Flashcards in Jaundice Deck (33):
What is heme?
- heme is the prosthetic group of hemoglobin, myoglobin, cytochromes, catalase, and peroxidase
When does jaundice occur?
- when serum bilirubin levels exceed 2 mg/dL
- (hyperbilirubinemia is greater than 1 mg/dL)
Normal Serum Bilirubin Levels
- between 0.1 and 1.0 mg/dL
- (majority is unconjugated bilirubin, only a small amount is conjugated)
What are the two types of bilirubin? Which is water-insoluble?
- unconjugated bilirubin: water insoluble (AKA indirect bilirubin)
- conjugated bilirubin: water soluble (AKA direct bilirubin)
What makes up conjugated bilirubin?
- bilirubin + 2 glucuronic acid
- (known as bilirubin diglucuronide)
What are the 5 general causes of hyperbilirubinemia/jaundice? Which type of bilirubin is increased in each?
- increased unconjugated: increased bilirubin production, decreased hepatic bilirubin uptake, disrupted intracellular conjugation
- increased conjugated: disrupted secretion of bilirubin into bile canaliculi, bile duct obstruction
T or F: all cells produce heme.
- however, major locations are in the liver and in the bone marrow (erythroid progenitor cells)
What is the main enzyme involved in heme production?
- ALA synthase
What do phenobarbitals do to heme synthesis? What about lead?
- phenobarbitals induce heme synthesis by activating ALA synthase
- lead inhibits several enzymes involved in heme production, so it prevents heme formation
How long do RBCs circulate the body before being degraded by the liver and/or spleen?
- between 90 and 120 days
____% of heme degradation is of old, worn-out RBCs; what is the remaining percentage of?
- 85% is old RBCs
- 15% is immature RBCs, myoglobin, and cytochromes
Hemoglobin gets broken down into ______ and ______.
- heme and globin
- heme --> iron + bilirubin --> excretion and/or reabsorption
- globin --> amino acids --> recycled into hemoglobin synthesis
Where does heme get broken down into bilirubin? List the steps involved.
- heme breakdown into bilirubin occurs in the MACROPHAGE (the bilirubin then leaves the cell and heads to the liver in the blood)
- heme oxygenase converts heme into biliverdin --> biliverdin reductase converts biliverdin into bilirubin
Why do we convert biliverdin into bilirubin? (ie: why don't we just stop at biliverdin?)
- because biliverdin is very insoluble!
- bilirubin is also insoluble, but less so than its precursor
Bilirubin is pretty hydrophobic (water-insoluble), so how does it move around the blood and into the liver?
- it gets joined by albumin! this makes it more soluble, allowing it to travel in the blood
What happens to bilirubin once it enters the liver?
- it gets acted on by UDP-glucoronosyl transferase and gets converted into bilirubin diglucuronide (conjugated bilirubin)
- this further increases the molecule's solubility
What happens to bilirubin diglucuronide once it is actively secreted into the duodenal lumen?
- it gets hydrolyzed by bacterial enzymes into urobilinogen
- some (20%) urobilinogen gets reabsorbed into the circulation where it is mainly returned via enterohepatic circulation to the liver (90%), or where it gets converted to urobilin and excreted by the kidneys (10%)
- most (80%) urobilinogen gets converted to stercobilin and is excreted with feces
What color is urobilinogen? Urobilin? Stercobilin? What color is conjugated bilirubin?
- urobilinogen: colorless
- urobilin: yellow (urine)
- stercobilin: brown (feces)
- conjugated bilirubin: dark brown
4 Classifications of Jaundice
- pre-hepatic/hemolytic, hepatic/hepatocellular, post-hepatic/obstructive, and neonatal
- AKA hemolytic jaundice
- increased hemolysis results in overproduction of bilirubin beyond liver's capacity to take it in
- main increase is in unconjugated bilirubin levels
- more bilirubin in blood = more in liver = more in bile, so patients will also have darker urine (b/c increased urobilin) and darker feces (b/c increased stercobilin)
What are three examples of disorders that can cause pre-hapatic jaundice?
- incompatible blood transfusion, malaria, and sickle-cell anemia
- AKA obstructive jaundice
- obstruction prevents bile secretion, leading to build-up of bilirubin
- main increase is in conjugated bilirubin levels
- lack of bilirubin in bile, so patients will have light colored, floating feces (no stercobilin and steatorrhea), but will have DARK urine
- conjugated bilirubin in serum also results in nausea and anorexia (loss of appetite)
In post-hepatic jaundice, bilirubin isn't entering the duodenal lumen, explaining why these patients have light colored, floating feces; why, then, do patients have dark urine? (ie: why isn't their urine also colorless?)
- because the elevated conjugated bilirubin enters the blood and the kidneys, and this gives urine a very dark color
- AKA hepatocellular jaundice
- liver dysfunction and/or damage results in a loss of function, causing an increase in unconjugated AND conjugated bilirubin
- patients will have light, floating feces, dark urine, nausea, and anorexia
- jaundice is common in many neonates because it takes about 2 weeks for the hepatic machinery to mature and develop
- mainly an increase in unconjugated bilirubin
- worrying because excess bilirubin can cross the immature blood-brain barrier, resulting in toxic encephalopathy
What are the most common causes of jaundice?
- hepatitis, biliary obstruction, and hemolytic anemia
- a benign (not associated with any increased morbidity), inherited condition resulting in mild, fluctuating increases in unconjugated bilirubin
- a result of decreased levels of bilirubin UDP glucuronyl transferase and decreased bilirubin uptake
- an inherited defect in the transport protein needed for hepatocellular excretion of bilirubin, leading to large increases in conjugated bilirubin
- patients have a VERY dark liver (but the color is NOT due to the conjugated bilirubin!)
Unconjugated bilirubin is also known as ______ bilirubin; conjugated bilirubin is also known as _______ bilirubin.
- unconjugated = indirect
- conjugated = direct
What is a major complication of physiologic jaundice of the newborn if left untreated? How do we treat this type of jaundice?
- kernicterus: a bilirubin induced brain dysfunction (can be fatal)
- (unconjugated bilirubin is very fat soluble and can therefore deposit in the brain)
- treat this jaundice with phototherapy, which makes unconjugated bilirubin water-soluble (note that it does NOT make it into conjugated bilirubin)
Crigler-Najjar Syndrome (types I and II)
- absence of UDP-glucuronosyltransferase, resulting in early and rapid onset of elevated unconjugated bilirubin, jaundice, kernicterus and death within a few years if untreated
- treat with plasmapheresis and phototherapy
- type I is more severe than type II
What is the difference between jaundice and cholestasis?
- jaundice = excess bilirubin that manifests as discoloration
- cholestasis = retention of bile (excess bilirubin, bile salts, and cholesterol) that manifests as pruritis and xanthomas
- (obstructive jaundice usually results in cholestasis as well)