8. Control of Function Flashcards
Describe the enteric nervous system?
• Plexuses of ganglia
- dense local network of nerves/supporting cells
- nerve and glial cells
• Can produce a coordinated response to specific stimuli independent of CNS
What can cause a dysfunction in the enteric nervous system?
- Inflammation
- Irritable bowel syndrome
- Ageing
What is the myenteric plexus?
- aka Auerbach’s plexus
- Between circular & longitudinal smooth muscle
- Contains efferent innervations
- Allows for motility
What is the submucosal plexus?
• aka Meissner's plexus • Afferent functions - senses environment within lumen - mechnoreceptors, chemoreceptors, osmoreceptors • Efferent functions - controls local blood flow - controls epithelial transport - controls secretory/paracrine/endocrine cell functions
What are the 4 main functions of the enteric nervous system?
S - secretion
• Controls the secretion of enzymes, paracrine signals and endocrine hormones
• To regulate local/non-local gut function
P - perfusion
• Careful control of blood flow
• Ensure high perfusion in regions of gut that are working (VSMCs, submucosal glands, enterocytes)
A - absorption
• controlling absorption by adjusting expression of luminal transport proteins
M - motility
• contraction/relaxing of smooth muscle cells in the circular and longitudinal muscle layers
• effective gut transit (accelerate after a meal, stop during exercise)
What are multipolar neurones?
- One axon
- One body
- Multiple dendrites
What do sensory enteric neurones do?
Respond to mechanical, thermal, osmotic and chemical stimuli
What do motor enteric neurones?
• Axons terminate on:
- smooth muscle cells (circular/longitudinal layers)
- secretory cells
- GI blood vessels
What do interneurons do?
Neurones between neurones that integrate sensory input and effector output
How would a disruption of autonomic innervation affect the gut?
- Small decrease in functionality
* Very independent
Summarise the sympathetic innervation of the gut
- Preganglionic neurones in splanchnic nerves from thoracic and lumbar regions
- Thoracic branches => foregut
- Lumbar branches => hindgut
(pre/postganglionic = short/long - close to spine)
Summarise the parasympathetic innervation of the gut
- Mostly from vagus nerve (X)
- Descending colon onwards - pelvic splanchnic nerves
(pre/postganglionic = long/short - close to target organ)
How do the sympathetic and parasympathetic pathways influence the GIT?
- Sympathetic - reduce activity (fight or flight)
* Parasympathetic - increase activity (rest and digest)
Describe the general structure of an enteroendocrine cell
• Small apical membrane
- Lot of sensory apparatus
• Broad basolateral surface
- Vesicles with secretory products ready for exocytosis
Where is gastrin produced?
- G-cells
- Distal end of stomach (gastric antrum)
- Proximal duodenum
- Pancreas (less)
What stimulates the release of gastrin?
• Peptides/amino acids in stomach
• Mechanoreceptors in stomach
• Parasympathetic system
(• inhibited under pH 3)
What does gastrin do?
- Increase acid secretion
- Increase gastric emptying
- Increase pepsinogen secretion
Where is secretin produced?
- S-cells
* Duodenum and jejunum
What stimulates the release of secretin?
Low pH
What does secretin do?
- Increase pancreatic HCO3- secretions
- Reduce acid secretion
- Reduce gastric emptying
Where is somatostatin produced?
- D-cells
* Stomach, pancreas and small intestine
What stimulates the release of somatostatin?
Presence of a meal
What does somatostatin do?
• Inhibits G-cells from secreting gastrin
• Inhibits enterochromaffin-like cells from secreting histamine
• Decreases gut motility
• Decreases absorption
(• inhibited by vagus nerve)
Where is cholecystokinin produced?
- I-cells
* Small intestine
What stimulates the release of cholecystokinin?
Fats and peptides
What does cholecystokinin do?
- Increases pancreatic enzyme secretion
- Reduces gastric emptying
- Increases gall bladder contraction
- Reduces appetite
Where is Glucose-dependent insulinotropic peptide (gastric-inhibitory peptide) produced?
- K-cells
* Duodenum and jejunum
What stimulates the release of Glucose-dependent insulinotropic peptide?
Glucose in small intestine
What does Glucose-dependent insulinotropic peptide do?
- Upregulation of insulin
* Reduces acid secretion/gastric emptying at high concentrations
Which part of the body is responsible for triggering appetite?
• Hypothalamus- combines peripheral signals
- Arcuate nucleus
- Paraventricular nucleus
Outline the role of the Arcuate nucleus in appetite
• Located at base of brain
• Incomplete brain barrier - allows peripheral signals to activate the circuitry
• Has 2 neuronal populations:
- NPY/Agrp: located medially, stimulates food intake
- POMC (proopiomelanocortin): located more laterally, inhibits food intake, peptide that can be cleaved in many ways for different purposes
• Neurones project into brain and paraventricular nucleus
Outline the role of the Paraventricular nucleus in appetite
- Axons from Arcuate nucleus secrete neuropeptides
- POMC - alpha melanocyte stimulating hormone
- Binds to Melanocortin 4 receptor (regulation of food uptake)
- Agoutin-related protein (Agrp) = competitive inhibitor => increases food uptake
What can a POMC deficiency or MC4R mutation lead to?
Morbid obesity
Outline the role of Leptin in obesity
• 167 amino acid hormone coded for by ob/ob gene
• Produced by fat, proportionate to adipose tissue
• Concentration sensed by hypothalamus
- causes alteration of neuropeptides
- regulates appetite
- regulates thermogenesis
• Leptin resistance - hormone cannot signal => obesity
• Ineffective as weight control drug
• Congenital leptin deficiency - very rare
What is Peptide YY?
- 36 amino acid chain
- Secreted from ileum and colon
- Released in proportion to calories released
- Inhibits paraventricular nucleus => inhibits neuropeptide Y release
- Stimulates POMC neurones
- Decreases appetite
What is Ghrelin?
- Peptide hormone released from the stomach
- Fatty acid chain on serine 3 enables binding to receptor
- Drives hunger before meals
- Stimultes Agrp neurones and paraventricular neurones (neuropeptide Y)
- Inhibits POMC neurones
- Increases appetite
How is water concentration regulated?
- Very tightly regulated (285-295mOsm/kg)
- Osmoreceptors in the hypothalamus (OVLT and SFO regions)
- Adjacent to structures with an incomplete blood brain barrier
- Cell bodies outside the blood brain barrier - bathed in ECF
- Threshold - 2-3% increase in osmolality, 10-15% decrease in volume/pressure
- Cells shrink and grow in concordance
- Changes firing rate of cells - adjusts to basal level of ADH secreted
What is vasopressin and what does it do?
- Hormone produced in the hypothalamus when there is low water
- Released from posterior pituitary gland
- Inserts aquaporin-2 channels into collecting ducts
- Increases water reabsorption
- Stimulates vasoconstriction
- Increases BP
- Stimulates thirst
How can thirst be satiated?
- Presence of water in GIT - short term feedback
* Correction of original stimulus (osmolality or BP) - long term feedback
Summarise the hormonal control of thirst
Low water => low BP => Angiotensin II:
• vasoconstriction
• upregulates sympathetic nervous system (vasoconstriction)
• stimulates aldosterone secretion => increased sodium reabsorption => (gradient) water reabsorption
• direct sodium reabsorption => water reabsorption
• stimulates ADH release and thirst
