Bile and Bile Salts Flashcards
80% of bilirubin comes from ____
red cells –> heme –> iron, CO, biliverdin –> bilirubin
Unconjugated bilirubin is polar/nonpolar
polar –> but insoluble b/c polar groups are hidden in tertiary structure
How is insoluble unconjugated bilirubin transported?
by hydrogen bonding to albumin –>separates at the hepatocyte membrane in the space of disse
Where in the cell does bilirubin become conjugated?
in endoplasmic reticulum –> e.g. if pt has elevated unconjugated bilirubin, we know the defect is at the conjugation step or after
What is the rate limiting step in bilirubin production?
ATP mediated pumping into canaliculus against a large concentration gradient
Most bilirubin is secreted as a ______
diglucoronide, few as monoglucoronide, <1% unconjugated
Is conjugated bilirubin water soluble?
yes –> glucuronidation opens up the molecule and exposes hydrophilic moieties
Where in the body is conjugated bilirubin normally found?
bile but not blood
Where in the body is unconjugated bilirubin normally found?
bile and blood
Mechanisms body employs to protect against neurotoxicity of unconjugated bilirubin
binding to albumin, blood brain barrier, conjugation, excretion
T/F all the body’s protective mechanisms against unconjugated bilirubin may be somewhat defective in the newborn.
T
What is delta bilirubin and when does it show up?
conjugated bilirubin COVALENTLY bonded to albumin (vs. H bonds in unconjugated bilirubin) –> serum of pts with long-standing hyperbilirubinemia
Why does it take a while for bilirubin levels to normalize after treatment?
delta bilirubin bound to albumin is too big to pass into urine and takes a while to get cleared
Bacteria convert bilirubin to colorless water soluble _____
urobilinogen –> some is absorbed, some reaches urine via serum
What are pyrroles?
bacteria act on urobilinogen to produce pyrroles to give stool its color
Unconjugated hyperbilirubinemia results in direct/indirect jaundice and conjugated hyperbilirubinemia results in direct/indirect jaundice.
indirect and direct
How does unconjugated hyperbilirubinemia lead to jaundice?
H bonds to albumin make molecules too large to pass into urine
How does conjugated hyperbilirubinemia lead to jaundice?
conjugated bilirubin is actually mixed –> conjugated part is water soluble and passes into urine, unconjugated part and delta part get stuck in circulation
What are the urine color differences in (un)conjugated bilirubin?
tea/red color = conjugated == + on dipstick
3 causes of unconjugated hyperbilirubinemia
overproduction, reduced uptake, defects in conjugation
2 etiologies of reduced hepatic uptake resulting in unconjugated jaundice
- altered circulation (portal shunting, right heart failure)
- effect of drugs (rifamycin)
Name a few etiologies of overproduction of bilirubin leading to unconjugated jaundice
hemolysis, extravasation/bruising, ineffective erythropoeisis/pernicious anemia
Lab findings in overproduction of bilirubin leading to unconjugated jaundice
normal liver histology/tests, serum bilirubin < 3X b/c of effective liver clearance AKA really high bilirubin is probably not due to overproduction
Name a few etiologies of conjugation defects leading to unconjugated jaundice
inherited: crigler najjar I and II (rare) and gilberts (benign, common)
acquired: testosterone, novobiocin, wilson’s/chronic heptatitis, hyperthyroidism, jaundice of newborn
