bilirubin Flashcards
what is the metabolism of heme ?
heme is released form old RBCs
macrophages engulf residual heme
converted to biliverdin then into bilirubin
how is bilirubin carried to the liver ?
bound to albumin
what happens to bilirubin in the liver ?
it is conjugated to glucoronic acid
making it very soluble and very polar
what is the enzyme that catalyzes the conjugation of bilirubin ?
UDP glucoronyltransferase
what happens to bilirubin in the intestines ?
bilirubin is deconjugated into urobilinogen in the duodenum
some is then converted into stercobilin and excreted in faeces
some is reabsorbed into the enterohepatic system
some reaches the kidney and creates urobilin
what form does bilirubin exist in in the intestines ?
converted back to unconjugated in the intestines
what are the enzymes that unconjugated the bilirubin ?
beta glucuronisade
what is the reaction associated with lab measurements of bilirubin ?
van den bergh reaction
with indirect bilirubin alcohol must be added first before carrying out the van der bergh reaction
what type of bilirubin is detected in the urine ?
urobilinogen - conjugated bilirubin only
normally there should be no bilirubin
at what level of bilirubin is jaundice usually seen ?
above 3 mg/dl
what are the four general causes of increased bilirubin ?
hemolysis
biliary obstruction
liver disease
spacial causes
what are the findings associated with jaundice cause by hemolysis ?
high levels of unconjugated bilirubin
no urine bilirubin
increased urobilinogen
what are the findings associated with cholestasis ?
rise in ALP
elevated direct bilirubin
conjugation is normal but no excretion
clay coloured stools due to lack of stercobilin
dark urine
absent urobilinogen ( no bilirubin in intestines)
what are the findings associated with jaundice in liver disease ?
mixed increase of both direct and indirect bilirubin levels
what is the difference in findings in primary liver diseases that cause hepatocyte damage vs intrahepatic cholestasis ?
hepatocyte damage - unconjugated hyperbilirubinemia
intrahepatic cholestasis - conjugated hyperbilirubinemia
what are the levels of urobilinogen levels in primary liver disease ?
high in early liver disease
lower in late stages of liver disease
what are the drugs associated with yper bilirubinemia ?
rifampin and probenecid (gout)
result in hig uncojugated bilirubin
all other liver enzymes are normal
what is gilberts syndrome ?
decrease in UDP glucronyl transferase enzyme
hence a lack of conjugation
so high levels of unconjugated bilirubin
when does jaundice occur in gilberts syndrome ?
fasting , stress, menses
anything that increases bilirubin production
what is criggler - najjar syndrome ?
abest UDP levels
type 1 is the more severe type - born with it
often fatal
due to kernictus
what is kernicterus ?
the passage of unconjugated bilirubin which is soluble in fats and easily crosses the blood brain barrier , and acts as a neurotoxin
what is type 2 criggler najjar treated with ?
less severe form
treated with phenobarbitol or clofibrate
phenobarbitol is a seizure drug
clofibrate is a lipid reducing drug
what is dubin johnson syndrome ?
benign hereditary liver disorder where conjugated bilirubin builds up due to a problem with bilirubin excretion
what are the findings associated with dubin johnson syndrome ?
bilirubin in urine
increased in conjugated bilirubin
liver turns black
no treatment required
what is the difference between gilberts syndrome and dubin johnson syndrome ?
gilberts syndome causes an increase in unconjugated bilirubin whilst dubin johnson causes an increase in conjugated bilirubin
what is rotor syndrome ?
similar to dubin johnson but no black liver thats it
what type of bilirubin is increased in neonatal jaunddice ?
unconjugated
what is the risk with neonatal jaundice ?
preterm infants are at a higher risk of kernicterus
what is the treatment for neonatal jaundice ?
phototherapy
converts bilirubin to lumirubin ( more water soluble)
