Physiology of the Pancreas

Question 1

Do the endocrine and exocrine parts of the pancreas interact?

Answer 1

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

Question 2

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

Answer 2

Insulin -> enzyme sythesis and secretion.

Somatosatin and glucagon inhibit enzyme secretion.

Question 3

What do the pancreatic ducts secrete?

What’s the major stimulus for secretion? How does that work?

Answer 3

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)

Question 4

Why is secretin called the GI fireman?

Answer 4

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

Question 5

Which 2 pancreatic digestive enzymes at secreted in active form?

Answer 5

Amylase and lipase.

The rest are proenzymes.

Question 6

How does trypsinogen get activated?

Answer 6

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

Question 7

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

Answer 7

PSTI (pancreatic secretory trypsin inhibitor) aka SPINK1.

Mutations lead to chronic, early onset pancreatitis.

Question 8

At what pH does amylase function?

Answer 8

Neutral pH.

Question 9

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

Answer 9

1,4-glycosidic linkages.

probably not important

Question 10

What finishes the job of cleaving polysaccharides that amylases start?

Answer 10

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

Question 11

At what pH do lipases function?

Answer 11

Neutral pH.

Question 12

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

Answer 12

At the border between aqueous and lipid phases.

Colipase, and bile salts help them break down TGs.

Question 13

4 causes of maldigestion of fat?

Answer 13

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)

Question 14

3 active pancreatic enzymes for protein digestion?

Answer 14

Trypsin
Chymotrypsin
Elastase

Question 15

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

Answer 15

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

Question 16

Can change in diet affect proportions of enzymes synthesized?

Answer 16

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

Question 17

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

Answer 17

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

Question 18

What is the major stimulus for pancreatic acinar secretion?

Answer 18

CCK

Question 19

4 effects of CCK on the gut?

Answer 19

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

Question 20

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

Answer 20

Monitor peptide

CCK-releasing peptide (CCK-RP)

Question 21

3 stimulatory phases of pancreatic secretion?

Answer 21

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

Question 22

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

Answer 22

It breaks down “monitor peptide” and CCK-RP… so these inhibit CCK release.

Question 23

What’s the “ileal break” (or brake?)? What might mediate this?

Answer 23

Oleic acid in distal ileum and pancreatic secretion.

Might be mediated by peptide YY.

Question 24

Is testing for fecal fat easy to do?

Answer 24

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

Question 25

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

Answer 25

Most of it, >90%.

Your pancreas has to be pretty messed up for you to get steatorrhea.

Question 26

What are tests for more mild pancreatic insuffiency?

Answer 26

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

Question 27

4 functions of bile?

Answer 27

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

Question 28

Do bile salts increase or decrease canalicular flow?

Answer 28

Some increase it, others decrease it.

Question 29

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

Answer 29

Tranportation into the canaliculus against a concentration gradient.

Question 30

What does Farnesoid X Factor (FXR) do?

Answer 30

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

Question 31

What are secondary bile salts?

Answer 31

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)

Question 32

What modifications happen to bile salts before secretion into bile?

Answer 32

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

Question 33

What is the critical micellar concentration?

Answer 33

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

Question 34

What is a mixed micelle?

Answer 34

Gets lecithin to help solubilize cholesterol.

Question 35

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

Answer 35

No. It must be actively resorbed.

Question 36

Where are bile salts reabsorbed?

Answer 36

In the ileum.

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

Question 37

Which bile salt is toxic to the liver?

Answer 37

Lithocholic acid.

Question 38

Which 2 bile salts are most prevalent?

Which secondary bile salt is most prevalent?

Answer 38

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

Question 39

How do bile salts and cholesterol work together?

Answer 39

Bile salts help with cholesterol excretion.

Cholesterol may protect gut from toxic effects of bile salts.

Question 40

How does small bowel bacterial overgrowth affect bile salts?

Answer 40

Deconjugation -> decreased solubility -> precipitation.

Bile salts aren’t around to make micelles -> fat and vit ADEK malabsorption.