67. Hereditary hyperbilirubinemias Flashcards Preview

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Flashcards in 67. Hereditary hyperbilirubinemias Deck (37)

hereditary hyperbilirubinemias - types , mode og inheritance for each

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


gilbert syndrome - mechanism

mildly decreased UDP- glucuronosyltransferase conjugation and impaired bilirubin uptake


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


Cringler - Najjal syndrome , type I - mechanism

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


Cringler - Najjal syndrome , type I - findings / symptoms

1. jaundice
2. kernicterus
3. increased UCB


Cringler - Najjal syndrome, type I - treatment

plasmapheresis and phototherapy


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

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


Dubin - Johnson syndrome - everything

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


Rotor syndrome - everything

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


Dubin - Johnson syndrome vs Rotor syndrome according to liver

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


• 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


• 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


• 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)


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

Unconjugated bilirubin (since UDP-glucuronosyltransferase activity is decreased)


• 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


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

Crigler-Najjar syndrome type I


• 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


• 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)


• 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)


• What is kernicterus?

Bilirubin deposition in the brain


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

Plasmapheresis and phototherapy (this is Crigler-Najjar syndrome)


• 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


• 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)


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

Excretion of bilirubin from hepatocytes


• 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


• 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


• 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


• 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)


• Unconjugated bilirubin is formed from ____.



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

Kupffer cells


• 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


• 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


• 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)


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

UDP-glucuronosyltransferase, it conjugates the bilirubin


• 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


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

The lumen of the bile canaliculus


• 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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