Physiology of the Pancreas

Question 1

What cells in the pancreas secrete enzymes?

Answer 1

acinar cells

Question 2

Do islet hormones have an influence on exocrine secretion?

Answer 2

yes –> venous blood from islets perfuse neighboring acini, insulin stimulates enzyme synthesis/secretion and somatostatin/glucagon inhibit enzyme secretion –> local effects only

Question 3

Functions of exocrine secretions of pancreas

Answer 3

digestive enzymes, neutralizing bicarbonate, receptors for hormones and neurotransmitters

Question 4

What hormone a major stimulus for water and bicarbonate?

Answer 4

secretin –> activates adenylate cyclase in duct cells –> opens CFTR that exchanges bicarbonate for intraluminal chloride

Question 5

Functions of secretin

Answer 5

increase bicarbonate secretion, retard gastric emptying/secretion, promotes mesenteric blood flow

Question 6

Which pancreatic enzymes are stored and secreted in an active form?

Answer 6

amylase and lipase

Question 7

How are most pancreatic enzymes stored and secreted

Answer 7

proenzymes

Question 8

How are proenzymes activated?

Answer 8

enterokinase of intestinal brush border activates trypsinogen to trypsin which activates other proenzymes

Question 9

Why are proteolytic enzymes stored in zymogen granules and secreted as inactive precursors?

Answer 9

to prevent autodigestion

Question 10

What is peptide inhibitor of trypsin?

Answer 10

PSTI/SPINK1 can inactivate 10% of trypsin in zymogen granules –> if inactive, linked to pancreatitis

Question 11

At what pH does amylase function?

Answer 11

neutral

Question 12

Products of amylase digestion

Answer 12

maltose, maltotriose, dextrins –> further digested by brush border enzymes

Question 13

Major source of triglyceride and phospholipid lipases

Answer 13

pancreas

Question 14

4 etiologies of steatorrhea

Answer 14

excess gastric acid/ZES, inadequate enzyme/bicarb excretion/pancreatic insufficiency, poor bile flow/cholestasis, intestinal dysmotility/scleroderma, mucosal malabsorption/crohns/infections

Question 15

3 main proteolytic pancreatic enzymes

Answer 15

trypsin, chymotrypsin, elastase

Question 16

Where are zymogen granules stored in pancreatic cells?

Answer 16

apical/apex side

Question 17

2 cellular controls of enzyme secretion in exocrine pancreas

Answer 17

1. vip/secretin increase cyclic amp/pka

2. cck, ach, grp, substance p increase IP3 –> calcium

Question 18

Functions of CCK

Answer 18

1. major stimulus of pancreatic secretion
2. contracts gallbladder, relaxes sphincter of Oddi
3. delays gastric emptying

Question 19

Where is CCK produced?

Answer 19

upper intestinal cells –> regulated by monitor peptide and CCK-RP

Question 20

Phases of pancreatic secretion

Answer 20

stimulatory: cephalic, gastric, intestinal
inhibitory: postprandial

Question 21

What nerve mediates the cephalic phase?

Answer 21

vagus nerve –> sham feeding produces about 50% of maximal enzyme secretion

Question 22

What inhibits the cephalic phase?

Answer 22

atropine

Question 23

What causes the intestinal phase?

Answer 23

acid and chyme in intestine –> ph below 4.5 releases secretin –> enzyme secretion

Question 24

What mediates postprandial inhibition?

Answer 24

1. excess intraluminal trypsin inhibits CCK release by digesting monitor peptide and CCK releasing peptide
2. oleic acid in ileum/colon via peptide YY
   glucose/iv AA

Question 25

Tests for pancreatic function

Answer 25

1. fecal fat (>10 abnormal)
2. sudan stain for fat
3. duodenal secretions
4. secretin stimulation test
5. imaging

–> need 90% loss of lipase to get a change in fecal fat

Question 26

Bile functions

Answer 26

1. excrete polar metabolites of lipid waste/bilirubin
2. fat and fatsoluble vitamin absorption
3. excrete cholesterol
4. IgA

Question 27

Where are different components of bile secreted?

Answer 27

1. organic components = hepatocytes into canaliculi
2. electrolyes and water= hepatocytes into ducts

some salts increase/reduce canalicular flow

Question 28

Rate limiting step in secretion of bile salts

Answer 28

secretion of components against concentration gradient in canaliculi

Question 29

Nuclear control of intracellular bile salts

Answer 29

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

Question 30

Rate limiting step in cholesterol synthesis

Answer 30

HMGCoA reductase

Question 31

How are primary bile salts formed?

Answer 31

7alpha hydroxylation and carboxylation side chain of cholesterol in liver

Question 32

How are secondary bile salts formed?

Answer 32

bacterial 7alpha dehydroxylation or isomerization in colon

Question 33

What does water solubility of bile salts depend on?

Answer 33

ionization of side chain –> secondary bile acids are more water soluble

Question 34

Bile salt conjugation

Answer 34

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

Question 35

Addition of what molecule increases ability to solubilize cholesterol in a mixed micelle?

Answer 35

lecithin

Question 36

What limits proximal intestinal absorption of bile salts?

Answer 36

ionization (conjugation)

Question 37

How do bile salts return to the liver?

Answer 37

portal vein

Question 38

What is the effect of small bowel stasis on bile salts?

Answer 38

premature deconjugation due to bacterial overgrowth leading to precipitation of bile salts and fat/vitamin malabsorption

Question 39

What products may protect mucosa against toxicity of bile salts?

Answer 39

cholesterol and phospholipids