Topic 6.4 Flashcards
How much of the pancreatic secretion is endocrine?
About 2%
What are the 2 main roles of pancreatic secretion?
- neutralize acid content from the stomach
- digestion using digestive enzymes
How much pancreatic juice is secreted per day?
700-900mL / day (depends on ingested food)
What are the characteristics of pancreatic juice secretion? (2)
- Isoosmotic
- Alkaline
What type of secretion mechanism for pancreatic juice?
Sequential secretion : both acinar and duct cells will produce PJ (duct > acinar)
What are the 3 main differences between salivary acinar secretion and pancreatic acinar secretion?
- secrete more enzymes than salivary gland, in the inactive form
- less fluid
- has CFTR chloride channel
Which of the pancreatic cells produce the majority of the fluid?
The duct cells
How do pancreatic duct cells make the pancreatic juice more alkaline?
By exchanging CL- for HCO3- (proximally)
What happens in the distal pancreatic duct cells?
Some HCO3- can be reabsorbed and exchanged for Cl-, the amount depends on the rate of secretion
What are the 3 ways of regulating pancreatic juice secretion?
- Neural regulation
- Hormonal regulation
- Feed forward regulation (look at food)
Which neural regulation dominates pancreatic juice secretion?
parasympathetic
How does Ach affect PJ secretion? (3)
- Acts on acinar cells
- Gq coupled (M3)
- Upregulates enzyme secretion
How does VIP affect PJ secretion? (3)
- Acts on vessels (or acinar cell)
- Gs coupled
- Causes vasodilation to increase volume of secretion
What are the 2 hormones that can affect PJ secretion?
CCK and secretin
When is secretin produced?
When there is low duodenal pH condition
What is the effect of secretin on pj secretion?
- acts on the duct cells
- increase HCO3- secretion
When is CCK produced?
When there is protein degradation / digested food in the stomach
What is the effect of CCK on the pj secretion?
will increase the secretion of digestive enzymes (Ca2+ signal)
What is the vagovagal reflex?
presence of food in the stomach (or intestine) increases pancreatic juice secretion
How much blood can the liver store?
0.5L
What are the 5 main roles of the liver?
- Metabolic role
- Blood reservoir
- Store for copper, Fe
- Immunological (kupffer)
- secretory and excretory functions
What is the secretory fluid of the liver?
bile, digestive fluid without proteins
What is the excretory fluid of the liver useful for?
removing substances that can’t be removed by kidneys (xenobiotics, heavy metals, drugs)
Bile production / day
200-1200mL/day
What are 4 characteristics of the bile?
- Isoosmotic
- Alkaline
- Mixture of hepatic and gallbladder bile
- Micellar formation
What happens to bile from the liver in between meals?
It can be redirected to the gallbladder for storage and concentration
What constitutes 50% of the dry weight of bile?
bile acids
What are the 4 most important components of bile?
bile acids, bile salts, H20, HCO3-
What are the primary bile acids?
Bile acids formed in the liver
2 examples of primary bile acids
- Cholic acid
- Chenodeoxycholic acid
What are bile salts?
Conjugated bile acids, for example to glycine or taurine (more water soluble)
What are the bile acids / salts important for?
they are necessary for the formation of micelles due to their amphipathic nature
What are other molecules than can be found in the micelles? (2)
- phosphatidyl choline
- cholesterol
When do gallstones happen?
When one of the constituents of the micelle is overproduced and can’t be integrated, thus forming crystals
What is the daily cholesterol balance?
input = output = 1.25 g/day
What are the 2 inputs of cholesterol?
- Diet (20%)
- Hepatic and extrahepatic synthesis (80%)
What are the 2 outputs of cholesterol?
- As cholesterol (75%) to bile
- As bile acids (25%) to bile
What are the 2 ways of entry of solutes into bile?
- Active secretion (bile acids, conjugated bilirubin, xenobiotics)
- Passive permeation (H20, glucose, calcium)
What are the 2 important transporters for transport of bile out of the cell?
- BSEP
- MDR (multi drug resistance)
What does MDR3 transport?
phosphatidyl choline
What does MDR1 transport?
cationic xenobiotics
What does BSEP transport?
bile acids
What are the 2 ways of transporting water to the bile canaliculi?
- Bile acid dependant flow
- Bile acid independant flow
What is bilirubin an end product of?
Porphyrin catabolism : hemoglobin - biliverdin - bilirubin
What does bilirubin need to be transported to bile?
It needs to be conjugated to glucuronic acid in the cell = bilirubin glucuronidase
Which cells can modify the bile in the ducts?
cholangiocytes, possess a lot of CFTR to attract Cl, H20 and HCO3-
What are the 3 factors of bile flow?
- Fluid secretion (cholangiocytes)
- bile acid dependant flow
- bile acid independant flow
What is the choleretic effect?
Aka primary regulation : if bile ACID secretion is higher, then the total bile FLOW will be higher as well
What are the 3 ways of regulating bile flow?
- choleretic effect
- neural regulation
- secretin
What are the 2 neural regulations of bile flow?
- sympathetic : decreases
- parasympathetic : vagus, increases
How does secretin regulate bile flow? (3)
- acts on duct cells
- upregulates CFTR number and function
- increases bile secretion
How is bile secretion compared to the plasma? (2)
Isotonic and alkaline
How is H20 reabsorbed from the gallbladder?
standing gradient osmotic mechanism
How much bile is lost per day?
0.6 g lost /day (same as daily production)
What is the enterohepatic circulation of bile?
One bile molecule is reused multiple times
How is bile released after a meal?
NO and VIP relax the sphincter of odi after activation of the parasympathetic system
What is VIP coupled to ?
Gs
How does Ach help with release of bile after a meal?
can constrict the gallbladder by binding to muscarinic 3, 4, 5 receptor
What can enhance the effect of Ach on the release of bile? (2)
- CCK (Gq), which is released in response to presence of food.
- CCK can also activate afferent vagal nerves for the vagovagal reflex
How much small intestine mucosa secretion / day?
1.5-2L / day
What are 4 features of small intestine secretion?
- Isoosmotic
- Mostly H20
- Most important electrolyte is HCO3-
- No production of digestive enzymes
What is the main regulation of small intestine secretion
mostly parasympathetic, with Ach and VIP : PKA phosphorylates CFTR
What is the effect of the cholera toxin?
activates all Galpha SU : continuous cAMP signal irreversibly
What are the 3 other regulators of small intestine secretion?
- sympathetic system (decrease secretion)
- ENS : distention of wall, activation of chemoreceptors
- Paracrine mediators : serotonin (increase fluid secretion)
4 properties of colonic secretion
- rich in mucin
- isotonic
- no digestive enzymes
- HCO3- rich
How much secretion is presented to the small intestine per day?
8.5 L / day
How much secretion does the small intestine remove in total / day?
6.5 L / day
How much secretion does the large intestine remove in total / day?
1.9 L / day
How much secretion leaves / day in the feces?
Around 1L / day
