Bilirubin metabolism. Hyperbilirubinemia of newborns. Physiological hyperbilirubinemia of newborns

A man with lemon-yellow skin and the same whites of his eyes evokes surprise, if not horror. This condition is popularly called jaundice; in medicine there is a term for it “hyperbilirubinemia”.

Hyperbilirubinemia can often be overcome only with the help of special treatment. But this is not an independent disease, but a symptom of many pathologies in the body.

Bilirubin (Bi), a bile pigment, is to blame for this disorder, the increase of which has characteristic signs. The most common hyperbilirubinemia is benign, in newborns. The causes and treatment of these and other cases of increased bilirubin are described below.

Is hyperbilirubinemia dangerous? What it is? To answer these questions, you need to understand the concept of “bilirubin”.

The average lifespan of an erythrocyte is one hundred and ten days. After this period, it ages and collapses. Hemoglobin emerges from the structure of the blood element. It binds to plasma haptoglobin and forms a complex with it. This compound does not pass through kidney filters. Therefore, all hemoglobin released from the erythrocyte structure undergoes a series of transformations and oxidations, resulting in the formation of the green pigment biliverdin, which is subsequently reduced into red-yellow bilirubin of bile.

Over the course of a day, a person produces about three hundred milligrams of this substance as a result of such destruction. It is poorly soluble in water, toxic and gives an indirect reaction with diazoreagent (a mixture used in the study of pigment metabolism) in the presence of caffeine. This is free, unconjugated or indirect bilirubin.

Its further transformations lead to combination with albumin in the blood plasma. This complex does not penetrate tissues well, but when all the possibilities of whey protein are exhausted, it can enter from the bloodstream into the organs and systems of the body (for example, into the nervous system, causing its damage, including kernicterus).

Bilirubin combined with albumin, due to the inability to be dissolved in water, cannot be excreted in the urine. It is removed from the plasma only by the liver. This is a complex process consisting of three stages:

• release from the complex with albumin and accumulation in hepatocytes (liver cells);
• connection with glucuronic acid (conjugation or ester formation);
• excretion into bile.

Each of these reactions is carried out by special mechanisms, the insufficiency of which leads to the development of an independent pathological syndrome associated with hyperbilirubinemia and requiring specific treatment.

The connection of Bi with glucuronic acid occurs in liver microsomes with the participation of the enzyme UDP-glucuranyltransferase. This process can be divided into the following sequential stages:

1. Bilirubin monglucuraninide is formed in hepatocytes.
2. In the bile canaliculi, a second molecule of glucuronic acid joins this formation, resulting in the formation of Bi-diglucuranide. It reacts with diazo mixture even without caffeine reagent. It is direct, bound or conjugated bilirubin. In bile, its concentration increases a thousand times compared to plasma.

   Glucuranides are a universal enzymatic system with the help of which they are excreted from the body. medicinal substances, hormones, products of decay in the intestines. They dissolve well in water, so they are excreted by the kidneys into the urine.

3. Next, the pigment combines with bile acids, cholesterol, lecithin and proteins.
4. Further transformations occur in the intestines, where a certain amount is absorbed in the form of urobilinogen and returned to the liver.
5. The other part in the colon is converted into strecobylenogen and is excreted from the body, coloring the stool.
6. A little stercobelinogen enters the kidneys through the hemorrhoidal veins, bypassing the liver, and is excreted in the urine.

Disturbance at any stage of these transformations leads to a pathology of pigment metabolism, one of the symptoms of which is hyperbilirubinemia, which occurs in many serious illnesses. Most of them require serious treatment. Normally, the concentration of total bilirubin in the blood ranges from 8 to 20 µmol/l. A condition from 20 to 27 µmol/l is considered borderline.

Hyperbilirubinemia is an increase in bilirubin in the blood serum above 27-35 µmol/l.

A slight increase in this indicator does not in any way affect the patient’s well-being. But higher concentrations of this pigment lead to significant deterioration in a person’s condition, changes in the color of the skin and discharge. Such conditions force a person to seek qualified treatment.

Benign hyperbilirubinemia (also functional) most often has a hereditary nature and is more pronounced in representatives of the stronger half of humanity.

Among such disorders are Dubin-Johnson and Rother syndromes. Some experts consider these conditions not diseases, but simply individual characteristics of the body.

Disorders that occur in the body of patients suffering from congenital syndromes Dubin-Johnson and Rotor have a similar character. These processes are also innate. Mostly men suffer. Direct (benign) hyperbilirubinemia is noted. Bilirubin increases from 28 to 74 µmol/l. The patient's general condition does not suffer significantly.

Among the disorders of pigment metabolism can be called conjugative (transient) hyperbilirubinemia, which occurs more often in newborns. It is associated with the failure and immaturity of the binding capacity of the liver.

Hereditary congenital pathology of pigment metabolism is also conjugative (functional) hyperbilirubinemia.

• Men suffer more often. The indirect fraction increases. The Bi level does not exceed 50-70 µmol/l. But, unlike, there are no signs of hemolysis of red blood cells. The patient may not even realize that he is sick, so the disease does not make itself felt until the second or third decade of life. The disease is benign, but during periods of exacerbation a slight deterioration in well-being is possible:
• bitterness in the mouth;
• irritability;
• sleep disturbance;
• weakness;

slight itching of the skin. A person practically does not need treatment, but must reconsider his lifestyle (exclude drinking alcohol, smoking, strong physical exercise

), stick to a diet.

Congenital disease has the same principle, but the prognosis of the disease is unfavorable. The pathology is based on a congenital defect of the enzyme UDP-glucuranyltransferase, which leads to the inability of the liver to convert indirect bilirubin into direct bilirubin.

The disease begins to progress on the third to seventh day of the patient's life and leads to death in infancy.

In case of cholelithiasis or cancer of the head of the pancreas, one has to deal with obstructive hyperbilirubinemia, when a stone or an overgrown tumor completely or partially closes the bile duct. The flow of bile into the intestines stops. Stercobelinogen is not formed, which leads to stool discoloration. The liver works normally, and the resulting bilirubin enters the blood in excess, and from the blood vessels into the urine. It darkens, and Bi is detected in the laboratory.

Causes of hyperbilirubinemia

• blood diseases (anemia), when the number of non-viable red blood cells increases sharply;
• increased lysis of red blood cells (this may also be a physiological condition - benign hyperbilirubinemia of newborns);
• pathologies of an immune nature (immunity becomes mistakenly aggressive towards normal red blood cells) - hemolytic disease of newborns, Rh conflict between the maternal and child organisms;
• effects of toxic and chemical substances on normal blood cells;
• hepatitis;
• if there is a violation of the outflow of bile: dyskinesia of the biliary tract, disruption of the pancreas, tumors;
• hypovitaminosis B12, pathological effects of medications, alcohol, infectious agents;
• congenital anomalies and genetic disorders (Gilbert, Crigler-Noyard, Dubin-Johnson, Rotor syndrome).

Symptoms of hyperbilirubinemia

What is hyperbilirubinemia and how does it manifest? Its symptoms are typical, but treatment depends on the reasons that led to this pathology.

1. The main and main sign of hyperbilirubinemia is skin color and eye whites in yellow color.
2. If direct hyperbilirubinemia is observed, then symptoms such as changes in the color of stool and urine are characteristic.
3. If the pigment concentration is low, then there may not be a deterioration in health. But usually mild forms are characterized by symptoms: general weakness, nausea, vomiting, loss of appetite.
4. There may be heaviness or Blunt pain in the right hypochondrium.
5. There is often a metallic taste in the mouth.
6. A common symptom is itchy skin.
7. In the absence of proper treatment, body weight decreases.

Treatment of hyperbilirubinemia

How is hyperbilirubinemia treated? The reasons for its occurrence are what doctors primarily struggle with. Therapeutic procedures are aimed at eliminating the factors that caused the disorder:

• antiviral and antibacterial agents;
• - substances that allow hepatocytes to maintain the necessary activity and viability;
• choleretic drugs;
• detoxification treatment is carried out to reduce or completely eliminate toxic effects excess bilirubin in the body;
• immunomodulators - to stimulate the body's immune system;
• prescribe barbiturates that have the ability to eliminate hyperbilirubinemia;
• enterosorbents are necessary to cleanse the intestines of bilirubin;
• phototherapy for hyperbilirubinemia - treatment using blue and ultraviolet lamps, the light of which can destroy excess bilirubin accumulated in tissues (do not forget about eye protection!);
• vitamin therapy;
• enzymatic agents - to stimulate digestion;
• avoid strenuous physical activity;
• exclude fatty, salty, smoked, fried foods from the diet (table No. 5), eat small meals (at least 5 times a day).

Hyperbilirubinemia in newborns

The norms for all laboratory parameters in newborns are somewhat different from the usual norms in children of other age groups. What is the cause of hyperbilirubinemia in newborns?

The body of a newborn person must adapt to life outside the womb of the mother. And this adaptation does not always happen favorably.

Normally, on the third day of a child’s life, bilirubin levels can increase to 190 µmol/l. This is transient hyperbilirubinemia or physiological benign jaundice of newborns.

It has no symptoms other than increased bilirubin and does not require any treatment.

This condition is caused by the accelerated breakdown of red blood cells (their lifespan in newborns is much shorter). Enzymatic reactions during this period, on the contrary, are somewhat slowed down, and the low content of albumin in the blood serum leads to limited transfer of bilirubin from tissues to the liver.

If hyperbilirubinemia in newborns is considered a physiological process, what are experts afraid of, why is so much attention paid to this problem? With jaundice that occurs during the newborn period, indirect bilirubin increases, which is toxic. At high enough numbers, it does not just cause disruption general well-being, but also dangerous for the health and life of the person born.

When the concentration of Bi in the blood serum increases to 500 µmol/l and above, the development of nuclear jaundice (destruction of brain cells) is possible, which cannot be treated and leads to death. The risk of developing hemolytic jaundice is especially high in premature babies, in whom most organs and systems (including the liver) are not yet ready to exist outside the mother’s body.

There is a high risk of developing pathological hyperbilirunemia with Rh and group incompatibility of mother and fetus. The body of a Rh-negative woman perceives a child with a positive Rh factor as a foreign body.

The blood of a woman with the first blood group does not have antigens A and B, and if her child is born with other blood groups, her body also reacts negatively to such a fetus.

The situation is complicated by the fact that in both cases, antibodies are produced in the woman’s milk, which are dangerous for newborns. Although the symptoms of such hyperbilirubinemia are obvious, the incompatibility must be confirmed by laboratory testing. After all, if the result is positive, the child is weaned and appropriate treatment is given, after which the baby’s health is usually restored.

Hyperbilirubinemia during pregnancy

Pregnancy is a serious test for the body. During this period, a woman’s immunity may weaken, which makes the expectant mother more vulnerable to various infections, as well as exacerbations of existing chronic processes.

Hyperbilirubinemia during pregnancy is quite common - 1:1500 cases. She may have different manifestation: persist for a long period of time or occur in waves. Hyperbilirubinemia that occurs during pregnancy is usually divided into two groups:

• associated with pathological conditions of pregnancy;
• arising due to infections and processes independent of future motherhood.

The first group of conditions accompanied by hyperbilirubinemia is associated with complications of pregnancy itself: early and late toxicosis, cholestasis and acute fatty degeneration.

But jaundice in an expectant mother may have causes of the second group: infection with hepatitis viruses A, B, C, D, E, pathogens of yellow fever and other dangerous infections, possible exacerbation of a long-dormant disease, including hereditary ones, which requires qualified treatment.

Forecast

Not a single disease goes away without leaving a trace on the body. But the liver is an organ that can take quite a long time to recover. With timely seeking medical help, appropriate treatment and compliance with all doctor’s instructions for many pathologies accompanied by hyperbilirubinemia, symptoms may disappear and full recovery.

But preventive examinations and monitoring of the condition of the liver are necessary for a long period after the disappearance of hyperbilirubinemia, symptoms and treatment.

In the case of hereditary diseases, a complete recovery is impossible, but a person can live a full life if he is treated and treated in a timely manner. healthy image life.

Hyperbilirubinemia often has the following consequences:

At the slightest suspicion of liver disease, you should contact medical institution for qualified treatment.

– a physiological or pathological condition caused by hyperbilirubinemia and manifested by icteric discoloration of the skin and visible mucous membranes in children in the first days of their life. Jaundice of newborns is characterized by an increase in the concentration of bilirubin in the blood, anemia, icterus of the skin, mucous membranes and sclera of the eyes, hepato- and splenomegaly, in severe cases– bilirubin encephalopathy. Diagnosis of jaundice in newborns is based on visual assessment of the degree of jaundice using the Cramer scale; determining the level of red blood cells, bilirubin, liver enzymes, blood type of mother and child, etc. Treatment of jaundice in newborns includes breastfeeding, infusion therapy, phototherapy, and replacement blood transfusion.

General information

Neonatal jaundice is a neonatal syndrome characterized by a visible icteric discoloration of the skin, sclera and mucous membranes due to increased levels of bilirubin in the baby’s blood. According to observations, in the first week of life, neonatal jaundice develops in 60% of full-term and 80% of premature infants. In pediatrics, physiological jaundice of newborns is the most common, accounting for 60–70% of all cases of the syndrome. Neonatal jaundice develops when bilirubin levels increase above 80-90 µmol/l in full-term infants and more than 120 µmol/l in premature infants. Prolonged or severe hyperbilirubinemia has a neurotoxic effect, i.e. causes brain damage. The degree of toxic effects of bilirubin depends mainly on its concentration in the blood and the duration of hyperbilirubinemia.

Classification and causes of jaundice in newborns

First of all, neonatal jaundice can be physiological and pathological. Based on the origin, newborn jaundice is divided into hereditary and acquired. Based on laboratory criteria, i.e., an increase in one or another fraction of bilirubin, a distinction is made between hyperbilirubinemia with a predominance of direct (bound) bilirubin and hyperbilirubinemia with a predominance of indirect (unbound) bilirubin.

Conjugation jaundice of newborns includes cases of hyperbilirubinemia resulting from reduced clearance of bilirubin by hepatocytes:

• Physiological (transient) jaundice of full-term newborns
• Jaundice of premature newborns
• Hereditary jaundice associated with Gilbert, Crigler-Najjar syndromes types I and II, etc.
• Jaundice due to endocrine pathology (hypothyroidism in children, diabetes mellitus in the mother)
• Jaundice in newborns with asphyxia and birth trauma
• Pregnane jaundice of breastfed children
• Drug-induced jaundice of newborns, caused by the administration of chloramphenicol, salicylates, sulfonamides, quinine, large doses of vitamin K, etc.

Jaundice of mixed origin (parenchymal) occurs in newborns with fetal hepatitis caused by intrauterine infections (toxoplasmosis, cytomegaly, listeriosis, herpes, viral hepatitis A), toxic-septic liver damage due to sepsis, hereditary metabolic diseases (cystic fibrosis, galactosemia).

Symptoms of newborn jaundice

Physiological jaundice of newborns

Transient jaundice is a borderline condition in the neonatal period. Immediately after the baby is born, excess red blood cells containing fetal hemoglobin are destroyed to form free bilirubin. Due to the temporary immaturity of the liver enzyme glucuronyl transferase and intestinal sterility, the binding of free bilirubin and its excretion from the newborn’s body in feces and urine is reduced. This leads to the accumulation of excess bilirubin in the subcutaneous fat and discoloration of the skin and mucous membranes yellow.

Physiological jaundice of newborns develops on days 2-3 after birth, reaching its maximum on days 4-5. Peak concentration not direct bilirubin averages 77-120 µmol/l; urine and feces are normal in color; the liver and spleen are not enlarged.

For transient jaundice of newborns mild degree yellowness of the skin does not extend below the umbilical line and is detected only with sufficient natural light. With physiological jaundice, the newborn’s well-being is usually not affected, but with significant hyperbilirubinemia, sluggish sucking, lethargy, drowsiness, and vomiting may occur.

In healthy newborns, the occurrence of physiological jaundice is associated with temporary immaturity of liver enzyme systems, and therefore is not considered a pathological condition. When monitoring a child, organizing proper feeding and care, manifestations of jaundice subside on their own by the age of 2 weeks in newborns.

Jaundice of premature newborns is characterized by an earlier onset (1–2 days), reaching a peak of manifestations by the 7th day and subsiding by three weeks of the child’s life. The concentration of indirect bilirubin in the blood of premature infants is higher (137-171 µmol/l), its increase and decrease occurs more slowly. Due to the longer maturation of liver enzyme systems, premature babies are at risk of developing kernicterus and bilirubin intoxication.

Hereditary jaundice

The most common form of hereditary conjugative jaundice of newborns is constitutional hyperbilirubinemia (Gilbert's syndrome). This syndrome occurs in the population with a frequency of 2-6%; inherited in an autosomal dominant manner. Gilbert's syndrome is based on a defect in the activity of liver enzyme systems (glucuronyl transferase) and, as a consequence, a violation of the uptake of bilirubin by hepatocytes. Jaundice of newborns with constitutional hyperbilirubinemia occurs without anemia and splenomegaly, with a slight increase in indirect bilirubin.

Hereditary jaundice of newborns in Crigler-Najjar syndrome is associated with very low glucuronyl transferase activity (type II) or its absence (type I). In type I syndrome, newborn jaundice develops already in the first days of life and steadily increases; hyperbilirubinemia reaches 428 µmol/l and higher. The development of kernicterus is typical, and death is possible. Type II syndrome, as a rule, has a benign course: neonatal hyperbilirubinemia is 257-376 µmol/l; Kernicterus rarely develops.

Jaundice due to endocrine pathology

At the first stage, the clinical signs of bilirubin intoxication predominate: lethargy, apathy, drowsiness of the child, monotonous cry, wandering eyes, regurgitation, vomiting. Soon, newborns develop classic signs of kernicterus, accompanied by stiff neck, spasticity of the body muscles, periodic agitation, bulging of the large fontanel, extinction of sucking and other reflexes, nystagmus, bradycardia, and convulsions. During this period, which lasts from several days to several weeks, irreversible damage to the central nervous system occurs. Over the next 2-3 months of life, a deceptive improvement is observed in the children’s condition, but already at 3-5 months of life, neurological complications are diagnosed: cerebral palsy, mental retardation, deafness, etc.

Diagnosis of jaundice in newborns

Jaundice is detected even at the stage of the child’s stay in maternity hospital by a neonatologist or pediatrician when visiting a newborn shortly after discharge.

The Cramer scale is used to visually assess the degree of jaundice in newborns.

• I degree – jaundice of the face and neck (bilirubin 80 µmol/l)
• II degree – jaundice extends to the level of the navel (bilirubin 150 µmol/l)
• III degree - jaundice extends to the level of the knees (bilirubin 200 µmol/l)
• IV degree - jaundice extends to the face, torso, extremities, with the exception of the palms and soles (bilirubin 300 µmol/l)
• V - total jaundice (bilirubin 400 µmol/l)

The necessary laboratory tests for the primary diagnosis of jaundice in newborns are: bilirubin and its fractions, general analysis blood, blood group of the child and mother, Coombs test, IPT, general urine test, liver tests. If hypothyroidism is suspected, it is necessary to determine the thyroid hormones T3, T4, and TSH in the blood. Detection of intrauterine infections is carried out by ELISA and PCR.

As part of the diagnosis of obstructive jaundice, newborns undergo an ultrasound scan of the liver and bile ducts, MR cholangiography, FGDS, plain radiography abdominal cavity, consultation with a pediatric surgeon and pediatric gastroenterologist.

Treatment of neonatal jaundice

To prevent jaundice and reduce hyperbilirubinemia, all newborns need early start(from the first hour of life) and regular breastfeeding. In newborns with neonatal jaundice, the recommended frequency of breastfeeding is 8–12 times a day without a night break. It is necessary to increase the daily volume of fluid by 10-20% compared to physiological need child, taking enterosorbents. If oral hydration is not possible, infusion therapy is performed: glucose drip, physical. solution, ascorbic acid, cocarboxylase, B vitamins. In order to increase the conjugation of bilirubin, phenobarbital may be prescribed to a newborn with jaundice.

The most effective treatment for indirect hyperbilirubinemia is continuous or intermittent phototherapy, which helps convert indirect bilirubin into a water-soluble form. Complications of phototherapy may include hyperthermia, dehydration, burns, and allergic reactions.

For hemolytic jaundice of newborns, exchange transfusion, hemosorption, are indicated. All pathological jaundice of newborns require immediate treatment of the underlying disease.

Prognosis of newborn jaundice

Transient jaundice of newborns in the vast majority of cases resolves without complications. However, disruption of adaptation mechanisms can lead to the transition of physiological jaundice in newborns to a pathological state. Observations and evidence indicate that there is no relationship between hepatitis B vaccination and neonatal jaundice. Critical hyperbilirubinemia can lead to the development of kernicterus and its complications.

Children with pathological forms of neonatal jaundice are subject to dispensary observation by a local pediatrician and

Currently, about 40 different types of jaundice are known, most of which occur in the newborn period. They are conventionally divided into 4 groups: hemolytic, conjugative, mechanical and hepatic.

Hemolytic jaundice. Greatest practical significance has hemolytic disease of newborns as a result of Rh conflict or ABO conflict. In accordance with the existing nomenclature, the following designations for antigens are accepted: Rh 0 (D), rh (C), rh (E). Hemolytic disease of newborns with Rh (D) and ABO incompatibility occurs in approximately one case per 250-300 births. When assessing the risk of this disease occurring in the fetus and newborns, certain conditions are taken into account under which sensitization of the mother’s body and the penetration of antibodies to the fetus occur. It has been established that only one out of 22-25 Rh-negative women is immunized with red blood cells from a D-positive fetus. For the rest, the immunological conflict does not arise even with repeated pregnancies. Consequently, for the occurrence of hemolytic disease of newborns, the penetration of fetal red blood cells into the maternal body is not enough. A normal placenta performs an immunoprotective function: the antibodies contained in it (globulin fractions) neutralize antigens coming from the fetus. The condition for increased sensitization of the mother’s body is a violation of the integrity of the placental barrier during late toxicosis of pregnant women and intercurrent diseases of the mother, causing vascular and dystrophic changes in the placenta. In these cases, fetal red blood cells are detected in the mother's blood in large quantities and the antigen-antibody reaction in the placenta is disrupted. Great importance have preliminary sensitization of the mother by transfusions of incompatible blood to her at any period of life and repeated abortions, especially in the later stages.

Hemolytic disease of newborns due to incompatibility of the blood of mother and fetus for antigens A and B also occurs less frequently than might be expected, given the presence of natural a- and p-antibodies in the mother’s blood.

As studies by L. S. Volkova have shown, this is explained by the release by the amniotic membrane of the fetus into the amniotic fluid of a large number of antigens identical to the fetal blood that neutralize group antibodies. A so-called peri-embryonic antigenic barrier zone is created, preventing the flow of group antibodies from maternal blood to the fetus. Amniotic fluid in most cases is devoid of Rh antigens, so Rh antibodies freely penetrate to the fetus, causing more severe forms of the disease than with ABO conflict.

Hemolytic disease of newborns due to Rh incompatibility occurs less frequently with simultaneous incompatibility of the blood of the mother and fetus due to group factors, since the mother’s natural antibodies (a and p) agglutinate the fetal red blood cells in the mother’s sinuses, and therefore D -, C - or E - antigens enter the mother’s blood in smaller quantities and do not have a long-term immunizing effect on her body.

Sometimes, during repeated pregnancies in sensitized women, there is no direct relationship between the height of the titer of anti-Rhesus antibodies in the blood and the severity of the hemolytic process in the child. This depends on the state of the placental barrier (with intact or slightly changed placental tissues, maternal antibodies do not penetrate to the fetus in such quantities as to cause a serious illness in him). A wide range of fluctuations in antibody titer in the 2nd half of pregnancy and its decrease shortly before birth are considered prognostically unfavorable for the fetus.

Since the Rh system antigens (-C, -D and -E) are contained in the blood of fetuses from the 10-14th week of pregnancy, and group antigens - from the 5-6th week, early sensitization of the mother’s body is possible under appropriate conditions. The depth of pathogenetic disorders in the body of the fetus and newborn depends on the duration of intrauterine sensitization. As a result of prolonged exposure to maternal antibodies on the fetus, it develops severe chronic anemia, tissue hypoxia, profound metabolic disorders (hypoproteinemia, hyperkalemia) and hemodynamics (hypervolemia, increased venous pressure). However, the development of hyperbilirubinemia does not occur, since bilirubin is transferred through the placenta into the mother's body. After the birth of a child, as a result of ongoing intensive hemolysis of sensitized red blood cells, a large number of indirect bilirubin.

Clinically, there are 3 forms of hemolytic disease of newborns: edematous, icteric and anemic. An edematous-icteric form of the disease is often encountered.

The most severe form is edematous. The child is born prematurely with severe swelling of all tissues, pallor of the skin and mucous membranes. Accumulation of transudate is noted in the serous cavities. Signs of cardiopulmonary failure quickly appear. The liver and spleen are sharply enlarged, dense, in the blood test there is a decrease in hemoglobin and red blood cells (Hb - 30-70 g/l, red blood cells 1-10 12 /l-1.5-10 12 /l). Color index about one. Signs of bone marrow irritation are anisocytosis, poikilocytosis, leukocytosis with a shift in the leukocyte blood count to the left. The placenta is usually enlarged and edematous. Children with the edematous form of the disease are not viable. They are stillborn or die in the first hours of life. The immediate cause of death is cardiopulmonary failure. Pathohistologically, swelling of the brain and other organs, dyscirculatory disorders, and signs of hypoxic encephalopathy are detected. There are reports of the possibility of saving the lives of children with the edematous form of the disease thanks to timely replacement blood transfusions.

The icteric form is the severe and most common form of hemolytic disease. The most important clinical symptoms are pallor and icteric discoloration of the skin, enlargement of the liver and spleen, in severe cases - hemorrhagic syndrome, damage to the central nervous system. The appearance of jaundice is observed immediately after birth or by the end of the 1st - beginning of the 2nd day. It reaches its maximum on the 2-3rd day of life. In the blood, anemia is determined, of a normo- or hyperregenerative nature with reticulocytosis and normoblastosis. Erythroblastemia, which is not a permanent feature, serves as an indicator of the severity of the disease.

The increase in free bilirubin in the blood serum is caused by hemolysis of sensitized erythrocytes. Its content in umbilical cord blood in hemolytic disease is increased and equals from 51 to 170 µmol/l. The hourly increase in bilirubin ranges from 3.5 to 17 µmol/l. Bilirubin reaches its maximum at the end of the 3rd day of life, when bilirubin intoxication most often develops. Important diagnostic method is a positive Coombs test with fetal red blood cells.

The anemic form is the mildest form of the disease. Its main clinical symptoms are pallor of the skin (sometimes with mild icterus), a slight enlargement of the liver, and less commonly, the spleen. A decrease in the amount of hemoglobin, red blood cells and reticulocytes is observed in the blood. Sometimes the symptoms of the anemic form are obvious at birth; more often, anemia develops rapidly in the 2nd week of the child’s life, while in the peripheral blood a sharp decline young forms of red blood cells, including reticulocytes.

Hemolysis of red blood cells in children with hereditary deficiency of erythrocytes and structural disorders of hemoglobin can be induced by exposure to unfavorable factors (birth stress, metabolic acidosis, administration of vitamin K and sulfonamides). Hemolysis occurs acutely, is accompanied by hyperbilirubinemia, and can reach critical values ​​with the development of kernicterus. To clarify the diagnosis, special studies are needed.

A large group of conjugation jaundices is a consequence of a violation of conjugation processes and is characterized by the presence of free bilirubin in the blood, normal content erythrocytes and hemoglobin, absence of enlargement of parenchymal organs and changes in the color of urine and feces. This group includes physiological jaundice of newborns, which appears on the 2nd or 3rd day of life, occurs with a low content of bilirubin (from 34 to 204 µmol/l) in the blood, on average 85-102 µmol/l, and disappears by end of 1st - 2nd week. Physiological jaundice does not affect the general condition of the child and does not require treatment. In 90-95% of premature and immature children, conjugation jaundice occurs, which lasts longer and can result in bilirubin encephalopathy. Conjugative hyperbilirubinemia poses the greatest danger to premature infants during the period of early adaptation. The likelihood of central nervous system damage in these children is associated not so much with the accumulation of toxic bilirubin, but with a violation metabolic processes and a number of other factors that facilitate the penetration of bilirubin into the central nervous system. This group of children does not have clear “critical” values ​​of bilirubin, which are associated with the development of bilirubin intoxication. Most often it occurs when the amount of bilirubin in the blood is 255 µmol/l, but can also develop at 153-170 µmol/l. What is decisive is not the concentration of bilirubin in the blood, but pathological factors that facilitate its transition into tissues. To premature babies increased risk The development of bilirubin encephalopathy includes immature premature babies with damage to the central nervous system of a hypoxic or traumatic nature, extensive cephalhematomas and soft tissue damage during childbirth, polycythemia (late cord ligation, acute asphyxia), severe edematous or hemorrhagic syndrome, early (first day of life) appearance of jaundice.

Conjugation jaundice with a relatively favorable but protracted course (up to 1 month) includes transient non-hemolytic (Ariasa) hyperbilirubinemia. It is caused by the presence in mother's breast milk of metabolites such as 3-a-20-p-pregnanediol, which inhibit the activity of glucuronyl transferase. Jaundice with this form of hyperbilirubinemia appears at the end of the 1st - beginning of the 2nd day and progressively increases in dynamics. No enlargement of parenchymal organs is observed, stool and urine are of normal color. Free bilirubin predominates in the blood, the concentration of which by the 4-5th day of life can exceed 306 µmol/l. The prolonged course of jaundice in children fed breast milk may also be due to the presence in breast milk of an increased amount of non-esterified fatty acids, which inhibit the activity of liver enzyme systems.

Transient inability of the liver to bind bilirubin due to hypoglycemia, hypoxia and dehydration is observed in newborns with diabetic fetopathy. Jaundice appears on the 1st day and reaches a maximum by the 3-5th day of life. The amount of bilirubin in the blood serum usually exceeds 204 µmol/l, but bilirubin intoxication occurs rarely. Less severe but prolonged jaundice (up to 2-3 months) may accompany congenital hypothyroidism. Moderate indirect hyperbilirubinemia, caused by a decrease in glucuronyltransferase activity against the background of dehydration and hypoglycemia, is observed in some newborns with pyloric stenosis. After pylorotomy it disappears quite quickly.

More rare hereditary forms conjugative hyperbilirubinemia: Crigler-Najjar syndrome - congenital absence of glucuronyltransferase with a high risk of developing kernicterus and Lutsey syndrome, caused by a transient defect in the glucuronyltransferase system. With the latter, jaundice begins as physiological, but long-term accumulation of free bilirubin can reach critical values ​​at the end of the 1st - 2nd week of life. With the elimination of a transient hereditary defect in the bilirubin binding system, jaundice disappears.

Hemolytic and conjugation jaundice of newborns can cause a serious complication - bilirubin encephalopathy. In premature babies, according to our observations, in the clinic of bilirubin intoxication, 2 phases can be noted. The first (asphyxial phase) is characterized by prodromal symptoms: weakening of the sucking reflex, muscle hypotonia, paradoxical reaction to mild irritations, decreased breathing, the appearance of prolonged apnea, which is accompanied by increased cyanosis, congestive wheezing in the lungs. Against the background of hypotension and areflexia, short-term tonic convulsions of the extensor muscles, local rigidity of the longissimus muscle of the head and neck, and a “mask-like face” with wide open “frightened” eyes appear. The asphyxial phase quite quickly turns into the second, spastic phase with a severe picture of damage to the nuclei of the brain: extensor hypertonicity, a piercing “brain” cry, rigidity of the longissimus muscle of the head and neck, gaze spasm, the “setting sun” symptom. The prognosis is unfavorable for the appearance of respiratory disorders. In full-term infants, the symptoms of bilirubin encephalopathy develop so quickly that it is impossible to distinguish these phases. TO early symptoms Bilirubin intoxication includes weakened sucking, hyporeflexia, and muscle hypotonia. Stiffness of the longissimus capitis muscle gradually becomes more pronounced. During development convulsive syndrome attacks of apnea and asphyxia appear. During this period, hyperthermia can be noted, since indirect bilirubin has a pyrogenic effect. After acute period neurological symptoms are temporarily smoothed out, but from the 2-3rd month persistent disorders occur (spastic paresis, pyramidal signs), vestibular and oculomotor disorders, hearing damage, retardation in physical development, icteric staining of baby teeth, and their hypoplasia.

Mechanical jaundice of newborns (presence of direct bilirubin in the blood, enlarged liver, change in color of urine and stool) includes malformations of the biliary system. Extrahepatic bile duct atresia is the most common. In the first days of life, it is difficult to diagnose atresia due to normal meconium staining and the absence of other symptoms of the disease at birth. The jaundice characteristic of atresia is masked by physiological jaundice until the end of the 2nd week of life. In the first weeks of life, stool may have a yellowish color, possibly due to the entry of pigment through the intestinal wall. Therefore, the earliest sign of biliary tract malformation should be considered colored urine from the 4-5th day of life.

Intrahepatic hypoplasia of the bile ducts is characterized by cholestasis unknown etiology. The disease is based on a delay in postnatal maturation of intralobular bile ducts and a violation of their differentiation. The disease occurs predominantly in boys. Jaundice most often appears from the 3-4th day of life, accompanied by an enlarged liver, discolored stool, and dark urine. Conjugated bilirubin predominates in the blood, and the amount of cholesterol is increased. The general condition of the newborns is not impaired; they gain weight normally and develop well. After 3-4 months, jaundice and these symptoms disappear. Differentiate hypoplasia of the bile ducts from developmental defects.

Jaundice– a violation of bilirubin metabolism, accompanied by hyperbilirubinemia and icteric staining of the skin and visible mucous membranes, is observed quite often in the neonatal period: in 32-86% of full-term and 90-95% of premature newborns. Hyperbilirubinemia in the neonatal period may be due to physiological characteristics exchange, however, in some cases it may be a consequence of a wide range of pathological conditions, in which timely diagnosis and adequate treatment determine not only the immediate and long-term outcome of the disease, but also the physical and psychomotor development of the child as a whole.

Hyperbilirubinemia is considered pathological and requires laboratory examination and therapy if the following signs are present:

– jaundice is present at birth or appears on the first day or second week of life;

– the duration of jaundice is more than 10 days in full-term infants and more than 14 days in premature infants;

– wave-like flow;

– the rate of increase in indirect bilirubin (BI) is more than 6 µmol/l per hour or more than 137 µmol/l/day;

– the level of NB in ​​the umbilical cord blood serum is more than 60 µmol/L or more than 85 µmol/L in the first 12 hours of life, 171 µmol/L on the 2nd day of life, the maximum value of NB on any day of life exceeds 221 µmol/L;

– direct bilirubin level more than 25 µmol/l.

There are 4 main mechanisms for the development of pathological hyperbilirubinemia:

– hyperproduction of bilirubin due to hemolysis;

– violation of bilirubin conjugation in hepatocytes;

– impaired excretion of bilirubin into the intestine;

– combined disorder of conjugation and excretion.

In this regard, from a practical point of view, there are 4 types of jaundice:

– hemolytic;

– conjugation;

– mechanical;

– parenchymatous.

In hemolytic and conjugation jaundices, the indirect fraction prevails; in mechanical and parenchymal jaundices, the direct fraction of bilirubin prevails.

One of the most important tasks doctor is the timely detection of hemolytic and conjugation jaundice, since the most dangerous complication indirect hyperbilirubinemia is bilirubin encephalopathy (kernicterus), which is based on irreversible changes in brain cells.

The most dangerous form of hemolytic jaundice is hemolytic disease of the newborn(GBN according to the Rh factor, according to the ABO system). The disease is characterized by the following clinical and laboratory criteria:

1. Presence of HDN in previous children in the family.

2. Conflict over Rh-factor ( Rh-negative woman and Rh-positive child) or according to the ABO system (I (O) blood group in the woman and II (A) or III (B) blood group in the child).

3. The presence of jaundice at birth or its appearance in the first 24 hours of life.

4. Jaundice is combined with pale skin.

5. Increase in the size of the liver and spleen in the first hours and days of life.

6. Deterioration of the child’s general condition, the degree of deterioration depends on the severity of hyperbilirubinemia.

7. The concentration of bilirubin in umbilical cord blood is usually more than 51 µmol/l.

8. The hemoglobin concentration in umbilical cord blood is at the lower limit of normal or reduced (less than 160 g/l).

9. The hourly increase in bilirubin in the first day of life is more than 5.1 µmol/l/hour, in severe cases – more than 8.5 µmol/l/hour.

10. The maximum concentration of total bilirubin (TB) in peripheral blood on days 3-4 is more than 256 µmol/l. OB increased due to NB.

11. During the first week of life, a further decrease in the level of hemoglobin, the number of red blood cells and an increase in the number of reticulocytes.

12. Positive Coombs test.

When diagnosing conjugation jaundice The following clinical and laboratory criteria are taken into account:

1. Jaundice appears after the 1st day of life and does not fade until the end of the 3rd week of life.

2. Jaundice has an orange tint.

3. The general condition of the child is satisfactory; with severe hyperbilirubinemia, the condition worsens.

4. The liver and spleen are not enlarged.

5. There is no anemia.

6. The maximum concentration of OB on the 3-4th day of life is more than 250 µmol/l in full-term infants and more than 170 µmol/l in premature infants. OB increased due to NB.

Bilirubin encephalopathy develops in initially healthy full-term children with a NB concentration above 425 µmol/l, in full-term children with risk factors - at a concentration above 342 µmol/l, cases of bilirubin encephalopathy have been described in premature children with a NB level of 170-204 µmol/l.

The likelihood of bilirubin encephalopathy increases when the child’s body is exposed to additional pathological factors:

- reducing the ability of albumin to firmly bind NB (hypoalbuminemia; hypoglycemia; increased levels of non-esterified fatty acids - observed when the child is fasting; acidosis; use of certain medications - furosemide, antibiotics).

– increasing the permeability of the blood-brain barrier and the sensitivity of neurons to the toxic effects of NB (severe or prolonged hyperbilirubinemia; immaturity; prematurity; hyperosmolarity, including due to hyperglycemia; acidosis; hypoxia; hypothermia; neuroinfections; cerebral hemorrhages; arterial hypertension);

The penetration of NP through the blood-brain barrier and accumulation in the neurons of the brain (mainly in the subcortical formations, primarily in the nuclei of the brain) blocks the respiratory enzymes of mitochondria, inhibits reactions involving adenylate cyclase and K-Na-ATPase, disrupts the functional state of the cell membrane, which leads to the death of neurons.

Clinical picture bilirubin encephalopathy includes 4 phases:

1. Predominance of signs of bilirubin intoxication: children are lethargic, inactive, suck poorly, they have decreased muscle tone, depressed physiological reflexes, regurgitation, “wandering eyes,” and bouts of cyanosis. The changes are reversible.

2. The appearance of classic signs of kernicterus: pronounced hypertonicity - the child’s body takes a forced position with opisthotonus, elongated limbs and clenched hands, rigidity of the neck muscles, tremor of the hands, clonus of the feet, convulsions, hyperesthesia, sharp “brain” cry, Graefe’s symptom are determined , bulging of a large fontanel. During this phase, bradycardia is observed and respiratory arrest is possible.

3. Phase of false well-being and complete or partial disappearance of spasticity (2–3rd month of life).

4. Formation period clinical picture neurological complications (3–5 months of life): children cerebral paralysis, paresis, athetosis, deafness, dysarthria, delay mental development and etc.

Intensive therapy for indirect hyperbilirubinemia pursues two goals: reducing the concentration of NB and preventing the development of bilirubin encephalopathy.

Therapy will be effective only if the child is adequately fed, hypothermia, hypoxia, hypoglycemia, hypoalbuminemia and other metabolic disorders are eliminated.

In a maternity hospital, a risk group for the development of tension-type headache is identified, since it is with this disease that the development of bilirubin encephalopathy is most likely. If a child born to an Rh-negative woman has clinical manifestations of a severe form of HDN (severe pallor, icteric discoloration of the skin and umbilical cord, swelling of the soft tissues, hepatosplenomegaly), an exchange transfusion (RT) operation is indicated. The technique of partial PCD is used, in which 45-90 ml/kg of the child’s blood is replaced with a similar volume of donor red blood cells of group 0 (I), Rh-negative.

In other cases, the management of children depends on the results of laboratory tests.

In newborns with HDN for any factor (Coombs test - positive) with an hourly increase in HDN of more than 6.8 µmol/l in the first hours of life, the prescription of standard immunoglobulins for intravenous administration at the rate of 0.5-1.0 g/kg (on average) is indicated 800 mg/kg) intravenously slowly (over 2 hours). If necessary, repeated administration is carried out after 12 hours.

The management tactics for children with tension-type headache over 24 hours of age depend on the absolute values ​​of bilirubin or the dynamics of these indicators.

In the maternity hospital, there is also a high-risk group for the development of severe hyperbilirubinemia not associated with tension-type headache; it consists of newborn children with pronounced signs of morpho-functional immaturity, multiple subcutaneous hemorrhages and extensive cephalohematomas, high risk early appearance of hereditary hemolytic anemia, as well as children requiring resuscitation and intensive care in the early neonatal period. As a rule, jaundice in such children appears after the first day of life; the management of children is determined by the level of bilirubin, birth weight and the presence of pathological factors.

Based on laboratory results, the question of whether the child needs phototherapy and PCP surgery is decided (Table 7).

Table 7. Indications for phototherapy and PCP in newborns 24-168 hours of life depending on body weight at birth

*Minimum bilirubin values ​​are an indication for treatment when the body is exposed to pathological factors that increase the risk of bilirubin encephalopathy.

Factors that increase the risk of bilirubin encephalopathy:

– hemolytic anemia,

– Apgar score at 5 minutes< 4 баллов,

– PaO 2< 40 мм рт.ст. длительностью более 1 часа,

– pH art. cr.< 7,15 (pН кап. кр. < 7,1) длительностью более 1 часа,

– rectal temperature ≤ 35° C,

– serum albumin concentration ≤ 25 g/l,

– deterioration of neurological status due to hyperbilirubinemia,

– generalized infectious disease or meningitis.

The method is based on ototherapy lies the ability of bilirubin molecules under the influence of light energy to change the chemical structure and associated physicochemical properties. Bilirubin absorbs light energy predominantly in the blue zone of the visible spectrum (maximum absorption at a frequency of 450-460 nm). Under the influence of light, two types of reactions occur in the skin: photoisomerization and photooxidation of bilirubin. As a result, spatial and structural changes bilirubin molecules, thereby reducing its toxic properties.

NB levels above which phototherapy is indicated for a child, depending on his weight and postnatal age, are indicated in Table 7.

Methodology:

1. It is optimal to place the child in an incubator.

2. The child’s eyes and genitals are protected with light-proof material.

3. The phototherapy source is placed above the child at a height of about 50 cm, the distance between the lamp and the lid of the incubator should be at least 5 cm to avoid overheating of the air in the incubator.

4. Every 1-2 hours of phototherapy, the position of the child in relation to the light source is changed; To increase the area of ​​skin irradiated, special phototherapy blankets can be used.

5. The child’s body temperature is monitored every two hours.

6. In the absence of contraindications, enteral nutrition is maintained in full.

7. If enteral nutrition is limited, the child is prescribed parenteral nutrition(10% glucose solution, if necessary - amino acid preparations, but not fat emulsions).

8. The daily volume of fluid administered to the child is increased by 10-20% (in children with extremely low body weight - by 40%) compared to the child’s physiological need.

9. When conducting phototherapy, hyperbilirubinemia cannot be assessed by skin color; the effectiveness criterion can only be biochemical analysis bilirubin level, carried out daily, if there is a threat of bilirubin encephalopathy - every 6-12 hours.

10. Phototherapy is stopped in the absence of a pathological increase in bilirubin and the concentration of bilirubin in the blood serum is below the values ​​that served as the basis for starting phototherapy.

There are various phototherapy regimens. In full-term infants, it is advisable to use the “classical” scheme: long-term exposure with short breaks for feeding, changing position, and medical manipulations. The maximum break between phototherapy sessions should not exceed 2-4 hours. With a rapid increase in bilirubin levels and critical hyperbilirubinemia, phototherapy is carried out continuously. The effectiveness of phototherapy depends not only on the total exposure time (at least 8-12 hours per day), but also on the uniformity of its use throughout the day. Phototherapy is not indicated for congenital porphyria (the first signs may be the appearance of blisters and severe anxiety in the child during phototherapy), liver disease, obstructive jaundice, and heart failure.

The main indications for PCP surgery are:

2. The hourly increase in bilirubin is above 6.8 µmol/l/hour.

3. The level of NB in ​​the blood serum is higher than critical figures (Table 7).

4. Decrease in hemoglobin at birth less than 120 g/l.

5. Clinical picture of severe HDN, signs of bilirubin encephalopathy.

Basic principles of carrying out a security check:

1. In case of Rh-conflict, single-group, Rh-negative erythromass is transfused with single-group plasma in a 2:1 ratio.

2. For ABO incompatibility, red blood cells of the O (I) group and plasma of the AB (IV) group are used in a 2:1 ratio.

3. In case of incompatibility both for the Rh factor and the blood group, use erythromass of group 0 (I), Rh-negative and plasma AB (IV) of group in a 2:1 ratio.

4. If the blood of mother and child is incompatible due to rare factors, blood from an individual donor is used.

5. For conjugative hyperbilirubinemia, use erythromass of the same group and Rh factor as the child and single-group plasma in a 2:1 ratio.

6. Only freshly prepared red blood cells are used, no more than 72 hours of storage.

7. ZPK is carried out with a double replacement of the circulating blood volume (BCV in a newborn is 80-90 ml/kg) - 160-180 ml/kg.

Preoperative preparation:

1. In children who are in in serious condition, eliminate acidosis, hypoxia, hypoglycemia, electrolyte disturbances, hemodynamic disorders, hypothermia.

2. The operation is performed in an operating room, treatment room or in a clean box.

3. Before transfusion, the child’s stomach is emptied and a cleansing enema is performed.

4. During transfusion, the child should be on a resuscitation table heated by a radiant heat source, or in an incubator, and the blood should be heated to 27-37° C.

Technique of the ZPK operation(according to Diamond):

1. ZKK is carried out in compliance with all rules of asepsis and antiseptics.

2. The umbilical vein is used for transfusion; if catheterization of the umbilical vein is impossible, the central vein is catheterized. The use of a peripheral vein is acceptable.

3. The volume of the excreted portion of blood during PCD, depending on the child’s body weight, is 5-20 ml and should not exceed 10% of the bcc. The withdrawn blood is replaced alternately with erythromass and donor plasma in an equivalent amount (every 2 syringes of erythromass, 1 syringe of plasma is injected). The transfusion rate is no more than 3-4 ml/min.

4. For every 100 ml of injected blood, 1-2 ml of a 10% calcium gluconate solution in 5-10 ml of a 10% glucose solution is injected.

5. The level of bilirubin in the blood serum before and after PCP is determined. The effectiveness of the operation is evidenced by a decrease in bilirubin concentration by more than 2 times.

6. At the end of the PCD operation, a broad-spectrum antibiotic is injected into the umbilical catheter at half the daily dose.

7. The average duration of the operation is 1.5-2.5 hours.

Complications of PCP:

– thromboembolic;

– cardiac dysfunction: arrhythmia, acute heart failure;

– electrolyte and metabolic disorders;

– transfusion;

– infectious;

– hemorrhagic syndrome.

Infusion therapy for indirect hyperbilirubinemia is indicated when phototherapy is carried out and it is impossible to replenish fluid losses by the enteral route. For infusion therapy use a 5-10% glucose solution. For hypoproteinemia (protein level less than 40 g/l), administration of 5% albumin is indicated. Infusion rate 1-2 drops/kg/min.

Features of bilirubin metabolism in the perinatal period.

In the fetus and newborn, the metabolism of bilirubin has features that, when certain conditions contribute

accumulation of pigment in the blood and facilitate its penetration into tissues.

This age period is characterized by increased formation of bilirubin from red blood cells with fetal hemoglobin

due to their shorter lifespan (70-80 days) and from immature red blood cells in bone marrow(normoblasts, reticulocytes

and etc.).

In the prenatal period of development, bilirubin practically does not undergo conjugation, which is currently explained

the absence of ligandin and Z-protein in the fetal liver, which ensure the uptake of bilirubin by hepatocytes, and inhibition of activity

enzymes uridine diphosphodehydrogenase and glucuronyltransferase by pregnancy hormones. The main body

The placenta is responsible for removing bilirubin from the fetal body. The concentration of bilirubin in fetal plasma is low.

Due to the concentrating ability of the placenta, hemolytic disease is not accompanied by a significant increase

bilirubin in the blood plasma, even in severe edematous-anemic form of the disease. For conjugated (direct) bilirubin

the placenta is impermeable in both directions, and therefore, with fetal hepatitis, jaundice can be observed in the fetus

staining of amniotic fluid, placenta membranes and skin.

Unconjugated bilirubin is a constant component of meconium, even in fetuses with biliary atresia.

The mechanism of entry of bile pigments into the fetal intestinal lumen is not clear enough. Apparently we have to agree with

It is believed that in the fetus the mucous membrane of the stomach and intestines has the ability to form glucuronides.

After birth, the content of bilirubin in the baby’s blood increases due to transient liver failure

newborns to conjugation. Hair loss plays a role in the activation of glucuronidation enzymes after childbirth.

inhibitory effects of pregnancy hormones and accumulation of unconjugated bilirubin in the blood.

“Launch” of the bilirubin conjugation system (formation of ligandin and Z-protein, activation of enzymes

uridine diphosphoglucose dehydrogenase, hepatocyte glucuronyltransferase and bilirubin glucuronyltransferase of bile

tubules) occurs normally within a period of several hours to several days after birth. However, activity

conjugating system of the liver increases slowly and reaches the level of adults by the end of the 3-4th week of life. However, in

During the first 3 days of life in healthy full-term infants, 410 µmol/l, or 24% of bilirubin, is formed only from red blood cells. IN

In reality, during the period of maximum physiological jaundice, the amount of bilirubin is 103-131 µmol/l. This

indicates the excretion of unconjugated bilirubin by the liver of the newborn. Research confirms

observation that the feces of newborns in the first days of life contain up to 50% of bilirubin isomers IX-β IX-γ and IX-σ, which

Unlike isomer IX-α, they are soluble in water and, apparently, are excreted by the liver into bile in an unconjugated state.

It is possible that in the first days of life, extrahepatic conjugation of bilirubin (kidneys, gastrointestinal mucosa) also persists.

intestinal tract). As a result, in healthy newborns, regardless of birth weight, within 3-4 days of life

physiological hyperbilirubinemia disappears.

Because of lack of activity the enzyme bilirubin glucuronyltransferase, involved in the conversion of bilirubin-

monoglucuronide (MGB) to bilirubin diglucuronide (DHB), the concentration of DHB in the bile of newborns is much lower than that of

adults, and MGB predominates.

The excretory function of the liver in newborns is significantly reduced due to the anatomical immaturity of the excretory system:

bile capillaries are narrow and their number is reduced. The mentioned features predispose to the development of cholestasis

(for example, “bile thickening syndrome” in hemolytic disease of the newborn). Excretory function of the liver

newborns reaches the eliminating capacity of the liver of adults by the end of the 1st month of life.

In newborns, due to the absence of putrefactive processes in the intestines, stercobilinogen is not formed, and bilirubin

is released unchanged. The accumulation of unconjugated bilirubin is also promoted by high activity

β-glucuronidase enzyme in the intestinal wall of newborns. This enzyme cleaves glucuronic acid from direct bilirubin.

acid, converting it into unconjugated bilirubin. The latter partially re-enters the blood from the intestine.

Violation of bilirubin metabolism in various diseases of newborns is associated with its peculiarities in this period.

Increased formation of bilirubin may be due to rapid hemolysis of sensitized or genetically

defective red blood cells, their instability in conditions of hypoxia, hypoglycemia, with a lack of vitamin E and the purpose

large doses of vitamin K. The accumulation of pigment is promoted by dehydration, hypothermia, and late ligation of the umbilical cord due to

increase in blood volume and hematocrit number. Additional suppliers of bilirubin are hemorrhages in the skin,

mucous membranes, internal organs due to hypoxia and mechanical damage to soft tissues during childbirth.

The risk of developing bilirubin toxicity in newborns with pathological hyperbilirubinemia largely depends on

bilirubin-binding capacity of albumin. Observations show that the greatest danger is not the general

the concentration of bilirubin in plasma, and the content of bilirubin capable of diffusion, i.e., not associated with albumin.

The bilirubin-binding capacity of plasma is significantly lower under conditions of pathological influences: with hypoalbuminemia,

hypoxemia, acidosis, hypothermia, hyperosmolarity, in the presence of infection, endogenous (hormones, non-esterified fatty

acids, etc.) and exogenous competitors for communication with albumin (corticosteroid drugs, antibiotics, sulfonamides and

etc.). The albumin-binding capacity of plasma is especially low in premature infants. Their development of kernicterus may

occur at a bilirubin concentration of 153-171 µmol/l.

The formation of the conjugative function of the liver is disrupted by hypoxia, metabolic disorders, dehydration, layering

infectious diseases. Hypoglycemia leads to a lack of energy resources and disruption of processes

gluconeogenesis, due to which a large amount of galactose is formed in the liver. Toxic effect on enzymes

liver systems are provided by vitamin K and its analogues, sulfonamide drugs, chloramphenicol, etc. When prescribed

drugs that are inactivated in the liver, their competition for bonding with glucuronic acid is important.

The peculiarity of the intestinal metabolism of bile pigments contributes to the return of unconjugated bilirubin to the blood and

increase or persistence of hyperbilirubinemia.

Transient hyperbilirubinemia, physiological jaundice of newborns (icterus neonatorum).

Develops in all newborns in the first days of life, while jaundice of the skin occurs only in 60-70%.

The normal concentration of bilirubin in umbilical cord blood serum is considered to be 26-34 µmol/l. Almost everyone

in newborns in the first days of life, the concentration of bilirubin in the blood serum increases at a rate of 1.7-2.6 µmol/l/h,

reaching an average of 103-107 µmol/l on days 3-5. Approximately 1/3 of full-term newborns have an increase in concentration

bilirubin is less and in 1/3 - more - reaches 171 µmol/l. With transient jaundice, the level of bilirubin increases

due to its unconjugated fraction - indirect bilirubin. Yellowness of the skin appears with transient jaundice

newborns on the 2-3rd day of life, when the concentration of indirect bilirubin reaches 51-60 in full-term newborns

µmol/l, and in premature infants - 85-103 µmol/l.

Transient jaundice is less common and less pronounced in children who are put to the breast early, often put to the breast

breasts located on artificial feeding having a hormonal crisis, compared with newborns,

attached to the breast on the 2nd day, fed strictly according to the clock, breastfed or not

having a hormonal crisis. It develops more often and is more pronounced in newborns with placental transfusion syndromes,

leading to polycythemia, as well as in premature infants, in whom it is accompanied by higher hyperbilirubinemia. Moreover,

In premature infants, kernicterus can occur with hyperbilirubinemia of about 171 µmol/l. Transient jaundice

It develops relatively less frequently in children with intrauterine meconium passage, i.e. born with asphyxia.

The pathogenesis of transient jaundice in newborns is associated with a number of factors:

1. Increased formation of bilirubin (137-171 µmol/kg/day in newborns on the first day of life and 60

µmol/kg/day. - in adults) due to:

A) shortened life expectancy of erythrocytes due to the predominance of erythrocytes with fetal hemoglobin;

B) pronounced ineffective erythropoiesis;

B) increased formation of bilirubin in the catabolic phase of metabolism from non-erythrocyte sources of heme

(myoglobin, hepatic cytochrome, etc.).

2. Reduced functional capacity of the liver, manifested in:

A) reduced uptake of indirect bilirubin by hepatocytes;

B) low ability to glucuronidate bilirubin due to low glucuronyl transferase activity and

uridine diphosphoglucose dehydrogenase, mainly due to their inhibition by maternal hormones;

C) reduced ability to excrete bilirubin from the hepatocyte.

3. Increased intake of indirect bilirubin from the intestine into the blood due to:

A) high activity of β-glucuronidase in the intestinal wall;

B) the flow of part of the blood from the intestine through the ductus venosus (Arantius) into the inferior vena cava, bypassing the liver, i.e.

disturbance of hepatoenterogenous circulation of bilirubin;

C) intestinal sterility and weak reduction of bile pigments.

There are genetic and ethnic features of the course of transient jaundice in newborns: in some families, and

also in Asian countries(China, Korea, Japan, etc.), among American Indians and Greeks the maximum bilirubin values ​​are more

high (up to 239 µmol/l).

Pathological jaundice, in contrast to physiological jaundice, is characterized by the following features (maybe

one or more traits):

Present at birth or appear on the first day or second week of life;

Combined with signs of hemolysis (anemia, high reticulocytosis, nuclear erythroid forms in the blood smear,

excess spherocytes +++, ++++), pallor, hepatosplenomegaly;

Lasts more than 1 week in full-term infants and more than 2 weeks in premature infants;

They occur in waves (the yellowness of the skin and mucous membranes increases in intensity after

period of its decrease or disappearance);

The rate of increase (increase) of unconjugated bilirubin (indirect bilirubin) is more than 9 µmol/l/h

(0.5 mg%/h) or 137 µmol/l/day (8 mg%/day);

The level of indirect bilirubin in umbilical cord blood serum is more than 60 µmol/l (3.5 mg%) or 85 µmol/l (5

mg%) - in the first 12 hours of life, 171 µmol/l (10 mg%) - on the 2nd day of life, maximum values ​​of indirect bilirubin in

any day of life exceeds 221 µmol/l (12.9 mg%);

The maximum level of bilirubin-diglucuronide (direct bilirubin) is more than 25 µmol/l (1.5 mg%).

Indirect hyperbilirubinemia.

There are three different mechanisms for the development of indirect hyperbilirubinemia: hyperproduction of bilirubin, violation

conjugation of bilirubin and increased reabsorption of bilirubin in the intestine.

The main cause of hyperproduction of bilirubin in newborns is increased hemolysis. For hemolytic jaundice

characterized by enlargement of the liver and spleen as a result of intense hemolysis of red blood cells, possible development of hemorrhagic

syndrome, but the color of urine and feces with this type of jaundice remains unchanged. In children with hemolytic jaundice

hyperregenerative anemia is observed (a clinical blood test shows a decrease in the number of red blood cells and

hemoglobin concentration, the number of reticulocytes increases), the concentration often decreases total protein in serum

blood.

Most often, the cause of hemolysis in the early neonatal period is the incompatibility of the blood of the mother and child according to

erythrocyte antigens. In this case, the term “hemolytic disease of the newborn” is used. Characteristic

The peculiarity of jaundice in this condition is its occurrence in the first 24 hours of life. Jaundice associated with hemolysis

can also occur in the acute course of a number of congenital infections (cytomegaly, herpes, rubella, toxoplasmosis,

syphilis, listeriosis) or be a sign of the development of neonatal sepsis. More rarely detected in the neonatal period

family hemolytic anemia(microspherocytic anemia of Minkowski-Choffard), erythrocyte enzymopathies (defect

glucose-6-phosphate dehydrogenase, pyruvate kinase, hexokinase) and hemoglobinopathies (defects in the structure and synthesis of globin or

heme), accompanied by jaundice.

Other (non-hemolytic) causes of bilirubin hyperproduction include severe neonatal

polycythemia (increased hematocrit in venous blood more than 70%), swallowed blood syndrome, massive

hemorrhages (including extensive cephalohematomas).

Impaired bilirubin conjugation. This mechanism of impaired bilirubin metabolism in newborns is recorded

most often. Various reasons leading to this type of disorders are often united by the term “conjugation

jaundice."

For conjugation jaundice, the typical occurrence of jaundice in a newborn over 24 hours of age is due to increased

level of indirect bilirubin fraction, absence of hepato- and splenomegaly, anemia and reticulocytosis, normal color of stool and

urine.

The main causes of impaired bilirubin conjugation include:

1) entry into the child’s blood (from the mother during childbirth or through breast milk or as a result of

direct treatment of the child) drugs that compete with bilirubin for glucuronyl transferase

(oxytocin, oxacillin, cephalosporins, etc.);

2) delayed “maturation” of the enzyme uridine diphosphate glucuronyltransferase in premature and immature infants

newborns (including those with congenital hypothyroidism and diabetes mellitus at the mother);

3) the entry into the baby’s blood during breastfeeding of substrates that competitively inhibit

liver glucuronyltransferase (jaundice from breast milk).

4) hereditary defects in the synthesis of the enzyme uridine diphosphate glucuronyltransferase (syndromes

Gilbert and Crigler-Najjar types 1,2).

Jaundice from mother's milk appears or sharply intensifies when the baby begins to receive enough

amount of mother's milk (from 3-7 days of life). Severe hyperbilirubinemia is observed in 0.5-2.5% of healthy full-term infants

children who are breastfed. Its development is associated with several reasons: increased content

progesterone metabolites (5β-pregnane-3α,20β-diol), high lipoprotein lipase activity in colostrum and breast milk and

increased reabsorption of free bilirubin in the intestines of a newborn baby. Maximum content increase

bilirubin in the blood is observed on the 10-15th day due to an increase in the content of the indirect fraction. In this case, the concentration

total bilirubin does not exceed 360 µmol/l; no cases of kernicterus have been described. Reliable differential

diagnostic sign This type of jaundice is a decrease in the level of total bilirubin by 85 µmol/l or more with

stopping breastfeeding for 2-3 days. Given the benign nature of hyperbilirubinemia associated

with breast milk, after confirmation of the diagnosis, breastfeeding can be resumed. If the child

continues to receive breast milk, jaundice persists for 4-6 weeks, then begins to gradually decrease.

Complete normalization of bilirubin in the blood occurs by the 12-16th week of life.

Crigler-Najjar syndrome - a hereditary disease characterized by the absence of glucuronyltransferase in

liver (type I) or very low (about 5%) activity (type II). In type I defect, inherited autosomal

recessive type, jaundice appears at the age of 2-3 days of life, steadily increasing by the 5-8th day (level of indirect

bilirubin more than 340 µmol/l), creating a risk of developing kernicterus. The effect of phenobarbital administration

absent, improvement occurs with long-term phototherapy. Parents of sick children are often relatives.

In type II of this syndrome, which is usually inherited autosomal recessively (families with autosomal dominant

inheritance), hyperbilirubinemia does not reach such high numbers (less than 340 µmol/l). However, in the neonatal period

possible development of kernicterus. There is a positive effect when using phenobarbital.

Gilbert's syndrome is a hereditary disease transmitted in an autosomal recessive manner and associated with a disorder

capture of bilirubin by the sinusoidal membrane of hepatocytes and a slight decrease in the activity of liver glucuronyltransferase.

The frequency of this syndrome in the population varies from 2 to 6%. Typically, jaundice in such children is moderate (80-120 µmol/l),

cases of kernicterus have not been described, the general condition is little affected. Clinical manifestations can be observed from 2-3

days of life or at any age up to 10 years, and the intensity of jaundice can change every 3-5 weeks. Diagnosis

confirmed by long-lasting jaundice due to unconjugated hyperbilirubinemia.

Jaundice associated with an increase in the serum concentration of unconjugated bilirubin due to increased

reabsorption of bilirubin in the intestine, can be observed with pyloric stenosis and high intestinal obstruction.

Direct hyperbilirubinemia

An increase in the intensity of jaundice, its greenish tint along with an increase in the size of the liver, the appearance of acholia

stool and dark urine indicate a violation of the excretory function of the hepatobiliary system - neonatal

cholestasis. Laboratory confirmation of this syndrome serves to increase the level of direct fraction of bilirubin in the blood

more than 15-20% of the total level, an increase in the concentration of cholesterol, β-lipoproteins, bile acids, and

enzymes alkaline phosphatase and γ-glutamine transferase. Transient direct hyperbilirubinemia during the neonatal period

may be due to the morphofunctional characteristics of the liver and bile ducts, characterized by high

the level of synthesis of bile acids and the immaturity of their hepatic-intestinal circulation. Neonatal cholestasis may be one

from manifestations of diseases of the liver and bile ducts, as well as a consequence of a combination of nonspecific pathological

factors of the perinatal period, i.e. have extrahepatic origin.

In the structure of extrahepatic causes of the formation of neonatal cholestasis, the leading place is occupied by conditions

accompanied by the development of hypoxia or ischemia of the hepatobiliary system, hypoperfusion of the gastrointestinal tract,

persistent hypoglycemia, metabolic acidosis and stagnant cardiovascular failure. Violation of excretory

functions of the hepatobiliary system may be due to increased bilirubin levels in hemolytic disease

newborns due to a significant change in the colloidal properties of bile, an increase in its viscosity, and in some cases -

direct toxic effect of bilirubin on hepatocyte membranes and cell mitochondria. An important place is occupied

systemic and localized bacterial infections, triggering the synthesis and excretion of a complex cascade of inflammatory mediators

Kupffer cells, as well as hepatocytes and endothelial cells of sinusoids, which has a direct

influence on the formation and excretion of bile. Therapeutic measures carried out for newborns in the department

resuscitation and intensive care, include potentially hepatotoxic drugs, total parenteral nutrition, which

also contribute to violation functional state hepatobiliary system.

The development of cholestasis is more often observed in premature newborns with the simultaneous action of several

pathological and iatrogenic factors on liver function and the condition of the bile ducts. The pathology is based on various

severity of destructive changes in the bile ducts, impaired permeability of hepatocyte membranes and

intercellular connections, which in most cases are reversible with timely therapy. Characteristic

A feature of neonatal cholestasis caused by extrahepatic causes is its dependence on the severity and

the duration of pathological conditions of the perinatal period and the effect of iatrogenic factors. As the overall

the child’s condition and resolution of the underlying disease, in most cases there is a reverse development of cholestasis. However

its residual effects can persist for a long time - up to 6-8 months of life. Diagnosis of neonatal

cholestasis is valid only if pathology of the hepatobiliary system is excluded.

Diseases of the hepatobiliary system can be caused by predominant damage to hepatocytes, as well as

intra- and extrahepatic bile ducts.

The main reasons for initial involvement in pathological process hepatocytes are infectious and

toxic liver damage; metabolic and endocrine disorders are less common.

Main manifestations predominant defeat hepatocytes infectious, toxic and

metabolic genesis:

Early appearance of jaundice and the wavy nature of the jaundice syndrome;

Enlarged liver and spleen;

Early appearance of hemorrhagic syndrome;

Intermittent acholia of stool;

Dark yellow color of urine;

Biochemical cholestasis syndrome (increased levels of direct bilirubin, cholesterol, β-lipoproteins, bile

acids, alkaline phosphatase and γ-glutamine transferase activity in the blood);

Increased activity of alanine and aspartate aminotransaminases when their ratio is greater than 1;

Violation of the synthetic function of the liver; decrease in the content of albumin, fibrinogen, prothrombin index

in blood);

Visualization of the gallbladder by ultrasound.

Infectious diseases. Etiological factors infectious hepatitis are viruses (cytomegaly, rubella,

mycoplasma). With the development of sepsis, the cause of neonatal hepatitis can also be nonspecific bacteria.

Infection can occur before, during and after childbirth. In most cases, neonatal hepatitis caused by

the above pathogens is considered as one of the manifestations of a generalized infection. Feature Detection

infectious process (violation of general condition, poor appetite, low weight gain, bloating, lethargy,

hemorrhagic syndrome, low-grade fever, anemia, thrombocytopenia, leukocytosis, neutrophilia with a shift in the leukocyte

formula to myelocytes, an increase in ESR) and the symptom complex characteristic of this infection is necessary

condition for diagnosing hepatitis. In addition, in the diagnosis of neonatal hepatitis, certain importance is attached

results of liver puncture biopsy. Most pathogens cause characteristic changes, for example, giant

cells with cytomegalovirus inclusions - “owl eye” cells with cytomegalovirus infection. General signs

These include giant cell transformation of hepatocytes, disorganization of lobular architecture, and intracellular cholestasis.

Immunological studies, detecting the presence of antibodies to the above pathogens, as well as testing

genome by polymerase chain reaction (PCR) or inoculation of the microorganism by cultural method is confirmed

diagnosis.

Toxic liver damage. Toxic liver damage in the neonatal period is detected quite rarely. However

However, it should be remembered that liver damage can be caused by a wide range of drugs, the primary

Among which are a number of antibiotics (erythromycin, clavulanic acid, ampicillin, chloramphenicol, gentamicin,

1st generation cephalosporins, tienam), nitrofurans (furagin, 5-NOK), sulfonamide drugs, diuretics (Lasix),

non-steroidal anti-inflammatory drugs (indomethacin), anticonvulsants and antipsychotics. Clinical and laboratory

signs of hepatitis appear while taking potentially hepatotoxic drugs and may persist for

long period, 3-6 months after their cancellation.

Metabolic disorders. Characteristic feature most diseases caused by metabolic