3 - GI Tract Flashcards
Detail the route of food through the GI tract
Mouth Oral cavity Pharynx Oesophagus Stomach Small intestine Large intestine Rectum Anus
What is the pH of the stomach?
1-2 pH
What is the main digestive enzyme in the stomach?
Pepsin
What is the major epithelial cell of the GI tract?
Columnar epithelium
What non-anatomically relevant, but equally important layer, sits just above the epithelial layer?
Mucus layer
What are the 3 layers of muscle around the stomach?
Inner oblique
Middle circular
Outer longitudinal
What are the 4 layers of the stomach wall?
Mucosa
Submucosa
Muscularis externa
Serosa
In what layer are nerves, lymph vessels and blood vessels found in the stomach?
Submucosal layer.
How many layers of muscle are within the small intestine?
What are they called? And what is their general function?
2
Inner circular
Outer longitudinal
Peristaltic movement
What macroscopic feature is different between the inner surface of the stomach and the small intestine?
Stomach is relatively flat.
Small intestine is largely undulating from presence of villi
What is the purpose of villi?
In what condition do these villi disappear?
Increase SA.
Coeliac disease.
What is the pathophysiology to Coeliac disease?
Chronic gut inflammation. Worsened in response to gluten.
Results in flattening of villi and enlargement of crypts.
Why might coeliac patients become deficient in vitamins?
What vitamin in particular?
Small intestine is area of vitamin absorption.
B12 - water soluble.
How many nerve plexuses are there in the small intestine, what are their names, and where are they found?
Submucosal plexus (submucosal layer)
Myenteric plexus (between inner circular / outer longitudinal)
What does the epithelial surface of the large intestine look like?
Flat
How are the layers of muscle arranged differently in the large intestine, compared to that of the small intestine?
Large intestine still has both layers.
Outer longitudinal layer is arranged into bands known as teniae coli.
What product is largely absorbed in the large intestine?
Water
How many extrinsic nerve endings are there in the gut?
100,000
MASSIVE sensory input.
Through what pathway has the enteric nervous system been shown to modulate inflammation?
Cholinergic anti-inflammatory pathway.
The ENS forms part of the ______ ______ nervous system?
Autonomic peripheral
The ENS has both EXTRINSIC and INTRINSIC input. What does extrinsic input refer to?
Nerves from CNS that enter into gut and synapse with ENS.
What feature of the ENS is important in its clinical importance?
It can work INDEPENDENTLY to the CNS.
What are the 3 types of neurones?
Sensory
Motor
Interneurons
What is the function of sensory neurones?
Respond to mechanical, thermal, osmotic and chemical stimuli.
What is the function of motor neurones?
Control GI motility and secretion
What is the function of interneurones?
Connect sensory info into motor neurones.
What are the main neurotransmitters released from the sympathetic nervous system?
Epineprine
Norepinephrine
What is the overall effect of the sympathetic nervous system?
What effect does this have on the gut?
Fight / flight
I.e. downregulation of the gut
Where can sympathetic nerves be found in the layers of the GI tract?
In both
- Myenteric
- Submucosal
plexuses.
Where are sympathetic nerves found predominantly along the length of the GI tract?
What specific function are sympathetic nerves important for?
Large intestine.
Defecation response.
What is the main neurotransmitter that is part of the parasympathetic pathway?
Acetylcholine (ACh)
What is the ‘slogan’ for the parasympathetic pathway in the context of its function?
Rest and digest
What is the main nerve associated with the parasympathetic pathway on the GI tract?
Vagus nerve
What functions does the parasympathetic nervous system have in the context of the GI tract?
Satiety
Defecation
Pain / chemical / noxious stimuli
What are the supportive cells of the intrinsic nerves (ENS) within the gut?
Glial cells
What 3 impacts occurs in light of deletion of enteric glial cells?
Severe gut inflammation
Increased mucosal permeability
Haemorrhagic necrosis.
Where do the glial cells sit in relation to the GI tract layers?
How does this lead to leakage occurring?
Sit in close proximity to the epithelium.
Issues will result in increased permeability.
In mice, how often are enteric nerves replaced completely?
What drives this process?
Every few weeks.
Driven by a network of neural precursors that regenerate about 5% of enteric nerves per day.
What 3 components are important in the processes of peristalsis and defecation?
1) Neurones
2) Smooth muscle cells
3) Interstitial cells of Cajal
What is the function of interstitial cells of Cajal?
Gut pacemaker cells
In the context of sphincters, neuronal input is triggered by which sensory neurones?
What source of sensory info is here?
Stretch-sensitive intrinsic mechanosensory neurones.
Extrinsic input.
What two reflexes are involved in the process of defecation?
1) Short reflex
2) Long reflex
What is the overall function of the long-reflex?
What is the general process?
Stimulate mass movements that push faeces towards rectum from descending / sigmoid colon.
1) Stretch stimuli
2) Stimulates parasympathetic arm of CNS in sacral spinal cord.
3) Motor neurones incited to increase peristalsis throughout large intestine.
What is the other function of the short reflex?
How does it work?
Local peristalsis for defecation.
1) Stretch
2) Stimulates myenteric plexus in sigmoid colon and rectum
3) Increased local peristalsis
What condition is Hirschsprung’s Disease?
Failure of GI peristalsis (extreme form) as a result of a deficiency / lack of ENS in terminal regions of the large intestine.
How does Hirschsprung’s disease usually present?
What % present in first 6 weeks? In first 5 years?
Failure of new-born to pass MECONIUM.
6 weeks = 75%
< 5 years = 90%
Hirschsprung’s disease is the most common cause of what?
Neonatal colonic obstruction.
Meconium usually passes within __-__ h?
24-48
What is Hirschsprung’s disease also known as?
Intestinal aganglionosis
What area of the large intestine does Hirschsprung’s disease most commonly present? What %?
Rectosigmoid colon
80%
What percentage of Hirshsprung Disease patients are affected up to the:
- Proximal sigmoid colon?
- Entire large intestine?
Proximal sigmoid colon = 15%
Entire large intestine = 5%
What clinical features occurs in Hirschsprung’s disease?
Megacolon
Abdominal distension
Absence of bowel movements.
Proceeds to vomiting.
How is Hirschsprung’s disease treated?
Surgically.
Name 5 examples of neurotransmitters that play a role within the gut.
Ach NAdr Nitric oxide Vasoactive intestinal peptide (VIP) Serotonin
What main functions does ACh have within the gut?
Excitatory
SM contraction
Increases intestinal secretion
Induces release of enteric hormones
Anti-inflammatory
What neurotransmitter opposes the actions of ACh?
Noradrenaline
What type of neurones is Nitric oxide the primary transmitter of?
Enteric inhibitory motor neurones to muscle.
What is the function of neurotransmitter: Vasoactive Intestinal Peptide (VIP) within the gut?
Primary inhibitory neurotransmitter for non-cholinergic secretomotor neurones.
What is the function of the neurotransmitter serotonin, within the gut?
Essential for proper ENS development.
What % of 5-HT is found within the ENS?
95%
What is the function of CCK?
Satiety hormone
Controlling appetite.
What is the main neurotransmitter in the vomiting reflex?
5-HT
What two areas within the brain are responsible for coordinating the vomiting reflex?
CTZ = chemoreceptor trigger zone
NTS = nucleus tractus solitarius
Where is the chemoreceptor trigger zone within the brain stem?
Area postrema
What is the function of ghrelin?
Provides hunger sensation.
What’s the general mechanism through which ghrelin functions?
Empty GI tract
Ghrelin released
Co-ordinates CNS response
Stimulates intake of food
What does IPANs stand for?
Intrinsic
Primary
Afferent
Neurones
In the ENS’ role of being anti-inflammatory, what two pathways are essential?
Parasympathetic:
- Cholinergic anti-inflammatory pathway
Sympathetic:
- Beta-adrenergic mediated pathway
What are the 5 normal functions of the ENS in maintaining gut homeostasis?
1) Secretion
2) Cytoprotective function
3) Regulating epithelial barrier function
4) Crypt cell proliferation
5) Epithelial cell proliferation
What cells are involved in secretory functions of the ENS?
Mast cells (histamine)
Glial cells
Goblet cells
What cells are responsible for facilitating the cytoprotective function?
Subepithelial enteric glia
What plexus acts as a modulator for crypt cell proliferation?
Myenteric plexus
Local activation of which gene is involved in epithelial cell proliferation?
TRPV1
Both of the anti-inflammatory pathways are controlled by which immune cell?
What does it secrete?
Macrophages
Secretes TNF-alpha.
Macrophages are located along which structure?
Nerves
Through what nerve does the cholinergic anti-inflammatory pathway work through?
Vagus nerve
What is the mechanism / pathway of the cholinergic anti-inflammatory journey?
1) Stimuli (pathogen, iscahemia, injury, cytokines)
2) Afferent vagus nerve
3) Efferent vagus nerve
4) Acts of organs (e.g. heart) but also on MACROPHAGES.
5) Binds to alpha-7 subunit on ACh-receptor.
6) Inhibits cytokine release.
How does the Beta-adrenergic anti-inflammatory pathway manifest?
Sympathetic stimulation produces norepinephrine. Binds to beta-adrenergic receptors.
= down-regulates TNF-alpha.
Give 5 examples of neuropeptides
Substance P Neuropeptide Y Somatostatin Vasoactive Intestinal Peptide Serotonin Somatostatin
What was it first noticed that IBD patients have REDUCED pan-enteric AUTONOMIC innervation?
Early 1990s
What were the findings from Komegae et al,. 2018?
specific nerve in vagal nerve stimulation
Removing the splanchnic nerve in rodents resulting in a COMPLETE removal of efficacy in vagal nerve stimulation for reducing GI inflammation.
What pathway is involved in the vagal-splenic pathway?
Cholinergic anti-inflammatory pathway
What is the proposed mechanism through which stimulating the splenic nerve results in anti-inflammatory effects?
.Splenic nerve stimulated .NE release .Acts on ChAT (choline acetyl-transferase enzyme) .ACH release alpha7-nicotinic-receptor on macrophage .Suppresses TNF-alpha secretion
How does SNS deficiency further contribute to unfavourable gut environment in IBD?
SNS also responsible for modulation of vessel constriction. Local inflammation with inadequate blood flow results in more issues.
What are the 4 ways in which the vagus nerve is involved in anti-inflammatory GI pathways?
1) HPA axis (corticosteroids)
2) Cholinergic anti-inflammatory pathway (alpha-7-nicotinic-ACh-receptor –> TNF-alpha)
3) Sympathetic anti-inflammatory pathway
4) Vagal-splenic pathway (NE –> B2 adrenergic on splenic lymphocytes –> ACh release –> Inhibits TNF-alpha from splenic macrophages)
Vagotomy studies in rodents have shown what 3 outcomes in the context of IBD?
1) Increased disease activity index
2) Greater histological disruption
3) Increased cytokine release
