Bilirubin is a breakdown product in hemoglobin metabolism. Macrophages continuously break down old erythrocytes in the liver and spleen to generate bilirubin. If this process is disturbed, the substance accumulates and jaundice develops.
What is bilirubin?
Bilirubin is the breakdown product of red blood pigment. This pigment is also known as hemoglobin. Red blood cells live only about 120 days. The renewal and elimination of old red cells takes place in the form of hemoglobin metabolism. Especially in the spleen and liver, macrophages thus permanently break down old erythrocytes. Hemoglobin is converted to the intermediate stage biliverdin in the so-called heme oxygenase, which yields bilirubin in biliverdin reductase. In the blood plasma, bilirubin binds to albumin. The degradation product has a yellowish-brown color and is present in the blood as albumin-bound to 90 percent. Albumin-bound bilirubin is also referred to as primary bilirubin. Conjugated bilirubin, on the other hand, is formed in the liver cells, where the substance couples to glucuronic acid. Together, conjugated and unconjugated bilirubin make up direct bilirubin. About 30 milligrams of bilirubin are formed in the human organism every day. A large proportion of this is excreted via the intestines and urinary tract.
Anatomy and structure
Bilirubin is always a bile pigment. There are several types of it that differ anatomically. The main distinction arises from the different pathways of blood metabolism alluded to above. Indirect bilirubin is non-covalent and is albumin-bound. It is the primary and unconjugated portion of bilirubin. Direct bilirubin, on the other hand, is glucuronidated and corresponds to conjugated, secondary bilirubin. Delta-bilirubin, which is covalently bound to albumin, also falls into this group. Covalent bonding is the term used for all chemical bonds that carry common electron pairs between molecular atoms. The bilirubin of animals and plants has a similar structure to that of humans. Only direct bilirubin is clinically measurable. The indirect component is usually calculated from the direct component.
Function and tasks
In the human body, bilirubin itself does not actually perform any functions or tasks. By and large, this is true for just about all of its breakdown products. The starting product, hemoglobin, on the other hand, actually performs vital functions in the human organism. The red blood pigment primarily transports oxygen and carbon dioxide. Each molecule of hemoglobin is thus equipped with a whole four oxygen molecules. In this way, oxygen first reaches the lungs and the tissues of the body. Through its ability to bind to nitric oxide, hemoglobin also regulates blood pressure. When nitric oxide is released from the hemoglobin molecules bound to it, blood vessels dilate, for example. Blood flow improves and blood pressure drops. Without the red blood pigment, therefore, life would not be possible, since the vital transport of oxygen could not take place. However, after 120 days of life, red blood cells with these vital tasks die off and new ones come in. For this to take place, the old blood cells must be broken down and excreted. Bilirubin is therefore merely such a degradation product of the blood pigment that makes old erythrocytes excretable. If the bilirubin were no longer excreted, it would be stored. This phenomenon discolors the skin yellowish. The liver in particular is responsible for breaking down the substance. The bilirubin value can therefore provide laboratory diagnostic indications of liver disease. However, an elevated value can also indicate a backlog of bile. In addition to these possible causes, a number of different syndromes are also associated with an elevated bilirubin level.
Diseases
One of the most well-known diseases associated with bilirubin is jaundice. In this phenomenon, the substance is stored. In the serum, there is a bilirubin level above 1.2 mg/dl in this phenomenon. At first, the white skin of the eye turns yellowish due to the deposits. Later, the rest of the skin is also affected. Jaundice with greatly increased concentrations of the breakdown product even discolors the organs yellow. Neonatal jaundice occurs most frequently because newborns break down fetal hemoglobin, which can result in elevated bilirubin concentrations.Because the blood-brain barrier is not yet fully developed in the newborn, this form of jaundice can also lead to developmentally impairing deposits in the cerebrum or basal ganglia. Jaundice at a later age may be due to a variety of causes. For example, jaundice can occur as part of Dubin-Johnson syndrome or Rotor syndrome. The same applies to Gilbert syndrome and Crigler-Najjar syndrome, a hereditary metabolic disorder of hemoglobin. All diseases of the liver are also frequently associated with jaundice. Extreme liver stress due to poisoning or alcohol addiction, for example, can cause jaundice to develop. The same applies to liver inflammation or liver metastases from tumors. The causal therapeutic approach differs with the cause of the jaundice and the elevated bilirubin level. In the case of disorders of hemoglobin metabolism, symptomatic treatment usually corresponds primarily to the degradation of the stored bilirubin. In the meantime, promising therapeutic options are available for the degradation from the skin. Phototherapy can be used to convert the stored degradation product into lumirubin, for example. This substance is water-soluble and can therefore be excreted.
