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57 Cards in this Set

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  • Back
How is the pancreas formed in embryology
2 buds (one ventral and one dorsal) which fuse
What is it called when the two ducts do not fuse to form one?
pancreas divisum
What percentage of the pancreas do the acinar cells compose?
84% (islet 2%)
Do the endocrine hormones of the pancreas affect exocrine release?
Yes (but not major contributor) - insulacinar portal system
What do the acinar cells synthesize?
various digestive enzymes for fat, carbs, and proteins
What do the ductal cells secrete?
ions and water
What are the three main purposes of increasing pH in the small intestine (via bile salt)?
1. optimize pancreatic enzyme function

2. maintain bile salt solubility

3. prevent intestinal mucosa damage
What volume does the pancreas secrete per day?
2.5 L
What is the major anion in pancreatic secretion?
Chloride at rest -> bicarb at higher flow
What is the major affect of the hormone secretin?
release of water and bicarb in the ducts
By what mechanism does secretin cause increased secretion of water and ions in the ducts?
activation of adenylate cyclase and CFTR -> exchanges bicarb for chloride
Which two enzymes are secreted in their active forms?
Amylase and Lipase
How are the other enzymes activated?
Brush border enterokinase activates trypsin which activates the remaining enzymes
What is the major protection against autodigestion of the pancreas?
Release as inactive enzymes
If trypsin becomes activated prematurely, what is responsible for its inactivation (only 10%)?
Pancreatic Secretory Trypsin Inhibitor (PSTI)
What two other mechanisms provide further prevention of autodigestion?
1. cytosolic proteases

2. Non-specific protease inhibitors in interstitium and blood
What is amylases main action?
hydrolyze 1,4-glucosidase linkages (not 1,6)
What 4 things are necessary for fat breakdown and absorption?
1. Lipase

2. bicarb (to neutralize acid)

3. intestinal motility (to promote mixing)

4. Bile salts
Lipase works in a complex with what else?
bile salt and colipase
What initiates protein digestion in the stomach?
Pepsin
What are three examples of enzymes involved in protein metabolism?
1. trypsin

2. chymotrypsin

3. elastase
Where does enzyme synthesis take place in the cell?
RER
Enzymes are packaged and released from what type of granules?
zymogen granules
Are the relative amounts of the different enzymes constant?
No - change based on diet
What are the 2 classes of agonists leading to enzyme secretion?
1. Those that increase cAMP (VIP, secretin)

2. Those that mobilize free calcium (CCK, ACh, GRP)
What is the major hormone leading to gall bladder contraction and pancreatic release?
CCK (cholecystokinin)
What are the other 5 effects of CCK?
1. Delays gastric emptying

2. Affects small bowel motility

3. Relaxes sphincter of Oddi

4. Increases insulin

5. Increases satiety
What are the 3 phases of pancreatic secretion?
1. Cephalic

2. Gastric

3. Intestinal
What is the major mediator of the cephalic phase?
Vagus nerve (via ACh)
Which reflex is responsible for the gastric phase?
Vagovagal reflex (gastric distention)
Acid in the duodenum triggers the release of what?
Secretin
Do the parent molecules or breakdown products stimulate hormone and enzyme release in the intestinal phase?
Breakdown products (therefore basal low level of enzymes need to be present to initiate process)
What is the major inhibitor of CCK and enzyme secretion?
Trypsin (that's not complexed with food, trying to digest it)
Why doesn't trypsin always inhibit CCK?
Because when luminal protein present it binds trypsin preventing inhibition
What are other triggers of inhibition?
IV amino acids or glucose, oleic acid (fats) in colon
How low do pancreatic enzymes need to be for steatorrhea (fat in stool) to become apparent?
10% of normal (pancreatic insufficiency)
What two methods are there for measuring fat content of stool?
1. 72 hr stool collection while on 100g/ day fat diet

2. Sudan stain test
Are measurements of CCK or bicarb following a meal usually done to test pancreatic function?
No - requires duodenal intubation and are not widely available
How does the body excrete cholesterol?
Via bile
What causes gallstones?
Precipitation of cholesterol and bilirubin
What is the major organic component of bile?
Bile salts
What is the first step in bile salt synthesis?
Form cholesterol from acetate
What is the rate limiting enzyme in forming cholesterol?
HMGCoA reductase
What is required to convert cholesterol to bile salts?
carboxyl side chains and hydroxyl groups (creating the hydrophilic side)
Where are primary bile salts formed?
Formed in the liver (ex. chenodeoxycholic acid and cholic acid
Where are secondary bile salts formed?
produced in colon by bacterial 7 alpha dehydroxylation (ex. deoxycholic acid)
What is it called when a molecule has a hydrophilic and hydrophobic side?
Amphipath
What is conjugation of bile salts?
Addition of a taurine or glycine to the carboxyl side chain
What is the purpose of conjugation?
Make the bile salts stronger acids and allowing easy ionization in small intestine

Prevents back diffusion in bile ducts and intestines
What is the critical micellar concentration?
concentration of bile salts at which micelles will form?
What are mixed micelles?
Micelles that have added lecithin (phospholipid) - increased solubility of cholesterol and other lipids
Where are bile salts reabsorbed and returned to liver?
Terminal ileum
What is the process of bile salt secretion and reabsorption called?
Enterohepatic circulation
In what two ways do bacteria affect bile salts?
1. Deconjugation

2. removal or change of 7 alpha hydroxyl to 7 beta (produce secondary bile salts)
What affect does bacterial overgrowth in the small intestine have on bile salts?
Causes them to precipitate -> malabsorption of fats
What is the rate limiting step in bile secretion?
ATP dependent canalicular pumps
What is the function of Farnesoid X factor (FXR)?
Senses intracellular bile salts and causes decreased synthesis and increased secretion