Bilirubin Metabolism and Mechanisms of Jaundice

Question 1

What is the end product of heme catabolism?

Answer 1

Bilirubin

Question 2

What is the brain injury to newborns caused by high concentrations of bilirubin?

Answer 2

Kernicterus

Question 3

What are the four steps of bilirubin transfer from the blood to the bile?

Answer 3

1. Uptake
2. Binding
3. Conjugation
4. Excretion

Question 4

What occurs to make bilirubin water soluble?

Answer 4

Conjugation in which it is conjugated to glucuronic acid in the ER which contains uridine diphosphate-glucuronyl transferase

Question 5

What are the general causes that lead to jaundice?

Answer 5

Overproduction of bilirubin, interference with hepatic uptake/intracellular metabolism of bilirubin and impairment of bile excretion are all cases of jaundice

Question 6

What are the causes of increased production of bilirubin?

Answer 6

Increased destruction of erythroytes or ineffective erythropoesis

Question 7

What type of hyperbilirubinemia is caused by uncomplicated hemolytic disease?

Answer 7

Unconjugated bilirubin

Question 8

What type of hyperbilirubinemia is caused by parenchymal liver disease?

Answer 8

Both conjugated and unconjugated hyperbilirubinemia

Question 9

What type of disease is caused by impaired hepatic uptake?

Answer 9

Hyperbilirubinemia of the unconjugated type

Question 10

What is the disease in which there is chronic, severe, unconjugated hyperbilirubinemia, due to the complete absence of hepatic UGT activity?

Answer 10

Crigler-Najjar Syndrome Type I

Question 11

What is Crigler-Najjar syndrome type II?

Answer 11

Similar but less severe than CNS type I disease and only entails a partial decrease in UGT activity

Question 12

What is the condition in which hyperbilirubinemia occurs due to the inadequate synthesis of the UGT enzyme (Much more mild than Crigler-Najjar)?

Answer 12

Gilbert Syndrome

Question 13

What is often the cause of decreased transport of conjugated bilirubin?

Answer 13

Mutations in the multidrug resistance protein family

Question 14

What is Dubin-Johnson syndrome?

Answer 14

Benign AR disease with chronic conjugated hyperbilirubinemia and conspicuous deposition of melanin-like pigment in the liver

Question 15

What mutation occurs in the Dubin-Johnson Syndrome?

Answer 15

ABCC2/MRP2 gene

Question 16

How is Dubin-Johnson syndrome distinguished from other conditions with conjugated hyperbilirubinemia?

Answer 16

Testing urinary coproporphyrin excretion

Question 17

What findings of urinary coproporphyrin excretion suggest Dubin-Johnson syndrome?

Answer 17

isomer I: isomer III ratio of 4:1 from the normal 1:3

Question 18

What are the uscopic findings of Dubin-Johnson Syndrome?

Answer 18

Coarse iron-free dark-brown granules in hepatocytes and Kupffer cells

Question 19

AR disease in which conjugated hyperbilirubinemia occurs but pigmentation of the liver is absent.

Answer 19

Rotor Syndrome

Question 20

Syx of Rotor Syndrome?

Answer 20

Patients are generally aSyx

Question 21

Disease in which episodic intrahepatic cholesttasis occurs but is generally self-limited and has no sequelae?

Answer 21

Benign recurrent intrahepatic cholestasis

Question 22

AR disease in which intrahepatic cholestasis progresses relentlessy to cirrhosis?

Answer 22

Progressive Familial Intrahepatic Cholestasis

Question 23

What hepatic condition can occur in pregnancy?

Answer 23

Intrahepatic cholestasis

Question 24

What type of hyperbilirubinemia is seen with sepsis?

Answer 24

Conjugated Hyperbilirubinemia

Question 25

Why do 70% of newborns have transient unconjugated hyperbilirubinemia?

Answer 25

The liver of a newborn assumes the responsibility for bilirubin clearance before its conjugating and excretory capacities are fully developed

Question 26

What is cholestasis due to intrinsic liver disease? Obstruction of the bile ducts?

Answer 26

Intrahepatic cholestasis, Extrahepatic cholestasis

Question 27

What does the inability to excrete bile acids into canaliculi cause?

Answer 27

An increase in serum and hepatocellular bile acid concentrations

Question 28

Three alterations that can cause cholestasis?

Answer 28

1. Damage to canalicular plasma membrane
2. Alteration in contractile properties of the canaliculus
3. Alterations in the permeability of the canalicular membrane

Question 29

Uscopically, how is cholestasis characterized?

Answer 29

Presence of brownish bile pigment w/i dilated canaliculi and in hepatocytes

Question 30

What are the gross characteristics found in a patient with prolonged biliary obstruction?

Answer 30

Liver is swollen and bile stained (Green). The bile becomes almost colorless (“white bile”) b/c bilirubin secretion is suppressed

Question 31

What is the name of the triad in which:

1. Hydropic swelling
2. Diffuse impregnation w/ bile pigment
3. Reticulated appearance

Answer 31

Feathery degeneration (This occurs in extrahepatic obstruction)

Question 32

What do ruptured bile ducts cause on uscopic analysis?

Answer 32

Bile lakes - focal, golden yellow deposits surrounded by degenerating hepatocytes

Question 33

What are the typical clinical presentations of cholestasis?

Answer 33

Pruritus. xanthomas (accumulation of cholesterol in the skin), malabsorption