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Questions and Answers
What is the characteristic feature of hepatitis A virus regarding chronic infection?
What is the characteristic feature of hepatitis A virus regarding chronic infection?
What is the typical incubation period for hepatitis A virus infection?
What is the typical incubation period for hepatitis A virus infection?
Which of the following is a reliable marker for acute hepatitis A infection?
Which of the following is a reliable marker for acute hepatitis A infection?
What percentage approximately indicates the fatality rate associated with hepatitis A virus?
What percentage approximately indicates the fatality rate associated with hepatitis A virus?
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In which environment is hepatitis A virus most commonly endemic?
In which environment is hepatitis A virus most commonly endemic?
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What symptom is least likely to be associated with hepatitis A infections?
What symptom is least likely to be associated with hepatitis A infections?
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What occurs after the IgM antibody response to hepatitis A virus declines?
What occurs after the IgM antibody response to hepatitis A virus declines?
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What characteristic of hepatitis A infections complicates the identification of previous exposure?
What characteristic of hepatitis A infections complicates the identification of previous exposure?
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Which group is least likely to show clinical symptoms from hepatitis A infection?
Which group is least likely to show clinical symptoms from hepatitis A infection?
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How does the presence of IgG anti-HAV contribute to immunity?
How does the presence of IgG anti-HAV contribute to immunity?
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What characterizes cholestasis in the context of bile form alterations?
What characterizes cholestasis in the context of bile form alterations?
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Which of the following describes unconjugated bilirubin?
Which of the following describes unconjugated bilirubin?
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What is the serum bilirubin level threshold for the clinical appearance of jaundice?
What is the serum bilirubin level threshold for the clinical appearance of jaundice?
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Which condition is associated with impaired bilirubin conjugation?
Which condition is associated with impaired bilirubin conjugation?
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Which mechanism primarily leads to unconjugated hyperbilirubinemia?
Which mechanism primarily leads to unconjugated hyperbilirubinemia?
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What is kernicterus and how is it related to bilirubin levels?
What is kernicterus and how is it related to bilirubin levels?
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What contributes to the development of neonatal jaundice?
What contributes to the development of neonatal jaundice?
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Which condition is most likely associated with conjugated hyperbilirubinemia?
Which condition is most likely associated with conjugated hyperbilirubinemia?
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Which of the following is a mechanism that leads to increased bilirubin production?
Which of the following is a mechanism that leads to increased bilirubin production?
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What defines conjugated bilirubin compared to unconjugated bilirubin?
What defines conjugated bilirubin compared to unconjugated bilirubin?
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What is the inheritance pattern of Dubin-Johnson syndrome?
What is the inheritance pattern of Dubin-Johnson syndrome?
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Which condition is characterized by absent UGT1A1 activity?
Which condition is characterized by absent UGT1A1 activity?
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Which disorder is likely to result in kernicterus, albeit occasionally?
Which disorder is likely to result in kernicterus, albeit occasionally?
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What distinguishes Gilbert syndrome from Crigler-Najjar syndrome type II?
What distinguishes Gilbert syndrome from Crigler-Najjar syndrome type II?
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Which syndrome is associated with impaired biliary excretion of bilirubin glucuronides?
Which syndrome is associated with impaired biliary excretion of bilirubin glucuronides?
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Study Notes
Jaundice and Cholestasis
- Jaundice (and icterus) is yellow discoloration of skin & sclera due to bilirubin retention
- Cholestasis is systemic retention of bilirubin and other bile solutes
- Bilirubin exists in two major forms: unconjugated and conjugated
Pathophysiology of Jaundice
- Unconjugated Bilirubin: Virtually insoluble, tightly bound to albumin, cannot be excreted in urine, can cross blood-brain barrier (potentially causing kernicterus).
- Conjugated Bilirubin: Water-soluble, non-toxic, loosely bound to albumin, can be excreted in urine; normal serum levels are 0.3-1.2 mg/dL, above 2.0-2.5 mg/dL causes jaundice
- Jaundice results from an imbalance between bilirubin production and clearance due to:
- Excessive bilirubin production (e.g., hemolytic anemias, thalassemia)
- Reduced hepatocyte uptake (e.g., some cases of Gilbert syndrome, drugs)
- Impaired bilirubin conjugation (e.g., newborn physiologic jaundice, breast milk jaundice, Gilbert syndrome, hepatitis)
- Decreased hepatocellular excretion (e.g., transporter deficiencies like Dubin-Johnson or Rotor syndrome)
- Impaired bile flow
- First three mechanisms typically lead to unconjugated hyperbilirubinemia
- Last two mechanisms typically lead to conjugated hyperbilirubinemia
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Genetic Mutations: Multiple genetic mutations can cause hereditary hyperbilirubinemia.
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Unconjugated Hyperbilirubinemia:
- Crigler-Najjar syndrome type I: Absence of UGT1A1 activity, fatal neonatal period.
- Crigler-Najjar syndrome type II: Decreased UGT1A1 activity, Generally mild, occasional kernicterus.
- Gilbert syndrome: Decreased UGT1A1 activity, Most common form, often innocuous.
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Conjugated Hyperbilirubinemia:
- Dubin-Johnson syndrome: Impaired biliary excretion of bilirubin glucuronides, generally innocuous, pigmented cytoplasmic globules; also, epinephrine metabolites
- Rotor syndrome: Decreased hepatic uptake and storage, decreased biliary excretion Innocuous
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Unconjugated Hyperbilirubinemia:
Neonatal Jaundice
- Newborn infants often experience transient, mild unconjugated hyperbilirubinemia (physiologic jaundice) due to immature hepatic machinery for bilirubin conjugation & excretion.
- Breastfeeding may exacerbate this jaundice due to bilirubin-deconjugating enzymes in breast milk.
Viral Hepatitis (General)
- Viral hepatitis is liver infection caused by hepatotropic viruses (HAV, HBV, HCV, HDV, HEV).
Hepatitis A Virus (HAV)
- HAV causes a self-limiting, benign disease with 2-4 week incubation.
- It rarely progresses to fulminant hepatitis and has a low fatality rate (<0.1%).
- Commonly found in areas with poor sanitation, acquiring antibodies common by age 10.
- Mild or asymptomatic illness, rare in adults.
- Symptoms: Fatigue, loss of appetite, jaundice.
- Diagnosis: Elevated IgM anti-HAV at illness onset (reliable marker).
- Fecal shedding stops with rising IgM: IgM declines in months, followed by IgG anti-HAV development for years, conferring long-term immunity.
- Chronic carrier state and hepatitis are uncommon
- IgG levels are inferred by the difference between total and IgM anti-HAV. No direct IgG test commonly available.
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Description
This quiz explores the concepts of jaundice and cholestasis, including their definitions, causes, and the types of bilirubin involved. Understand the pathophysiology of jaundice and how it affects bilirubin production and clearance in the body. Test your knowledge on these critical topics in medical science.
