Total bilirubin in the blood

Bilirubin is a bile pigment formed during the breakdown of heme proteins. Indirect bilirubin is lipid-soluble and transported in blood plasma bound to albumin. Its conjugation occurs in the liver to form water-soluble conjugated bilirubin. Conjugated bilirubin is excreted through the bile ducts into the duodenum, where it is metabolized, transforming into unconjugated bilirubin, colorless urobilinogen, and then into orange-colored urobilins, which are mainly excreted in the feces.

Reference values (norm) of total bilirubin concentration in blood serum are less than 0.2-1.0 mg/dl (less than 3.4-17.1 μmol/l).

Hyperbilirubinemia occurs due to hypersecretion of bilirubin, suppression of reuptake and conjugation of bilirubin in the liver, and decreased biliary excretion. The content of total, mainly unconjugated, bilirubin in the blood plasma does not exceed 1.2 mg/dL (< 20 μmol/L). Fractionation can be used to determine the content of conjugated bilirubin (or direct, i.e., determined directly). Fractionation is necessary only in neonatal jaundice or if an increase in bilirubin is observed with normal values of other liver tests, which indicates another cause of jaundice.

An increase in the level of unconjugated bilirubin (indirect fraction of bilirubin greater than 85%) reflects an increase in the formation of bilirubin (for example, during hemolysis), a violation of the processes of reuptake or conjugation of bilirubin in the liver (for example, Gilbert's syndrome ). In this case, unconjugated bilirubin increases no more than 5 times [< 6 mg/dl (< 100 μmol/l)] in the absence of concomitant liver disease.

Associated hyperbilirubinemia (fraction of direct bilirubin > 50%) develops due to decreased formation or excretion of bile (cholestasis). Serum bilirubin is not sensitive to liver dysfunction and does not differentiate cholestasis from hepatocellular damage. At the same time, severe hyperbilirubinemia may be a harbinger of an unfavorable outcome in liver cirrhosis, primary biliary cirrhosis, alcoholic hepatitis, and acute liver failure.

Unconjugated bilirubin cannot be excreted in the urine because it is insoluble in water and bound to albumin. Thus, bilirubinuria usually indicates high serum conjugated bilirubin and hepatobiliary disease. Bilirubinemia can be detected by dipstick (urinalysis) in acute viral hepatitis or other hepatobiliary disorders before jaundice occurs. However, the diagnostic value of this urine test is limited because false-negative results may occur if the urine sample is stored for a long time, if vitamin C is taken with food, or if nitrates are present in the urine (eg, in urinary tract infection). Similarly, the diagnostic value of elevated urobilinogen levels is limited; these tests are neither specific nor sensitive.

An increase in the concentration of bilirubin in the blood serum above 17.1 μmol/l is called hyperbilirubinemia. This condition may be due to the formation of bilirubin in quantities exceeding the ability of the normal liver to excrete it; liver damage that disrupts the excretion of bilirubin in normal quantities, as well as due to blockage of the bile ducts, which prevents the excretion of bilirubin. In all these cases, bilirubin accumulates in the blood and, upon reaching certain concentrations, diffuses into the tissues, coloring them yellow. This condition is called jaundice. A distinction is made between mild jaundice (bilirubin concentration in the blood up to 86 μmol/l), moderate (87-159 μmol/l) and severe (over 160 μmol/l).

Depending on the type of bilirubin present in the blood serum - unconjugated (indirect) or conjugated (direct) - hyperbilirubinemia is classified as posthepatitis (unconjugated) and regurgitant (conjugated), respectively. In clinical practice, the most common division of jaundice is hemolytic, parenchymatous and obstructive. Hemolytic and parenchymatous jaundice is unconjugated, and obstructive - conjugated hyperbilirubinemia. In some cases, jaundice can be mixed in pathogenesis. Thus, with a long-term violation of the outflow of bile (mechanical jaundice) as a result of secondary damage to the liver parenchyma, the excretion of direct bilirubin into the bile capillaries can be disrupted, and it directly enters the blood; In addition, the ability of liver cells to synthesize bilirubin glucuronides decreases, as a result of which the amount of indirect bilirubin also increases.

In clinical practice, determination of bilirubin concentration in blood serum is used to solve the following problems.

• Detection of increased bilirubin levels in the blood in cases where jaundice is not detected during examination of the patient or its presence is questionable. Jaundice of the skin appears when the bilirubin level in the blood exceeds 30-35 μmol/l.
• Objective assessment of the degree of bilirubinemia.
• Differential diagnosis of various types of jaundice.
• Evaluation of the course of the disease through repeated studies.

The bilirubin content in the blood may be reduced with low hemolysis, which is observed in posthemorrhagic anemia and alimentary dystrophy. A decrease in bilirubin content has no diagnostic value.