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6/18/2019

Bilirubin Metabolism
a.) Extravascular Hemolysis (75% in neonates)
RBC ke RES di phagocytosis dan dipecah menjadi heme dan globin. Besi lepas diambil transferrin. Heme yang
sdh tidak mengikat besi ( catalyzed by heme oxygenase) menjadi biliverdin dan berubah (catalyzed by biliverdin
reductase) menjadi unconjugated bilirubin lalu masuk ke sirkulasi dan berikatan dengan albumin di bawa ke

Neonatal Jaundice liver (dengan bantuan Organic anion transport protein 2 OATP-2).
Di dalam hepatocyte bilirubin berikatan dengan ligandin ( a cytostolic protein) untuk dibawa ke RE. Di RE
bilirubin akan bertemu uridine-diphospate glucoronyl transferase (UDPGT) untuk dikonjugasi menjadi bilirubin
glucoronide (if two are formed can combine to diglucoronide but it is reversible).
Excreted with bile through small intestine. A.) degradasi oleh bakteri menjadi urobilinogen b.) hidrolisis oleh
beta-glucoronidase dan terdekonjugasi masuk kembali ke enterohepatic circulation dan dibawa kembali ke
liver. Sejumlah urobilinogen di reabsorpsi dan diantar ke ginal dan mewarnai urin. Yang tetap di usus akan
teroksidasi dan menjadi stercobilin yg mewarnai feces.

b.) Intravascular Hemolysis


Methemoglobin – hemopexin
Hemoglobin dimer – haptoglobin –> Haptoglobin cuman bawa ke mcrophage aja lanjutan sama seperti atas

Adaptation of Liver Metabolism Neonatal Jaundice


lower concentrations of the hepatocyte binding protein Kramer 1. Gestational age when jaundice start
2. Family history: ethnicity, rbc
low activity of glucuronosyl transferase Testing morphology disease, rbc enzyme,
• First line tests: galactosemia, cystic fibrosis
increased enterohepatic circulation • unconjugated bilirubin 3. ABO and rhesus
• direct antibody test
• blood group 4. Mother infections, drugs, disorder
• full blood count (FBC) and red cell 5. Labor history: complication, etc.
morphology 6. Birth condition
• Directed test (eg. Infection 7. Present condition: feeding,
screening,G6PD assay) urination, stooling
8. Treatment given to baby

Things to note:
6/18/2019

Risk Factors (6) Uncojugated Bilirubin 4. Breastmilk Jaundice


• Asphyxia Some breastmilk contain high β-
• Temperature instability 1. Physiological Jaundice
glucuronidase  increase enterohepatic
• Significant Lethargy Due to neonatal liver competence and circulation  reabsorption of bilirubin
• Acidosis high number of Hb when born high bilirubin
• Sepsis 2. Infection
• glucose-6-phosphate dehydrogenase (G6PD) deficiency 5. Delayed passage of meconium
prematurity Bacterial infection may cause

hepatocellular damage conjugated.
6. Gilberts syndrome
• low birth weight
TORCH is usually conjugated Single gene mutation affecting UDPGT
• jaundice in the first 24 hours of life
• mother with blood group O or rhesus negative 3. Breastfeeding Jaundice
• rapid rise of total serum bilirubin (TSB) Fluid deprivationless pooping and Conjugated bilirubin
• lactation failure in exclusive breastfeeding urination high bilirubin need to
• high predischarge bilirubin level breastfeed more
• family history of severe NNJ in siblings

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