Pancreatic and Biliary Secretions

Question 1

name the four pancreatic proteases

Answer 1

trypsinogen, chymotrypsinogen and procarboxypeptidases A and B

Question 2

name the two pancreatic lipases

Answer 2

lipase and phospholipase

Question 3

what causes the activation of trypsinogen? chymotrypsin?

Answer 3

enteropeptidase in the mucosa of the gut

trypsin cleaves chymotrypsinogen

Question 4

what occurs in pancreatitis?

Answer 4

the pancreas becomes inflammed and the digestive enzymes are activated before they reach the intestine

Question 5

what are the exocrine secretions of the pancreas?

Answer 5

aqueous juice with HCO3- (centroacinar and duct cells) and enzyme juice (acinar cells)

Question 6

what are the endocrine secretions of the pancreas?

Answer 6

somatostatin, insulin and glucagon from the islets of langerhans

Question 7

what is the function of the aqueous secretion?

Answer 7

inactivate pepsin and HCl and dilute the enzyme juice

Question 8

describe zymogen production in the acinar cell.

Answer 8

large condensing vacuoles from the golgi reduce in size and form mature zymogen granules that reside in the apical portion of the cell. these fuse with the apical membrane during secretion

Question 9

what cellular structures are abundant in bicarb secreting pancreas cells?

Answer 9

mitochondria and microvilli

Question 10

what is the action of ACh, gastrin and CCK on acinar cells?

Answer 10

they increase intracellular Ca

stimulate NaCl secretion through channel phosphorylation of channels

Question 11

what is the action of secretin and VIP acinar cells?

Answer 11

increase cAMP

Question 12

how do CCK and secreten act together?

Answer 12

they are synergists- sum of effects is greater than when they act alone

Question 13

when is VIP important in pancreatic secretion?

Answer 13

when too much VIP is excreted-resulting in watery diarrhea (vipoma)

Question 14

what is the initial step in bicarbonate secretion by the duct cells?

Answer 14

diffusion of CO2 from blood into cell

carbonic anhydrase hydrates it to carbonic acid> H+ and bicarbonate

Question 15

what happens to the H+ produced during bicarb formation? what is the drive for this mechanism?

Answer 15

it is pumped by a Na/H exchanger into the blood

Na/K pump creates the gradient for this exchange

Question 16

which channel releases bicarbonate into the lumen?

Answer 16

Cl/ bicarbonate exchanger- depends on bicarb and Cl availability
Cl imported in by CFTR (ion channel)

Question 17

what activates the CFTR channel?

Answer 17

secretin- increases cAMP

Question 18

what happens to the K gradient formed by the Na/K pump in duct cells? what hormone modulates its activity?

Answer 18

there is a Ca activated K channel that is activated by CCK (increases intracellular calcium)
primes the Na/K pump to increase the rate of secretion by the duct cell

Question 19

what is the electrical consequence of bicarbonate excretion?

Answer 19

net luminal negative transmembrane potential

driving force to move Na and K into the lumen (cation selective paracellular pathway)

Question 20

what are the two changes in blood pH that occur with HCl and HCO3- secretion?

Answer 20

bicarbonate is introduced to the blood with acid secretion- alkaline tide and the secretion of HCO3- adds H+ to the blood to negate that

Question 21

how does the composition of pancreatic juice change wihth flow rate?

Answer 21

Na and K concentrations stay the same
bicarbonate increases with increased flow and chloride decreases (because of apical exchanger)
if rate of secretion is slow- bicarb and chloride concentrations resemble plasma

Question 22

what pancreatic events occur with cystic fibrosis?

Answer 22

CFTR channel is defective- pancreatic secretions are viscous and clog the pancreatic ducts

Question 23

what occurs in the pancreas with the three phases of ingestion?

Answer 23

cephalic: vagal stimulation increases acini secretion
gastric: vasovagal reflex induces enzyme secretion and gastrin stimulates acini
intestinal: CCK and secretin stimulate duct cells

Question 24

what stimulates secretin release?

Answer 24

acid in the duodenum

Question 25

what are the effects of CCK?

Answer 25

acinar cell secretion, potentiation of aqueous secretion, gallbladder contraction and slows gastric emptying

Question 26

what is bile made up of?

Answer 26

bild salts, bild pigments (mostly bilirubin), cholesterol, neutral fats, phospholipids, and electrolytes

Question 27

what do bile salts do?

Answer 27

emulsify fat, solubilize cholesterol and facilitate their absorption

Question 28

what recycles bile salts?

Answer 28

enterohepatic circulation
bile is absorbed in ileum by Na coupled transporters
goes to the liver via the portal vein
absorbed with NTCP and OATP into hepatocytes and reused

Question 29

what is the rate limiting step in bile acid formation? why is formation so tightly regulated?

Answer 29

7 alpha hydroxylase (hydroxylates C7)- uses feedback inhibition by product (bile acids)
important because they can be carcinogenic

Question 30

what is choleretic? name one type

Answer 30

agent that stimulates bile output

bile acid sequestrants- prevent reabsorption in gut

Question 31

how are bile acids transformed into bile salts? why is this done?

Answer 31

by conjugation with glycine or taurine

this is done to decrease the pK to make more of the salts ionized (increase solubility)

Question 32

where does bile go when it is secreted by hepatocytes?

Answer 32

bile canaliculi that empty into bile ducts

Question 33

what occurs when the sphincter of Oddi is closed?

Answer 33

bile is made continuously- it is diverted back up the duct and into the gallbladder where it is stored and concentrated

Question 34

how much bile is lost in feces and replaced by synthesis in the liver?

Answer 34

about 0.5 g of the 12-25 g secreted by the liver daily

Question 35

how does the liver maintain the bile amounts throughout the meal?

Answer 35

all of the bile salts are reabsorbed and secreted again during the meal

Question 36

what is secreted by the bile ducts?

Answer 36

an aqueous solution similar to that of the pancreas

high in bicarbonate

Question 37

what is the feedback inhibition of bile salt production?

Answer 37

reabsorption of the bile acids from the portal blood

Question 38

what happens to the bile acids that are deconjugated by bacteria in the gut? what else can the bacteria do?

Answer 38

they are passively absorbed by nonionic diffusion

bacteria also dehydroxylate bile acids to secondary bile acids

Question 39

what causes the concentration of gallbladder contents?

Answer 39

active transport of Na, Cl and HCO3- out of the cell
driven by Na/K pump
water flows passively following the ions

Question 40

what is the transport of ions at the luminal side of the gallbladder cell? the basolateral side?

Answer 40

Na/H exchanger and Cl/HCO3 exchanger (H pumped out faster than bicarbonate- lumen acidification)
K channel, Cl channel and Na/K pump

Question 41

what two signals cause gallbladder emptying?

Answer 41

CCK and vagal stimulation

Question 42

why are both liver and gallbladder bile isosmotic to plasma?

Answer 42

micelles form in the bile that only contribute 1 unit of concentration

Question 43

what is the difference between a simple and mixed micelle?

Answer 43

simple- only bile salts

mixed also contains cholesterol and phosphatidylcholine

Question 44

what are the most common type of gallstones in the US? how do they form?

Answer 44

cholesterol gallstones
supersaturation of choleterol in the liver causes it to precipitate from the bile solution forming crystals> microstones> macrostones

Question 45

what is cholesystitis?

Answer 45

inflammation of the gallbladder most commonly caused by blockage of the cystic duct by a gallstone