Bilirubin Metabolism and Mechanisms of Jaundice Flashcards
What is the end product of heme catabolism?
Bilirubin
What is the brain injury to newborns caused by high concentrations of bilirubin?
Kernicterus
What are the four steps of bilirubin transfer from the blood to the bile?
- Uptake
- Binding
- Conjugation
- Excretion
What occurs to make bilirubin water soluble?
Conjugation in which it is conjugated to glucuronic acid in the ER which contains uridine diphosphate-glucuronyl transferase
What are the general causes that lead to jaundice?
Overproduction of bilirubin, interference with hepatic uptake/intracellular metabolism of bilirubin and impairment of bile excretion are all cases of jaundice
What are the causes of increased production of bilirubin?
Increased destruction of erythroytes or ineffective erythropoesis
What type of hyperbilirubinemia is caused by uncomplicated hemolytic disease?
Unconjugated bilirubin
What type of hyperbilirubinemia is caused by parenchymal liver disease?
Both conjugated and unconjugated hyperbilirubinemia
What type of disease is caused by impaired hepatic uptake?
Hyperbilirubinemia of the unconjugated type
What is the disease in which there is chronic, severe, unconjugated hyperbilirubinemia, due to the complete absence of hepatic UGT activity?
Crigler-Najjar Syndrome Type I
What is Crigler-Najjar syndrome type II?
Similar but less severe than CNS type I disease and only entails a partial decrease in UGT activity
What is the condition in which hyperbilirubinemia occurs due to the inadequate synthesis of the UGT enzyme (Much more mild than Crigler-Najjar)?
Gilbert Syndrome
What is often the cause of decreased transport of conjugated bilirubin?
Mutations in the multidrug resistance protein family
What is Dubin-Johnson syndrome?
Benign AR disease with chronic conjugated hyperbilirubinemia and conspicuous deposition of melanin-like pigment in the liver
What mutation occurs in the Dubin-Johnson Syndrome?
ABCC2/MRP2 gene
How is Dubin-Johnson syndrome distinguished from other conditions with conjugated hyperbilirubinemia?
Testing urinary coproporphyrin excretion
What findings of urinary coproporphyrin excretion suggest Dubin-Johnson syndrome?
isomer I: isomer III ratio of 4:1 from the normal 1:3
What are the uscopic findings of Dubin-Johnson Syndrome?
Coarse iron-free dark-brown granules in hepatocytes and Kupffer cells
AR disease in which conjugated hyperbilirubinemia occurs but pigmentation of the liver is absent.
Rotor Syndrome
Syx of Rotor Syndrome?
Patients are generally aSyx
Disease in which episodic intrahepatic cholesttasis occurs but is generally self-limited and has no sequelae?
Benign recurrent intrahepatic cholestasis
AR disease in which intrahepatic cholestasis progresses relentlessy to cirrhosis?
Progressive Familial Intrahepatic Cholestasis
What hepatic condition can occur in pregnancy?
Intrahepatic cholestasis
What type of hyperbilirubinemia is seen with sepsis?
Conjugated Hyperbilirubinemia
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
What is cholestasis due to intrinsic liver disease? Obstruction of the bile ducts?
Intrahepatic cholestasis, Extrahepatic cholestasis
What does the inability to excrete bile acids into canaliculi cause?
An increase in serum and hepatocellular bile acid concentrations
Three alterations that can cause cholestasis?
- Damage to canalicular plasma membrane
- Alteration in contractile properties of the canaliculus
- Alterations in the permeability of the canalicular membrane
Uscopically, how is cholestasis characterized?
Presence of brownish bile pigment w/i dilated canaliculi and in hepatocytes
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
What is the name of the triad in which:
- Hydropic swelling
- Diffuse impregnation w/ bile pigment
- Reticulated appearance
Feathery degeneration (This occurs in extrahepatic obstruction)
What do ruptured bile ducts cause on uscopic analysis?
Bile lakes - focal, golden yellow deposits surrounded by degenerating hepatocytes
What are the typical clinical presentations of cholestasis?
Pruritus. xanthomas (accumulation of cholesterol in the skin), malabsorption
