Jaundice Pathophysiology

Jaundice is a symptom of an underlying condition that impairs the excretion of bilirubin from the body.

As the 120-day lifespan of a red blood cell comes to an end or the cell becomes damaged, the cell membrane becomes weak and susceptible to rupture. As this old or damaged cell circulates through the reticuloendothelial system, the fragile membrane eventually ruptures and the contents of the cell are expelled into the bloodstream. One of the cellular components released when this happens is hemoglobin, which is ingested by phagocytic cells called macrophages. This phagocytosis splits the hemoglobin into its constituent heme and globin portions.

The globin portion is a protein that breaks down into amino acids and plays no role in the pathogenesis of jaundice. The heme, on the other hand, undergoes an oxidation reaction catalyzed by the enzyme oxygenase, to give biliverdin, iron and carbon monoxide. The biliverdin is a green-colored pigment which then undergoes a reduction reaction to yield a yellow pigment called bilirubin. This reaction is catalyzed by the cytosolic enzyme biliverdin reductase.

Nearly 4 mg of bilirubin for each kg of blood is produced in the body every day, mainly as a result of heme from expired red blood cells being broken down. The remainder is produced from other sources of heme such as failed red blood cell synthesis and from the breakdown of proteins that contain heme such as cytochromes and myoglobin.

This insoluble bilirubin is referred to as “free,” “indirect” or “unconjugated” bilirubin and it moves towards the liver through the bloodstream, while bound to albumin. In the liver, the bilirubin is conjugated with glucuronic acid (catalyzed by UDP-glucuronyl transferase) to give bilirubin diglucuronide or “conjugated” bilirubin, which is the water soluble form of bilirubin that can be excreted. This conjugated bilirubin leaves the liver and enters the biliary tree and cystic ducts as part of bile. Bacteria in the intestine then convert the bilirubin into urobilinogen. This urobilinogen is then either converted into stercobilinogen and excreted in the feces, or it is reabsorbed by the intestinal cells and taken to the kidneys via the blood to be excreted in the urine.

Jaundice is a yellowing of the skin, nail beds and whites of the eyes that is caused by a build-up of bilirubin in the body’s tissues. The condition is divided into three forms, depending on what has caused the bilirubin to accumulate. The different types of jaundice are described below.

  • Pre-hepatic jaundice – Here, the bilirubin level is disrupted prior to transportation of blood to the liver. Examples of conditions that cause this type of jaundice are hemolytic anemia and sickle cell disease.
  • Hepatocellular jaundice – Here, the disrupted bilirubin is caused by disease in the liver and examples of conditions that cause this include liver cirrhosis and Gilbert’s syndrome.
  • Post-hepatic jaundice or obstructive jaundice – Here, bile and therefore the bilirubin contained inside, is obstructed and prevented from draining into the digestive system from the gallbladder. Examples of factors that may cause this are tumors and gallstones.

Further Reading

Last Updated: Jun 17, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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