2History Earliest work on jaundice from Baumes-1785, and Hervieux-1847 Kernicterus was first described by Johannes Orth, 1875He postulated that jaundice might have hematologic originsHe noted that the brain in jaundiced adults wasn’t affectedChristian Schmorl coined the term in 1904Translated, Kernicterus means jaundice of the “kern” or nuclear region of the brain
3Jaundice… Exaggerated Hyperbilirubinemia PolycythemiaHemolysisRh incompatibilityABO incompatibilityAbnormal RBCs—G6PD, spherocytosis, thalassemiaBirth Trauma—Bruising, CephalohematomaMetabolic Abnormalities—Crigler Najjar, Gilbert Syndrome, GalactosemiaMedications—SulfonamidesDisplaces bilirubin from albumin; same binding site
8Pathophysiology RBCs are broken down Bilirubin is an end product of heme metabolismBilirubin is conjugated in the liverEnzyme: UDP-Glucuronyl TransferaseConjugated bili is excreted via the GI tractEnzyme: Beta-Glucuronidase can unconjugate bili in the small intestine and bili is reabsorbed
9Pathophysiology of Newborn Hyperbilirubinemia Relatively high hematocrit; more cells to break downUDP-Glucuronyl Transferase is not fully functional until 3- 4 months of lifeRelative starvation state and slow transit time, especially in breastfeedersBreastmilk contains beta-glucuronidase; enterohepatic circulation is increased
10Pathophysiology UCB is lipophilic and crosses the Blood-Brain Barrier In vitro, free UCB will not precipitate out of solution unless in the presence of a polar lipid membraneIn theory, only free UCB crosses, albumin-bound does not.BBB of infants is more permeable than adults, and acidosis causes it to be even more permeable.
11Pathophysiology…cont UCB has an affinity for the basal ganglia, hippocampus, cranial nerve nucleiMechanism is widely studied, but still unknownUCB interrupts metabolism in glial cells and causes apoptosis of neuronsExact mechanisms are unknown, but definitely separate pathways.Age of the cell is inversely proportional to susceptibility
17Physiological Jaundice Immature hepatic function + increased bilirubin load from RBCs hemolysis..
18Breast feeding associated jaundice-early milk intake few caloriesEnterohepatic shuntingIn the intestine the enzyme (B- glucuronidase is able to convert conjugated bilirubin into unconjigated form reabsorbed by the intestinal mucosa transported to the liver
19Hemolytic diseaseBreast-milk jaundice (late onset)Blood antigen incompatibility cause hemolytic or large numbers of RBCs where liver is unable to conjugate and excrete excess bilirubin from hemolysis.Caused by possible factors in the breast milk that prevent bilirubin conjugation, or less frequent stooling.
20Diagnostic evaluation Dx: serum level of bilirubin.Normal values: Unconjugated bilirubin= 0.2 to 1.4 mg/dl.Clinical dx depends on:TSB (Total serum bilirubin level)time on onset for the S&SGA at birthage in days post delivery.Family Hx and mother’s Rh factorevidence of hemolysisfeeding methodInfant physiological status
21Laboratory MeasuresThere is currently no lab value that correlates well with the development of kernicterus; there seem to be many factors that lead to its developmentGuidelines for initiating therapy for hyperbilirubinemia currently include the variables of UCB and age of baby.There are no good guidelines for preterm infantsAn unconjugated bilirubin level of 25 or less in TERM, HEALTHY babies has not been correlated with kernicterusPediatrics 1995; Case reports of Term, Healthy, Breastfed babies—UCB levels associated with clinical Kernicterus were 39-50It has been hypothesized that measuring UNBOUND UCB can be correlated, but not well supported as of yet
22Pathological Jaundice Appearance of jaundice within 24 hours of birth.Persistent jaundice after 1 week in full-terms babies, and more than 2 weeks for pre- term neonates.TSB > 12mg/dl.Increase in serum bilirubin 5mg/dl/dayDirect bilirubin > 1.5 mg/dl.
24Complications… Kernicterus (Bilirubin encephalopathy) Def: is a syndrome of sever brain damage resulting from the deposition of unconjugated bilirubin In brain cells.The damage occurs when the serum concentration reaches toxic levels and crosses the BBB.
26The yellow staining in the brain of a neonate is known as kernicterus. There is a coronal section of medulla on the left and cerebral hemisphere on the right demonstrating kernicterus in deep grey matter of hemisphere and brain stem.Kernicterus is more likely to occur with prematurity, low birth weight, and increased bilirubin levels.
27Complications…….contSerum bilirubin level can’t predict the risk for brain injury alone, other factors put the newborn at high risk for encephalo-pathy are:Metabolic acidosislow serum albumin levelsIntracranial infection as meningitisincreased blood pressureany conditions that may increase metabolic demands for oxygen or glucose, (e.g. fetal distress, hypoxia, hypthermia, hypoglycemia).S&S:CNS depression or excitation, Lethargy and decreased activity, Irritability, Hypotonia and seizures…. May progress to defness, cerebral palsy, or mental retardation.
29Prevention: Treatment of Hyperbilirubinemia PhototherapyInitiate based on UCB level and baby’s ageIsomerizes UCB to Lumirubin, soluble in water and excreted via the kidneyExchange transfusionInitiate if phototherapy fails, repeat as neededIncidence of kernicterus has dropped since the adventSn-MesoporphyrinInhibits Heme-oxygenase, which is the rate-limiting enzyme in heme catabolism.Only case reports thus far, where exchange transfusion was refused
32Phototherapy ………( blue fluorescent light) Bilirubin by photoisomerization soluble lumirubin (best in 1st 24-48hrs)What are the major nursingintervention at this stage?Pharmacological action of phenobarbital are:Increase bilirubin conjugation&hepatic clearance of the pigment in the bile2. Increase albumin level thus increasing binding sitesFeeding ( intestinal motility, establish N.Flora, ) hepatic shunting.
33Some infants may also benefit from a fiberoptic pad underneath them, especially in the breastfed infant who is encouraged to feed 8-12 times in 24 hours.Serum bilirubin levels above 25 mg/dL or higher at any time is a medical emergency and the infant should be evaluated immediately for exchange transfusion
38When drwing blood samples, turn the light off, cover the sample
39Jaundice maskDef: an excessive level of accumulated billirubin in the blood.
40MRI of an infant who suffered from severe Erythroblastosis Fetalis
41SourcesAhlfors, CE: Unbound Bilirubin Associated with Kernicterus: A Historical Approach. Journal of Pediatrics 2000; 137(4):Brodersen, R and L. Stern: Deposition of Bilirubin Acid in the CNS—A Hypothesis for the Development of Kernicterus: Acta Paediatr Scand 1990; 79:Hansen, TR: Pioneers in the Scientific Study of Neonatal Jaundice and Kernicterus. Pediatrics 2000; 106(2): e15.Kappas, A, et al: Sn-Mesoporphyrin Interdiction of Severe Hyperbilirubinemia in Jehovah’s Witness Newborns as an Alternative to Exchange Transfusion. Pediatrics 2001; 108(6):