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WBC pathology.pdf
- 1. Etiology and pathogenesisof white blood cell pathology. Leukemia: classification, pathogenesis, main types. Ivano-Frankivsk National Medical University Department of Pathophysiology Assistant Professor Fedorchenko Yu.V.
- 2. Lecture plan Leukopoiesis. Leukocytosis. Definition.Classification. Pathogenesis of leukocytosis. Leukopenias. Definition. Classification. Pathogenesis of leukopenias. Agranulocytosis. Leukemias. Definition. Classification. Pathogenesis. Clinical signs. Leukemoid reactions.
- 3. The stem cell can differentiate intomany different cell types.
- 4. Eosino Eosino phils phils Baso Baso phils phils Neutrophils Neutrophils Lymp hocyt es Lymp hocyt es Mono Mono cytes cytes myelo myelo cyte cyte metamy elocyte metamy elocyte band band segm ented segm ented 1-4 1-4 0-1 0-1 0 00 0 2-5 2-5 50-70 50-70 20 -40 20 -40 3-10 3-10 Leukocytic formula % correlation between different forms of WBC Absolute value =
- 5. Degenerative forms ofleukocytes • • • Leukocytes with Döhle bodies infections poisoning burns • • Leukocytes with toxic granulation severe inflammation tumor necrosis • Gumprecht’s cells (shadows) smudge cells cell’s partial breakdown during preparation of a smear (CLL) • • Neutrophils with hypersegmented nucleus level of glucocorticoids B12 deficiency.
- 6. Leukocytosis This is anincrease in the total content of leukocytes in the peripheral blood more than 9 *109/L
- 7. Classification By the causalagent: physiological and pathological. By pathogenesis: Reactive, redistributive and tumorous. By wbc form: neutrophilic, eosinophilic, basophilic, lymphocytic, monocytic. Absolute and relative.
- 8. Absolute Relative Leukocytosis 1. Stimulationof leukopoiesis 2 . I n c r e a s e o f l e u k o c y t e s transport from bone marrow 3 . I n c r e a s e o f tumorous type of leukopoiesis during leukosis 1.Hemoconcentrationa l 2.Redistributional
- 9. Physiological leukocytosis alimentary – developsin 2-3 hours after food intake; myogenic - caused by physical work ; emotional – caused by strong emotions; acclimatization – caused by changing of climatic zone; static – caused by changing recumbent position to plantigrade position; leukocytosis in pregnant
- 10. Pathological leukocytosis is relatedto the presence of the pathological process in the organism: infectious diseases, inflammation or allergic process.
- 11. Reactive leukocytosis Is areaction of red bone marrow to pathogenic influences. It is characterized by enhanced leukocyte proliferation in red bone marrow (increased production of colony stimulating factors) and mobilization of reserve pool of leukocytes from red bone marrow into the circulation under the action of IL-1, TNF.
- 12. Redistributive leukocytosis Is atransition of leukocytes from marginal pool into circulating pool. Characterized by short duration Leukogram is not changed, No degenerative changes of leukocytes.
- 13. Neutrophilic Leukocytosis acute bacterialinfections (caused by pyogenic organisms); tissue necrosis (myocardial infarction, burns). Eosinophilic Leukocytosis (Eosinophilia) allergic disorders (asthma, hay fever, allergic skin diseases); parasitic infestations; drug reactions; some malignancies Basophilic Leukocytosis (Basophilia) chronic myelogenous leukemia Monocytosis Chronic infections (tuberculosis, brucellosis), rickettsiosis, malaria; Lymphocytosis chronic disorders (tuberculosis, brucellosis); some viral infections (hepatitis A, Epstein-Barr virus).
- 14. Analysis of Leukoformula Left-sidenuclear shift of neutrophils: elevated content of immature forms neutrophils in the blood (myelocytes, metamyelocytes, bands). Right-side nuclear shift of neutrophils: prevalence of the mature neutrophils (with many segments, 5-6 and more) with absence of young cells.
- 15. Regenerative Hyperregenerative Regenerative- Degenerative Degenerative There are fourtypes of nuclear shift to the left
- 16. Regenerative NNS tothe left – of band neutrophils , appearance of metamyelocytes (moderate infection/inflammation); Eosino Eosino phils phils Baso Baso phils phils Neutrophils Neutrophils Lympho cytes Lympho cytes Mon o Mon o cytes cytes myelo myelo cyte cyte metamyelocyt e metamyelocyt e band band segme nted segme nted 4 4 0 0 0 0 2 2 8 8 57 57 20 20 9 9
- 17. Hyperregenerative NNS tothe left - it is an excessive hyperplasia of the hemopoietic tissue with disorder of maturation of the cells (can be tumorous origin or so-called leukemoid reaction), increased amount of immature neutrophils up to myelocytes, promyelocytes and myeloblasts. Eosino Eosino phils phils Baso Baso phils phils Neutrophils Neutrophils Lymp hocy tes Lymp hocy tes Mono Mono cytes cytes promyel ocytes promyel ocytes myelo myelo cyte cyte metamy elocyte metamy elocyte band band segm ented segm ented 2 2 0 0 3 3 4 4 5 5 12 12 51 51 18 18 4 4
- 18. Regenerative-Degenerative-hyperpro duc tion o f pathologically changed wbc (degenerative) and impairment of their maturation in the bone marrow. Eosino Eosino phils phils Baso Baso phils phils Neutrophils Neutrophils Lymph ocytes Lymph ocytes Mono Mono cytes cytes myelo myelo cyte cyte metamyeloc yte metamyeloc yte band band segmented segmented 4 4 0 0 2 2 7 7 16 16 42 42 20 20 9 9
- 19. Leukopenia is adecrease of a total content of leukocytes in the peripheral blood below 4*109 /L • • By origin: acquired and inherited leukopenia. Depending on the alteration in total leukocyte number: absolute and relative. By wbc form: neutropenia, eosinopenia, lymphopenia and monocytopenia.
- 20. Leukopenias Hereditary Acquired - - 1. Deficitof maturity factors constant hereditary neutropenia periodic hereditary neutropenia 2. Deficit of myeloperoxidase, G-6-PhDG - hereditary monocytopenia with phagocytic insufficiency deficit (disease of Chediak- Higashi) 1. Inhibition of leukopoiesis 2. Increase of leukodieresis 3. Increase of leukocyte loss 4. Decrease of leukocyte emigration from bone morrow 1. Redistributional shock, muscular work etc. 2. Hemodilutional transfusion of blood substitutes, hydremia etc. Absolute Relative
- 21. By pathogenesis : De c r e a s e d l e u k o c y t e prod uc tion i n the bone marrow; Slow release of leukocytes from the bone marrow into the circulation; Time reduction of leukocyte staying in the peripheral blood; Redistribution of leukocytes in the vessels.
- 22. 1. 2. 3. 4. Decreased production ofleukocytes is linked with disturbance of leukopoiesis under effect of poisons and ionizing radiation, genetic and immune factors, in deficit of leukopoetins. Inherited: chronic benign neutropenia, Kostmann’s syndrome Acquired : cytolytic (damaging effect of ionizing radiation, heavy metals) antimetabolic ( substances effecting stem cell division – antibiotics, antitumor drugs) def i ciency of substances required for leukopoiesis (vitamin B12, folic acid) idiosyncrasy to certain medicines .
- 23. • • • • Slow release ofleukocytes from the bone marrow into the circulation : can be associated with genetic defects of leukocyte mobility ( syndrome of lazy leukocytes’’ ). Time reduction of leukocyte staying in the peripheral blood due to : shortening of granulocytes’ life span leukocytic destruction by antibodies increased leukocytic loss (chronic suppurative processes, cough with sputum) hypersplenism Redistribution of leukocytes in the vessels : may be a reason of relative leukopenia. I t i s o b s e r v e d , f o r e x a m p l e , i n h e m o t r a n s f u s i o n s h o c k , a n d i s characterized by altered ratio between the circulating and marginal pools of leukocytes.
- 24. Leukopenia is adecrease of a total content of leukocytes in the peripheral blood below 4*109 /L • • By origin: acquired and inherited leukopenia. Depending on the alteration in total leukocyte number: absolute and relative. By wbc form: neutropenia, eosinopenia, lymphopenia and monocytopenia.
- 25. Agranulocytosis – totalWBC 1-3*109/L granulocytes than 750/μL Clinically - resistance to infection fever inflammation of the mouth, nose and eyes furunculosis pneumonia septicemia
- 26. Myelotoxic Immune AGRANULOCYTOSIS Damage ofred bone marrow Destruction by antibodies
- 27. Leukaemoid reaction isdefined as a reactive excessive leucocytosis in the peripheral blood resembling that of leukaemia in a subject who does not have leukaemia. It differs from it by etiology, pathogenesis and signif i cance. The cause is often known (it is always infection) on the contrary to leukemia. Pathogenesis is different as well – it is a hyperreactive but not neoplastic hyperplasia of the leukopoietic tissue. Leukemoid reaction is temporary, reversible and does not turn into leukemia. There are two types of leukemoid reaction - myeloid and lymphoid in dependence with type of cells, which underwent proliferation.
- 28. CAUSES of LeukaemoidReaction: Infections e.g. infectious mononucleosis, cytomegalovirus infection, chickenpox, measles, infectious lymphocytosis, staphylococcal pneumonia, tuberculosis, Intoxication; Severe haemorrhage and severe haemolysis; Laboratory findings Leucocytosis Proportion of immature cells mild to moderate, comprised by metamyelocytes, myelocytes (5-15%), and blasts fewer than 5% Toxic granulation and Döhle bodies in the cytoplasm of neutrophils. Neutrophil alkaline phosphatase score in the cytoplasm of mature neutrophils is high (difference from from chronic myeloid leukaemia ) Negative Philadelphia chromosome in myeloid leukaemoid reaction but positive in cases of CML.
- 29. Leukemia are malignanciesof hematopoietic cells or tissues in which there is abnormal proliferation of hemopoietic cells with infiltration of bone marrow and lymphatic tissues Features of leukemia: Boundless and unregulated growth ; Arises up from one transformed initially changed cell ; apoptosis of leukemic cells; Suppression of normal hemopoiesis; Characterized by systemic damage.
- 30. HAEMATOLOGIC NEOPLASMS Lymphoblastic (ALL) Acute Myeloid(AML) Lymphatic (CLL) Chronic Myeloid (CML)
- 31. Etiology of leukemia ionizingradiation, certain kinds of chemicals (benzene and other aromatic hydrocarbons), some viruses (human T-lymphotrophic virus, Epstein-Barr virus), genetic predisposition.
- 32. Pathogenesis of leukemia 1)mutation of hemopoetic cells under the action of oncogenic viruses, ionizing radiation,chemicals (initiation stage), 2) monoclonal proliferation (promotion) - development of primary leukemia of some hemopoetic stem. 3) polyclonal proliferation (tumor progression stage) - tumor obtains malignant character.
- 33. Myeloid maturation myeloblast promyelocytemyelocytemetamyelocyte band neutrophil MATURATION MATURATION
- 34. Leukemia types Acute leukemia Cellslose ability to differentiation cells of the bone marrow of I-IV classes being able to unlimited growth and uncontrolled proliferation hiatus leukemicus” (leukemic gap) - a lack of cell stages of maturation between blasts and mature cells in leukocytic formula occur in children and young adults rapid progression and spread to the organs of the body Chronic leukemia cells of the bone marrow of I-IV classes being able to unlimited growth and uncontrolled proliferation more slowly rate of tumor progression mostly occurs in older people, but can theoretically occur in any age group
- 35. Leukemia classification leukopenic form- WBC count lower than 4*109/L aleukemic form – WBC count doesn’t change. subleukemic form – to 20 *109/L, a few blasts in peripheral blood. leukemic form – leukocytosis 20-100 *109/L, blasts prevalence in peripheral blood.
- 36. Acute Myeloblastic leukemia Thespecial feature of leukoformula is that only the youngest forms (myeloblasts) and the mature neutrophiles (segmentonuclear) are present. The intermediate forms promyelocytes, myelocytes, metamyelocytes, stab-nuclear are absent. This phenomenon is called leukemic gap (hiatus leukemicus). Leukemic (nuclear) gap— loss of an ability of neoplastic cells to differentiate. Maturation of neutrophils in bone marrow does not occur. Only myeloblasts are multiplied, and they fall into the peripheral blood. The mature neutrophils, which are determined in peripheral blood, are those, which were formed earlier, before the beginning of a disease. The lifetime of mature neutrophils is short.
- 37. Acute myeloblastic leukemia Myeloblasts Peripheralblood Bone marrow
- 38. Acute myeloblastic leukemia myeloblastsin a peripheral blood and their prevalence in marrow. hiatus leukemicus -lack of cell stages of maturation between myeloblasts and mature neutrophils Eosino Eosino phils phils Basophil s Basophil s Neutrophils Neutrophils Lymph ocyte s Lymph ocyte s Mono Mono cytes cytes myelo myelo blasts blasts pro pro myelo myelo cytes cytes myelo myelo cytes cytes metamyeloc ytes metamyeloc ytes band band segment ed segment ed 0 0 0 0 62 62 0 0 0 0 0 0 1 1 25 25 11 11 1 1
- 39. 39 • • • Predominant proliferation ofgranulocytic cells. Consistently associated with the BCR-ABL1 fusion gene located in the Philadelphia (Ph) chromosome which results from t(9;22) Absence of hiatus leukemicus Chronic Myeloid Leukemia (CML) myeloblast promyelocyte myelocyte metamyelocyte band neutrophil MATURATION MATURATION
- 40. Chronic Myeloid Leukemia(CML) In chronic myeloleukemia, neoplastic clone appears in stem cells but the larger part of them maturate in the bone marrow. In the peripheral blood it is possible to see the granulocytes of any degree of maturity. The hyperregenerative nuclear shift to the left is noted, but the leukemic nuclear gap is absent. Increased number of neutrophilic metamyelocytes, myelocytes, promyelocytes and single myeloblasts is typical for chronic leukemia. The number of eosinophilic and basophilic granulocytes is increased (eosinophilic and basopholic leukocytosis).
- 41. Chronic Myeloid Leukemia(CML) detecting the Philadelphia chromosome absence of hiatus leukemicus eosinophil-basophil association Eosino Eosino phils phils Basophil s Basophil s Neutrophils Neutrophils Lympho cytes Lympho cytes Mono Mono cytes cytes myelo myelo blasts blasts pro pro myelo myelo cytes cytes myelo myelo cytes cytes metamy elocytes metamy elocytes band band segmen ted segmen ted 8 8 4 4 6 6 10 10 16 16 15 15 13 13 12 12 10 10 6 6
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- 43. Philadelphia chromosome Due toreciprocal translocation between the long arm of chromosomes 9(9q) and 22(22q) (9:22 translocation) It is found in all haematopoietic precursors of CML patients. This result in the transfer of the Abelson's (abl) oncogene to an area of chromosome 22 termed the break-point cluster region (bcr) This results in a fused bcr-abl gene and production of an abnormal tyrosine kinase protein. This protein causes disordered myelopoiesis in CML
- 44. Acute lymphoblastic leukemia Lymphoblasts inperipheral blood smear Eosino Eosino phils phils Baso phils Baso phils Neutrophils Neutrophils Lymphocytes Lymphocytes Mono Mono cytes cytes mye locy tes mye locy tes juve nile juve nile band band segm. segm. lympho blasts lympho blasts prolymp hocytes prolymp hocytes lympho cytes lympho cytes 0 0 0 0 0 0 0 0 1 1 16 16 61 61 0 0 19 19 3 3
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- 46. Chronic lymphogenous leukemia Lymphoidleukemia is the neoplastic transformation of lymphoid tissue. Lymphocytes are mostly mature. The majority of the lymphoblasts is matured up to the end and reaches 80-90% (relative and absolute lymphocytosis with relative neutropenia). There are single prolymphocytes and lymphoblasts in the leukoformula . Absolute number of neutrophils may remain normal taking into consideration a significant increase of total quantity of leukocytes (above 120 G/l). The course of a disease is chronic and flows for years.
- 47. Chronic lymphogenous leukemia Eosino Eosino phils phils Baso phils Baso phils Neutrophils NeutrophilsLymphocytes Lymphocytes Mono Mono cytes cytes myel ocyt es myel ocyt es metamyelo cute metamyelo cute band band segm. segm. lymphob lasts lymphob lasts proly mpho cytes proly mpho cytes lymph ocytes lymph ocytes 0 0 0 0 0 0 0 0 2 2 36 36 5 5 9 9 21 21 3 3 lymphocytes
- 48. Clinical syndromes ofleukemias: 1. 2. 3. 1. 2. 3. 4. 1. 2. 3. 4. Hematological syndrome (substitution the normal hemopoietic tissue by tumor ) : Pancytopenia-diminishing of amount of all blood cells ; Anemia Hemorrhagic syndrome – thrombocytopenia Syndromes, related to the features of functioning of cells of leukemia: Fever Intoxication Increased amount of uric acid in the blood ( breakdown of purines releasing from neoplastic cells ) Autoimmune processes Syndromes, related to metastasis: Enlargement of lymph nodes, liver, spleen Skin infiltrates of tumor cells Pain in bones Cardiac insufficiency
- 49. Literature Kumar V, AbbasA., Aster J. (eds.) Robbins Cotran Pathologic Basis of Disease 10th edition. Elsevier; 2020. p.586-587, 592-594,597-599, 616-622 Kumar V, Abbas Abul K, Aster JC, editors. Robbins Basic Pathology. 10th ed. Philadelphia: Elsevier; 2017. p.459-484. Kubyshkin AV. General and Clinical Pathophysiology. 3rd ed. Vinnytsya: Nova Knyha; 2017. p.588-612. Robert J Hubert, Karin C. VanMeter, editors. Gould's Pathophysiology for the Health Professions. 6th ed. St. Louis: Saunders Elsevier; 2018. p.263-271 McCance KL, Huether SE, editors. Pathophysiology: The Biologic Basis for Disease in Adults and Children. 8th ed. St. Louis: Mosby; 2018. 1720 p. Huether SE, McCance KL, editors. Understanding Pathophysiology. 6th ed. St. Louis: Elsevier; 2017. p.105-111. Grossman SC, Porth CM, editors. Porth’s Pathophysiology.Concepts of Altered Health States. 10th ed. Philadelphia: Lippincott Williams Wilkins; 2018.1688 p. Simeonova NK, Mikhnev VA editors. Pathophysiology: textbook. 3rd ed. Кyiv: AUS Medicine Publishing; 2017. 544p. + 4 p. colour insert.
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