Bilirubin

Question 1

how does the body get ride of iron?

Answer 1

RBCs/hemoglobin is broken down into heme

Heme is converted to biliverdin and then bilirubin via heme oxygenate and biliverdin reductase, respectively

Bilirubin goes into the blood, from which it will eventually get conjugated in hepatocytes and go into the GI tract for excretion

Question 2

What transporter sends bilirubin into the hepatocyte?

Answer 2

OATP = organic anion transporting protein

Question 3

What ATPase pumps conjugated bilirubin into the hepatic duct, from which it’ll get into the GI tract?

Answer 3

MRP-2 = multidrug resistance-associated protein

Question 4

What is bilirubin conjugated to

Answer 4

Glucuronic acid

Question 5

What is total bilirubin?

Answer 5

Unconjugated + conjugated (to glucuronic acid)

Question 6

Why is unconjugated bilirubin called “indirect”?

Answer 6

Because while bilirubin is attached to albumin, it cannot be directly measured

Question 7

Differentiate between unconjugated and conjugated bilirubin

Answer 7

Unconjugated = “indirect”
Not water soluble
Albumin bound = “bound”
Doesn’t filter into kidney

Conjugated
Water soluble
"Free"
"Direct"
Filters into kidney
Bilirubinuria => dark urine

Question 8

What happens (with either type) with high concentration of bilirubin?

Answer 8

Jaundice = yellow skin

Icterus = yellow conjunctiva of eyes

kernicterus = CNS damage

Question 9

What are causes of hyperbilirubinemia?

Answer 9

1) unconjugated hyperbilirubinemia
2) conjugated hyperbilirubinemia
3) liver damage

Question 10

What can lead to indirect hyperbilirubinemia?

Answer 10

1) Problem with OATP = decreased transport of bilirubin into hepatocyte
2) Hemolysis from breakdown of RBCs = release of large amount of bilirubin => accumulation of bilirubin
3) Problem with UGT (enzyme in hepatocyte that does the conjugation) = decreased conjugation = Crigler-Najar syndrome, Gilbert syndrome

Question 11

What factors cause “direct” hyperbilirubinemia?

Answer 11

1) problem with MRP = decreased transport into bile => won’t go into hepatic duct, so then a lot of conjugated bilirubin returns to the blood
2) cholestasis: gall stones, tumor, neonatal biliary atresia

Question 12

What can liver damage cause that would lead to hyperbilirubinemia

Answer 12

Decreased conjugation (since damage means hepatocytes are having issues doing their job) => more bilirubin attached to albumin

Conjugated bilirubin leaks into blood*

*may have bilirubinuria if conjugated is high enough