HYPERBILIRUBINEMIA Fatima C. Dela Cruz

Jaundice  Yellowish discoloration of the skin, sclera and other mucous membranes of the body

Jaundice  Accumulation in skin of unconjugated, non-polar, lipid-soluble bilirubin pigment formed from Hgb by the action of heme oxygenase, biliverdin reductase, & non-enzymatic reducing agents in the reticuloendothelial cells  Deposition of the pigment after it has been converted in the liver cell microsome by the enzyme uridine diphosphoglucuronic acid (UDP)-glucuronyl transferase to the polar, water-soluble ester glucuronide of bilirubin (direct reacting)

Jaundice  Face (total serum bilirubin ~ 5mg/dl)  Midabdomen (TSB ~15 mg/dl)  Feet (TSB ~20mg/dl)

Jaundice Dermal Zones of Jaundice (Kramer, 1969) Zone Range of TSB (mg/dL) – – – – >15

Bilirubin Macrophages Bloodstream Liver Gut RBCs  Heme  Unconjugated  Unconjugated bilirubin-  Conjugated  Urobilinogen bilirubin albumin complex bilirubin Albumin Indirect Bilirubin Direct bilirubin Uridine Glucuronyl transferase 80% -feces 20% 10%-urine 90%-liver

Jaundice  Unconjugated hyperbilirubinemia is bright yellow or orange  Direct hyperbilirunemia is greenish or muddy yellow

Differential Diagnoses Jaundice appearing at birth <24 hours  Sepsis  Erythroblastosis fetalis  Concealed hemorrhage  Cytomegalic inclusion disease  Rubella  Congenital toxoplasmosis

Differential Diagnoses Jaundice appearing on the 2nd or 3rd day  Physiologic hyperbilirubinemia of the newborn  Criggler-Najjar syndrome (familial nonhemolytic icterus)

Differential Diagnoses Jaundice appearing after the 3rd day, within the 1st week  Septicemia  Syphilis  Toxoplasmosis  Cytomegalic inclusion disease  Other causes of early jaundice (Intrauterine transfusions, Extensive ecchymosis or hematomas, Polycythemia)

Differential Diagnoses Jaundice appearing after the 1st week  Breast milk jaundice  Septicemia  Congenital atresia of the bile ducts  Hepatitis  Rubella  Galactosemia, hypothyroidism  Spherocytosis (congenital hemolytic anemia)  Other hemolytic anemias (G6PD deficiency, Glutathione synthetase deficiency, Peroxidase deficiency, Pyruvate kinase deficiency)

Physiologic Jaundice  Result of increased bilirubin production following breakdown of fetal red blood cells and limitation of liver bilirubin conjugation  Indirect bilirubin: 1-3 mg/dL; rises at a rate <5mg/dL/24h  Usually visible by the 2nd-3rd day and disappears by the 5th-7th day

Pathologic Jaundice  Jaundice appears in the first h of life  Total serum bilirubin (TSB) rises by > 5 mg/dL/day  Serum bilirubin >12 mg/dL term and mg/dL in preterm infants  Jaundice persists after days of life  Direct-reacting bilirubin >2 mg/dL at any time

Pathologic Jaundice 1. Hemolytic disease  Rh incompatibility  ABO incompatibility  Drugs (vitamin K)  Congenital hypothyroidism  Increased hemolysis  Cephal hematoma 2. Hepatocellular injury  Biliary atresia  Cholestasis  Hepatitis  Infection 3. Mixed hemolytic and hepatotoxic factors  Infection (bacterial and viral) 4. Hyperbilirubinemia secondary to metabolic factors  Hypoxia  Respiratory distress  Hypoglycemia  Hypothyroidism

Breastfeeding Jaundice   bilirubin during the first week of life in breastfed infants due to both caloric and fluid deprivation  Resolves with increased breast feeding frequency and amount of milk intake

Breastmilk Jaundice  Jaundice among breastfed infants probably secondary to hormones (pregnanediol) in milk acting on infant’s hepatic metabolism and an enzyme (glucuronidase) facilitating intestinal reabsorption of bilirubin

Treatment  Phototherapy  Exchange transfusion  Intravenous immunoglobulin  Metalloporphyrins

Treatment Phototherapy  Exposure to a high intensity of light in the visible spectrum  Bilirubin absorbs light maximally in the blue range  Photoisomerization  converts unconjugated bilirubin (4Z, 15Z) into unconjugated isomer (4Z, 15E) which is excreted in the bile  Structural change  converts unconjugated bilirubin to lumirubin, which is excreted in the urine in an unconjugated state

Treatment Exchange transfusion  Partial removal of the infant’s circulating antibody coated RBCs as well as unattached antibodies and replace