Bilirubin formation and excretion

Question 1

What is bilirubin?

Answer 1

metabolic waste product of heme molecule

Question 2

What are the 2 main forms of bilirubin in the body?

Answer 2

conjugated vs unconjugated bilirubin

Question 3

What type of solutions can dissolve conjugated bilirubin

Answer 3

aqueous solutions

Question 4

What type of solutions can dissolve unconjugated bilirubin

Answer 4

lipid solutions

Question 5

Where does bilirubin undergo conjugation

Answer 5

liver hepatocytes

Question 6

What is the effect of conjugating bilirubin on

• its solubility
• intestinal absorption

Answer 6

• makes it more water soluble

- bigger molecule, harder for intestine to reabsorb

Question 7

how is unconjugated bilirubin transported in the blood

Answer 7

by binding with albumin

Question 8

What is direct bilirubin, etymology

Answer 8

another name for conjugated bilirubin

- conjugated bilirubin could be directly tested for

Question 9

What is indirect bilirubin, etymology

Answer 9

another name for unconjugated bilirubin
- in order to measure unconjugated bilirubin, an extra reagent needed to be added to disrupt the hydrogen bonds of unconjugated bilirubin. You then get total bili, and total - conj = unconj

Question 10

how is bilirubin normally excreted from the body, and in what form

Answer 10

usually conjugated bilirubin gets excreted thru bile ducts

Question 11

which form of bilirubin is most readily excreted in urine

Answer 11

conjugated bilirubin

Question 12

broadly, mechanisms that can lead to unconjugated hyperbilirubinaemia

Answer 12

• excess heme in blood (think hemolysis)

- hepatocyte damage means you can’t conjugate bilirubin

Question 13

What is Gilbert’s syndrome

• clinical manifestation
• pathophysiology
• prognosis

Answer 13

• above normal unconjugated bilirubin in blood
• its because you genetically have less active bilirubin conjugators (UGT enzyme)
• considered harmless

Question 14

broadly, mechanism leading to conjugated hyperbilirubinaemia

Answer 14

cholestasis ie bilirubin can’t get into biliary ducts

- either intrahepatic from hepatocyte damage, or extrahepatic from an obstructive process

Question 15

what is the mechanism underlying physiological jaundince in neonates

Answer 15

conjugating enzyme (UGT) doesn’t fully mature until a few days after being born, so you get extra unconj bilirubin

Question 16

what effect would hepatocyte damage have on bilirubin formation and excretion

Answer 16

lead to build-up of conjugated and unconjugated bilirubin

• damage means you can’t conjugate well, so excess unconj
• also means you’ll get bile canaliculi blocks, and therefore excess conj