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Catabolism of Heme, Hyperbilirubinemia and Jaundice

Heme is a cyclic tetrapyrrole containing iron and makes up the chemical group of hemoglobin, myoglobin, and cytochromes.

Catabolism of Heme

  • Heme is a cyclic tetrapyrrole containing iron and makes up the chemical group of hemoglobin, myoglobin, and cytochromes.
  • This small molecule of globin is essential for oxygen transport, among other functions.
  • Around 80% of heme that can be degraded or excreted comes from senescent erythrocytes that have been in circulation for an average of 3 months.
  • Twenty percent of the remaining erythrocytes are pre-erythrocytes created in the bone marrow and destroyed before being released into the circulation, and a minor proportion comes from other types of cells.

Location

In the liver, reticuloendothelial system, and intestine, heme degradation occurs through multiple mechanisms.

Substrates – 2 UDP-glucuronic acid, NADPH, heme

Products – Fe2+, stercobilin, carbon monoxide, urobilinogen.


  • As erythrocytes age (senescent), they become damaged and damaged macrophages in the spleen destroy them.
  • Activated reticuloendothelial cells engulf RBCs. In the citric acid cycle, globin is catabolized into amino acids, which are in turn catabolized from amino acids into intermediates.
  • Heme is oxidized; heme oxygenase opens the heme ring. In an oxidation reaction, some carbons produce linear tetrapyrrole biliverdin, ferric iron (Fe 3+), and carbon monoxide (CO).
  • Bilirubin is produced by reducing second bridging methylene by biliverdin reductase in the next reaction. Thus, bilirubin is converted from green pigment into red-orange pigment.
  • The liver produces bilirubin glucuronyl transferase, which conjugates bilirubin with glucuronate and excretes it as bilirubin glucuronyl transferase in the bile.
  • The gastrointestinal tract deconjugates bilirubin, converting it to urobilinogen and stercobilin.
  • The kidneys reabsorbed some of the urobilinogen and excreted it as urobilin. Feces are mostly made up of stercobilin, which is oxidized in the feces to urobilinogen.

Hyperbilirubinemia and Jaundice

A condition called hyperbilirubinemia is characterized by a build-up of bilirubin in the blood, which causes yellow discoloration of the skin and eyes. It is normal for newborns to have low levels of bilirubin, which are not harmful. They will typically disappear by the end of the first week. In certain conditions though, such as prematurity, infection, or some types of blood disorder, bilirubin can accumulate rapidly, eventually reaching toxic levels. Depending on the cause, hyperbilirubinemia can lead to jaundice during pregnancy or afterward.

Causes

When red blood cells break down, bilirubin is produced as a natural byproduct. Conjugated bilirubin is excreted by the liver, which converts unconjugated bilirubin into it. When a baby is born, the immature liver must take over the excretion of bilirubin from the placenta during pregnancy. Jaundice and hyperbilirubinemia can be caused by several factors, including:

Physiological jaundice - Jaundice is a "normal" reaction to a baby's limited ability to remove bilirubin from the body during the first few days of life because the liver is immature. Within the first week, this will usually resolve itself.

Breastfeeding failure jaundice - A baby suffering from low milk supply and difficulty latching and feeding during the first few days of breastfeeding may become dehydrated. A buildup of bilirubin results from decreased urination and infrequent stooling since bilirubin is eliminated in urine and stool. Full-term babies tend to suffer from this problem, but premature babies and late preterm babies are more susceptible since they may have uncoordinated sucking and are more prone to fatigability. The problem will go away once breastfeeding is established.

Breast milk jaundice - In the first week after a breast-fed baby is born, approximately 2 percent will develop jaundice. During the first three to twelve weeks of life, it peaks at about two weeks of age. A substance in breast milk may cause bilirubin to be re-absorbable through the intestinal tract and cause breast milk jaundice. Usually, breastfeeding can be continued or only temporarily interrupted.

Jaundice from hemolysis - Jaundice may occur if there is an increase in the breakdown of red blood cells (hemolysis), such as when maternal and fetal blood types are incompatible, or when the newborn suffers from a hemolytic disease (Rh disease). The baby can also experience increased hemolysis if the bruise or hematoma occurs during delivery.

Jaundice related to inadequate liver failure - A prolonged liver dysfunction may result in jaundice and be caused by infection as well as other factors.

A very large percentage of term newborns and nearly all premature babies develop jaundice due to hyperbilirubinemia.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of pharmaguideline.com, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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