Regulation of Gut Function Flashcards
What are the methods of of regulation of gut function?
Nervous system
- intrinsic (enteric)
- extrinsic
Gut hormones
- paracrine
- endocrine
- neurocrine
Describe the gut nervous system.
Describe the sympathetic nervous system for the gut.
Sympathetic preganglionic neurons arise from the thoracic and lumbar spinal cord
- Stomach (T6-9)
- Colon (L2-5)
Postganglionic neurons innervating
- Stomach
- coeliac ganglion
- Small intestine
– superior mesenteric ganglion
- Colon
– inferior mesenteric and pelvic ganglion
Neurotransmitter: norepinephrine
Activation of sympathetic nervous system inhibit activities of gastrointestinal tract
Describe the parasympathetic nervous system for the gut.
Parasympathetic innervation to stomach, small intestine and proximal colon is supplied by the vagus nerve.
Preganglionic neurons originate in dorsal vagal complex within brainstem from sacral spinal cord.
Neurotransmitter – acetylcholine
Activation of parasympathetic nervous system stimulates the gastrointestinal tract.
How do the para and symp NS work on gut?
What is the enteric (intrinsic) NS?
“The 2nd brain”
Autonomous
Can also interact with sympathetic and parasympathetic nervous system
The wall of the gastrointestinal tract contains many neurons – 2nd only to the brain
Where is the location of the different plexi in the wall of the GI tract?
Myenteric and submucosal plexus
What is the function of the myenteric plexus?
Myenteric (Auerbach’s) plexus
- controls activity of muscularis propria
- controls gut motor (motility) function
- tone, velocity of contraction and intensity of contraction.
What is the function of the submucosal plexus?
Submucosal (Meissner’s) plexus
- senses the local environment (gut lumen)
- controls secretion, blood flow, epithelial and endocrine cell function
What is the local reflex of the enteric nervous system?
Food enters gut lumen and stretches the intestinal smooth muscles->
Distension of the gut causes stimulation of the sensory neurons in the myenteric plexus
Chemicals in food stimulates sensory neurons in submucosal plexus->
Sequential contraction/relaxation of circular and longitudinal muscle by inhibitory/excitatory neurotransmitter cause peristalsis, which allows food to move along the GI tract
Describe peristalsis.
What muscle are involved in segmentation?
circular
What muscles are involved in peristalsis?
longitudinal
What does the sympathetic NS trigger in the GI tract?
- reduces peristalsis
- reduces absorption
- reduces secretion
- reduces blood flow (via enteric nervous system and also directly)
What does the parasympathetic NS trigger in the GI tract?
- increases peristalsis
- increases absorption
- increases secretion
- increases blood flow
Describe the interaction of the extrinsic NS and intrinsic (enteric) NS.
What is Hirschsprung’s disease?
Congenital absence of ganglion of myenteric and submucosal
Tonal contraction without reciprocal relaxation
Intestinal distension proximal to aganglionic segment of bowel
Most will require surgery
What part is the proximal and distal bowel?
What are endocrine gut hormones?
- secreted by enteroendocrine cells
- hormone released into bloodstream
- gastrin, cholecystokinin, secretin, glucose-dependent insulinotropic peptide (GIP), motilin
What are paracrine gut hormones?
- secreted by enteroendocrine cells
- hormone that acts only within the vicinity that it is released
- diffuses through extracellular space
- somatostatin and histamine
- hormones with both endocrine and paracrine mechanisms: glucagon-like peptide-1 (GLP-1), pancreatic polypeptide, and peptide YY
What are neurocrine gut hormones?
- secreted by postganglionic non-cholinergic neurons of the enteric nervous system
- hormone that affects ‘nerves’
- 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
possess hormone-containing granules concentrated at the basolateral membrane, adjacent to capillaries, that secrete their hormone in response to a wide range of stimuli
these stimuli include small peptides, amino acids, fatty acids, oral glucose, distension of an organ, and vagal stimulation
Where are the locations of the gut hormones?
more activating hormones at the top
more inhibiting hormones near the bottom
What is gastrin?
Synthesised in gastric antrum and upper small intestine
Release stimulated by:
- amino acids and peptides in the lumen of the stomach
- gastric distension
- vagus nerve
Stimulates gastric acid secretion by parietal cells in stomach
Release inhibited when pH of stomach falls below pH 3
Trophic (growth) effects on the mucosa of the small intestine, colon and stomach
What is secretin?
Secreted by the S cells of the upper duodenum and jejunum
Major stimulus is the presence of acid in the duodenum (pH falls below 4.5)
Function:
- 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 the exocrine pancreas
What is cholecystokinin?
Secreted by cells most densely located in the small intestine
Release stimulated by fat and peptides in the upper small
intestine
Function:
- 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 the exocrine pancreas and gallbladder
What is GIP?
Glucose-dependent insulinotropic peptide
Also known as Gastric inhibitory polypeptide
Secreted by mucosal K cells (predominant in the duodenum and jejunum)
GIP released following ingestion of a mixed meal
The only hormone with a response to all 3 macronutrient types (glucose, amino acid, fatty acids)
Likely stimulated by change in intraluminal osmolarity
Stimulates insulin secretion
What is motilin?
Increases gastrointestinal motility
What is somatostatin?
Synthesized in endocrine D cells of the gastric and duodenal mucosa, pancreas
Somatostatin is a universal inhibitor (Endocrine Cyanide)
Release in response to a mixed meal
Inhibition of:
- gastric secretion
- motility
- intestinal and pancreatic secretions
- release of gut hormones
- intestinal nutrient and electrolyte transport
- growth and proliferation
What is GLP-1?
Glucagon-like peptide-1 (GLP-1)
Produced in the small intestine and secreted from L cells
Release stimulated by the presence of hexose and fat
Induces satiety
§Increases sensitivity of pancreatic beta-cells to glucose
What is pancreatic polypeptide?
Secreted by PP cells in the pancreas
Secretion stimulated by fat
Potential role in satiety
What is peptide Y?
Secreted from cells found throughout the mucosa of the terminal ileum, colon and rectum
Released from L cells postprandially (particularly protein)
Reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion
What are Neurocrines: VIP, GRP and enkephalins?
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 is the relevance of gut hormones in clinical practice?
Neuroendocrine tumours
- Tumours of the neuroendocrine cells (which are found predominantly in the gastrointestinal tract and pancreas)
What is an example of neuroendocrine tumours?
For example, Zollinger Ellison syndrome – tumour of gastric cells causing overproduction of gastrin and acid resulting in stomach and intestinal ulceration
- treatment with proton pump inhibitor to inhibit acid secretion
- role for somatostatin analogues to halt tumour growth and reduce secretion
What are the phases of gastric secretion?
Describe the cephalic phase.
Smell, thought, sight and taste of food and tactile sensations of food in the mouth stimulate brain stem->
Parasympathetic nervous system via the vagus nerves stimulate the enteric plexus->
Postganglionic neurons stimulate secretion of gastrin, acid (parietal cells) and digestive enzymes (chief cells)->
Gastrin released into bloodstream and induces secretion by parietal and chief cells
Describe the gastric phase.
This phase lasts 3-4 hours
Food arrives in stomach and distension causes signals via the vagus nerve to the brainstem->
This in turn stimulates stomach secretion->
Distension of the stomach and chemicals in food also activate the enteric nervous system to increase stomach secretion
Describe the intestinal phase.
Chyme in the duodenum with pH<2 or lipids stimulate stretch and chemoreceptors that generate action potentials to the brainstem whereby they inhibit the parasympathetic nervous system, thereby inhibiting gastric secretions.->
Local reflexes activated by acid and lipids also act on the enteric nervous system to inhibit gastric secretions.->
Secretin, gastric inhibitory polypeptide and cholecystokinin, released by the duodenum inhibit gastric secretions.
What are the conclusion from all of regulation of gut function?
The autonomic and enteric nervous systems modulate the activity within the gut
Sympathetic: inhibit motor and secretory activity
Parasympathetic: stimulate motor and secretory activity
Gut hormones produced by endocrine cells of the GI tract aid digestion
The phases of gastric secretion depend on the relationship between the nervous system and its effect on gut hormone secretion
What are the endocrine gut hormones? (5)
gastric, cholecystokinin, secretin, GIP, motilin
What are the paracrine gut hormones? (2)
somatostatin and histamine
What are the neurocrine gut hormones? (3)
VIP, GRP, enkephalins
Vasoactive intestinal peptide (VIP)→ relaxation of gut smooth muscle
Gastrin releasing peptide (GRP)→ induces gastrin release
Enkephalins→increase smooth muscle tone
