11.7 - Regulation of Gut Function Flashcards
What are the two components to the gut nervous system?
- autonomic (extrinsic) nervous system - made of sympathetic (fight/flight) and parasympathetic (rest/digest) nervous systems
- enteric (intrinsic) nervous system
Where do sympathetic preganglionic neurones arise from?
- thoracic and lumbar spinal cord
- stomach is supplied by T6-9 neurones
- colon is supplied by L2-5 neurones
Which sympathetic postganglionic neurones innervate which parts of the GI system?
- stomach supplied by coeliac ganglion
- small intestine supplied by superior mesenteric ganglion
- colon supplied by inferior mesenteric and pelvic ganglion
What neurotransmitter is used in the sympathetic nervous system?
Norepinephrine (noradrenaline)
What does activation of the sympathetic nervous system do to the GI tract?
Inhibits the activities of GI tract
What nerve gives parasympathetic innervation to the stomach, small intestine and proximal colon?
Vagus nerve
Where do parasympathetic preganglionic neurones originate?
- dorsal vagal complex within brainstem from sacral spinal cord
- also originate separately from sacral spinal cord
What neurotransmitter is used in the parasympathetic nervous system?
Acetylcholine
What does parasympathetic activity do to the GI tract?
Stimulates activity of the GI tract
What are sympathetic ganglia like?
- near spinal cord in a row
- myelinated preganglionic axons (short)
- unmyelinated postganglionic axons (long)
What are parasympathetic ganglia like?
- near target organ
- myelinated preganglionic axons (long)
- unmyelinated postganglionic axons (short)
What is the enteric nervous system?
- the second brain
- autonomous but can also interact with sympathetic and parasympathetic nervous system
- the walls of the GI tract contain many neurones (2nd only to the brain) - contain enteric NS neurones
What is a plexus?
Network of intersecting nerves
What are the two plexuses of the enteric NS?
- Meissner’s (submucosal) plexus
- Auerbach’s (myenteric) plexus - lies between circular and longitudinal muscles in muscularis layer
What does the submucosal (Meissner’s) plexus do?
- senses the local environment in the gut lumen
- controls secretion, blood flow, epithelial and endocrine cell function
What does the myenteric (Auerbach’s) plexus do?
- controls activity of muscularis propria
- controls gut motor (motility) function
- controls tone, velocity of contraction and intensity of contraction
Describe the local reflex of the enteric NS when food enters the gut lumen.
- food enters gut lumen and stretches the intestinal smooth muscles
- distension of the gut causes stimulation of the sensory neurones in the myenteric plexus –> coordinates a peristaltic wave by sequential contraction/relaxation of circular and longitudinal muscle by inhibitory/excitatory NTs = moves food through gut
- chemicals in food also stimulate sensory neurones in submucosal plexus –> stimulates release of gut secretions and increases local blood flow to promote digestion and nutrient absorption
Describe how and where circular and longitudinal muscles work during peristalsis.
- circular muscles contract behind the bolus of food (up/down)
- longitudinal muscles contract ahead of the bolus (food), causing it to shorten and widen to receive the bolus (horizontal squish/stretch)
- wave of muscular contractions (peristalsis) move the bolus through the small intestine
- circular and longitudinal muscles work in opposite way e.g. one contracts while the other relaxes
What are the sympathetic NS effects on the enteric NS?
- ‘fight or flight’
- inhibits digestion:
- reduces peristalsis
- reduces absorption
- reduces secretion
- reduces blood flow (via enteric NS and also directly)
What are the parasympathetic NS effects on enteric NS?
- ‘rest and digest’
- promotes digestion
- increases peristalsis
- increases absorption
- increases secretion
- increases blood flow
What is Hirschsprung’s Disease?
- commonest cause of neonatal bowel obstruction
- congenital absence of ganglion of myenteric and submucosal plexus
- total contraction without reciprocal relaxation
- affected bowel segment remains contracted and proximal unaffected bowel becomes dilated
- intestinal distension proximal to aganglionic segment of bowel
- most require surgery - resection of affected segment usually at 6-12 months
What are endocrine hormones and what are they secreted by?
- released into bloodstream
- secreted by enteroendocrine cells
- e.g. gastrin, cholecystokinin, secretin, glucose-dependent insulinotropic peptide (GIP), motilin
What are paracrine hormones and what are they secreted by?
- hormone that acts only within vicinity it is released in - diffuses through extracellular space
- secreted by enteroendocrine cells
- e.g. somatostatin, histamine
Which hormones have both endocrine and paracrine mechanisms?
- glucagon-like peptide 1 (GLP-1)
- pancreatic polypeptide
- peptide YY
What are neurocrine hormones and what are they secreted by?
- hormone that affects nerves
- secreted by postganglionic non-cholinergic neurons of enteric NS
- e.g. vasoactive intestinal peptide (VIP), gastrin release peptide (GRP) and enkephalins
What are enteroendocrine cells?
- specialised epithelial cells located at the base of intestinal crypts throughout the GI tract, from stomach to colon
- have hormone-containing granules concentrated at basolateral membrane next to capillaries that secrete hormone in response to many stimuli
What are some stimuli that enteroendocrine cells respond to?
- small peptides
- amino acids
- fatty acids
- oral glucose
- distension of an organ
- vagal stimulation
Give examples of enteroendocrine cells.
- K cell
- I cell
- L cell
Which hormones are released in the stomach?
- gastrin
- ghrelin
- somatostatin
- histamine
Which hormones are released in the duodenum?
- secretin
- CCK
- somatostatin
Which hormones are released in the pancreas?
- insulin
- glucagon
- somatostatin
- pancreatic polypeptide
Which hormones are released in the small bowel?
- peptide YY
- GIP - gastric inhibitory peptide
- GLP-1
- GLP-2
- oxyntomodulin
- neurotensin
- somatostatin
Which hormones are released in the large bowel?
- peptide YY
- GLP-1
- oxyntomodulin
- neurotensin
- somatostatin
Where is gastrin synthesised?
Gastric antrum and upper small intestine by G cells
What is the release of gastrin stimulated by?
- amino acids and peptides in lumen of stomach
- gastric distension
- vagus nerve
What is the role of gastrin?
- stimulates gastric acid secretion by parietal cells in stomach
- has trophic (growth) effects on mucosa of small intestine, colon and stomach
What inhibits the release of gastrin?
When pH of stomach falls below 3
Where is secretin secreted and what stimulates this?
- secreted by S cells of upper duodenum and jejunum
- major stimulus is the presence of acid in duodenum (pH < 4.5)
What are the functions of secretin?
- stimulates pancreatic bicarbonate secretion (effect potentiated by CCK)
- inhibition of gastric acid and gastric emptying
- inhibits gastrin, acid secretion and growth of stomach mucosa
- stimulates biliary secretion of bicarbonate and fluid
- trophic effect on exocrine pancreas
What secretes cholecystokinin and what stimulates this?
- secreted by I cell most densely located in the small intestine
- release stimulated by fat and peptide in the upper small intestine
What are the functions of cholecystokinin (CCK)?
- stimulates pancreatic enzyme release (lipase, amylase, proteases)
- stimulates gallbladder contraction and relaxation of the sphincter of Oddi
- delays gastric emptying
- decreases food intake and meal size
- trophic effects on exocrine pancreas and gallbladder
What secretes GIP (aka gastric inhibitory peptide) and when is it secreted?
- secreted by mucosal K cells predominant in duodenum and jejunum
- released following ingestion of a mixed meal
- likely stimulated by a change in intraluminal osmolarity
What is GIP the only hormone to do?
Only hormone with a response to all three macronutrient types (glucose, amino acids, fatty acids)
What are the functions of GIP?
- stimulates insulin secretion from the pancreas
- decreases gastric acid release in stomach
Where is motilin released?
Proximal small bowel
What does motilin do?
Increases gastrointestinal motility
Where is somatostatin synthesised and when is it released?
- synthesised in endocrine D cells of the gastric and duodenal mucosa and pancreas
- released in response to a mixed meal - fat, glucose, bile salts
What is somatostatin known for and how does this relate to its functions?
- it is a universal inhibitor (endocrine cyanide) - inhibits:
- gastric secretion
- motility
- intestinal and pancreatic secretions
- release of gut hormones
- intestinal nutrient and electrolyte transport
- growth and proliferation
Where is glucagon-like peptide 1 (GLP-1) produced and what stimulates its release?
- produced in the small intestine and secreted from L cells
- release stimulated by presence of hexose and fat
What are the functions of GLP-1?
- induces satiety
- increases sensitivity of pancreatic beta-cells to glucose
Where is pancreatic polypeptide secreted from and when?
- secreted by pancreatic polypeptide (PP) cells in pancreas
- secretion is stimulated by fat
What is the role of pancreatic polypeptide?
Potential role in satiety
Where is peptide YY (aka peptide tyrosine-tyrosine) secreted from and when?
- by L cells found throughout the mucosa of the terminal ileum, colon and rectum
- released post-prandially (particularly protein)
What does peptide YY do?
Reduces:
- intestinal motility
- gallbladder contraction
- pancreatic exocrine secretion
What are neurocrines?
- located within nerves in the gut
- vasoactive intestinal peptide (VIP) - relaxation of gut smooth muscle
- gastrin releasing peptide (GRP) - induces gastrin release
- enkephalins - increase smooth muscle tone
What are neuroendocrine tumours?
- tumours of the neuroendocrine cells which are predominantly found in GI tract and pancreas
- most originate in GI tract but 20-30% in lungs and 15% in skin/thymus/others
What is Zollinger Ellison syndrome?
- neuroendocrine tumour
- gastrinoma - tumour of gastric cells causes overproduction of gastrin and acid resulting in stomach and intestinal ulceration
- treatment with protein pump inhibitor to inhibit acid secretion
- role for somatostatin analogues to halt tumour growth and reduce sensation
What are the three phases of gastric secretion?
- cephalic phase
- gastric phase
- intestinal phase
What happens in cephalic phase?
- smell, thought, sight and taste of food and tactile sensations of food in mouth stimulate brainstem
- parasympathetic NS via vagus nerve stimulates the enteric plexus
- postganglionic neurones stimulate secretion of gastrin, acid (parietal cells) and digestive enzymes (chief cells)
- gastrin released into bloodstream and induces secretion by parietal and chief cells
What happens in the gastric phase?
- this phase lasts 3-4h, food arrives in stomach and gastric distension causes signals via vagus nerve to the brainstem
- this stimulates stomach secretion
- distension of the stomach and chemicals in food activate the enteric NS to increase stomach secretion
What happens in the intestinal phase?
- chyme in duodenum with pH<2 or lipids stimulates stretch and chemoreceptors that generate APs to brainstem whereby they inhibit parasympathetic NS, thereby inhibiting gastric secretions
- local reflexes activated by acid and lipids also act on enteric NS to inhibit gastric secretions
- secretin, GIP and CCK released by duodenum inhibit gastric secretions
