Bilirubin is a dark yellow pigment
It is formed during the breakdown of heme-containing proteins: hemoglobin – a protein of red blood cells that carries oxygen; myoglobin – its analogue in skeletal and cardiac muscles; and cytochromes – enzymes of various biochemical cycles.
Blood serum contains 2 fractions of bilirubin: free and bound. From the point of view of laboratory diagnostics: direct and indirect. In total, they form the concentration of total bilirubin – an indicator of the state of the liver. Bilirubin is a poison, but in the blood it is always associated with protein or glucuronic acid.
The mechanism of bilirubin formation
In the cells of the reticuloendothelial system (RES), which include the Kupffer cells of the liver, macrophages of the bone marrow and spleen, and where the erythrocytes that have exhausted their resource go, the hemoglobin is broken down into globin and heme – a non-protein component, a compound of iron and an organic pigment. Heme is oxidized, iron is split off and a yellow pigment, bilirubin, remains.
It is toxic, especially for nervous tissue, is able to dissolve in lipids, and therefore easily passes through membranes and disrupts the work of the energy systems of the cell – mitochondria.
From the RES cells, the pigment enters the bloodstream. It is associated with albumin, but can form complexes with metals, amino acids and other low molecular weight substances. This is called free bilirubin. It is insoluble in water, circulates in the body, does not pass through the kidney filtration system and is not excreted in the urine.
Free bilirubin is transported to liver cells by a special transport protein. Here bilirubin, under the action of various enzymes, binds with glucuronic acid, with the formation of mono- and digluuronides. Phosphates, sulfates, glycosides can also participate in the process.
Bound bilirubin is secreted into bile and enters the intestines. Some of the bound bilirubin enters the bloodstream from bile through the intercellular spaces. This process is not a pathology. Therefore, normal blood serum contains up to 96% free bilirubin and up to 4% bound bilirubin.
In the intestine, bacterial enzymes convert bound bilirubin back to free, and then it is reduced to stercobilinogen and urobilinogen, and is excreted from the body through the intestines and kidneys, respectively.
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Why is free bilirubin called indirect, while bound bilirubin is called direct
This designation of these fractions appeared due to the method for determining the concentration. Mono- and diglucuronides react well with diazolin. Using the method of photometry, the concentration of direct bilirubin is directly determined. To determine the total amount of indirect and direct bilirubin, a caffeine reagent must be added to the reaction mixture.
Caffeine precipitates the albumin associated with bilirubin, it is released and also reacts. The reaction mixture acquires a crimson color; its intensity determines the concentration of both fractions in total. From the amount of total bilirubin, subtract the amount of direct (the figure obtained as a result of direct reaction with diazolin) and get the amount of indirect. That is, this indicator is measured indirectly, not directly.
Total bilirubin. What does it show
When reading the results of studies for bilirubin, as well as other biochemical parameters, the age of the patient must be taken into account. In a newborn the age of the first two days, this indicator will be almost 100 times higher than in an adult. This is due to the massive breakdown of red blood cells, as they are completely renewed. Hemolytic jaundice occurs in newborns. During the first month of life, his concentration usually returns to normal.
It is important to understand that specific numbers for serum bilirubin levels in a child or adult may differ from laboratory to laboratory. In addition to the patient’s age, the norms depend on the technique, apparatus and reagent with which the analysis is performed.
Why it is necessary to test the level of bilirubin
To assess the state of the body, doctors recommend performing a biochemical blood test. If jaundice is suspected, they will pay special attention to the value of bilirubin fractions.
Analysis can be assigned:
• a therapist;
• infectious disease specialist;
Bilirubin rises for two main reasons:
Diseases of the liver and biliary tract.
Processes of mass hemolysis (breakdown of erythrocytes).
An increase in its level is called hyperbilirubinemia.
Symptoms of increased bilirubin
A high concentration of this substance in the human body causes a number of characteristic symptoms. The degree of severity is directly proportional to its amount.
At the initial stage, a yellowish coloration of the albuminous membrane of the eyes appears. Then the mucous membrane of the mouth turns yellow, with a further increase in concentration, yellowness spreads to all parts of the face, palms, feet and other parts of the body. Severe itching often occurs on yellowed skin.
Sometimes a similar picture is observed with excessive use of carotene or a violation of its metabolism. But the sclera of the eyes remain white.
Diagnostic value of increased bilirubin
For the differentiation of jaundice or hyperbilirubinemia, it matters which fraction is increased.
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If the indicator of direct bilirubin grows, we can talk about the difficulty in the outflow of bile.
- Cholidocholithiasis. With gallstone disease, stones clog the ducts. This situation is dangerous for the development of cirrhosis and pancreatic necrosis. An operation to remove stones or the entire gallbladder is indicated.
- Primary sclerosing cholangitis. Inflammation and overgrowth of the tissues of the gallbladder ducts. Protective immune reactions are turned on and the body begins to produce antibodies against the tissues of the biliary system, eventually biliary cirrhosis develops.
- Dabin-Johnson Syndrome and Rotor Syndrome… A genetic disorder in which pigment flows back from the gallbladder to the liver. Chronic jaundice develops.
- Alcoholic liver damage. Destruction of hepatocytes due to prolonged (10 – 15 years) alcohol poisoning of the body. Causes alcoholic hepatitis, liver cancer and cirrhosis.
An increase in the concentration of indirect bilirubin occurs with the following pathologies:
- Hemolytic anemia of various etiologies. Death of erythrocytes and release of hemoglobin and its decay products into the bloodstream. Hemolytic anemia, which has an autoimmune nature, is of particular interest. It occurs when red blood cells die under the influence of autoimmune antibodies called heat antibodies. Their peculiarity is that they react only at elevated temperatures (37 ° C). Certain medications and leukemia provoke their production.
- Megaloblastic anemia. It occurs with a lack of vitamin B12. With this disease, an increased content of hemoglobin is observed in erythrocytes. As a result, the amount of products of its metabolism increases.
Hereditary microspherocytosis. The presence of defects in the structure of the membrane of erythrocytes, which accelerates their degradation and the release of hemoglobin into the blood.
- Cooley’s anemia – genetic disorder, synthesis of hemoglobin with an abnormal structure, when it breaks down, more bilirubin is obtained than when normal hemoglobin breaks down. Leads to mental retardation.
- Gilbert’s syndrome. Genetically determined liver disease, impaired transport of free bilirubin for the formation of a complex with glucuronic acid in the liver. The disease is benign.
- Crigler-Nayar Syndrome. Genetic pathology. Lack of essential enzymes for the formation of a bond between glucuronic acid and bilirubin. The disease is malignant, accompanied by damage to the nervous system.
Malaria. Protozoal disease. The life cycle of the pathogen has a stage of reproduction in erythrocytes, when their mass death occurs. A huge amount of hemoglobin breakdown products enter the bloodstream.
If the increase in bilirubin is proportional, then the following types of pathologies are possible:
Hepatitis is toxic or viral.
Cirrhosis of the liver.
Epstein-Barr virus infection.
Yellowing and itching of the skin can indicate liver pathologies. Hyperbilirubinemia is hazardous to health. This substance is toxic and especially detrimental to its effect on the nervous system. In acceptable concentrations, it is necessary for the body. According to experts, bilirubin is a powerful antioxidant and prevents the oxidation of metabolic products and nutrients, stimulates the renewal of body cells.