Neonatal Hyperbilirubinemia [ ‘Jaundice’ ] Flashcards
What are Hyperbilirubinaemia?
Increased concentration of bilirubin in the blood which occurs when the normal pathways of bilirubin metabolism and/or excretion are altered.
What is Jaundice?
- A clinical sign of Hyperbilirubinemia which occurs when bilirubin becomes deposited in the subcutaneous and adipose tissues and the sclera.
- It is due to impaired excretion and excessive production or when there is in imbalance between production of bilirubin and its final elimination in the bile
What may jaundice be a sign of?
- Intravascular Haemolysis / Haemolytic Disease of Newborn (HDN)including Foetal-maternal ABO or Rhesus incompatibility
- Sepsis
- Liver disease
- Inherited Metabolic Diseases inc A1AT deficiency, CHT, CF, Hypopituitarism, GSD etc etc
What are the effects of Bilirubin?
- There is a risk of irreversible brain damage due to Acute Bilirubin Encephalopathy / Kernicterus (only diagnosed postmortem so best to prevent it)
- Jaundice may the first and only warning sign
Describe the steps of Haem Biosynthesis?
- Step 1: δ-Aminolevulinic acid is formed by condensation of glycine and succinyl CoA
- Step 2: 2 molecules of Aminolevulinic acid dimerise to form Porphobilinogen. This is another condensation reaction
- Steps 3: Four molecules of Porphobilinogen link up to make a linear tetrapyrrole.
- Step 4: This then internally cyclises to form uroporphyrinogen
- Steps 5, 6 and 7: Internal rearrangements, sequential decarboxylations and, finally, incorporation of iron complete the process
- Steps 8 and 9: Oxidation of heme and reduction of biliverdin results in production of bilirubin
How is Bilirubin Metabolised?
- Bilirubin is hydrophobic, and very insoluble in water.
- Conjugation of bilirubin with glucuronic acid makes it much more water soluble, and it can then be eliminated in the bile and the stool.
- This step tends to go wrong due to immaturity of the liver. Prolonged beyond 10 day in term baby and 2 weeks in premature baby then the problem needs to be resolved
What are blood concentration fractions of Bilirubin?
- Unconjugated Bilirubin - 80% of total
- Conjugated Bilirubin - 10-15%
- δ (Delta)-Bilirubin [Covalently bound to Protein] - 5-10%
- Free, unbound bilirubin is ~1/10,000 of total [bili]
What is the effect of free bilirubin?
Measure total and conjugated bilirubin
- Free bilirubin is the one that crosses the barrier to cause kernicterus. Cytokines affect permeability of the blood brain barrier allowing the bilirubin to cross
How is biblirubin measured?
Bilirubin + azo dye → Red product [A592nm]
- [+acid + ‘accelerator’ = total bilirubin]
Bilirubin + azo dye → Red product [A592nm]
- [+acid BUT no ‘accelerator’ = ‘direct’ bilirubin
Direct is a measure of the conjugated bilirubin. Same method except without the accelerator
What is Phototherapy?
- Phototherapy is the use of visible light for the treatment of hyperbilirubinaemia in the newborn.
- Therapy lowers the serum bilirubin level by transforming bilirubin into water-soluble isomers that can be eliminated without conjugation in the liver.
- The dose of phototherapy largely determines how quickly it works; the dose, in turn, is determined by the wavelength of the light, the intensity of the light (irradiance), the distance between the light and the infant, and the body surface area exposed to the light. 460nm is a typical wavelength of blue light used in commercial phototherapy devices
What are side effects of Phtotherapy?
Can cause
- Diarrhea (dangerous in babies due to dehydration)
- Cataracts
What are the sign of Clinical Jaundice?
- Yellow sclera of eyes
- Pale (acholic) stools / Dark urine
- Pruritis
- Serum total bilirubin > 80 mmol/l
What are cutoffs for jaundice?
- Hyperbilirubinemia >225 mmol/l is RARELY physiologic
- Hyperbilirubinemia >300 mmol/l is NEVER physiologic
- Conjugated >20% or >20 mmol/l is NEVER physiologic
When is jaundice never physiological?
Term baby visibly jaundiced in 1st 24 h
- Total bil ≥ 200 mmol/l @ 24-48 h
- Total bil ≥250 mmol/l @ 49-72 h
- Total bil ≥ 290 mmol/l @ >72 h
Jaundice is NEVER physiological when:
- Total bil Rising > 80 mmol/day. Requires action, regardless of starting [Tbil]
- Prolonged > 2/52 (>3/52 premature)
What is the purpose of laborotory monitoring of Jaundice?
- To help diagnose problems of bilirubin metabolism or of liver dysfunction with a treatable underlying cause
- To guide manoeuvres aimed at minimising direct damage from bilirubin itself
- To monitor response to therapy
