Unit 6 - Pancreatic and Biliary Secretions Flashcards Preview

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Flashcards in Unit 6 - Pancreatic and Biliary Secretions Deck (57)
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1

what are zymogens secreted by pancreas? what are they activated by?

trypsinogen (activated by enteropeptidase)
chymotrypsinogen (activated by trypsin)
procarboxypeptidase A and B

2

what causes inflammation in pancreatitis?

digestive enzymes are activated before they reach the intestine

3

what kind of enzymes does the pancreas secrete?

proteases
lipases
amylases
nucleases (ribonuclease and deoxyribonuclease)

4

what are the exocrine VS endocrine secretions of the pancreas? what do they do?

exocrine: into ducts to lumen
-aqueous juice: has bicarbonate made by duct and centro-acinar cells
-enzyme juice: secreted by acinar cells into intercalary ducts that merge into secretory ducts
--secretions flow thru ducts of Wirsung and Sontorini to duodenum

endocrine secretions: into blood from islets of Langerhans regulate blood sugar and metabolism
-glucacon: from alpha cells
-insulin: from beta cells
-somatostatin: from delta cells

5

what are the actions of pancreatic aqueous secretion

bicarbonate neutralizes acid from stomach, and allows pancreatic enzymes to function at their optimal neutral pH
-pepsin is inactivated at neutral pH, so cannot attack duodenal mucosa
-neutralization of pH prevents damage to duodenal and intestinal mucosa by gastric acid
-aqueous secretion also serves to dilute enzyme juice

6

how is the exocrine pancreas organized?
-structure and function of acinar and duct cells

fundamental secretory unit is acinus + intercalated duct
-IDs merge to form intralobular ducts, which merge to form interlocular ducts, then the main pancreatic duct
-acinar cell is specialized for PRO secretion
--large condensing vacuoles are gradually reduced in size, and form mature zymogen granules that store digestive enzymes in apical region
-duct cell is cuboidal cell with abundant mitochondria and secretes bicarbonate
--small microvilli project from its apical membrane

7

what is the order of synthesis and secretion of enzymes in a cell? how does this relate to pancreatitis?

ribosomes on RER --> Golgi --> condensing vacuoles --> zymogen granules --> fuse with apical membrane so contents are discharged
-in pancreatitis, enzymes are released into the cell instead of being packaged in granules

8

how is VIP related to pancreatic secretion

vasoactive intestinal peptide (nt in gut) is not usually important in pancreatic secretion, but it's important in pancreatic tumors (vipomas) that cause watery diarrhea

9

what do CCK, ACh, gastrin, secretin, and VIP do?

CCK, ACh, and gastrin --> Gq --> PLC --> DAG for PKC, and IP3 to increase intracellular Ca++

secretin and VIP --> Gs --> AC --> cAMP --> PKA

will alter phosphorylation of these regulatory PRO to cause vesicle insertion and PRO secretion

10

how do secretin and CCK act together?

synergistically

11

how does secretion of Cl- by acinar cells occur? what does this do to Na+?

Na/K pump causes inward Na+ gradient across basolateral membrane
-Na/K/Cl cotransporter (all going inside cell) produces net Cl- uptake driven by Na+ gradient
-increase intracellular [K+] is shuted by basolateraly [K+] channels
-intracellular [Cl-] establishes electrochemical gradient that drives Cl- secretion into acinar lumen thru apical membrane Cl- channels
-movement of Cl- into lumen makes transepithelial voltage more lumen-negative, driving Na+ into lumen via tight junctions

12

what stimulates NaCl secretion and how?

ACh and CCK stimulate it via phosphorylation of basolateral and apical ion channels

13

what is the membrane potential of pancreatic duct cells at rest and during secretion?

-1 mV at rest
-5 mV during secretion

14

what makes up 25% and 75% of pancreatic secretions?

25% is NaCl from acinar cells
75% is HaHCO3 from duct cells

15

how does secretion of isotonic NaHCO3 happen in pancreatic duct cells?

Cl-HCO3 exchanger puts Cl- into cell and HCO3 into lumen
-some HCO3- that enters lumen directly enters cell via Na/HCO3 cotransporter on basolateral membrane
-additional intracellular HCO3- is made by carbonic anhydrase via CO2 + OH-
--OH- comes from splitting of H2O driven by extrusion of H+ into interstitial space by pump and Na/H exchanger
-lumen-negative voltage pulls Na+ into lumen via tight junction

16

what is the most powerful stimulus for HCO3- secretion from pancreatic duct cells? what else affects this? what are their mechanisms?

secretin
-activates AC, increases cAMP, stimulates PKA, and phosphorylates CFTR to activate it and replenish luminal Cl- for Cl-/HCO3- exchange

ACh and CCK also stimulate HCO3- secretion by activating Gq, to stimulate PLC, to release DAG (to stimulate PKC) and IP3, which releases Ca++ from internal stores
-apical K+ channel is activated by Ca++
-increased K+ effluz primes Na/K-ATPase

17

what does the rate of the apical Cl-/HCO3- exchanger depend on?

availability of substrate, including luminal Cl, which depends on the opening of the CFTR apical Cl- channel (cystic fibrosis transmembrane regulator)
-CFTR is activated by secretin

18

what are features of the aqueous secretion of pancreas?

venous blood is acidified during secretion by electrogenic H+ pump and Na/H exchange in basolateral membrane
-this negates the alkaline tide
-in intestinal phase, both secretin and CCK stimulate aqueous secretion by pancreatic duct cells

19

relationship between composition of pancreatic juice and pancreatic flow rate

electrolyte composition of aqueous secretion is function of rate of secretion
-when pancreatic flow rate changes, the [Na] and [K] concentrations in pancreatic juice remain constant, but [HCO3-] and [Cl-] change in reciprocal manner (maintained by Cl-/HCO3- exchanger in apical membrane of ductal cells)
-if rate is fast, will be high in HCO3-
-if rate is slow, will resemble plasma and extracellular fluid (higher in Cl-)

20

what does the "exchange hypothesis" mean?

HCO3- exchanges with Cl- in ducts when rate of secretion is low
-accounts for increase in bicarbonate with increased secretory rate

21

how does cystic fibrosis occur?

when CFTR channel is defective, pancreatic secretions are thick and viscous (enzymes), clogging pancreatic ducts and interfering with digestion, because aqueous secretion isn't made
-pulmonary mucous is also thick and viscous, causing dyspnea and premature death

22

how is pancreatic secretion in the 3 stages:
1. cephalic
2. gastric
3. intestinal

first 2 are low in volume and high in enzyme content
1. cephalic phase: vagal stimulation has greater effect on enzyme secretion from acini than on ductal aqueous secretion
2. distension of body induces pancreatic enzyme secretion by vaso-vagal reflex
-antral distension releases gastrin, which shares CCK receptor to stimulate acinar cells to secrete enzymes, and oxyntic parietal cells to secrete HCl
3. secretin and CCK released from intestinal cells in response to products of digestion

23

secretin
-structure
-what releases it and why
-what it does

27 AA peptide hormone released into blood by S cells in duodenal mucosa in response to acid entering intestine
-"nature's antacid" b/c inhibits gastric acid secretion and gastrin release
-instead stimulates gastric chief cells to secrete pepsinogen, and causes aqueous secretion by pancreatic duct cells, with secondary effect on acinar cells

24

what is the volume, HCO3- concentration, and enzyme content of pancreatic aqueous secretion VS pancreatic enzyme secretion?

AS: high in volume and [HCO3-], low in enzyme content

ES: high in enzyme content, low in volume

25

CCK
-structure
-what releases it and why
-what it does

33 AA peptide released into blood by I cells in duodenal mucosa in response to FA or AA entering duodenum
-causes enzyme secretion by acinar cells, and potentiates aqueous secretion during intestinal phase
-causes GB contraction and relaxes sphincter of Oddi to release bile from GB into duodenum
-slows gastric emptying

26

what is butter an effective releaser of?

CCK

27

composition of bile

yellow-green, alkaline solution with bile salts/acids (50%), bile pigments (2%), cholesterol (4%), neutral fats, phospholipids (25%), IgA, and electrolytes

28

what are bile salts? what do they do?

cholesterol derivatives that:
-emulsify fat
-facilitate fat and cholesterol absorption
-help solubilize cholesterol

29

what does enterohepatic circulation do?

recycle bile salts

30

what is the chief pigment of bile?

bilirubin (waste product of heme)

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