GI Motility

Question 1

Functional characteristics of Smooth muscle

Answer 1

Contraction is initiated by increased cytoplasmic calcium

SR (a specialized ER for calcium release) associates with PM at indentations known as cavaeoli

Contractile action-myosin filaments are obliquely arranged

Cytoskeleton filaments are anchored at dense body junctions

Cells are physically and electrically coupled at Gap Junctions

Question 2

Smooth muscle contraction - thick filament regulation
- process of SM contraction

Answer 2

The Ca2+ switch in a SM cell is an enzyme called myosin light chain kinase (MLCK)
- when intracellular calcium increases, Ca binds to calmodulin and the complex then activates MLCK
- MLCK posphorylates myosin light chain so it can bind to actin
- phosphate is then removed by myosin light chain phopshatase (MLCP)
- de-phosphorylated myosin can no longer bind actin and contraction is terminated

Question 3

How does intracellular calcium increase?

Answer 3

1) Depolarization of SM membrane activates voltage gated calcium channels at base of caveolae and Ca influx activates SR calcium release channel in adjacent SR membrane
- smooth muscle cell exhibits Calcium-induced calcium release

2) a second type of SR calcium release channel exists - IP3 receptor - does not respond to cytosolic calcium but does to IP3
- a wide variety of compounds can trigger production of IP3 at the sarcolemma that then diffuses through cytosol to activate IP3 receptor
- Ca then diffuses out of SR into cytosol to initiate contraction (called pharmaco-mechanical coupling because it occurs without any change in membrane potential)
- contraction is terminated as Ca release from SR is pumped back into SR or out of cell via Ca pumps

Question 4

Regulation of GI system motility

Answer 4

1) intrinsic electrical properties of smooth muscle cells
2) the enteric nervous system
3) the autonomic nervous system
4) other systems - brain, immune, hormones

Question 5

Intrinsic smooth muscle activity

Answer 5

Specialized smooth muscle cells in GI undergo spontaneous transient membrane depolarisations
- non-contractile pacemaker cells
- interstitial cells of Cajal
- depolarising potentials are termed slow waves

Slow waves propagate from pacemaker cells into adjacent smooth muscle cells through gap junctions - electrical flow between cells creating smooth muscle network

AP depends on the duration that the slow wave remains above threshold - greater number of APs = greater intracellular Ca = greater strength of contraction (tension)

Question 6

Smooth muscle slow contractions

Answer 6

The rise in calcium concentration in the mycoplasm is very short compared to skeletal and cardiac muscle
- the kinetics of contraction are equally slow and occur 15-20 seconds after the stimulus

Question 7

Enteric nervous system

Answer 7

• composed of two nerve plexuses (Submucosal and myenteric)
• 10^6 neurons in the ENS
• can operate entirely within the GI wall without external input - considered reflexive
• ENS functions via electrical communication and the release of NT between neurons

Question 8

Components of ENS

Answer 8

Sensory neurons - mechanoreceptors, chemoreceptors and osmoreceptors

Inter neurons - excitatory and inhibitory

Secretomotor cells which influence:
- smooth muscle
- epithelial cells that secrete or absorb fluid/electrolytes
- enteric endocrine cells

Question 9

Intrinsic reflex arc for motility

Answer 9

Mucosa senses mechanical, chemical or thermal changes that then synapse in submucosal plexus that sends projections to myenteric plexus that has inter neurons to motor neurons that synapse with circular muscle and longitudinal muscle

• responses can be either excitatory (contraction) or inhibitors (relaxation) of SMCs

Question 10

Autonomic nervous system effect on GI

Answer 10

1) influence ENS activity
2) directly affects smooth muscle and glands
3) alters GI hormone levels

• preganglionic sympathetic fibres synapse in prevertebral ganglia - postsynaptic fibres (NE) synapse in the ENS
• preganglionic parasympathetic fibres synapse with a postganglionic fibre (ACh) within the ENS

Question 11

Smooth muscle en passant innervation

Answer 11

Motor axons have multiple varicosities (swelling containing packets of neurotransmitter)

Release the NT in the vicinity of the SM

The NT diffuses to its targets

A method for a single nerve can cause multiple cells to contract

Question 12

Sympathetic vs parasympathetic in GI

Answer 12

Sympathetic results in decreased motility and decreased volume of secretions (occurs during a stress response)

Parasympathetic input increases motility and GI secretions (occurs during and immediately after following the ingestion of a meal)

Question 13

Parasympathetic nervous system input

Answer 13

Vagal and sacral nerves

Question 14

Swallowing

Answer 14

GI motility associated with the mouth and pharynx is sawllowing (C9, 10 and 11)
- the initiation is voluntary
- once initiated, it becomes reflexive and is coordinated by the swallowing centre in the medulla
- is divided into 3 phases:
1) oral phase
2) pharyngeal phase
3) esophageal phase

Question 15

Oral phase of swallowing

Answer 15

Pushing a food bolus toward the back of the oral cavity and up against the palate
- requires the tongue

Question 16

Pharyngeal phase of swallowing

Answer 16

Touch and pressure receptors in the pharyngeal palate are activated by the food bolus and information is sent to the medulla via the trigeminal nerve (CN 5) and initiates the reflexive component of swallowing

• contraction of the pharyngeal wall behind the bolus pushes food towards the esophagus and tongue positioning prevents bolus from travelling back into mouth
• uvula elevates to seal nasal passages
• vocal cords contract and epiglottis closes over the trachea preventing bolus from entering the trachea and bronchi

Question 17

Esophageal phase of swallowing

Answer 17

The swallowing center relaxes the pharyngoesophageal sphincter and then initiates primary peristaltic waves by interactive with ENS (takes 5-9 seconds to move from beginning to end of esophagus)

Gastroesophageal sphincter opens when peristaltic wave pushes bolus against this region
- reflexive relaxation mediated by the vagus nerve
- this sphincter then contracts again to prevent gastric reflux

Question 18

Secondary peristalsis

Answer 18

Reflexive and does not involve the swallowing centre
- occurs when luminal contents become lodged
- the distension of the GI wall activates stretch receptors that stimulate the ENS causing a strong peristaltic wave to dislodge the luminal contents

Question 19

Two mobility paradigms in the small intestine

Answer 19

Segmentation - ensures mixing during the processing of chyme

Migrating mobility complex - moves luminal contents along the small intestine in the period between meals

Question 20

Segmentation of small intestine

Answer 20

Occurs during a meal - alternating contractions and relaxations of adjacent sections of SI

Initiated by:
- distension of the lumen
- presence of the enterogastrone gastrin
- parasympathetic input (sympathetic input decreases segmentation)

• segmentation also helps move chyme towards the SI

Question 21

Migrating motility complex of SI

Answer 21

Following absorption of a meal, segmentation is replaced by migrating motility complex
- begins at duodenal-gastric junction
- consists of weak peristaltic contractions that travel a short distance
- a second wave begins slightly more dismally than the initiation site of the first wave and travels slightly further

2 hour travel time from stomach to Large intestine

Cycle repeats itself until the ingestion of another meal initiates segmentation again