An Approach to Jaundice Block 10. Dr AJ Terblanche Department of Paediatrics and Child Health

Transcription

1 An Approach to Jaundice Block 10 Dr AJ Terblanche Department of Paediatrics and Child Health

2 JAUNDICE (ICTERUS) Yellow discoloration skin, sclerae, mucous membranes Observed 60% term, 80% preterm infants Children and adults: bilirubin > 35umol/l Neonates :85umol/l May be associated Benign self-limiting conditions Earliest sign progressive liver disease

3 Neonate (unconjugated) Prolonged jaundice (cholestatic ) Older child / adolescent

4 Source of bilirubin 75% : senescent red blood cells 25% : early labeled bilirubin ineffective erythropoeisis other heme containing proteins free heme

5 PRODUCTION Reticuloendothelial system BILIRUBIN MATERNAL UPTAKE Placenta B-Albumin Maternal conjugation, excretion TRANSPORT Circulation B-Albumin Albumin B-Albumin REAPSORPTION UPTAKE, CONJUGATION, SECRETION Hepatocyte B(GA)2 + BGA DECONJUGATION, UROBILINOID PRODUCTION Intestine Bile B, Urobilinogens, Urobilins EXCRETION; Feces

6 Bilirubin pathway Bilirubin produced from haemolysed red cells in RES Unconjugated bilirubin carried in blood stream both in a free form and attached to albumen binding sites In liver transferred into the hepatocytes by carrier proteins across the cell membrane In hepatocytes conjugated by enzyme glucuronyl transferase Secreted into bile and excreted into the gut May be deconjugated in gut and reabsorbed into circulation (enterohepatic circulation)

7 Jaundice Accumulation of bilirubin in the circulation, due to: Increased production (red cell haemolysis) Interference with intrahepatic processes Uptake into hepatocyte Conjugation Secretion into bile Obstruction to bile flow Increased enterohepatic circulation (stasis of gut contents) [applicable mostly to neonates]

8 Bilirubin measurement Bilirubin 4 forms blood Unconjugated tightly bound to albumin Unconjugated free / unbound (kernicterus) Conjugated (urine) fraction conjugated covalently bound albumin Unconjugated Hemolysis, increased production, reduced hepatic removal, deranged metabolism Conjugated Decreased excretion damaged parenchymal cells disease of the biliary tract, which may be due to obstruction, sepsis, toxins, inflammation, and genetic or metabolic disease

9 Several aspects not fully developed newborn Shorter life span Higher red cell mass Less efficient Binding albumin unconjugated biliribin Mechanism of conjugation Decreased bile flow Inefficient bile acid uptake and conjugation decreased hepatocellular excretion Physical structure neonatal liver decreased efficiency bile excretion Increased enterohepatic circulation

10 Physiologic hyperbilirubinemia Increased bilirubin production Increased enteropathic circulation Defective uptake Defective conjugation Decreased hepatic excretion

11 Non-physiologic jaundice Onset before 24h Rise > 8.5 mmol/l/h Signs underlying illness vomiting, lethargy, poor feeding, excessive weight loss, apnea, tachypnea, temp instability > 8d term, 14d premature Direct bilirubin > 34 mmol/l at any time

12 A Clinical Approach to Neonatal Jaundice

13 Indicators from the history Prenatal course, gestational age Family history jaundice, anemia, splenectomy, liver disease Ethnic / geographic origin Sibling jaundice / anemia Maternal illness Labour / delivery history Infant stooling/ vomiting/ caloric intake Breast feeding: Breast-milk vs Breast-feeding jaundice

14 Physical examination 1. Prematurity 2. SGA 3. Microcephaly 4. Extravascular blood 5. Pallor 6. Petichiae 7. Hepatosplenomegaly 8. Omphalitis 9. Chorioretinitis 10. Evidence of hypothyroidism

15 Clinical tests 1. screen Total s-bilirubin, fractions 2. Blood group, Coombs of infant and mother 3. Peripheral smear for RBC morphology and reticulocyte count 4. Hematocrit 5. Antibody on infant RBC if Coombs + 6. Prolonged jaundice : Lft, cong infx, sepsis, metabolic defects, hypothyroidism. 7. G6PD

16 Bilirubin toxicity Kernicterus Acute bilirubin enchephalopathy 1. Hypotonia, lethargy, high pitched cry 2. Hypertonia 3. Hypotonia Chronic bilirubin encephalopathy

17 Management Photo therapy Exchange transfusion Phenobarbital Decrease enterohepatic circulation Inhibit bilirubin production Inhibit hemolysis

18 > 14 days Total bilirubin and fractions Unconjugated Conjugated

19 Cholestatic jaundice Conjugated Conjugated fraction >20% of total bili Hepatobiliary dysfunction Early detection and accurate diagnosis important successful treatment, favourable diagnosis Investigate > 2w of age 1/2500 Critical to distinguish noncholestatic conditionsmore likely serious

20 Cholestasis Obstructive Hepatocellular Genetic/metabolic Toxic / Secondary

21 Investigation History Clinical picture Jaundice, pale stools, dark urine Clinical examination Liver sonar HIDA scan Liver biopsy Blood investigations Bilirubin, total and fractions LFT Enzymes AST, ALT, GGT, ALP Function INR, albumin, glucose, (NH3) FBC, diff, plt Exclude bacterial infection- BC, UMCS STORCH, Hep studies, HIV TFT, a-1-antitripsin, GALT, u-reducing substances

22 Treatment Underlying etiology Kasai etc Medical treatment Ursodeoxycholic acid MVT Vit ADEK, One alpha Zinc sulphate Neonatal hepatitis: prednisone Pruritis: Phenobarbitone, Rifampisin, Questran Dietary management: MCT oils, frequent high energy meals, supplements Complications

23 Child and adolescent with acute onset jaundice Different aetiology History Duration symptoms and co-existent symptoms Infancy -? unrecognized congenital defects Fever, malaise - infection Recent exposure blood products / Hepatitis A or B viral hepatitis Sexual contact Drug exposure epilepsy, TB, HIV Herbal medication! Alcohol intake Previous history jaundice and liver disease preexisting chronic disease

24 Clinical features ACUTELY ILL Fulminant hepatic failure Sepsis Acute cholangitis Metabolic liver disease Toxic liver disease WELL LOOKING Acute hepatitis A EBV: sore throught, LAD, fever Cryptogenic cirrhosis Growth failure, delayed onset puberty HSM Hard hepatomegaly, clubbing: cirrhosis Massive hepatomegaly: RHF, Budd Chiari, neoplasm

25 Diagnosis Fractionated bilirubin Unconjugated hyperbilirubinaemia: Gilbert s, hemolysis Conjugated: Hepatitis A/B, EBV, CMV, autoimmune hepatitis, gallstones, toxins, drugs, metabolic disorders Liver function tests AST/ALT/ALP/GGT Hepatitis studies S and u-copper, s-ceruloplasmin Evaluate function liver: alb, INR, NH3, glucose

26 Management Treat according to underlying condition Ill, encephalopathic, bleeding tendency: admit and treat for acute liver failure