Leukocyte formula. Neutrophils - structure and function, the norm in children and adults, the reasons for the increase and decrease

High accuracy (analysis of more than 2000 cells; the doctor analyzes the cells)

High reproducibility of the results of the study due to the analysis of a large number of cells, the homogeneity of the test material, the exclusion of the subjective factor

The automatic counter does not divide the subpopulation of neutrophils into stab and segmented, however, with a large number of young forms of neutrophils (stab, young, myelocytes), it displays the message “left shift”, which is a mandatory requirement for counting the leukocyte formula under a microscope

Assess the state of immunity

Diagnosis and differential diagnosis of leukemia

Determine the stage and severity of an infectious disease

Differential diagnosis of viral and bacterial infections

Stab neutrophils 2-4% (0.080-0.350 x109 / l)

Segmented neutrophils% (2,900 x109 /l)

Eosinophils 0.5 - 5.0% (0.440 x109 / l)

Basophils% (0 - 0.088 x109 / l)

Lymphocytes% (1,000 x109 /l)

Monocytes% (0.080-0.530x109 /l)

Neutrophils - the main function of neutrophils is penetration into the tissues of the body from the blood and the destruction of foreign, pathogenic microorganisms by their phagocytosis (capture and digestion); depending on the degree of maturity and shape of the nucleus in the peripheral blood, stab (younger) and segmented (mature) neutrophils are isolated; younger cells of the neutrophilic series - young (metamyelocytes), myelocytes, promyelocytes - appear in the peripheral blood in case of pathology and are evidence of stimulation of the formation of cells of this type

Basophils are a type of leukocyte involved in allergic reactions; an increase in the number of these cells occurs with various allergic reactions, chronic and viral infections, and together with eosinophilia can be a sign of chronic myeloid leukemia; contain biologically active substances such as heparin and histamine (similar to connective tissue mast cells), basophilic leukocytes during degranulation initiate the development of an immediate anaphylactic hypersensitivity reaction

Lymphocytes - are the main cells of the immune system for the formation of cellular immunity; they form antibodies that bind foreign substances and lead to the destruction of cells infected by microorganisms; they are able to "recognize" and "kill" cancer cells; provide acquired immunity (resistance of the disease upon secondary contact with the pathogen)

Monocytes - the largest cells among leukocytes, do not contain granules; participate in the formation and regulation of the immune response, performing the function of antigen presentation to lymphocytes and being a source of biologically active substances, including regulatory cytokines; have the ability to local differentiation - are the precursors of macrophages (into which they turn after leaving the bloodstream) - macrophages are able to absorb up to 100 microbes, while neutrophils - only 20-30; they appear in the focus of inflammation after neutrophils and show maximum activity in an acidic environment in which neutrophils lose their activity; in the focus of inflammation, macrophages phagocytize microbes, as well as dead leukocytes, damaged cells inflamed tissue, cleansing the focus of inflammation and preparing it for regeneration (monocytes are the "scavengers" of the body, they absorb microbes and bacteria, as well as dead leukocytes, damaged cells of inflamed tissue, cleanse the focus of inflammation and prepare it for regeneration)

Neutrophilia - increase total leukocytes at the expense of neutrophils

Neutropenia - a decrease in the content of neutrophils

Lymphocytosis - an increase in the content of lymphocytes

Lymphopenia - a decrease in the content of lymphocytes

Eosinophilia - an increase in the content of eosinophils

Eosinopenia - a decrease in the content of eosinophils

Monocytosis - an increase in the content of monocytes

Monopenia (monocytopenia) - a decrease in the content of monocytes

Infections (caused by bacteria, fungi, protozoa, rickettsiae, certain viruses, spirochetes)

Inflammatory processes (rheumatism, rheumatoid arthritis, pancreatitis, dermatitis, peritonitis, thyroiditis)

Condition after surgery

Ischemic tissue necrosis (heart attacks) internal organs- myocardium, kidneys, etc.)

Endogenous intoxications ( diabetes, uremia, eclampsia, hepatocyte necrosis)

Physical stress and emotional stress and stressful situations: exposure to heat, cold, pain, burns and childbirth, pregnancy, fear, anger, joy

Oncological diseases (tumors of various organs)

Reception of some medicines eg corticosteroids, digitalis preparations, heparin, acetylcholine

Lead, mercury, ethylene glycol, insecticide poisoning

Some infections caused by bacteria (typhoid and paratyphoid, brucellosis), viruses (flu, measles, chicken pox, viral hepatitis, rubella), protozoa (malaria), rickettsiae ( typhus), protracted infections in the elderly and debilitated people

Diseases of the blood system (hypo- and aplastic, megaloblastic and iron deficiency anemia, paroxysmal nocturnal hemoglobinuria, acute leukemia, hypersplenism)

Congenital neutropenia (hereditary agranulocytosis)

The impact of cytostatics, anticancer drugs

Drug-induced neutropenia associated with hypersensitivity of individuals to the action of certain drugs (non-steroidal anti-inflammatory drugs, anticonvulsants, antihistamines, antibiotics, antiviral agents, psychotropic drugs, drugs that affect cardiovascular system, diuretics, antidiabetic drugs)

Allergic sensitization of the body (bronchial asthma, allergic rhinitis, pollinosis, atopic dermatitis, eczema, eosinophilic granulomatous vasculitis, food allergy)

Drug allergy (often to the following drugs - aspirin, aminophylline, prednisone, carbamazepine, penicillins, levomycetin, sulfonamides, tetracyclines, anti-tuberculosis drugs)

Skin diseases (eczema, dermatitis herpetiformis)

Acute period of infectious diseases (scarlet fever, chicken pox, tuberculosis, infectious mononucleosis, gonorrhea)

Malignant tumors (especially metastasizing and with necrosis)

Proliferative diseases hematopoietic system(lymphogranulomatosis, acute and chronic leukemia, lymphoma, polycythemia, myeloproliferative diseases, condition after splenectomy, hypereosinophilic syndrome)

Inflammatory processes of connective tissue (nodular periarteritis, rheumatoid arthritis, systemic scleroderma)

Pulmonary disorders - sarcoidosis, pulmonary eosinophilic pneumonia, Langerhans cell histiocytosis, eosinophilic pleurisy, pulmonary eosinophilic infiltrate (Leffler's disease)

Myocardial infarction (adverse sign)

The initial phase of the inflammatory process

Severe purulent infections

Intoxication by various chemical compounds, heavy metals.

Chronic myeloid leukemia (eosinophilic-basophilic association)

Hypersensitivity to food or drugs;

Reaction to the introduction of a foreign protein

Chronic hemolytic anemia

Condition after splenectomy

Treatment with estrogens, antithyroid drugs

Infectious diseases: infectious mononucleosis, viral hepatitis, cytomegalovirus infection, whooping cough, SARS, toxoplasmosis, herpes, rubella, HIV infection

Diseases of the blood system: acute and chronic lymphocytic leukemia; lymphosarcoma, heavy chain disease - Franklin's disease

Poisoning with tetrachloroethane, lead, arsenic, carbon disulfide

Treatment with drugs such as levodopa, phenytoin, valproic acid, narcotic analgesics

Acute infections and diseases

Loss of lymph through the intestines

Systemic lupus erythematosus

Terminal stage of oncological diseases

Immunodeficiencies (with T-cell deficiency)

Taking drugs with a cytostatic effect (chlorambucil, asparaginase), glucocorticoids, administration of antilymphocyte serum

Infections (viral, fungal, protozoal and rickettsial etiology), as well as the period of convalescence after acute infections

Granulomatosis: tuberculosis, syphilis, brucellosis, sarcoidosis, ulcerative colitis (non-specific)

Systemic collagenoses (systemic lupus erythematosus), rheumatoid arthritis, periarteritis nodosa

Blood diseases (acute monocytic and myelomonocytic leukemia, myeloproliferative diseases, multiple myeloma, lymphogranulomatosis)

Poisoning with phosphorus, tetrachloroethane

Aplastic anemia (bone marrow damage)

Regenerative shift - the number of stab and young neutrophils is increased against the background of a general increase in leukocytes - this is an indicator of increased bone marrow activity, which is observed in inflammatory and purulent-septic diseases

Degenerative shift - an increase in the number of stab neutrophils, the appearance of degenerative changes in cells - such a shift indicates a functional inhibition of the bone marrow, which can occur both with an increase in leukocytes and with a decrease in leukocytes

With general leukocytosis, it happens with: salmonellosis, toxic dysentery, acute peritonitis, uremic and diabetic coma

Against the background of a decrease in leukocytes, it happens with: viral infections, typhoid and paratyphoid diseases

Yu - young neutrophils

C - segmented neutrophils

Severe - index from 1.0 and above

Medium degree - index 0.3-1.0

Light degree - index no more than 0.3

Normally in 20 percent of practically healthy people

For Addison-Birmer's anemia

With radiation sickness

"blast crisis" - the presence of only regional cells: acute leukemia, metastases of malignant neoplasms, exacerbation chronic leukemia

"Failure" of the leukocyte formula - blast cells, promyelocytes and mature cells, there are no intermediate forms: typical for the onset of acute leukemia

along the myeloid line

along the lymphoid line

Myeloblast - in the granulocytic series is the first morphologically distinguishable cell; it has a non-structural core, single nucleoli; the shape of the nucleus is round, the dimensions are slightly smaller than those of the erythroblast; myeloblast differs from undifferentiated blasts from the class of progenitor cells by the presence of granularity in the cytoplasm; the shape of the cell is often round, even

Promyelocyte (neutrophilic, eosinophilic and basophilic) - the next stage in the maturation of granulocytes - the round or bean-shaped nucleus of the promyelocyte is almost twice as large as the myeloblast nucleus, although this cell is not polyploid; it is often located eccentrically, and the remains of nucleoli can be seen in it; the structure of chromatin already loses the delicate filamentous structure of blast cells, although it does not have a coarse clumpy structure; the area of ​​the cytoplasm is approximately equal to the area of ​​the nucleus; the cytoplasm is abundantly saturated with granularity, which has features characteristic of each row

"maternal myelocyte" - in all respects corresponds to the described promyelocyte, but differs from it in a coarser nucleus (in practice, this form is not taken into account, it was not included in the myelogram) - is a transitional form from the promyelocyte to the next stage of cell maturation

Myelocyte - is a cell with a round or oval, often eccentrically located nucleus that has lost any signs of blast; the cytoplasm is colored in a grayish-bluish tone, its granularity in a neutrophilic myelocyte is smaller than in a promyelocyte; the relative area of ​​the cytoplasm increases; eosinophilic myelocyte has a characteristic uniform orange-red granularity, basophilic myelocyte - polymorphic large basophilic granularity

Metamyelocyte - characterized by a bean-shaped large-lumpy nucleus, usually located eccentrically; the area of ​​its cytoplasm is greater than the area of ​​the nucleus and the cytoplasm contains the same granularity as the myelocyte, but in neutrophilic metamyelocytes it is more scarce than in myelocytes.

Lymphoblast - in the lymphocytic series (large lymphocyte) has all the features of an undifferentiated blast, but is sometimes characterized by single large nucleoli; detection in a smear from a lymph node or spleen of a blast without granularity allows it to be attributed to lymphoblasts; an attempt to differentiate a lymphoblast, a monoblast and an undifferentiated blast by the size and shape of the nucleus, by the width of the cytoplasm rim is not successful, since the lymphoblast under the influence of antigenic stimulation can undergo a variety of changes

Prolymphocyte - has a relatively homogeneous structure of the nucleus, often the remains of nucleoli, but it does not have large clumps of chromatin characteristic of a mature lymphocyte

Plasmablast - has a blast nucleus, granular purple-blue cytoplasm

Proplasmocyte - in comparison with the plasmocyte, it has a denser nucleus, usually located eccentrically, with a relatively larger blue-violet cytoplasm.

Plasma cell - characterized by a wheel-shaped dense nucleus, lying eccentrically; cytoplasm - blue-violet, sometimes with a few azurophilic reddish granules; and in normal and pathological conditions, it can be multinuclear

Stages of a blood test for calculating the leukocyte formula:

1. Blood smear on a glass slide. Carefully washed and fat-free glass slide (its edge) is touched to a drop of blood at the injection site. A smear is made with a grinding glass, placing it at an angle of 45 ° to the glass slide in front of the drop. Bringing the glass to this drop, they wait until the blood spreads along its rib, then with a quick, light movement, they pass the grinding glass forward, not tearing it off the object before the whole drop dries up. A correctly made smear has a yellowish color (thin), does not reach the edges of the glass and ends in a trace (whiskers).

2. Fixation. The best fixation is achieved in absolute methylene alcohol (3-5 min) or in a mixture of Nikiforov from equal parts of absolute ethyl alcohol and ether (30 min).

3. Coloring. The main hematological dyes include methylene blue and its derivative - azure I (methylene azure) and azure II (a mixture of equal parts of azure I and methylene blue), acidic - water-soluble yellow eosin.

Romanovsky-Giemsa paint (factory preparation) has the following composition: azure II - 3 g, water-soluble yellow eosin - 0.8 g, methyl alcohol ml and glycerin ml. The working paint solution is prepared at the rate of 1.5-2 drops of finished paint per 1 ml of distilled water. The paint is poured onto the smear with the highest possible layer, the duration of the coloring is min. After this period, the smears are washed with water and dried in air. With this method, it is possible to differentiate the nucleus well, but much worse - the neutrophilic granularity of the cytoplasm, therefore it is widely used for staining a peripheral blood smear.

A ready-made dye is poured onto a fixed smear with a pipette - the May-Grunwald fixative, which is a solution of eosinmethylene blue in methylene alcohol, for 3 minutes. After 3 minutes, an equal amount of distilled water is added to the paint covering the solution and staining is continued for another 1 minute. After that, the paint is washed off and the smear is dried in the air. Then the dried smear is stained with a freshly prepared aqueous solution of Romanovsky's paint for 8-15 minutes. This method is considered the best, especially for staining smears of bone marrow punctures.

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Shift index

Shift index - the ratio of indicators: (myelocytes + metamyelocytes + stab neutrophils) / segmented neutrophils. Normally, the shift index is 0.06.

An increase in the level of neutrophils (neutrophilosis, neutrophilia) indicates the presence of an infectious or oncological disease, an inflammatory process, it happens after surgical interventions, with ischemic infarctions of internal organs (myocardium, kidneys, etc.), endogenous intoxication (uremia), taking a number of drugs (glucocorticoids , digitalis preparations, sodium heparin, acetylcholine), poisoning, as well as during physical stress and emotional stress.

Neutropenia (granulocytopenia) - a decrease in the number of neutrophils. Isolated neutropenia caused by a deficiency of granulocyte precursors in bone marrow may be congenital or acquired.

● Congenital autosomal recessive neutropenia in combination with pancreatic insufficiency - Shwachman-Diamond-Oski syndrome. Recurrent infections with steatorrhea in the first years of life are characteristic.

● Acquired absolute granulocytopenia (less than 1.8–10 9 /l) occurs with whooping cough, infectious mononucleosis, typhoid fever, panmyelopathy, acute leukemia, severe infectious-toxic processes (sepsis, diphtheria), immune granulocytopenia that occurs under the influence of anti-leukocyte antibodies ( auto- and isoantibodies), after radiation or cytostatic therapy, in the treatment of drugs that are toxic to granulocytopoiesis, the action of benzene, aniline, nitrophenol, etc.

Diagnostic significance of changes in individual hemogram parameters

Acute infectious and inflammatory diseases, exacerbation of chronic diseases, chronic and acute myeloid leukemias, malignant neoplasms non-hematopoietic organs (cancer, sarcoma) in the phase of tumor destruction, erythromyelosis, acute posthemorrhagic anemia, height of graft rejection, burns, early period after large surgical interventions, early phase of massive radiation injury, coma (uremic, diabetic, hepatic coma), intoxication with arsenic, carbon monoxide, epilepsy

Completion of infectious and inflammatory diseases, a number of viral infections (mumps, pappatachi fever, whooping cough), acute and chronic lymphoblastosis, severe thyrotoxicosis (very rarely), chronic radiation sickness

Leukocytosis with absolute zosinophilia

Leukopenia with absolute neutropenia

Decompensation of severe infectious and inflammatory processes, occasionally remission of chronic inflammatory diseases (tuberculosis, gonorrhea, etc.). Avitaminosis (scurvy, pellagra, etc.). Cachexia, dystrophy, starvation. cytostatic disease. Chronic benign familial neutropenia. Chronic benign granulocytopenia childhood(chronic recurrent childhood agranulocytosis). Cyclic neutropenia, autoimmune leukopenia. Chronic intoxication with benzene. Hyperchromic macrocytic anemia (B12 deficiency). Hypersplenism. Leukopenic variants of acute leukemia, chronic lymphocytic leukemia

Leukopenia with absolute lymphocytopenia

Radiation sickness (severe form), cytostatic disease, acquired immunodeficiency syndrome, chronic aleukemic myelosis, leukopenic forms of chronic lymphocytic leukemia

Mononucleosis, monocytic leukemia, viral hepatitis, tuberculosis, most autoimmune processes (rheumatic endocarditis)

Severe septic processes, leukemia

Neutrophilia without shift to the left

Physiological neutrophilia (physical and emotional stress, eating, etc.), convulsions, epilepsy, mild inflammatory processes (superficial infections, polyarthritis), early stages of uncomplicated tumors, mild thyrotoxicosis

Neutrophilia with a slight or moderate shift to the left

Neutrophilia with a pronounced shift to the left

Extensive inflammatory processes caused by highly pathogenic microorganisms

The most severe course of the inflammatory process, autoimmune neutropenia. Neutropenia with a shift of the nuclear formula to the right (overripe hypersegmented forms of neutrophils predominate): B 12 -deficiency anemia, avitaminosis, cachexia, starvation

Leukemias (myeloid leukemia, eosinophilic leukemia). hereditary eosinophilia. Lymphopenia with relative eosinophilia (children's genetic agranulocytosis, B 12 deficiency anemia, chronic benign hereditary neutropenia)

The beginning of an infectious disease, intoxication with chemical compounds, heavy metals

Chronic myeloid leukemia (in parallel with eosinophilia), erythremia, chronic ulcerative colitis, erythroderma, etc.

Shift to the left of the leukocyte formula. Leukogram: transcript

Doctors often use the expression "Shift of the leukocyte formula to the left." But what does this mean for those who are far from the language of medicine? Perhaps this is a harbinger serious illness or option physiological norm, but without special knowledge, this is not easy to understand.

An accurate diagnosis is not made on the basis of a blood test alone, but a leukogram can tell a lot to someone who understands. Sometimes it is enough to look at the blood formula in order to isolate several of the most probable from dozens of alleged states. Virtuosos (especially radiologists and oncologists) have even learned to predict symptoms by looking at the ratio of leukocyte fractions.

Leukogram

The leukogram or leukocyte formula is the ratio of the absolute and relative number of white blood cells. Their number is determined simultaneously with erythrocytes, platelets, hemoglobin level and color index, and included in the general blood test, as well as an immunogram.

The shift of the leukocyte formula to the left implies an increase in the number of young and immature forms of neutrophils, the appearance of reticulocytes, metamyelocytes and myelocytes in the peripheral circulation. Such a picture may indicate a compensatory state after blood loss, an inflammatory reaction, bone marrow damage, or radiation sickness. Therefore, in addition to a blood test, it is important to do a complete examination.

The shift of the leukogram to the right is an increase in the absolute and relative number of "obsolete" neutrophils (segmented). This behavior of the blood indicates anemia, diseases of the parenchymal organs, as well as a compensatory window after the transfusion of blood components.

Counting Methods

In order to determine whether there is a shift of the leukocyte formula to the left, it is necessary universal ways counting blood cells. They should be simple and accessible to any laboratory, because clinical analysis blood is basic in any medical research.

Blood cells are distributed unevenly on the glass slide, as they have different densities:

• the peripheral position is occupied by neutrophils, basophils and eosinophils;
• closer to the center of the glass are monocytes and lymphocytes.

To calculate the number of leukocytes, two methods are most often used - Schilling and Filipchenko.

The Schilling method involves determining the number of cells in four opposite areas on a glass slide. In total, about a hundred or two hundred cells are obtained. Based on this amount, the ratio between the fractions is calculated.

The Filipchenko method assumes that the laboratory assistant mentally divides the smear into three parts:

Cells are counted along a conditional line drawn across the smear. In each part, the same number of cells is counted. In total, about two hundred leukocytes are obtained. All cells are recorded in a table or Egorov grid. In order to quickly and accurately determine the leukocyte formula, in addition to differential table use a special 11-key calculator.

Age norm

The shift of the leukocyte formula to the left is a fairly general concept, depending on the basic indicators, the specifics of the disease, and also on age, since the absolute number of leukocytes varies depending on the period of a person's life.

In the first year, the norm of white blood cells is from 6 to 17 thousand leukocytes in one microliter of blood. By the age of four, this level drops to 15.5 thousand. In six years, the figure drops by another thousand. Over the next 4 years, the number of leukocytes slowly decreases to 4.5-13 thousand per microliter. When a child enters puberty, the level of white cells approaches that of an adult and the physiological increase is no longer observed, except perhaps only in certain fractions.

How to determine the shift of the leukocyte formula? To do this, it is necessary to break down the absolute number of leukocytes first into granulocytes and agranulocytes, then among granulocytes also differentiate into neutrophils, eosinophils and basophils, and then calculate how many young cells are among neutrophils and how many are mature. If young neutrophils predominate, then there is a shift. To make this process easier, there are special techniques and indexes.

How the analysis is done

Each patient who comes to the therapist needs to determine the leukocyte blood count. The analysis is deciphered by a doctor, but in order for the results to be reliable, it is important to properly prepare for the study. Luckily, it's not that hard:

• do not eat at least 4 hours before blood sampling;
• do not play sports;
• avoid stress.

For research, venous blood is taken. A drop of liquid is transferred to a glass slide and the number of cells is counted. The results of the analysis can be obtained the very next day. How to determine the shift of the leukocyte formula to the left? The easiest way is to ask your doctor, but if this is not possible, then you need to look at the ratio of stab and segmented neutrophils. If the former prevail, then there is a shift. But it is better to consult with a specialist.

Deciphering the leukogram

And now, in the patient's arms leukocyte formula blood. Deciphering her is a responsible matter, requiring specific knowledge and experience, therefore, with the results, the patient goes straight to the doctor. There are several standard situations that can be observed in the leukocyte formula:

1. Shift of the leukocyte formula to the right. This is a state when the number of segmented neutrophils prevails over other fractions of these cells. As a rule, such a picture appears with radiation sickness, B12-deficiency anemia, diseases of the liver and kidneys, as well as in patients who have recently had a blood transfusion.
2. The shift of the leukocyte formula to the left is an increase in young, undifferentiated blood cells. What does the shift of the leukocyte formula to the left mean? Usually, it's spicy inflammatory process. However, after taking certain medications, as well as in case of poisoning, the blood picture may be similar.

It is worth remembering that a lot can be learned from a leukogram, but not everything. Therefore, it is imperative to additional examination and in no case do not engage in self-diagnosis.

Neutrophils

Neutrophils are one of the types of leukocytes that have a fragmented nucleus. These cells are so named because when stained according to Romanovsky-Giemsa, they stain equally well with both acidic and basic dyes. Their function in the body is to eliminate foreign proteins and cytolysis products. This process is called phagocytosis. The residence time of neutrophils in the peripheral blood is only 6-7 hours, after which they seep into the tissues, where they fulfill their obligations.

In the leukocyte formula, the neutrophil fraction is presented in several forms at once. This is the total percentage, which should normally be within the percentage of the presented leukocyte mass. The entire pool of neutrophils is also divided into:

• young cells (normal up to 5%) - whole nucleus;
• stab (also up to 5%) - the nucleus is divided into only two parts;
• segmented (up to 40 to 68%) - the nucleus is fragmented into three or more parts.

The shift of the leukocyte formula to the right means that the fraction of young and stab neutrophils prevails. Even if the absolute number of cells remains within the normal range, a violation of the ratio between mature and young cells indicates the presence of a disease.

In children at five days of age and at five years old, the so-called physiological crossover of neutrophils occurs. Immediately after the birth of a child, the leukocyte formula practically repeats that of an adult. This is due to the fact that most of the cells were provided by the mother's body. Over time, the composition of leukocytes changes, and lymphocytes begin to predominate over neutrophils. And at the age of five, everything falls into place.

The degenerative shift of the leukocyte formula is manifested in a selective increase in the number of stab neutrophils. This warning sign indicating depletion and inhibition of bone marrow function.

Eosinophils

Eosinophils are one of the types of leukocytes, so named because of staining with predominantly acidic dyes. Their nucleus consists of two segments connected by a constriction. These cells are able to independently move through the vessels and tissues, and are prone to chemotaxis during inflammation or injury. They are also able to absorb and digest foreign microorganisms and proteins.

In adults, they should normally be no more than 5 percent, in children this figure is slightly higher - up to 7 percent. A shift of the leukogram to the left (an active inflammatory process) implies a decrease in the number of eosinophils, since the release of adrenal hormones leads to a delay in the cells in the bone marrow and inhibits their proliferation.

Basophils are one of the types of leukocytes that have a round or C-shaped nucleus and stain with alkaline dyes. The cells are large, contain many granules in the cytoplasm with inflammatory mediators inside.

They take part in allergic reactions along with eosinophils. In addition, basophils bind toxic substances and prevent them from spreading throughout the body and regulate blood clotting processes due to the release of heparin molecules. Like eosinophils and mast cells, basophils have receptors for immunoglobulin E on their surface. If an allergen enters the body, the basophil “explodes” (degranulates) and releases all accumulated chemical substances into the bloodstream. This contributes to the development of an anaphylactic reaction, and also provides a typical local picture of inflammation.

In a healthy body, they should contain no more than one percent. An increase in the amount occurs during allergies, blood diseases, viral, bacterial or autoimmune liver damage, endocrinological disorders. A decrease in the level of basophils is observed after prolonged exposure to radioactive rays, with acute infection, stress, and excessive function thyroid gland.

Monocytes

Monocyte is translated from Greek as "lonely cell" or "one cell". These are large cells without granules with a large non-segmented nucleus. Belongs to the class of phagocytes. The cytoplasm contains a large number of organelles - lysosomes, which are involved in the digestion of foreign proteins and microorganisms.

Normally, they should be no more than 11 percent in peripheral blood. In addition, most of them quickly move into the tissues to perform their functions. An increase in the number of monocytes occurs in severe infectious processes, malignant tumors, systemic autoimmune diseases connective tissue, diseases of the hematopoietic system, and during convalescence. In addition, a rise in monocytes is often observed after surgical interventions.

A decrease in the number of these cells is associated with long-term use of steroid drugs, sepsis, the development of aplastic anemia and hairy cell leukemia, Salmonella infection. typhoid fever, as well as physiological childbirth.

Lymphocytes

Lymphocytes are the main cells that provide our immunity and regulate the number and activity of other blood cells. They are of three types:

• natural, or natural killers (controlling the timely death of "broken" and old cells);
• T-lymphocytes - provide the cellular link of immunity;
• B-lymphocytes are responsible for the production of immunoglobulins.

An adult should normally have at least 19% of lymphocytes in peripheral blood, but not more than 37. In children, this figure is higher - up to 50. An increase in the number of cells can be both physiological and pathological. A natural rise in the level of lymphocytes occurs after hard physical labor, and in women at the beginning of the menstrual cycle. An excessive number of these cells indicates the presence of a viral infectious disease.

A decrease in lymphocytes is possible with immunodeficiency states, taking hormones of the adrenal cortex, malignant oncological processes, insufficiency of peripheral circulation, as a rule, at the same time there is a shift of the leukocyte formula to the left. An example of such a condition is a severe viral or bacterial infection.

Leukocyte indices

The leukocyte index is the ratio between different fractions of leukocytes. The following are distinguished:

1. The Harkavy index is the ratio of lymphocytes and segmented neutrophils.
2. The Kalf-Kalif index indicates the level of intoxication and is calculated as the ratio of the sum of all granulocytes multiplied by the number of plasma cells and divided by the absolute number of agranulocytes multiplied by the number of eosinophils.
3. The index of the degree of toxicosis is the ratio between the total pool of monocytes, metamyelocytes and stab cells with mature neutrophils.
4. The shift index of the leukocyte formula is the ratio between the number of young and mature neutrophils.
5. The immunoreactivity index is calculated as the division of the number of lymphocytes and eosinophils by monocytes.

There are also more specific indices, but they are in general practice not used, but rather needed for scientific research.

The leukocyte formula is an indicator of the state of peripheral blood, reflecting percentage leukocyte cells of various types. Normally, the ratio of cells of the lecopoietic series has characteristics depending on the age of the child.

The situation with the formula in healthy children

Healthy newborns have shift of the leukocyte formula with a shift index of 0.2 (at a rate of 0.06 in adults). At the birth of a child in the formula, 60-65% of the leukogram is represented by neutrophils and 30-35% by lymphocytes. By the end of the first week of life, the number of these cells equalizes to ~ 45% and the “first crossover” of the leukocyte formula occurs, and by the 10-14th day, physiological lymphocytosis is formed in the blood of the newborn. The content of lymphocytes in the leukocyte formula is 55-60%. In addition, an increase in the number of monocytes up to 10% is characteristic. The second crossover in the leukocyte formula occurs at the age of 5-6, after which, by the age of 10, the blood leukogram acquires the features of an adult:

• stab neutrophils - 1-6%,
• segmented neutrophils 47-72%
• lymphocytes 19-37%,
• monocytes 6-8%,
• eosinophils 0.5-5%,
• basophils 0-1%.

A sharp increase in the number of lymphocytes in the blood in the first week after birth and their predominance in the "white" blood formula up to 5-6 years of age is a physiological compensatory mechanism associated with a pronounced stimulation of the child's body with antigens and the formation of the child's immune system. According to a number of authors, there is currently an earlier crossover in the leukocyte formula, a tendency to eosinophilia, relative neutropenia, and an increase in the number of lymphocytes.

Lymphocyte changes

Estimating the number of lymphocytes in a blood test in children, first of all, take into account the age characteristics of the leukocyte formula. So, in children under the age of 5-6 years, lymphocytosis is considered to be an increase in the number of lymphocytes over 60% and their absolute number over 5.5-6.0 x10 9 /l. In children older than 6 years with lymphocytosis leukocyte blood count demonstrates the content of lymphocytes more than 35%, and their absolute number exceeds 4 thousand. in 1 µl.

Functions of lymphocytes

The number of lymphocyte cells in the blood can be influenced by various physiological processes in the body. For example, a tendency to lymphocytosis is noted in children whose diet is dominated by carbohydrate foods, among residents of the highlands, during menstruation in women. In children with constitutional anomalies in the form of lymphatic diathesis, there is also a tendency to increase the content of lymphocytes in the blood.

The main function of lymphocytes is participation in the formation of the immune response. Therefore, secondary blood lymphocytic reactions are most often encountered in pediatric practice, accompanying:

• viral infections (measles, influenza, rubella, adenovirus, acute viral hepatitis);
• bacterial infections (tuberculosis, whooping cough, scarlet fever, syphilis)
• endocrine diseases (hyperthyroidism, panhypopituitarism, Addison's disease, ovarian hypofunction, thymus hypoplasia);
• allergic pathology (bronchial asthma, serum sickness);
• immunocomplex and inflammatory diseases (Crohn's disease, ulcerative colitis, vasculitis);
• taking certain medications (analgesics, nicotinamide, haloperidol).

Lymphocytosis in viral infections is recorded, as a rule, in the stage of convalescence - the so-called lymphocytosis of recovery.

Familial benign eosinophilias that are asymptomatic and inherited in an autosomal dominant manner have been described.

Change in the number of basophils

Basophilic granulocytes are involved in the formation of the immune (often allergic) and inflammatory response in the human body. With basophilia leukocyte formula of blood demonstrates the content of basophilic cells over 0.5-1%. Basophilia is rare. An increase in basophilic cells up to 2-3% occurs more often in chronic myeloid leukemia, lymphogranulomatosis, hemophilia, tuberculosis lymph nodes, with allergic reactions.

Conclusion

The tactics of the practitioner in various cellular reactions of the blood in children primarily depend on the clinical picture of the disease. If changes in the blood are a symptom of the disease, then, first of all, its treatment is carried out. If after the patient's clinical recovery in the blood test, pathological changes, then additional diagnostic measures for the purpose of diagnosing complications or concomitant diseases. In some cases, it may be necessary to consult a pediatric hematologist or oncologist.

Sepsis is a generalized form of purulent-inflammatory infection caused by opportunistic bacterial microflora, the pathogenesis of which is associated with dysfunction of the immune system (mainly phagocytic) with the development of an inadequate systemic inflammatory response (SVR) in response to the primary septic focus.

Systemic inflammatory response is a general biological non-specific immunocytological reaction of the body in response to the action of a damaging endogenous or exogenous factor. In the case of sepsis, SVR occurs in response to the primary purulent-inflammatory focus. SVR is characterized by a rapid increase in the production of pro-inflammatory (in more) and anti-inflammatory (to a lesser extent) cytokines, inadequate to the action of the damaging factor, which induces apoptosis and necrosis, causing the damaging effect of SVR on the body.

Sepsis of newborns

Epidemiology of sepsis

In the domestic literature, there are no reliable data on the frequency of sepsis among newborns, which is largely due to the lack of generally accepted diagnostic criteria diagnosis. According to foreign data, the frequency of sepsis among newborns is 0.1-0.8%. A special contingent of patients are children in intensive care units and intensive care(ICU), as well as premature newborns, among them the incidence of sepsis is on average 14%.

In the structure of neonatal mortality, according to the Russian Federation, sepsis averages 4-5 per 1000 live births. Mortality rates from sepsis are also fairly stable at 30-40%.

Sepsis classification

There is currently no generally accepted clinical classification of sepsis (both in Russia and abroad). Last accepted in Russia clinical classification sepsis of newborns was published more than 15 years ago and does not meet modern requirements. In the International Classification of Diseases X Revision (ICD-10), which defines the diagnosis code for statistics, “bacterial sepsis of the newborn”, code P36, is highlighted.

In contrast to the coding classification, when compiling the clinical classification of the disease, it is necessary to take into account the time and conditions for the onset of sepsis - which developed before the birth of the child, after birth; localization of the entrance gate and / or primary septic focus, clinical features diseases. These parameters characterize the etiological spectrum of the disease, the volume and nature of therapeutic, preventive and anti-epidemic measures. It is these parameters that should be used in the classification of neonatal sepsis.

By development time:

❖ early neonatal sepsis;

❖ late neonatal sepsis.

By localization of the entrance gate (primary septic

❖ umbilical;

❖ pulmonary;

❖ skin;

❖ nasopharyngeal;

❖ rhinoconjunctival;

❖ otogenic;

❖ urogenic;

❖ abdominal;

❖ catheterization;

❖ other.

According to the clinical form:

❖ septicemia;

❖ septicopyemia.

By the presence of symptoms of multiple organ failure:

v septic shock;

❖ acute pulmonary insufficiency;

❖ acute heart failure;

❖ acute renal failure;

❖ acute intestinal obstruction;

❖ acute adrenal insufficiency;

❖ cerebral edema;

❖ secondary immune dysfunction;

❖ DIC.

With antenatal or intranatal infection of the fetus with a clinical manifestation of the disease in the first 6 days of a child's life, it is customary to speak of early sepsis of newborns. Its features: intrauterine infection, the absence of a primary infectious focus and the predominance of the clinical form without metastatic pyemic foci (septicemia).

With the clinical manifestation of sepsis on the 6-7th day of life and later, it is customary to speak of late neonatal sepsis. Its feature is postnatal infection. In this case, the primary focus of infection is usually present, and the disease in 2/3 cases proceeds in the form of septicopyemia.

The above clinical classification of neonatal sepsis is closely related to the spectrum of the most likely pathogens, knowledge of which is extremely important for the rational choice of primary antibiotic therapy. The range of possible pathogens varies depending on the location of the entry gate of the infection, and therefore it is advisable to indicate this parameter in clinical diagnosis sepsis. The localization of the entrance gate has a certain epidemiological significance and is important for the development of anti-epidemic and preventive measures. There are umbilical, cutaneous, otogenic, nasopharyngeal, urogenous, catheter, pulmonary, abdominal and other less common types of sepsis.

Septicemia is a clinical form of sepsis characterized by the presence of microbes and / or their toxins in the bloodstream against the background of severe symptoms infectious toxicosis, but without the formation of pyemic foci. Morphologically and histologically, signs of microbial damage and myelosis of parenchymal organs can be detected.

Septicopyemia is a clinical form of sepsis characterized by the presence of one or more pyemic, metastatic, pyoinflammatory foci. The criterion for septicopyemia is the uniformity of the pathogen isolated from the foci of inflammation and the blood of the patient.

Syndromes of organ failure determine the severity and outcome of the disease, requiring specific treatment, and therefore it is also advisable to single them out in the clinical diagnosis. Among them, due to the severity of the prognosis, the symptom complex of septic (infectious-toxic) shock deserves special attention.

Septic shock refers to the development of a progressive arterial hypotension, not associated with hypovolemia, in conditions of an infectious disease. Despite the name, septic shock is not considered a predictor of sepsis - the condition can occur in other severe infectious diseases (peritonitis, meningitis, pneumonia, enterocolitis).

Etiology of sepsis

Sepsis is caused exclusively by conditionally pathogenic microflora. In some cases, for example, with immunodeficiency of the newborn, sepsis can be integral part generalized mixed infection - viral-bacterial, bacterial-fungal, etc.

The cause of sepsis in children can be over 40 conditionally pathogenic microorganisms, but most often sepsis is caused by streptococci, staphylococci, E. coli, Klebsiella and other gram-negative bacteria and anaerobes.

The etiological structure of neonatal sepsis depends on the time of infection of the fetus and newborn (Table 7-1).

Early (congenital) neonatal sepsis is most often caused by gram-positive cocci S. agalacticae, belonging to group B streptococci. This pathogen can cause antenatal and intranatal infection of the fetus; E. coli and other members of the intestinal Gram-negative bacillus family are much less likely to cause fetal infection.

Table 7-1. The most probable etiology of early sepsis of newborns depending on the time of infection of the fetus and newborn

Late neonatal sepsis usually results from postnatal infection. The main pathogens are E. coli, S. aureus and Klebsiella pneumoniae; group B streptococci are rare. The importance of group A streptococci, pseudomonads and enterococci is increasing.

In the structure of gram-negative causative agents of sepsis, which make up about 40%, some changes have occurred over the past 10 years. The role of Pseudomonas spp., Klebsiella spp. and Enterobacter spp. As a rule, these pathogens cause sepsis in ICU patients who are on artificial ventilation lungs (IVL) and parenteral nutrition, surgical patients.

The etiological structure of postnatal morbidity is significantly affected by the localization of the primary septic focus. For example, in the etiology of umbilical sepsis, staphylococci and E. coli play a leading role, and in the etiology of skin and rhinoconjunctival sepsis, staphylococci and group A (3-hemolytic streptococci) also play a leading role. the role is played by staphylococci or a mixed generalized infection caused by the association of staphylococci with fungi of the genus Candida.In abdominal hospital sepsis, enterobacteria, anaerobes are often isolated (Table 7-2).

Table 7-2. The most likely causative agents of sepsis in newborns, depending on the localization primary focus infections

The etiology of generalized infections in immunocompromised patients (including deeply immature newborns) also has a number of features and depends on the nature of immunosuppression (acquired immune system dysfunction, secondary immune deficiency, drug-induced immunosuppression, congenital, hereditary or acquired neutropenia, primary immunodeficiencies and HIV infection). It is far from always that an infection that develops against such a background is sepsis (Table 7-3).

The pathogenesis of sepsis

The starting point of the disease is the presence of a primary purulent focus against the background of the initial failure of anti-infective protection. In this situation, massive microbial contamination, exceeding the possibilities of antimicrobial protection, leads to a breakthrough of the infectious principle into the patient's systemic circulation (bacteremia).

Table 7-3. The most likely causative agents of generalized infections in immunodeficiencies in newborns

Bacteremia, antigenemia and toxemia trigger a cascade of body defense systems - SVR, which involves immunity and mediators, proteins of the acute phase of inflammation, blood coagulation and anti-coagulation systems, kinin-kallekrin system, complement system, etc. In the systemic reaction of the child's body to the breakthrough of the infection into the bloodstream important role play neutrophilic granulocytes, which determine the adequacy of the functioning of other cells and body systems. Neutrophil granulocytes have a high effector potential and almost instantly respond to changes in the tissues and cells of the body, they are able to quickly change metabolism in response to any stimulating effect, up to the development of a "respiratory explosion" and secretory degranulation with the release of bactericidal enzymes that generate toxic oxygen radicals. These cells synthesize not only inflammatory mediators, components of coagulation and fibrinolysis systems, but also biologically active substances that stimulate cell growth. Neutrophil granulocytes are able to interact with cascade inflammatory humoral systems of the body. The degree of bactericidal activity and cytotoxicity also largely depend on the activity of neutrophilic granulocytes. The cationic peptides of these cells (“peptide antibiotics”, defensins) have bactericidal, fungicidal and antiviral activity.

In addition to the above, neutrophils play the role of phagocytes. The significance of phagocytosis carried out by neutrophils and macrophages differs significantly - true phagocytosis is carried out by macrophages. Neutrophilic phagocytosis, although it proceeds more intensively than in mononuclear cells, is due to other biochemical processes, because their task is different. The main function of neutrophils is to initiate an inflammatory response. Biologically active substances secreted by neutrophilic granulocytes have a pro-inflammatory focus; Among them, there are cytokines that work in the foci acute inflammation(IL-8, IL-1, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor) and involved in the regulation of chronic inflammation (IL-6, interferon-γ, transforming growth factor). Neutrophils synthesize wide range surface adhesive molecules, with the help of which they interact with vascular endothelial cells, the immune system, tissues and organs. As a result of adhesion, the sensitivity of neutrophils themselves to cytokines and other mediators changes, which allows them to adequately respond to changes in tissues and organs. The cytotoxicity of neutrophils is significantly higher than that of killer lymphoid cells (T-lymphocytes) and natural killer cells (NK-cells). Neutrophil cytotoxicity factors target the nuclear structures of target cells, structural elements the genetic apparatus of the absorbed object, the destruction of the genome using factors that induce apoptosis (FIA). Cells undergoing apoptosis become objects of phagocytosis and are rapidly destroyed.

Neutrophils actively phagocytize microorganisms, not caring about their true digestion, they are thrown into the intercellular space significant quantities FIA in order to cause damage to the genetic apparatus of pathogenic microorganisms as quickly as possible. The influence of the release of the contents of neutrophilic granules on the processes of inflammation is enormous. The content of neutrophilic granules induces platelet aggregation, the release of histamine, serotonin, proteases, arachidonic acid derivatives, blood coagulation activators, the complement system, the kinin-kallecrein system, etc. Neutrophil PIAs are detrimental to any cells, as they cause the destruction of nucleoprotein complexes of the genome.

Thus, under the conditions of the infectious process, neutrophils initiate SVR, participate in the presentation of the pathogen antigen to activate the specific immune response of the organism. With excessive activation of neutrophils (sepsis), their cytotoxic effect is not limited to foreign cells, being realized in relation to own cells and body tissues.

Excessive SVR underlies the hyperactivation of the hypothalamic-pituitary-adrenal system, which normally provides an adequate response of the body to stress. Activation of this system leads to the release of ACTH and an increase in cortisol in the blood. Excessive activation of the hypothalamic-pituitary-adrenal system in septic shock, fulminant sepsis leads to an inadequate response to the release of ACTH. Along with this, the functional activity of the thyroid gland is significantly reduced, which is associated with a slowdown in oxidative metabolism, which limits the adaptive capabilities of the newborn's body. In severe sepsis (fulminant course, septic shock), in a number of patients, the content of somatotropic hormone (GH) drops. Low maintenance STH in conditions of basal hypercortisolemia contributes to the rapid development of necrotic processes (STH inhibits the inflammatory process).

Another manifestation of inadequate SVR is uncontrolled activation of the blood coagulation system, which inevitably leads to thrombocytopathy and consumption coagulopathy under conditions of increasing depression of fibrinolysis.

Thus, SVR induced by excessive activation of peripheral blood neutrophils, activation of the hypothalamic-pituitary-adrenal system and the hemostasis system underlies the formation of multiple organ failure, leading to profound homeostasis disorders, sometimes incompatible with life.

For mononuclear cells, neutrophils are helper cells. The main role of monocytes and macrophages is true phagocytosis with further thorough digestion of target cell particles half-destroyed by neutrophils, the neutrophils themselves and the inflammatory cell dendrite. Phagocytosis, carried out by macrophages, contributes to the subsidence of inflammation processes and the healing of damaged tissues.

The formation of a mediator response to a bacterial infection, underlying the SVR syndrome, is a genetically controlled process involving ToH-like cell receptors that recognize various structures of microbial origin and induce the expression of nonspecific resistance factors.

As noted above, the SVR syndrome underlies the progressive organ dysfunction, in some cases reaching the degree of organ failure. The pathogenesis of sepsis is characterized by the rapid development of multiple organ failure and profound homeostasis disorders. One of the signs of homeostasis disturbance in sepsis is a pronounced proliferation of opportunistic microflora, which creates the prerequisites for the emergence of new infectious foci and additional translocation of the infectious principle into the systemic circulation. Currently, there is a popular concept that homeostasis disorders are associated with the ingress of endotoxin or lipopolysaccharide endotoxin complex of gram-negative bacteria into the blood, which rapidly colonize the upper sections of the small intestine under conditions of tissue hypoxia. Endotoxin significantly enhances SVR, provokes homeostasis disorders, hypotension refractory to treatment. The entry of antigens into the bloodstream leads to the disorganization of the SVR - mediator chaos. Antigenic overload is the cause of pronounced immunosuppression in conditions of bacteremia and microcirculation disorders, which contributes to the formation of metastatic purulent foci that support SVR, toxinemia, and antigenemia. SVR disorganization is the basis for the development of septic shock.

Clinical picture of neonatal sepsis

The clinical picture of sepsis, regardless of the form (septicemia or septicopyemia), is characterized by severity general condition newborn. Disturbances in thermoregulation are expressed (in full-term morphofunctionally mature newborns - fever, in premature, underweight children, on a aggravated premorbid background - progressive hypothermia), impaired functional state CNS (progressive depression). A dirty-pale or grayish shade of the skin with yellowness and hemorrhages, areas of sclera is characteristic. Marbling of the skin is expressed, acrocyanosis is possible. Jaundice develops early and progresses rapidly. Often there is a general edematous syndrome. A tendency to spontaneous bleeding is characteristic. Facial features are often pointed.

Respiratory insufficiency develops without inflammatory changes on the x-ray, often there is damage to the heart by the type of toxic cardiopathy, accompanied by the development of acute heart failure. Characterized by an increase in the size of the spleen and liver, bloating, pronounced venous network in the anterior abdominal wall, regurgitation, vomiting and anorexia, dysfunction of the gastrointestinal tract up to intestinal paresis are often observed. Typically, the absence of weight gain, the formation of malnutrition.

For premature babies, a subacute course of sepsis is typical in the form of a syndrome respiratory disorders(shortness of breath with periods of bradypnea or apnea), bradycardia, impaired sucking reflex, tendency to hypothermia. These symptoms reflect various degrees development of multiple organ failure. The most typical syndromes of multiple organ failure in neonatal sepsis, as well as their characteristic changes detected in laboratory and instrumental examination methods, are shown in Table. 7-4.

Primary septic focus

As noted above, studying the clinical picture of the disease in late neonatal sepsis, in most cases it is possible to detect a primary septic focus.

After the introduction of primary surgical treatment cord remnant, there was a decrease in the incidence of omphalitis and umbilical sepsis; at present, these diseases occur in no more than a third of cases. Against this background, the incidence of pulmonary (up to 20-25%) and intestinal sepsis (at least 20%) has increased significantly. Other localizations of the primary focus are much less common and do not exceed 2-6%. IN individual cases the entrance gate of infection cannot be established. This is especially true for children with low gestational age, in which alteration processes are mild.

Table 7-4. Clinical and laboratory criteria for organ failure in sepsis (Balk R. et al., 2001*, modified)

The end of the table. 7-4

Note: Pa02 - partial oxygen pressure, Sa02 - arterial oxygen saturation, APTT - activated partial thromboplastin time, ACT - aspartate aminotransferase, AJIT - alanine aminotransferase, LDH - lactate dehydrogenase.

Septicemia

Septicemia is clinically characterized by the development of toxicosis and multiple organ failure against the background of a primary pyoinflammatory focus. Congenital early septicemia is characterized by the presence of isolated symptoms of infectious toxicosis and organ failure in the absence of a primary purulent focus.

Septicopyemia

Septicopyemia is characterized by the development of one or more foci that determine the features of the clinical picture and the course of the disease. Among the metastatic foci of sepsis in newborns, meningitis occupies the first place (more than half of the cases), the second and third are osteomyelitis and abscess pneumonia. Other localizations of pyemic foci (abscesses of the liver and kidneys, septic arthritis, mediastinitis, panophthalmitis, phlegmon of the wall of the stomach, intestines, etc.) are much less common, accounting for no more than 10% of all cases of sepsis in newborns.

Septic shock

Septic shock, according to various authors, is observed in 10-15% of neonatal sepsis, with the same frequency in septicemia and septicopyemia. In 80-85% of cases, septic shock develops in sepsis caused by gram-negative bacilli. The coccal etiology of the disease rarely leads to the development of shock. The exceptions are group B streptococci and enterococci (70-80%). Mortality in the development of septic shock is more than 40%.

The clinical picture of septic shock in newborns is characterized by a rapid, sometimes catastrophic, increase in the severity of the condition, progressive hypothermia, pallor of the skin, inhibition of unconditioned reflexes, tachycardia and bradycardia, increasing dyspnea in the absence of infiltrative changes on lung radiographs, bleeding from injection sites, petechial rash or bleeding from the mucous membranes, pastosity or swelling of the tissues. Exsicosis is possible against the background of edema of tissues and organs, especially parenchymal ones.

The most characteristic symptom is increasing arterial hypotension, refractory to the introduction of adrenomimetics. Shock is also characterized by the development of disseminated intravascular coagulation (DIC) syndrome with thrombocytopenia and consumption coagulopathy, fibrinolysis depression. Along with bleeding, multiple necrosis is rapidly formed, including the walls of the small intestine, cortical parts of the kidneys, myocardium, brain and other organs, which determines the severity of the patient's condition.

Shock is accompanied by severe hormonal dysfunction in the form of hypercortisolemia, a drop in the concentration of thyroid hormones, thyroid-stimulating and growth hormones of the pituitary gland, and hyperinsulinism. In shock, there are pronounced violations of almost all cascade mechanisms of homeostasis regulation, including the systemic mediator response of the body, which acquires the character of "mediator chaos".

The course and outcomes of sepsis

Sepsis is classified as an acyclic infectious disease; untreated or with inadequate therapy, the condition is almost always fatal.

The development of septic shock at the onset of the disease can lead to a fulminant course of sepsis with catastrophic deterioration, multiple organ failure, and symptoms of DIC. Death occurs within 3-5 days of illness. Sepsis of newborns proceeds at lightning speed in approximately 15% of cases; among surgical patients and in hospital sepsis, the incidence of this form reaches 20-25%.

In the blood formula during the fulminant course of sepsis, a tendency to leukopenia is expressed, a shift of the leukocyte formula to the left, an increase in the neutrophil index (NI) *, absolute lymphopenia, thrombocytopenia, aneosinophilia, monocytosis are observed. These changes are typical for severe SVR.

If there is no septic shock at the onset of the disease, or it has been managed to stop, there is an acute course of the disease, the duration of which is up to 8 weeks. This variant of the course of sepsis is observed in 80% of cases. A lethal outcome can occur on the 3-4th week of illness from severe multiple organ failure, incompatible with life.

The period of acute manifestations of the infectious process is up to 14 days, then comes the reparation period, which is characterized by the extinction of the symptoms of toxicosis, the gradual restoration of the functional activity of individual organs and systems, the sanitation of metastatic foci. Splenomegaly, pallor of the skin, lability of the functions of the central and autonomic nervous system, dysbacteriosis of the skin and mucous membranes, body weight deficiency up to degree I-III hypotrophy persist.

During this period, characterized by a decrease in the body's resistance, the risk of superinfection of bacterial, fungal or viral etiology is high. Often the source of superinfection is the rapid proliferation of the intestinal microflora of the child; nosocomial infection is also possible.

Hematological picture in the acute period of sepsis: pronounced leukocytosis (less often - normal values ​​or leukopenia), shift of the leukocyte formula to the left, increased NI. Possible thrombocytopenia, eosinopenia, lymphopenia, a tendency to monocytosis.

During the reparation period, anemia of a redistributive nature develops, moderate monocytosis. Neutrophilia in a third of cases is replaced by neutropenia. A tendency to eosinophilia is characteristic. Basophils and plasma cells can be found in peripheral blood.

Diagnosis and treatment of sepsis in newborns

Diagnostics

Diagnosis of sepsis consists of several stages. First of all, it is necessary to establish or suspect the diagnosis of sepsis. The second stage is the etiological diagnosis of the disease. The third stage is the assessment of dysfunctions of organs and systems, shifts in homeostasis.

The first level of diagnosis is the most difficult - despite many years of studying sepsis, in pediatric practice there are still no generally accepted clinical and laboratory diagnostic criteria that meet the requirements of evidence-based medicine. One of the reasons for this is the absence of a primary infectious focus in a patient; it is localized in the mother's body or in the placenta. In addition, pronounced signs of SVR in children occur in many severe diseases of non-infectious (respiratory distress syndrome, hereditary aminoaciduria, etc.) and infectious (necrotizing enterocolitis of a newborn, phlegmon, meningitis, etc.) nature.

Based on modern ideas about the diagnosis of sepsis, the disease must be assumed in a newborn for the first 6 days. life in the presence of severe infectious toxicosis and signs of SVR:

Prolonged (more than 3 days) fever (>37.5 °C) or progressive hypothermia (<36,2 °С);

Hyperleukocytosis in the first 1-2 days of life >30x109, on the 3rd-6th day of life - >20x109, in children older than 7 days of life - >15x109/l or leukopenia<4х109/л, НИ >0.2-0.3, thrombocytopenia<100х109/л;

An increase in the content of C-reactive protein in the blood serum of more than 6 mg / l;

An increase in the content of procalcitonin in the blood serum of more than 2 ng / ml;

An increase in the content of IL-8 in the blood serum of more than 100 pg / ml.

The presence of at least three of the above signs is a good reason for assuming a diagnosis of sepsis and the immediate appointment of empirical antibiotic therapy, carrying out the necessary therapeutic measures.

In newborns older than 6 days of age, the diagnosis of sepsis should be assumed in the presence of a primary infectious-inflammatory focus (associated with the environment) and at least three of the listed signs of SVR. Given that the diagnosis of sepsis still has the status of a clinical diagnosis, it is advisable to retrospectively confirm or reject it within 5 to 7 days. The absence of a connection between the clinical symptoms of SVR and infection speaks against the diagnosis of sepsis and requires further diagnostic search.

The diagnosis of sepsis is confidently established in the presence of a primary infectious-inflammatory focus or metastatic purulent foci with a pathogen also isolated from the blood, provided that at least three signs of SVR are present.

Bacteremia is not considered diagnostic of sepsis; this condition can be observed in any infectious disease of a bacterial nature. The establishment of bacteremia is important for determining the etiology and substantiating rational antibacterial treatment (the second stage of diagnosis). Along with the study of blood culture, the etiological diagnosis of sepsis includes a microbiological study of discharge from the primary and metastatic foci.

Microbiological examination of loci that are in contact with the environment (conjunctiva, mucous membrane of the nasal and oral cavity, skin, urine, feces) and not involved in the primary pyoinflammatory focus cannot be used to establish the etiological diagnosis of sepsis. At the same time, a microbiological study of these media is indicated to assess the degree and nature of dysbacteriosis, one of the constant companions of sepsis due to a decrease in the immunological reactivity of the patient's body (the third stage of diagnosis). Above (see Tables 7-4) are the main clinical, laboratory and instrumental characteristics of multiple organ failure that accompanies neonatal sepsis and determines its outcome. Monitoring of these indicators is necessary for the organization of adequate treatment of patients.

Differential diagnosis of sepsis

Differential diagnosis of sepsis should be carried out with severe purulent-inflammatory localized diseases (purulent peritonitis, purulent mediastinitis, purulent destructive pneumonia, purulent meningitis, purulent hematogenous osteomyelitis, necrotizing enterocolitis of newborns), also occurring with signs of SVR. In contrast to sepsis, such diseases are characterized by a close relationship between the presence of a purulent focus and the pronounced signs of SVR, as well as the relief of these signs soon after the focus is sanitized. However, the main directions of treatment and principles of antibiotic therapy for sepsis and severe pyoinflammatory diseases of a bacterial nature are identical.

Sepsis must be differentiated from generalized (septic) forms of bacterial infections caused by pathogenic pathogens (Salmonella septicemia and septicopyemia, disseminated tuberculosis, etc.). The correct diagnosis of these diseases determines the nature and extent of anti-epidemic measures, the appointment of specific antibiotic therapy. The basis of differential diagnosis is an epidemiological history and data from a bacteriological and serological study of materials taken from a patient.

When conducting a differential diagnosis of sepsis and congenital generalized forms of viral infections (cytomegalovirus, herpetic, enterovirus, etc.), confirmation of the latter justifies specific antiviral and immunocorrective treatment, limiting the use of antibiotics. For this purpose, an immunocytological study is carried out by the method of polymerase chain reaction (PCR) of blood, cerebrospinal fluid and urine, serological tests.

Sepsis must be differentiated from generalized mycoses, primarily candidiasis, much less often from aspergillosis, in order to justify the appointment of antimycotics, limit or cancel antibiotics, and clarify the tactics of immunocorrective treatment. Differential diagnosis is based on the results of microscopic and mycological (inoculation on Sabouraud's medium) examination of blood, cerebrospinal fluid, discharge of pyemic foci.

In newborns, sepsis must be differentiated from a hereditary pathology of amino acid metabolism, accompanied by all the signs of SVR, but not requiring antibiotic therapy. With hereditary defects in amino acid metabolism, a rapid deterioration in the condition of the newborn occurs soon after birth, shortness of breath, pulmonary heart failure, depression of the central nervous system, hypothermia, leukopenia, thrombocytopenia, and anemia progress. A distinctive sign of a defect in amino acid metabolism is persistent intense metabolic acidosis, and a pronounced odor from the patient is possible. Bacteremia is not excluded, demonstrating severe dysbacteriosis and a decrease in the body's resistance. The main method of differential diagnosis is a biochemical blood test (detection of pathological acidemia) in combination with intractable metabolic acidosis.

Total white blood cell count in healthy adults it is 4.00–9.00x10 9 /l. In newborns - 12.00–15.00x10 9 /l, by the age of 5 it decreases to 10.00x10 9 /l, and from the age of 10 it is set at the same level as in an adult. The number of leukocytes in the blood fluctuates during the day, reaching a maximum in the evening. An increase in the number of leukocytes in the blood is called leukocytosis, decrease - leukopenia.

Leukocyte formula

under physiological conditions is subject to fluctuations, depending on the individual characteristics of the body, food intake, time of day and some other factors. The percentages of certain types of leukocytes are as follows: eosinophils 0–5%, basophils 0–1%, myelocytes are absent, metamyelocytes 0–1%, stab neutrophils 1–6%, segmented neutrophils 45–70%, lymphocytes 18–40%, monocytes 2–9%.

In addition to the percentage of individual types of leukocytes, their absolute numbers are calculated, i.e. how many of each type of cells are contained in 1 liter of blood.

There are norms for the absolute quantities of certain types of leukocytes in 1 liter of blood:

Eosinophils - 0–0.30x10 9 / l.

Basophils - 0–0.65x10 9 / l.

Myelocytes are absent.

Metamyelocytes - 0–0.065x10 9 / l.

Stab neutrophils - 0.04–0.30x10 9 / l.

Segmented neutrophils - 2.00–4.20x10 9 / l.

Lymphocytes - 1.20–3.00x10 9 / l.

Monocytes - 0.09–0.60x10 9 / l.

The assessment of each type of leukocytes (with the exception of the subpopulation of neutrophils) is based on their absolute and relative (%) content in the peripheral blood. The principle of assessing the state of individual leukocytes is explained by us using the example of assessing the state of lymphocytes.

An increase in the number of lymphocytes in the peripheral blood is called lymphocytosis, a decrease in the number of lymphocytes is called lymphocytopenia (lymphopenia). Lymphocytosis and lymphocytopenia (lymphopenia) are divided into absolute and relative.

1. Relative lymphocytosis (lymphocytopenia) is an increase (decrease) in percentage of the proportion of lymphocytes among other leukocytes. Normally, the proportion of lymphocytes among other leukocytes ranges from 18–40%. Thus, an increase in the relative number of lymphocytes over 40% is called relative lymphocytosis. A decrease in the percentage of lymphocytes less than 18% is called relative lymphocytopenia.

Absolute lymphocytosis is an increase in the absolute number of lymphocytes above the upper limit of normal. Absolute lymphocytopenia is a decrease in the absolute number of lymphocytes below the lower limit of normal. Thus, absolute lymphocytosis is the state when the number of lymphocytes in the peripheral blood becomes more than 3.00x10 9 /l. Absolute lymphocytopenia is a condition when the number of lymphocytes becomes less than 1.20x10 9 / l.

Features of assessing the state of neutrophils

The assessment of the state of neutrophils, in comparison with other leukocytes, has two features:

1. In quantitative terms, the content of neutrophils is estimated as the sum of subpopulations of neutrophils, regardless of their degree of maturity. At the same time, the limit of the relative norm of neutrophils is 50–70%. For example, in a patient Ivanov I.I. leukocytes 10.00x10 9 /l, myelocytes 2%, metamyelocytes 4%, stab neutrophils 6%, segmented neutrophils 57%.

A) the relative number of neutrophils in total is equal to

2% + 4% + 9% + 67% = 82% (relative neutrophilia).

B) the absolute number of neutrophils is 82% of 10.00x10 9 /l, i.e. (82% x 10.00x10 9 / l) / 100 \u003d 8.20x10 9 / l (absolute neutrophilia).

1. In addition to quantitative assessment, neutrophils are evaluated qualitatively according to their degree of maturity.

Assessment of the qualitative state of neutrophils is carried out using the calculation nuclear shift index(INS) or the Solovyov-Bobrov index.

NAI is calculated as the ratio of the sum of the relative number of all immature forms of neutrophils present in a given patient to the relative number of mature neutrophils. Mature neutrophils are segmented neutrophils. Under immature neutrophils are meant stab neutrophils, metamyelocytes, myelocytes, promyelocytes and myeloblasts. For example, in a patient Ivanov I.I. myelocytes 2%, metamyelocytes 4%, stab neutrophils 9%, segmented neutrophils 67%. RSI = (2% + 4% + 9%) / 67% = 0.22.

Normally, IAS fluctuates within 0,04–0,08 .

Decrease in IAS less than 0.04 called shift of the neutrophil formula to the right (hyporegenerative nuclear shift). A hyporegenerative nuclear shift is noted with inhibition of neutrophil production in the bone marrow and the predominance of mature forms of neutrophils in the peripheral blood.

Increase in IAS above 0.08 called shift of the neutrophilic formula to the left. This indicates the rejuvenation of peripheral blood neutrophils as a result of increased myelopoiesis in the bone marrow.

There are three types of shift of the neutrophilic formula to the left. If the IAS increases within 0,08–0,50 , the nuclear shift is called regenerative. The regenerative nuclear shift indicates, on the one hand, the presence and sufficient severity of a pathological process in the body (often inflammatory), on the other hand, an adequate protective and adaptive response of the body to this pathological process.

If the IAS increases within 0,50–1,00, the shift is called hyper-regenerative. The presence of such a shift indicates, on the one hand, the high severity of the pathological process, on the other hand, an inadequate reaction of the body. With a nuclear shift of this type, the bone marrow is re-irritated, as a result of which most of the neutrophils are released from it into the blood in immature functionally inactive forms. The protective potential of neutrophils does not increase, but decreases.

If the IAS increases over 1.00, a shift in the neutrophil formula is called degenerate. The appearance of a degenerative nuclear shift indicates a primary violation of the processes of differentiation and maturation of neutrophils. This form of shift of the neutrophil formula to the left is observed most often in leukemia (myeloid leukemia).

Shift left

This phrase describes an increase in the number of stab neutrophils in the leukogram, as well as the appearance of young forms. A similar picture occurs with purulent processes, burns, intoxication, leukemia, extensive bleeding or hemolytic anemia. A slight shift to the left occurs with stress and high physical activity.

shift right

This is the name for a decrease in the number of "rods" in the blood and an increased percentage of segmented forms. Similar results of the analysis are less common than a shift to the left and may indicate polycythemia, anemia, leukemia, blood transfusion, acute bleeding, and other pathologies.

Change in the number of basophils

An increased number of such leukocytes is observed in chronic diseases, for example, ulcerative colitis, hypothyroidism, nephrosis, chronic leukemia. Also, elevated basophils are characteristic of allergies, chicken pox, hemolytic anemia, conditions after removal of the spleen or after treatment with hormonal agents.

A decrease in basophils in the blood is observed very rarely and is not a diagnostically important sign.