INHERITED DISORDERS OF BILIRUBIN METABOLISM Flashcards
Unconjugated
GILBERT’S SYNDROME
Bilirubin transport deficit; cant transport into
the hepatocyte
GILBERT’S SYNDROME
Characterized by impaired cellular uptake of
bilirubin due to genetic mutation in UGT1A1
gene (chromosome #2)
GILBERT’S SYNDROME
Affected individuals may have no symptoms but
may have mild icterus and predisposed
acetaminophen toxicity.
GILBERT’S SYNDROME
GILBERT’S SYNDROME
Laboratory findings:
Indirect Bilirubin
1.5-3.0 mg/dL INCREASE
Conjugation deficit
CRIGLER-NAJJAR SYNDROME
CRIGLER-NAJJAR SYNDROME
Responsible for conjugation bilirubion
UDGPT
Chronic non-hemolytic unconjugated
hyperbilirubinemia; Bilirubin 1 ; cant be
conjugated
CRIGLER-NAJJAR SYNDROME
CRIGLER-NAJJAR SYNDROME
Laboratory result:
elevated indirect bilirubin
CRIGLER-NAJJAR SYNDROM
Treatment:
phototherapy because they are
photo sensitive
Complete deficiency of UDGPT
Crigler-Najjar Syndrome Type I
Crigler-Najjar Syndrome Type I
Laboratory result:
Indirect bilirubin: ?
Direct bilirubin: ?
Indirect bilirubin: >25 mg/dL
Direct bilirubin: none
Crigler-Najjar Syndrome Type I
Symptoms:
kernicterus, colorless bile
Partial deficiency of UDGPT
Crigler-Najjar Syndrome Type II
Crigler-Najjar Syndrome Type II
Laboratory results:
Indirect bilirubin: 5-20 mg/dL
direct bilirubin: small amount
Familial form of unconjugated
hyperbilirubinemia caused by a circulating
inhibitor of bilirubin conjugation
LUCEY-DRISCOLL SYNDROME
UDGPT is present but there is inhibitor present
which doesn’t not conjugate causing increase
indirect bilirubin.
LUCEY-DRISCOLL SYNDROME
LUCEY-DRISCOLL SYNDROME
Laboratory findings:
Indirect bilirubin: increased (2-3 weeks of
life)
CONJUGATED HYPERBILIRUBINEMIA
DUBIN-JOHNSON SYNDROME
Bilirubin excretion deficit
DUBIN-JOHNSON SYNDROME
Defective excretion of direct bilirubin into the
canaliculi caused by hepatocyte membrane
defect. B2
DUBIN-JOHNSON SYNDROME
Characterized of an intense dark pigmentation
of the liver due to accumulation of LIPOFUSCIN
PIGMENT= black liver
DUBIN-JOHNSON SYNDROME
CONJUGATED HYPERBILIRUBINEMIA
ROTOR SYNDROME
Similar with dubin without the black liver
ROTOR SYNDROME
The cause is unknown
ROTOR SYNDROME
Rotor Syndrome
Laboratory findings:
Elevation in direct bilirubin and total bilirubin: ?
Delta Bilirubin: ?
Elevation in direct bilirubin and total bilirubin
(2-5mg/ dL)
Delta Bilirubin: increase
Sample: SERUM ; covered with carbon paper or
aluminum foil
BILIRUBIN METHODOLOGY
BILIRUBIN METHODOLOGY
If sample is prepared and stored properly:
o Room temperature: ?
o Refrigerator (4˚C): ?
o Freezer (-20˚C): ?
If sample is prepared and stored properly:
o Room temperature: 2 days
o Refrigerator (4˚C): 1 week
o Freezer (-20˚C): indefinite
BILIRUBIN METHODOLOGY
Fasting sample is ________ but not required. Because Lipemia may cause false increased in bilirubin
preferred FASTING
BILIRUBIN METHODOLOGY
Interferences:
decrease reaction of bilirubin with
diazo reagent (decreased bilirubin)
Hemolysis
BILIRUBIN METHODOLOGY
Interferences:
increased bilirubin concentration
Lipemia
diazotization
of bilirubin to form azobilirubin; indirect bilirubin
because it cant directly act on reagent
VAN DEN BERG REACTION
to measure indirect bilirubin
because it is slow reacting bilirubin hence measured
total bilirubin.
Add accelerants
Principle: Van den berg reaction
Evelyn and Malloy Method
Reagents:
a.Coupling accelerator: ?
b. Diazo reagents: direct bilirubin
o Diazo A – ?
o Diazo B – ?
o Diazo blank – ?
Coupling accelerator: methanol
b. Diazo reagents: direct bilirubin
o Diazo A – 0.1% sulfanilic acid + HCL
o Diazo B – 0.5% sodium nitrate
o Diazo blank – 1.5% HCL
Performed at pH near 1.0
Evelyn and Malloy Method
Evelyn and Malloy Method
Final reaction:
PINK TO PURPLE (with maximal absorption at
560 nm
Evelyn and Malloy Method
DISADVANTAGE:
The methanol will cause
precipitation in the sample which lead to turbidity
that interferes with the test.
Most commonly used because it is more sensitive,
does not caused turbidity due to precipitation of
proteins. More safe much neutral Ph.
Jendrassik and Grof Method
Popular technique for discreet analyzers
) Jendrassik and Grof Method
Jendrassik and Grof Method
Main reagent:
Diazo reagent
Jendrassik and Grof Method
Accelerator:
Caffeine sodium benzoate
Jendrassik and Grof Method
Buffer:
sodium acetate
jendrassik and Grof Method
terminates the accelerator and
destroys excess diazo reagent
ASCORBIC ACID
Jendrassik and Grof Method
provides alkaline
pH after addition of ascorbic acid
ALKALINE TARTRATE SOLUTION
Jendrassik and Grof Method
Final Reaction:
blue azobilirubin (measured at
600nm)
