Flashcards in Lecture 10 and 11: Functions of the Liver Deck (65):
What are the 3 major functions of the liver?
How are hepatocytes arranged in the liver?
in anastomosing cords that form plates
What it the main benefit of the high blood flow received by hepatocytes?
high quantities of O2 and nutrients
What are sinusoids?
low-resistance cavities that supply the plates of hepatocytes
(sinusoids are supplied by branches of portal vein and hepatic artery)
What comprises the hepatic triad?
hepatic artery, portal vein, and bile duct
Which cells are closest to the triad?
zone 1/periportal cells
Where are the pericentral cells?
Zone 3 (furthest from the triad)
Which cells receive the largest supply of nutrients and O2?
periportal cells (nearest to the triad)
Which cells are most sensitive to oxidative damage?
periportal cells (require the most O2)
Which cells are most active in detoxification?
True or false: zone 2 and 3 cells can function as zone 1 cells in liver disease
What are Kupffer cells?
resident liver macrophages
apical membranes of adjacent hepatocytes form channels called ____________
What is the function of the cancaliculi?
Name the cell type that lines the biliary ductules
trace the path of bile from formation to storage
hepatocyte --> canaliculus --> biliary ductules --> hepatic ducts --> common hepatic ducts --> gall bladder or intestine
What roles do the liver play in carb metabolism?
2) Glycogen storage, buffering excess glucose
What roles do the liver play in lipid metabolism?
1) fatty acid oxidation (rich store of enzymes)
2) convert products of carb metabolism into lipids (make lipoproteins, cholesterol, phosphlipids)
3) Convert cholesterol to bile acids
What roles do the liver play in protein metabolism?
1) makes all non-essential amino acids
2) makes all plasma proteins (albumin, clotting factors)
3) converts ammonia to urea
What are the 2 steps of first pass metabolism?
1) Phase 1 reactions (oxidation, hydroxylation)
2) Phase 2 reactions (conjugate substances with glucuronide, sulfate, amino acids, glutathion)
What enzymes catalyze Phase 1 reactions of detoxification? (oxidation)
What role does the liver play in excretion?
gets rid of large water-soluble catabolites and molecules bound to plasma proteins, steroid hormones, etc that cannot fit through the kidney
Name the components of bile
What are the 2 primary bile acids produced by the hepatocytes?
1) cholic acid
2) chenodeoxycholic acid
What produces secondary bile acids?
colonic bacterial enzymes
What are the 3 secondary bile acids?
1) ursodeoxycholic acid
2) deoxycholic acid
3) lithocholic acid
What are bile acids conjugated with?
glycine or taurine
What is the benefit of conjugated bile acids?
more water solube
Where are conjugated bile acids ACTIVELY absorbed?
What transporter absorbs bile acids?
asbt (Na+ dependent bile salt transporter)
If bile acids are not absorbed in the terminal ileum, what happens to them?
they are deconjugated by colonic bacterial enzymes then passively reabsorbed in colonic epithelium
What does bile acid synthesis depend on?
the body's needs
(ex: ileal resection requires increased bile synthesis since it is not getting absorbed)
What is the avenue for bile acid recycling?
True or false: conjugated bile acids are able to passively cross the intestinal epithelial lining?
FALSE (they cannot)
Bile absorption is __________ in the small intestine (ileum) and _________ in the large (colon).
How do cholangiocytes modify bile?
1) reclaim glucose and amino acids
2) exchange Cl- for HCO3- (making bile alkaline)
3) Absorb glutathione
4) diluted (secretin stimulates aquaporin water channels)
Ejection of bile form the gall bladder begins within ____ _____ of meal injestion
What is the stimulus for bile release?
gallstones are composed of ___________ or ____________
cholesterol; Ca++ bilirubinate
What normally inhibits the precipitation of cholesterol in bile?
What factors increase chance of bile nucleation?
What is the distinguishing feature of pigment stones?
What is the first product of heme degradation?
biliverdin (then converted to bilirubin)
Bilirubin binds to __________ in the bloodstream to increase solubility
What transporter uptakes bilirubin in hepatocytes?
What enzyme conjugates bilirubin with glucoronic acid?
UDP glucuronyl transferase
What deficiency do newborns born with jaundice have?
UDP glucuronyl transferase
Walk through the bilirubin formation and excretion pathway
RBCS --> hemoglobin --> biliverdin --> bilirubin --> bilirubin/albumin --> bilirubin --> conjugated bilirubin --> urobilinogen --> urobilin
What is the benefit of conjugating bile?
makes it water soluble
After bile is deconjugated by bacterial enzymes, it is metabolized into _____________.
Does the enterohepatic circulation absorb urobilinogen?
yes, a portion of it
What happens to the urobilinogen that is not absorbed via the enterohepatic system?
converted into urobilin and stercobilin and excreted in feces
What form of bilirubin can cross the BBB?
What are 2 possibilities that lead to increases in unconjugated bilirubin in the plasma?
1) loss or absense of UGT (enzyme responsible for conjugating bilirubin to glucuronic acid)
2) oversupply of heme
Why is high bilirubin in the urine in CONJUGATED bilirubinemia?
1) defect in transporter that secretes conjugated bilirubin in bile
2) blockage of bile flow (gallstone)
What is the root cause of jaundice?
accumulation of free and conjugated bilirubin in the blood (hepatic dysfunction)
What is pruritus?
itching of skin due to increased bile acids in serum leading to skin deposit
What do bilirubin levels need to be at in order for jaundice to be diagnosed?
(aka what is the threshold for hyperbilirubinemia?)
Name a few causes of hyperbilirubinemia?
1) hemolytic anemia (produce too much bilirubin)
2) decreased bilirubin uptake by hepatocytes
3) disturbed intracellular protein binding and conjugation
4) disturbed secretion of conjugated bilirubin into bile canaliculi
5) bile duct obstruction
6) potent antibiotics (no bacteria)
7) lack of UGT in newborns
What are the 2 sources of ammonia (NH3) in the body?
1) catabolism of protein
2) colonic bacteria
Which form is membrane permeable, NH3 or NH4?
What is hepatic encephalopathy?
passage of NH3 into brain because liver is damaged and not detoxifying it
Can hepatic encephalopathy be fatal?
What causes portal hypertension?
increased bp in the sinusoids