Give the examples of physiological and pathological leukocytosis.
Physiological leukocytosis is the physiological response of the organism to some actions.
emotionogenic leukocytosis ? develops at strong emotions;
myogenic ? develops at intense physical exertion;
static ? when the body moves up;
alimentary ? develops after meal;
leukocytosis at pregnancy;
leukocytosis of newborn.
Pathological leukocytosis is related with the pathologic process in the organism. As a rule, it develops at:
infection; inflammations and allergic processes; intoxications of exogenous and endogenous origin.
26.2.7. What is reactive leukocytosis? What mechanisms are at the basis of its development?
Reactive leukocytosis develops as a result of red bone marrow response to pathogenic effect. It develops at infections, inflammations, effect of low closes of toxic substances.
In the origin of the development of reactive leukocytosis are two mechanisms:
1. Enhanced proliferation and maturation of leukocytes in red bone marrow. It may be related eighther with the increased leukopoietin production in the organism, substances stimulating the production of leukocytes or with the decrease of leukopoiesis inhibitors.
Among leukopoietins the most researched are colony-stimulating factors ? a substance secreted by activated macrophages and stimulating the production of granulocytes in red bone marrow.
High molecular inhibitor of blood serum ? lipoprotein, keylons and lactopherin plays the part of leukopoiesis inhibitors.
2. The increase of transmission of leukocytes from red bone marrow into the blood. It?s due to interleukin-1 and bacterial endotoxins increasing the wall permeability of the blood vessels of red bone marrow.
26.2.8. What is particular for redistributive leukocytosis?
This is leukocytosis developing in the result of transmission of leukocytes from parietal pool to circulatory one.
Its particularities are:
temporary character with quick returning of the number of leukocytes to normal after the causative action is over;
keeping to normal the quantitative ratio of various types of leukocytes (leukocytic form doesn?t change);
absence of degenerative changes of leukocytes.
The majority of forms of physiological leukocytosis according to the mechanism of their development are redistributive.
26.2.9. Give the examples of neutrophillic, eosynophillic, basophillic, lymphocytic and monocytic leukocytosis:
Monocytic leukocytosis is characteristic for: chronic infections (tuberculosis, brucellosis); infectious mononeucleosis; infections caused by ricketsia and protosoa (epidemic typhus, malaria)
26.2.10. What is leukopenia? How is it classified?
Leukopenia is the decreased number of leukocytes in peripheral blood below 4?109/l. Leukopenia is very often a manifestation of a disease. Though there are nosologic units where leukopenia is the leading manifestation of a disease, factually defining its clinical course and the rest of the symptoms.
Classifications of leukopenia:
1. According to the origin it may be acquired and hereditary. Acquired leukopenia mat be mediated by physical (ionizing radiation), chemical (benzol, cytostatics, drugs), biological (hepatic viruses, infectious mononeucleosis) and immune factors. The examples of hereditary leukopenia are Kostman?s granulopenia inherited granulopenia of autosomno-dominant type, syndrome of ?lazy leukocytes?, cyclic granulopenia.
2. According to the type of leukocytes the number of which is decreased:
granulocytopenia, lymphopenia, eosinopenia.
3. According to pathogenesis:
leukopenia mediated by disorders of admission of leukocytes from the red bone marrow into the blood;
leukopenia related with the shortering of term existence of leukocytes in peripheral blood;
redistributive leukopenia.
4. There are several clinico-hematologic syndromes, where leukopenia is the leading sign. Among them are agranulocytosis, hypoplastic anemia, hemorrhagic aleikia.
26.2.11. What mechanisms are at the bases of development of leukopenia connected with the disorders of leukocytes admission from the red bone marrow into the blood?
1. Impairments of hemolytic cells. In this case myelotoxic leukopenia develops. There are three main mechanisms of hemolytic cell impairments:
a) cytolitic is connected with the effect of ionic radiation, cytostatic medicines, immune factors (antibodies, T-lymphocytes) on the cells. The lead of impairment of red bone marrow in this case develops on the dose and longevity of action of these factors.
b) antimetabolic. At its basis there are agents which interrupt the exchange of purine and pyramidal basements breaking the processes of trunk cell division. According to this principle some antineoplastic medicines and antibiotics act.
c) idiosyncratic, is realized at repeated introduction of drugs. The sensitivity of the organism to which is increased. More often these are drugs containing benzene rings in their structure. In case of idiosyncrasy there is no relation between the probability of the development of leukopenia and dose as well as the term of drug effect.
2. Disorders of mitosis ? ineffective leukopoiesis. The most common causes are:
a) insufficiency of substances necessary for cell diversion, particularly vitamin B12 and folic acid
b) disorders of mitosis regulation ? deficiency of leukopoietins
3. Disorders of leukocyte maturation. The cause of it may be genetically mediated defects of hemolytic cells themselves (for example, Kostman?s neutropenia), as well as the cells of ?microinvirenment? (for example, leukopenia in ?steal? mice of SL/SLd line). Alongside, the cell maturation reaches a certain stage (for example, promielocytes) and stops.
4. Disorders of leukocyte exit from red bone marrow into the blood. Similar disorders are often connected with genetic defects of leukocytes breaking their main functions and properties (mobility). The examples are the syndrome of ?lazy? leukocytes, neutropenia of Jemen Jews.
5. Decrease of the plazdarm of leukopoiesis, takes place at replacing hemolytic tissue by leukemic cells, metastases of neoplasia etc.
26.2.12. What mechanisms are at the basis of leukopenia, connected with the shortering of time existence of leukocytes in peripheral blood?
1. Destruction of leukocytes, may be mediated by:
a) autoimmune mechanisms (atrophic arthritis, systemic lupus erythematosus)
b) haptene mechanisms (amydopirine acute granulocytopenia)
c) hypersplenism (increase of phagocytic activity of spleen macrophages
2. Enhanced usage of leukocytes. Accelerated exit of leukocytes from the blood to tissues is precursor in case of chronic recurrent inflammation.
3. Enhanced excretion of leukocytes from the organism. Evident chronic loss of neutrophils is observed in smokers: 0,5-2?108 granulocytes and 0,8-1,6?108 macrophages are lost with sputum during morning cough
26.2.13. What is agranulocytosis?
It is a clinic-hematologic syndrome characterized by full blown decrease of granulocytes, below 0,75?109/l at total decrease of the number of leukocytes below 1?109/l.
At the basis of it there are two mechanisms:
myelotoxic ? impairments of red bone marrow;
immune ? breaking of granulocytic row cells by leukocytic antibodies.
Agranulocytosis is accompanied by weakening of body?s response because of the protective disfunction of leukocytes.
26.2.14. What is the shift of leukocytic formula?
Nucleic shift is breaking of ratio between immature and mature forms of neutrophils.
On count of leukograms it is determined the existence of nucleic shift of neutrophilic granulocytes to the left or the right. This terminology is related with the particularity of location the immature neutrophilic granulocytes (myelocytes, metamyelocytes, stab neutrophils) in the left part of Arnette and Shilling?s formula, but mature segmentoneucleac neutrophils are conditionally put in the right position. The increase numbers of young forms of neutrophilic granulocytes in the blood manifestates the nucleic shift to the left, the majority of mature neutrophils with a large number of segments (5-6) on the background of disappearing of younger cells ? nucleic shift to the right.
26.2.15. What are the variations of the shift of leukocytic formula to the left?
There are such variations of it:
1. Regenerative shift is the index of reactive activation of granulocytopoiesis (on the background of moderate general leukocytosis the number of stab neutrophils and metamyelocytes is increased, single myelocytes can also appear)
2. Hyperregenerative shift expresses the overhyperplasia of leukopoietic tissue with the disorders of cell maturation and evident rejuvenation of blood composition. In this case the number of stab granulocytes and myelocytes is greatly increased, myelocytes and promyelocytes appear; the total number of leukocytes may be increased unchanged or even decreased due to the development of myeloid depletion after activation.
3. Degenerative shift manifestates the inhibition and deep disorders of leukopoiesis, when of the background of general leukopenia in leukogramms the number of stab neutrophilic granulocytes with degenerative changes in their cytoplasm and nucleus increases, at the same time the number of segment-nucleus forms decreases and metamyelocytes are absent.
4. Regenerative ? degenerative shift is observed at hyperproduction of pathologically changed leukocytes and disorders of their maturation in bone marrow. In this case there is leukocytosis, in blood smear the myelocytes with the signs of degeneration increases.
26.2.16. What degenerative changes are characteristic for leukocytes at pathology?
Degenerative changes of leukocytes declare themselves in a form of anisocytosis, the presence of vacuoles in cytoplasm, toxic granulosity of inclusions like Knyaskov-Dele bodies (basophilically stained pads of cytoplasm), large asurophilic granulosity, disappearance of common granulosity, pyknosis or swelling of the nucleus, its hyper- and hyposegmentation, as well as inadequency of degree of nucleus swelling and cytoplasm, karyorrhexis, cytolisis.
Degenerative changes are mostly observed in neutrophilic granulocytes and monocytes. The cause of their developments is the production of leukocytes with impairedmetabolism which forms structural defects (at leukemia, hereditary enzymopathy), and also the damage of leukocytes in hemolytic organs and blood under the influence of various pathogenic factors (bacteria, viruses, antibodies).