Lecture 25 - GI Tract Regulation Flashcards
What is the distance ENS regulation can occur over in the GI tract?
Very short (cm)
What is the distance CNS regulation can occur over in the GI tract?
Long distances
(Via the autonomic nervous system)
What distance can hormonal regulation occur over in the GI tract?
Long distances
What are the ENS regulation action sites in the GI tract?
Very local, generally only effectors within one organ?
What are the CNS regulation action sites in the GI tract?
Coordinates fast and complex actions involving several sites of action (e.g. swallowing)
What are the hormonal action sites in the GI tract?
Each hormone regulates more than one cell type in more than one organ
What is the speed and duration of ENS response in the GI tract?
Fast and short duration
What is the speed and duration of CNS response in the GI tract?
Fast and short duration
What is the speed and duration of hormonal response in the GI tract?
Slow and sustained
What are the stimuli for ENS response in the GI tract?
Intrinsic - chemo/ osmo /mechano receptors within the GI tract
What are the stimuli for CNS response in the GI tract?
Extrinsic - Special senses, emotional responses.
Long reflex pathway - receptors within the GI tract
What are the stimuli for hormonal response in the GI tract?
Stimuli include both the GI tract luminal content and external / extrinsic stimuli
Can the ENS act independently of other systems in the GI tract?
Yes – ENS is sometimes called the brain of the gut
Can the CNS act independently of other systems in the GI tract?
No, only ENS directly innervates GI tract structures so must act via the ENS
Can hormones act independently of other systems in the GI tract?
Yes – some hormones released from the GI tract in response to GI tract luminal conditions act on the GI tract.
What are the ENS control signals/signal molecules in the GI tract?
Neural / action potentials
Neurotransmitters:
- Ach - stimulates
- NOS- inhibits
What are the CNS control signals/signal molecules in the GI tract?
Neural / AP’s
Neurotransmitters:
Parasympathetic: Ach - stimulates
Sympathetic: adrenaline - inhibits
What is the hormonal signalling pathway in GI tract?
Enteroendocrine cells
-> Peptide hormones
-> extracellular receptors.
Endocrine (Blood) and paracrine (diffusion)
What is the advantage of ENS regulation in the GI tract?
Fast local responses to conditions within a region of the GI tract
What is the advantage of CNS regulation in the GI tract?
Fast coordination of complex movements of short duration over long distances
What is the advantage of hormonal regulation in the GI tract?
Slow but sustained coordinated response over long distances / several organs of the GI tract
What does motility/motility pattern refer to?
Any pattern of contraction or relaxation of GI tract smooth muscle for a specific function.
What can motility patterns be?
- Simple
- Combination of two or more simpler patterns
- Complex series of events
- Relaxation
What motility patterns specifically move or propel GI contents along the tract?
Movement or Propulsion
What are the two types of contraction in the GI tract?
Phasic
Tonic
Where do phasic contractions occur in GI tract?
Esophagus, gastric antrum (stomach), small intestine
Where do tonic contractions occur in GI tract?
Lower esophageal sphincter, oral (near mouth) stomach, ileocecal and internal anal sphincters
How long are phasic contractions?
Several seconds
How long are tonic contractions?
Minutes-hours
What are the two main stages of motility patterns in the GI tract?
Fasting and fed
What is the function of fasting motility patterns?
- Clearing undigested material & secretions
- Regulating intestinal microflora
What is the function of fed motility patterns?
- Storage
- Propulsion and Movement at a controlled rate
- Mixing (and exposure to absorptive surfaces)
In what stage does MMC occur?
Fasting
What is the MMC?
Migrating Motor Complex
When does MMC start?
Starts 4-5 hours post meal absorption
What is the duration of MMC?
Duration – 2 hours from the stomach to the end of the large intestine
What are the 3 phases of the MMC?
(1) intense
(2) inactive
(3) intermittent
Where is the MMC coordinated?
Coordinated in stomach then small intestine
What is the function of the MMC?
Clears undigested material & secretions
Regulates intestinal microflora
Epithelial cell turnover
What is the regulation of the MMC?
Hormonal - Motilin released by intestinal m-cells
Neuronal - Motilin stimulates both the enteric and autonomic NS
What does storage involve in the GI tract?
Relaxation of smooth muscle allows the volume of luminal contents to increase without change in pressure
Where does storage occur in the GI tract?
Occurs in the stomach and the colon
What is receptive relaxation in the stomach?
Swallowing triggers reduced muscle tone as food is moved down the esophagus.
Allows food to enter the stomach without a change in pressure in the stomach
- Prevents gastric reflux in the stomach
What is the accommodation in the stomach?
Progressive relaxation in response to a volume change
Where does propulsion occur?
Occurs in the oesophagus, stomach, small intestine and large intestine
What are the steps of propulsion in the GI tract?
1) Arrival of bolus
2) Ascending circular muscle contraction behind bolus. Descending circular muscle relaxation ahead of bolus.
3)Longitudinal muscle shortening (contraction)
What is segmentation?
Circular muscle contraction in alternating segments.
Mixing function.
Where does segmentation occur?
Small intestine
Describe the GI tract smooth muscle
Single unit or unitary smooth muscle
Act as a syncytium (cells contract together)
Extensive intercellular communication - Gap junctions (electrical)
Cells physically connected - Adherens junctions
Arranged in layers with a neural plexus between
What is the arrangement of intestinal smooth muscle?
Cells are 5 – 20 µM diameter and ~ 500 µM long
Individual muscles interact with ~10 surrounding cells
- Gap junctions and Adherens junctions
Contain actin and myosin filaments
- irregular arrangement (not striated as in SKM)
Describe the MP of intestinal smooth muscle
The membrane potential of intestinal smooth muscle is not stable - fluctuates cyclically
Varies between -40 and -80 mV
Fluctuates in a pattern of Slow Waves or Basic Electrical Rhythm
- Generated by Interstitial Cells of Cajal
What do the Interstitial cells of Cajal (ICC) do?
Generate slow waves
Function as pacemakers
Rhythmic changes in:
- Activity of Na+/K+-ATPase
- Membrane K+ conductance
Where are the Interstitial cells of Cajal (ICC) located?
Stomach and small intestine
- In smooth muscle layer close to myenteric plexus
Colon
- Boundary of muscle layer and submucosal layer
What is the arrangement of Interstitial cells of Cajal (ICC)?
Send multiple branching processes to surrounding smooth muscle cells
Electrically linked to other ICC & muscle cells by gap junctions
What determines frequency of contraction in GI tract?
Slow waves ALWAYS determine the frequency of contraction
Frequency of slow waves is a property of the ICC in each region
What is the frequency of contraction in different areas of the GI tract?
- Faster in the proximal regions of the GI tract (digestion)
- Duodenum 12 – 20 per minute
- Slower in the distal regions of the GI tract (absorption)
- Colon 6-8 per minute
What determines the force of contraction in the GI tract?
Action potentials
Small / no contractions occur in absence of action potentials
Greater the number of action potentials the greater the force of contraction
What is mechanism 1 of contraction in GI tract smooth muscle?
AP and membrane depolarisation
Opening of voltage gated calcium channels
Increased cytosolic Ca2+
Ca2+ binds to calmodulin
Ca2+ /calmodulin complex activates myosin light chain (MLCK)
MLCK uses ATP to phosphorylate myosin
Actin and myosin interact and cross bridge cycles produce tension
What is mechanism 2 of contraction in GI tract smooth muscle?
Pharmomechanical contraction.
Hormones & neurotransmitters bind to a receptor to induce Ca2+ release.
Gαq - Signalling pathway activated
- Receptor activation of phospholipase C
- Production of IP3
- IP3 induces release of Ca2+ from sarcoplasmic reticulum
What is the down-regulation of smooth muscle contractions in the GI tract?
- Hyperpolarisation of smooth muscle cell membrane (or decrease Ca2+)
- Increased activity of Myosin Light Chain Phosphatase
- Inhibition of excitatory ENS neurotransmission
How does increased activity of Myosin Light Chain Phosphatase down-regulate GIT smooth muscle contraction?
Dephosphorylates myosin so reduced force of contraction – Nitric Oxide inhibitory neurotransmitter
