HyperBilirubinaemia Flashcards
process of bilirubin synthesis
- globin removed from HB to form haeme
-haeme acted on by HAEME OXIDASE to form Biliverdin - reduced by BILIVERDIN REDUCTASE to form Bilirubin
- transported to liver & conjugated there
what level of bilirubin is described as hyperbilirubinaemia
above 1.5mg/dl (25.5umol/L)
when does jaundice occur in hyperbilirubinaemia
above 2.0mg/dl (34umol/L)
Pathophysiology of Hyperbilirubinaemia
1) increased RBC destruction
2) hepatic uptake disorder
3) drug displacement of bilirubin from binding sites
4) hepatic conjugation disorder
5) interference with albumin transport
__ hydrolyses conjugated bilirubin and increases its absorption
beta-glucoronidase in meconium
which type of hyperbilirubinaemia is Indirected?
unconjugated
in unconjugated hyperbilirubinaemia, bilirubin is found in the urine,
True/False ?
false !
*it is lipid soluble but not water soluble
where does bilirubin deposit in unconjugated hyperbilirubinaemia?
the basal ganglia & brain stem
__ has been added to bilirubin to conjugate it in conjugated hyperbilirubinaemia ?
glucoronic acid
Breast milk jaundice is due to the presence of _ in milk
alpha - glucoronidase
types of UN-HYPERB
1) physiological jaundice
2) breast milk jaundice
3) haemolytic disorders eg G6PD deficiency
4) haemoglobinopathies eg Thalassemia
5) inherited syndrome eg Gilbert, Crigler Najjar, Lucey Driscoll
UN-HyperB occurs when there sis a problem _ of conjugation.
upstream
what happens to urobilinogen in UN-HyperB
its level is increased in urine
_ is the most common congenital cause of UN-HYPERB
Gilbert’s syndrome
Gilbert’s syndrome is caused by a mutation of what gene ?
UGT1A1 gene (leads to reduced activity of glucuronosyltransferase)
*helps process bilirubin
in type 1 of Crigler-Najjar Syndrome there is deficiency of what enzyme ?
uridyl-diphosphoglucuronyl transferase
(UDPGT)
_ type of Crigler-Najjar syndrome responds to phenobarbital treatment
type 2 (there’s partial deficiency of UDPGT)
what syndrome has a circulating inhibitor of bilirubin conjugation ?
Lucey -Driscoll syndrome
(*familial)
extrahepatic causes
1) stones
2) infection
3) tumors
4) compression of biliary duct
5) primary sclerosing cholangitis
intrahepatic causes
1) familial/hereditary disorders
2) drugs
3) sepsis
4) post op state
5) biliary cirrhosis
6) hepatocellular disease
7) neoplasms
what is bilirubin level in physiological neonatal jaundice
Less than 15mg/dl
what happens to unconjugated bilirubin levels in PREHEPATIC jaundice
it is ELEVATED
Unconjugated bilirubin is NOT present in any type of jaundice
TRUE
in what forms of jaundice are conjugated bilirubin levels elevated in the blood & urine
hepatic & post hepatic
Urobilinogen is elevated in Urine & faeces in what type of jaundice
pre hepatic
*levels normal in hepatic & absent in post hepatic
when AST & ALT are elevated it is most likely what type of jaundice ?
hepatic
ALP is elevated in what type of jaundice ?
post hepatic
Jendrassik-Groff uses _ as an accelerator
while methanol is used as an accelerator in _
caffeine
Malloy-Evelyn
*Diazo reaction
Enzymatic method uses _
bilirubin oxidase
component of fouchets reagent
1) trichloroacetic acid - 25gms
2) distilled water -100ml
3) 10% ferric chloride solution - 10ml
*add 10% barium chloride to acidified urine
* 1 drop of Fouchets
*blue/green indicates bilirubin
colorimetric strip raegent test is based on what principle ? i
coupling of bilirubin with diazotized 2,4-dichloroaniline in a strong ACID medium to form a brown/purple azobilirubin compound
*results - negative, small(+), moderate (++), large (+++)
what test is used for detection of urobilinogen ?
Qualitative Ehrlich’s Test
components of Ehrlich’s reagent
paradimethylaminobenzaldehyde
20% 5HCL
*pink color if urobilinogen is present
*cherry red if excess
*use fresh urine, exposure to air oxidizes urobilinogen to urobilin
test for detection of bile salts
- hay test
*sprinkle flowers of sulphur in urine
*if bile salts present they sink to the bottom (bile salts lower surface tension)
test for detection of bile pigments
1) foam test (yellow foam indicates bile pigments)
2) Gmelins test
*yellow nitric acid in test tube with urine
*play of colored rings, most distinct being green indicates bile pigments
de ritis ratio
ratio of AST/ALT (used to differentiate btwn viral & non viral hepatitis)
<1 = viral hepatitis
>1= non viral hepatitis (alcohol liver dx usu >3)
AST & ALT levels in acute liver disease vs chronic liver disease
both elevated in acute
AST higher in chronic
*AST in cytosol & mitochondria
*ALT in only cytosol
type 1 Crigler Najjar syndrome is what
autosomal recessive
type 11 crigler najjar syndrome is
autosomal dominant
