hyperbilirubinemia

 Hyperbilirubinemia

Hyperbilirubinemia is known as Neonatal jaundice/icterus neonatrum

Jaundice is visible manifestation of hyperbilirubinemia.

Excessive accumulation of unconjugated bilirubin in blood resulting in yellowish discoloration of skin, sclera and mucus membrane.

Indirect bilirubin level more than 5mg/dl manifest as jaundice.

Direct bilirubin; conjugated bilirubin 

Indirect bilirubin; unconjugated bilirubin 

Due to liver immature; accumulation of unconjugated bilirubin.

Pathophysiology

(RBCs) Break

Hemoglobin

-Reticuloendothelium system

Biliverdin+Iron +Co

-Biliverdin reductase

Bilirubin

-Binds with serum albumin

Enter liver Cytoplasmic Ligandin

Smooth endoplasmic reticulum

-UDGT; uridine diphosphate glucuronyl transferase

Conjugated bilirubin

1. Urobilinogen 2. Stercobilinogen

Jaundice occur when liver cannot excrete sufficient bilirubin from plasma.

Classification of Jaundice

1. Physiological jaundice

2. Pathological jaundice

3. Breast milk jaundice

4. Breast feeding jaundice

1. Physiological jaundice/ Icterus Neonatrum 

60% of term and 70% of preterm babies develop jaundice within 1st week of life. 

In term babies; maximum intensity of jaundice is on 4th day and decline by 7th day.

In term babies; maximum intensity is on 5th-6th day and decline by 14th day.

Causes of Physiological Jaundice

1. Immature hepatic function; increased bilirubin load on liver cells.

a. Increase erythrocyte destruction due to shorter life span (in children 90 days, 120 days in adults

b. Increased Erythrocyte volume

c. Increased enterohepatic circulation of bilirubin

2. Defective bilirubin conjugation

UDPGT activity;uridine diphosphate glucuronosyltransferases

3. Defective hepatic uptake of bilirubin from plasma

1. Decreased cytoplasmic ligandin

2. Decreased serum albumin concentration

2. Breast milk jaundice

Late onset of jaundice.

Begins at age of 5-7 days occurs in 2-3% of breastfed infants.

Peak bilirubin level; during 2nd week and then gradually diminished.

Etiology factor

Caused by breast milk; pregnanediol, fatty acids, beta glucuronidase that either inhibit conjugation or decrease secretion of bilirubin.

Treatment

Increase frequency of breastfeeding.

No supplementation such as glucose water or complementary feeding is given.

3. Brestfeeding jaundice 

Early onset of jaundice, begins at 2-4 days of age, occurs in 10-25% of breastfed babies.

Inadequacy of breast feeding results in decreased caloric and fluid intake by breastfed infants before milk supply established.

Fasting causes decrease hepatic clearance of bilirubin resulting in jaundice in inadequately breast fed infants.

Treatment

Frequent Breastfeeding (10-12times/day).

4. Pathological Jaundice (Hemolytic Disease)

Jaundice occuring within 24 hours of birth called pathological jaundice.

In terms; jaundice decline within 10 days 

In preterm; jaundice decline within 14 days 

Major causes of pathological jaundice is Hemolysis due to ABO/Rh incompatibility and intrauterine infections.

Pathological jaundice Features

1. Clinical jaundice appear within 24 hours of birth.

2. Increase in level of bilirubin by more than 5mg/dl/24hours.

3. Total bilirubin level may be more than 15mg/dl

4. Direct bilirubin >2mg/dl

Etiology of Pathological Jaundice 

1. Excessive Red cell hemolysis leading to increased bilirubin production.

2. Hemolytic disease in Newborn

3. Increased red cell fragility

4. G6PD deficiency; Deficient red cell enzyme causing hemolytic anaemia.

5. Neonatal sepsis

2. Metabolic disorders

1. Galactosemia

2. Hypothyroidism

3. Decreased conjugation or decreased clearance

a. Congenital deficiency of hepatic glucuronyl transferase enzyme (Criggler-Najjar syndrome)

b. In preterm baby; impaired liver function 

4. Drugs;

Affect binding of bilirubin to Albumin such as; aspirin, sulphonamides.

5. Congenital obstruction or atresia of biliary canal, viral Hepatitis.

Clinical features of Pathological Jaundice

1. Yellow discoloration of skin, sclera or nail bed

2. Lethargy

3. Refusal to food

4. Dark urine and stool

Diagnostic Evaluation

1. Clinical estimation of jaundice

Jaundice is detected by skin blanching with digital pressure.

Dermal Zone Bilirubin (mg/dl)

Face;               5

Chest;.            10

Thigh;.             12

Knee;.              15

Whole body; >15

2. Serum bilirubin estimation

Level of 5mg/dl or above indicates jaundice.

3. Non-invasive methods

a. Transcutaneous bilirubinometer

b. Ingram icterometer

Management of Pathological Jaundice

Management of Pathological Jaundice depends on cause.

1. Pharmacological management

a. Phenobarbitone

Phenobarbitone promotes hepatic glucuronyl transferase synthesis which increases bilirubin conjugation.

 Promotes synthesis of albumin which increases hepatic uptake of bilirubin for conjugation.

b. Metalloporphyrins

Inhibit heme oxygenase activity.

Metalloporphyrins especially tin- protoporphyrin and tin-mesoporphrin inhibit heme oxygenase activity thus reducing breakdown of heme to biliverdin.

2. Exchange blood transfusion

Bilirubin can removed from blood by exchange transfusion.

Exchange blood transfusion used when;

1. Serum bilirubin level is more than 20mg/dl in term infants 

2. Serum bilirubin level is more than 15mg/dl in preterms infants.

3. Serious complications of hyperbilirubinemia

3. Phototherapy

In phototherapy use of fluorescent light for conversion of unconjugated bilirubin into conjugated bilirubin.

Working Principles of Phototherapy

1. Geometric photoisomerization 

Unconjugated bilirubin changes in more soluble form of bilirubin.

2. Structural isomerization 

Bilirubin converted into lumirubin which excreted into bile.

3. Oxidation 

Resulting colorless product that excreted by liver and kidney without conjugation.

Technique of Phototherapy

Bilirubin absorbs light in range of 420-500nm

Blue light range; 420-480nm

White light and day light range; 550-600nm

Combination of blue and white light preferred. 

Baby kept with diaper on genital area and eye of infants shielded with eye patches to prevent damage to retina.

Child kept at distance about 45cm from light source but now placed at 10-15 cm.

Position of baby change frequently to expose all body surface.

IV fluid intake or expressed breast milk increase by 10% during phototherapy.

Complication of phototherapy

1. Retinal damage; if eye sexposed to phototherapy

2. Bronze baby syndrome; grey brown skin

3. Testicular damage

4. Congenital Erythropoietin porphyria; hypersensitivity of skin to light and photosensitivity

5. Increase in environmental and baby body temperature 

Complications of Jaundice

If hyperbilirubinemia not treated; result in unconjugated bilirubin penetrating brain leading to neurological dysfunction.

1. Transient encephalopathy

Reversible; rise level of bilirubin but recovery occurs after exchange transfusion.

2. Kernicterus

Kernicterus includes bilirubin toxicity leads to staining and necrosis of neurons in basal ganglia and cerebellum.

Kernicterus has 3 phases;

1. Phase l; poor sucking, lethargy, hypotonia, depressed sensorium in affected baby.

2. Phase ll; manifested by fever, hypertonia, progresses to opisthotonus position.

3. Phase lll; High pitch cry, convulsion and fatal for baby.

3. Upward gaze palsy

4. Mental retardation