Bilirubin Metabolism and Mechanisms of Jaundice Flashcards

1
Q

What is the end product of heme catabolism?

A

Bilirubin

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2
Q

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

A

Kernicterus

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3
Q

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

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

What occurs to make bilirubin water soluble?

A

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

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5
Q

What are the general causes that lead to jaundice?

A

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

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6
Q

What are the causes of increased production of bilirubin?

A

Increased destruction of erythroytes or ineffective erythropoesis

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7
Q

What type of hyperbilirubinemia is caused by uncomplicated hemolytic disease?

A

Unconjugated bilirubin

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8
Q

What type of hyperbilirubinemia is caused by parenchymal liver disease?

A

Both conjugated and unconjugated hyperbilirubinemia

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9
Q

What type of disease is caused by impaired hepatic uptake?

A

Hyperbilirubinemia of the unconjugated type

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10
Q

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

A

Crigler-Najjar Syndrome Type I

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11
Q

What is Crigler-Najjar syndrome type II?

A

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

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12
Q

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

A

Gilbert Syndrome

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13
Q

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

A

Mutations in the multidrug resistance protein family

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14
Q

What is Dubin-Johnson syndrome?

A

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

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15
Q

What mutation occurs in the Dubin-Johnson Syndrome?

A

ABCC2/MRP2 gene

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16
Q

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

A

Testing urinary coproporphyrin excretion

17
Q

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

A

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

18
Q

What are the uscopic findings of Dubin-Johnson Syndrome?

A

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

19
Q

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

A

Rotor Syndrome

20
Q

Syx of Rotor Syndrome?

A

Patients are generally aSyx

21
Q

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

A

Benign recurrent intrahepatic cholestasis

22
Q

AR disease in which intrahepatic cholestasis progresses relentlessy to cirrhosis?

A

Progressive Familial Intrahepatic Cholestasis

23
Q

What hepatic condition can occur in pregnancy?

A

Intrahepatic cholestasis

24
Q

What type of hyperbilirubinemia is seen with sepsis?

A

Conjugated Hyperbilirubinemia

25
Why do 70% of newborns have transient unconjugated hyperbilirubinemia?
The liver of a newborn assumes the responsibility for bilirubin clearance before its conjugating and excretory capacities are fully developed
26
What is cholestasis due to intrinsic liver disease? Obstruction of the bile ducts?
Intrahepatic cholestasis, Extrahepatic cholestasis
27
What does the inability to excrete bile acids into canaliculi cause?
An increase in serum and hepatocellular bile acid concentrations
28
Three alterations that can cause cholestasis?
1. Damage to canalicular plasma membrane 2. Alteration in contractile properties of the canaliculus 3. Alterations in the permeability of the canalicular membrane
29
Uscopically, how is cholestasis characterized?
Presence of brownish bile pigment w/i dilated canaliculi and in hepatocytes
30
What are the gross characteristics found in a patient with prolonged biliary obstruction?
Liver is swollen and bile stained (Green). The bile becomes almost colorless ("white bile") b/c bilirubin secretion is suppressed
31
What is the name of the triad in which: 1. Hydropic swelling 2. Diffuse impregnation w/ bile pigment 3. Reticulated appearance
Feathery degeneration (This occurs in extrahepatic obstruction)
32
What do ruptured bile ducts cause on uscopic analysis?
Bile lakes - focal, golden yellow deposits surrounded by degenerating hepatocytes
33
What are the typical clinical presentations of cholestasis?
Pruritus. xanthomas (accumulation of cholesterol in the skin), malabsorption