Pancreatic and Biliary Function Flashcards
1
Q
proteases
A
- digest proteins
- trypsinogen
- chymotrypsinogen (trypsin activates)
- procarboxypeptidase A and B
2
Q
zymogens
A
- inactive form of protein have no enzymatic activity
- activated in gut
- if activated too early-pancreatitis
3
Q
pancreas
A
- most important digestive gland
- 1 liter secreted per day
- exocrine secretions into ducts and lumen
- aqueous juice high in HCO3 from centro acinar and duct cells
- enzyme juice from acinal cells
- endocrine secretions from islets regulate blood sugar and met
- glucagon by alpha
- insulin by beta
- somatostatin by delta
4
Q
pancreatic aqueous secretion
A
- bicarbonate neutralizes acid from stomach and allows pancreatic enzyme to function at their optimal pH
- pepsin is inactivated at neutral pH, and can’t attack duodenal mucosa
- neutralization of pH prevents damage to duodenal and intestinal mucosa
- dilutes enzyme juice
- from centro acinar and epithelial cells of intercalary ducts
5
Q
organization of exocrine pancreas
A
- fundamental secretory unti is acinus and intercalated duct
- acinar specialized for secretion
- large condensing vacuoles are gradually reduced in size and form mature zymogen granules that store enzymes in the apical region
6
Q
synthesis and secretion of enzymes
A
- originates in pancreatic acinar cells
- RER to golgi to condensing vacuoles to zymogens
7
Q
secretin
A
- activates Gs protein and leads to PKA activation and increase cAMP
- regulated by hormones
- VIP also can activate this system
- cAMP activates CFTR for exchanger
8
Q
Ach and CCK
A
- activate Gq protein and activate PIP, IP3, and PKC
- increases intracellular calcium
- secretin and CCK are synergistic
9
Q
VIP
A
-important in vipomas- watery diarrhea
10
Q
secretion of chloride by acinar cells
A
- Na-K pump creates inward directed NA gradient across basolateral membrane
- Na/K/Cl cotransporter produces the net Cl uptake, driven by Na gradien
- rise in intracellular K that results is shunted by basolateral K channels
- intracellular accumulation of Cl establishes gradient that drives Cl into acinar lumen through apical membrane Cl channels
- movement of Cl makes trans epithelial voltage more lumen negative, drives Na into lumen (with water)
* CCK and ACh stimulate this
11
Q
isotonic Na and HCO3 secretion by pancreatic duct cells
A
- bicarbonate secretion into the lumen occurs via a Cl-HCO3 exchange mechanism
- some of the HCO3 that enters the lumen directly enters the cell across the basolateral membrane via a Na/HCO3 transporter
- additional HCO3 is generated by carbonic anhydrase
- OH needed by CA comes from splitting water, which is driven by removing excess H by Na-H exchanger and H pump
- lumen negative voltage pulls Na into the lumen
* *HCO3 secretion stimulated by secretin (through cAMP and PKA and phosphorylated CFTR)
- CFTR puts Cl out and makes gradient for exchanger in first step
- Ach also stimulates HCO3-Gq-increase Ca, primes na/k ATPase for secretin
12
Q
features of aqueous solution
A
- venous blood is acidified during secretion by and electrogenic proton pump and Na/H exchanger and negates alkaline tide
- in intestinal phase- secretin and CCK stimulate aqueous secretion by pancreatic duct cells
13
Q
composition of pancreatic juice and flow rate
A
-HCO3 increases the faster the flow rate
14
Q
CF
A
- CFTR channel defective
- pancreatic secretions thick and viscous-clogging ducts and interfering with digestion
- pulmonary mucous is also thick and viscous, causing dysnpea and premature death
15
Q
regulation of pancreatic secretion
A
- during cephalic and gastric phase, stimulation from vagus fibers causes release of pancreatic juice
- in gastric phase, distension of the stomach results in the release of gastrin from the G cells
- acidic chyme entering the duodenum causes the enteroendocrine cells of the duodenal wall to release secretin, whereas fatty, protein rich chyme induces release of CCK
- CCK and secretin enter blood stream
- upon reaching the pancreas, CCK induces enzyme juice, secretin causes HCO3 juice
16
Q
cephalic phase
A
-vagal stimulation has a greater effect on enzyme secretion from acini than on ductal aqueous secretion
17
Q
gastric phase
A
- distension of body of stomach induces pancreatic enzyme secretion by vago-vagal replex
- antral distension release gastrin
18
Q
intestinal phase
A
-secretin and CCK released into blood from intestinal cells in response to products of digestion
19
Q
intestinal phase regulation-secretin
A
- secretin is a 27 aa peptide hormone released into blood by S cells in duodenal mucosa in repsonse to acid
- natures antacid
- inhibits gastric acid secretion and release of gastrin
- stimulates chief cells to secrete pepsinogen
- aq secretion by pancreatic duct cells
- secretion is then high in vol, high in HCO3, low in enzyme content
20
Q
intestinal phase regulation-CCK
A
- 33 aa peptide from I cells in duodenal mucosa in response to FA and aa
- elicits enzyme secretion by acinar cells and potentials aq secretoin during intestinal phase
- causes gallbladder contraction and relaxes sphincter of Oddi to release bile
- slows gastric emptying
21
Q
composition of bile
A
- yellow-green
- alkaline solution
- bile salts, bile pigments, cholesterol, neutral fats, phospholipids, electrolytes
- cholesterol derivatives that emulsify fat, facilitate fat and cholesterol absorption, help solubilize cholesterol
- enterhepatic circulation recycles bile salts
- chief pigment is bilirubin, a waste product of heme
22
Q
biosynthesis of bile salts
A
- rate limiting step is addition of hydroxyl group at position 7 by cholesterol 7 alpha-hydroxylase
- that enzyme is reduced when excess bile acid and increased in excess cholesterol
- made by liver and activate nuclear hormone receptor to regulate expression
- choleretic agent stimulates the liver to increase bile
- liver conjugates primary and secondary bile acids with glycine or taurine to their respective bile salts
- the bile salt is named for the acid and the conjugating amino acid
- see picture
23
Q
bile acids
A
- salts
- 2 primary (70%) synthesized in the liver and 2 secondary
- conjugated with glycine or taurine in the liver
- conjugation reduces pK from 7 to below 4
- anionic at neutral pH and water soluble
- amphipathic- helps them emulsify and solubilize ingested fats and steroids
24
Q
path of bile
A
- secreted into canaliculi
- canaliculi are guarded by tight junctions
- produced by hepatocytes into canaliculi and then to ducts
- then to sphincter, if closed back into gallbladder for storage
25
Q
path of bile 2
A
bile ducts-hepatic ducts-common bile duct-duodenum-cystic duct-gall bladder
- stored and concentrated in gallbladder
- CCK contracts gallbladder
- 50% bile acids, 25% phospholipids, 4% cholesterol, 2% bile pigments, inorganic ions and IgA
26
Q
daily bile salt turnover
A
total pool 3-4g
- secretion by liver 12-25 grams
- reabsorbed and secreted twice during a meal and several times daily via the enterohepatic circulation
- daily loss in feces and replaced by synthesis in liver is 0.5g
- absorbed as conjugated bile salts
27
Q
biliary secretion
A
- bile from intestine flows through the liver via the portal vein
- absorbed by hepatocytes
- secreted into canaliculus
- returns to liver bound to albumin
- taken up by sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptide (NTCP, OATP)
28
Q
bile acid-independent secretion
A
-watery HCO3 rich fluid by cholangiocytes of the ducts and ductules similar to pancreatic aq secretion, stimulated by secretin
29
Q
bile acid dependent secretion
A
- by hepatic parenchymal cells
- stimulated to secrete by bile acids returning to liver in portal blood
- synthesis of bile acids is inhibited by bile acids returning to the liver via portal blood
30
Q
terminal ileum
A
- reabsorbed as bile salts through Na+ coupled cotransporter (ASBT)
- bacteria de conjugate some
- passively absorbed by nonionic diffusion
- bacteria also take some to secondary acids from primary, some are captured and some are excreted
31
Q
BA concentration in gallbladder
A
- active transport of Na, Cl, HCO3 out of lateral membrane and continued micellar formation
- na-h exchange and Cl-HCO3 exchange in apical
- basolateral Nacl absorption by Na/K pump and Cl channels
- K channels for recycling
32
Q
release of bile from gallbladder
A
- responds to cephalic stimuli
- neural or hormonal
- sphincter of Oddi relaxes and contracts gallbladder
33
Q
composition of salts
A
- bile salts concentrated and form micelles
- salts are less concentrated due to secretion
- removal of normal salts concentrates the bile salts
34
Q
bile micells
A
- lecithin and cholesterol
- solvents for hydrophobic waste products to be removed from body and hydrophobic components of diet to be captured from the intestine
35
Q
formation of gallstones
A
- cholesterol most common
- pigment in far east and africa
- supersaturation of cholesterol in liver
- nucleation and precipitation- seeding of cholesterol crystals or microstones
- growth of microstones to macrostones
- below a certain point cholesterol is soluble but not above it
