AS Lecture 14 - Regulation of function: Enteric NS and gut hormones Flashcards
What are the 3 types of regulatory signal systems?
Nervous stimulation, paracrine and endocrine
What is nervous stimulation?
Neurotransmitters released from neurones innervate target cells.
What is paracrine?
Hormones released by cells in the vicinity of the target cell and reach target cell by diffusion
What is endocrine?
Hormones produced by endocrine cells, released into the blood where they reach their targets via the circulation.
What does the enteric (intrinsic) nervous system consist of?
Rich plexus of ganglia interconnected by tracts of fine, unmyelinated nerve fibres
What does the enteric NS do?
Integrates the motor and secretory activities of the GI system - can function independently of central control
Name 4 reasons as to what would cause enteric neural dysfunction/degeneration
Inflammation (ulcerative colitis/Crohn’s) Post-operative injury IBS Ageing (constipation)
What does the enteric nervous system regulate?
Motility, Blood flow, water and electrolyte transport, secretion and absorption
What are the 3 types of neurons?
Sensory, motor and interneurons - most are multipolar
What does a sensory neuron do?
Respond to mechanical, thermal, osmotic and chemical stimuli
What does a motor neuron do?
Axons terminate on smooth muscle cells of the circular or longitudinal layers, secretory cells of the gastrointestinal tract, or gastrointestinal blood vessels
What do interneurons do?
Neurons between neurons integrate the sensory input and effector output.
Fill in the blanks of the organisation of the plexi in the GIT
Where is the myenteric plexus located and what is its function?
Located between circular and longitudinal smooth muscle layers - controls activity of muscularis externa -> gut motor function
Where is the submucosal plexus located and what does it do?
Located in between submucosa and muscularis layer - senses environment in lumen such as blood flow, epithelial and endocrine cell function
What are some minor plexuses and what do they supply?
Deep muscular plexus (inside muscular plexus) and the ganglia supplying the biliary system and pancreas
What is the location of the cell bodies of the preganglionic, postganglionic neurones of the sympathetic NS?
Preganglionic neurons in the thoracic and lumbar spinal cord Postganglionic neurons in the pre/paravertebral ganglia
What do the thoracic and lumbar splanchnic nerves carry?
Thoracic: inntervation to fore and midgut Lumbar: sympathetic innervation to the remainder of the gut
What neurotransmitter is used in the lumbar and thoracic splanchnic nerves (sympathetic NS)?
Norepinephrine
What happens when sympathetic nerves are activated?
Usually inhibit the activities of the GI system
Where are the cell bodies of the pre/postganglionic neurons in the parasympathetic NS located?
Pre: brainstem and sacral spinal cord Post: close to target organs Pre synapse on ganglia close to gut wall/directly with enteric plexi
What nerve branches to supply most of the GIT down to transverse colon?
Vagus nerve
How is the transverse colon to the anus supplied with parasympathetic innervation?
Receive parasympathetic fibres from the pelvic nerves
What neurotransmitter is used in the parasympathetic NS?
Acetyl Choline
What does excitation of parasympathetic NS cause in the GIT?
Stimulates activities of GI
How is the autonomic nervous system divided to include the enteric nervous system?
What do the majority of sympathetic fibres not directly innervate?
Structures in GIT, instead they terminate on neurons in the intramural plexuses APART from vasoconstrictor sympathetic fibres directly innervate the blood vessels of the GIT (coeliac and sup/inf mesenteric)
What does the CNS control in the GI system and what feeds back to the CNS for regulation?
What is the GIT innervated by?
Intrinsic innervation: neurons of enteric nervous system Extrinsic innervation: afferents (pain/nausea/fullness), efferents (coordination - symp/parasymp NS) COMPLEXITY allows fine control of the gut
How does the parasympathetic NS innervate the gut?
Via long preganglionic neurones (mostly vagus nerve) and short preganglionic neurones to promote gut motility, secretion and digestion
How does the sympathetic NS innervate the gut?
Via short preganglionic and long postganglionic fibres to inhibit gut motility and secretion, and cause constriction of blood vessels and contraction of sphincters
What is the function of the GI endocrine system?
Produced by endocrine cells in the mucosa/submucosa of the stomach, intestine and pancreas - can act as paracrine or neurocrine factors
What are the different gut hormones and where are they secreted from?
What are the hormones that are secreted from the stomach?
Gastrin, ghrelin, somatostatin and histamine
What are the hormones that are secreted from the duodenum?
Secretin, CCK, somatostatin
What are the hormones that are secreted from the pancreas?
Insulin, glucagon, somatostatin, pancreatic polypeptide
What are the hormones that are secreted from the jejunum/ileum?
PYY, GIP, GLP-1, GLP-2, oxyntomodulin, neurotensis and somatostatin
What are the hormones that are secreted from the ascending colon?
PYY, GLP-1, oxyntomodulin, neurotensin, somatostatin
How do enteroendocrine cells sense nutrients?
They are set back behind mitotic figures as it wants to be sat in front of the blood vessel, with a ‘foot process’ which extends to the lumen of the GIT, so it can know what is happening in the gut lumen - secretory granules are present in the basal part of the cell
What are the 2 regulatory functions of the Gastrointestinal endocrine system?
Regulation of mechanical processes of digestion (SM of GIT) Regulation of chemical and enzymatic processes of digestion (secretory cells loacated in wall of GIT, pancreas and liver)
What are 2 non-regulatory functions of the gastrointestinal system?
Control of post absorptive processes involved in assimilation of digested food and CNS feedback regulating intake. Effects on growth and development of GIT
What is an example of a paracrine action in the GIT?
Histamine released from stomach walls acts as key physiological stimulus to HCl secretion by parietal cells Somatostatin from stomach can inhibit acid secretion by paracrine mechanisms
What is the function of Gastrin and where is it synthesised?
Synthesised in gastric antrum and upper small intestine Gastrin stimulates gastric acid secretion.
What is gastrin release stimulated and inhibited by?
Release stimulated by: Amino acids and peptides in the lumen of the stomach, Gastric distension, Vagus nerve directly. Release inhibited when pH of stomach falls below 3
Where is somatostatin synthesised and why is it released?
Synthesised in endocrine D cells of gastric and duodenal mucosa, pancreas Released in response to mixed meal (but carefully regulated by other hormones and depending on situation)
What is the function of somatostatin?
Inhibits: gastric secretion, motility, intestinal and pancreatic secretions, release of gut hormones, intestinal nutrient and electrolyte transport, growth and proliferation
What are somatostatin analogues used to treat?
Treat neuroendocrine tumours (difficult to pick up as they produce non specific effects, so have low 5yr survival rate)
What is secretin and what does it do?
Secreted by S cells in upper duodenum and jejunum - major stimulus is presence of acid in the duodenum Stimulates pancreatic bicarbonate secretion
What happens if there are high concentrations of secretin?
Inhibition of gastric acid and gastric emptying
What is CCK and what does it do?
Secreted by cells most densely located in small intestine Stimulates pancreatic enzyme release, delays gastric emptying, stimulates gall bladder contraction and decreases food intake and meal size
What is the release of CCK stimulated by?
Stimulated by fat and peptides in the upper small intestine - independent from vagus
What is gastric inhibitory peptide/ glucose-dependent insulinotropic peptide and what does it do?
Secreted by mucosal K cells (mainly in duodenum/jejunum) Stimulates insulin secretion
What causes the release of GIP?
Ingestion of a mixed meal - receptor antagonists reduce postprandial insulin release
What is PYY and where is it found?
Peptide YY is found in cells throughout the mucosa of the terminal ileum, colon and rectum Released from L cells post prandially
What is the function of PYY?
Reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion Inhibits intestinal fluid and electrolyte secretion PY3-36 inhibits food intake
Why are both the sympathetic and ENS connected to blood vessels in the GIT?
When sympathetic is activated, usually GIT having a blood supply is not a priority. This means that sympathetic can have a constrictor effect on the vessels
How are enteroendocrine cells specialised for nutrient sensing?
Receptors for all macronutrients and they respond respectively, with cells releasing certain hormones
What is octreotide?
It is a somatostatin analogue used to treat gut cancers
Why don’t we give somatostatin directly to people instead of nucleoside analogues to treat?
Protein hormones have really short half lives, so can be easily controlled - around 1-10 minutes BUT drugs need to have longer half lives as they don’t want to be infusing many times, also may interfere with negative feedback. Peptide binding sites for hormones are quite large, so it is difficult to find a different version. Also, can be specific to certain receptors, so can have different effects, without causing certain side effects
