Script:

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Definitions:

• Jaundice, Hyperbilirubinemia, or Icterus: is the yellow discoloration of the skin and sclera due to elevated levels of bilirubin in plasma.

• Bilirubin: is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and is excreted in bile.

 

Bilirubin pathway:

• RBCs are taken up by the spleen and broken down into globin & heme. Globin goes back to the blood stream to be utilized and heme is further broken down into bilirubin & iron. Now bilirubin is a toxic substance because it is fat-soluble and can cross cell membranes causing complications like Kernicterus, which will touch upon a little later. 

• So, bilirubin binds to albumin, which is a carrier protein in the blood stream, and the complex makes its way to the liver where the albumin drops off the bilirubin.

• In the liver, the bilirubin binds to glucouronic acid, and at this point the conjugated bilirubin is excreted with the bile into the gut where it is broken down by gut bacteria into stercobilinogen and urobilinogen.

• Stercobilinogen is excreted with feces and urobilinogen is reabsorbed and excreted with urine --> and this explains the colors of both.

 

 Pathophysiology of jaundice:

• Any problem in the pathway of bilirubin excretion will cause the accumulation of it in the body and thus the appearance of the yellow discoloration.

• It is generally categorized into 3 types, pre hepatic, hepatic, and post hepatic, in which bilirubin is unconjugated in pre-hepatic, conjugated in post hepatic, and either in hepatic.

• In neonatal jaundice or what is called physiological jaundice, the bilirubin is almost always unconjugated because the liver is not fully functionally developed and so the conjugation did not happen, yet. 

• Other pathological causes of neonatal jaundice include:

  • Hemolytic causes in which bilirubin is also un-conjugated  

  • Biliary atresia, in which the biliary duct is absent so the conjugation has already happened but is stuck post hepatically.

  • And the list goes on.

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Neonatal jaundice:

• Now moving on to our main topic, neonatal jaundice.

• The importance of this topic lies behind it being one the commonest conditions affecting neonates. It affects 50 -70 % of term babies and up to 80% of preterm babies, which makes it one important risk factor for this condition.

• The reason why neonatal jaundice appears is that before birth the placenta does most of the work for the baby, including the excretion of bilirubin.

• But at birth, the baby’s liver starts handling it although as we said before, it is not yet fully functionally developed. In addition to that, the life span of a neonatal RBC is about 70 days, which is markedly less than an adult’s RBC life span, which is about 120 days. And this in fact increases the hemoglobin levels in the blood and thus bilirubin levels exceed albumin-binding capacity causing jaundice.

• Physiological jaundice typically appears at 2-4 days of age and never before, and resolve spontaneously in 1-2 weeks.

• If neonatal jaundice appears during the first 24 hours of life it is definitely pathological. So tests should be run to check for hemolytic disorders like:

  • Rhesus hemolytic disease

  • ABO incompatibility

  • G6PD deficiency

  • And Spherocytosis

  • Another cause for early neonatal jaundice could be congenital infections.        

• If jaundice appears in its typical form which is, as we said, after 24 hours and before 2 weeks, it could be physiological jaundice or what is called: breastfeeding jaundice. Breastfeeding jaundice happens when milk intake is low and the reabsorption of bilirubin from the gut is increased.

• Now if jaundice appears after 2 weeks we run a bilirubin test, if it is unconjugated: we think about “prolonged physiological jaundice” or “breast milk jaundice”. How breast-milk jaundice happens is not clearly understood, but the hypothesis is that certain substances in the milk will affect the breakdown of bilirubin. If bilirubin is conjugated we think of post hepatic causes like biliary atresia. 

• Lets take a moment and compare breastfeeding jaundice to breast-milk jaundice:

  • In breastfeeding jaundice the time frame in which the it appears at the typical age of 2 days and disappears by the second week while breast milk jaundice appears at around day 7 and may last for up to a month or more.

  • Another difference is that breastfeeding jaundice gets better with feeding while breast milk jaundice will worsen with feeding.

• Risk factors for jaundice include: preterm newborns, male gender, drugs which dis-place bilirubin from albumin like sulphonamides and diazepams so these drugs are avoided in newborns, also other risk factors for hemolytic disease like being afro-caribbean or Mediterranean in G6Pd.

• As for signs or symptoms they range in severity. But typically it is discoloration that can be confined to just the face or extending to the rest of the body AND poor feeding. Other symptoms will appear as bilirubin levels rise.

• Diagnosis:

  • The diagnosis of neonatal jaundice starts with taking good history which includes things like the age of the baby, was he or she a preterm baby, history of hemolytic diseases in the family, the blood type of the mother and the blood type of the baby… and so on.

  • Then we move to the physical examination, and the key examination is the jaundice blanch test.

  • A suspected case of jaundice is confirmed by lab investigations. First thing is checking bilirubin levels, and this is done by 2 way: 1st non-invasively by a sensor placed on the skin called transcutaneous bilirobinometer, the 2nd is the blood test. A CBC blood test is also done to check hematocrit, reticulocyte count for bone marrow function and albumin levels.

  • Coomb’s test is done to rule out some types of hemolytic anemia.

• Treatment:

  • As we previously mentioned, physiological neonatal jaundice usually resolves spontaneously within the first 2 weeks. Parent’s reassurance is important & recommendations about encouraging bowel movement by feeding more often, i.e. up to 12 times a day, should be given to the mother.

  • A couple of points should be taken in consideration before considering medical intervention. Things like bilirubin level, how fast it has been rising, how old the baby is, & whether or not baby was born early... because preterm babies are more likely to be treated at lower levels than term babies.

  • So, in severe cases, phototherapy or exchange transfusions are used. The concept of phototherapy it polymerizes unconjugated bilirubin to make it more water soluble and thus making it easier to be excreted by the kidneys and preventing it from crossing the BBB.

• Kernicterus:

  • If bilirubin crosses the BBB it will lead to a condition called: Kernicterus, or bilirubin encephalopathy. In kernicterus: free, fat soluble bilirubin crosses the BBB into the brain and accumulates particularly in the basal ganglia causing symptoms like lethargy, transient disturbance, irritability, opisthotonos, and can even lead to seizures or coma. Later on, a patient who’s had kernicterus might develop choreoathetoid cerebral palsy, sensorineural deafness, or learning difficulties.