Regulation of Gut Function and Appetite Flashcards
How is the gut nervous system divided?
Gut nervous system is made up of the autonomic (extrinsic) and enteric (intrinsic) nervous system
The autonomic nervous system can be further divided into the sympathetic (fight or flight) and parasympathetic (rest and digest)
Where do the sympathetic nerves arise from?
Sympathetic preganglionic neurons arise from the thoracic and lumbar spinal cord:
Stomach: T6-9
Colon: L2-5
Preganglionic nerves innervating:
Stomach- coeliac ganglion
Small Intestine- superior mesenteric ganglion
Colon- inferior mesenteric and pelvic ganglion
What post-ganglionic neurotransmitter is involved in the sympathetic nervous system?
The neurotransmitter is norepinephrine (noradrenaline)
What is the role of the sympathetic nervous system?
It inhibits activities of the GI tract
What does the parasympathetic system innervate?
Innervates the stomach, small intestine and proximal colon
What supplies the parasympathetic system?
The vagus nerve
Where do parasympathetic nerves arise from?
Preganglionic neurons originate in dorsal vagal complex within brainstem in the medulla and from sacral spinal cord
What is the post-ganglionic neurotransmitter in the parasympathetic nervous system?
Acetylcholine
What is the role of the parasympathetic nervous system?
Stimulates the GI tract
Where do sympathetic and parasympathetic pre- ganglia synapse with post-ganglia?
Sympathetic: Near spinal cord in a row
Parasympathetic: Near target organ
How do fibre lengths for sympathetic and parasympathetic ganglia compare?
Sympathetic: short preganglionic fibre, long postganglionic fibre
Parasympathetic: Long preganglionic, short postganglionic
What is the enteric nervous system?
Intrinsic nervous system
“2nd brain”
Autonomous- Has intrinsic microcircuits to carry out GI functions independent of the brain and spinal cord
Can interact with SNS and PNS
Wall of GI tract contains many neurons in the myenteric plexus and submucosal plexus
How is the gut structured?
Innermost first:
Mucosa:
epithelium
lamina propria
muscularis mucosa
Submucosal:
meissner’s (submucosal) plexus- inner plexus
Muscularis Propria:
circular muscle
auerbach’s (myenteric) plexus (outer plexus)
longitudinal muscle
Serosa or adventitia
Has mainly control over GI movements- motility of bowel wall
What is the function of the myenteric (Auerbach’s) plexus?
Controls activity of muscularis propria
Controls gut motor (motility) function
Mediates tone, velocity of contraction and intensity of contraction
What is the function of the submucosal (meissner’s plexus)?
senses the local environment (gut lumen)
controls secretion, blood flow, epithelial and endocrine cell function and alters electrolyte and water transport
How does the enteric nervous system bring about a local reflex?
Food enters gut lumen and stretches the intestinal smooth muscle
Distension of the gut causes stimulation of the sensory neurons in the myenteric plexus
Chemicals in the food stimulate sensory neurones in submucosal plexus
This causes coordination of a peristaltic wave by contracting the smooth muscle behind the bolus and relaxing the smooth muscle in front of the bolus to push it forward- this is controlled by excitatory and inhibitory neurotransmitters
How does peristalsis happen?
Circular muscles contract behind the bolus of food
Longitudinal muscles contract ahead of the bolus causing it to shorten and widen to receive bolus
Circular and longitudinal muscles work antagonistically
What does activation of the sympathetic nervous system lead to?
reduces peristalsis
reduces absorption
reduces secretion
reduces blood flow (via enteric nervous system and directly)
What does activation of the parasympathetic nervous system lead to?
Increased peristalsis
Increased absorption
Increased secretion
Increased blood flow
What is Hirschsprung’s disease?
Congenital absence of ganglion of myenteric and submucosal
Tonal contraction without reciprocal relaxation- affected part of the bowel remains contracted
Intestinal distention proximal to aganglionic segment of bowel - the unaffected part is distended
Most will require surgery (usually carried out at 6-12 months old)
What are endocrine hormones?
Secreted by enteroendocrine cells
Hormone released into bloodstream
E.g. gastrin, cholecystokinin, secretin, glucose-dependent insulinotropic polypeptide (GIP), motilin
What is paracrine hormone?
Secreted by enteroendocrine cells
Hormone only acts within the vicinity that its released
Diffuses through extracellular space
E.g. somatostatin and histamine
hormones with both endocrine and paracrine mechanisms: glucagon-like peptide-1 (GLP-1), pancreatic polypeptide and peptide YY
What is neurocrine hormone?
Secreted by postganglionic non-cholinergic neurons of the enteric nervous system- acts like neurotransmitters
Hormone that affects nerves
E.g. vasoactive intestinal peptide (VIP), gastrin releasing peptide (GRP) and enkephalins
What are enteroendocrine cells?
Specialised epithelial cells located at the base of the intestinal crypts throughout the GI tract from stomach to colon
They have hormone containing granules concentrated at the basolateral membrane adjacent to capillaries that secrete their hormone in response to wide range of stimuli
Examples: K cell, I cell, L cell
What kind of stimuli do enteroendocrine cells respond to?
Small peptides, amino acids, fatty acids, oral glucose, distension of an organ and vagal stimulation
Where are gut hormones located?
Stomach: Gastrin, Ghrelin, Somatostatin and Histamine
Duodenum: Secretin, CCK and Somatostatin
Pancreas: Insulin, Glucagon, Somatostatin and pancreatic polypeptide
Small intestine: PYY, GIP (gastric inhibitory peptide), GLP-1, GLP-2, Oxyntomodulin, Neurotensin, Somatostatin
Large intestine: PYY, GLP1, Oxyntomodulin, Neurotensin, Somatostatin
Where is gastrin synthesised?
Hormone synthesized in gastric antrum and upper small intestine
What is the release of gastrin stimulated by?
Amino acids and peptides in the lumen of the stomach
Gastric distension
Vagus nerve
What does gastrin stimulate?
stimulates gastric acid secretion by parietal cells in stomach
Its release is inhibited when pH of stomach falls below pH3
Trophic (growth) effects on mucosa of the small intestine, colon and stomach
What is secretin secreted by?
Secreted by S cells of upper duodenum and jejunum
What stimulates the 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 is cholecystokinin?
Hormone secreted by I cells in duodenum
its release is stimulated by fat and peptides in the upper small intestines
What is the function of cholecystokinin?
stimulates pancreatic enzyme release (lipase, amylase, proteases)
stimulates gallbladder contraction and relaxation of sphincter of Oddi
Delays gastric emptying
Decreases food intake and meal size
trophic effects on the exocrine pancreas and gallbladder
What is the role of GIP?
Glucose-dependent insulinotrophic polypeptide
Also known as gastric inhibitory polypeptide
Secreted by mucosal K cells (predominant in the duodenum and jejunum)
GIP released following ingestion of mixed meal
It’s the only hormone with a response to all 3 macronutrients (glucose, amino acids, fatty acids)
Likely stimulated by change in intraluminal osmolarity
Stimulates insulin secretion
What is the function of motilin?
Hormone which increases gastrointestinal motility
Where is somatostatin synthesised?
Endocrine D cells of the gastric and duodenal mucosa and pancreas
What is somatostatin?
A universal inhibitor
Released in response to a mixed meal
What does somatostatin inhibit?
Gastric secretion Intestinal and pancreatic secretions Motility Release of gut hormones Intestinal nutrient and electrolyte transport growth and proliferation
Where is GLP-1 produced?
Glucagon-like peptide-1
Produced in small intestine and secreted from L cells
Why is GLP-1 secreted and what does it do?
Release stimulated by presence of hexose and fat
Induces satiety
Increases sensitivity of pancreatic beta cells to glucose
What is pancreatic polypeptide secreted by?
Secreted by PP cells in pancreas
Why is pancreatic polypeptide secreted and what does it do?
Stimulated by fat
Potential role is satiety
What is peptide YY secreted by?
Aka. peptide tyrosine tyrosine
Secreted from cells found throughout the mucosa of terminal ileum, colon and rectum
Released from L cells postprandially (particularly protein)
What is the role of peptide YY?
Reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion
What are the different neurocrines?
VIP, GRP, enkephalins
Located in the nerves within 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 neuroendocrine cells (which are found predominantly in gastrointestinal tract and pancreas)
What is an example of a neuroendocrine tumor?
E.g. zollinger ellison syndrome- tumour of gastric cells causing overproduction of gastrin and acid resulting in stomach and intestinal ulceration
Treated 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?
Cephalic phase via Vagus Parasympathetics excite pepsin and acid production Gastric Phase: 1. Local venous secretory reflexes 2. Vagal reflexes 3. Gastrin- histamine stimulation Intestinal phase: 1. Nervous mechanisms 2. Hormonal mechanisms
What happens in the cephalic phase?
Smell, thought, sight and taste of food and tactile sensations of food in mouth stimulate brain stem
PNS via vagus stimulation of enteric plexus
Postganglionic neurons stimulate secretion of gastrin, acid (parietal cells) and digestive enzymes (chief cells)
Gastrin released into blood stream and induces secretion by parietal and chief cells
What happens in the gastric phase?
Lasts 3-4 hours
Food arrives in stomach and distension causes signals via vagus nerve to the brainstem
This in turn stimulates stomach secretion
Distension of the stomach and chemicals in food activate enteric nervous nervous system to increase stomach secretion
What. happens in the intestinal phase?
- Chyme in duodenum with pH less than 2 or lipids stimulate stretch and chemoreceptors that generate AP to the brainstem where they inhibit the PNS therefor inhibit gastric secretions
- Local reflexes are activated by acid and lipids also act on the enteric nervous system to inhibit gastric secretions
- Secretin, gastric inhibitory polypeptide and cholecystokinin released by duodenum inhibit gastric secretions
