Lecture 30 - Heme metabolism

Lesley Howard
Flashcards by Lesley Howard, updated more than 1 year ago
Lesley Howard
Created by Lesley Howard about 4 years ago
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Lecture 30
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Sequence of bilirubin metabolism Formation and transport of bilirubin in liver Uptake and conjugation of bilirubin by liver Secretion and catabolism of CB Enterohepatic resorption of UB Urinary excretion of UB
Majority of RBCs degraded in? Spleen
Immature or defective RBC precursors degraded where? Bone marrow
Cytochromes degraded where? Tissue
Heme oxygenase Removes the iron at the core of heme, converting it to green biliverdin In macrophage
Biliverdin reductase Converts biliverdin to UCB In macrophage
Why is UCB so stable? Removal of the iron from the heme causes the formation of intramolecular hydrogen bonds
UCB is transported to the liver via? Serum albumin binds it, neutralizes its toxicity, and carries it through circulation
OATP ATP independent transporter on hepatocytes Transports UCB into hepatocyte, from circulation, releases albumin back into circulation
GST Entraps UCB in hepatocyte and tags it for further modification
UGT Attaches a pair of glucuronic acids to UCB, creating CB
CB Amphipathic thanks to two glucuronic acids attached via UGT Less toxic than UCB
MRP2 Uses ATP to transport CB from the hepatocyte into the bile duct against its concentration gradient Rate limiting step
Urobilinogen Colorless, formed as intestinal bacteria hydrolyze and reduce CB
Stercobilin Formed as intestinal urobilinogen is auto-oxidized. Gives feces characteristic brown color
Excretion in stool 90% of urobilinogen is converted to stercobilin and excreted
Reabsorption into enterohepatic circulation 10% of urobilinogen is reabsorbed 9% of the reabsorbed urobilinogen is reabsorbed into the liver and re-excreted into the bile duct
Urinary excretion 1% of the reabsorbed urobilinogen is auto-oxidized to urobilin (yellow) and excreted in urine
Diazo reaction Dye is added to serum and the rate of purple color formation is measured
TBIL Total bilirubin Diazo reaction + methanol Unfolds and solubilizes CB so the diazo can react Gives a measurement of total serum UB
DBIL Directly reacting bilirubin Diazo only, no methanol Reacts with 100% of the unfolded and soluble CB, and 10-15% of the folded and insoluble UCB Gives a measurement of serum CB and a little serum UCB
IBIL Indirectly reacting bilirubin TBIL-DBIL Considered to be the measurement of UCB only
Hyperbilirubinemia values 2-3 mg/dL instead of 1 mg dL
Physiologic jaundice Common in neonates due to immature liver Low hepatic UGT Low production of albumin Accelerated neonatal RBC destruction
Phototherapy Blue light alters the conformation of UCB creating photoisomers that are more polar They cannot enter brain and are excreted from urine or bile without further modification
Kernicterus Excess UCB that is not bound to albumin enters brain and forms precipitates on basal ganglia Can result in neuronal damage ranging from hearing loss to death Infants more susceptible due to immature BBB
Prehepatic jaundice Caused by hemolytic anemia Destruction of damaged RBC = increased production of heme metabolites and increased serum UCB No pathology of liver or bile duct
Hepatic Jaundice Caused by liver damage or infection Excretion of CB to bile duct is impaired Damaged tight junctions allows CB to leak back to circulation Damaged liver cells compromise reabsorption of urobilinogen
Posthepatic jaundice Bile duct obstruction blocks from of CB into duodenum Little to no urobilinogen Damaged liver cells allow CB to leak into circulation
Prehepatic jaundice lab values IBIL: Increased DBIL: Normal Urinary urobilinogen: Increased Fecal urobilinogen: Increased
Hepatic jaundice IBIL: Increased DBIL: Increased Urinary urobilinogen: Increased Fecal urobilinogen: Decreased
Posthepatic labs IBIL: Normal to increased DBIL: Decreased Urinary urobilinogen: Decreased Fecal urobilinogen: Decreased
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