Total bilirubin

DESCRIPTION: Bilirubin is the end product of the breakdown of heme-containing proteins. About 80% of bilirubin is produced by the breakdown of hemoglobin from erythrocytes (after 120 days of erythrocyte life in the blood) in the reticuloendothelial system (RES). The remaining 20% of daily bilirubin is produced from erythrocyte precursors in the bone marrow (inefficient erythrocytopoiesis) and other heme proteins (myoglobin, cytochromes, catalase). The breakdown of hemoglobin begins with the opening of the porphyrin ring of heme. A biliverdin-iron-globin compound called verdoglobin is formed. Then, iron and globin are separated, and bilirubin is formed by the reduction of biliverdin. In contrast to iron and globin, which can be reused in metabolism, bilirubin is a final and toxic product that must be efficiently excreted from the body. Bilirubin produced in the reticuloendothelial system is not soluble in water, so after entering the blood it binds to albumin (unconjugated or free bilirubin). By binding to albumin, it is possible to transfer bilirubin to the liver, where it is conjugated and excreted. After separation from albumin on the hepatocyte membrane, bilirubin is bound to specific carriers and transported inside the cell to the place where it is conjugated with glucuronic acid to form bilirubin-diglucuronide and bilirubin-monoglucuronide. Through this process, the insoluble form of bilirubin turns into soluble, and is called conjugated or bound bilirubin. After conjugation, bilirubin is excreted from hepatocytes via bile into the small intestine. Through the action of bacteria, it is converted into urobilinogen (stercobilinogen), which changes into urobilin (stercobilin) through oxidation. Part of it is excreted through the large intestine in the stool, while the remaining part is returned to the liver and bile through the enterohepatic circulation. A small part of urobilinogen reaches the kidney through the blood, where it is excreted in the urine. The coordinated action of the reticuloendothelial system and the liver and the patency of the bile ducts maintain the concentration of bilirubin in the plasma within very low concentrations (1.7 – 22 mmol/L). a quarter of bilirubin in plasma is in conjugated form. Bilirubin cannot be detected in the urine of healthy people, while urobilinogen is a normal component of urine. Bilirubin, urobilinogen and urobilin are called bile pigments. An increase in the concentration of bilirubin in the plasma (hyperbilirubinemia) causes the appearance of yellow skin or jaundice (icterus). Hyperbilirubinemia can occur due to an increase in the concentration of unconjugated or conjugated bilirubin. ODETERMINATIONE: The method for determining the concentration of bilirubin in serum or plasma (Li heparin) is a photometric method with a diazo reagent. The sample for analysis must not be hemolytic or lipemic. CLINICAL SIGNIFICANCE: Determination of bilirubin is of great importance in the differential diagnosis of jaundice. According to the concentration of conjugated and unconjugated bilirubin in the serum, the following types of jaundice are distinguished: 1) Hemolytic (prehepatic) jaundice with increased breakdown of hemoglobin with normal liver function. 2) Parenchymal (hepatic) jaundice is caused by damage to liver cells. Conjugated bilirubin cannot be excreted into the bile capillaries, but is excreted back into the blood. 3) Obstructive (posthepatic) jaundice occurs due to blockage of bile ducts in or outside the liver. 4) Functional jaundice occurs due to changes in the intracellular metabolism of bilirubin (eg Gilbert’s syndrome, Crigler-Najjar hyperbilirubinemia, Dubin-Johnoson hyperbilirubinemia). 1) Physiological changes in bilirubin concentration From the reticuloendothelial system, bilirubin reaches the circulation, where it binds to albumin and as such enters the liver sinusoids and from them into the cells of the liver parenchyma. About 300 mmol (18 mg) of bilirubin enters the liver daily. In the smooth endoplasmic reticulum, bilirubin is separated from albumin and conjugated with glucuronic acid into bilirubin-monoglucuronide and bilirubin-diglucuronide. In this way, the insoluble bilirubin changes into the soluble form of bilirubin and is excreted in the bile. The ratio between conjugated and unconjugated bilirubin in healthy individuals is constant. An increase in serum bilirubin concentration occurs in: newborns in the first days after birth and at high altitudes in people without fitness (untrained people??). 2) Pathological changes in bilirubin concentration A) Increased values of bilirubin concentration in: Acute and subacute liver necrosis / Acute hepatitis A / Acute hepatitis B / Acute hepatitis C / Acute and chronic alcoholism / Acute pancreatitis / Liver abscess (pyogenic) / Biliary cirrhosis / Drug-induced liver diseases / Liver cirrhosis / Cytomegalic inclusion diseases / Crigler-Najjar syndrome / Dubin-Johnson syndrome / Extrahepatic biliary obstruction / Gilbert’s disease / Hemolytic diseases in newborns (Erythroblastosis fetus) / Hepatocellular carcinoma / Hepatolenticular degeneration, Infectious mononucleosis, Liver carcinoma / Pancreatic carcinoma / Cholangitis / Cholestasis / Congestive heart failure / Chronic active hepatitis / Leptospirosis / Leishmaniasis (hemolytic anemia) / Malaria / Malignant neoplasms of intrahepatic bile ducts / Miliary tuberculosis (minimal increase) / Hereditary spherocytosis / Pernicious anemia / Polycythemia rubra vera / Reye’s syndrome / Rotor’s syndrome / Acquired hemolytic anemia (autoimmune) / Thrombotic thrombocytopenic purpura (TTP) / Viral hepatitis / Liver failure / Yellow fever RESULT: The reference interval depends on age, gender and work method. The reference interval is displayed on each validated result.