Seeing Yellow: Understanding Hyperbilirubinemia

April 28, 2021

Terms

Bilirubin – an orange-yellow compound (pigment) that occurs from the breakdown of heme

Hyperbilirubinemia – a high amount of bilirubin in the blood

Jaundice - a medical condition in which the skin, whites of the eyes, and mucous membranes turn yellow due to a high level of bilirubin, a yellow-orange pigment.

Scleral icterus – yellow color in the whites of the eyes

Where does bilirubin come from?

  • Most bilirubin (80%) comes from the breakdown of red blood cells (pictured below).                                   

  • Hemoglobin is found in the red blood cell and is broken down to heme and globin.

  • Then heme is broken down to biliverdin, which is then broken down to bilirubin.

The body needs to get rid of the bilirubin. To do this, the bilirubin in the blood stream has to get to the liver.

Bilirubin in the blood stream can be in two forms:

  • Unconjugated and

  • Conjugated.

    Bilirubin gets conjugated in the liver - but first let’s talk about what happens before it gets to the liver.

  • To review, red blood cells break down into heme and globin.

  • Heme breaks down to biliverdin, which becomes bilirubin.

  • In this form (before getting to the liver), bilirubin is in an unconjugated form.

  • Bilirubin in an unconjugated form is fat soluble.

  • This is a problem because unconjugated bilirubin can cross the blood brain barrier.

  • In the blood, unconjugated bilirubin is transported to liver bound to the protein, albumin. Think of albumin as an UBER – picking up unconjugated bilirubin in the blood stream, putting it in a seat belt, holding on tight, and delivering it to the liver. Any bilirubin that is free, that is not bound to albumin, can cross the blood brain barrier.

  • A high level of bilirubin in the blood stream can overwhelm the amount of albumin that is available, float around in a free form, and become quite dangerous. If too much gets into the brain, it can cause a serious condition called kernicterus.

  • You can see the yellow staining in the slice of brain below - bilirubin has crossed the blood brain barrier and is in the brain. This is what we are working so hard to prevent.

Our albumin-unconjugated bilirubin package has arrived at the liver. In the liver, three things happen:

  1. The bilirubin is taken up into the liver

  2. Within the liver cells (hepatocytes), the bilirubin is conjugated.

    • Bilirubin + glucuronic acid (glucuronyl transferase)

    • = Conjugated bilirubin

    • Conjugated bilirubin is water soluble; it cannot cross blood brain barrier

  3. Conjugated bilirubin is excreted into the gut and, ideally, pooped out.

But here is the kicker.

Conjugated bilirubin can be converted by intestinal bacteria back to unconjugated bilirubin. If it sits in the gut, the unconjugated bilirubin gets sucked back into the blood stream via enterohepatic circulation. And here we go again. 

That is why we love stool!!! Stooling helps get the bilirubin out. (Fact- meconium is the dark color it is due to bilirubin pigment.)

Two kinds of high bilirubin in the infant: physiologic and non-physiologic.

Physiologic jaundice is jaundice that we expect to happen.

Non-physiologic jaundice means there is a problem which can be due to an

  • Over production of bilirubin or

  • A decreased clearance of bilirubin

Overproduction causes include:

  • Mother and baby blood groups differ causing hemolytic disease which means the excessive breaking up of red blood cells

  • Excessive bruising

  • Cephalohematoma. This is a collection of blood typically seen on one or both sides of the head in the parietal region. It is differentiated from a caput in the a cephalohematoma does not cross suture lines.

A common cause of decreased clearance is a baby who is not stooling.

Breastfeeding associated jaundice1 (or what I call lack of breastfeeding jaundice)

  • Onset of clinical jaundice at 48-72 hours

  • Peaks at days 3-5 days of life

  • Cause: starvation, delayed pooping

  • Clinically: excessive weight loss, sleepy or fussy baby, poor feeding, decreased urine and stool output

  • Treatment: feed the baby, monitor closely, fix whatever the breastfeeding problem is (supplemental feeding plan)

  • Infant may need to “go under the lights” - phototherapy works by converting unconjugated (fat soluble) bilirubin to an isomer of itself which is water soluble and can be peed out in the urine.

Key points to understand

  • Unconjugated bilirubin is fat soluble, is measured in the lab as indirect bilirubin

  • Conjugated bilirubin is water soluble, is measure in the lab as direct bilirubin

  • Physiologic vs. non-physiologic hyperbilirubinemia

  • A little increase in bilirubin level is thought to be a good thing, acts as an antioxidant.

  • A big increase in bilirubin level is a ver y bad thing and is associated with kernicterus

  • Breastfeeding associated jaundice (or lack of breastfeeding jaundice)

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Core Curriculum for Lactation Consultant Practice, 3rd edition. Edited by Rebecca Mannel, Patricia J. Martens, and Marsha Walker. Jones & Bartlett Learning. 2013