What is the conjugating enzyme that everyone keeps talking about?
UDP-glucuronosyltransferase
High bilirubin level that is less than 20% indicates which cause?
Most likely due to hemolysis
Rarely is it a liver issue if it is less than 20%
Direct bilirubin measures _____ bilirubin. Indirect measures _____ bilirubin. While total bilirubin test measures_____
Conjugated
Unconjugated
Total measures both conjugated and unconjugated (“indirect” is actually calculated by getting the total bilirubin subtracting direct to get the unconjugated bilirubin)
Conjugated bilirubin is aka _______
Bilirubin diglucuronide
Notable receptors on the apical membrane of the hepatocyte are (receiving bilirubin from the sinusoids):
OATP1B1
OATP1B3
Receptors on the basolateral membrane of the hepatocytes are (exporting conjugated bilirubin out to the bile canaliculi):
MRP2
ABCG2
Most prevalent cause of jaundice is ____. And this causes increased ______ bilirubin
Hemolysis (prehepatic jaundice)
Indirect (a lot of unconjugated bilirubin)
UDP-glucuronsyltransferase is encoded by which gene?
UGT1A1 gene
Which syndrome results from mutation to UGT1A1 gene? What is mutated?
Gilbert syndrome
UDP-glucuronsyltransferase is mutated
Gilbert syndrome is a _____ cause of hyperbilirubinemia, with increased _____ bilirubin, since ___( gene) coding for ____(enzyme) is mutated
hepatic
Indirect
UGT1A1 gene
UDP-glucuronsyltransferase
T/F: Gilbert syndrome is autosomal dominant
False; it is autosomal recessive, loss-of-function
What is Crigler Najjar type 1 syndrome?
Autosomal recessive, severe, lethal early in life.
Complete or near complete loss of UDP glucuronosyltransferase activity
True//false: Crigler-Najjar type 1 and type 2, Gilbert syndrome are each caused by mutations of the gene UGT1A1 that encodes for UDP glucuronosyltransferase
True
Syndromes due to loss of function mutations of UGT1A1, rank it from somewhat high bilirubin to lethal level of hyperbilirubinemia:
Gilbert (fluctuating high)
Crigler-Najjar type 2 (permananetly high)
Crigler-Najjar type 1 (lethal)
What is Dubin-Johnson syndrome?
Caused by autosomal recessive loss-of-function of MRP2 or ABCG2 – which are transporters on the basolateral hepatocyte that ships conjugated bili to the canaliculi en route to the gallbladder
Mutations of MRP2 or ABCG2 receptors is _______ syndrome. This is a ___ Cause of hyperbilirubinemia, with increase ___ test
Dubin-Johnson
Hepatic
Direct
T/F: backup of conjugated bilirubin will also cause some buildup of unconjugated bilirubin in Dubin-Johnson syndrome
True
What is Rotor syndrome?
Loss-of-function mutations affecting OATP1B1 and OAT1B3 transporters on the apical membrane
T/F: rotor syndrome leads to increase in Direct bilirubin
TRUE; weird, but true. This is because there are some sort of hopping action that occurs that still allows conjugated bilirubin to hop to the central vein
These syndromes lead to increased indirect bilirubin:
Crigler Najjar 1, Crigler-Najjar 2, Gilbert
These syndromes lead to increased direct bilirubin
Dubin-Johnson
Rotor
Biliverdin is ___ soluble. Bilirubin is _____soluble
