Flashcards
Lecture 30 - Heme metabolism
Flashcards do conjunto (32)
- 1Sequence of bilirubin metabolismFormation 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 - 2Majority of RBCs degraded in?Spleen
- 3Immature or defective RBC precursors degraded where?Bone marrow
- 4Cytochromes degraded where?Tissue
- 5Heme oxygenaseRemoves the iron at the core of heme, converting it to green biliverdin
In macrophage - 6Biliverdin reductaseConverts biliverdin to UCB
In macrophage - 7Why is UCB so stable?Removal of the iron from the heme causes the formation of intramolecular hydrogen bonds
- 8UCB is transported to the liver via?Serum albumin binds it, neutralizes its toxicity, and carries it through circulation
- 9OATPATP independent transporter on hepatocytes
Transports UCB into hepatocyte, from circulation, releases albumin back into circulation - 10GSTEntraps UCB in hepatocyte and tags it for further modification
- 11UGTAttaches a pair of glucuronic acids to UCB, creating CB
- 12CBAmphipathic thanks to two glucuronic acids attached via UGT
Less toxic than UCB - 13MRP2Uses ATP to transport CB from the hepatocyte into the bile duct against its concentration gradient
Rate limiting step - 14UrobilinogenColorless, formed as intestinal bacteria hydrolyze and reduce CB
- 15StercobilinFormed as intestinal urobilinogen is auto-oxidized. Gives feces characteristic brown color
- 16Excretion in stool90% of urobilinogen is converted to stercobilin and excreted
- 17Reabsorption into enterohepatic circulation10% of urobilinogen is reabsorbed
9% of the reabsorbed urobilinogen is reabsorbed into the liver and re-excreted into the bile duct - 18Urinary excretion1% of the reabsorbed urobilinogen is auto-oxidized to urobilin (yellow) and excreted in urine
- 19Diazo reactionDye is added to serum and the rate of purple color formation is measured
- 20TBILTotal bilirubin
Diazo reaction + methanol
Unfolds and solubilizes CB so the diazo can react
Gives a measurement of total serum UB - 21DBILDirectly 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 - 22IBILIndirectly reacting bilirubin
TBIL-DBIL
Considered to be the measurement of UCB only - 23Hyperbilirubinemia values2-3 mg/dL instead of 1 mg dL
- 24Physiologic jaundiceCommon in neonates due to immature liver
Low hepatic UGT
Low production of albumin
Accelerated neonatal RBC destruction - 25PhototherapyBlue 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 - 26KernicterusExcess 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 - 27Prehepatic jaundiceCaused by hemolytic anemia
Destruction of damaged RBC = increased production of heme metabolites and increased serum UCB
No pathology of liver or bile duct - 28Hepatic JaundiceCaused 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 - 29Posthepatic jaundiceBile duct obstruction blocks from of CB into duodenum
Little to no urobilinogen
Damaged liver cells allow CB to leak into circulation - 30Prehepatic jaundice lab valuesIBIL: Increased
DBIL: Normal
Urinary urobilinogen: Increased
Fecal urobilinogen: Increased - 31Hepatic jaundiceIBIL: Increased
DBIL: Increased
Urinary urobilinogen: Increased
Fecal urobilinogen: Decreased - 32Posthepatic labsIBIL: Normal to increased
DBIL: Decreased
Urinary urobilinogen: Decreased
Fecal urobilinogen: Decreased