Bilirubin, or bile pigment, is a substance formed as a result of the breakdown of hemoglobin in liver cells. Normally, its concentration is in the range of 3.4-22.2 micromoles per liter. At the same time, unconjugated bilirubin is 96, and direct - only 4 percent. An increase in its concentration occurs as a result of the destruction of liver cells, increased breakdown of hemoglobin, and failure of the outflow of bile from the liver. In some individuals, elevated bilirubin levels are caused by hereditary factors.
General information
In the cells of the liver and spleen, during the splitting of red cells (erythrocytes), one of the blood elements is released - hemoglobin, which is further transformed into bilirubin. In an adult individual, about 250-350 mg is produced per day. Initially, bilirubin is formed in plasma in an unconjugated form associated with albumin (indirect, freebilirubin).
He can't get past the kidney barrier. In the liver, bilirubin is transferred from albumin to the sinusoidal surface of the cells of the parenchyma of the organ, i.e., hepatocytes. In them, indirect bilirubin undergoes chemical reactions and is converted into conjugated bilirubin, which enters the gallbladder or intestines, where it is converted into urobilinogen. One part of this substance is absorbed in the small intestine and again enters the liver and is oxidized there. Bile bilirubin is converted to stercobilinogen in the large intestine. In the lower part of this intestine, it oxidizes and becomes brown and passes out with feces. A small part is absorbed into the blood, then into the kidneys and excreted in the urine. Free bilirubin enters the urine if its elevated content in the blood serum coincides with a violation of the permeability of the glomerular membrane.
Unconjugated bilirubin: structure, chemical properties
In its pure form, it is a crystalline substance with a red-brown or yellow-orange color, insoluble in water, the crystals of which are rhomboid-prismatic in shape. In another way, it is also called indirect or suprahepatic bilirubin, which is conjugated by liver enzymes before excretion. Before transport, which is carried out by plasma, it binds to most often albumin.
In this form, it is transferred to other proteins. Under normal conditions, the bond between bilirubin and protein is very strong. However, fatty acids, hydrogen ions and somedrugs can compete with bilirubin for protein binding. Prehepatic bilirubin, due to its properties, is not filtered in the glomeruli of the kidneys and is not normally found in urine. The structure of the trans-form of unconjugated bilirubin is presented in the article.
Diagnosis
A blood test is performed to identify the negative impact of elevated bilirubin levels on the liver.
A blood test determines the amount of direct, indirect and total bilirubin. The terms "direct" and "indirect" have come into use because of the reactions by which they are detected. To detect conjugated bilirubin, the Ehrlich reaction is carried out. The pigment present in the blood reacts with the reagent, and to determine the free one, several operations are necessary, since it is not soluble in water.
Unconjugated bilirubin is the difference between total and bound pigment.
Determination of bilirubin in urine is also of great diagnostic value and is one of the most sensitive and specific tests. In practical medicine, jaundice of a certain type in its pure form is quite rare, often a combination of different types. Therefore, when diagnosing hepatitis, this point should be taken into account. For example, with hemolytic jaundice, in which the level of indirect bilirubin rises, various organs are affected, including the liver. In this case, the patient has signs of parenchymal hepatitis (the concentration of direct bilirubin increases in urine and blood).
Increased free bilirubin in newborns
This situation is observed in newborns in the first three days of life. Due to the insufficient maturity of liver enzymes and the increased breakdown of red blood cells with fetal hemoglobin, physiological jaundice occurs. If such a condition in the baby dragged on, then the doctor conducts research to exclude congenital pathology of the biliary tract and liver, hemolytic disease.
Rhesus conflict between mother and child provokes an increased breakdown of red blood cells in the latter. As a result, unconjugated bilirubin rises. The negative consequences of this phenomenon is a toxic effect on the cellular tissue of the nervous system, which can lead to brain damage in a newborn (bilirubin encephalopathy). Hemolytic disease in newborns is subject to immediate treatment. In addition, hepatitis is detected in crumbs with both an increased level of free and direct bilirubin. The causes of jaundice and the choice of treatment tactics are based on the clinical picture, as well as changes in the level of fractions of conjugated and unconjugated bilirubin. In INVITRO, whose laboratories are represented in many cities, you can take both blood and urine tests at affordable prices.
Factors contributing to hyperbilirubinemia
Often, an increase in bilirubin in the blood of an adult indicates he alth problems. However, among the kids, its increase is not always a pathology. For example, in newborns, the cause of this phenomenonphysiological. Most of the diseases in which this indicator is above the norm are acquired and amenable to therapy. One of the main factors affecting the increase in unconjugated bilirubin is the low level of albumin proteins in the blood, as well as the inability of albumin to bind the bile pigment in full. Medicines such as antibiotics of the cephalosporin, penicillin series, as well as Furosemide, Diazepam, can provoke a rise in bilirubin in the blood. This phenomenon is due to the fact that the substances that make up the drug, competing with the pigment, bind to albumins.
The most common pathologies that occur against the background of an increase in the level of bile pigment in the blood are liver diseases, gallbladder and other gastrointestinal organs.
As well as conditions in which there is an increased breakdown of red blood cells.
Reasons for an increase in free bilirubin above the norm
The increase in unconjugated bilirubin is caused by some pathological processes occurring in the body. A high release of free bilirubin occurs as a result of hemolysis provoked by diseases such as:
- toxin poisoning;
- malaria;
- genetic defects in red blood cells and hemoglobin;
- autoimmune processes involving red blood cells;
- hemolytic anemia, both congenital and acquired.
Also,contributes to its increase damage to liver tissues in the following pathologies:
- all types of hepatitis;
- cirrhosis of the liver;
- leptospirosis;
- infectious mononucleosis;
- liver damage from long-term use of certain medications;
- liver cancer;
- alcohol abuse.
Excess free bilirubin caused by hemolysis
If the cause of high bilirubin is associated with hemolysis, then the patient develops suprahepatic jaundice. The dermis acquires a light yellow tint. Against the background of an enlarged spleen, which is detected by ultrasound, a pain syndrome may appear in the left side. In the analyzes - a decrease in the number of red blood cells, a change in their shape and size.
Treatment is carried out both conservatively (enzyme and hormonal therapy, immunosuppressants) and surgically. When there is a defect in red blood cells against the background of the disease, doctors recommend the removal of the spleen. The choice of medicines directly depends on the cause of the pathology.
Increased free bilirubin caused by damage to liver tissue
Jaundice in this case is manifested by the yellow-saffron color of the mucous membranes and dermis. The palms acquire a red tint and so-called spider veins appear on them. The liver is enlarged. The stool becomes colorless. In some long-term diseases, varicose veins of the esophagus and stomach occur, and fluid accumulates in the abdominal cavity.
Indirect bilirubin
Bilirubin unconjugated dissolvesgood in fats, however it is insoluble in water. It is not excreted in urine, as it is not able to pass through the renal filtration system. The rate of free bilirubin, which is measured in micromoles per liter, ranges from 15.4 to 17.1. Its content in the body, of the total, is 96 percent.
Free bilirubin freely enters the cells, where it interacts with the lipids of cell membranes, gets to the mitochondria and causes a failure in their metabolic processes and cellular respiration, the penetration of potassium ions through the cell membrane, as well as the creation of protein. The most susceptible to high levels of free bilirubin is brain tissue.
Conclusion
Unconjugated bilirubin, which is formed as a result of the breakdown of hemoglobin, is very toxic, easily soluble in cytolemma fats. Penetrating into it, it interferes with the processes of cellular metabolism and disrupts them. From the spleen to the liver, it passes along with albumin, where it interacts with glucuronic acid. The result is water-soluble, direct bilirubin, which is less toxic.