Panc phys Flashcards
Embryology of panc
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.
How do islet cells influence acinar cells?
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.
What is secretin?
- 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
What causes secretin release?
-inc acid in intestine
List two tyrosine peptide inhibitors
PSTI or SPINK1
What pH do lipases fxn at?
Neutral
How much lipase output do you need to lose before you get steatorrhea?
90%
List some causes of steatorrhea
- ZES
- Panc insufficiency
- Cholestasis
- Intestinal dysmotility (no mixing)
- Mucosal disease
Change in diet does what to the enz?
changes their concentrations
What are the two classes of agonists and what stimulates which?
- cAMP
- VIP1 secretion - Ca2+
- CCK, ACh, GRP, Substance P
–>synergistic
What does CCK do?
Major stim for pancreatic secretion
-contracts gallbladder, relaxes oddi, delays gastric emptying
What stimulates CCK release?
-peptides, amino acids, fatty acids, mucosa (in animal models), CNS, peripheral nerves
Where is CCK produced?
Upper intestinal cells
What are the 3 stimulatory phases of panc secretion?
- Cephalic
- Gastric
- Intestinal
What is the inhibitory phase of panc sec?
Postprandial
What nerve mediates the cephalic phase?
Vagus (can produce 50% of max enz sec)
inhibited by atropine
What nerve regulates gastric phase?
Vagovagal reflex
-gastric distention produces enzyme rich pancreatic secretion
What causes intestinal phase of panc sec?
Acid and chyme in intestine, CCK
What pH causes release of secretin from mucosa?
pH 4.5
What causes postprandial panc sec phase
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.
How do we test pancreatic fxn in the lab?
- 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
How do we do a functional test of panc fxn?
- Stimulate the pancreas and collect panc sec in the duodenum via a nasal-duod tube
- Better for mild cases
How do we test panc fxn structurally?
endoscopic US, MRI, CT
Which bile salts increase canalicular flow?
Ursodeoxycholic acid
What bile salts decrease canalicular flow?
Lithocholic acid
MDR3
Transports phospholipids into canaliculi
MRP2
Transports glucuronides (bilirubin) into canaliculi
SPGP
Transports bile salts into canaliculi
FXR (farnesoid x factor)
Nuclear receptor that senses intracellular bile salt. It’s stimulation suppresses bile salt synth and inc canalicular secretion
What are the primary bile salts?
Cholic and chenodeoxycholic
What are the secondary bile salts?
- 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
What enzyme converts cholesterol to acetate
HMGCoA reductase in the liver
RLS to bile salt production?
7a hydroxylation and COOH side chain (conversion of cholesterol to bile salt)
RLS in general
Always the active transport into canaliculi
Which is more water sol bile salt?
Ursodeoxycholic has OH in beta position making it more water soluble
What is a mixed micelle?
Lipids and lecithin (which inc ability to solubilize cholesterol)
Why are bile salts conjugated?
Conjugation results in ionization which prevents back diffusion in bile ducts and intestine and also limits proximal intestinal absorption
What kind of bile salts are reabsorbed?
- 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
Where are bile salts re-absorbed?
Ileum (conj)
Colon (secondary)
What is a consequence of secondary bile salts
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
