Heme Degradation and Jaundice Flashcards
characteristics of jaundice
hyperbilirubinemia, bilirubin bound to connective tissue, yellowish discoloration of skin, mucous membrane, sclera, and nail beds
organs involved in formation and excretion of bilirubin
spleen, liver, and kidney
where does bilirubin arise
from heme containing proteins like myoglobin, cytochromes, and most importantly hemoglobin
enzymes from heme –> biliverdin (green)
heme oxygenase (also convert Fe2+ to Fe3+ and lose CO)
enzyme from biliverdin to biliribun
biliverdin reductase
where does heme –> bilirubin take place
spleen
what binds unconjugated (indirect) bilirubin in the blood
albumin
what drugs can displace bilirubin from albumin
salicylates and sulfonamides
what happens when bilirubin is displaced from albumin the blood
you will have free unconjugated bilirubin which can cross blood brain barrier to cause kernicterus
when bilirubin enters the liver, what is it bound to
ligandin
what happens to unconjugated bilirubin in the liver
it is converted to conjugated bilirubin using microsomal UDP glucuronyl transferase
what donates the glucuronic acid used in conversion of bilirubin to its conjugated form
UDP glucuronic acid
fate of bilirubin after being conjugated in the liver
actively transported to bile caniculus by ABC transporter where it is released into the second part of the duodenum
disease associated with defective ABC transporter in bilirubin transportation
Dubin-Johnson syndrome
diseases associated with defect with UDP glucuronyl transferase
Crigler Najjar syndrome Type I and II
and Gilbert
what happens to bilirubin in the large intestine
it is acted upon by bacterial flora and deconjugated and converted to urobilinogen (colorless)
fate of urobilinogen
most excreted in urine as urobilin (yellow), absorbed into the portal blood, excreted into bile caniculus, or acted upon by bacteria to form stercobilin
fate of stercobilin
excreted in feces
lab test done to detect type of bilirubin
van den bergh reaction
how does van den bergh reaction work
conjugated bilirubin readily react with diazo reagent to prove it is water soluble
unconjugated would react in presence of methanol
how to calculate total bilirubin
unconjugated bilirubin + conjugated bilirubin
how do we classify jaundice
prehepatic (hemolytic), hepatic, and posthepatic (obstructive)
what type of bilirubin in elevated in prehepatic jaundice
unconjugated bilirubin
characteristics of prehepatic jaundice
elevated serum total bilirubin, normal serum conjugated bilirubin, elevated unconjugated bilirubin, absent urine bilirubin, and increased urine urobilinogen
why is bilirubin not found in urine in prehepatic jaundice
unconjugated bilirubin is bound to albumin
type of bilirubin elevated in hepatic jaundice
both unconjugated and conjugated
type of bilirubin found in urine in hepatic jaundice
conjugated
characteristic of hepatic jaundice
serum total bilirubin is increased, both conjugated and unconjugated bilirubin increased, urine bilirubin in present, and urine urobilinogen can either be normal, decreased, or increased
cause of prehepatic jaundice
increased breakdown of RBC
cause of hepatic jaundice
decreased conjugation capacity of liver and decreased excretion of bilirubin
cause of posthepatic jaundice
decreased excretion of bilirubin via bile
type of bilirubin elevated in post hepatic jaundice
conjugated bilirubin
characteristic of posthepatic jaundice
serum tot bilirubin elevated, serum conjugated bilirubin elevated, unconjugated bilirubin is normal, urine bilirubin present, and urine urobilinogen is either decreased or absent depending on if it is completer or partial obstruction
why is there jaundice in the newborn period
low activity of hepatic UDP glucuronyl transferase hence increased unconjugated bilirubin
fixes itself at about 7th day of life
what can increased the amount of unbound unconjugated bilirubin
hypoalbuminemia, low pH (weaken albumin-bilirubin bond), sulfonamides, salicylates
symptoms of kernicterus
neurological symptoms like choreoathetosis, spasticity, muscular rigidity, ataxia, mental retardation
use of phototherapy in neonatal jaundice
light converts bilirubin to more polar, water soluble isomers that can be excreted in bile without conjugation (bili-lights)
most severe unconjugated hyperbilirubinemia
crigler najjer syndrome I (arias syndrome)
percentage of UDP glucuronyl transferase activity and treatment of Crigler Najjar syndrome type I
10-20%
phenobarbitol
percentage of UDP glucuronyl transferase activity in Gilbert
50%
