Normal Physiology• Bilirubin -breakdown of hemoglobin• Unconjugated bilirubin (insoluble in water) transported to liver- Bound to albumin• Transported into hepatocyte (Ligandin / y- protein ) & conjugated - With glucuronic acid → now water soluble• Secreted into bile
Normal Physiology• Secreted into bile• In ileum & colon, converted to stercobilin• 10-20% (Deconjugated by β glucuronidase) reabsorbed into portal circulation (Enterohepatic circulation )and re-excreted into bile or into urine by kidneys - urobilinogen
NEWBORN JAUNDICE (PHYSIOLOGICAL) Etiology1. Decreased RBC survival 90 days, increased RBC vol /Kg, polycythemia of NB2. Poor hepatic uptake due to immature liver- decreased ligandin or Y- protein3. Poor conjugation due to enzyme deficiency- UDPG-T activity
NEWBORN JAUNDICE (PHYSIOLOGICAL)4. Increased enterohepatic circulation due to - High level of intst beta-glucoronidase - delayed colonization by bacteria - Decreased gut motility5.Decreased hepatic excretion of bilirubin
PHYSIOLOGICAL JAUNDICE• Seen both in term and preterms• Self limiting• Develops after 24 hours• Peaks by day 4- 5 in terms and day 7-8 in preterms• Peak levels -12mg/dl in term & 15mg/dl in preterm• Gradually subsides by 10-14 days• No Treatment necessary
PATHOLOGICAL JAUNDICESuspect if...• Jaundice in first 24 hours • Rise of >5mg/24 hours or 0.5 mg/dl/hr • Jaundice beyond physiological limits • Conjugated bilirubin- >2mg or 20% of total • Beyond 2 weeks • Signs of underlying illness ++
Pathological Jaundice - Hemolytic causes (unconjugated)Coombs test positive Coombs test – Rh incompatibility negative – ABO – Red blood cell incompatibility membrane defects – Red blood cell enzyme defects – Drugs – Hemoglobinopathies – Sepsis
3) Lab investigations1. Hemoglobin, PCV with peripheral smear2. Total Bilirubin (Total / Direct & Indirect) - >12 mg /<24hr - <12 mg/ >24 hr3. Bilirubin level –Special tests – – TORCH titres - Thyroid function tests – Metabolic work up - Sepsis screen – USG / X ray abdomen• Blood group and Rh typing• Reticulocyte count
Investigations in RH incompatibility• Antenatal - (mother Rh-ve, previous baby Rh + ve, father Rh +ve.1) H/o of abortion, H/o having taken Anti D gammaglobulin2) USG for baby maturation ,HSM, ascites, hydrominos, gen. anasraca
Investigations in RH incompatibility• Antenatal - - Blood grp (ABO & Rh) of father ,earlier baby - Indirect Coomb’s test – to detect antibodies in mother’s serumIgG Anti body Titre to D TO be estimated at 12-16,28- 32 and 36 weeks. If anti D antibody Titre 1:16 it should be tested serially - Ab titre in mother’s blood ->1:64 dignostic of HDN- TO CONSIDER TERMINATION OF PREGNANCY.
Investigations in RH incompatibility• Anmiocentesis:- Look for lecithin sphingomyelin ratio to suggest maturity.- Shake test for 15 sec. with equal vol etanol 95%- allowed to stand-ring of buble at the disc- Optical density-by spectrophotometer OD.>0.15 denotes maturity of lungs- Alpha feto protein level increased –rh issoimun- Fetal bloob grp prenatally – amniocentesis
POSTNATAL INVESTIGATION BABYCord blood—all babies of Rh-ve mothers, all Unknown blood groups, all with prior h/o jaundice in earlier babiesBlood group-both mother and baby- For evidence of hemolysis – Direct Coombs test Reticulocyte count - >10 suggest hemolysis. Hemoglobin cord Peripheral smear -RBC morphology Bilirubin
Phototherapy• Safe and effective method for treatment of neonatal jaundice• Bilirubin absorbs light maximum at 420-460 nm
Mechanism of ActionConversion of insoluble Bilirubin into soluble bilirubin1.Photo-isomerization-conversion into soluble form – takes place in extravascular space of skin – conversion to less toxic polar isomer-diffuses into the blood –excreted easily into bile2.Structural isomerization - conv to lumirubin - rapidly excreted in bile and urine3. Photo-oxidation- of Bilirubin to water soluble polymers colourless by product.
Indications for Phototherapy• TSB > 15 mg % in term• TSB > 12 mg% in preterm• TSB > 5 mg% within 24 hours• Adjuvant to exchange transfusion• Prophylactic PT – ELBW, bruised babies, hemolytic disease of NB,VLBW with Perinatal risk factors
Indications• Precautions – Cover the eyes and Genitals – Supplemental hydration – Watch for side effects
Procedure• Best is narrow spectral blue lights (425- 475nm)• White lamps (380-700nm)• Distance from skin – 45cm • Intensive PT – 15-20 cm• Shield eyes & genitalia• Space of 5-8cm between phototherapy unit & incubator
• Double surface PT – can be given by fiber-optic blankets (biliblankets)• Change position once in every 2-4 hrs• Skin bleached by PT• Level to be checked every 10-20 hrs• Frequent temperature monitoring & daily weight check
DRUGS• Phenobarbitone – increase y and z ligands -induces liver ezymes - ↑↑ conjugation phenobarbitone• Metalloporphyrins (tin and zinc porphyrins and meso prophyrins) -inhibits heme oxygenase
• IVIG - Inhibit haemolysis• Oral agar, Cholestyramine-↓ enterohepatic circ• Albumin infusionsInc albumin binding
• Exchange blood transfusion -- changing the babies blood with the other blood.• Usually in hemolytic disease of newborn.• It removes partially hemolysed and antibody coated RBCs and also billirubin
Methods of exchange• Single volume exchange- 80ml/kg• Double volume exchange- 160ml/kg (87% of infant blood volume exchanged with new blood)• Triple volume exchange.
Exchange TransfusionIndications:• Rh and ABO incompatibility• Unconjugated billirubin > 20 -25mg/dl in term, >15 -18mg/dl preterm babies. Sick neonates exchange at lower level• Septicemia /DIC/ sclerema• Neonatal ITP• Severe anemia due to any cause with HF
Exchange Transfusion (Indications)• Early Kernicterus• Cong H Sperocytosis• G-6- PD deficiency• Hepatic coma
In Hemolytic disease of the newborn (ABO / Rh)• H/O previous severely affected infant• Cord Hb <10gm% & bilirubin > 5mg/dl• Rate of rise of bilirubun > 0.5mg/100ml/hr• Jaundice in first 24 hrs of life• Signs of hemolysis-clinical or lab• Maternal ab titer > 1in 64• Positive DCT• Preterm LBW with hyperbilirubinemia• Reticulocyte >10
Rh incompatibility• Due to Rh D-Ag• < 1 mL of Rh-positive fetal blood is sufficient to sensitize the mother• 90% sensitization during delivery/abortion• So , most first born infants are not affected due to the short period of exposure which is insufficient to produce a significant maternal Ig G antibody response.
Rh incompatibility• Sensitized mother produces Ab –IgG types— crosses placenta• Once sensitized –small doses of Ag stimulate high Ab titer .• So, risk and severity of sensitization response increases with each subsequent pregnancy with Rh-positive blood fetus
ABO incompatibility• Mother is type O and the baby is either type A or B.• O +ve Mothers makes antibodies which are IgM & (IgG) types - IgG types crosses the placenta• No effects if the mother & baby have same blood group or baby is grp O, as there is nothing to make antibodies against.
ABO incompatibility• If mother - type A or B Makes antibodies (IgM) type so does not cross the placentaSo, even if baby has a different blood type no effect
Selection of blood• Blood group O – no antigen Ab –anti -A, anti-B• Blood group A – antigen A Ab - Anti-B• Blood group B –antigen B Ab – anti -A
Selection of blood• In Rh incompatibility: (O,A,B,AB-Negative) choice -Rh negative – - Preferably baby’s ABO - O group cross matched against maternal serum• In ABO incompatibility – “O” blood group same as baby’s Rh ( +/-) with low titre of Anti A and Anti B antibodies OR ABO type specific blood cross matched against infant serum- Septicemia – Same as baby’s ABO and Rh
Investigations• Pre exchange: Hb%, PCV, billirubin, glucose K+, Ca+.• Post exchange: Hb%, PCV, billirubin, glucose, Calcium, K+, culture.
Procedure• IN NICU OR OT• Radiant warmer, Monitor HR, BP and other vitals, infants arms and legs are restrained.• Assistant to record volume in & out, to check vitals.• Blood pre warmed to 37 c• Dried umbilical cord soaked with wet gauze.• Canulation of umbilical vein- 12 o’clock
• Catheter inserted till free flow of blood or SHOULDER UMBILICAL LENGTH.• Small aliquots of blood removed 5 to10ml -PUSH PULL method.• Blood in the bag gently mixed.• Procedure over 1 to 2 hr.• Tie around the cord for 1 hr, or hold tightly at the end of procedure.
Complications• Hypocalcemia and Hypomagnesemia - Citrate in CPD blood.• Hypoglycemia• Metabolic alkalosis or acidosis.• Hyperkelemia.• CVS: overload and arrythmias• Infections: HBV HIV• Hemolysis• Hypothermia, NEC.
Other roots for exchange• Umbilical vein cut down- incision above umbilicus in midline.• Femoral vein canulation with radial artery canulation.
Breast milk jaundice• Late onset• Due to factors in breast milk –Interfere with bilirubin conjugation: - Pregnanediol - Free fatty acids - β-glucoronidase• Instead of ↓by 7 days it continues to rise may go upto 20-30mg/dl by 2nd-3rd wks of age & return to normal by 4-12 wks
Management• Stop breast feeding -48 hrs• Again resume it, bilirubin may rise again but not reach previous high level
Breast feeding jaundice• Decreased intake of milk leads to increased enterohepatic circulation• Higher levels on day 4 compared to formula fed babies due decreased intake of milk
Prevention1. Anti D to be given to the mother after delivery of the baby-within 48hrs. Also can be given to all unsensitized mothers at 28-32 weeks of gestation2. Amniocentesis and IU transfusion to severely affected babies3. Preterm delivery of severely affected babies4. Cord blood studies-followed by Phototherapy5. Exchange transfusion
KERNICTERUS• Entry of unbound bilirubin into brain as free or albumin bound bilirubin• Acidosis affects bilirubin solubility• Hyperosmolarity, anoxia and hypercarbia disrupt BBB
• Yellow staining of brain assc with neuronal injury• Affects basal ganglia, cranial nerve nuclei, brain stem nuclei, hippocampus and AHC of spinal cord (cortex usually spared)• Necrosis, neuronal loss and gliosis …pathological findings
ACUTE BILIRUBIN ENCEPHALOPATHY• STAGE 1: hypotonia, lethargy, high pitched cry and poor suck (D1-3)• STAGE 2: hypertonia, opisthotonus, rigidity, oculogyric crisis, retrocollis, fever, seizures. (2nd week)• Those who survive develop chronic bilirubin encephalopathy• STAGE 3: Hypotonia replaces hypertonia after 3rd week age
CHRONIC BILIRUBIN ENCEPHALOPATHY• Choreo-Athetosis• Partial or complete sensorineural hearing loss• Limitation of upward gaze• Dental dysplasia• Intellectual deficits
LOW BILIRUBIN KERNICTERUS• In LBW babies, preterms• Overt changes not seen• Other factors: IVH, drugs, benzyl alcohol• More likely to suffer from anoxia, hypercarbia and sepsis
TREATMENT• Phototherapy• Exchange transfusion• Albumin infusion• Anticonvulsants: phenobarbitone• BERA at follow up
Neonatal cholestasisIntrahepatic extrahepaticHepatocyte injury bile injury EH –biliary atresiametabolic viral intrahepatic bile duct paucity idiopathic neonatal hepatitis
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