PHYS: GI Regulation Flashcards
List the 4 functions of the GI tract.
Motility
Secretion
Digestion
Absorption
What is the most important part of the GI system for digestion?
small intestine
What is the most important part of the GI system for absorption?
small intestine
What do preganglionic sympathetic fibers do?
release Ach at nictoinic receptors of sympathetic ganglia
What do postganglionic sympathetic fibers do?
innervate blood vessels, nerves, interneurons, mucosa, or epithelial cells (by releasing EPI or NOREPI)
What parts of the GI system does the vagus nerve innervate?
from the mouth to the transverse colon
True or false: the vagus nerve is 75% efferent–sending commands to the endocrine secretory cells in the GI tract?
FALSE: 75% AFFERENT, carrying information from the gut to the medulla
What do preganglionic parasympathetic fibers do?
releases Ach on ganglia in myenteric (Auerbach) or submucosal (Meissner) plexuses in the GI tract
What do postganglionic parasympathetic fibers do?
release Ach at the muscularis mucosa and endocrine/ secretory cells in the GI tract
What part of the GI system is innervated by the pelvic nerve?
transverse colon to rectum
Why is the enteric nervous system unique?
information can be relayed up and down the tract without ever leaving the gut
How does the enteric nervous system achieve its ability to relay information solely within the gut?
information is sent via interneurons that interact with one another and are totally contained within the GI tract
What is a vago-vagal reflex?
reflexes that originate in the gut (ex. chemoreceptors) that can be sent as an afferent signal up the vagus nerve to the medulla and relayed back down the vagus nerve to cause an effect
List the two nerves that control parasympathetic innervation in the GI tract.
Vagus nerve
Pelvic Nerve
What is the role of the enteric nervous system?
controls contractile, secretory and endocrine functions of the GI tract
What are the two components of the enteric nervous system?
Myenteric Plexus
Submucosal Plexus
What stimulates the enteric nervous system?
1) Sympathetic Nervous System
2) Parasympathetic Nervous System
3) Mechanoreceptors and Chemoreceptors in the mucosa
What category of agents are released into portal circulation so they are transported though the liver before they are able to pass throughout the rest of the body?
Endocrine
What cells do not receive signaling from endocrine agents?
brain (BBB blocks this)
True or false: endocrine agents must bind a receptor to have an effect.
True
What type of agent is released by an endocrine cell to act on a cell next to it (that has a receptor for the agent)?
Paracrine
Describe the paracrine role of somastatin?
somatostatin releasing cells located next to parietal cells and gastrin releasing cells to inhibit them and will have finger like projections that “cup” target cells
What category of peptides are released from axons of nerve onto a cell?
neurocrine
List the 5 major GI hormones
Gastrin CKK Secretion GIP Motilin
What part of the gastrin structure controls its actions?
the 4 C-terminal amino acids (in a mid group)
Why is it important that the 4 C-terminal amino acids of gastrin are in a mid-group?
it prevents this active portion from getting de-carboxylated in the liver
What N-terminal feature of gastrin is responsible for preventing destruction by the liver?
N-terminal AA #1 is a glutamine that is isomerized among itself
True or false: In gastrin, the tyrosine in the sixth position from the carboxy end may have a hydrogen or a sulfate as the R group without affecting activity.
TRUE
What is little gastrin also called?
G17
When is little gastrin released?
in response to a meal
What is big gastrin also called?
G34
When is big gastrin secreted?
during the interdigestive period (between meals)
What cells release gastrin? Where are they located?
G cells in the antrum of the stomach (and the duodenum)
What are the physiologic stimuli for gastrin release?
protein digestion products, distention of the stomach by food, vagal stimulation (all related to the ingestion of food)
What are the major protein digestion products that stimulate gastrin release?
phenylalanine and tryptophan
How does vagal stimulation of gastrin release work?
Local vagal reflexes (neurocrine release of GRP (bombesin) from vagal nerve endings onto G cells)
What are the inhibitors of gastrin release?
acidic pH of gastric contents and somatostatin
What are the two major actions of gastrin?
1) Stimulate acid secretion by parietal cells
2) Trophic effect (stimulate growth of the gastric mucosa)
What are the gastrin receptors?
CCKb receptor
CCK is very similar to what other protein?
gastrin (same 5 C-terminal AAs)
What is interesting about the structure of CCK?
Tyr group in position 7 from C-terminal that is ALWAYS sulfated—if it is not, it will act like gastrin! (unless at SUPER high doses).
What cells release CCK?
I cells of the duodenal, jejunal, and ileum (small amount) mucosa
What are the physiological stimuli for CCK release?
1) monoglycerides and fatty acids (NOT Tg’s)
2) Small peptides and amino acids
What are the actions of CCK?
1) Stimulation of gall bladder contraction/relaxtation of sphincter of Oddi
2) Stimulation of pancreatic HCO3- secretion (with secretin present)
3) Stimulation of pancreatic enzyme secretion
4) Trophic effect (pancreatic and gallbladder growth)
5) Inhibits gastric emptying
What is the receptor for CCK?
CCKa
True or false: each of secretin’s 27 AAs are needed for activity?
TRUE
Where is secretin released?
S (secretin) cells of hte proximal duodenum (acidic environment)
What is the major stimuli for secretin release?
pH of below 4.5 in the duodenum (acidic environment)
What are the roles of secretin?
1) stimulation of pancreatic HCO3- secretion (very small amounts)
2) stimulation of bile HCO3- secretion
3) some stimulation of pancreatic growth
4) inhibits acid secretion by blocking gastrin’s effects on parietal cells
What is the significance of secretin in the GI system?
KEEPS ACID OUT OF DUODENUM. (neutralizes the H+ in the lumen of the small intestine to between 6 and 8 for optimal pancreatic lipase action (fat digestion))
What does GIP stand for?
Glucose Insulinotrophic-Depenent Peptide
At pharmacological doses, GIP can act like what peptide?
secretin (share 9 common AAs)
What cells secrete GIP?
K cells of the duodenal and jejunal mucosa
What is unique about GIP?
only GI hormone that is released in response to all three types of nutrients (protein, fat, carbohydrate breakdown products)
What is the major action of GIP?
releases insulin (reason while patients handle oral glucose loads faster than glucose loads in blood stream)
What is the other action of GIP?
inhibition of acid secretion
Where are the cells that secrete motilin located?
upper duodenum and jejunum
When is motilin secreted?
every 90 minutes in a FASTING individual
What stimulates motilin release?
nerves
What is the function of motilin?
produces an increase in motility of the stomach and small bowel (initiate interdigestive myoelectric complexes that occur every 90 minutes)
List the 3 important neurocrines of the GI tract.
VIP
GRP (bombesin)
Enkephalins
What is the source of VIP?
neurons of mucosa and SM of GI tract
What is the action of VIP?
Stimulates synthesis of nitric oxide which leads to:
1) Relaxation of smooth muscle (relaxes sphincters and gut circular muscle)
2) Stimulation of intestinal secretion
3) Stimulation of pancreatic secretion.
What is the source of GRP (bombesin)?
vagus stimulates the release of GRP from the neurons of gastric mucosa
What is the action of GRP?
Stimulates gastrin release
What is the source of enkephalin (opiod) in the GI tract?
neurons of mucosa and SM of the GI tract
What are the actions of enkephalins?
1) stimulation of smooth muscle contraction
2) Inhibits intestinal secretion
List the important paracrines of the GI tract.
Somatostatin
Histamine
What is the site of release of somatostatin?
D cells of the GI mucosa and pancreatic islets
What is the stimulus for somatostatin release?
decreased luminal pH (when stomach is properly acidified, you do not need more acid)
What is the action of somatostatin?
Inhibits GI hormone (gastrin) release
Inhibits secretion of acid from parietal cells
What inhibits the action of somatostatin?
Vagus nerve
Where is histamine released?
ECL cells of oxytinic gland mucosa
What stimulates histamine release?
gastrin and Ach
What is the role of histamine?
stimulates acid secretion from parietal cells
What is a gastrinoma?
gastrin-secreting tumor (slow growing)
Where are gastrinomas usually located?
pancreas or small intestin
True or false: gastrinomas are inhibited with increased stomach acidification?
FALSE! (they are NOT located there, so this feedback regulation does not work)
What is the consequence of a gastrinoma in some patinets?
increased gastrin secretion that leads to high rates of acid secretion and predisposes to Zollinger-Ellison syndrome
What are the features of Z-E syndrome?
- Duodenal ulcers (further away from the stomach correlates with more acid production)
- Steatorrhea (pancreatic lipase inactivated by acid)
- Diarrhea (osmotic)
How do you confirm the diagnosis of gastrinoma?
Give secretin in large doses to make serum gastrin go way up
How do you treat Z-E syndrome?
PPIs (inhibit gastric acid secretion)
Pancreatic cholera, or Werner-Morison Syndrome is characterized by the over-production of what neuropeptide?
VIP
What are the consequences of over-production of VIP?
high rates of intestinal secretion (diarrhea, metabolic acidosis (lose bicarbonate), dehydration and hypokalemia)
