Lec 18 Control of GI function Flashcards
What are the layers of GI tract in order?
- epithelium
- lamina propria
- muscularis mucosa
- submucosa
- submucosal plexus
- circular muscle
- myenteric plexus
- longitudinal muscle
- serosa
Where is auerbach’s plexus?
aka myenteric plexus
- between circular and longitudinal muscle
Where is meissner’s plexus?
aka muscosal plexus
- between submucosa and circular muscle
pathway of GI hormone action?
- endocrine cell of GI tract secretes hormone
- -> enters portal circulation –> liver –> systemic circulation –> target cell
pathway of GI paracrine action?
- endocrine cell of GI tract secretes –> diffuses to target cells
- release hem transmitters into interstitial space surrounding nearby cells
pathway of GI neurocrine action?
- neuron of GI tract secretes at action potential to target cell
- reach target receptor on adjacent tissue
pathway of GI autocrine action?
- type of paracrine communication, provides feedback inhibition to reduce further secretion
How does parasympathetic act on GI function? Where does it primarily act?
- stimulates digestion via vagus
- especially acts at esophagus and stomach
- diminishes distally
What 2 parts of GI under voluntary response?
- control of swallowing
- contraction of external anal sphincter
3 actions of parasympathetic on GI?
- stimulates flow of saliva
- stimulates peristalsis and secretion
- stimulates release of bile
4 actions of sympathetic on GI?
- inhibits flow of saliva
- inhibits peristalsis and secretion
- converts glycogen to glucose
- secretion adrenaline/noradrenaline
What kind of transmitters in parasympathetic innervation of GI [pre and post ganglionic?]
preganglionic: ACh
postganglionic ACh or neuropeptide [peptidergic transmitters]
What kind of transmitters in sympathetic innervation of GI [pre and post ganglionic?]
preganglionic: ACh
postganglionic: NE
Via what nerves does parasympathetic reach GI?
- vagas
- pelvic cholinergic nerves
Where is parasympathetic stimulation of GI mostly directed [2 places]?
- esophagus + stomach
- decreased effect in distal GI tract
Via what nerves does sympathetic reach GI?
- through splanchnic nerve
- paravertebral, celiac, superior mesenteric, and inferior mesenteric ganglia
Does enteric nervous system have more or fewer neurons than spinal cord?
more!
What does myenteric plexus do [2 things]? where is it located?
- in between longitudinal and circular muscle layers
- provides motor innervation to both layers
- provides secretomotor innervation to mucosa
Where are cell bodies of the enteric nervous system located?
submucosal plexus [meissners]
True or false: most neurons in ENS have only 1 transmitter
FALSE – most neurons in ENS release more than 1 transmitter
What is function of NO in ENS?
- primarily inhibitor neurotransmitter
- responsible for sphincter relaxation
- formerly called “non-adrenergic, non-cholinergic [NANC]”
Where are GI hormone secreting cells located?
- islets of pancreas
- interspersed between mucosal cells throughout epithelium [columnar cells]
What are GI homrone secreting cells in the mucosa called?
enterochromaffin cells
What is the biggest endocrine organ in the body?
GI
What are most abundant type of chemical transmitters in GI tract? What is another name for them?
- regulatory peptides
- brain gut peptides
What are 8 things normally secreted in GI as hormones?
- gastrin
- secretin
- GIP
- glucagon, GLP1, GLP2
- motilin
- pancreatic polypeptide
- peptide YY
- Ghrelin
What are 4 things normally secreted in GI as neuropeptides?
- Gastrin releasing peptide [GRP]
- VIP
- substance P; tachykinin
- neuropeptide Y
What are 2 things secreted in GI as hormones or neuropeptides or paracrine?
- CCK
- somatostatin
Where is gastrin released from? What stimulates/inhibits its release? What type of release/action?
- released from G cells in antrum [mostly] and duodenum
- stimulated by high pH and AA
- inhibited by gastric acid [via somatostatin + secretin]
- mainly as hormone
What are 2 actions of gastrin?
- promotes gastric acid secretion from parietal cells
- acts as growth factor for ECL [enterochromaffin like cells]
- -> tells ECL to make histamine = indirect parietal stimulation
- -> in excess can lead to tumors
What does gastrin bind to?
CCK receptor
What 3 things act on parietal cell to induce acid secretion? And where do they bind?
Gastrin –> CCK receptor
Histamine –> H2 receptor
ACh –> M3 receptor
What are direct and indirect pathways that gastrin activates parietal cell acid secretion?
direct: gastrin activates parietal cells to secrete acid
indirect: gastrin tells ECL cells to grow and secrete histamine –> histamine activates parietal to secrete acid
What stimulates CCK release?
- amino acids and fatty acids
Where is cholecytokinin released from? what type of release
- I cells in proximal small intestine
- mainly acts as hormone
What family of proteins is gastrin in?
gastrin/CCK family
what family of proteins is CCK in?
gastrin/CCK family
What are 2 main actions of CCK?
- gallbladder contraction
- stimulates pancreatic enzyme secretion [and HCO3]
also less important: slows gastric emptying, induces satiety
What is secretin secreted from? where is it released from?
- S cells in proximal small intestine
What stimulates secretion of secretin?
- gastric acid [pH < 4.5]
- other acid [fatty acid, bile acid, spicy food, EtOH]
What are the 3 actions of secretin?
- induces secretion HCO3 from pancreas/duodenum/bile duct = MAIN FUNCTION
also
- inhibits gastrin release [and thus inhibits gastrin]
- inhibits intestinal motility
What hormone opposes the action of gastrin?
secretin
What mech is secretin normally secreted?
as a hormone
What family is secretin part of?
secretin/VIP/glucagon/GIP family
What is vasoactive intestinal peptide [VIP]?
A neuromediator from enteric nervous system
What are 3 possible actions of VIP?
- stimulate epithelial cell contraction
- stimulate smooth muscle [sphincter] relaxation
- VIP-secreting tumors
What are symptoms of a VIP-oma?
- watery diarrhea
- hypokalemia [low K]
- achlorhydria [low gastric acid]
What is glucagon? Where is it made
hormone
made by:
- pancreatic alpha cells
- cells of small intestine/colon [L cells]
what is proglucagon? where is it broken down into which things?
- precursor gene transcript
- in pancreas: processed into glucagon
- in small intestine: processed to GLP1/2 [glucagon-like peptides]
What is function of glucagon?
regulate glucose homeostasis [with GLP-1]
What is function of GLP-1?
regulate glucose homeostasis [with glucagon]
What is function of GLP-2?
acts as intestinal growth factor, helps maintain GI mucosal mass
What other 3 things are in same family as glucagon?
secretin/VIP/glucagon/GIP family
What is glucose-dependent insulinotropic polypetide [GIP]? Where is it released from
- a hormone
- released from small intestine [k cells]
What stimulates GIP release?
- released in response to hyperglycemia
What is action of GIP?
- stimulates pancreatic B cells to secrete insulin
What x things are in the tachykinin family of proteins?
- substance P
- Gastrin releasing peptide [GRP]
what family is substance P? By what 2 mech does substance P act?
- Tachykinin family
- acts by neurocrine and paracrine
- in CNS/PNS
What are actions of substance P?
- pain sensation [PRIMARY function]
- pro-inflammation
- inhibition of: somatostatin, biliary secretion
What two things does substance P inhibit?
- somatostatin
- biliary secretion
What family is gastrin releasing peptide [GRP]? What is normal mech of release?
- part of tachykinin family
- neurocrine, released by post-ganglionic parasympathetic
What 2 actions of GRP?
- mediates vagal release of gastrin
- stimulates pancreatic secretion and GI motility
What is motilin? where is it released from? What family of proteins?
- hormone
- made in duodenum
- motilin family of proteins
What are actions of motilin?
- binds receptors on smooth muscle through gut = pro-motility
- increases phase III contraction of MMC [increases peristalsis]
What drug is motilin agonist?
erythromycin
What family of protein is grhelin? Where is it made?
- part of motilin family
- made in gastric fundus [PD1 cells]
What proteins are in motlin family?
- motilin
- ghrelin
Action of ghrelin?
- increases food intake
- high levels during fasting, low levels when fed
What is Prader-Willi syndrome?
extra high ghrelin [so always hungry]
What family is pancreatic polypeptide [PP]? Where is it released from?
- pancreatic polypeptide family
- released from pancreatic islet cells [PP cells]
What stimulates pancreatic polypeptide release?
- vagus
- amino and fatty acids
- gastrin/CCK
- secretin
What are functions of pancreatic polypeptide?
MAINLY: inhibit pancreatic exocrine secretion
also
- gall bladder contraction
- gut motility
What family is peptide YY? WHere is it released from?
- pancreatic polypeptide family
- released from distal small intestine [L cells]
What stimulates PYY secretion?
meals, fat, bile acids
What are the actions of PYY?
- ileal break –> slow small intestine motility to increase absorption time
- inhibits pancreatic and gastric acid secretion
What is neuropeptide YY [NPY]
- neurocrine homologue of PYY
- found in CNS/PNS
- binds sam receptors as PYY
What is function of NPY?
- mimics PYY [ileal break, inhibition pancreatic/gastric acid secretion]
- also stimulates appetite
What are 4 inhibitory signals of gastric emptying
- low pH –> inhibits secretin
- AA and fatty A –> inhibit cholecystokinin
- osmolality –> inhibits vagal afferents
- carbohydrates –> inhibit PYY
Where is somatostatin made? [KNOW THIS CELL NAME]
- D cells in antrum
- also less importantly: by cells in small intestine, pancreatic islets, enteric neurons
What 3 things stimulate somatostatin release?
- gastric acid in lumen
- diet [protein, fat, glucose]
- muscarinic stimulation
What inhibits somatostatin?
high pH
What are the major actions of somatostatin?
GLOBAL INHIBITOR
- inhibits gastric acid [via G and parietal cells]
- inhibits pancreatic secretion
- reduces bile flow
- slows motility
- reduces splanchnic blood flow
