Bilirubin fraction. Causes of increased bilirubin in the blood

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 results by email. email as soon as it's ready.

Preparation for analysis

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

24 hours before blood sampling:

Limit fatty and fried foods, do not take alcohol.

Eliminate heavy physical activity.

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

Do not smoke for 60 minutes prior to blood sampling.

15-30 minutes before blood sampling to be in a calm state.

Analysis Information

Index

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 neutralized and ready for excretion with bile. Only indicators such as total and direct bilirubin are amenable to laboratory diagnosis, and indirect is calculated by subtracting the associated from the total.

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

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

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

Research method - Colorimetric photometric test, calculated

Material for research - Blood serum

Composition and results

Bilirubin and its fractions: total, direct and indirect

Learn more about popular analyses:

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

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

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

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

There are jaundices with an increase in the level of direct bilirubin, indirect and mixed form. The reasons that develop jaundice with an increase in the level of indirect bilirubin can be: hyperproduction of bilirubin by the reticuloendothelial system (for example, hemolysis), impaired transport of bilirubin or its consumption by liver cells, impaired binding of indirect bilirubin to transport proteins (Table 1).

If there is a violation of the consumption of bilirubin by liver cells 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 the excessive formation of bilirubin, a violation of the binding of bilirubin to proteins, or a violation of its excretion hepatic cells.

Table 1. Factors affecting the concentration of bilirubin in blood serum.

With combined disorders of consumption and excretion of bilirubin by liver 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 differential diagnosis various forms of jaundice is important clinical picture diseases, age of the patient, state of health and the nature of the accompanying symptoms. The pathogenetic classification of jaundice is presented in (Table 3).

Table 3. Pathogenetic classification of jaundice (hyperbilirubinemia)

Unit: µmol/l

Reference values:

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Bilirubin is a red-brown bile pigment. It is a product of hemoglobin catabolism, formed in the liver. Bilirubin tests - The best way identify severe liver disease.

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

What is bilirubin, meaning

The bilirubin molecule consists of 4 pyrrole rings interconnected. The molecular weight of the molecule is 548.68. Pure bilirubin is a sparingly soluble crystalline substance.

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

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

The sum of fractions can give a generally normal value of total bilirubin, but it often happens that primary bilirubin is elevated, and associated is below normal. Such a 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 norms by age

Blood test for bilirubin

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

First of all, the doctor focuses on due to the universality 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 evaluates the work of the liver, pancreas and gallbladder. The special significance of the "bilirubin" indicator and its relationship with other blood characteristics will be confirmed by any medical forum with numerous questions on this topic.

Elevated bilirubin in the blood - what does it mean

If the results of the analysis show an increase in bilirubin in the blood, this may indicate 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 liver metastases from other organs;
• avitaminosis B12;
• injuries with multiple hematomas.

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

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

How is bilirubin related to other blood parameters

Bilirubin and hemoglobin. Hemoglobin and bilirubin are substances linked by a single 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 in the process of erythrocyte renewal into globin chains and heme, which, with the help of enzymes, is converted into poisonous indirect bilirubin.

Therefore, high levels of hemoglobin and bilirubin are indicative of hemolytic anemia or injuries with bruises and bruising with a large number of destroyed red blood cells. If low hemoglobin and high unconjugated bilirubin are observed, then the pathology may be associated with a lack of albumin, which is responsible for moving the yellow pigment to the liver.

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

Urinalysis for bilirubin: bilirubinuria

In healthy people, the bile pigment bilirubin may be contained in urine in small amounts and is not detected by standard laboratory methods. That's whynormal bilirubin in urineis the absence of bile pigment.

Elevated bilirubin in the urine

At various diseases direct and indirect bilirubin fractions can be found in urinary 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 occurs with the following diseases:

• various etiologies.
• Ga-nephropathy (Berger's disease)
• systemic lupus erythematosus;
• Schonlein-Henoch purpura
• nodular periarteritis;
• hemolytic uremic syndrome (HUS);
• idiopathic thrombocytopenic purpura (ITP).

The cause of increased direct bilirubin in urine is jaundice. A positive reaction is detected already in cases where bilirubin is contained in the blood within 30– 34 µmol/l. This indicates a violation of the excretion of bile in duodenum and exceeding the bilirubin norm in adults and children in plasma. If the blood test for bilirubin is normal, then 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:

How is bilirubinuria tested?

To determine bilirubin in the 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. Increased bilirubin in the urine causes the paper to stain in the form of multi-colored concentric rings, counting from the outside - green, blue, purple, red and in the center - yellow. Without a green ring, the sample is considered negative.

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

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

Urinalysis for the presence of this liver enzyme provides excellent opportunities:

• with early detection of hepatitis and differential diagnosis various kinds 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 harmful substances;
• as a rapid test for the condition of the liver in patients taking drugs that can cause disturbances in its activity.

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

Examination of feces for bilirubin

The bile pigment - bilirubin, is normally found only in the feces of very young children who are on breastfeeding. The presence of this pigment in the feces of the baby 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 in the feces should not be detected, although a small amount of this substance is sometimes observed in the feces during the first year of a child's life. This is due to the instability and underdevelopment of the microflora of the children's intestines.
• In adults in the coprogram, bilirubin readings should be negative. Its presence, especially in combination with a decrease in the concentration of stercobilinogen, indicates the presence of dysbacteriosis (explicit or latent) and the presence of pathogenic and microflora in the intestine.
• Another reason for the appearance of this substance in the feces is dyspepsia. In the event of gastrointestinal pathologies, accompanied by frequent stool disorders, 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 a violation of the digestion of food. In such cases, in biochemical analysis blood norm of bilirubin fractions is also increased.
• This substance may appear in the results of the coprogram when 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 be metabolized into stercobilin and stercobilinogen, and is found in feces. In this case, indirect bilirubin in the blood is often elevated.

How is bilirubin determined in feces?

The content of pigment bilirubin in the 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 a reagent is added drop by drop. In the presence of bilirubin traces, the test sample turns blue.

The sublimate reaction also makes it possible to 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 dichloride (sublimate) and left in a fume hood for a day. The presence of bilirubin in them is judged by the color of the feces. Normally, the biomaterial should turn pink or reddish, however, when positive reaction, the color of the stool is 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 decoding 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, its acute and chronic forms are distinguished.

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

Causes of hepatargia

• The condition is often a consequence of the development of viral hepatitis and cirrhosis of the liver. In this case, the presence of slowly progressive hepatargia 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 infection of a person with Epstein-Barr viruses, herpes, adenovirus, etc. When a woman is infected with cytomegalovirus, intrauterine infection of the fetus occurs and its death. In this case, total bilirubin is elevated during pregnancy.
• The most common cause of this condition is exposure to poisons and medicines. 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 acutely and is accompanied by nausea, vomiting, hemorrhagic syndrome, "liver" odor from the mouth, neuropsychiatric disorders, elevated bilirubin in the blood.
• Very often this condition is associated with the presence of malignant tumors in the body. In the liver, both the main focus can be located, and metastasis to this organ can be observed. With cancer, symptoms increase gradually, accompanied by 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 variant of "addiction". However, over time, still elevated bilirubin exceeds the norm many times over.

Symptoms of hepatargia

With this pathology gradually increase; jaundice, weight loss edema, fever, telangiectasia, and dull abdominal pain. "Liver signs" appear on the body: palmar erythema, hemorrhages, Chistovich's asterisks, 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, tremor of the fingers, impaired coordination. Analysis common blood and biochemistry show significant deviations from the norm.

With further progression of insufficiency, hepatic coma occurs. Its harbingers are: drowsiness, lethargy, skeletal muscle rigidity, confusion, muscle twitching, convulsions, uncontrolled urination. Very high levels of liver tests are observed in the blood. A blood test for total bilirubin can show up to 500 µmol / l. Patients who fall 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 elevated, 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 is physiological and pathological. With physiological jaundice, its manifestations disappear on their own and general state the newborn is not affected. The concentration of total bilirubin is normal in children in this case, it increases only due to its unbound fraction. To determine the degree of the problem in children, they take tests for bilirubin.

Severe physiologic jaundice

If the rate of free bilirubin is significantly exceeded, then the general condition of the child may suffer. Such babies are lethargic, lethargic, suck badly, they may have a fever and vomiting. However, the condition of the newborn should not be judged by these signs, but by the bilirubin index.

When the total bilirubin in newborns exceeds the norm significantly, the albumin produced by the children's liver cannot fully conjugate it and it enters the CNS through the blood-brain barrier. At the same time, this pigment, which is, in fact, a poison, has a toxic effect on the brain. As a result, the baby may subsequently develop paralysis, mental retardation, deafness and blindness.

Treatment of jaundice

In order to prevent such complications, in the case of severe and prolonged jaundice, specific treatment has to be carried out.

Previously, children were injected with various solutions to normalize bilirubin levels, but now this has been abandoned. Now light therapy is being carried out, during which the skin of the newborn is illuminated with a special installation. Under the influence of light, the pigment decomposes and is removed from the body. Neonatologists observe such children until direct bilirubin returns to normal. Most often, it is possible to normalize bilirubin in 9 days or less.

A great way to beat jaundice is to start breastfeeding your baby as early as possible, because colostrum helps to remove meconium and cleanse the intestines of the newborn.

It is noted that this condition is more often observed in children born prematurely, with multiple pregnancies and difficult births. Children prone to jaundice from mothers suffering from chronic diseases such as diabetes mellitus. Contrary to popular belief, the increased bilirubin level in the mother during pregnancy and the yellowing of the skin in the newborn baby are absolutely unrelated.

Bilirubin tests reveal pathological jaundice

This type of neonatal pathology 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 can be observed. Unlike physiological hyperbilirubinemia, with its pathological course, the norm of direct bilirubin in the blood is noticeably 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 mother and baby according to the group and Rh factor can cause hemolysis of red blood cells and icteric staining of the sclera of the newborn.
• Sometimes a child becomes infected with the hepatitis virus or protozoa from the mother and develops an infection. In this case, specific therapy is carried out for mother and baby, since the norm 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 by 6 or more times. Only surgeons can help here.
• There is a large group of hereditary hyperglobulinemias (Crigler-Najjar, Dubin-Johnson, Rotor syndromes), which are caused by genetic metabolic defects. In this case, you need to prepare for a long-term diagnosis and lifelong maintenance therapy.

To conduct a correct diagnosis of jaundice in newborns, and only a doctor can find out its cause. The diagnosis can be established only by the results of the tests.

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

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

For the study of 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 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 have high specificity and sensitivity;

3. Colorimetric diazo methods, are based on the interaction of bilirubin with diazotized sulfanilic acid to form azo pigments. Under the influence of acid, the tetrapyrrole structure of bilirubin is broken with the formation of two dipyrroles, the carbon atoms of the methylene groups enter into a direct reaction 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 the addition of 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 purple, in a slightly alkaline and weakly 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, the property of free bilirubin after absorption at 430 nm to emit light with a length of 520 nm is used. They allow to determine the concentration of unconjugated bilirubin and, after treatment with 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 Jendrassik-Cleggorn-Groff method for diazoreaction in an alkaline or slightly acidic environment in the presence of an accelerator.

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

Principle

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

Normal values

Influencing factors

Overestimated 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 its binding by the elastic fibers of the skin and conjunctiva, which manifests itself in the form of jaundice. For differential diagnosis of jaundice, it is necessary to determine which fraction causes bilirubinemia:

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

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

In newborns, hemolytic jaundice may 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: the extraction of bilirubin from the blood by liver cells, its conjugation and secretion into bile. It is observed in viral and other forms of hepatitis, cirrhosis and tumors of the liver, fatty degeneration, in case of poisoning with toxic hepatotropic substances, in congenital pathologies.

Since all reactions of bilirubin conversion do not pass sufficiently in the liver, hyperbilirubinemia develops due to both factions, predominantly 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.

Determined in urine bilirubin(color of strong black tea), moderately increased concentration urobilin, level stercobilin feces are normal or reduced.

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

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

As a result of stagnation of bile, the bile capillaries stretch, and the permeability of their walls increases. Having no outflow to bile direct bilirubin enters the bloodstream and develops hyperbilirubinemia by increasing the concentration direct bilirubin. Levels in the urine are sharply increased bilirubin(the color of dark beer) and the amount of urobilin is reduced, practically absent in feces stercobilin(greyish-white coloration).

In severe cases, due to the overflow of hepatocytes with direct bilirubin, its conjugation with glucuronic acid may be impaired 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 (increased levels of conjugated bilirubin in serum), but is absent in hemolytic jaundice. In hepatitis, bilirubin can be detected in the urine before jaundice appears.

amniotic fluid

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

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Determination of the level of bilirubin in the blood is carried out when detecting a violation of the functioning of the liver and bile ducts, as well as anemia (anemia). A high level of bilirubin is an important diagnostic indicator that indicates a number of serious pathologies. Moreover, each of these pathologies requires the selection of certain methods of treatment. It is important not only to establish the fact of the presence of the disease, but also to differentiate it as soon as possible. The prognosis of the outcome largely depends on how quickly the correct diagnosis was made.

First you need to understand what is bilirubin and where does it come from?

Bilirubin is a yellow-brown pigment that is formed as a result of the breakdown of proteins containing heme (hemoglobin in erythrocytes, myoglobin and cytochrome). The pigment colors bile, urine and feces in the appropriate color.

The functions of bilirubin are not fully understood. According to the main hypothesis, it performs the function of the strongest antioxidant. Its role is reduced to the inhibition of the oxidation process, which is subjected to natural human waste products and nutrients that enter the body with food. It is believed that antioxidants can slow down the aging process by activating cell renewal processes.

The total pigment fraction is divided into direct and indirect bilirubin. The indirect fraction predominates in the blood (up to 96%) - rhombic crystals connected to simple protein molecules (albumins). In the case of addition of sugar-containing substances (glucuronic acid) in the liver, direct (bound) bilirubin is formed, its concentration normally does not exceed 4% of the total fraction. The direct form of bilirubin, unlike the indirect fraction, is soluble in water and can be excreted in the urine after filtration by the kidneys.

The norm of bilirubin in adults differs significantly from children, so it is extremely important to consider age when interpreting the results of the analysis. It should be noted that the value of normal bilirubin levels is identical for patients of both sexes.

The value of the indirect fraction is determined by calculation by subtracting the value of the direct fraction from the total content of bilirubin.

Main stages of bilirubin metabolism

Hemoglobin breaks down to bilirubin in the cells of the reticuloendothelial tissue. You can visually observe the process with the transformation of the shade of subcutaneous bruising (bruises). Up to 4 days, the affected area has a purple-blue or dark blue color. After 4-7 days, biliverdin and green verdoglobin are formed at the site of the bruise. After 4 weeks, the bruise acquires a dirty yellow color due to the synthesis of bilirubin.

The decay products of hemoglobin (indirect fraction) enter the human systemic circulation. Further metabolism is realized in the liver and consists of 3 stages:

• absorption from the blood of the indirect fraction by the epithelial cells of the liver parenchyma;
• binding of the indirect fraction with sugar-containing substances in the endoplasmic reticulum (ER) of the cell;
• release of direct bilirubin from EPS into bile.

It is noted that a large concentration of the indirect fraction has toxic properties.

Due to the high degree of affinity for organic compounds, the indirect fraction is able to dissolve in the lipid component of the cell membrane. After entering the cell, it is introduced into the mitochondria, disrupting the process of respiration and oxidative phosphorylation. In addition, there is a failure of the normal biosynthesis of peptide molecules and ion transport through the cell membrane. Such disorders negatively affect the state of the human nervous system, provoking the development of neurological symptoms.

The indirect fraction is able to penetrate the blood-brain barrier between the nervous and circulatory systems, inducing organic damage to the brain. Such serious pathologies explain the importance of the normal course of the process of transformation of the indirect fraction into a direct one.

Symptoms of increased bilirubin

The severity of symptoms directly depends on the degree of increase in total bilirubin in the blood. The clinical picture with elevated bilirubin at the initial stage is characterized by the appearance of an icteric shade of the sclera of the eyes (jaundice). Subsequently, the symptom spreads to the oral cavity, and with critical increases in the amount of pigment - to the entire face, feet, palms and various parts of the body. Often, the affected areas are very itchy.

It should be noted that a similar picture is also characteristic of a violation of the metabolism of carotene and excessive consumption of vegetables (tomatoes, carrots). However, in this case, the whites of the eyes are not stained.

Often, elevated bilirubin is the cause of pain and heaviness in the hypochondrium on the right, discoloration of feces and urine.

A referral for analysis can be issued by a general practitioner, gastroenterologist, hematologist, endocrinologist or infectious disease specialist. Indications for appointment:

• suspicion of pathology of the liver and bile ducts;
• the need for examination of infants with jaundice;
• jaundice in adults;
• hereditary jaundice (syndrome) Gilbert;
• signs of hemolytic anemia;
• diagnosis of patients who abuse alcohol;
• the need for early detection of side effects of drugs with hepatotoxic or hemolytic properties;
• chronic hepatitis in history;
• liver pathology (cirrhosis, liver failure, stones in the bile ducts).

Bilirubin is generally elevated - what does it mean in an adult how to treat?

If direct bilirubin is slightly elevated (no more than 5 µmol/l), a second study is prescribed after 3-5 days in order to exclude internal and external factors that affect the result. For example, the daily fluctuation of all laboratory blood parameters or the neglect of the subject of the rules for preparing for the collection of biomaterial.

So, bilirubin in the blood - 3 is considered a slight downward deviation, which may be caused by the recent use of alcohol, large amounts of coffee or medications.

Treatment of any pathology is the task of a doctor. Self-diagnosis and independent choice of methods of therapy can lead to a worsening of the disease, up to a fatal outcome.

The reasons why total bilirubin is elevated are different and are always pathological. Of particular importance in differential diagnosis is which fraction exceeds the norm.

What does it mean if an adult has increased direct bilirubin?

The reasons for the increase in the value of total bilirubin in the blood, mainly due to the direct fraction, include:

• cholidocholithiasis- a pathological condition that occurs with cholelithiasis. It manifests itself in the form of the formation of stones that clog the lumen of the bile ducts. The importance of early detection is due to frequent complications. Lack of adequate treatment contributes to the development of cirrhosis, pancreatitis or pancreatic necrosis. The preferred method of treatment is endoscopic or liparoscopic stone removal. Recurrence in 25% of cases within 5 years. Reoperation is accompanied by removal of the gallbladder;
• hepatitis C- an infectious disease that provokes inflammation of the liver. According to statistics, 150 million people are infected with the hepatitis C virus. It is called the "gentle killer" because the patient may not know about the infection for a long time. The patient can live up to 40 years without the manifestation of serious pathological signs. The prognosis depends on the presence of concomitant diseases. Thus, HIV-positive status significantly increases the risk of developing cirrhosis or liver cancer;
• primary sclerosing cholangitis- a rather rare pathology in which the tissues of the bile ducts become inflamed and grow. The outcome is biliary cirrhosis, accompanied by impaired immune regulation. In this case, the immune system begins to destroy its own normal cells of the bile ducts, perceiving them as genetically alien material (antigens);
• malignant neoplasms in the pancreas;
• Dubin-Johnson syndrome- non-violation of the process of release of the bound fraction from the liver cells, as a result, its abnormal movement in the opposite direction occurs. In other words, bilirubin is not excreted from the liver, but on the contrary, it comes from the bile ducts into it. Pathology is genetic in nature and manifests itself in the form of chronic jaundice. The prognosis of the disease is extremely favorable, since it does not affect life expectancy in any way;
• Rotor syndrome- similar to the previous disease, however, has a less pronounced degree of severity;
• alcoholic liver disease- violation of the normal functioning of liver cells due to long-term (more than 10 years) intoxication with alcohol and its decay products. Possible consequences: alcoholic hepatitis, cirrhosis, cancer and fatty liver.

Increase in total bilirubin due to indirect fraction

List of diseases accompanied by high levels of indirect bilirubin in the blood:

The reasons for the increase in total bilirubin in the blood, while the direct and indirect fractions are increased in equal proportions, are:

• hepatitis of a viral or toxic (alcohol or drugs) nature;
• liver cirrhosis;
• infection with the herpes virus type 4, which is characterized by an increase in body temperature, damage to the liver and spleen, as well as a change in the cellular composition of the blood;
• damage to the liver by a tapeworm (echinococcosis). Once in the liver, the larvae begin to form echinococcal cysts in the form of blisters, reaching sizes up to 20 cm. The slow growth of cysts makes it difficult to detect infection earlier, and if they rupture, the larvae spread throughout the body;
• liver abscess - the formation of a cavity with pus in the organ, is a consequence of appendicitis, cholelithiasis or sepsis. In 90% of cases, with a competent approach to treatment, it is possible to achieve a complete recovery.

Summing up

It should be noted:

• a direct relationship between the severity of the pathology and an increase in the amount of bilirubin was not revealed;
• an increase in any of the fractions of bilirubin is always a sign of pathology and requires immediate clarification of the diagnosis. The patient is assigned a comprehensive examination using ultrasound methods and additional tests;
• it is important to properly prepare for the delivery of biomaterial, since many factors distort the accuracy of the results obtained. So, 1 day before the study, an intravenous contrast agent should not be administered. It should be borne in mind that UV and fatty foods reduce the concentration of bilirubin in the blood. And physical or emotional overload, as well as nicotine, lead to an increase. At least 3 days in advance, you need to stop using any medications, since many of them have a direct effect on the metabolism of bilirubin.

Bilirubin refers to substances involved in the pigment metabolism of the body. It is formed from the breakdown products of red blood cells. An increase in the amount of bilirubin in the blood is called hyperbilirubinemia and occurs in certain types of diseases associated with impaired liver function. Outwardly, in a patient, an increase in the content of this pigment is manifested by jaundice.

Where does bilirubin come from in the blood?

Erythrocytes, red blood cells live on average for about 4 months, after which they are destroyed in the organs of the reticuloendothelial system (most of all in the spleen, less in the liver and bone marrow). Approximately 1% of red blood cells are degraded per day. In the process of decomposition, hemoglobin is released - a protein pigment in the blood, which undergoes further decay with the formation of verdoglobin. Protein is split off from it - globin and iron, resulting in biliverdin, which is restored to bilirubin - an orange pigment, which enters the bloodstream. RBC decomposition reactions release approximately 300 mg of bilirubin. Thus, about 85% of bilirubin appears in the blood, 15% is formed during the breakdown of other substances containing hemes (organic compounds in iron) - myoglobins, cytochromes.

Stages of bilirubin formation

After the breakdown of an erythrocyte, bilirubin goes through the following stages of changes:

• Initially, it is free (free bilirubin) and practically insoluble in water (hence the name - insoluble), forms a complex with proteins and circulates in the blood. Its second name - "indirect bilirubin", because it is not capable of producing the so-called direct Van den Berg reaction. This type of bilirubin is highly toxic to the body and cannot be excreted by the kidneys.
• Indirect bilirubin in the liver cells is neutralized by binding to glucuronic acid (conjugation), and forming a new form called bilirubin glucuronide. This type of bilirubin is already able to dissolve well ( soluble), does not have toxic properties and is able to be excreted with bile into the intestinal lumen. Gives a direct Van den Berg reaction, hence the name "straight" bilirubin.
• With bile (excretion), bilirubin enters the intestinal lumen, where it is restored to stercobilinogen. Part of it is transformed into stercobelin and excreted in the feces (from 50 to 300 mg). It is this pigment that colors the feces in a dark color. The main part of stercobilinogen is absorbed into the bloodstream and enters the kidneys, where it passes into urobilinogen, which changes into urobilin and is excreted in the urine, staining it in a specific straw color. The amount of urobilin excreted by the kidneys is approximately 4 mg per knock.

Indirect bilirubin is constantly converted into a direct form.

The blood contains and evaluates bilirubin of two types:

• indirect (free, unconjugated, insoluble) - toxic. Appears immediately after the breakdown of red blood cells. Normally, its content does not exceed 17 µmol/l;
• direct (bound, conjugated, soluble). Formed in cookies after combining with glucuronic acid. It is already non-toxic and harmless to the body. Normally contains up to 2.5 µmol/l;

Total bilirubin is also isolated. The norm of content in the blood is about 20 µmol / l.

Various pathological conditions can cause an increase in the total content of bilirubin - hyperbilirubinemia, which is accompanied by jaundice. Depending on the cause of the disease process, an increase in bilirubin occurs due to its direct or indirect fractions.

Important:in severe cases, the numbers of bilirubin are several tens of times higher than the norm, which indicates the need for immediate assistance to such patients.

The doctor tells about the problem of increasing bilirubin in infants:

What are pigment metabolism disorders associated with?

The exchange of pigments can be disturbed for the following reasons:

• the impossibility of the free fraction of bilirubin from the blood to the liver cells;
• decrease in the transition (conjugation) of free bilirubin to bilirubin glucuronide;
• decrease in the release of direct bilirubin from the liver cells into the bile.

Any kind of metabolic disorders leads to an increase in bilirubin in the blood. Patients with this problem develop icteric coloration of the skin and sclera of the eye. At the beginning, the face turns yellow, then the palms of the hands, soles and the rest of the skin surface. The intensity of jaundice may depend on the appearance of the patients. In overweight people, it is less noticeable, and in people of thin build, it comes out more clearly.

But you should not call any discoloration of the skin jaundice, since the causes of discoloration of the skin are different, for example, when eating foods high in carotene (carrots). Also, skin color can change in diseases that are not related to problems of pigment metabolism (pathology of the thyroid and pancreas). A distinctive feature in this case is the normal color of the sclera.

Note: bilirubin is able to accumulate in the nervous system, cause poisoning (intoxication). Also in this case, the balance of the ratio of direct and indirect bilirubin is disturbed.

What does "increased bilirubin" mean, what causes this condition

What processes occur in the body, why does the normal metabolism suddenly change?

High bilirubin occurs when:

• Pathological processes leading to increased breakdown of red blood cells (hemolysis). Arises suprahepatic jaundice or hemolytic. This type of disorder can be caused by various types of anemia (anemia), infectious diseases, toxic lesions, a group of hereditary jaundices (, Dubin-Jones, Crigler-Nayar, Rotor), taking antibiotics, hormones, anti-inflammatory drugs.

The liver does not have time to "utilize" large amounts of indirect bilirubin and convert it into direct. An excess amount of indirect bilirubin accumulates in the blood. The content of urobilin in the urine, stercobilin in the feces increases.

• Infectious inflammation of the liver (hepatitis), cirrhotic processes causing damage to liver cells (hepatocytes). In these cases, it develops hepatocellular jaundice. In damaged liver cells, indirect bilirubin does not turn into direct bilirubin. Increased membrane permeability of hepatocytes promotes the release of indirect and direct bilirubin into the blood. Stercobilin in the feces decreases, so the color of the stool becomes light. Also, as a result of insufficiency of the enzyme that converts indirect bilirubin into direct, an increase in total bilirubin in the blood due to the indirect fraction is observed. In the urine, the content of bilirubin and urobilin increases.

• Congestion in the bile ducts, in violation of the normal outflow due to blockage of the duct by stones, a tumor, due to edema during inflammation. At the same time, the bile vessels swell, their permeability increases, and direct bilirubin goes directly into the blood, obstructive jaundice.
• Insufficient intake of cyanocobalamin in the body(vitamin B12);

A detailed classification of jaundice is given in the video review:

Features of increased bilirubin in children

In childhood, jaundice appears more often. This is due to the fact that the infant has a large number of red blood cells. After childbirth, hemolysis is much faster than before childbirth. The neutralizing function of the liver is still imperfect. The child has high bilirubin with external manifestations of icteric skin coloration.

Children have some features of bilirubin metabolism. The occurrence of conjugative jaundice caused by inadequate binding of the free fraction of bilirubin leads to its accumulation in the blood. This condition occurs in 80% of newborns and is called physiological jaundice. It manifests itself after 3 days from the moment of birth and lasts about 2 weeks. Jaundice gradually spreads to the face, trunk, arms, legs, mucous membranes of the mouth, nasopharynx and conjunctiva of the eyes.

The level of bilirubin becomes maximum at the end of the first week and reaches values ​​from 140 µmol/l to 240 µmol/l. Jaundice appears more often in children born with prematurity. Its duration in this case can be delayed up to 4-5 weeks.

If from birth there is a deficiency of the enzyme glucuronyl transferase, then children develop a rare disease called congenital non-hemolytic hyperbilirubinemia with kernicterus. The numbers of bilirubin in the blood can reach 200-800 µmol / l. The norm of bilirubin content in a newborn is 51-60 µmol/l.

In some cases, there is a genetic link to glucuronyltransferase deficiency. The uptake of free bilirubin by liver cells is impaired. Indirect bilirubin is kept at the level of 80-140 µmol/l.

In older children, bilirubin values ​​​​increase against the background of taking antibiotics, hormonal drugs, sulfanilamide drugs, non-specific infections that cause other diseases.

What to do to reduce bilirubin

In any case, if signs of icteric staining of the skin and sclera appear, you should immediately consult a doctor.

Important:you can not self-medicate and use drugs and traditional medicine until the cause of jaundice and an increase in bilirubin are established, especially in young children.

In case of detection of infectious hepatitis, toxic liver damage, hospitalization and treatment with the introduction of detoxification solutions will be required.

The patient needs to create an adequate drinking regimen, apply dietary nutrition, limit physical activity.

Stepanenko Vladimir, surgeon