Pediatric Jaundice & Hyperbilirubinemia Lecture 3 PDF

Lecture 3 Pediatric Jaundice & Hyperbilirubinemia Department of Pediatrics Prof Malak Shaheen By the end of this lecture the student should be able to:  Define Jaundice  Describe pathophysiologic mechanism of jaundice  Differentiate between direct and indirect hyperbilir...

Lecture 3 Pediatric Jaundice & Hyperbilirubinemia Department of Pediatrics Prof Malak Shaheen By the end of this lecture the student should be able to:  Define Jaundice  Describe pathophysiologic mechanism of jaundice  Differentiate between direct and indirect hyperbilirubinemia  List different causes of jaundice  Understand how to investigate a child with jaundice  Outline the management of jaundice What is the definition of Jaundice?  Definition Jaundice is yellowish discoloration of the skin, sclerae, and mucous membranes resulting from deposition of the bile pigment bilirubin.  The presence of jaundice on clinical examination indicates hyperbilirubinemia, which is defined as a total serum bilirubin greater than 1.5 mg/dL. In general, jaundice becomes evident at serum bilirubin concentrations greater than 3 mg/dL in older children and greater than 5 mg/dL in newborns. Hyperbilirubinemia is typically characterized by the fraction of bilirubin that is increased, unconjugated (indirect), or conjugated (direct). Elevation of either of these fractions results in jaundice. Conjugated hyperbilirubinemia refers to a direct bilirubin greater than 2 mg/dL or greater than 20% of the total bilirubin concentration. The presence of conjugated hyperbilirubinemia suggests hepatobiliary tract conditions.  Classification Jaundice Direct Indirect (Conjugated) (unconjugated) Neonatal Childhood Neonatal Childhood  Neonatal jaundice UNCONJUGATED HYPERBILIRUBINEMIA CONJUGATED HYPERBILIRUBINEMIA Increased production of bilirubin Liver diseases Cephalohematoma resorption Infection (hepatitis) (sepsis, TORCH [toxoplasmosis, rubella, CMV, herpes simplex]) Polycythemia Toxins and drugs (ethanol, acetaminophen, isoniazid, Hemolysis (ABO-Rh incompatibility, phenytoin) spherocytosis, G6PD) Acute liver damage (ischemia, hypoxia, acidosis) Parenteral nutrition associated liver disease Metabolic liver disease (galactosemia, tyrosinemia, mitochondrial defects) Decreased hepatocellular uptake or conjugation Obstruction of biliary system Physiological jaundice Congenital anomalies (biliary atresia, choledochal cyst) Prematurity Congenital hypothyroidism Breast milk jaundice Gilbert syndrome, Crigler-Najjar syndrome Drug toxicity Defects of bilirubin transport Dubin-Johnson syndrome, Rotor syndrome When evaluating patients with jaundice, factors such as early onset, rapid progression, and persistence of jaundice beyond 2 weeks of life always suggest a pathologic cause.  Childhood jaundice UNCONJUGATED HYPERBILIRUBINEMIA CONJUGATED HYPERBILIRUBINEMIA Increased production of bilirubin Liver disease Polycythemia Viral hepatites (hepatitis A, B, C, E) (Epstein-Barr virus,CMV) Hemolysis (Spherocytosis, G6PD, DIC) Toxins and drugs (ethanol, acetaminophen, isoniazid, phenytoin (Thalassemia, sickle cell anemia) Acute liver damage (ischemia, hypoxia, acidosis) Parenteral nutrition associated liver disease Metabolic liver disease (1-antitrypsin deficiency, tyrosinemia, Wilson disease, mitochondrial defects) Nonalcoholic fatty liver disease Malignancy Autoimmune hepatitis Decreased hepatocellular uptake or conjugation Obstruction of the biliary system Gilbert, Crigler-Najjar syndrome Congenital anomalies (Choledochal cyst) Drug toxicity Cholelithiasis Cholecystitis Diseases of the bile ducts (primary sclerosing cholangitis) Defects of bilirubin transport Dubin-Johnson syndrome, Rotor syndrome Approach to an infant or a child with Jaundice Determine the type of jaundice (conjugated or unconjugated): Conjugated Unconjugated History Dark green-yellow sclera, skin Bright yellow scleral, skin, and and mucous membranes mucous membranes Clay colored stools Normal (colored) Dark urine Normal (amber yellow) May be red + itching No itching Examination Hepatomegaly Mostly present + Splenomegaly If there is portal hypertension + Chronic liver disease manifestations + absent (spider naevi, palmar erythema, wasting, dilated superficial abdominal veins)  History Age of onset / Duration of jaundice. Associated symptoms (pallor, abdominal pain, prodrome of viral infections, etc.). Antenatal and post natal history. Family history Travel History Drug History: hepatotoxic or herbal medications.  Hepatitis risk factors History of  Blood transfusion  Toxins  Inherited disorders including hemolytic conditions and liver diseases  Parenteral nutrition  Autoimmune disease  Abdominal pain/ operations  Kaiser Fleisher ring General examination 1. Growth pattern and developmental milestones. 2. Eye: Chronic liver  Color of the sclera, skin , mucous membranes disease  Corneal examination for Wilson Disease 3. Evidence of vitamin deficiency (ADEK ex: bleeding tendency) 4. Evidence of chronic liver disease (ex: Palmar erythema) Jaundice in mucous membranes and skin  Local examination o Abdominal swelling. o Hepatomegaly. o Splenomegaly. o Divarication of recti. o Abdominal wall vascular pattern. o Ascites.  Investigations Laboratory 1. : Bilirubin total and direct. 2. Blood group, CBC, Retics count 3. Liver Panel tests: Serum ALT, AST, GGT, Alk ph, albumin 4. Coagulopathy profile: PT, PTT 5. Other lab tests: according to history and initial lab tests. I. HB electrophoresis II. G6PD III. Osmotic fragility tests, etc. IV. Hepatitis markers and TORCH V. Blood culture VI. Ceruloplasmin/ Enzyme essay for storage ds VII. Auto immune markers  Radiology: It is not a routine but depends on the history, examination and initial labs: 1. Abdominal U/S: The most useful initial imaging investigation for assessment of intra and extrahepatic biliary systems. 2. MRCP: Magnetic resonance cholangiopancreatography (MRCP) May be useful in diagnosing obstruction of the biliary system. 3. Liver biopsy: Indications: 1- Hepatitis of unknown etiology 2- Tumor 3- Cysts 4- Parasites 5- Differentiate between hepatic and biliary problem when other methods failed Hazards: 1- Hemorraghe 2- Missed lesion 3 – Liver parenchymal damage  Treatment 1. Jaundice is a sign and not a disease. 2. Indirect hyperbilirubinemia may be harmful in case of crossing blood brain barrier (kernicterus). 3. Direct hyperbilirubinemia is harmful as indicates liver is being damaged.  Treatment 1. Management of the underlying cause Correction of hemodynamic instability in case of severe hemolysis. Management of Hemolytic disease of newborn if present. Management of underlying liver disease 2. Vitamin A, D, E, K replacement in direct hyper bilirubinemia 3. Management of itching if present 4. Nutritional management Neonatal Jaundice: more details…. Introduction Jaundice occursin approximately 60% of newborns but only a few will require investigation and treatment. LFTs: Infection screen: Toxoplasmosis, rubella, herpes simplex Surface swabs including umbilicus, throat swabs, urine culture, blood culture, lumbar puncture, CXR.  Hemolytic work-up : BBlood type and Rh determination in mother and MReciculocyte count. 8 Haemoglobin and haematotrit values. GDirect coombs test B Peripheral blood film forerythrocyte morphoJo B Red cell enzyme assays- glucose-6-phosphate dehydrogenase activity (G6PD deficiency), pyruvate kinase deficiency. Ultrasound, radionuclide scan, liver biopsy may be required for cholestatic jaundice in the differentiation between hepatitis and biliary atresia.  Draw up a treatment plan on the basis of the probability diagnosis? Doctors, nurses, and family members will watch for signs of jaundice at the hospital and after the newborn goes home. When treatment is needed, the type will depend on: The baby's bilirubin level. How fast the level has been rising. Whether the baby was born early. lF Physiological jaundice : This type is seen in most newborns -- does not require aggressive treatment. IF baby has more severe jaundice, she/he may need treatment including:  Phototherapytreatment Indication ??:  Phototherapytreatment >Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water- sOluble and can be excreted rapidly by the liver and kidney. It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus. Treatment with phototherapy is successful for almost all infants.  Phototherapy is stopped when bilirubin levels decline to a safe level. Side effects: Phototherapy is very safe; but it can have temporary side effects, including a skin rash and loose bowel movements.  Exchange transfusion : It is done to prevent or minimize biliiubin-related brain damage. 4 The transfusion replaces an infant's blood with donated blood in an attempt to quickly lower bilirubin levels. 4 performed in infants WhD have nDt responded to other treatments Indications ??: oBilirubin >34 micromoI/L oWho have signs of or are at significant neurologic risk ot’ bilirubin toxicity Risks of exchange transfusions: (include: bradycardia vasospasm air embolism infection thrombosis  Would it make any difference to your differential diagnosis if the child was 1 day old rather than 3 dav old ? OR 10 da old? Give reasons for your answer. Best classified by a_g_e of onset and duration: 1. Early: within 24 hrs of life. 2.Intermediate: 2 days to weeks. 3. Late: persists for >2 we Hemolytic causes: Rh incompatibility A8O incompatibility C6PD deficiency Congenital Infection. Other Congenital causes: Maternal autoimmune hemolytic anemia: eg, systemic lupus. Crigler-Najjar syndrome. Gilbert's syndrome. Intermediate: Physiological jaundice  Conjugated (dark urine, pale stools ): —Bile duct obstruction — Breast milk jaundice —Biliary arresia —Neonatal hepatitis  Lecture 3 Neonatal Respiratory Distress Department of Pediatrics Prof Malak Shaheen  Respiratory distress Cause of significant morbidity and mortality Incidence 4 to 6% of live births Many are preventable Early recognition, timely referral, appropriate treatment essential Teaching Aids: NNF RD60 -  Respiratory distress RR > 60/ min* Retractions Grunt + Cyanosis * Tachypnea Teaching Aids: NNF RD61 -  Causes of respiratory distress Pulmonary Cardiac- Congenital heart disease CNS- Asphyxia, IC bleed Metabolic-Hypoglycemia, acidosis Teaching Aids: NNF RD62 - Causes of respiratory distress - Medical Respiratory distress syndrome (RDS) Meconium aspiration syndrome (MAS) Transient tachypnoea of newborn (TTNB) Asphyxial lung disease Pneumonia- Congenital, aspiration, nosocomial Persistent pulmonary hypertension (PPHN) Teaching Aids: NNF RD63 -  Surgical causes of respiratory distress Tracheo-esophageal fistula Diaphragmatic hernia Lobar emphysema Pierre -Robin syndrome Choanal atresia Teaching Aids: NNF RD64 -  Approach to respiratory distress History Onset of distress Gestation Antenatal steroids Predisposing factors- PROM, fever Meconium stained amniotic fluid Asphyxia Teaching Aids: NNF RD65 -  Approach to respiratory distress Examination Severity of respiratory distress Neurological status Blood pressure, CFT Hepatomegaly Cyanosis Features of sepsis Look for malformations Teaching Aids: NNF RD66 -  Assessment of respiratory distress Score * 0 1 2 1. Resp. rate 80 2. Central None None with Needs cyanosis 40% FiO2 >40% FiO2 3. Retractions None Mild Severe 4. Grunting None Minimal Obvious 5. Air entry Good Decreased Very poor Teaching Aids: NNF RD67 * Score > 6 indicates severe distress -  Approach to respiratory distress Chest examination Air entry Mediastinal shift Adventitious sounds Hyperinflation Heart sounds Teaching Aids: NNF RD68 -  Preterm - Possible etiology Early progressive - Respiratory distress syndrome or hyaline membrane disease (HMD) Early transient - Asphyxia, metabolic causes, hypothermia Anytime - Pneumonia Teaching Aids: NNF RD69 -  Term – Possible etiology Early well looking - TTNB, polycythemia Early severe distress - MAS, asphyxia, malformations Late sick with - Cardiac hepatomegaly Late sick with shock - Acidosis Anytime - Pneumonia Teaching Aids: NNF RD70 -  Suspect surgical cause Obvious malformation Scaphoid abdomen Frothing History of aspiration Teaching Aids: NNF RD71 -  Investigations Gastric aspirate Polymorph count Sepsis screen Chest X-ray Blood gas analysis Teaching Aids: NNF RD72 -  Shake test Take a test tube Mix 0.5 ml gastric aspirate + 0.5 ml absolute alcohol Shake for 15 seconds Allow to stand 15 minutes for interpretation of result Teaching Aids: NNF RD73 -  Respiratory distress - Management Monitoring Supportive - IV fluid - Maintain vital signs - Oxygen therapy - Respiratory support Specific Teaching Aids: NNF RD74 -  Oxygen therapy* Indications All babies with distress Cyanosis Pulse oximetry SaO2 < 90% Method Flow rate 2-5 L/ min Humidified oxygen by hood or nasal prongs * Cautious administration in pre-term Teaching Aids: NNF RD75 -  Pulse oximetry Effective non invasive monitoring of oxygen therapy Ideally must for all sick neonates and those requiring oxygen therapy Maintain SaO2 between 90 – 93 % Teaching Aids: NNF RD76 -  Respiratory distress syndrome (RDS) Pre-term baby Early onset within 6 hours Supportive evidence: Negative shake test Radiological evidence Teaching Aids: NNF RD77 -  X-ray - RDS Teaching Aids: NNF RD78 -  Pathogenesis of RDS Decreased or abnormal surfactant Alveolar collapse Impaired gas exchange Respiratory failure Teaching Aids: NNF RD79 -  RDS - Predisposing factors Prematurity Cesarean born Asphyxia Maternal diabetes RDS - Protective factors PROM IUGR Steroids Teaching Aids: NNF RD82 -  Antenatal corticosteroid - Simple therapy that saves neonatal lives Preterm labor 24-34 weeks of gestation irrespective of PROM, hypertension and diabetes Dose: Inj Betamethasone 12mg IM every 24 hrs X 2 doses; or Inj Dexamethasone 6 mg IM every 12 hrs X 4 doses Multiple doses not beneficial Teaching Aids: NNF RD83 -  Surfactant therapy - Issues Should be used only if facilities for ventilation available Cost Prophylactic Vs rescue Teaching Aids: NNF RD87 -  Surfactant therapy - Issues Prophylactic therapy Extremely preterm