Hiperbilirubinemia

UNCONJUGATED (INDIRECT) HYPERBILIRUBINEMIA

Rate of bilirubin production exceeds the rate of bilirubin elimination

Increase total serum bilirubin (TSB) concentration — hyperbilirubinemia (jaundice)

Physiologic jaundice

Almost every newborn infant

First week of life (2nd-3rd day)

Resolves spontaneously

If develops in 1st 24 h of life — considered pathologic until proven otherwise

Exclution criteria:

Unconj bilirubin level >12.9 mg/dL in term

Unconj bilirubin level > 15 in preterm

Bilirubin level increase at rate >5 mg/dL/day

Jaundice in the 1st 24 h of life

Conj bilirubin level >2 mg/dL

Clinical jaundice persisting >1 week in full

term or >2 weeks in preterm

Mechanisms:

Increase bil load because the larger RBC volume, the

shorter life span of RBC, increase enterohepatic

recirc of bil in newborn.

Defective uptake by the liver because

Decrease concentration of bil binding protein (ligandin).

Defective conjugation because decrease glucoronyl

transferase activity.

Impaired excretion into bile.

Overall impairment/immaturity of liver function.

Hemolytic anemia

RBC defects: def G6PD, def piruvat kinase,

halassemia. Etc

Acquired hemolytic anemia: ABO

incompatibility.

Polycitemia. The liver not have capacity to metabolize the increase bil load à increase blood vol

Blood extravasation

Defects of conjugation

Congenital def of glucoronyl transferase

Cligler-Najjar syndrome type I: severe def uridine diphosphate (UDP) glucoronyl transf.

àUnresposive to phenobarbital therapy.

Cligler-Najjar syndrome type II: moderate def UPD glucoronyl transf à responsive to phenobarbital therapy.

Gilbert syndrome: mild def UDP) glucoronyl

transf àresponsive to pheno therapy

Glucoronil transferase inhibition:

Drugs (novobiocin)

Lucey-Driscoll syndrome: unspecified

maternal gesation hormone in infant

interferes with the conj of bil.

Breast milk jaundice (late onset)

Prolongation of increaseenterohepatic circ of bil because of a factor in human milk that promote intestinal absorbtion.

Higher peak (10-30 mg/dL) by days 10-15.

Metabolic disorders: galactosemia, hypothyroidism, maternal diabetes, ect.

increase enteohepatic recirc: pyloric stenosis, duodenal atresia, ileus, ect.

Unconj bil à cross blood brain barrier à brain cell à neuronal dysfunction à depress O2 consumption à death.

ENCEPHALOPATHY

KERNICTERUS

Post mortem diagnosis

Risk if bi level >25 mg/dL

Joundice at face, especially at nose, descending to the torso and lower extremities.

Areas of bleeding (cephalhematoma, ptechiae) indicates blood extravasation.

Hepatosplenomegaly (hemolytic disease, liver disease, or infection)

Sign of prematurity, IUGR, postmaturity.

Plethora (polycitemia)

Pallor (hemolytic disease)

Neurologic signs: lethargy, poor feeding, vomiting, hypotonia.

Laboratory studies

Total and direct bilirubin

Complete blood cell count and reticulocyte count.

Blood type and Rh status in mother and infant

Direct Coomb’s test

Measurement of serum albumin

Urine test

Radiologis studies: intestinal obstruction

Transcutaneous bilirubimentry (TcB)

measures the degree of yellow color by selective wavelength reflection.

Expired carbon monoxide breath analyzer.

Phototherapy

TSB level 20 mg/dL ar 48 h of life maybe treated initially with phototherapy.

If TSB decrease by 1-2 mg/dL within 4-6 h, exchange transfusion maybe not necessary.

Light source: blue fluorescent tubes.

Distance from the light to the infant: 12-16 inches

Eye should be covered with opaque patches

Termination of phototherapy: bil level is low enough to eliminate the risk of kernicterus and the infants is old enough to handle the bil load.

Complication: retinal degradation, increased insensible water loss (à increasefluid requirements by 25%), bronze baby syndrome (destruction of protoporphirin àurine and skin become bronze)

Exchange transfusion

TSB 25-30 mg/dL (increasebil >0.5 mg/dL/h)

Presence of hypoxia, acidosis, sepsis or hypoproteinemia.

Albumin transfusions maybe useful if bil level >20 mg/dL and serum albumin level❤ g/dL.

Infusion of 1 g of albumin 1 h before exchange transfusion may improve the yield of bil removal.

Exchange transfusion

Pharmacology

Phenobarbital

increaseligandin in liver, increase production of glucoronyl transferase, and enhancing bil excretion.

Takes 3-7 day to become effective à less effective in the newborn

More useful to give pheno 1-2 week before delivery to pregnant woman whose fetus documented hemolytic disease.

Metalloporphyrins

Inhibit heme oxygenase (HO) by acting as a competitive inhibitor.

Supportive management breast feed

CONJUGATED (DIRECT) HYPERBILIRUBINEMIA

A sign of hepatobiliary dysfunction

After the first week of life

Direct bil level > 2.0 mg/dL or is >20% of the TSB

Caused by a defect or insufficiency in bile secretion, biliary flow, or both resulting in an inability to remove conj bil from the body.

Extrahepatic biliary disease

Biliary atresia

Choledochal cysts — dilatations of extrahepatic tree.

Biliary diseases: duct stenosis, cholelithiasis, and neoplasm.

Intrahepatic biliary disease

Intrahepatic bile duct paucity

Progressive intrahepatic cholestasis

Inspissated bile

Hepatocellular disease

Metabolic and genetic defects: cystic fibrosis, Dubin-Johnson and Rotor’s Syndrome, Galactosemia, etc.

Infection

Total parenteral nutrition (TPN) cholestasis

Idiopathic neonatal hepatitis

Miscellaneous: shock or hyperperfusion

CLINICAL PRESENTATION

Jaundice

Acholic stools

Dark urine

Hepatomegaly

Splenomegaly

Pruritus

Failure to thrive

Decrease feeding

Ascites

Portal hypertention

Alagille’s syndrone: peripheral pulmonal stenosis, vertebral anomalies, peculiar faces

Zellweger’s syndrome or cerebrohepatorenal syndrome: hypotonia, seizures, dysmorphic features.

Congenital infection: microcephaly, intracranial calcifications, IUGR.

Laboratory studies

Bilirubin levels (total and direct)

Liver function test

Prothrombin time an partial trhomboplastin time

Gamma-glutamil transpeptidase, 5-nucleaotidase, serum bile aced: increase in cholestasis

A complete blood cell count and reticulocyte count

Serum cholesterol, triglycerides, and albumin levels: assessment of liver failure

Ammonia levels: assessment of liver failure

Serum glucose levels

Urine testing

TORCH

Alpha-fetoprotein (AFP)

Other tests: hepatitis, sepsis, metabolic disorders.

Radiologic studies: USG, hepatobiliary imaging.

Other studies: persutaneus liver biopsy, exploratory laparatomy.

Medical management

Phenobarbital

Cholestiramine: increasefecal excretion of bile salts and increasehepatic synthesis of bile salt from cholesterol.

Actigall (ursodeoxycholic acid), sucsessfully used in conjunction with phenobarbital and cholestyramine.

Dietary management

Medium-chain triglycerida (MCT): can be absorbed without the action of bile salt.

Vitamin supplementation: A,D,E, and K

Dietary restriction: removal galactose, lactose,fructose, and sucrose may prevent cirrhosis.

Surgical management

Laparatomy with biopsy

Kasai procedure: to establish biliary drainage

Liver transplantation.

Other treatments

Infectious diseases (hepatitis, bacterial infections)

TPN-induced conjugated hyperbilirubinemia: will usually resolve once TPN is stopped.

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