SOLUTIONS GRADED A++ LATEST UPDATE
Outline and discuss the basic aspects of bilirubin trafficking and metabolism.
1. Spleen Only
1) Phagocytes in spleen separates heme and globin (also Fe2= to Fe3+)
2) heme oxygenase converts it to biliverdin (CO is exhaled and Fe3+ is recycled)
3) Biliverdin reductase converts it to unconjugated bilirubin
Outline and discuss the basic aspects of bilirubin trafficking and metabolism.
2. Blood Flow
Unconjugated bilirubin binds to albumin because it is insoluble in water. Travels from
spleen to Liver.
Outline and discuss the basic aspects of bilirubin trafficking and metabolism.
3. Liver
1. Hepatic Uptake: unconjugated bilirubin binds to transport protein to cross the hepatic
cell membrane and leaves albumin.
2. In hepatocytes, unconjugated bilirubin binds to ligandin because it is insoluble in
water
3. conjugation: UDP-glucuronyl transferase adds one or two glucuronyl group (very
polar group) --> conjugated bilirubin (water soluble)
4. conjugated bilirubin is excreted to the bile canaliculus and becomes a component of
bile.
,Outline and discuss the basic aspects of bilirubin trafficking and metabolism.
4. Bile Duct
1. intestinal flora converts conjugated bilirubin to urobilinogen's (colorless)
2. Enterohepatic circulation: some of urobilinogen's are reabsorbed at ileum (end of
intestine) -> portal vein -> either re-excreted to bile or excreted from kidney.
Urobilinogen in urine --> urobilin's (color of urine)
3. Intestinal flora convert urobilinogen's -> urobilin's -> stercobilin's (brown color of
feces)
Neonatal jaundice
What causes it?
What can happen as a result?
What is the treatment?
Newborn does not have UDP-glucuronyl transferase yet (unconjugated cannot be made
into conjugated at liver), jaundice occurs when albumin become saturated with
unconjugated bilirubin. Note- newborn RBC also have shorter life
Kernicterus can happen as a result- where unconjugated bilirubin passes through blood-
brain barrier. once it accumulates in the brain it cannot be removed - fatal effects
Blue light (450nm) treatment converts unconjugated bilirubin ("trans" 4Z,15Z) into water
soluble unconjugated bilirubin ("cis" 4E, 15E) which can be excreted into the bile without
conjugation process.
,Crigler-Najjar Syndrome
what causes it?
what increases as a result?
Hereditary UDP-glucuronyl transferase defect
indirect bilirubin increases
Gilberts Disease
what causes it?
what increases as a result?
reduced UDP-glucuronyl transferase activity by mutation
mildly increased indirect bilirubin
Dubin-Johnson syndrome
what is the defect?
what increases as a result?
causes defect in canicular secretion of conjugated bilirubin
direct bilirubin increases
Pre-Hepatic Jaundice
What is the cause?
characteristics?
overproduction of unconjugated bilirubin (hemolytic anemia)
1. indirect bilirubin increased
2. urobilinogen increased in stool, serum, and urine
3. No bilirubin in urine because it is unconjugated bilirubin (water insoluble)
, Hepatic Jaundice
Cause
Characteristics
Hepatitis (viral, drug or toxin induced)
1. direct bilirubin increased: conjugated bilirubin is leaking out from liver
2. indirect bilirubin increased: unconjugated bilirubin is accumulated because it is
processed too slowly in the liver
3. Urine bilirubin (+): because conjugated bilirubin increased
4. Urine urobilinogen normal to increased: reuptake of urobilinogen by liver is decreased
and more is secreted out to the urine.
Post-Hepatic jaundice
Cause
Characteristics
obstruction - gallstones, tumor, parasite enters from duodenum
1. Direct bilirubin increased (makes urine bilirubin positive)
2. Low/no urobilinogen in serum, urine: because low.no bilirubin enters intestine
3. Less/no brown color stool: because low/no bilirubin enters intestine -> low.no
stercobilin's.
Direct Bilirubin
how is it measured?