67. Hereditary hyperbilirubinemias Flashcards Preview

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Flashcards in 67. Hereditary hyperbilirubinemias Deck (37):
1

hereditary hyperbilirubinemias - types , mode og inheritance for each

1. Gilbert syndrome
2. Crigler-Najjar syndrome , type I
3. Dubin--johnson syndrome
4. ROtor syndrome
ALL AR

2

gilbert syndrome - mechanism

mildly decreased UDP- glucuronosyltransferase conjugation and impaired bilirubin uptake

3

Gilbert syndrome - frequrncy / presentation/ findings

-very common and no clinical consequences
-asymptomatic or mild jaundice
-increased UCB without overt hemolysis
-more increasing UCB and Jaundice in fasting, stressm infection

4

Cringler - Najjal syndrome , type I - mechanism

Absent of UGT ( present early in life) --> die within a few years

5

Cringler - Najjal syndrome , type I - findings / symptoms

1. jaundice
2. kernicterus
3. increased UCB

6

Cringler - Najjal syndrome, type I - treatment

plasmapheresis and phototherapy

7

Cringler - Najjal syndrome, type II ( vs type I)

less severe and responds to phenobarbital , which increases liver enzyme synthesis

8

Dubin - Johnson syndrome - everything

deficiency of bilirubin canalicular transport protein ( defective excretion ) --> conjugated hyperbilirubinemia
Grossly black liver ( Benign)

9

Rotor syndrome - everything

similaar to DUbin - johnson but milder in presentation without black liver
DUE TO : impaired hepatic uptake (?) + excretion

10

Dubin - Johnson syndrome vs Rotor syndrome according to liver

dubin - johnson syndrome --> black
Rotor syndrome --> no black

11

• A college student with no prior medical history presents with scleral icterus during final exams. What is the likely diagnosis?

Gilbert syndrome, likely precipitated by fasting or stress secondary to studying

12

• The parents of a child with Gilbert syndrome want to know what complications to expect. What do you tell them?

Gilbert syndrome has no clinical consequences other than jaundice

13

• A woman occasionally has jaundice instigated by stress that goes away without treatment. What is the pathogenesis of this benign condition?

Slightly decreased UDP-glucuronosyltransferase activity or decreased bilirubin uptake by hepatocytes (this is Gilbert syndrome)

14

• Which levels are elevated in Gilbert syndrome: conjugated bilirubin, unconjugated bilirubin, or both?

Unconjugated bilirubin (since UDP-glucuronosyltransferase activity is decreased)

15

• A 1-y/o girl has a new unconjugated hyperbilirubinemia with no laboratory indications of hemolysis. What asymptomatic condition is likely?

Gilbert syndrome, which can be triggered by fasting and stress in predisposed individuals

16

• A newborn has defective activity of UDP-glucuronosyltransferase, usually resulting in death within a few years of birth. Diagnosis?

Crigler-Najjar syndrome type I

17

• A 2-week-old boy is diagnosed with Crigler-Najjar syndrome type I. What do you tell the parents about the prognosis?

Death occurs in childhood

18

• A patient has jaundice, kernicterus, and high unconjugated bilirubin levels. He dies at age 3 years. What enzyme is missing in his disease?

UDP-glucuronosyltransferase (the patient has Crigler-Najjar syndrome type I)

19

• The parents of a jaundiced newborn are concerned that he has Crigler-Najjar syndrome. What type of bilirubinemia would rule this out?

Conjugated hyperbilirubinemia (as Crigler-Najjar causes impaired conjugation, leading to an unconjugated hyperbilirubinemia)

20

• What is kernicterus?

Bilirubin deposition in the brain

21

• What would a neonate with absent UDP-glucuronosyltransferase and cerebral palsy be treated with?

Plasmapheresis and phototherapy (this is Crigler-Najjar syndrome)

22

• A baby has hyperbilirubinemia from low UDP-glucuronosyltransferase. How can a drug-enhancing liver enzyme synthesis help you prognosticate?

Phenobarbital enhances enzyme synthesis in Crigler-Najjar syndrome type II (less severe/a better prognosis), but has no effect for type I

23

• A newborn has persistent hyperbilirubinemia despite phototherapy. What type of bilirubinemia supports a diagnosis of Dubin-Johnson syndrome?

Conjugated hyperbilirubinemia (Dubin-Johnson is a defect of hepatic excretion of bile)

24

• What physiologic process is defective in patients with Dubin-Johnson syndrome?

Excretion of bilirubin from hepatocytes

25

• A patient has defective excretion of direct bilirubin. Gross pathology shows a black liver. Diagnosis?

Dubin-Johnson syndrome, which has the characteristic black liver on gross pathology

26

• You diagnose Dubin-Johnson syndrome in a neonate with conjugated hyperbilirubinemia. How do you explain the prognosis to the parents?

There are no clinical consequence, as this condition is benign

27

• A patient has disease symptoms similar to Dubin-Johnson syndrome, but you do not find a grossly black liver. Does the prognosis change?

No (this is Rotor syndrome, which is a milder form of Dubin-Johnson syndrome

28

• A 22-year-old new to your practice has a history of benign unconjugated hyperbilirubinemia. Which hepatic enzyme is likely affected?

Glucuronosyltransferase (specifically UDP-glucuronosyltransferase in the case of Gilbert syndrome)

29

• Unconjugated bilirubin is formed from ____.

Hemoglobin

30

• What cells within the liver are part of the mononuclear phagocyte system, aiding in the conversion of hemoglobin to unconjugated bilirubin?

Kupffer cells

31

• Describe the properties of circulating bilirubin (in normal healthy individuals). What allows it to be transported through the bloodstream?

Circulating bilirubin is unconjugated and water-insoluble; must be bound to albumin for transport

32

• To enter hepatocytes for processing, what two spaces must circulating bilirubin pass through?

Junctions between endothelial cells in the hepatic sinusoid, followed by the space of Disse

33

• A man has a rare mutation that slightly inhibits passage of bilirubin through the space of Disse. This presents similarly to what syndrome?

Gilbert syndrome (can consider this to be a form of impaired bilirubin uptake)

34

• Within hepatocytes, what enzyme is tasked with converting unconjugated bilirubin into conjugated bilirubin? What function does it perform?

UDP-glucuronosyltransferase, it conjugates the bilirubin

35

• After being acted on by UDP-glucuronosyltransferase, how does bilirubin differ from a previously circulating form?

It is now conjugated (bilirubin diglucuronide) and is more water soluble

36

• Conjugated bilirubin is secreted into what structure so that it may become a part of bile?

The lumen of the bile canaliculus

37

• A patient has jaundice and RUQ pain. A common bile duct gallstone is detected. This most directly impairs what step of bilirubin metabolism?

Secretion of conjugated bilirubin into the lumen of the bile canaliculus due to obstruction/stasis

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