Panc phys

Question 1

Embryology of panc

Answer 1

The pancreas is formed from a ventral and dorsal pancreatic bud. The ventral bud migrates dorsally and fuses with the dorsal bud. The ventral bud becomes the uncinate process and head of the pancreas. The dorsal bud becomes the neck, body, and tail of the pancreas.

In ~90% of individuals, the main pancreatic duct (of Wirsung) from the ventral bud is the major source of pancreatic drainage. In ~10% of the population, the accessory pancreatic duct (of Santorini) from the dorsal bud is the major source of drainage due to incomplete bud fusion during development. This is referred to as pancreas divisum.

Question 2

How do islet cells influence acinar cells?

Answer 2

In addition to their endocrine function, islet hormones influence exocrine secretion by perfusing acini on their way to the portal vein. Insulin stimulates enzyme secretion, while somatostatin and glucagon inhibit enzyme secretion.

Question 3

What is secretin?

Answer 3

• Major stimulus for bicarb and water sec into duodenum. -Activates adenylyl cyclase in duct cells
• Opens CFTR which exchanges bicarb for Cl-
• Decreases gastric emptying and secretion, promotes blood flow for digestion

Question 4

What causes secretin release?

Answer 4

-inc acid in intestine

Question 5

List two tyrosine peptide inhibitors

Answer 5

PSTI or SPINK1

Question 6

What pH do lipases fxn at?

Answer 6

Neutral

Question 7

How much lipase output do you need to lose before you get steatorrhea?

Answer 7

90%

Question 8

List some causes of steatorrhea

Answer 8

• ZES
• Panc insufficiency
• Cholestasis
• Intestinal dysmotility (no mixing)
• Mucosal disease

Question 9

Change in diet does what to the enz?

Answer 9

changes their concentrations

Question 10

What are the two classes of agonists and what stimulates which?

Answer 10

1. cAMP
   - VIP1 secretion
2. Ca2+
   - CCK, ACh, GRP, Substance P

–>synergistic

Question 11

What does CCK do?

Answer 11

Major stim for pancreatic secretion

-contracts gallbladder, relaxes oddi, delays gastric emptying

Question 12

What stimulates CCK release?

Answer 12

-peptides, amino acids, fatty acids, mucosa (in animal models), CNS, peripheral nerves

Question 13

Where is CCK produced?

Answer 13

Upper intestinal cells

Question 14

What are the 3 stimulatory phases of panc secretion?

Answer 14

1. Cephalic
2. Gastric
3. Intestinal

Question 15

What is the inhibitory phase of panc sec?

Answer 15

Postprandial

Question 16

What nerve mediates the cephalic phase?

Answer 16

Vagus (can produce 50% of max enz sec)

inhibited by atropine

Question 17

What nerve regulates gastric phase?

Answer 17

Vagovagal reflex

-gastric distention produces enzyme rich pancreatic secretion

Question 18

What causes intestinal phase of panc sec?

Answer 18

Acid and chyme in intestine, CCK

Question 19

What pH causes release of secretin from mucosa?

Answer 19

pH 4.5

Question 20

What causes postprandial panc sec phase

Answer 20

Postprandial (inhibitory): uncomplexed intraluminal trypsin inhibits CCK release by digesting monitor peptide and CCK-RP. (ie too much trypsin shuts it all off)

Oleic acid (from colon), peptide YY, glucagon, and somatostatin also play inhibitory roles.

Question 21

How do we test pancreatic fxn in the lab?

Answer 21

• reduced panc sec will lead to steatorrhea or protein in stool
• do 72 hour fecal fat
• ->normal is <7g/d
• Do microscopic sudan stain of stool

Question 22

How do we do a functional test of panc fxn?

Answer 22

• Stimulate the pancreas and collect panc sec in the duodenum via a nasal-duod tube
• Better for mild cases

Question 23

How do we test panc fxn structurally?

Answer 23

endoscopic US, MRI, CT

Question 24

Which bile salts increase canalicular flow?

Answer 24

Ursodeoxycholic acid

Question 25

What bile salts decrease canalicular flow?

Answer 25

Lithocholic acid

Question 26

MDR3

Answer 26

Transports phospholipids into canaliculi

Question 27

MRP2

Answer 27

Transports glucuronides (bilirubin) into canaliculi

Question 28

SPGP

Answer 28

Transports bile salts into canaliculi

Question 29

FXR (farnesoid x factor)

Answer 29

Nuclear receptor that senses intracellular bile salt. It’s stimulation suppresses bile salt synth and inc canalicular secretion

Question 30

What are the primary bile salts?

Answer 30

Cholic and chenodeoxycholic

Question 31

What are the secondary bile salts?

Answer 31

• converted by bacteria from primary or by isomerization in the colon
• These are formed by deconjugation of amino acids and removal or isomerization of the 7α –OH group
• include deoxycholic, urso and lithocholic

Question 32

What enzyme converts cholesterol to acetate

Answer 32

HMGCoA reductase in the liver

Question 33

RLS to bile salt production?

Answer 33

7a hydroxylation and COOH side chain (conversion of cholesterol to bile salt)

Question 34

RLS in general

Answer 34

Always the active transport into canaliculi

Question 35

Which is more water sol bile salt?

Answer 35

Ursodeoxycholic has OH in beta position making it more water soluble

Question 36

What is a mixed micelle?

Answer 36

Lipids and lecithin (which inc ability to solubilize cholesterol)

Question 37

Why are bile salts conjugated?

Answer 37

Conjugation results in ionization which prevents back diffusion in bile ducts and intestine and also limits proximal intestinal absorption

Question 38

What kind of bile salts are reabsorbed?

Answer 38

• Active ileal transport of conjugated bile salts which are returned to the liver via the portal vein
• secondary bile salts can be passively absorbed in the colon

Question 39

Where are bile salts re-absorbed?

Answer 39

Ileum (conj)

Colon (secondary)

Question 40

What is a consequence of secondary bile salts

Answer 40

If there is bacterial overgrowth in the small intestine, the deconjugation of bile salts causes bile acids to precipitate, leading to inadequate micelle formation and fat malabsorption