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Flashcards in Physiology of the Pancreas Deck (40):

Do the endocrine and exocrine parts of the pancreas interact?

Yes. Islet hormones have a local influence on exocrine secretion via the "insuloacinar portal system" - but this is less important than systemic stimuli.


Specific(ish) effects of islet hormones on exocrine function?

Insulin -> enzyme sythesis and secretion.
Somatosatin and glucagon inhibit enzyme secretion.


What do the pancreatic ducts secrete?
What's the major stimulus for secretion? How does that work?

Water and bicarb.
Secretin -> adenylate cyclase -> cAMP activates CFTR -> Cl- and water secretion.
Lumenal Cl- is then exchanged for bicarb.
(if CFTR is mutated, cystic fibrosis, and pancreas problems)


Why is secretin called the GI fireman?

In response to acid in the intestine (which burns...), it promotes bicarb secretion, delays gastric emptying and secretion, and promotes mesenteric blood flow.


Which 2 pancreatic digestive enzymes at secreted in active form?

Amylase and lipase.
The rest are proenzymes.


How does trypsinogen get activated?

Enterokinase on the brush border converts trypsinogen to trypsin.
Trypsin then activates the other pancreatic proenzymes.


What's the main molecule that stops trypsin from working in the pancreatic acinar cell cytosol? What do mutations in this lead to?

PSTI (pancreatic secretory trypsin inhibitor) aka SPINK1.
Mutations lead to chronic, early onset pancreatitis.


At what pH does amylase function?

Neutral pH.


What kind of glycoside linkages do pancreatic and salivary amylases split?

1,4-glycosidic linkages.
(probably not important)


What finishes the job of cleaving polysaccharides that amylases start?

Brush border enzymes. (can cleave 1,6-glycosidic linkages).


At what pH do lipases function?

Neutral pH.


Where do lipases act? What helps them break down triglycerides?

At the border between aqueous and lipid phases.
Colipase, and bile salts help them break down TGs.


4 causes of maldigestion of fat?

Excess gastric acid (eg. ZES) - lipase likes neutral pH.
Inadeuqate enzyme or bicarb secretion (pancreatic insufficiency).
Poor bile flow.
Intestinal dysmotility. (grinding very important for exposing fat for digestion)


3 active pancreatic enzymes for protein digestion?



What happens when amino acids, peptides, and fatty acids are detected in the gut? (4 things)

Hormone release - esp CCK - that stimulates pancreatic secretion, inhibits gastric emptying, alters motility, and induces satiety.


Can change in diet affect proportions of enzymes synthesized?

Yep. (why vegetarians can have a hard time switching back to meat)


What are 2 second messenger systems that agonists for pancreatic enzyme secretion use?

cAMP (secretin)
Ca++ (CCK, Ach, GRP, substance P)
(different pathways have synergistic effects)


What is the major stimulus for pancreatic acinar secretion?



4 effects of CCK on the gut?

Gallbladder contraction
Sphincter of Oddi (ampulla of Vater) relaxation.
Delays gastric emptying.
Pancreatic secretion.


What are 2 non-food molecules shown in animals to increase CCK secretion?

Monitor peptide
CCK-releasing peptide (CCK-RP)


3 stimulatory phases of pancreatic secretion?

Cephalic - chewing,seeing, smelling
Gastric - mainly distention
Intestinal - acid, amino acids, FAs, etc.


How does trypsin contribute to negative feedback to pancreatic secretion? (probably)

It breaks down "monitor peptide" and CCK-RP... so these inhibit CCK release.


What's the "ileal break" (or brake?)? What might mediate this?

Oleic acid in distal ileum and pancreatic secretion.
Might be mediated by peptide YY.


Is testing for fecal fat easy to do?

No. A good test requires 72 hour fecal fat after eating 100g of fat..
Spot testing of stool can be done, but..


How much lipase must you lose before there's fecal fat?

Most of it, >90%.
Your pancreas has to be pretty messed up for you to get steatorrhea.


What are tests for more mild pancreatic insuffiency?

Sample contents of post-prandial duodenum, or after CCK or secretin stimulation.
Also can do structural tests (ultrasound, MRI, CT).


4 functions of bile?

Waste removal (esp. bilirubin)
Fat and Vitamin ADEK absorption.
Excrete cholesterol
?Secretory IgA


Do bile salts increase or decrease canalicular flow?

Some increase it, others decrease it.


What's the rate-limiting step in bile salt secretion?

Tranportation into the canaliculus against a concentration gradient.


What does Farnesoid X Factor (FXR) do?

Senses intracellular bile salts. If too high, suppresses synthesis and promotes secretion into canaliculi.


What are secondary bile salts?

Bacteria take primary bile salts made by the liver and convert them in the colon to secondary bile salts. (the bile salts are often de-conjugated)


What modifications happen to bile salts before secretion into bile?

Conjugation - makes stronger acids so they ionize and don't back diffuse (and makes them more water soluble)


What is the critical micellar concentration?

The concentration threshold at which bile salts (and other ampipathic molecules) with spontaneously form micelles.


What is a mixed micelle?

Gets lecithin to help solubilize cholesterol.


Does the liver produce all the bile salts you need in a day?

No. It must be actively resorbed.


Where are bile salts reabsorbed?

In the ileum.
If you lose too much ileum, you can have a problem with bile salt resorption.


Which bile salt is toxic to the liver?

Lithocholic acid.


Which 2 bile salts are most prevalent?
Which secondary bile salt is most prevalent?

Cheondeoxycholates (both primary)
Deoxycholic acid is the most common secondary bile salt.
(.... seems low yield)


How do bile salts and cholesterol work together?

Bile salts help with cholesterol excretion.
Cholesterol may protect gut from toxic effects of bile salts.


How does small bowel bacterial overgrowth affect bile salts?

Deconjugation -> decreased solubility -> precipitation.
Bile salts aren't around to make micelles -> fat and vit ADEK malabsorption.