360 - Iron & Bilirubin Flashcards
The majority of the body’s iron, approximately 94% is distributed in…
hemoglobin, ferritin, and hemosiderin
Less than 0.1% of the body’s iron is present in plasma as…
transferrin
a plasma protein that transports ferric iron (Fe3+) from one organ to another
apotransferrin
Normally, approximately ___ of the iron binding sites of transferrin are occupied by iron
1/3
Plasma iron levels are highest in the ___________ and progressively ______ over the day
morning; decline
causes of increased serum iron
hemochromatosis
iron meds
hormonal contraceptives
aplastic anemia
causes of decreased serum iron
IDA
hemorrhage
menstruation
medication
anemia of chronic disease
TIBC
total iron binding capacity
- serum iron is measured as described
- ferric iron (Fe3+) is added in excess to the sample to saturate the binding sites on transferrin
excess iron is removed by either a silica or anion exchange column, or by the addition of magnesium carbonate; serum iron assay performed after to compare to first measurement
increased TIBC
IDA
pregnancy
oral contraceptives
decreased TIBC
chronic inflammatory disease
malignanacy
hemochromatosis
major storage form of iron
ferritin
- acute phase protein
- found in BM, liver, spleen
- detected by immunoassay
increased ferritin
malignancies
chronic infections
hemochromatosis
chronic inflammatory diseases (SLE)
hepatitis (eg. viral)
decreased ferritin
IDA
where is apotransferrin produced?
produced by the liver and carries ferric iron in the blood; the iron/apotransferrin complex is known as transferrin
how can we measure apotransferrin?
immunoturbidimetry
immunonephelometry
increased transferrin
pregnancy
administration of estrogen
iron deficiency
decreased transferrin
negative AP: rxn to inflammation, malignancy
decreased synthesis: chronic liver disease, malnutrition
protein loss: nephrotic syndrome
fecal immunochemical testing (FIT)
detects hemoglobin in feces
screening test for colorectal cancer
recommended for 50y/o; test every 2 years
FIT test reaction
monoclonal or polyclonal Ab + Hb => Ab-Ag product
a degradation production of heme
bilirubin
main sources of heme
aged red blood cells, myoglobin, cytochromes, and peroxidases
how is bilirubin transported in blood
bound to albumin
what happens to bilirubin in the liver?
it is conjugated to produce bilirubin monoglucuronide and diglucuronide
both products excreted into intestine with bile
intestine = bilirubin monoglucuronide is hydrolyzed and reduced to form urobilinogen => may further degraded to urobilin
method for measuring total bilirubin
diazo method (modified Jendraski-Grof method)
Bilirubin + Diazotized sulfanilic acid -> azobilirubin
this is used as an accelerant in diazo method as it frees unconjugated bilirubin from albumin
caffeine-benzoate-acetate
which wavelength is used to measure bilirubin?
530 nm
interefernece in measuring bilirubin
- lipemia = false INCREASE
- hemolysis = false DECREASE
- exposure to light = false DECREASE
Direct spectrophotometry for Unconjugated Bilirubin
- exclusively used for newborn children
- [bilirubin] directly determined at 454 nm
- bichromatic measurement is used to eliminate interference from oxyhemoglobin
> absorbance at 454 nm minus the absorbance at 540 nm equals the true bilirubin absorbance
interference of direct spectrophotometry for unconjugated bilirubin
carotenoids absorb at 454 nm, but newborn children do not have carotene
neonatal jaundice
- immature livers cannot conjugate bilirubin = cannot synthesize proteins
- HbF = increased catabolism of Hb
- neonates, intestinal flora not fully developed = conjugated bili does not get reduced to urobilinogen for excretion
- hemolytic disease of newborns = increased Hb catabolism
- may be treated with UV light therappy
Critical levels of unconjugated bilirubin may cause THIS which can result in brain damage (neonatal jaundice)
KERNICTERUS
critical balue of total bilirubin in children <30 days old
> 300 umol/L
pre-hepatic jaundice
Hemolytic anemia may produce more bilirubin than the liver can process
hepatic jaundice
Damage to the hepatocytes, or inherited disorders result in the inability to conjugate or excrete conjugated bilirubin, or inability to take up unconjugated bilirubin for conjugation and excretion
post-hepatic jaundice
cholestasis
- gallstones, spasms, or neoplasms may prevent bilirubin-glucuronide from reaching the intestine
inherited disorders of bilirubin metabolism (hepatic jaundice)
Crigler-Najjar Syndrome Type I
“ Type II
Dubin-Johnson Syndrome
Rotor Syndrome
Gilbert Syndrome
Lucey-Driscoll Syndrome
Crigler-Najjar Syndrome Type I
complete absence of UDP-glucuronyltransferase, resulting in very high concentrations of unconjugated bilirubin
autosomal recessive
Kernicterus results in severe brain damage and usually results in death
Crigler-Najjar Syndrome Type II
autosomal dominant disorder is the result of a partial deficiency in UDP-glucuronyltransferase. Normal life is expected with phenobarbital administration
Dubin-Johnson Syndrome
- autosomal recessive condition with jaundice
- elevated levels of conjugated bilirubin with only a slight increase in unconjugated bilirubin
- problem involves the excretion of conjugated bilirubin from the hepatic microsomes into the canaliculi
Rotor Syndrome
similar to Dubin-Johnson Syndrome.
Gilbert Syndrome
probably autosomal recessive with mild unconjugated hyperbilirubinemia. No treatment is required
Lucey-Driscoll Syndrome
- caused by an inhibitor of bilirubin conjugation
- unconjugated bilirubin levels are increased
- occurs in the early neonatal period lasting about 2 -3 weeks post-delivery
