AN SC 311 ch.11 notes
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What are mixed micelles?
Bile acids and cholesterol that is mixed with phosphatidycholine
What are the 2 functions of bile?
- the excretion of hydrophobic waste
- the digestion and absorption of lipids
What products are completely reliant on micellar solubilization for absorption?
saturated long chain fatty acids and fat soluble vitamins
What are Bile acids?
- amphipathic molecules
- form micelles
Where are bile acids derived from, and where does it occur?
- occurs in pericentral hepatocyte
What enzyme is involved when cholesterol is changed to bile acids?
7 alpha hydroxycholesterol
Why are bile acids kinked?
because they are highly water soluble (hydrophilic) when ionized.
what are the two primary, and secondary acids derived from cholesterol?
- primary: chenodeoxycholic acid and cholic acid
- secondary: lithocholic acid from chenod and deoxycholic acid from cholic acid
How are secondary bile salts created?
when the primary bile salts enter the distal small intestine they can be acted on by the bacterial enzymes to yield secondary bile acids
What does conjugation do to bile acids. What are the 2 molecules that are used from conjugation?
- it makes them more water soluble
- taurine and glycine in the hepatocyte
Why can lithocholic acid be beneficial?
it can be sulfated which decreases cytotoxic effects which could have lead to liver injury
What do bile acids form?
mixed micelles with phosphatidylcholine
Because bile acids are fully ionized what do they need for their secretion and uptake?
active transport mechanisms
Where are bile acids first secreted across?
What are some secondary solutes that passively mix with the bile?
glutathione, glucose, AA, and urea
What does the multi drug resistance protein do (flippase)?
- It is a member of the ABC transporters
- it flips molecules of phospatidylcholine in the inner canalicular membrane into the lumen in the form of vesicles where it mixes with the bile acids to form mixed micelles
What are the transporters responsible for the secretion of cholesterol into bile?
ABC 5, ABC 8
What colour does conjugated bilirubin make bile?
Where does bile move next after the canaliculi?
What are bile ductules lined with?
What is the permeability of cholangiocytes and what kind of cells are they?
- is selective to electrolytes but is permeable to water and the bile becomes isotonic.
- they also allow reabsorption of glucose and AA. This prevents bacteria growth by limiting nutrient availability.
- they are columnar epithelial cells
What do cholangiocytes secrete?
HCO3 in response to secretin release
What do the ductules release (immune)?
IgA into the bile gives host defence.
Where does bile get reabsorbed? and what is the transporter responsible?
- in the ilium
- apical sodium dependent bile salt transporter
- secondary bile transporter OST present at basolateral domain of ilium epithelial cells
What happens to bile acids that enter the colon?
they are deconjugated by bacteria this leads to a higher pKa and they can be reabsorbed passively.
What are bile acids bound to in the portal circulation?
What happens when bile acids return to back to the liver after reabsorption?
return to the liver, leave portal circulation in sinsuoids than taken up across basolateral membrane of periportal hepatocytes. The unconjugated bile acids are then re conjugated.
Are bile salts found in the blood, urine?
a bit will be found in the blood after meals. Should never be seen in urine because of being bound to albumin.
How is bile acid production regulated?
Is regulated by negative feedback inhibition on cholesterol 7 alpha hydroxylase.
What is cholestatis?
production of bile is impaired or bile flow is obstructed
What is primary biliary cirrhosis?
inflammatory destruction of cholangiocytes lining intralobular bile ductules
what is primary schlerosing cholanglands (PSC)?
inflammation and fibrosis of both intra and extrahepatic bile ducts.
what is congental biliary atrusion?
pediatric condition intrahepatic bile ducts do not form properly. leads to becoming jaundiced. Cannot excrete cholesterol or other consistuents via bile. Need a liver transplant
what is obstructive jaundice?
blockage of one of the extrahepatic bile ducts with gallstone. This leads to cytotoxic effects of retained bile acids.
What is hereditary cholestasis syndrome?
progressive familial intrahepatic cholestasis. It is an autosomal recessive disorder from a mutation in BSEP, leading to total absence of bile acids.
What happens when there is a mutation in the MDR3 protein in PFH patients?
absence of phosphatidylcholine in the bile. Mixed micelles dont form. Concentration of monomeric bile acids in the biliary systems increase.
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