Lecture 26

Question 1

Bilirubin

Answer 1

Product of hemoglobin that circulates in the plasma prior to undergoing hepatic conjugation and biliary excretion -> RBCs taken up by phagocytic cells of spleen and Kupffer cells of liver -> Hb degraded into heme and globin by these cells -> Heme loses its iron and is transformed into bilirubin -> Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion

Question 2

Explain the excretion of bilirubin.

Answer 2

1. Bilirubin is released into blood and bound to albumin (unconjugated bilirubin: not water-soluble)
2. Taken up by hepatocytes and conjugated with one or two glucuronic acid residues (glucuronide) by uridine diphosphate glucuronyl-transferase (UDPGT) to become water-soluble bilirubin mono- and di- glucuronides
3. Conjugated bilirubin is excreted in bile and participates in fat digestion in the intestine (cannot be absorbed in the SI)
4. Some unused bilirubin conjugate is converted back into bilirubin by bacteria in terminal ileum and colon -> converted into urobilinogen

Question 3

What happens to urobilinogen?

Answer 3

1. Small fraction is absorbed in colon and re-circulated and re-excreted by the liver and kidneys
2. If it enters the plasma and is filtered by the kidneys -> oxidized to urobilin (gives urine the yellow color)
3. If it remains in the colon -> compound is further converted to stercobilin (main pigment of feces)

Question 4

What part of bilirubin metabolism occurs in the reticuloendothelial system?

Answer 4

Hemoglobin:
1. Globin
2. Heme -> Fe and Biliverdin -> Bilirubin

Question 5

What part of bilirubin metabolism occurs in plasma?

Answer 5

Bilirubin -> albumin bound bilirubin <-> free unconjugated bilirubin

Question 6

What part of bilirubin metabolism occurs in the liver?

Answer 6

Free unconjugated bilirubin -> membrane transport proteins (uptake) -> Bilirubin (ER: UDPGT) -> Bilirubin mono- and diglucuronide

Question 7

What part of bilirubin metabolism occurs in the biliary system?

Answer 7

Bile

Question 8

What part of bilirubin metabolism occurs in the intestines?

Answer 8

Bile -> Bilirubin -> Urobilinogen

Question 9

What can happen to urobilinogen?

Answer 9

1. Feces
2. Systemic circulation -> filtration and excretion (kidneys) -> urine
3. Portal enterohepatic circulation -> liver

Question 10

How is bilirubin metabolism impacted by the presence of liver disease?

Answer 10

The hepatic fraction decreases and the urinary fraction increases, accounting for the rise in urinary urobilinogen

Question 11

How does obstruction to bile flow or intestinal obstruction impact bilirubin metabolism?

Answer 11

Urinary urobilinogen falls to zero (no bilirubin reaches the colon)

Question 12

Unconjugated hyperbilirubinemia

Answer 12

Prehepatic origin

Question 13

Conjugated hyperbilirubinemia

Answer 13

Posthepatic obstruction

Question 14

Mixed unconjugated and conjugated hyperbilirubinemia

Answer 14

Hepatic origin

Question 14

What does prehepatic mean?

Answer 14

RBC -> Hemoglobin -> Bilirubin

Question 15

What does hepatic mean?

Answer 15

Liver

Question 16

What causes prehepatic/ hemolytic jaundice?

Answer 16

Hemolysis

Question 17

What causes hepatic jaundice?

Answer 17

Viral hepatitis, drugs, cirrhosis, tumors

Question 18

What does post hepatic refer to?

Answer 18

Gallbladder, bile duct, intestines, pancreas

Question 19

What causes post hepatic/obstructive jaundice?

Answer 19

Gallstones, cancer of bile ducts

Question 20

Gilbert Syndrome

Answer 20

• Unconjugated hyperbilirubinemia
• Mutation of UGT1A1 gene (involved in glucuronidation by UDP-glucuronosyltransferases
• Autosomal recessive