Term
| What is the basic structure of the autonomic ENS? |
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Definition
1) ENS neurons are neural crest cells that migrate into the developing gut with oral-to-anal progression.
2) ENS neurons form Myenteric (between smooth muscle layers) and Submucosal (gather sensory information and regulate secretions) plexuses
3) Interstitial cells of Cajal (ICC) are mesenchymal cells that act as gut smooth muscle pacemakers by generating slow wave calcium transients
4) Afferent sensory neurons are either Extrinsic primary afferents (EPAN) that have cell bodies in nodose ganglia and provide signals to vagal centers in medulla or Intrinsic (IPAN) cells that have bodies in submucosal plexus and synapse with ENS interneurons and ganglia in myenteric and submucosal plexus.
** mainly release 5-HT**
5) Efferent motor neurons are excitatory (ACh) and inhibitory (VIP and NO), and regulate smooth muscle contraction and glandular secretion. |
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Term
| What are the major neurotransmitter players in the ENS? |
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Definition
1) 5-HT is main afferent transmitter that senses mechanical changes, transmits information to the CNS (EPAN) and regulates presynaptic transmitter release from ENS interneurons.
2) ACh is main transmitter in ganglia and at post-synaptic excitatory motor neurons.
3) NO and VIP are transmitters of inhibitory motor neurons |
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Term
| What is the parasympathetic anatomy and regulation of the GI tract? |
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Definition
Relax, secrete, digest and move slowly.
- End organs bocked by atropine!
1) Afferent
- EPAN stimulate parasympathetic vagal centers (smooth muscle
- Parasympathetic stimulation leads to ACh release and binding to nAChR (ganglia) and mAChR (effectors)
2) Afferent
- CNS regulation is from dorsal vagal complex in medulla (DMN, NTS, area postrema, NA) and pelvic nerves from sacra; spinal chord
- Efferent vagal fibers synapse with motor neurons in ENS in esophagus, stomach, small intestine and colon, as well as the gallbladder and pancreas (CNS regulation is greater in upper tract)
- Efferent pelvic fibers synapse with ganglia on serosal surface of colon and the ENS in the wall of the large intestine. |
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Term
| What is the sympathetic anatomy and regulation of the GI tract? |
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Definition
Shut blood flow to skeletal muscle and reduce flow to viscera (there is no parasympathetic regulation of vessels).
1) Pre-ganglionic sympathetic neurons project from thoracic and upper lumbar segments of spinal cord, and release ACh onto pre-vertebral ganglia (celiac, superior mesenteric and inferior mesenteric)
2) Post-ganglionic sympathetic neurons release NE, which binds to alpha-adrenergic receptors on splanchnic vessels.
- Decreased blood flow leads to decreased secretions |
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Term
| How can CNS inputs serve to regulate GI motor function? |
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Definition
1) Vagal and spinal afferents (5-HT) respond to GI irritation and distension
2) CN IX senses pharyngeal activity and contributes to gag
3) Chemical trigger zone (area postrema) in dorsal motor complex and regulate emesis
**anti-nasusea drugs like Zofran inhibit 5-HT in CTZ and solitary tract**
4) CX VIII has M1 and H1 receptors creating potential for GI manifestations of motion sickness
**block with anti-muscurinic drugs like scopolamine, or anti-histamines like dramamine** |
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Term
| Why might you treat motion sickness with scopolamine and/or dramamine? |
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Definition
| Antagonize mAChR and H1 receptors in CN VIII to prevent GI manifestations. |
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Term
| Why might you Nasuea with Ondansetron (Zofran)? |
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Definition
| Inhibits 5-HT3 recepors in central trigger zone (area postrema) and nucleus solitarius, both of which are in the dorsal motor nucleus in the medulla. |
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Term
| What is the effect of opioid hetero-receptor stimulation on the GI tract? |
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Definition
1) Opioid u-type populate myenteric neurons in small intestine and block transmission of inhibitory contractile signals.
- Opioids have greater effect in duodenum relative to ileum due to more muscle and more slow waves to inhibit in the duodenum.
2) Opiates increase contractility, but decrease coordinated peristalsis or motility |
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Term
| How do excitatory motor neurons create smooth muscle contraction and secretion from mucosal glands? |
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Definition
1) Smooth muscle
- Project orally from ganglia and release ACh and substance P
- Bind mAChr in smooth muscle, leading to L-type calcium channel stimulation and AP generation on top of ICCC slow waves
**this is why L-Ca2+ inhibitors cause nausea and constipation!**
2) Secretion
- Secretomotor neurons release ACh onto mucosal secretory glands and epithelial cells, leading to calcium entry and secretion.
** Suppression of excitabiltiy (opioids) inhibits secretion to promote constipation** |
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Term
| How do inhibitory motor neurons generate inhibitory junctional potentials (IJP) and what is their function? |
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Definition
IJP suppresses contraction of smooth muscle in GI (decreased peristalsis)
1) Neurons project caudally from ganglia and release NO (opposed calcium-mediated contraction) and VIP onto circular muscle of stomach, intestine, gallbladder and sphincters.
2) Little innervation of small intestinal longitudinal smooth muscle to allow better receiving or opening of lumen in advance of food bolus. |
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Term
| Explain how smooth muscle contraction patterns are generated? |
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Definition
Slow waves created by ICCs.
1) Slow waves raise threshold of electrical activity in circular and longitudinal muscle layers at the same frequency, without neuronal input.
2) Contraction frequency cannot exceed the slow wave frequency, and frequency varies by location.
3/minute in antrum
11-12/minute in duodenum (decreases towards ileum)
2-13/minute in colon depending on segment.
3) Inhibitory neurons control number of APs generated from slow waves (stretch of contraction is a function of active inhibitory neurons) |
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Term
| What is Peristalsis and how is it regulated? |
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Definition
Stereotypic propulsive motor reflex during feeding/digestion (reversed during emesis in upper tract)
1) AP is generated by vagal stimulation in response to swallowing, distention or feedback from mucosal brushing
- APs in excitatory neurons spread orally to block inhibitory neurons and stimulate circular muscle contraction
- APs in inhibitory neurons spread caudally to relax circular muscle (receiving) producing physiological ileus. |
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Term
| Describe neuromuscular regulation of sphincters. |
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Definition
1) Tonically kept shut by low-level mAChR stimulation
- treat spastic sphincters with anti-muscarinics or Botox
2) Sphincters open in response to high level vagal activity and/or distention of esophageal wall stimulating inhibitory neuron NO release.
- Loss of NO release causes Achalasia (can't swallow) |
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Term
| What is the importance of the Migrating Motor Complex (MMC)? |
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Definition
Main intestinal motility pattern of the inter-digestive (unfed) state that is responsible for
- injection/propulsion of bile acid to clean gut
- sweeping indigestible debris during fasting
- keeping bacteria from small intestine.
Depends on intrinsic ENS networks and does not depend on vagal input
1) MMC occurs when digestion/absorption of nutrients are complete, starting as large amplitude 3/minute contractions in antrum through duodenum, small intestine to illeum.
2) 3 Phases reflect way of activity
- Phase 1 is physiological ileus (no contraction)
- Phase 2 is advancing front of irregular contractions
- Phase 3 is advancing front of regular contractions.
**Cycling continues until food is ingested |
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Term
| How do digestive motility patterns promote mixing in the fed state? |
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Definition
Driven by vagal input, terminating ENS-driven MMC pattern during un-fed state.
- Short peristaltic propulsion provides segmented movements to break down and digest chime |
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Term
| What are the unique colonic motility patterns for resorption and elimination? |
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Definition
1) Orthograde/retrograde mixing in transverse colon provides extraction and reclamation of water from intestinal contents.
2) Large propulsive contractions sweep through colon , transferring contents to rectum to promote urge to defecate. |
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