HYPERBILIRUBINEMIA

• Increased plasma concentrations of bilirubin

(> 3 mg/dL) occurs when there is an imbalance
between its production and excretion .
Recognized clinically as jaundice
• .
•
 Definition:

• Hyperbilirubinemia refers to an excessive level

of accumulated bilirubin in the blood and is
characterized by jaundice, a yellowish
discoloration of the skin sclerae,mucous
membranes and nails
 TWO TYPES OF JAUNDICE

• 1.PHYSIOLOGIC
2.NON PHYSIOLOGIC
 PHYSIOLOGIC JAUNDICE (non-pathologic
unconjugated hyperbilirubinemia):

• Characteristics
• Appears after 24 hours
• Maximum intensity by 4th-5th day in term& 7th day in
preterm
• Serum level less than 15 mg / dl
• Clinically not detectable after 14 days
• Disappears without any treatment
• Note: Baby should, however, be watched for worsening
jaundice
• Term Infants:
– 50-60 % of all newborns are jaundiced in the first
week of life.
– Total serum bilirubin peaks at age 3–5 d (later in
Asian infants).
– Mean peak total serum bilirubin is 6 mg/dL
(higher in Asian infants).
• Preterm Infants:
– Incidence of visible jaundice is much higher than
in term infants.
– Peak is later (5-7d).
– Because of ↑ risk of bilibubin encephalopathy (see below),
“physiologic” jaundice is more difficult to define and
jaundice should be followed closely.
–
• DEFINITION of NON-PHYSIOLOGIC JAUNDICE:
– Jaundice in the first 24 hours •Bilirubin rising
faster than 5 mg/dL in 24 hours
– Clinical jaundice >1 week •Direct bilirubin >2
mg/dL
– In healthy term infants total serum bilirubin
concentration >15 mg/dL
• Lower levels in preterm infants, “sick” infants,
and hemolytic disease
• BILIRUBIN
• Non-polar, water insoluble compound
requiring conjugation with glucuronic acid to
form a water soluble product that can be
excreted.
• It circulates to the liver reversibly bound to
albumin
• Increased production in neonate due to larger
red cell volume, which produces bilirubin as
cells are broken down and shorter RBC life
span, so broken down faster.
• Heme is catabolized within the
reticuloendothelial system by heme oxygenase
to form biliverdin.
• Biliverdin is metabolized to bilirubin in the
presence of biliverdin reductase.
• BILIRUBIN METABOLISM: As red blood cells are
lysed, they release hemoglobin. Heme molecules
(from hemoglobin) are converted to bilirubin.
Bilirubin (unconjugated or indirect) is bound to
serum albumin and transferred to the liver where
it is conjugated to glucuronate by glucuronyl
transferase. Conjugated (direct) bilirubin is
excreted into bile. A fraction of bilirubin from the
stool is reabsorbed into the blood via the portal
circulation (enterohepatic circulation).
(Liver,
Bone marrow,
& Spleen)

Phagocytosis & Lysis

Hemoglobin

Globin Heme Bilirubin

Amino acids Fe2+

Amino acid pool Excreted

• BILIRUBIN ENCEPHALOPATHY: The mildest
form of bilirubin encephalopathy is
sensorineural hearing loss due to damage to
the cochlear nuclei. Severe encephalopathy
causes kernicterus. Factors predisposing to
neurotoxicity of unconjugated
hyperbilirubinemia include:
• •When bilirubin concentration exceeds the
binding capacity of serum albumin
• Displacement of bilirubin from albumin by
acidosis or certain drugs (e.g., sulfonamides,
ceftriaxone)
• Sepsis
• Preterm infants due to↑ risk due lower
serum albumin concentrations and ↑ risk for
acidosis and sepsis.
 ENTEROHEPATIC CIRCULATION
•
• Meconium contains 100-200mg of conjugated
bilirubin at birth.
• Conjugated bilirubin is unstable and easily
hydrolyzed to unconjugated bilirubin.
• This process occurs non-enzymatically in the
duodenum and jejunum and also occurs in the
presence of beta-glucuronidase, an enteric mucosal
enzyme, which is found in high concentration in
newborn infants and in human milk.
 CONJUGATION

• Since conjugated bilirubin crosses the placenta very

little, conjugation is not active in the fetus with levels
of UDPGT(Uridine Diphosphate Glucuronyltransferase
( about 1% of adult levels at 30 - 40 weeks gestation)
• After birth, the levels of UDPGT rise rapidly but do
not reach adult levels until 4-6 weeks of age.
• Ligandins, which are necessary for intracellular
transport of bilirubin, are also low at birth and reach
adult levels by 3-5 days.
•
 CAUSES of UNCONJUGATED (INDIRECT) HYPERBILIRUBINEMIA:

• Increased lysis of RBCs (i.e., increased

hemoglobin release)
– Isoimmunization (blood group incompatibility: Rh,
ABO and minor blood groups)
– RBC enzyme defects (e.g., G6PD deficiency,
pyruvate kinase deficiency)
 Increased lysis of RBCs Contd….
– RBC structural abnormalities (hereditary
spherocytosis, elliptocytosis)
– Infection (sepsis, urinary tract infections)
– Sequestered blood (e.g., cephalohematoma,
bruising, intracranial hemorrhage
• Polycythemia
• •Shortened life span of fetal RBCs (80 vs. 120
d)
• Decreased hepatic uptake and conjugation of
bilirubin
– Immature glucuronyl transferase activity in all newborns:
term infants have 1% of adult activity, preterm infants
have 0.1%.
– Gilbert Syndrome
– Crigler Najjar Syndrome (Non-hemolytic Unconjugated
Hyperbilirubinemia): inherited conjugation defect (very
rare)
• Breastmilk Jaundice (pregnanediol inhibits glucuronyl
transferase activity
Decreased hepatic uptake and conjugation of bilirubin contd….

– Pyloric stenosis (mechanism is unknown)

– Hypothyroidism
– Infants of Diabetic Mothers (polycythemia is also
common)
• Breastmilk Jaundice (pregnanediol inhibits
glucuronyl transferase activity
• Increased enterohepatic reabsorption
– Breast feeding jaundice (due to dehydration from
inadequate milk supply)
– Bowel obstruction
– No enteric feedings
Prehepatic (hemolytic) jaundice
 Results from excess production
of bilirubin (beyond the livers
ability to conjugate it) following
hemolysis

 Excess RBC lysis is commonly

the result of autoimmune
disease; hemolytic disease of
the newborn (Rh- or ABO-
incompatibility); structurally
abnormal RBCs (Sickle cell
disease); or breakdown of
extravasated blood

 High plasma concentrations of

unconjugated bilirubin (normal
concentration ~0.5 mg/dL)
Intrahepatic jaundice
• Impaired uptake, conjugation,
or secretion of bilirubin

• Reflects a generalized liver

(hepatocyte) dysfunction

• In this case,
hyperbilirubinemia is usually
accompanied by other
abnormalities in biochemical
markers of liver function
Posthepatic jaundice
 Caused by an obstruction of the
biliary tree

 Plasma bilirubin is conjugated,

and other biliary metabolites,
such as bile acids accumulate in
the plasma

 Characterized by pale colored

stools (absence of fecal
bilirubin or urobilin), and dark
urine (increased conjugated
bilirubin)

 In a complete obstruction,
urobilin is absent from the
urine
 EVALUATION of JAUNDICE (UNCONJUGATED)

• Initial evaluation:
– Total and direct bilirubin •Blood type and Rh (infant &
mother)
– Hematocrit •Direct Antiglobulin (Coombs) Test on infant
• Later evaluation (as indicated):
– RBC smear, reticulocyte count (if evidence or suspicion
of hemolytic disease)
– Blood culture, urinalysis, urine culture
• Thyroid function tests, G6PD assay, Hgb
electrophoresis
 Risk factors for jaundice

– JAUNDICE
– J - jaundice within first 24 hrs of life
A - a sibling who was jaundiced as neonat
U - unrecognized hemolysis
– N – non-optimal sucking/nursing
D - deficiency of G6P
I - infection
– C – cephalhematoma /bruising
– E - East Asian/North Indian
 MANAGEMENT of UNCONJUGATED
HYPERBILIRUBINEMIA
• Healthy Term Newborn
Treatment
Age (h) Bilirubin (mg/dL) Phototherapy Exchange Transfusion
 24 Visible Jaundice Consult attending physician
25-48  15 X
 20 X X

49-72  18 X
 25* X X

> 72  20 X
 25* X X
• Recent data suggest that even healthy term
infants may suffer mild neurologic damage
with bilirubin concentrations >20 mg/dL.
• Sick Term Newborns: Start above therapies at
lower total serum bilirubin levels. Consult
attending physician for specific values
• Preterm Infants: Because of ↑ risk of
bilibubin encephalopathy, therapy should be
started at lower bilirubin concentrations. In
general, bilirubin shoud not be allowed to
exceed the infant’s weight in kg x 10 (e.g., for
1.0 kg infant, keep bilirubin <10 mg/dL).
•
 Complication

• Bilirubin encephalopathy or kernicterus

• Clinical Features of kernicterus----lethargy,
refusal of feeds, shrill cry, setting sun,
convulsion and episthotomous
• Moro reflex is sluggish or abnormal.
 Factors enhancing bilirubin
encephalopathy
• Metabolic acidosis, lowered serum albumin
level, intracranial infection, any condition that
demand for increased oxygen -fetal
distress,hypoxia,hypothermia,or
hypoglycemia.
CONJUGATED (DIRECT) HYPERBILIRUBINEMIA (CHOLESTASIS):

• Clinically, jaundice is green compared to

jaundice due to unconjugated
hyperbilirubinemia (yellow).
causes
• Hepatocellular diseases:
– Hepatitis:
• Neonatal idiopathic hepatitis
• Viral (Hepatitis B, C, TORCH infections)
• Bacterial (E. coli, urinary tract infections)
 Contd…..
– Hepatic ischemia (post-ischemic damage)
– Erythroblastosis fetalis (late, “Inspissated Bile
Syndrome”)
– Metabolic disorders (partial list):
• Alpha-1 antitrypsin deficiency •Galactosemia,
tyrosinemia, fructosemia
• Glycogen storage disorders •Cerebrohepatorenal
disease (Zellweger)
• Cystic fibrosis •Hypopituitarism
• Biliary tree abnormalities:
– Extrahepatic biliary atresia: In first 2 weeks,,
unconjugated bilirubin predominates; elevated
conjugated bilirubin is late.
– Paucity of bile ducts (Alagille’s vs. non-syndromic)
– Choledochal cyst
– Bile plug syndrome
• EVALUATION and MANAGENMENT of CHOLESTASIS:
• Initial evaluation:
– Total and direct bilirubin
– AST, ALT, GGT, urine reducing substances
– Hepatic ultrasound
• Later evaluation (as indicated):
– Hepatitis B and C serology •1-antitrypsin deficiency
studies
– Very long chain fatty acids •Brain sonogram
– HIDA scan •Cholangiogram
–
• Management:
– Conjugated bilirubin is not toxic.
– Management is treatment of cause.
• Phototherapy will cause “bronzing” with
conjugated hyperbilirubinemia
 BREAST-FEEDING AND JAUNDICE

• Exclusively breast-fed infants have a different pattern

of physiological jaundice as compared to artificially fed
babies.
• Jaundice in breast-fed babies usually appears between
24 – 72 hours of age, peaks by 5 – 15 days life and
disappears by the third week of life.
• One third of all breast-fed babies are detected to have
mild clinical jaundice in the third week of life,

•
• Breastfeeding jaundice
• is seen in breastfed babies during the first
week of life, especially in babies who do not
nurse well or if the mother's milk is slow to
come in.
• Breast milk jaundice
• may appear in some healthy, breastfed babies
after day 7 of life. It usually peaks during weeks
2 and 3. It may last at low levels for a month or
more. It may be due to SOME substances in
the breast milk affect how bilirubin breaks
down in the liver. Breast milk jaundice is
different than breastfeeding jaundice.
•
 Care of the child under phototherapy

• What is phototherapy?
• Phototherapy (light therapy) is a way of
treating jaundice. Special lights help
break down the bilirubin in your baby's
skin so that it can be removed from his or
her body. This lowers the bilirubin level
in your baby's blood.
• What is phototherapy?
Application of fluorescent light to
the infant’s exposed skin used to
breakdown the bilirubin in the
skin
 Indication of phototherapy
• • Treatment of Hyperbilirubinemia
• • The phototherapy will help the
liver to process bilirubin, bringing
your baby's level down to normal
• • Prevent Kernicturus
 FACTORS AFFECTING EFFICACY OF
PHOTOTHERY
• • 1-TYPE OF LIGHT USED
• • 2-LIGHT INTENSITY
• • 3-SURFACE AREA OF SKIN EXPOSED TO
LIGHT
• • 4- The distance of the light source from the
baby, the optimum distance being 35 - 50 cm
in conventional lights.
Assessment should be Before Phototherapy

• • GA Of the baby
• • Weight The baby
• • Postnatal Age
• • Types of Jaundice
• • the level of jaundice
 Nursing Care for Infant Receiving
Phototherapy
• Baby will need to be in an incubator whilst
under photo therapy to keep warm,
• • The photo therapy unit will be placed over
the top of the incubator occasionally more
than one unit may be used. This can be
switched off when your baby needs to come
out to be fed
 Nursing Care for Infant Receiving
Phototherapy …Contd
• ’ Proper covering and shielding of gonad .
Assess skin exposure
• . Proper position
• Assess and adjust thermoregulation device
• . Promoting elimination and skin integrity .
• Hydration.
• -Assure effective of phototherapy -
provide eye protection Eyes are
covered with eyepatches to prevent
damage to the retina
• Baby is placed naked 45 cm away from the
tube lights in a crib or incubator. • If using
closer, monitor temperature of the baby. •
Baby is turned every two hours or after each
feed.
• During phototherapy, the bilirubin level in
your baby’s blood will be checked at least
once every day.
• Phototherapy is stopped when the bilirubin
level decreases.
• Temperature is monitored every two to four
hours. – Weight is taken at least once a day. –
More frequent breastfeeding or 10-20% extra
fluid is provided. – Urine frequency is
monitored daily.
• Serum bilirubin is monitored at
least every 12 hours. •
Phototherapy is discontinued if
two serum bilirubin values are <
10 mg/dl.
• • Baby should spend as much time as possible
under the phototherapy lights for it to be
most effective, but your baby can come out
for feeding or cuddles if he or she is upset. •
Baby will need to have regular (usually daily)
blood tests whilst under photo therapy to
assess the levels of bilirubin and ensure the
phototherapy is effective.
• Promoting infant parent interaction.
 Side effect of phototherapy
• • Bronze – baby syndrome.
• • Loss , greenish stool .
• • Transient skin rashes.
• • Hyperthermia
• . • Increasing metabolic rate. • Dehydration .
• • Electrolyte disturbance .
•