Lecture 13: Enteric Nervous System 2 Flashcards
What is segmentation (mixing)?
local constrictions alternating with relaxations
depends on ENS
What is peristalsis (propulsion)?
strong constrictions that propagate anally along the intestine (or colon) preceded by a relaxation
depends on ENS
What is retropulsion?
peristalsis-like contractions that propagate orally
What is receptive relaxation?
relaxation of smooth muscle to prepare a segment for arrival of content
In which parts of the gastrointestinal tract does receptive relaxation occur?
stomach
small / large intestine
What are the three phases of the migrating motor complex that appear to propagate from either gastric antrum or the proximal duodenum to the ileo-caecal junction?
phase 1 - quiescence lasting about an hour at any one site
phase 2 - irregular contractions that build to…
phase 3 - strong, rhythmic contractions lasting 10-15 min
What does the migrating motor complex clear? How often does this occur?
debris and bacteria from small intestinal lumen
repeats every 90 - 120 min
What happens during feeding?
migrating motor complex stops clearing debris and bacteria from small intestinal lumen
What are intrinsic sensory neurons immunoreactive for and what do they contain?
calbindin
acetylcholine and substance P
What do excitatory motor neurons contain?
acetylcholine and substance P
What do inhibitory motor neurons contain?
nitric oxide synthase (NOS)
What are ascending interneurons immunoreactive for? What are descending interneurons immunoreactive for?
calretinin
NOS, somatostatin or 5-HT
(both are cholinergic)
What happens when intrinsic sensory neurons are activated at one site?
leads to simultaneous excitation of local excitatory motor neurons, local inhibitory motor neurons, ascending interneurons and descending interneurons
Where do excitatory motor neurons project? Where do inhibitory motor neurons project?
excitatory motor neurons project orally while inhibitory motor neurons project anally
What has modelling shown about segmentation and anal propagation?
that segmentation and anal propagation can come from a polarised circuit
What is the basic neural circuit involved in Bayliss and Starling’s law of intestine initiated by?
activation of intrinsic sensory neurons (ISNs) at one site
What can activation of ISNs stimulate?
local interneurons and motor neurons whose projections are polarised
Where do excitatory motor neurons project and what do they mediate? Where do inhibitory motor neurons project and what do they mediate?
excitatory motor neurons project orally to mediate contractions
inhibitory motor neurons project anally to mediate relaxations below the stimulation
What accounts for the propagation of the motor patterns as well as motor neurons?
interneurons extend the range of this polarisation by contacting other interneurons
How many classes of descending interneurons have been identified and where do they project?
three classes
project anally
What are some descending interneurons connected to and what does this allow?
some are connected to ascending interneurons and excitatory motor neurons and this allows anally directed constriction to follow relaxation, hence allowing propagation of motor patterns
What do immunofluorescence studies show?
that descending interneurons do make synapses with ascending interneurons (and excitatory motor neurons)
What will a local disruption in the circuit produce?
stationary contractions on either side of the disruption
How does chemical composition of the contents of the gut influence behaviour of the gut?
high nutrient contents favour segmentation over propulsion
How does volume of the contents of the gut influence behaviour of the gut?
large volumes trigger propulsive contractile patterns and receptive relaxation
How does viscosity and texture of the contents of the gut influence behaviour of the gut?
low viscosity contents move rapidly, but do not deform the mucosa
high viscosity contents move slowly and produce mechanical stimulation of mucosa
Which neurons influence behaviour of the gut?
chemoreceptive and mechanoreceptive intrinsic sensory neurons
What does the mucosal epithelium contain which may act as sense cells?
many types of endocrine cells
What are the characteristics of enteroendocrine cells?
> 10 different types, have apical membrane exposed to lumen, basal membrane exposed to lamina propria
Which type of cell do enteroendocrine cells make up a significant proportion?
enterochromaffin (EC) cells
What do enterochromaffin cells synthesise, store and release?
serotonin
What do both 5-HT enterochromaffin cells and PYY enteroendocrine cells have?
neuropods
What is the role of neuropods?
contact terminals of sensory neurons (afferents) and can get input from efferent enteric or extrinsic neurons
What do neuropods have proteins involved in?
proteins involved in transmitter release
also receptors for efferent transmitters
What does blocking of 5-HT uptake with an SSRI result in?
increases segmenting motor activity in the jejunum
What does blocking of 5-HT receptors in the mucosa result in?
reduces nutrient induced segmenting motor activity
What does releasing 5-HT from mucosa with cholera toxin rapidly increase?
propulsive motor activity
Blocking 5-HT uptake with an SSRI increases segmenting motor activity in the jejunum because…
serotonin can act on enteric neurons
What can amino acids excite via release of 5-HT and/or ATP?
local reflexes
What is mucosal 5-HT an example of?
a sensory mediator but it is not also a circulating hormone
Why is secretion of water and salt essential for digestion?
both digestion of macronutrients and the turbulent flow that brings nutrient molecules to the absorptive epithelium depend on there being adequate amounts of water in the lumen
What is the volume of water transported across the mucosa per day equivalent to?
the whole blood volume of an animal
How is secretion controlled by neurons?
Cl- ions are transported into lumen from enterocytes in mucosal crypts via CFTR channels in the apical membrane -> water and Na+ ions follow passively
What is secretion enhanced by?
vasodilation of mucosal and submucosal blood vessels
What are the two types of secretomotor neurons in the submucosal plexus and how do they work?
cholinergic: release ACh onto M3 muscarinic receptors to increase Cl- concentration gradient
non-cholinergic: release vasoactive intestinal peptide (VIP) to activate adenylyl cyclase which results in cAMP opening CFTR channels
What are both types of secretomotor neurons regulated by?
enteric circuits
______ is electroneutral, while ______ is electrogenic.
absorption, secretion
How is absorption controlled by enterocytes?
Na+ is transported from lumen into enterocytes (via NHE3 sodium hydrogen exchanger) at tips of villi (SI) and mucosal surface of colon
When does diarrhoea occur? What are the two circumstances in which this occurs?
when secretion of water into the lumen exceeds absorption of water from the lumen -> can be due to increased secretion in the duodenum and jejunum or increased transit speed through the ileum and colon
How does cholera toxin cause diarrhoea?
acts via neurons in duodenum and jejunum -> hypersecretion that swamps absorption in ileum and colon
What is the mechanism by which cholera toxin causes diarrhoea?
acts by activating adenylyl cyclase
releases 5-HT from EC cells -> leads to increased propulsive contractions as well as hypersecretion
Need ____ exposure to cholera toxin to produce ____, so ____ changes in affected neurons are relatively ____.
prolonged, hypersecretion, plastic, slow
