contractions
  • Segmentation (ascending & transverse colon)
  • Giant Migrating Contractions
  • Propulsion (transverse & descending colon)

Control of Motility in Colon

  • Autonomic Nervous Control
    • Sympathetic inhibit; parasympathetic increase motility
    • Vagal stimulation causes RPCs of the proximal part of the colon.
    • Stimulation of the pelvic nerves brings about expulsive movements (GMCs) of the distal colon and sustained contraction of some segments.

Regulation of Colon Motility

  • Feces in the cecum and distention of the colon trigger a stress reflex.
  • Activation of stress receptors signals to the myenteric nerve plexus, triggering haustral contractions.
  • Distention in the stomach causes G cells to secrete gastrin.
  • Gastrin triggers mass movement in the colon (gastrocolic reflex).
  • Distention of the pylorus leads to the secretion of acetylcholine, increasing motility in the colon.

Defecation Reflex - Long and Short Reflexes

  • Short Reflex:
    • Distension of the rectum stimulates stretch receptors.
    • Increased local peristalsis in the rectum moves feces toward the anus.
    • Contraction of the internal anal sphincter.
  • Long Reflex:
    • Coordinated by the sacral parasympathetic system.
    • Stimulation of parasympathetic motor neurons in the sacral spinal cord (S1-S2).
    • Increased peristalsis throughout the large intestine and stimulation of the myenteric plexus in the sigmoid colon and rectum.
    • Relaxation of the internal anal sphincter.
  • Voluntary Control:
    • Voluntary relaxation of the external anal sphincter can override the contraction directed by somatic motor neurons.
    • Involuntary contraction of the external anal sphincter occurs if the external sphincter is not voluntarily relaxed.

Defecation Reflex

  • Feces in the sigmoid colon and rectum initiate stretch reflexes.
  • Stretch receptors are activated, stimulating the parasympathetic nervous system.
  • Acetylcholine is released, causing contraction of the sigmoid colon and rectum.
  • The internal anal sphincter (involuntary smooth muscle) is activated by the PNS, leading to relaxation.
  • The external anal sphincter (voluntary smooth muscle) is innervated by the somatic nervous system.
  • The CNS sends a signal to the external anal sphincter to relax, allowing feces to be expelled.