Physiology of the Pancreas Flashcards
What cells in the pancreas secrete enzymes?
acinar cells
Do islet hormones have an influence on exocrine secretion?
yes –> venous blood from islets perfuse neighboring acini, insulin stimulates enzyme synthesis/secretion and somatostatin/glucagon inhibit enzyme secretion –> local effects only
Functions of exocrine secretions of pancreas
digestive enzymes, neutralizing bicarbonate, receptors for hormones and neurotransmitters
What hormone a major stimulus for water and bicarbonate?
secretin –> activates adenylate cyclase in duct cells –> opens CFTR that exchanges bicarbonate for intraluminal chloride
Functions of secretin
increase bicarbonate secretion, retard gastric emptying/secretion, promotes mesenteric blood flow
Which pancreatic enzymes are stored and secreted in an active form?
amylase and lipase
How are most pancreatic enzymes stored and secreted
proenzymes
How are proenzymes activated?
enterokinase of intestinal brush border activates trypsinogen to trypsin which activates other proenzymes
Why are proteolytic enzymes stored in zymogen granules and secreted as inactive precursors?
to prevent autodigestion
What is peptide inhibitor of trypsin?
PSTI/SPINK1 can inactivate 10% of trypsin in zymogen granules –> if inactive, linked to pancreatitis
At what pH does amylase function?
neutral
Products of amylase digestion
maltose, maltotriose, dextrins –> further digested by brush border enzymes
Major source of triglyceride and phospholipid lipases
pancreas
4 etiologies of steatorrhea
excess gastric acid/ZES, inadequate enzyme/bicarb excretion/pancreatic insufficiency, poor bile flow/cholestasis, intestinal dysmotility/scleroderma, mucosal malabsorption/crohns/infections
3 main proteolytic pancreatic enzymes
trypsin, chymotrypsin, elastase
Where are zymogen granules stored in pancreatic cells?
apical/apex side
2 cellular controls of enzyme secretion in exocrine pancreas
- vip/secretin increase cyclic amp/pka
2. cck, ach, grp, substance p increase IP3 –> calcium
Functions of CCK
- major stimulus of pancreatic secretion
- contracts gallbladder, relaxes sphincter of Oddi
- delays gastric emptying
Where is CCK produced?
upper intestinal cells –> regulated by monitor peptide and CCK-RP
Phases of pancreatic secretion
stimulatory: cephalic, gastric, intestinal
inhibitory: postprandial
What nerve mediates the cephalic phase?
vagus nerve –> sham feeding produces about 50% of maximal enzyme secretion
What inhibits the cephalic phase?
atropine
What causes the intestinal phase?
acid and chyme in intestine –> ph below 4.5 releases secretin –> enzyme secretion
What mediates postprandial inhibition?
- excess intraluminal trypsin inhibits CCK release by digesting monitor peptide and CCK releasing peptide
- oleic acid in ileum/colon via peptide YY
glucose/iv AA
Tests for pancreatic function
- fecal fat (>10 abnormal)
- sudan stain for fat
- duodenal secretions
- secretin stimulation test
- imaging
–> need 90% loss of lipase to get a change in fecal fat
Bile functions
- excrete polar metabolites of lipid waste/bilirubin
- fat and fatsoluble vitamin absorption
- excrete cholesterol
- IgA
Where are different components of bile secreted?
- organic components = hepatocytes into canaliculi
- electrolyes and water= hepatocytes into ducts
some salts increase/reduce canalicular flow
Rate limiting step in secretion of bile salts
secretion of components against concentration gradient in canaliculi
Nuclear control of intracellular bile salts
farnesoid X factor senses intracellular bile salt –> stimulation suppresses bile salt synthesis and increase in canalicular secretion –> feedback suppression of toxic cellular bile salt level
Rate limiting step in cholesterol synthesis
HMGCoA reductase
How are primary bile salts formed?
7alpha hydroxylation and carboxylation side chain of cholesterol in liver
How are secondary bile salts formed?
bacterial 7alpha dehydroxylation or isomerization in colon
What does water solubility of bile salts depend on?
ionization of side chain –> secondary bile acids are more water soluble
Bile salt conjugation
before secretion into bile, salts are conjugated with taurine/glycine –> stronger acids which ionize upper small intestine and prevent back diffusion of bile –> bind to specific ileal receptors and form clusters/micelles once above critical micellar concentration
Addition of what molecule increases ability to solubilize cholesterol in a mixed micelle?
lecithin
What limits proximal intestinal absorption of bile salts?
ionization (conjugation)
How do bile salts return to the liver?
portal vein
What is the effect of small bowel stasis on bile salts?
premature deconjugation due to bacterial overgrowth leading to precipitation of bile salts and fat/vitamin malabsorption
What products may protect mucosa against toxicity of bile salts?
cholesterol and phospholipids
