Regulation of Gut Function Flashcards
What are the two parts of the nervous system involved in git function?
Autonomic (extrinsic)
Enteric (intrinsic)
What is the autonomic nervous system further divided into?
Sympathetic ‘fight and flight’
Parasympathetic ‘rest and digest’
Where does the sympathetic neurones come from?
Preganglionic neurons arise from the thoracic and lumbar spinal cord
Stomach (T6-9)
Colon (L2-5)
What terminates in ganglions?
Short pre-ganglionic axon
What are the important ganglions in the GI tract?
Stomach - coeliac ganglion
Small intestine – superior mesenteric ganglion
Colon – inferior mesenteric and pelvic ganglion
What sympathetic neurotransmitter is key in the GI tract?
Norepinephrine
What does the sympathetic nervous system do to the GI tract?
Inhibits GI function
What provides the parasympathetic innervation to the GI tract?
Vagus nerve
What is the structure of parasympathetic neurones in the GI tract?
Preganglionic neurons originate in dorsal vagal complex within brainstem from sacral spinal cord.
Long myelinated pre-ganglionic axons
Short un-myelinated post-ganglionic axons
What parasympathetic neurotransmitter is key in the GI tract?
Acetylcholine
What does activation of the parasympathetic nervous system do?
Stimulates the GI tract
What is the enteric nervous system?
2nd brain
functions autonomously
Interacts with autonomic nervous system
Resides within gut itself
What are the two plexus’ in the intrinsic nervous system?
Meissner’s (submucosal) plexus
Auberbach’s (myenteric) plexus
Where do you find Meissner’s plexus?
Submucosa
Where do you find Auberbach’s plexus?
In muscular propria
In-between circular and longitudinal muscle
What does the Meissner’s plexus do?
- senses the local environment (gut lumen)
- controls secretion, blood flow, epithelial and endocrine cell function
- plays small role in motility of gut
What does Auberbach’s plexus do?
- controls activity of muscularis externa
- controls gut motor (motility) function
- tone, velocity of contraction and intensity of contraction
- responsible for peristalsis
Describe the first step of the local reflex of the enteric nervous system?
Food enters gut lumen and stretches the intestinal smooth muscles
Describe the second step of the local reflex of the enteric nervous system?
Distension of the gut causes stimulation of the sensory neurons in the myenteric plexus
Chemicals in food stimulates sensory neurons in submucosal plexus
Describe the third step of the local reflex of the enteric nervous system?
Sequential contraction/relaxation of circular and longitudinal muscle by inhibitory/excitatory neurotransmitter cause peristalsis, which allows food to move along the GI tract
What is peristalsis?
Wave of muscular contraction that moves the blows of food along the GI tract
What do the muscles behind bolus of food do in peristalsis?
Circular muscles behind food bolus contract
Longitudinal muscles behind food bolus relax and stretch
What do the muscles in front bolus of food do in peristalsis?
Circular relax
Longitudinal contract
How to the extrinsic and intrinsic nervous systems interact?
Feedback via sensory neurones from epithelium of gut to pre-vertebral ganglia, spinal cord and brainstem
What are the overall effects of the sympathetic nervous system on the GI tract?
'fight and flight’ reduces peristalsis reduces absorption reduces secretion reduces blood flow (via enteric nervous system and also directly)
What are the overall effects of the parasympathetic nervous system on the GI tract?
‘rest and digest’ increases peristalsis increases absorption increases secretion increases blood flow
What is Hirschsprung’s disease?
Congenital absence of ganglions of myenteric and submucosal plexus’
Tonal contraction without reciprocal relaxation
Intestinal distension proximal to aganglionic segment of bowel
Most will require surgery
What are the three categories of gut-hormone?
Endocrine
Paracrine
Neurocrine
What are the main features of Endocrine hormones?
secreted by enteroendocrine cells
hormone released into bloodstream
What are the main features of paracrine hormones?
secreted by enteroendocrine cells
hormone that acts only within the vicinity that it is released
diffuses through extracellular space
What are the main features of neurocrine hormones?
secreted by postganglionic non-cholinergic neurons of the enteric nervous system
hormone that affects ‘nerves’
Give example of endocrine hormones?
gastrin, cholecystokinin, secretin, glucose-dependent insulinotropic peptide (GIP), motilin
Give example of paracrine hormones?
somatostatin and histamine
Give example of neurocrine hormones?
vasoactive intestinal peptide (VIP), gastrin release peptide (GRP), and enkephalins
Where do you find enteroendocrine cells?
specialised epithelial cells located at the base of intestinal crypts throughout the GI tract, from stomach to colon
What are the function of enteroendocrine cells?
Possess hormone-containing granules concentrated at the basolateral membrane, adjacent to capillaries, that secrete their hormone in response to a wide range of stimuli
What stimulates enteroendocrine cells to secrete hormones?
small peptides, amino acids, fatty acids, oral glucose, distension of an organ, and vagal stimulation
What gut hormones are released in the stomach?
Gastrin
Ghrelin
Somatostatin
Histamine
What gut hormones are released in the duodenum?
Secretin
CCK
Somatostatin
What gut hormones are released in the pancreas?
Insulin
Glucagon
Somatostatin
Pancreatic Polypeptide
Where is gastrin synthesised?
gastric antrum and upper small intestine
What stimulates the release of gastrin?
amino acids and peptides in the lumen of the stomach
gastric distension
vagus nerve
What does gastrin stimulate?
gastric acid secretion by parietal cells in stomach
When is the release of gastrin inhibited?
when pH of stomach falls below pH 3
What effects can gastrin have?
Trophic (growth) effects on the mucosa of the small bowel, colon and stomach
What secreted secretin?
Secreted by the S cells of the upper duodenum and jejunum
What stimulates release of secretin?
Major stimulus is the presence of acid in the duodenum (pH falls below 4.5)
What is the function 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 the exocrine pancreas
What secretes cholecystokinin (CCK)?
Secreted by cells most densely located in the small intestine
What stimulates release of CCK?
Release stimulated by fat and peptides in the upper small bowel
What is the function of CCK?
stimulates pancreatic enzyme release (lipase, amylase, proteases)
delays gastric emptying
stimulates gallbladder contraction and relaxation of the sphincter of Oddi
decreases food intake and meal size
trophic effects on the exocrine pancreas and gallbladder
What is GIP?
Glucose-dependent insulintropic peptide
a.k.a Gastic inhibitory peptide
What secreted GIP?
mucosal K cells (predominant in the duodenum and jejunum)
What stimulates release of GIP?
Ingestion of 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
What is the function of GIP?
Stimulates insulin secretion from pancreas
What is the function of motilin?
Increases GI motility
Where is somatostatin synthesised?
Synthesized in endocrine D cells of the gastric and duodenal mucosa, pancreas
Released in response to meal
What is the function of somatostatin?
Somatostatin is a universal inhibitor (Endocrine Cyanide)
What does somatostatin inhibit?
gastric secretion motility intestinal and pancreatic secretions release of gut hormones intestinal nutrient and electrolyte transport growth and proliferation
Where is GLP-1 produced?
Small bowel and secreted from L cells
What stimulates release of GLP-1?
Presence of hexose and fat
What is the function of GLP-1?
Induces satiety
Increases sensitivity of pancreatic beta-cells to glucose
What cells secrete pancreatic polypeptide?
PP cells in the pancreas
What stimulates PP secretion?
Fat
What is the function of PP?
Potential role in satiety
What cells secrete peptide YY?
Secreted from cells found throughout the mucosa of the terminal ileum, colon and rectum
Released from L cells post- prandially (particularly protein)
What is the function of peptide YY?
Reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion
What are the three neurocrines active in the gut?
Vasoactive intestinal peptide (VIP)
Gastrin releasing peptide (GRP)
Enkephalins
What is the function of VIP?
relaxation of gut smooth muscle
What is the function of GRP?
Induces gastrin release
What is the function of enkephalins?
Increase smooth muscle tone
What are neuroendocrine tumours?
Tumours of the neuroendocrine cells (which are found predominantly in the gastrointestinal tract and pancreas)
Does not behave like other cancers
What is 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 three phases of gastric secretion?
Cephalic phase
Gastric phase
Intestinal phase
What is the cephalic phase (1)?
Smell, thought, sight and taste of food and tactile sensations of food in the mouth stimulate brain stem
What is the second step of the cephalic phase?
Parasympathetic nervous system via the vagus nerves stimulate the enteric plexus
What is the third step of the cephalic phase?
Postganglionic neurons stimulate secretion of gastrin, acid (parietal cells) and digestive enzymes (chief cells)
What is the fourth step of the cephalic phase?
Gastrin released into bloodstream and induces secretion by parietal and chief cells
What is the first step of the gastric phase?
This phase lasts 3-4 hours
Food arrives in stomach and distension causes signals via the vagus nerve to the brainstem
What is the second step of the gastric phase?
This in turn stimulates stomach secretion
What is the third step of the gastric phase?
Distension of the stomach and chemicals in food also activate the enteric nervous system to increase stomach secretion
What is the first step of 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.
What is the second step of the intestinal phase?
Local reflexes activated by acid and lipids also act on the enteric nervous system to inhibit gastric secretions.
What is the third step of the intestinal phase?
Secretin, gastric inhibitory polypeptide and cholecystokinin, released by the duodenum inhibit gastric secretions.
