HYPERBILIRUBINEMIA

Nico Angelo P. Copo

 To
learn how to assess and diagnose hyperbilirubinemia in
neonates and enumerate the possible differentials.

 To learn how to manage patients with hyperbilirubinemia

clinically and prevent its complications

OBJECTIVES
DEMOGRAPHIC DATA

NAME N.J.C. AGE 8 days old GENDER Female

ADDRESS Brgy. Butong Cabuyao, Laguna

BIRTHDATE July 2, 2019 BIRTHPLACE Binan, Laguna

7-Day
CIVIL STATUS Child NATIONALITY Filipino RELIGION
Adventist

ADMISSION
DATE
July 10, 2019 ADMISSION TIME 12:23 PM
 Jaundice

CHIEF COMPLAINT
 Few hours
PTA

2 days
PTA

5 days
PTA

Poor suck, cry & activity

Fair suck Poor suck & cry + prominent jaundice

HISTORY OF PRESENT ILLNESS

 GEN. HEENT LUNGS HEART GASTRO GUT MSK HEMA NEURO

(+) (-) vomi- (-) li- (-) sei-

(+) (-) (-) SOB (-) blee- zure
weight ting, (-) (-) hem- mited
colds at cough (-) ding
loss diarrhea aturia ROM (-) LOC
home (-) orthop- (-) bruis-
(-) cons- (-) (-)
(-) fever (-) head dyspnea nea (-) ing
tipation oliguria tremor
injuries rash

REVIEW OF SYSTEMS
 • 40 year old
Mother • G3P2 (2002)

• UTI -12 wks

(Cefuroxime)
Illness • Preterm labor –
34 wks
(Isoxsuprine)

• Regular FA,
FeSo4, & Ca
Exposure
• No radiation/
teratogen

MATERNAL HISTORY
 • 37 weeks AOG via
2°CS (twin pregnancy)
Delivery at UPH on 07/02/19
• Good cry,
spontaneous resp.

• APGAR 8,9
• BW 2.21kg SGA,
BS 37 weeks
Status
• BL 48.5, HC 33,
CC 29, AC 29
cm

• No cord coiling
Compli-
cations • No meconium
staining

BIRTH HISTORY
 • No jaundice
1st
24 • (+) UO and BM
hours

• Slightly sallow
skin
After • Fair suck, good
3 days activity and cry
up to discharge
(7/7/19)
• Newborn
screening
Tests done
• Hearing test -
normal

NEONATAL HISTORY
Birth-Day 5 Day 6-7 Day 8
Exclusively Mixed Formula and
Breastfed (with S26 1:1)
Breastfeeding not
tolerated

NUTRITIONAL HISTORY
IMMUNIZATION
•1 No hospitalization

•2 No illnesses

•3 No allergies

•4 No blood transfusions

PAST MEDICAL HISTORY

• 1 Diabetes Mellitus- maternal

• 2 Bronchial Asthma - paternal

• 3 No hypertension

• 4 No allergies

FAMILY MEDICAL HISTORY

 Single detached
Two bedrooms
Well ventilated
Well lit
Flush-type toilet
Distilled drinking water
Regular garbage
disposal

ENVIRONMENTAL HISTORY
 Lives with 4 other family
members:

1. Father
2. Mother
3. Brother
4. Twin sister

ENVIRONMENTAL HISTORY
 GENERAL SURVEY
• Awake
• Not in cardiorespiratory distress
• Poor suck, cry and activity

VITAL SIGNS
• CR: 150 bpm RR: 55 cpm T: 36.5°C

ANTHROPOMETRICS
ANTHROPOMETRICS ACTUAL Z-SCORE INTERPRET
BMI 33.5 At -3 S. Wasted • Weight: 2.2 kg (BW 2.21 kg) Height: 48.5 cm
Weight 2.2 At -2 Underweight • HC: 33.5 cm CC: 31 cm AC: 33 cm
Height 48.5 At 0 Normal

PHYSICAL EXAM
 SKIN
• Jaundice from head to toe
• Warm to touch
• No cyanosis

HEENT
• Normocephalic
• Icteric sclera
• Pink palpebral conjunctiva
• No nasoaural discharge
• No tonsillopharyngeal congestion
• Soft, open anterior & posterior fontanel

PHYSICAL EXAM
 CHEST AND LUNGS
• Symmetrical chest expansion
• No retractions
• Clear breath sounds

HEART
• Adynamic precordium
• Normal rate, regular rhythm
• No murmurs

ABDOMEN
• Globular, intact umbilical stump

PHYSICAL EXAM
 ABDOMEN (Cont.)
• Normoactive bowel sounds
• Liver edge non-palpable
• Soft, non tender abdomen

GENITALS
• Labia majora, minora equally prominent
• No deformities

EXTREMITIES
• Full equal pulses
• CRT less than 2 secs
• No deformities

PHYSICAL EXAM
 CRANIAL NERVES
• CN II – fixes and follows
• CN III, IV, VI – no nystagmus, no deviation
• CN V – intact rooting reflex
• CN VII – no facial asymmetry
• CN VIII – startles to loud noises
• CN IX, X – uvula at midline
• CN XII – tongue at midline
REFLEXES
• (+) Moro, Tonic Neck, Rooting, Babinski, Grasp
• Poor sucking reflex

MOTOR/SENSORY
•With good muscle tone
•Cries upon blood withdrawal

NEURO EXAM
SALIENT FEATURES

• Poor suck, cry and activity

• (+) colds at home
• Short for gestational age (SGA) = BW of 2.21kg
• Icteric sclera
• Jaundice from head to toe
• No jaundice in the 1st 24 hour

• Elderly gravid, diabetic mother (40y/o)

• Mother had UTI (12w) and Preterm labor (34w) but resolved
• Twin pregnancy
Hyperbilirubinemia

INITIAL DIAGNOSIS
 Infant of Sepsis, Late Breastfeeding
diabetic mother onset Jaundice
• Diabetic mother • Poor suck, cry and • Poor suck
activity • Jaundice
• Jaundice
• Jaundice • Onset at first week of
• (+) Colds at home life
• RULE OUT
• Short for Gestational Age
• CANNOT TOTALLY RULE • CANNOT TOTALLY RULE
OUT OUT

DIFFERENTIAL DIAGNOSES
 Hyperbilirubinemia
probably secondary to
breastfeeding jaundice, to consider neonatal sepsis,
late onset

FINAL DIAGNOSIS
HYPERBILIRUBINEMIA
BILIRUBIN
 Produced from heme metabolism
 Degradation of hemoglobin by macrophages in the blood, liver and spleen
 Hemoglobin = Heme + Globin (recycled in the marrow for erythropoiesis)
 HEME = Biliverdin + Iron (recycled in the marrow for erythropoiesis)
 BILIRUBIN
 Unconjugated (Indirect) Bilirubin –
poor solubility in water, good
solubility in fats
 Carried by albumin to the liver

 Conjugated (Direct) Bilirubin – good

solubility in water, poor in fats
 Unconjugated bilirubin is conjugated
by UDP glucuronyltransferase in liver
 Facilitates excretion in urine (15%)
and feces (85%)
UGT

ENTEROHEPATIC CIRCULATION
 NEONATAL JAUNDICE
 Physiologic Jaundice – usually occurs on the 2nd to 3rd day of life
1. Bilirubin production in neonates (6-8mg/kg/day) is two to three times higher than in
adults (3-4mg/kg/day)
2. Newborns have more RBC (HCT between 50 to 60 percent)
3. Fetal red blood cells have a shorter life span (85 days) than those in adults (120 days)
4. Bilirubin clearance is decreased due to the deficiency of the enzyme UGT approx 1%
activity. Takes 14 weeks to reach adult level of 100% activity.
5. Increase in the enterohepatic circulation of bilirubin

 Pathologic Jaundice – at the first 24 hours of life

 HYPERBILIRUBINEMIA
 Hyperbilirubinemia is defined as total
bilirubin of :
>15mg/dl (255 umol/L) = in newborns
>1mg/dl (17 umol/L) = in adults
 Jaundice is observed during the 1st wk
after birth (face = 5 mg/dL; abdomen=
15 mg/dL; soles = >20 mg/dL)
 More prone to preterms.
 SEVERE Hyperbilirubinemia is TB >25
mg/dl (425 umol/L)
 CAUSED BY:
1. Increase load (hemolysis, infection)
2. Reduced activity of enzymes
(genetic and thyroid deficiency)
3. Drugs that blocks enzymes
(sulfonamides, rifampin, etc.)
4. Reduction of bilirubin uptake by liver
(prematurity, liver damage)
5. Biliary obstruction (cholestasis)
 DISEASE BILIRUBIN TYPE
Gilbert Syndrome Indirect Low UGT activity; can be caused by stress,
menses, fasting or fever.
Crigler-Najjar Indirect Decreased (type II) or absent (type I) UGT.
Syndrome Causes kernicterus, usually fatal
Dubin-Johnson Direct Defective liver transport/excretion.
With liver discoloration to black
Rotor Syndrome Direct Defective liver transport/excretion.
Milder, without discoloration
KERNICTERUS
Three Phases:’
 Usually occurs in severe
hyperbilirubinemia >25mg/dl
1. Early phase – sleepy but arousable,
 Unconjugated Bilirubin – is fat soluble hypotonic, high-pitched cry
2. Intermediate phase - febrile,
 Can cross blood-brain barrier
lethargic with a poor suck, or
 Acts as neurotoxin in basal ganglia and irritable and jittery with a strong
brainstem suck.
3. Advanced phase - apnea, inability
to feed, fever, seizures, and coma
leading to death
BHUTANI CHART
 Direct, Indirect, and Total Bilirubin Levels
 Urine Bilirubin
 Urobilinogen

 ALT, AST, ALK Phosphatase

DIAGNOSIS
 PHOTOTHERAPY
 Decreases 2 to 3mg/dl (34 to 51 umol/L)
of total bilirubin within 4 to 6 hours
 Mechanisms:
1. Converts bilirubin to lumirubin for easier
excretion to the urine
2. Photoisomerization to less toxic isomer=
4z,15z isomer to 4z,15e isomer
3. Photo-oxidation to polar molecules

For TB levels ≥20 mg/dL (342 micromol/L),

phototherapy should be administered
continuously, until the TB falls below
20 mg/dL (342 micromol/L).
 EXCHANGE TRANSFUSION
 A life-saving emergency procedure that
rapidly reduces the level of bilirubin.
 Used to remove bilirubin from the circulation
when intensive phototherapy fails
 Decreases 50% of actual total bilirubin

 Procedure — The infant's circulating blood

volume is approximately 80 to 90 mL/kg. A
double-volume exchange transfusion (160 to
180 mL/kg) replaces approximately 85
percent of the infant's circulating red blood
cells