Bilirubin Metabolism and Excretion (Choudhury) Flashcards
UDPGT
adds glucuronides to uncon bilirubin to make it conjugated bilirubin ( in liver)
majority of bile salts go where
recycled through enterohepatic circulation
can indirect bilirubin flow through blood
no must be attached to carrier protein-albumin
where does bilirubin get conjugated and by what
in liver by UDP-GT
What happens to conjugated bilirubin in intestine
degraded by bacteria to make urobillinogen-> stercobilinogen
What do you need to convert hemoglobin to unconj bilirubin?
O2(heme oxygenase) and NADPH(biliverdin reductase)
where does heme come from
diet, myoglobin, p450 in mm cells, Hb
where can you find heme oxygenase, and what does it do
phagocytes, kupffer cells, spleen and bone marrow cells. Converts heme into biliverdin
Only place in body where we make CO
via heme oxygenase. production of biliverdin
conditions that increase unconjugated or indirect bilirubin
hemolysis, Cirgler-Najjar syndromes, Gilbert syndrom, low levels of conjugation enzymes in newborn, hepatic damage
Conjugated reacts quickly with what acid
diazosuluronic acid- azobilirubin
Conditions that increase conjugated bilirubin
hepatic damage, bile duct obsturction (clay colored stool), dubin-johnson, and rotor syndrome
abnormal levels of total bilirubin for jaundice
above 2 mg/dl
cholestasis
impaired bile flow, increase conc of bilirubin, bile acids and cholesterol in blood
kernicterus
[ ] of unconjugated bilirubin in newborn blood. when bilirubin enters CNS->mental retardation
hemolytic anemia has what affect on liver
increase indirect bilirubin. seen in G6PD deficiency, PK deficiency and Vit K deficiency
Crigler-Najjar
no UDP-GT- cannot conjugate bilirubin. sever congenital jaundice. death 6 mo-1 year
Gilbert Syndromes
UDP-GT mutated(point). Indirect bilirubin levels slightly elevated- no jaundice unless stressed
Kernicterus
newborns due to massive destruction of RBCs, and doesn’t respond to 2,3 BPG
or early birth and takes time for Hb to completely convert
causes of direct bilirubin
intra or extrahepatic obstuction
defective canalicular transport
Dubin-johnson
defective canalicular transport. black liver, brown urine
Rotor Syndrome
asymptomatic direct hyper-bilirubinemia. problem of storage of bilirubin, so it leaks into blood,
Causes that lead to increase both conj and unconj bilirubin
liver malfunction, cirrhosis, hepatic virus, Wilson’s-Cu disease
main difference of type I and II circler-najjar
type I die in infancy. type II rare late onset of kernicterus with fasting
alchol cirrhosis leads to
hyperbilirubinemia due to dec excretion of bilirubin into bile
Prehaptic jaundice
excessive bilirubin presented.. can be caused by anemias. Inc serum unconj bilirubin
Haptic causes of jaundice
abnormal hepatocyte function
enzyme mutation/impaired for hepatocellura upatake (unconjugated)
enzyme mutation/defective conjugation increase in unconj bilirubin
defective secretion of hepatocyte- increased conj bilirubin
hepatitis with lowered conjugation or excretion
Post hepatic Jaundice
impaired excretion of bilirubin- mechanical obstruction of flow of bile into intestines
gall stones or tumors. increase serum and urine conjugated bilirubin and dec urobilin and stercobilin
why are sulfonamides not give to infants less than 2 months
increase unconjugated bilirubin leading to kernicterus
