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An approach to jaundiceAn approach to jaundice

Dr. M. S. Prasad

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ObjectivesObjectives

• By end of this period, you will be able to explain the clinical and pathological approach to a patient suffering from jaundice.

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DefinitionDefinition

• Jaundice is defined as yellowish discolouration of skin, conjunctivae, sclerae and mucous membrane due to increased level of bilirubin in blood.

• Syn:– Icterus,– Hyperbilirubinaemia (Hyperbil)

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IntroductionIntroduction

• French word, ‘jaune’ means yellow.

• Serum Bilirubin levels < 2 mg/dl (30 μmol/ liter) in adults does not cause jaundice.

• Serum Bilirubin level < 5 mg/dl (75 μmol/L) in newborn does not cause jaundice.

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Differential DiagnosisDifferential Diagnosis• Carotenemia:

– Palms and soles are yellow,– Skin may also be yellow, but– Sclera is never yellow,– Not found in newborn.

• Chloroquine (?).

• Turmeric application.

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CategoriesCategories

• Pre-hepatic/haemolytic,

• Hepatic/hepatocellular,

• Post-hepatic/cholestatic.

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Pre-hepatic CausesPre-hepatic Causes• Congenital Haemolytic Anaemias:

– ABO/Rh incompatibilty,– Hereditary spherocytosis,– Thalassemia,– Sickle cell anaemia,– G6PD deficiency.

• Defects in bilirubin metabolism:– Gilbert’s syndrome,– Crigler-Najjar Syndrome.

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Pre-hepatic ……….Pre-hepatic ……….

•HUS,

•Malaria.

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Hepatic/hepatocellularHepatic/hepatocellular

• Physiologic Jaundice of Newborn,

• Intra-hepatic Congenital Biliary Atresia (CBA),

• Hepatitis,

• Hepatotoxicity,

• Cirrhosis of liver,

• Leptospirosis.

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Post-Hepatic/cholestatic

• Extra-hepatic CBA,

• Choledochal cyst,

• Pancreatitis,

• Pancreatic cyst,

• Gall stones.

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Some clues to diagnosis

• Fever, pain abdomen, vomiting, acute onset, tender hepatomegaly with jaundice:– Acute Viral Hepatitis.

• Chronic jaundice, low grade fever or afebrile, features of liver failure with or without features of portal hypertension:– Chronic Liver Disease (CLD)

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Clues:Clues:

• Mild jaundice (lemon yellow) with severe pallor with splenomegaly, sometimes hepatomegaly also, typical facial features:– Congenital Haemolytic Anaemia.

• Preceding h/o diarrhoea, pallor, jaundice, oliguria or even anuria:– HUS.

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CluesClues

• Biphasic course with fever, mild jaundice, haemorrhages, meningitis and h/o rats in kitchen or access to food stored in house:– Leptospirosis.

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Neonatal Neonatal HyperbilirubinaemiaHyperbilirubinaemia

Neonatal Neonatal HyperbilirubinaemiaHyperbilirubinaemia

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How to look for jaundice?

• To look for jaundice, press the infant’s skin over the forehead with your fingers to blanch, remove your fingers and look for yellow discolouration under natural light.

• If there is yellow discoloration, the infant has jaundice.

• To assess severity, repeat the process over chest, abdomen, thighs, legs and palms and soles.

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Clinical Assessment of Jaundice

6

9

12

15

18-20

6

9

12

15

18-20

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According to age of According to age of appearance of jaundiceappearance of jaundice

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According to age of appearance of jaundice

• Early Jaundice (< 10 days):– First 24 hours,– After 24 hours.

• Prolonged Jaundice (> 10 days):– Prolonged unconjugated hyperbilirubinaemia– Prolonged conjugated hyperbilirubinaemia

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Early JaundiceEarly Jaundice

• First 24 hrs:– Rh/ABO incompatibility,– Congenital Hereditary Spherocytosis,– RBC enzyme defects.

• After 24 hrs:– Physiologic jaundice,– Cephalhematoma,– Sepsis,– Galactosemia,– Polycythemia.

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Early JaundiceEarly JaundiceCauseCause ConfirmationConfirmation

Rh/ABO incompatibility

1. DCT

2. MBG

3. BBG

G6PD deficiency1. Family History

2. G6PD estimation

Spherocytosis1. Blood Film

2. Full Blood Count

Sepsis Sepsis screening.

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Prolonged JaundiceProlonged Jaundice• Breast Milk Jaundice,

• Hypothyroidism,

• CBA,

• Neonatal Hepatitis,

• Galactosemia,

• Crigler-Najjar Syndrome,

• Gilbert Syndrome,

• Sepsis

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Jaundice persisting beyond one month of age

• CBA,

• Neonatal Hepatitis,

• Hypothyroidism.

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Approach to the newborn with jaundiceApproach to the newborn with jaundice

Jaundice inin a termNeonate

< 24 hours old > 24 hours old

• Rule out hemolysis.• No discharge.• Appropriate Therapy• Close monitoring.

DiagnosisTreatment

AAP guideline Disposition

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Approach Approach (continued)

Diagnosis

Conjugatedbilirubinaemia

UnconjugatedHyperbilirubinaemia

Non-haemolytic Haemolytic

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IMNCI ApproachIMNCI Approach

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And if the infant has jaundice

And if the infant has jaundice

SIGNS CLASSIFY AS

• Palms and soles yellow or

• Age < 24 hours or

• Age 14 days or more.

SEVERE SEVERE JAUNDICEJAUNDICE

•Palms and soles not yellow JAUNDICE

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Need of investigation• Check if,

– Onset of jaundice is within 24 hrs of life, or– Baby is more than 14 days of age, or– Jaundice is below abdomen on clinical

assessment.

• If any of the above is ‘yes’ then do the investigations.

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InvestigationsInvestigations

• Serum bilirubin (total/direct/indirect)

• Hemoglobin/hematocrit

• Blood groups of baby and mother

• Other investigations as needed.

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Conjugated Conjugated HyperbilirubinaemiaHyperbilirubinaemia

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Conjugated HyperbilirubinaemiaConjugated Hyperbilirubinaemia

• Pale stools,

• Dark urine,

• Hepatomegaly,

• Dysmorphism,

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Causes of conjugated bilirubinaemiaCauses of conjugated bilirubinaemia

• Sepsis,

• Inborn Errors of Metabolism,

• Biliary Atresia,

• Hypothyroidism.

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Clinical Features and Recommended Tests for

Genetic Syndromes presenting with ConjugatedConjugated

Hyperbilirubinaemia

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Cystic FibrosisCystic Fibrosis

• Features:– Pancreatic insufficiency,– Pulmonary diseases,– Meconium ileus,– Infertility

• Tests:– Sweat analysis,– CFTR common mutation panel and full

sequence analysis.

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GalactosemiaGalactosemia• Features:

– Hyperbilirubinaemia,– Hypoglycaemia,– Bleeding diathesis,– Oedema,– Ascites, and – Cataract.

• Tests:– Galactose 1 Phosphatase level,– GALT enzyme activity,– GALT DNA analysis.

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UnconjugatedUnconjugatedHyperbilirubinaemiaHyperbilirubinaemia

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Unconjugated HyperbilirubinaemiaUnconjugated Hyperbilirubinaemia

Non-hemolytic

• DCT negative,• Stable haemoglobin,• Normal reticulocyte

• Bruising,• Poor stooling,• Hypothyroidism,• Criggler Najjar

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Unconjugated HyperbilirubinaemiaUnconjugated Hyperbilirubinaemia

Haemolysis

Physiological Pathological

• Well appearing,• DCT negative,• Peaks at day 3,• Disappears by day 5,• Peak < 12 mg/dl.

• ABO/Rh incompatibility,• RBC defects,• Enzyme defects

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Clinical Features and Recommended Tests for Genetic Disorders with UnconjugatedUnconjugated Hyperbilirubinaemia.

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Crigler Najjar Type ICrigler Najjar Type I• Features:

– Severe lifelong jaundice with high risk of kernicterus,

– No haemolysis or significant hepatocellular dysfunction.

• Tests:– UGT1A1 enzyme assay in liver.

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Gilbert SyndromeGilbert Syndrome• Features:

– Chronic mild fluctuating unconjugated hyperbilirubinaemia,

– No haemolysis or hepatocellular dysfunction.

• Tests:– UGT1A1 targeted mutation analysis.

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G6PD deficiencyG6PD deficiency

• Features:– Haemolytic anaemia,– Frequently precipitated by illness or

oxidizing drugs.

• Tests:– Quantitative G6PD analysis.

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Pyruvate Kinase deficiencyPyruvate Kinase deficiency

• Features:– Haemolytic anaemia of variable severity.

• Tests:– Pyruvate kinase isoenzyme analysis.

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Indicators of HaemolysisIndicators of Haemolysis

• Rapidly rising bilirubin,

• Falling hemoglobin.

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History and Physical Examination• Note adequacy of feeding, passing stools, and

voiding (risk factors for increased enterohepatic circulation of bilirubin).

• Examine for the following:– Well being (no sepsis),– Growth parameters,– Bruising and cephalhematoma (increased bilirubin

production),– Pallor, oedema, and hepatosplenomegaly (indicators

of haemolysis and CHF).

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Growth ParametersGrowth Parameters

• SGA infants are likely to be plethoric resulting in higher bilirubin and requiring earlier phototherapy.

• This may be symptomatic of intrauterine infection and hence likely conjugated jaundice.

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Prolonged JaundiceProlonged Jaundice

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DefinitionDefinition

Jaundice persisting in newborn beyond 10 (14) days of life is said to be prolonged.

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Types of Prolonged JaundiceTypes of Prolonged Jaundice

• Unconjugated Hyperbilirubinaemia.

• Conjugated Hyperbilirubinaemia.

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Causes of ProlongedCauses of ProlongedUnconjugated HyperbilirubinaemiaUnconjugated Hyperbilirubinaemia

• Breast Milk Jaundice.

• Hypothyroidism.

• Intestinal Stasis.

• Hemolytic causes.

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Breast Milk JaundiceBreast Milk Jaundice• Most common cause of prolonged

unconjugated Hyperbilirubinaemia.

• Total Serum Bilirubin usually < 200 mcg/L

• Conjugated bilirubin < 20% (Normally > 25%)

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Breast Milk JaundiceBreast Milk Jaundice (continued)

Beta glucuronidase present in Breast Milk

Bilirubin diglucuronide

UC Bilirubin Glucuronic Acid

Absorbed from GIT

Hyperbilirubinaemia(Unconjugated)

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Breast Milk Jaundice Breast Milk Jaundice (continued)

• Baby well,

• No treatment required,

• Settles by 6 weeks

(occasionally up to 4 months.

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Lucy Driscoll SyndromeLucy Driscoll Syndrome

• Inhibitors of bilirubin glucuronide is present in the mother’s milk.

• Sometimes severe enough to require exchange transfusion.

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HypothyroidismHypothyroidism

• A heavy weight, sluggish baby with feeding difficulty and prolonged jaundice s/o congenital hypothyroidism.

• Investigation:– Thyroid Function Test.

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Intestinal StasisIntestinal Stasis

• 2nd most common cause of prolonged unconjugated hyperbilirubinaemia.

• Due to increased enterohepatic circulation of bilirubin.

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MechanismMechanism

• Normally 75% of conjugated bilirubin is excreted in feces and 25% of is broken down to unconjugated form in duodenum and is absorbed into circulation.

• When there is stasis, the break-down to unconjugated form increases significantly to cause hyperbilirubinaemia.

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Causes of Intestinal StasisCauses of Intestinal Stasis• Hirschsprung disease.

• Intestinal atresia.

• Pyloric Stenosis.

• Meconium ileus of Cystic Fibrosis.

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ProlongedProlongedConjugatedConjugated

HyperbilirubinaemiaHyperbilirubinaemia

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Causes of prolonged Causes of prolonged conjugated hyperbilirubinaemiaconjugated hyperbilirubinaemia

• Cholestasis syndrome– Intrahepatic cholestasis

• Neonatal Hepatitis• Intrahepatic biliary atresia.

– Extrahepatic cholestasis• Congenital Biliary Atresia.

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InvestigationsInvestigations

• Serum Bilirubin:– Total– Direct (conjugated)– Indirect (Unconjugated)

• Hepatobiliary ultra-sound study or

• Technetium-99 HIDA cholescintigraphy.

• Percutaneous liver-biopsy.

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Stool ColourStool Colour

• Stool partially pale or intermittently pale + IUGR = Neonatal Hepatitis (intrahepatic cholestasis).

• Stool completely and persistently pale and lasting longer that 2 weeks + hard liver or unconjugated hyperbilirubinaemia = Extrahepatic cholestasis (congenital biliary atresia)