Hyperbilirubinemia in the newborn. Flashcards
where does haemoglobin get catabolised ?
in the reticuloendothelial system
how much more bilirubin do newborn produce compared to adults
two to 3 times moe
what is the cause of increased bilirubin production in newborns ?
increased RBC , or hematocrit ,
shorter erythrocyte life span
inefficient erythropoesi
decreased albumin binding = lower albumin con
decreased ligandin so less hepatic uptake
decreased secretion
indirect bilirubin is particularly harmful to which part of the body
toxic to the CNS
what can increase indirect bilirubin rather than liver and spleen and reticuloendothelial probes
organic acids such as fatty acids and drugs can displace the bilirubin from albumin
which enzyme represents the rate limiting step of bilirubin conjugation
glucuronosyltransferase
for hepatic conjugation to occur bilirubin myst dissociate from albumin and bind to which liver protein
ligandin
conc of ligandin and glucuronosyltransferase is particularly low in whom
newborn and preterm
can indirect bilirubin cross the placenta
yes it can cross the placenta and become conjugated by the maternal hepatic enzymes
clinical pattern of physiological jaundice is what
hyperbilirubinemia can start no before than 24 hrs and no more than 12MG/DL in the 3rd day of life
in preterm = 15mg/dl in the fifth day of life
jaundice is unphysiological if what ?
appears on the first day of life
bilirubin levels increases more than 0.5MG/DL/HR
if the peak bilirubin is greater than 13mg/dl in term infants
if direct bilirubin fraction is greater than 1.5MG/DL
heaptosplenomegaly and anemia is present
what is crigler-najjar syndrome ?
autosomal dominant disease
or autosomal recessive
rare but permanent deficiency of gluconosyltransferase
what can treat AUTOSOMAL DOMINANT crigler-najjar syndrome ?
some variety respond to enzyme induction by phenobarbitural = producing and increase in enzyme activity and reduction of bilirubin lives
what can treat autosomal recessive format of the crigler-najjar syndrome ?
it does not respond to phenobarbitutal and manifest as perisirant indirect hyperbilirubinemia
what is gilbert disease ?
mutation of the promoter region of glucuronsyltransferase = mild indirect hyperbilirubinemia results
if gilbert disease was concomitant with what other disease can lead to severe jaundice formation
other icterogenic factor such as hemolysisi
breast milk jaundice have appearance when in a baby’s life
first or second week
what is a sign and symptom of breast milk jaundice ?
bilirubin rarely increases more than 20mg/dl and interruption of breast feeding for 1 or 2 days results in rapid decline of bilirubin which do not increase significantly after breastfeeding resumes
why is there breast milk jaundice ?
breast milk may contain the inhibitor of bilirubin conjugation
increase the enterohepatic recirculation of bilirubin because of breast milk glucuronidase
early onset of jaundice scubas in the first days are due to ?
hemolytic diseases
internal haemorrhage = cephalohematoam ,, hepatic or splenic hematoma
OR infection sepsis
delayed cord clamping
Inherited red cell enzyme, membrane defects
(e.g., spherocytosis, glucose 6-phosphate-dehydrogenase deficiency,
physical evidence of jaundice is brough about when bilirubin levels reach what level
5-10mg/dl
unlike 2 mg/dl in adults
bilirubin greater than what in first day of life and second day of life should be evaluates
first day of life greater than 5mg/dl
second day greater than 13mg/dl
what are the diagnostic pathways to determine the etiology of the bilirubin
test direct and indirect bilirubin levels
Coombs test - for autoimmune haemolytic anemia
complete blood count
blood smear
reticulocyte count
what are the hemolysis absent causes of jaundice which is common
physiological
breast milk
internal haemorrhage
polycethma in diabetic mother
Mutations of glucuronyl transferase enzyme (Crigler- Najjar syndrome,
Gilbert isease),
pyloric stenosis, hypothyroidism
what are the hemolysisi present causes of jaundice
ABO blood group incompatibility
rh incompatibility
kell
duffy
Red blood cell enzyme defects: glucose-6- phosphate dehydrogenase, pyruvate kinase Red blood cell membrane disorders: spherocytosis, ovalocytosis
hemoglobinopathy - thalessemia
bilirubin encephalopathy or kernicterus is caused by bilirubin deposited where ?
basal ganglia
how can the indirect bilirubin cross the blood brain barrier
because of its lipid solubility and water insolubility
kernicterus usually develop in term infants when the bilirubin is ?
above 25mg/dl
In extremely immature infants weighting less than 1000 g when bilirubin
levels are less than 10 mg/dL because of
a more permeable bloodbrain barrier
associated with prematurity
the risk of kernicterus increases in the presence of what concomitant diseases
meningitis hemolysisi asphyxia hypoxia hypothermia hypoglycaemia bilirubin displacing drugs
what are the earliest clinical manifestation of kernicterus ?
lethargy hypotonia irritability poor moro reflex poor feeding high pitched cry emesis
when are the early signs of kerincterus noted ?
4 days of life
what are the late signs of kerincterus
bulging fontanel
opisthotonos posturing = when the bad becomes extremely arched due to muscle spasm seen in serious brain conditions such as meningitis and tetanus
pulmonary haemorrhage
fever
hypertonicity
paralysis of upward gaze
seizures
what are the late complication of kernicterus
spasticity resolves however nerve deafness choreoathetoid cerebral palsy mental retardation enamel dysplasia discolouration of teeth
early signs of kernicterus may be reversed using what
institute change transfusion
what is the treatment for hyperbilirubinemia ?
blue light phototherapy = esp when reaching between 16-18mg/dl
bilirubin is converted into isomers which are water soluble and easily excreted
infants with mild haemolytic disease can be managed how ?
occasionally by blue light phototherapy
when is exchange transfusion given ?
dangerously high levels of
as a rule of thumb 10 percent of the baby’s weight is used as the change number for indirect bilirubin
20mg/dl of bilirubin can be exchanged for a baby weight 2000g
depending on size of baby 5-20ml of of blood is withdrawn and new is infused per cycle the procedure lasting 45-90 minutes
total amount of blood exchanges = twice the infants blood vol
calculated
weight (kg) x85ml/kg x 2
this volume should remove 85 percent of infants RBC source of bilirubin , maternal antibodies
exchange transfusion is usually performed through what ?
umbilical venous catheter placed in the inferior end cava or the confluence of the umbilical vein and portal system
what are the complications of transfusion ?
transfusion reaction
metabolic instability
infection
vessel perforation - haemorrhage
hypotension
nectrositing enterocolitis
transfusion is also conjugated with what therapy o reduce the amount of transfusion needed ?
phototherapy
at what level is there direct conjugated hyperbilirubinemia
more than 2mg/dl or more than 20 percent of total bilirubin
is direct conjugated hyperbilirubinmia physiological
it is NEVER physiological
what causes direct conjugated hyperbilirubinemia ?
cholestasis Choledochal cysts billary atresia hepatocellular injury alpha 1 antitrypsin def CMV infection TORCH neonatal hepatitis sepsis cystic fibrosis inborn errors of metabolism neonatal iron storage disease
what is the diagnosis of conjugated direct hyperbilirubinemia ?
measure liver enzymes
bacterial and viral cultures
metabolic screening tests
hepatic ultrasound
sweat chloride test
what is a strong sign of binary atresia
dark urine
grey white stool after th second week
is direct bilirubin neurotoxic ?
Direct bilirubin cannot cross BBB and thus is not neurotoxic to the infant
