by mtoom


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What is the purpose of gastrointestinal motility (2)?
  • Facilitates movement of food/material from oral cavity/pharynx to rectum/anus
  • Also facilitates mixing of contents in defined regions of GI tract 
How much of gastrointestinal motility is carried out by smooth muscle cells?
All, except for:
  • Pharynx
  • Upper 1/3 of esophagus
  • Upper esophageal sphincter
  • External anal sphincter 
Review of basic characteristics of smooth muscle cells (5)
  • Spindle-shaped
  • Contraction initiated by cytoplasmic calcium
  • Sarcoplasmic reticulum (SR)
  • Contractile filaments are obliquely arranged and anchored at cell-ECM junctions
  • Cells are electrically coupled at gap junctions
How does the initial depolarization in smooth muscle cells of the GI tract occur?
Ca2+ ions move from the Interstitial Cells of Cajal (ICC) into the cytoplasm of smooth muscle cells via gap junctions
What initiates slow waves?
ICC cells initiate slow waves
  • Slow waves are more than 1 second in duration
What do ICC cells form?
An interconnected network that is linked to smooth muscle cells (SMCs).
What is the function of ICC cells in the GI tract?
They are "pacemakers" for smooth muscle cells.

The ICC cells cause the periodic release of Ca2+ from intracellular stores, which initiates "slow waves"of depolarization.

The Ca2+ from ICCs is passed through communicating gap junctions to initiate slow waves in SMCs.
What controls the duration and amplitude of slow waves?
  • Neurotransmitters/agonists released by enteric motor neurons, located in the wall of the GI tract
What is the enteric nervous system?
  • Nervous system of the gut
  • Can function autonomously
  • Modulated by autonomic nervous system (ANS) and endocrine, paracrine factors
  • Responds to inflammation, and physical/chemical changes in gut 
In what 2 plexuses are enteric neurons clustered? Where are they located?
  • Myenteric 'Auerbachs' plexus

    Inner and longitudinal layers of the Muscularis externa
    (from esophagus to rectum)
     
  • Submucosal 'Meissners' plexus

    CT of the Submucosa
    (only small/large intestine
In what fashion do enteric neurons release neurotransmitters?
'En passage'
  • Neurotransmitters are released from varicosities (located close to ICC and SMC cells, but do not form true synapses)

Individual ICCs and SMCs can be activated, en passage
What happens when the plateau phase of membrane depolarization remains above threshold?

How is the membrane repolarized?
If plateau phase is above threshold, rapid depolarization spikes occur which increase the force and duration of SMC contraction
  • Voltage-dependent Ca2+ channels  open/close rapidly to generate spikes of depolarization (and subsequently contractions)
     
  • Repolarization: Then, Ca2+ levels trigger Ca2+-dependent K+ channels to open and move K+ out of the cell to repolarize it
What neurotransmitter increases amplitude of slow wave?

What neurotransmitter decreses amplitude of slow wave?
Acetylcholine: Increase amplitude

Vasoactive Intestinal Protein (VIP): Decrease amplitude
Where does the myenteric plexus run?
Esophagus to rectum
Where does the submucosal plexus run?
Small and large intestine only
Do the myenteric and submucosal plexuses contain cell bodies, synapses and ganglia?
Yes
Is the enteric nervous system (ENS) an intrinsic system?
Yes
What is an "intrinsic system"?
It can function completely independently from the brain and spinal cord
  • ENS neurons include what 3 functional types?
  • What do they form?

Functions:
  • Sensory
  • Motor
  • Interneuron (that connect plexuses)
Form functional 'enteric reflex arcs'
  • Reflex arcs can be both excitatory or inhibitory
Describe 4 functions of Myenteric plexus and the major excitatory/inhibitory neurotransmitters

Functions:
  • GI motility (muscularis externa)
  • Sphincter contraction
  • Glandular/exocrine, endocrine/paracrine secretions
GI motility excitatory neurotransmitters:
  • Ach, Substance P, Serotonin
GI motility inhibitory neurotransmitters:
  • VIP, Nitric oxide, Purines
Describe functions of Submucosal plexus and the major excitatory/inhibitory neurotransmitters?
Functions:
  • Contraction of muscularis mucosa muscle, vascular muscle
  • Regulate glandular/exocrine and endocrine/paracrine secretions by epithelial cells
Major excitatory neurotransmitter:
  • Ach
Major inhibitory neurotransmitter:
  • VIP
Are individual ENS neurons restricted to one type of neurotransmitter/factor?
No, ENS neurons can produce more than one neurotransmitter/factor.
What 3 "external" factors can influence the Enteric Nervous System (ENS)?
  • Autonomic nervous system
    e.g. vagus, S2,3,4 
  • Higher CNS brain centers
    e.g. hormonal factors that can stimulate immune cells
  • Immune system
    e.g. local paracrine stimulation 
In general, parasympathetic motor nerve stimulation generally does what in the GI?
  • Stimulates GI motility and secretion
  • Relaxes most sphincters
What are the 3 general types of GI tract smooth muscle contraction?
  • Peristalsis, propulsive contractions
     
  • Mixing, non-propulsive contractions
     
  • Tonic contraction
Describe peristalsis/propulsive contractions
  • Occurs in esophagus, stomach, small/large intestines
  • Involves contraction of both layers of muscularis externa
  • Contractions occlude lumen to move contents in anal direction
  • Relaxation occurs ahead of contractile wave
  • Facilitated by the intrinsic peristaltic reflex
Describe mixing/non-propulsive contractions (2 types)
Segmental muscle contraction (non-oscillatory)
  • Small/large intestines
  • Ring-like, simultaneous circular contraction at closely adjacent points
  • Chyme displaced in both directions
Segmental muscle contraction (oscillatory)
  • Small/large intestines
  • Contraction of longitudinal muscle over restricted distances, causes mucosa to slide over intestinal contents to increase efficiency of mixing
Describe tonic contraction
  • Prolonged contraction of a thickened circular layer of muscularis externa at defined positions along GI tract
  • Functions to structurally/functionally separate GI compartments
  • Prevents reflex; halts movement of chyme
Give 4 examples where Tonic Contraction occurs
  • gastro-estophageal junction
  • gastro-duodenal junction
  • ileocecal sphincter
  • between rectum and anal canal (internal anal sphincter)
Describe the Peristaltic Reflex

1. Mechanical/chemical stimulation by food bolus causes epithelial 'enteroendocrine' cells to release 5HT/serotonin, which acts in a paracrine fashion

2. Sensory neurons synapse with interneurons causing contraction of muscular externa behind the bolus

3. Sensory neurons synapse with interneurons causing relaxation of muscular externa after the bolus

4. Bolus is pushed in the anal direction 
1. What peptide hormone is secreted between meals?

2. What does this hormone do?
1. Motilin

2. Facilitates slow propulsive waves of GI motility
How can you assess esophageal motility?
By using monitoring the intraluminal esophageal pressure using a pressure transducer
Describe the pharynx, UES, esophagus, LES during swallowing.
1. Swallowing center in the medulla initiates pharyngeal contraction (skeletal muscle)

2. Distension (bolus) initiates reflex relaxation of UES, which promptly contracts close after bolus passes

3. Primary peristalsis moves bolus through esophagus

4. Distension (bolus) initiates reflex relaxation of LES, allowing bolus to pass
Describe difference between primary and secondary peristalsis
Primary: Extrinsically-initiated (i.e. by swallowing), typically moves bolus from UES to stomach

Secondary:  Reflex-initiated, can occur in absence of swallowing if food gets stuck
Normally, the LES has what type of tone?

What causes loss of reflex relaxation of the LES? What does this cause?
Normally, the LES has chronic tone.

Loss of relex relaxation of LES is often caused by inhibitory neuron defects

This can result in inefficient passage of the food bolus into the stomach (known as Achlasia).
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