Associated fraction of bilirubin. Bilirubin tests detect severe liver disease. Free and bound fraction of a substance

To study total bilirubin and its fractions, the following are used:

1. Straight spectrophotometric methods based on measuring the absorption of bilirubin at 440-460 nm, the source of errors here is the interference of yellow non-bilirubin pigments;

2. Enzymatic methods are based on the oxidation of the pigment by the copper-containing enzyme bilirubin oxidase (EC 1.3.3.5.), With the formation of biliverdin and the disappearance of absorption at 460 nm. The methods of this group are accurate and highly specific and sensitive;

3. Colorimetric diazo methods, are based on the interaction of bilirubin with diazotized sulfanilic acid with the formation of azo pigments. Under the influence of the acid, the tetrapyrrole structure of bilirubin is broken to form two dipyrroles, the carbon atoms of the methylene groups react directly with diazotized sulfonic acid (diazo mixture) to form pink-violet isomers of azodipyrrole with an absorption maximum at 530 nm. Bound bilirubin reacts quickly, unbound - only after adding an accelerator (caffeine, methanol, urea, benzoate or sodium hydroxide, acetic acid, and others). The latter releases bilirubin from the complex with proteins and thereby accelerates the azo coupling reaction. The resulting azo dye behaves as an acid-base indicator with several color transitions: in a strongly acidic medium it is colored violet, in a weakly alkaline and slightly acidic medium it is pink, and in a strongly alkaline medium it is blue or green.

4. Electrochemical methods using platinum and mercury electrodes;

5. Chromatographic separation of individual fractions of bilirubin;

6. Fluorometric Methods that use the property of free bilirubin after absorption at 430 nm to emit light with a length of 520 nm. Allows to determine the concentration of unconjugated bilirubin and, after treatment with a detergent, total bilirubin, the main advantage of the method is the ability to use trace amounts of serum.

Unified the method for determining the amount of bilirubin in serum is the Jendrashik-Cleghorn-Grof method by diazo reaction in an alkaline or weakly acidic medium in the presence of an accelerator.

Determination of the concentration of bilirubin and its fractions
in blood serum by diazo reaction

Principle

Bilirubin reacts with diazotized sulfonic acid in the presence of caffeine to form colored azo pigments.

Normal values

Serum (diazo reaction) Direct bilirubin
Adults 2.2-5.1 μmol / L
Total bilirubin
Children Full-term Premature
cord blood < 34,2 мкмоль/л < 34,2 мкмоль/л
age up to 2 days < 136,8 мкмоль/л < 205,2 мкмоль/л
age up to 5 days < 205,2 мкмоль/л < 273,6 мкмоль/л
afterwards 3.4-17.1 μmol / l
Adults 8.5-20.5 μmol / L
Urine
(diazo reaction on diagnostic strips or tablets)
lack of bilirubin
Amniotic fluid (oxidation method) 28 weeks <1,28 мкмоль/л
40 weeks <0,43 мкмоль/л
Feces missing
Bile hepatic 513.1-1026.2 μmol / L
vesicular average 2394.6 μmol / l

Influencing factors

Inflated results are caused by hemolysis, taking steroid drugs, erythromycin, phenobarbital, eating food containing carotenoids (carrots, apricots). Prolonged exposure of serum to light causes oxidation of bilirubin and underestimates the values.

Clinical and diagnostic value

Serum

The accumulation of bilirubin in the blood over 43 μmol / l leads to binding of it by elastic fibers of the skin and conjunctiva, which manifests itself in the form of jaundice. For the differential diagnosis of jaundice, it is necessary to determine due to which fraction bilirubinemia occurs:

1. Hemolytic or suprahepatic jaundice - accelerated formation of bilirubin as a result of intravascular hemolysis. These are hemolytic anemias of various origins: sulfonamide poisoning, thalassemias, sepsis, radiation sickness, blood incompatibility, congenital spherocytosis, sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency.

In this case hyperbilirubinemia develops at the expense of the faction indirect bilirubin. Hepatocytes strenuously convert indirect bilirubin into a bound form, secrete it into bile, as a result, the content in the feces increases stercobilin, intensively coloring it. In urine, the content of urobilin, bilirubin is absent.

In newborns, hemolytic jaundice can develop as a symptom of hemolytic disease of the newborn.

2. Parenchymal(hepatocellular) jaundice - the cause may be a violation at all stages of the conversion of bilirubin in the liver: extraction of bilirubin from the blood by hepatic cells, its conjugation and secretion into bile. It is observed in viral and other forms of hepatitis, cirrhosis and liver tumors, fatty degeneration, in case of poisoning with toxic hepatotropic substances, in congenital pathologies.

Since all the reactions of bilirubin conversion are insufficient in the liver, hyperbilirubinemia develops due to both factions, mainly fractions of direct bilirubin. Quantity indirect bilirubin increases due to functional insufficiency of hepatocytes and / or a decrease in their number, and direct- due to an increase in the permeability of the membranes of liver cells, also due to a violation of secretion into bile.

In the urine is determined bilirubin(strong black tea color), moderately increased concentration urobilin, level stercobilin feces are normal or decreased.

In infants, variants of parenchymal jaundice are jaundice of newborns and premature babies: physiological jaundice, jaundice caused by mother's milk, etc. Hereditary jaundice of hepatic origin are syndromes Gilbert-Meilengracht, Dubin-Johnson, Crigler-Nayar.

3. Mechanical or subhepatic jaundice develops as a result of a violation of the outflow of bile with blockage of the bile duct - gallstones, neoplasms of the pancreas, helminthiasis. Also, subhepatic jaundice is detected with neoplasms of the pancreas and helminthiasis.

As a result of stagnation of bile, the bile capillaries are stretched, and the permeability of their walls increases. Not having an outflow into bile direct bilirubin enters the bloodstream and develops hyperbilirubinemia by increasing concentration direct bilirubin... The level in urine is sharply increased bilirubin(dark beer color) and reduced amount of urobilin, practically absent in feces stercobilin(grayish-white coloration).

In severe cases, due to the overflow of hepatocytes with direct bilirubin, its conjugation with glucuronic acid may be disrupted and the amount of unbound bilirubin in the blood will increase, i.e. joins hepatocellular jaundice.

Urine

Blockage of the extrahepatic biliary tract is the classic cause of bilirubinuria. The indicator is useful in the differential diagnosis of jaundice, since bilirubinuria is characteristic of obstructive and parenchymal jaundice (an increase in the level of bound bilirubin in the serum), but is absent in hemolytic jaundice. In hepatitis, bilirubin can be found in the urine before jaundice appears.

Amniotic fluid

Bilirubin is found almost exclusively in non-esterified form in combination with albumin and accumulates in erythroblastosis, infectious hepatitis and sickle cell crisis in the mother.

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For almost all types of diseases in adults or children, one of the first laboratory blood tests is a biochemical analysis. At the discretion of the doctor, it can be carried out according to the minimum or extended profile. In both cases, the analysis form will certainly indicate the level of content of two fractions of bilirubin - total and direct. Deciphering the results obtained is important for clarifying the diagnosis and treatment regimen.

So what is bilirubin, what are the differences between its varieties, what do they affect, what does the increase in their indicators depend on, and what is the diagnostic value of such a study?

Bilirubin is a yellowish-brown pigment that is one of the main constituents of bile in humans and animals. It is bilirubin that gives the characteristic brown range of feces. It also stains bruises and bruises after ink in green, then in a dirty yellow color, and a significant increase in serum bilirubin stains the entire skin and eyeballs in all kinds of yellow shades.

At its core, the formation of bilirubin pigment, the exchange of one form for another and excretion from the body is a natural defense mechanism against the effects of toxic residues of destroyed erythrocytes.

These processes also occur constantly, like the birth and death of the respiratory blood cells themselves. Every day, 200 million erythrocytes die in the body, and from the released 6-8 g of hemoglobin, from 250 to 300 μg of bilirubin is formed.

Where is it going

The formation of bilirubin pigment begins in places where erythrocytes are supposed to be destroyed and bilirubin is formed:

  • 80% - in the Kupffer cells of the liver;
  • 19% - in histocytic cells of the spleen and bone marrow macrophages;
  • 1% - in the rest of the histocytes of any connective tissues.

Construction material

Bilirubin pigment can be formed exclusively from heme-containing proteins - products of the breakdown of hemoglobin, myoglobin and cytochrome enzymes. In a healthy person, the bulk of the metabolite is formed by 85% from hemoglobin released from erythrocytes that have outlived their due date.

Therefore, massive death of red blood cells (hemolysis) can significantly affect the level of bilirubin and cause a serious increase.

The remaining 15% were called "shunt bilirubin". It is formed from:

  • Immature and defective red blood cells who could not leave their place of birth (red bone marrow) and are immediately disposed of. Normally, their percentage can be up to 7% of the total mass of bilirubin pigment. If this percentage rises, then this indicates the presence of one of the hereditary diseases affecting the processes of hematopoiesis.
  • Myoglobin, which, although in small quantities, is always present in plasma due to the constant renewal of muscle cells. Therefore, trauma, as well as extensive muscle damage, can be the cause of a short-term rise in bilirubin levels.
  • Large protein cytochromes and peroxidases, which are released as a result of aging of any cells from their destroyed membranes and septa.

How does this happen

After hemoglobin, myoglobin or cytochromes break down into components, the released hemes are absorbed by macrophages and go through the following path:

  1. Heme + heme oxygenase = water-soluble biliverdin.
  2. Bileverdin + Bileverdine transferase = water-insoluble bilirubin.

This process is the only source of carbon dioxide emission in the human body. On this basis, a promising research method is being developed, which will make it possible to judge the rate of heme breakdown by the amount of carbon dioxide in the exhaled air.

Fractions of bilirubin

In medical practice, the "pure" use of the term "bilirubin in the blood" is quite rare. Usually, it is accompanied by the adjectives general, direct, indirect, free, connected, and the phrase "you have an increased level of bilirubin in your blood" can be considered illiterate. Why?

Total bilirubin

As such, total bilirubin does not physically exist in the human body. It always consists of two components - direct and indirect bilirubin fraction.

Normally, their ratio can be represented by the following formula:

25% direct (tied) + 75% indirect (free) = 100% total.

Why does the term total bilirubin exist, and even more so why is its blood level measured?

A biochemical blood test for bilirubin in modern diagnostic laboratories can be performed using a lot of methods based on 7 known reactions of interaction of this bile pigment with various substances. Some of them allow you to measure the level of both fractions, but they are too expensive, require special conditions and therefore are performed only when carrying out research work.

In practice, the Van den Berg diazo method and its modifications are used. They are quite convenient, inexpensive and take little time. But unfortunately, with their help, only the level of direct (bound) and total bilirubin can be determined. But free (indirect) bilirubin is calculated on paper - the direct indicator is subtracted from the total level indicator.

Therefore, despite the fact that the general level of bilirubin is present in the biochemical blood test, it does not have a valuable diagnostic value. It is indicated so that the attending specialist can assess the correspondence of the above, normal ratio between fractions and the real picture.

Free and bound fraction of a substance

First, in the complex chain of bilirubin pigment formation, its indirect or free fraction is synthesized. In terms of its composition, it is especially toxic and must be removed from the human body as soon as possible.

But the free fraction is practically insoluble in water and needs to be transformed into a soluble form. Such an exchange or transformation occurs in special liver cells - hepatocytes. In them, with the help of a special enzyme, free bilirubin molecules bind with glucoronic acid and are converted into a bound (direct) fraction ready for elimination. In the future, the direct fraction becomes the main component of bile and is excreted from the body along with feces.

Despite the fact that the exchange of one form for another is carried out in the liver, this does not mean that the reasons for the increase in bilirubin lie in its unsatisfactory work. Other diseases can also be grounds for exceeding the norm of the substance content. High bilirubin can be caused by:

  • hereditary diseases of the hematopoietic organs;
  • lesions of other organs involved in the utilization of erythrocytes - the spleen, bone marrow;
  • diseases that can interfere with the excretion of bile from the body: pathology of the gallbladder, bile ducts and / or the gastrointestinal tract.

Clarification of the diagnosis lies exclusively in the plane of a competent comprehensive interpretation of the results of biochemical analysis, and if this is required, then the appointment of additional studies.

Bilirubin rate

What is the normal level of bilirubin? Despite all the advantages, the Van den Berg method and its modifications can give excellent performance and overestimated values.

Moreover, theoretically, a blood test for bilirubin in adults and healthy men and women should be slightly different from each other, since there is a difference in the normal values ​​of the number of red blood cells. However, in practice, the resulting errors, depending on the modification of the applied technique and laboratory reagents, neutralize such a difference.

Therefore, it is important for a specialist to know not the amount of bilirubin pigment itself, but its dynamics. As a result, if in the first analysis the bilirubin is elevated, then you need to be ready to take the analysis not once, but several times, and at different times and in different laboratories.

And so, the norm of bilirubin in the blood in women and the norm of bilirubin in the blood in men, in practice, can fluctuate between:

  • general - from 3.4 to 20.5 μmol / l (100%);
  • indirect - less than 19 μmol / l (75%);
  • straight line - up to 7.9 μmol / l (25%).

Common Symptoms of Elevated Bilirubin

If the level of bilirubin pigment in the blood rises, the following symptoms and signs will inevitably occur:

  • increased fatigue;
  • dizziness;
  • headache;
  • attacks of nausea.

Increased bilirubin (total) certainly causes obstructive jaundice, which can occur in varying degrees of severity:

  • light - 30-85 μmol / l;
  • average - 85-170 μmol / l;
  • severe - more than 170 μmol / l.

Diseases that increase the level of a substance

  1. Hemolysis (destruction) of erythrocytes;
  2. Violation of the outflow of bile;
  3. Violation of the formation and excretion of bilirubin.

Based on this, diseases are also divided into three main groups.

Hemolytic jaundice

Such conditions are caused by an increased breakdown of erythrocytes in the blood plasma and high indirect bilirubin, which can be the result of the following causes and hereditary diseases:

  • sickle cell anemia;
  • spherocytosis;
  • typhoid fever;
  • malaria;
  • mycoplasmosis;
  • poisoning with mercury or lead;
  • snake or other poisonous insect bites;
  • mushroom poisoning;
  • errors in blood transfusion;
  • malignant lesions of the hematopoietic organs;
  • massive blood loss;
  • sepsis.

Hemolytic jaundice is characterized by the following symptoms: pain in the left side, color of the skin and sclera yellow with a lemon tint, possibly an increase in the spleen and an increase in body temperature, tachycardia, migraines, feces and urine can be painted in dark (up to black) tones.

Subhepatic jaundice

Such diseases are accompanied by the following symptoms: bouts of nausea, belching bitter, flatulence, diarrhea or constipation, pain in the right side (hepatic colic), maximum (severe) severity of the icteric color of the skin and eyeballs, severe itching, white feces, dark urine ...

Hereditary jaundice

Disturbances in the metabolism of hereditary bilirubin are represented by the Crigler-Nayyard, Gilbert and Dabin-Johnson syndromes.

In practice, the most common Gilbert's syndrome responds well to supportive care because it is caused by a defect in the gene responsible for the production of an enzyme.

Quite often, Gilbert's syndrome proceeds without symptoms, sometimes, against a background of stress or after physical exertion, there may be mechanical jaundice of varying intensity.

Acquired jaundice

Acquired jaundice is divided into the following types:

  • suprahepatic - diseases with an excessively high metabolism of bilirubin;
  • parenchymal - hepatitis and cirrhosis of the liver.

The most common viral hepatitis is characterized by symptoms: fever, fever, signs of general poisoning, muscle weakness, pain in the joints and right side, obstructive jaundice, skin rashes, discoloration of feces and urine.

Untimely started or incorrect treatment can lead to the rapid development of hepatic-renal failure, which is a real threat to life.

For cirrhosis of the liver, in addition to the symptoms that are inherent in hepatitis, the following symptoms are characteristic:

  • severe itching of the skin;
  • marked enlargement of the liver and spleen;
  • accumulation of fluid in the abdominal cavity;
  • varicose veins of the digestive tract;
  • progressive liver failure;
  • decreased blood clotting;
  • internal hemorrhage and brain damage.

It should always be remembered that any jaundice and the causes of increased bilirubin require diagnosis, adequate decoding of laboratory tests and appropriate treatment.

A reminder would be useful - you must take a biochemical blood test observing the basic rules: be sure to be on an empty stomach, and also do not smoke 30 minutes before delivery and sit quietly near the office.

And in conclusion, we present an interesting fact. In the light of new discoveries, it is proved in practice that bilirubin pigment is not only a "slag". It turns out that its antioxidant activity is much higher than that of vitamin E. It has been proven that increased bilirubin has a positive effect on the functioning of the nervous and muscle tissue, therefore, people with chronically elevated levels of the metabolite are much less likely to suffer from atherosclerosis, cardiovascular diseases, and are less susceptible to tumor processes.

Bilirubin is a red-brown bile pigment. It is a product of hemoglobin catabolism, which is formed in the liver. Bilirubin tests are the best way to check for severe liver disease.

The price of a complex analysis for bilirubin is 350 rubles. The price includes determination of the values ​​of fractions: total bilirubin, direct bilirubin, indirect bilirubin. Taking venous blood - 170 rubles.

What is bilirubin, meaning

The bilirubin molecule consists of 4 pyrrole rings connected to each other. The molecular weight of the molecule is 548.68. Pure bilirubin is a poorly soluble crystalline substance.

As a product of the breakdown of erythrocytes, bilirubin is toxic. Its indirect form is constantly formed in tissues and blood and is not excreted from the body. The liver processes the poisonous substance, converts it into a direct form, soluble in water. The direct form is excreted in feces or urine, staining them brown.

Of great importance in diagnostics is the study of the relationship between the indicators of bilirubin in the blood, urine and feces. Even if the blood test shows total bilirubin is normal, but the absolute values ​​and the ratio of pigment fractions have deviations, a differential diagnosis of the disease should be made.

The sum of the fractions can give a generally normal value of total bilirubin, but it often happens that the primary bilirubin is increased, and the associated one is below the norm. This fractional ratio is observed in the initial forms of liver enzyme deficiency and the threat of excessive accumulation of toxic indirect bilirubin in the tissues.

Bilirubin rates by age

Bilirubin type

Children: the first 3 days after birth, μmol / l

Children: from 3 to 6 days of life, μmol / l

Children: older than 1 month, μmol / l

Adults, μmol / l

General

24 - 190

28 - 210

3,5 - 20,4

8 - 20,5

Straight

0,5 - 10,2

1 - 12,4

0 - 5,1

0 - 5,1

Indirect

23,5 - 179,8

27 - 197,6

Up to 16.5

Up to 16.5

Bilirubin blood test

The outcome of the treatment of any disease largely depends on the accuracy of the diagnosis. Quite often, the doctor has to carry out differential diagnostics, analyzing the indicators of laboratory, instrumental and hardware studies, since different diseases can have similar symptoms.

First of all, the doctor focuses on the versatility of the characteristics of this complex test. Among the basic indicators, one of the most important is the content of bilirubin in the blood, which assesses the functioning of the liver, pancreas and gallbladder. The special value of the "bilirubin" indicator and its relationship with other blood characteristics will be confirmed by any medical forum with numerous questions on this topic.

Increased bilirubin in the blood - what does it mean

If an increase in bilirubin in the blood is noted in the analysis results, this may mean the presence of serious diseases and pathological conditions:

  • hereditary or caused by other diseases, enzyme deficiency of the liver;
  • cirrhosis of the liver and hepatitis;
  • diseases of the biliary tract and gallbladder;
  • hemolytic anemia;
  • cancerous tumor or metastases to the liver from other organs;
  • vitamin deficiency B12;
  • trauma with multiple hematomas.

An exception is infant physiological jaundice, which occurs in connection with the restructuring of the newborn's body after intrauterine development. In all other cases, it is required to determine the exact cause of the high bilirubin level.

It is not always possible to identify the true disease on the basis of one indicator, therefore the doctor compares the values ​​of different indicators, obtaining more detailed information about the pathological process.

How bilirubin is related to other blood parameters

Bilirubin and hemoglobin. Hemoglobin and bilirubin are substances linked by one chain of chemical reactions, which increases interest in comparing their values ​​in a blood test and serves as additional information in the diagnosis of diseases. Hemoglobin breaks down during the renewal of erythrocytes into globin chains and heme, which, with the help of enzymes, is converted into toxic indirect bilirubin.

Consequently, high levels of hemoglobin and bilirubin indicate hemolytic anemia or bruising and bruising trauma with a large number of destroyed red blood cells. If there is low hemoglobin and high unconjugated bilirubin, then the pathology may be associated with a lack of albumin, which is responsible for moving the yellow pigment into the liver.

Bilirubin and cholesterol... Elevated cholesterol and bilirubin may indicate an improper diet, as a result of which the biliary system suffers, and fatty liver hepatosis is possible. As a rule, such a diagnosis is clarified after considering the fractions of bile pigment, other indicators from a detailed biochemical blood test, ultrasound of the abdominal organs.

Urine bilirubin tests: bilirubinuria

In healthy people, bile pigment bilirubin may be contained in urine in insignificant amounts and cannot be determined by standard laboratory methods. Sothe rate of bilirubin in the urine- this is the absence of bile pigment.

Increased bilirubin in urine

With various diseases, direct and indirect bilirubin fractions can be found in urine samples. This condition is called bilirubinuria.

Indirect bilirubin appears if its content in the blood significantly exceeds the norm and at the same time the permeability of the glomerular membrane is increased. This happens with the following diseases:

  • of various etiology.
  • Ga-nephropathy (Berger's disease)
  • systemic lupus erythematosus;
  • purple Schönlein-Genoch
  • periarteritis nodosa;
  • hemolytic uremic syndrome (HUS);
  • idiopathic thrombocytopenic purpura (ITP).

The reason for the increased direct bilirubin in urine is jaundice. A positive reaction is already detected in cases when the blood contains bilirubin within 30– 34 μmol / L. This indicates a violation of the excretion of bile into the duodenum and an excess of the bilirubin norm in adults and children in plasma. If the blood test for total bilirubin is normal, this pigment will not be in the urine.

The presence and absence of this bile pigment in urine in various forms of hepatitis is shown in the table:

Type of jaundice

Try

Norm (healthy person)

Negative

Hemolytic

Negative

Parenchymal, at the onset of the disease

Weakly positive

Parenchymal, in the midst of the disease

Strongly positive

Parenchymal, convalescent

Weakly positive

Obturation

Positive

How are tests done for bilirubinuria?

To determine bilirubin in urine, special tests are carried out:

The Gmelin test (Rosenbach's modification) is carried out as follows: 1-2 drops of acetic acid are added to 100-150 ml of urine and the solution is filtered several times through a paper filter. After that, the wet filter is left on the Petri dish to dry, after which a drop of a mixture of nitrous and nitric acids is applied to its surface. The increased bilirubin in the urine causes the paper to become stained in the form of multicolored concentric rings, counting outside - green, blue, purple, red and in the center - yellow. Without a green ring, the sample is considered negative.

Rosin's test is carried out by adding to 9-10 ml of urine taken for research, a few drops of 1% alcohol solution of iodine or Lugol's solution. In the presence of bilirubin fractions in the sample, a persistent, noticeable green ring forms at the liquid interface.

To determine the amount of direct bilirubin fraction, a screening test on standard strips is also used. The content of this pigment is determined after applying urine to it, and evaluating the resulting color according to the attached scale.

Analysis of urine for the presence this liver enzyme provides excellent opportunities:

  • with early detection of hepatitis and differential diagnosis of various types of jaundice;
  • to determine the effectiveness of treatment in the treatment of many hepatic ailments;
  • in the diagnosis of kidney pathologies, accompanied by an increase in the permeability of the glomerular membrane;
  • to monitor the presence of pigment in the urine during pregnancy and preventive examination of persons working with hazardous substances;
  • as a quick test for the condition of the liver in patients taking drugs that can cause disruption of its activity.

Urine tests for bilirubin are very simple, but quite informative.

Stool test for bilirubin

Bile pigment - bilirubin, is normally found only in the feces of very young children who are breastfed. The presence of this pigment in the feces of infants gives the feces a greenish tint. This is an absolutely normal phenomenon and has nothing to do with high bilirubin in the blood of a newborn or newborn and with infantile jaundice, which is characterized by increased indirect bilirubin.

By the fourth month, microflora begins to appear in the baby's intestines, partially metabolizing this pigment to stercobilinogen, and by about nine months, this substance is completely metabolized in the intestine to stercobilin and stercobilinogen.

Reasons for the presence of bilirubin fractions in feces

  • In older children, positive bilirubin should not be detected in the feces, although during the first year of a child's life, a small amount of this substance is sometimes observed in the feces. This is due to the instability and underdevelopment of the microflora of the children's intestines.
  • In adults, bilirubin readings in the coprogram should be negative. Its presence, especially in combination with a decrease in the concentration of stercobilinogen, indicates the existing dysbiosis (overt or latent) and the presence of pathogenic and microflora in the intestine.
  • Another reason for the appearance of this substance in feces is dyspepsia. In the event of gastrointestinal pathologies accompanied by frequent stool disorder, the microflora is "washed out" and bilirubin traces appear in the feces. This condition is observed in acute and chronic disorders of the gastrointestinal tract or conditions accompanied by impaired digestion of food. In such cases, in a biochemical blood test, the norm of bilirubin fractions is also increased.
  • This substance can appear in the results of the coprogram in acute poisoning. In this case, the work of the gastrointestinal tract and liver is disrupted, due to which the content of bilirubin compounds in the body increases, and the evacuation of intestinal contents is accelerated. As a result, a large amount of this pigment enters the intestinal lumen and it leaves the intestine too quickly, not having time to metabolize into stercobilin and stercobilinogen, and is found in feces. In this case, indirect bilirubin in the blood is often increased.

How is bilirubin in feces determined?

The content of pigment bilirubin in feces is determined using the Fouche reaction, for this a reagent is made from 100 ml of distilled water, 25 g of trichloroacetic acid and 10 ml of a 10% solution of ferric chloride. A piece of feces is triturated with water in a ratio of 1:20 and the reagent is added dropwise. In the presence of bilirubin traces, the test sample turns blue.

The sublimate reaction can also detect the content of bilirubin in the feces, but it is less sensitive. To do this, a small lump of feces is ground in a mortar with 3-4 ml of a solution of mercury chloride (mercuric chloride) and left in a fume hood for a day. By the color of the stool, the presence of bilirubin in them is judged. Normally, the biomaterial should turn pink or reddish, however, with a positive reaction, the color of the feces turns out to be greenish.

If even a small amount of this pigment is found in the feces of an adult, a consultation with a gastroenterologist and an infectious disease specialist is needed, especially if, in parallel, the total bilirubin index is also increased in the deciphering of the blood test.

Bilirubin and Acute and Chronic Liver Failure (Hepatargia)

Liver failure occurs with pronounced changes in the liver parenchyma (fibrous, dystrophic or necrotic). Depending on the speed of occurrence, there are acute and chronic forms.

With hepatgia, the detoxification function of the liver is sharply reduced, due to which the endotoxins that should have been excreted enter the bloodstream and cause poisoning of the body. In the blood, direct and total bilirubin rises to critical levels (260–350 µmol / l), which causes damage to the central nervous system. The mortality rate is 50–80%. Liver failure is acute and chronic. Reveal the degree of danger through tests for bilirubin.

Causes of hepatgia

  • The condition is often a consequence of the development of viral hepatitis and liver cirrhosis. In this case, the presence of slowly progressive hepatgia is characteristic. Hepatitis and cirrhosis may be asymptomatic for a long time, and the rate of direct bilirubin in the blood may not be exceeded for a long time;
  • Sometimes the reason is human infection with Epstein-Barr viruses, herpes, adenovirus, etc. When a woman is infected with cytomegalovirus, intrauterine infection of the fetus and its death occurs. In this case, total bilirubin is increased during pregnancy.
  • The most common cause of this condition is exposure to poisons and medications. In some cases, poisoning occurs due to the use of drugs in the wrong dosage, and sometimes it is the result of a failed suicide. In this case, the process develops sharply and is accompanied by nausea, vomiting, hemorrhagic syndrome, "liver" bad breath, neuropsychiatric disorders, increased total bilirubin in the blood.
  • Very often this condition is associated with the presence of malignant tumors in the body. In the liver, there can be both the main focus, and metastasis to this organ can be observed. With cancer, symptoms increase gradually, with severe jaundice, nausea, vomiting, and cachexia. At the beginning of the development of the tumor process, there may be a normal level of bilirubin - 7-18%, but gradually its concentration in the blood increases and it begins to exceed the norm by 10-15 times.
  • Another cause of liver failure is alcohol and drug abuse. In this case, the process can proceed both quickly and slowly, it all depends on the specific version of "addiction". However, over time, the increased bilirubin still exceeds the norm many times over.

Symptoms of hepatgia

With this pathology, they gradually increase; jaundice, weight loss edema, fever, telangiectasia, and dull abdominal pain. On the body appear "liver signs": palmar erythema, hemorrhages, Chistovich's stars, varicose veins of the abdomen in the form of a "jellyfish head".

In the future, they are joined by: heavy breath, neurosis, apathy, unstable emotional state. There may be slurred speech, writing disorders, tremors of the fingers, and impaired coordination. Analysis of total blood and biochemistry show significant deviations from the norm.

With further progression of the failure, a hepatic coma occurs. Its precursors are: drowsiness, lethargy, rigidity of skeletal muscles, confusion, muscle twitching, convulsions, uncontrolled urination. In the blood, there are very high indicators of liver function tests, a blood test for total bilirubin can show up to 500 μmol / l. Patients, falling into a coma, die.

In order not to become victims of this disease, you need to take care of your liver, monitor your health, periodically take tests and, if the biochemistry is "bad" and the total bilirubin is increased, the reasons for this phenomenon need to be clarified. You should not self-medicate, because only a doctor knows exactly what bilirubin and other blood parameters should be.

Physiological and pathological jaundice in newborns

Jaundice (jaundice) in newborns is associated with the breakdown of fertile hemoglobin in the first days of life. It can be physiological and pathological. With physiological jaundice, its manifestations go away on their own and the general condition of the newborn does not suffer. The concentration of total bilirubin is the norm in children in this case, it increases only due to its unbound fraction. To determine the extent of the problem, the children are tested for bilirubin.

Severe physiological jaundice

If the norm of free bilirubin is significantly exceeded, then the general condition of the child may suffer. Such babies are lethargic, inhibited, suck poorly, their temperature may rise and vomiting may occur. However, the condition of the newborn should be judged not by these signs, but by the bilirubin indicator.

When the total bilirubin in newborns exceeds the norm significantly, albumin produced by the infant's liver cannot fully conjugate it and it penetrates into the central nervous system through the blood-brain barrier. In this case, there is a toxic effect of this pigment, which is, in fact, a poison, on the brain. As a result, the baby may subsequently develop paralysis, mental retardation, deafness and blindness.

Jaundice treatment

In order to prevent such complications, in the case of a severe and prolonged course of jaundice, it is necessary to carry out specific treatment.

Previously, children were injected with various solutions to normalize the bilirubin level, but now this has been abandoned. Now phototherapy is carried out, during which the skin of the newborn is illuminated with a special installation. When exposed to light, the pigment decomposes and is removed from the body. These children are monitored by neonatologists until the direct bilirubin returns to normal. Most often, it is possible to normalize bilirubin in 9 days or less.

A great way to defeat jaundice is to start breastfeeding your baby as early as possible, because colostrum helps to release the meconium and cleanse the newborn's intestines.

It is noticed that a similar condition is more often observed in children born prematurely, with multiple pregnancies and difficult childbirth. Children from mothers suffering from chronic diseases such as diabetes mellitus are susceptible to jaundice. Contrary to popular belief, the mother's increased bilirubin level during pregnancy and the yellowing of the skin in the baby who is born are absolutely not related.

Bilirubin tests reveal abnormal jaundice

This type of pathology of newborns manifests itself in the first days of life. Such a baby may have: acholic feces, dark urine, hemorrhages and bright yellowness of the skin and sclera. In contrast to physiological hyperbilirubinemia, with its pathological course, the norm of direct bilirubin in the blood is markedly exceeded. In this case, a comprehensive examination and treatment is necessary.

The causes of the phenomenon are most often known:

  • The incompatibility of the blood of the mother and the baby in the group and the Rh factor can cause hemolysis of erythrocytes and icteric staining of the sclera of the newborn.
  • Sometimes a child becomes infected with the hepatitis virus or protozoa from the mother and becomes infected. In this case, specific therapy for the mother and baby is carried out, since the rate of total bilirubin in a woman is also increased in this case due to infection.
  • Due to congenital anomalies of the liver and biliary tract, obstructive jaundice may occur, characterized by an increase in direct bilirubin levels by 6 or more times. Only surgeons can help here.
  • There is a large group of hereditary hyperglobulinemias (Crigler-Nayyar, Dabin-Johnson, Rotor syndromes), which are caused by genetic metabolic defects. In this case, you need to prepare for long-term diagnosis and lifelong maintenance therapy.

To correctly diagnose jaundice in newborns, and only a doctor can find out its cause. The diagnosis can only be established by test results.

Where to get tested for bilirubin in St. Petersburg, prices

You can pass any tests in St. Petersburg, including for bilirubin, in a modern one. You can also go here. We work seven days a week. The prices for tests are low; a discount is provided for the diagnosis of infections.

To study total bilirubin and its fractions, the following are used:

1. Straight spectrophotometric methods based on measuring the absorption of bilirubin at 440-460 nm, the source of errors here is the interference of yellow non-bilirubin pigments;

2. Enzymatic methods are based on the oxidation of the pigment by the copper-containing enzyme bilirubin oxidase (EC 1.3.3.5.), With the formation of biliverdin and the disappearance of absorption at 460 nm. The methods of this group are accurate and highly specific and sensitive;

3. Colorimetric diazo methods, are based on the interaction of bilirubin with diazotized sulfanilic acid with the formation of azo pigments. Under the influence of the acid, the tetrapyrrole structure of bilirubin is broken to form two dipyrroles, the carbon atoms of the methylene groups react directly with diazotized sulfonic acid (diazo mixture) to form pink-violet isomers of azodipyrrole with an absorption maximum at 530 nm. Bound bilirubin reacts quickly, unbound - only after adding an accelerator (caffeine, methanol, urea, benzoate or sodium hydroxide, acetic acid, and others). The latter releases bilirubin from the complex with proteins and thereby accelerates the azo coupling reaction. The resulting azo dye behaves as an acid-base indicator with several color transitions: in a strongly acidic medium it is colored violet, in a weakly alkaline and slightly acidic medium it is pink, and in a strongly alkaline medium it is blue or green.

4. Electrochemical methods using platinum and mercury electrodes;

5. Chromatographic separation of individual fractions of bilirubin;

6. Fluorometric Methods that use the property of free bilirubin after absorption at 430 nm to emit light with a length of 520 nm. Allows to determine the concentration of unconjugated bilirubin and, after treatment with a detergent, total bilirubin, the main advantage of the method is the ability to use trace amounts of serum.

Unified the method for determining the amount of bilirubin in serum is the Jendrashik-Cleghorn-Grof method by diazo reaction in an alkaline or weakly acidic medium in the presence of an accelerator.

Determination of the concentration of bilirubin and its fractions
in blood serum by diazo reaction

Principle

Bilirubin reacts with diazotized sulfonic acid in the presence of caffeine to form colored azo pigments.

Normal values

Serum (diazo reaction) Direct bilirubin
Adults 2.2-5.1 μmol / L
Total bilirubin
Children Full-term Premature
cord blood < 34,2 мкмоль/л < 34,2 мкмоль/л
age up to 2 days < 136,8 мкмоль/л < 205,2 мкмоль/л
age up to 5 days < 205,2 мкмоль/л < 273,6 мкмоль/л
afterwards 3.4-17.1 μmol / l
Adults 8.5-20.5 μmol / L
Urine
(diazo reaction on diagnostic strips or tablets)
lack of bilirubin
Amniotic fluid (oxidation method) 28 weeks <1,28 мкмоль/л
40 weeks <0,43 мкмоль/л
Feces missing
Bile hepatic 513.1-1026.2 μmol / L
vesicular average 2394.6 μmol / l

Influencing factors

Inflated results are caused by hemolysis, taking steroid drugs, erythromycin, phenobarbital, eating food containing carotenoids (carrots, apricots). Prolonged exposure of serum to light causes oxidation of bilirubin and underestimates the values.

Clinical and diagnostic value

Serum

The accumulation of bilirubin in the blood over 43 μmol / l leads to binding of it by elastic fibers of the skin and conjunctiva, which manifests itself in the form of jaundice. For the differential diagnosis of jaundice, it is necessary to determine due to which fraction bilirubinemia occurs:

1. Hemolytic or suprahepatic jaundice - accelerated formation of bilirubin as a result of intravascular hemolysis. These are hemolytic anemias of various origins: sulfonamide poisoning, thalassemias, sepsis, radiation sickness, blood incompatibility, congenital spherocytosis, sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency.

In this case hyperbilirubinemia develops at the expense of the faction indirect bilirubin. Hepatocytes strenuously convert indirect bilirubin into a bound form, secrete it into bile, as a result, the content in the feces increases stercobilin, intensively coloring it. In urine, the content of urobilin, bilirubin is absent.

In newborns, hemolytic jaundice can develop as a symptom of hemolytic disease of the newborn.

2. Parenchymal(hepatocellular) jaundice - the cause may be a violation at all stages of the conversion of bilirubin in the liver: extraction of bilirubin from the blood by hepatic cells, its conjugation and secretion into bile. It is observed in viral and other forms of hepatitis, cirrhosis and liver tumors, fatty degeneration, in case of poisoning with toxic hepatotropic substances, in congenital pathologies.

Since all the reactions of bilirubin conversion are insufficient in the liver, hyperbilirubinemia develops due to both factions, mainly fractions of direct bilirubin. Quantity indirect bilirubin increases due to functional insufficiency of hepatocytes and / or a decrease in their number, and direct- due to an increase in the permeability of the membranes of liver cells, also due to a violation of secretion into bile.

In the urine is determined bilirubin(strong black tea color), moderately increased concentration urobilin, level stercobilin feces are normal or decreased.

In infants, variants of parenchymal jaundice are jaundice of newborns and premature babies: physiological jaundice, jaundice caused by mother's milk, etc. Hereditary jaundice of hepatic origin are syndromes Gilbert-Meilengracht, Dubin-Johnson, Crigler-Nayar.

3. Mechanical or subhepatic jaundice develops as a result of a violation of the outflow of bile with blockage of the bile duct - gallstones, neoplasms of the pancreas, helminthiasis. Also, subhepatic jaundice is detected with neoplasms of the pancreas and helminthiasis.

As a result of stagnation of bile, the bile capillaries are stretched, and the permeability of their walls increases. Not having an outflow into bile direct bilirubin enters the bloodstream and develops hyperbilirubinemia by increasing concentration direct bilirubin... The level in urine is sharply increased bilirubin(dark beer color) and reduced amount of urobilin, practically absent in feces stercobilin(grayish-white coloration).

In severe cases, due to the overflow of hepatocytes with direct bilirubin, its conjugation with glucuronic acid may be disrupted and the amount of unbound bilirubin in the blood will increase, i.e. joins hepatocellular jaundice.

Urine

Blockage of the extrahepatic biliary tract is the classic cause of bilirubinuria. The indicator is useful in the differential diagnosis of jaundice, since bilirubinuria is characteristic of obstructive and parenchymal jaundice (an increase in the level of bound bilirubin in the serum), but is absent in hemolytic jaundice. In hepatitis, bilirubin can be found in the urine before jaundice appears.

Amniotic fluid

Bilirubin is found almost exclusively in non-esterified form in combination with albumin and accumulates in erythroblastosis, infectious hepatitis and sickle cell crisis in the mother.

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Synonyms: Total bilirubin, direct bilirubin, indirect bilirubin, TBIL, DBIL, Total bilirubin, bound bilirubin, free bilirubin, unconjugated bilirubin

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Period of execution

The analysis will be ready within 1 day (except for the day of taking the biomaterial). You will receive the results by email. mail immediately when ready.

Deadline: 2 days, excluding Saturday and Sunday (except for the day of taking biomaterial)

Preparation for analysis

In advance

Do not take a blood test immediately after radiography, fluorography, ultrasound, physiotherapy.

The day before

24 hours before blood collection:

Limit fatty and fried foods, do not drink alcohol.

Eliminate strenuous physical activity.

From 8 to 14 hours before donating blood, do not eat, drink only clean, non-carbonated water.

On the day of delivery

Do not smoke 60 minutes before blood sampling.

Be calm for 15-30 minutes before taking blood.

Analysis Information

Indicator

Bilirubin is a bile pigment, 80% of which is formed in the liver and 19% in the spleen. Bilirubin is divided into direct - associated with glucuronic acid, and indirect (free), that is, insoluble in water and therefore precipitated. The combination of these two fractions is called total bilirubin.

Indirect bilirubin is toxic, while direct bilirubin is already detoxified and ready to be excreted in the bile. Only such indicators as total and direct bilirubin are amenable to laboratory diagnostics, and indirect bilirubin is calculated by subtracting the associated from the total.

Appointments

The ratio of the concentration of bound and free forms may indicate various disorders - obstruction of the biliary tract, hepatitis, neonatal jaundice, cirrhosis, liver cancer, and poisoning. At the same time, in children in the first days of life, these indicators can vary upward. This happens because babies are switching to an unusual diet for them.

Specialist

It is prescribed in a complex of biochemical studies or separately, by a therapist or hepatologist.

Important

Before the study for three to four days, you need to abandon the factors affecting the liver. It is not recommended to take alcohol, eat fatty foods.


Research method - Colorimetric photometric test, calculated

Research material - Blood serum

Composition and results

Bilirubin and its fractions: general, direct and indirect

Learn more about popular analyzes:

A comprehensive study that includes the determination of total bilirubin, direct bilirubin and the calculation of indirect bilirubin.

Interpretation of the results of the study "Bilirubin and its fractions: general, direct and indirect"

Interpretation of test results is for informational purposes only, is not a diagnosis and does not replace medical advice. The reference values ​​may differ from those indicated depending on the equipment used, the actual values ​​will be indicated on the results sheet.

Interpretation of research results should be carried out taking into account all indicators. For an accurate diagnosis of jaundice, it is also necessary to investigate the level of total and direct bilirubin, as well as the determination of the concentration of urobilinogen and bilirubin in the urine.

There are jaundice with an increase in the level of direct bilirubin, indirect and mixed forms. The reasons for the development of jaundice with an increase in the level of indirect bilirubin can be: overproduction of bilirubin by the reticuloendothelial system (for example, hemolysis), impaired transport of bilirubin or its consumption by hepatic cells, impaired binding of indirect bilirubin with transport proteins (Table 1).

If the consumption of bilirubin by hepatic cells is disturbed or its delivery to them, the concentration of indirect bilirubin usually does not exceed 68.4 μmol / l, therefore, by its higher figures, one can judge about the excessive formation of bilirubin, about the violation of the binding of bilirubin to proteins, or a violation of its excretion liver cells.

Bilirubin fraction

Factors leading to increased concentration

Factors leading to a decrease in concentration

Direct bilirubin

Liver lesions of infectious etiology, including viral hepatitis

Pathology of the biliary tract (cholangitis, cholecystitis, biliary cirrhosis, obstruction of the intrahepatic and extrahepatic bile ducts caused by cholelithiasis, tumor of the head of the pancreas, helminthic invasion)

Acute toxic hepatitis, taking hepatotoxic medications

Oncological diseases (primary hepatocarcinoma of the liver, metastatic liver damage)

Functional hyperbilirubinemia (Dabin-Johnson syndrome, Rotor syndrome)

Glucocorticoid hormones

Indirect bilirubin

Intravascular and extravascular hemolysis
Ineffective erythropoiesis
Gilbert's syndrome
Crigler-Nayyar Syndrome
Hepatitis, liver cirrhosis
Physiological jaundice of newborns
Sepsis
Prolonged fasting
Ultra-violet rays

Glucocorticoid hormones

Table 1. Factors affecting serum bilirubin concentration.

With combined disorders of consumption and excretion of bilirubin by hepatic cells, due to their generalized damage, mixed hyperbilirubinemia develops. With congenital anomalies, most often any one fraction of bilirubin (direct or indirect) increases, while the concentration of total bilirubin remains within the normal range (Table 2).

Table 2. Causes of congenital hyperbilirubinemia.

For the differential diagnosis of various forms of jaundice, the clinical picture of the disease, the age of the patient, the state of health and the nature of the accompanying symptoms are important. The pathogenetic classification of jaundice is presented in (Table 3).

Clinical conditions

Hyperbilirubinemia due to indirect bilirubin

I. Excessive production of bilirubin

A. Hemolysis (intra- and extravascular)

B. Ineffective erythropoiesis

II. Decreased uptake of bilirubin in the liver

A. Prolonged fasting

B. Sepsis

III. Impaired bilirubin conjugation

A. Hereditary glucuronyl transferase deficiency:

1. Gilbert's syndrome

2. Crigler-Najjar syndrome type II

3. Crigler-Najjar syndrome type I

B. Physiological jaundice of newborns

B. Acquired glucuronyl transferase deficiency:

1. Taking certain medications (for example, chloramphenicol)

2. Jaundice from breast milk

3. Damage to the liver parenchyma (hepatitis, cirrhosis)

Hyperbilirubinemia due to direct bilirubin

I. Impaired excretion of bilirubin into bile

A. Hereditary disorders:

1. Dabin-Johnson syndrome

2. Rotor Syndrome

3. Benign recurrent intrahepatic cholestasis

4. Cholestasis of pregnant women

B. Acquired violations:

1. Damage to the liver parenchyma (viral or drug hepatitis, liver cirrhosis)

2. Taking certain medications (oral contraceptives, androgens, chlorpromazine)

3. Alcoholic liver damage

5. Postoperative period

6. Parenteral nutrition

7. Biliary cirrhosis of the liver (primary or secondary)

II. Extrahepatic bile duct obstruction

A. Obturation:

1. Choledocholithiasis

2. Malformations of the biliary tract (strictures, atresia, cysts of the bile ducts)

3. Helminthiasis (clonorchiasis and other hepatic trematodes, ascariasis)

4. Malignant neoplasms (cholangiocarcinoma, cancer of the Vater papilla)

5. Hemobilia (trauma, tumors)

6. Primary sclerosing cholangitis

B. Compression:

1. Malignant neoplasms (cancer of the pancreas, lymphomas, lymphogranulomatosis, metastases to the lymph nodes of the liver hilus)

2. Benign volumetric formations of the pancreatoduodenal region (cysts, adenomas)

3. Inflammation (pancreatitis)

Table 3. Pathogenetic classification of jaundice (hyperbilirubinemia)

Measurement unit: μmol / l

Reference values:

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