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Dysfunctions of granulocytes - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Thrombocytopenia
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
Trobotsitopatiya
Anemias
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

Granulotsitarny leukocytes play a large role in antimicrobic protection of an organism. They are capable to take and destroy foreign debris. The main function of granulocytes — phagocytosis. From all cells neutrocytes possess the strongest phagocytal and bactericidal properties. Absorption and destruction of bacteria takes place in several stages. At implementation in fabric microorganisms emit substances which lead to education in an organism of chemotactic factors. As a result of influence of these factors the chemotaxis of leukocytes is activated and they migrate towards a foreign particle. At the second stage — opsonization — occurs superficial fixing of a microorganism to a neutrocyte. Several factors take part in reaction of opsonization. Neutrocytes bear on the surface receptors to an immunoglobulin Fc-fragment. Immunoglobulin is attached by one part to a microbe, and other part — a Fc-fragment — connects to a neutrocyte receptor. Thus, contact of a leukocyte and microorganism is carried out. IgG directly participates in reaction of opsonization. At opsonization complement components — Ci, C2, Sz, Sa and fixators of IgM have the mediated effect. The following stage of phagocytosis is the absorption phase.
Pseudopodiums of neutrocytes take a bacterium and conclude it in a phagocytal vacuole. Then process of digestion of microorganisms begins. It is composite reaction which is followed by sharp increase of metabolic activity of cells. Digestion of microbic particles is carried out by the enzymes which are contained in cytoplasmatic granules of neutrophils. Distinguish two types of granules: primary — azurophilic and secondary — specific. Azurophilic granules contain a miyeloperoksidaza, a lysozyme, hydrolases. Specific granules — an alkaline phosphatase, a collagenase, a lysozyme, fagotsitin. At formation of a phagocytal vacuole cytoplasmatic granules approach it and empty the contents in a phagosoma. Many of enzymes of granules possess the expressed bactericidal properties. High antimicrobic activity is noted at the miyeloperoksidaza possessing a broad spectrum of activity. It is active concerning gram-positive and gram-negative bacteria, mushrooms, viruses, a mycoplasma. The lysozyme possesses antibacterial action though its activity in relation to gram-negative flora is small. Also possesses bactericidal properties fagotsitin. Process of destruction of microbic bodies is carried out by means of a set of hydrolases. However bactericidal activity of leukocytes is not limited to this system. Big if not the leading role belongs to so-called system of respiratory explosion. More than twice consumption by an oxygen cell increases. Glycolysis and direct oxidation of glyukozo-6-phosphate at the first stages of a pentozny cycle with accumulation of NADF-N amplifies. Activation of oxidases in the presence of molecular oxygen leads to oxidation of NADF-N with formation of NADF and peroxide of hydrogen (H2O2). In turn the oxidized form of a coenzyme stimulates the glyukozomonofosfatny shunt with accumulation of NADF-N at which oxidation new portions of peroxide of hydrogen are formed. Peroxide of hydrogen is the main antimicrobic factor. Now it is proved that bacterial activity of peroxide of hydrogen are considerably potentiated under the influence of a miyeloperoksidaza. It is established that the system hydrogen peroxide — a miyeloperoksidaza — halogens possesses the expressed bactericidal properties (L. Klebahoff, 1969).

The informative reaction allowing to estimate a condition of an oxidizing metabolism is the NBT-test (paint nitroblue tetrazoliya — nitroblum tetrazolium NBT.). Nitroblue tetrazoliya it is englobed by a cell and in the course of oksidazny reactions it is recovered, forming dark glybk of an insoluble formazan which is defined by tsitokhimichesk or calorimetric.
Phagocytosis — difficult multi-stage process in which mechanical, chemical and biochemical systems of a cell participate. Breakdown of any link of these reactions leads to dysfunction of phagocytosis of neutrocytes. Dysfunctions on character can be hereditary and acquired. In the majority it is hereditary defects. Now syndromes at which disturbances of a chemotaxis, degranulation, digestion are observed are described. Hereditary dysfunctions of granulocytes meet seldom. The general symptoms of these diseases are frequent and long infectious processes as a result of disturbance of antimicrobic functions of neutrocytes. In literature cases with disturbance of opsonization which were characterized by recurrent infections and dystrophies are described. The disease is probably inherited on autosomal recessively type and transmitted on the maternal line as it is revealed at mothers and children. At female persons also disturbances of a chemotaxis of neutrocytes are described.
The raised risk group is made by newborns as they note imperfection of some phases of phagocytosis. And it is most expressed at premature children that defines the raised susceptibility them to infections.
Dysfunction of neutrocytes defines development in children of a serious illness — the chronic granulomatosis differently called by a septic granulomatosis. The disease is described in the early sixties our century and so far well studied. It is pathology with an autosomal and recessive mode of inheritance, perhaps, linked to a floor. Boys are ill mainly. If girls, then in rather easy form get sick. Inspection of families revealed that at. fathers of disturbances of phagocytal function of leukocytes are not revealed whereas both healthy, and defective population of neutrocytes occurs at mothers. Clinical displays of a disease at mother usually are absent. At a chronic granulomatosis the main defect of neutrocytes consists in disturbance of the digesting ability at a safe chemotaxis and opsonization. Granulocytes lose bactericidal ability, incomplete phagocytosis is observed. Thus, destruction of the taken bacteria does not happen. At research of the digesting ability a certain deficiency of process of degranulation — slow and incomplete release of granules is revealed. However it is the minor mechanism. The leading link belongs to disturbance of system of respiratory explosion and considerable decrease in formation of peroxide of hydrogen. In neutrocytes the increased intake of oxygen and activation of the metabolic processes inherent to normal phagocytosis is not observed. Low formation of peroxide of hydrogen is demonstrated by almost total absence of granules of a formazan at statement of the NBT-test. On the basis of results of biochemical researches suggested that the main defect at a chronic granulomatosis is the defect NAD*N-oksidazy catalyzing reaction of formation of peroxide of hydrogen. Deficits and other forms of oxidases are possible. In an organism the powerful bactericidal system is switched off. The microorganisms taken by a cell remain in it live. Besides, the cellular membrane of neutrocytes protects bacteria from influence of the medicinal substances and antibodies of an organism which are not diffusing inside granulocytes. The live and reliably protected microorganisms in the course of migration of leukocytes with a blood flow disseminate on all organism, getting into lungs, a liver, a spleen, lymph nodes, skin. At death of cells of a bacterium are released and in places of accumulation granulomas, perhaps, being defense reaction of the organism trying to limit the defeat center form. As the number of contacts of a human body with microorganisms is huge, it leads to forming of a generalized chronic granulomatosis.
Immunological researches demonstrate that the content of immunoglobulins in blood is normal or is even raised. Clinical symptoms of a disease are shown already at early age, till 1-2 flyings. Retsidividuyushchy purulent infections of various localization are noted. Lymph nodes are constantly involved in process, they slightly increase in sizes, are painful, almost at all patients abscess. Not less often a respiratory organs is surprised. Pneumonia constantly recurs, does not give in to an antibioticotherapia. In pulmonary fabric multiple granulomas form. At a chronic granulomatosis damages of skin — furuncles, abscesses are typical. At most of the sick children living several years, a constant symptom is increase in a liver, spleen. Bone defeats in a type of osteomyelites are frequent. The forecast bad, most of children perish from a persistent purulent infection, is more often than pulmonary localization. In peripheral blood the neutrocytosis is noted. Neutrocytes have unusually large granules and vacuoles. As a result of chronic infectious process at most of patients anemia is often noted. There are no effective remedies of therapy now. Use of the antibiotics capable to get in a cell (rifampicin), and sulfanamide drugs, perhaps, the granulocytes increasing bactericidal activity is recommended.
The clinical picture similar to chronic granulomatosis is observed at a family lipokhromny histiocytosis. The bactericidal digesting function of neutrocytes is broken. NBT-the test demonstrates low formation of peroxide of hydrogen. Generalized granulematozny defeat of bodies is noted. Find the histiocytes containing lipokhromny material in patients. In a clinical picture, except a recurrent purulent infection, damage of joints of negranulematozny genesis is observed. The disease is inherited on autosomal dominantly type.
In 1966 S. D. Davis described the state similar in a clinical picture to a chronic granulomatosis. And this syndrome is observed at girls with red hair and light skin. A mode of inheritance — autosomal and recessive. Disturbance of bactericidal function of granulocytes with sharp decrease in the NBT-test is noted. The disease is shown by a recurrent purulent infection of various localization, but with preferential skin defeat — eczemas, abscesses. Disease is easier, than at a chronic granulomatosis.
The combined dysfunction of granulocytes which is combined with a leukopenia is observed at Chediak's syndrome — Higasi. The disease is for the first time described in 1952 by M. Chediak and O. with Higachi in 1953 is added. At patients nonspecific mechanisms of protection owing to disturbance of phagocytal ability of granulocytes are considerably reduced. As a result of defect of lizosomalny membranes the incomplete and slowed-down outpouring of contents of granules in phagocytal vacuoles with simultaneous decrease in the digesting ability of cells is noted. At Chediak's syndrome — Higasi also broke a chemotaxis of granulocytes. Breakdown of phagocytes happens in several links at once: a chemotaxis — degranulation — digestion. The leukopenia pathogeny is up to the end not clear. Assume that leukocytes have the shortened term of life and quicker collapse. The disease has family character with an autosomal and recessive mode of inheritance, is shown at the gomozigot having breakdown of two genes. A half of patients come from related marriages. Girls and boys are ill with an identical frequency. A typical type of patients — they are albinos, the iris of the eye is transparent, pupils with a red shade, an eyeground pale. The reduced slezootdeleniye, a photophobia are noted. Pigmental damages of skin are characteristic. Sites of hyperpegmentation are located asymmetrically on skin of a trunk, the person, extremities, mainly on open body surfaces. Patients excessively sweat.
At children lymph nodes, a liver, a spleen increase. The hepatomegalia can be followed by jaundice symptoms. As the heaviest and typical displays of an illness serve frequent infectious diseases with development of purulent complications. Also recurrent damages of skin are observed. Purulent otitis, quinsy, pneumonia, development of sepsis are frequent. At the long course of a disease the state is aggravated for century of communication with a lymphocytic infiltration of different bodies. Temperature increases, lymph nodes, a liver considerably increase, the pancytopenia accrues, defeat of a nervous system is possible. In peripheral blood the neutropenia, anemia, thrombocytopenia are noted. At Chediak's syndrome — Higasi observe morphological anomalies of all forms of leukocytes. Neutrocytes, monocytes, contain huge granules up to 4 microns. Kernels of neutrocytes have the small sizes, chromatin in them is structurally changed. Forecast of a disease adverse. The children suffering from Chediak's syndrome — Higasi, usually do not live up to youthful age. There are no effective remedies of treatment now. At a purulent infection use antibiotics of a broad spectrum of activity, symptomatic means. There are messages on positive influence on function of granulocytes of high doses of ascorbic acid. At a limfogistiotsitarny infiltration purpose of Prednisolonum and Vincristinum is possible.
In literature the hereditary pathology of the phagocytal function of neutrocytes (digesting abilities), caused by the isolated deficit of a miyeloperoksidaza is described. As the important sign distinguishing this pathology from a chronic granulomatosis serves the normal NBT-test (at this pathology formation of peroxide of hydrogen is not broken). The disease is inherited on an autosomal retsissivnomu to type. The syndrome proceeds is rather good-quality, without heavy infectious and purulent processes.
Cases of the isolated deficit of a glutationperoksidaza and glyukozo-6-fosfatdegidrogenazy neutrocytes are so far described. The disease carries probably an autosomal and recessive mode of inheritance. It is characterized by recurrent purulent infections. On a current it is similar to a chronic granulomatosis and also leads to formation of multiple granulomas in different bodies.
At some hematologic syndromes there are accurate anomalies of morphological structure of leukocytes, however they are not followed by dysfunction of cells.
Widespread hereditary pathology of leukocytes is the pelgerovsky anomaly for the first time described by the Dutch hematologist O. of Pelger in 1928. The symptom has family character and is transferred on autosomal dominantly type. Usually comes to light at geterozigot though gomozigot have descriptions. Pelgerovsky anomaly with an identical frequency is observed at persons man's and female. The pathogeny of this pathology is not studied, is suggested about the genetic nature (J. Kallo, 1985). The essence of anomaly consists that granulocytes have not segmented kernel. At healthy faces in peripheral blood the main percent of neutrocytes makes segmentoyaderny forms. The kernel of these leukocytes consists of 3 — 4 segments. At pelgerovsky anomaly neutrocytes have a two-segment kernel or one round. Morphologically cells remind band neutrocytes, metamyelocytes, myelocytes. Such picture can serve as the reason of diagnostic confusion. At research of peripheral blood the impression of rejuvenation of cellular structure — neutrophylic shift is made to the left which is regarded as manifestation of infectious process. It forces doctors to undertake long and persistent intrigues of a nonexistent inflammatory disease. From literature cases when it is not proved are known appendectomy was carried out. Therefore the clinical physician estimating a blood count needs to remember pelgerovsky anomaly, especially in those situations when neutrophylic shift to the left without any symptoms of an infectious disease is noted. Abnormal neutrocytes are mature cells, function of phagocytosis at them is not broken. The sizes of cells normal, structure of a kernel dense, cytoplasm usual, with the small granularity inherent to mature segmentoyaderny cells. Except neutrocytes, not segmented kernels occur at eosinophilic, and also at basphilic granulocytes. Perhaps full and partial manifestation of pelgerovsky anomaly. At a partial carriage the quantity of pathological neutrocytes is small, within 10%, at full manifestation in peripheral blood 20 — 30% of abnormal leukocytes meet. Other hematologic indicators — quantity of erythrocytes, hemoglobin, reticulocytes — remain normal. The bleeding duration, a blood clotting time, SOE are not changed. In marrow punctate among yadrosoderzhashchy cells abnormal forms of granulocytes prevail. Pelgerovsky anomaly, irrespective of a heterozygous or homozygous carriage, clinically documents nothing itself. People are almost healthy, with a usual susceptibility to an infection. The increased risk of incidence at them is not observed. Often carriers reveal accidentally at research of blood smears. Increase of cases of registration of people with pelgerovsky anomaly is connected with more wide-ranging studies of blood. At identification of a pelgerovsky anamoliya at children in the diagnostic purposes it is necessary to investigate blood at their parents, quite often at them it is possible to find similar changes.
Now so-called psevdopelgerovsky anomaly is described. It is characterized by the morphological changes of neutrocytes similar to pelgerovsky anomaly. This syndrome is observed at serious infectious diseases, intestinal infections, an agranulocytosis, an acute miyeloblastny leukosis. Unlike true anomaly at psevdopelgerovsky structure of a kernel more gentle, mesh. The hematologic syndrome is passing — after recovery these changes take place.
A peculiar anomaly is the hereditary hypersegmentation of kernels of neutrocytes described E. Undritz in 1950. It has family character and is inherited on autosomal dominantly type. Anomaly is as if contrast pelgerovsky. Find a large number of neutrocytes with four and more segments of kernels in peripheral blood. The essence of this anomaly is unknown. Phagocytal activity of cells is not broken. People are almost healthy, no deviations at them are noted. In the clinical plan it is necessary to remember that neutrocytes with the hyper segmented kernels occur at children at B12-scarce anemia. Existence of huge forms of neutrocytes is a differential sign at anemia. Under the influence of specific therapy by B12 vitamin these changes take place.
E. Undritz is also described hereditary hypersegmentation of kernels of eosinophilic granulocytes which can be combined with segmentation of kernels of monocytes. Anomaly has family character of not clear genesis. Its essence is that the kernel of eosinophilic granulocytes instead of usual two consists of 3 segments. Function of cells is not broken. There are no clinical manifestations. At B12-scarce anemia hypersegmentation of kernels of eosinophilic granulocytes can be passing and at treatment to disappear.
Rare pathology of leukocytes is Aljder's anomaly which is characterized by existence in cytoplasm of large azurophilic granularity. Granularity very plentiful and in the painted smears of a kernel of cells are almost not visible. Anomaly is found in all leukocytes — neutrocytes, lymphocytes, monocytes. Functions of cells are not broken. Alder's anomaly is combined with a gargoilizm — the disease relating to group of mukopolisakharidoz. It allows to assume that anomaly of leukocytes is caused by the main process — disturbance of an exchange of mucopolysaccharides. As a result of enzymatic defect of a - L - giluronidazy in cytoplasm of cells collect acid mucopolysaccharides. The disease has hereditary character and is transmitted on autosomal recessively type.
Dysfunctions of granulocytes can have secondary character. Symptomatic dysfunctions of neutrocytes are caused by toxic action of different factors on marrow. As well as at hereditary pathology, the acquired dysfunctions of granulocytes are characterized by disturbance of phagocytosis at various stages — hemosaksis, opsonization, absorption, digestion. They are observed at autoimmune diseases — a system lupus erythematosus, a pseudorheumatism. Phagocytosis function (opsonization, bactericidal action) suffers at treatment from corticosteroids, salicylates, streptocides, antibiotics. At children with a Down syndrome the absorbing capacity in relation to gram-positive flora decreases. Dysfunction of granulocytes is observed at a diabetes mellitus, cirrhosis. Defects of leukocytes have reversible character and at successful therapy of a basic disease these changes take place.



 
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