Brain To Gut, Gut To Brain Signalling Flashcards
What is the role of afferent neurones?
Signal from gut to brain
What is the role of efferent neurones?
Signal from brain to gut
What are the autonomic neurones of GI tract?
Vagal (parasympathetic) efferents - act via enteric neurones
Sympathetic efferents - act on blood vessels and enteric neurones
What do enteric neurones do?
Control motility, secretion, blood flow, mucosal growth
What does gastric distension stimulate?
Mechanoreceptors
What do intestinal nutrients stimulate?
Hormone, paracrine mediators
What is secreted in the inter digestive period?
Ghrelin
What do the mechanoreceptors and nutrients and paracrine mediators stimulate?
Vagal afferents to brain
Out of brain vagal efferents
What is stimulated down the vagal efferents?
Decrease gastric emptying
Increase pancreatic secretion
Increase gastric secretion
Increase gut immune responses
What are the 3 phases of gastric acid secretion?
Cephalic, gastric, intestinal
What happens in cephalic phase?
Release of acetylcholine and gastric releasing peptide
What happens in the gastric phase?
Release of gastrin
What happens in intestinal phase?
Release of inhibitory factors
What is the role of the greater T5-T9 splanchnic nerves?
Ganglion - celiac
Viscera - foregut
Region of referred pain - epigastric
What is the role of the lesser T10/T11 splanchnic nerves?
Ganglion - superior mesenteric
Viscera - midgut
Region of referred pain - periumbilical
What is the role of the least T12 splanchnic nerves?
Ganglion - aortico-renal
Viscera - kidneys
Region of referred pain - lower thoracic
What is the role of the lumbar L1/L2 splanchnic nerves?
Ganglion - inferior mesenteric
Viscera - hindgut
Region of referred pain - hypogastric
What are 2 types of nociception?
Hyperalgesia and allodynia
What is hyperalgesia?
Increased response to painful stimulus
What is allodynia?
Painful response to a normal innocuous stimulus
What are 2 types of acid peptic related pain?
Heartburn and peptic ulcer
What is heartburn?
Reflux of acid into oesophagus
What is distension?
Mechanoreceptor responses to stretch above ‘threshold’
What is satiety?
Fullness that persists after eating
What is satiation?
Prompts the termination of eating
What controls food intake?
Satiation - amount consumed at one sitting
Satiety - length of time until next occasion
What are enteroendocrine cells?
Largest endocrine organ in body
Approx 12 cell types
Many respond to nutrients
What are nodose ganglion?
Vagal afferent neurones
Express receptors for many gut hormones
Receptors transported from cell soma to peripheral
What kind of receptors are there in nodose ganglion?
CCK receptors
Where is GLP-1 released?
L-cells
What increases / suppresses GLP-1 secretion?
Increase in macronutrients
Increase in bariatric surgery
Decrease somatostatin
Decrease calorie restriction
What is the GLP-1 receptor?
GLP-1R
What is the site of action from GLP-1 thought to mediate effects on food intake?
Vagus; brainstem; hypothalamus
What is the role of GLP-1 in body weight regulation?
Increases satiation and satiety, potentiates insulin release
Where is ghrelin released?
Gastric mucosa
What increases / suppresses ghrelin secretion?
Circadian rhythms ;
Increase by lack of sleep, increase by calorie restriction, decrease by macronutrients, decrease by bariatric surgery
What is the ghrelin receptor?
GHS-R1a
What is the site of action of ghrelin thought to mediate effects on food intake?
Vagus; brainstem; hypothalamus
What is the role of ghrelin in body weight regulation?
Meal initiator; long term regulator of body weight
Where is CCK released?
Proximal small intestine I cells
What factors increase or suppress secretion of CCK?
Increased by fat and protein rich chyme, increased by coffee, decreased by bile acids
What is the CCK receptor?
CCK1
What is the site of action of CCK thought to mediate effects on food intake?
Vagus; brainstem; hypothalamus
What is the role of CCK in body weight regulation?
Increases satiation
What is the role of cck?
Regulator of small intestine digestion and integrator of brain and gut function
What does CCK stimulate?
Pancreatic enzyme secretion, gall bladder contraction ( for release of bile into SI to digest lipids )
What does CCK inhibit?
Inhibits foo intake and gastric emptying, via vagal afferent neurons ( thereby delaying nutrient delivery to small intestine )
What happens to vagal afferent neurons during obesity?
Insensitive to CCK so does not inhibit food intake and gastric emptying
What is the role of GLP-1?
Regulator of nutrient utilisation, integrator of brain and gut function
What does GLP-1 stimulate?
Insulin secretion
What does GLP-1 inhibit?
Inhibits food intake and gastric emptying, via vagal afferent neurons (thereby delaying nutrient delivery to small intestine)
What occurs during GLP-1 based therapy?
DPV-IV inhibitors delay GLP-1 breakdown, GLP-1 analogues mimic the effect of GLP-1
What is the role of ghrelin?
Stimulator of nutrient intake, integrator of gut and brain function
When is secretion of ghrelin highest?
Highest in blood immediately before a meal
What does ghrelin stimulate?
Food intake and gastric emptying
Where are ghrelin receptors expressed?
Expressed on vagal afferent and hypothalamic neurones
What does ghrelin inhibit?
Actions of CCK on vagal afferent neurones
