LEUKOPOIESIS (WBC FORMATION) & Its REGULATION with CLINICAL IMPORTANCE OF WBC ppt.x

WBC FORMATION (LEUKOPOIESIS) & ITS REGULATION with CLINICAL IMPORTANCE

1. WBC TOPIC : LEUKOPOIESIS & ITS REGULATION WITH CLINICAL IMPORTANCE Presented by- Sayandip majumdar Samat mallick Sukanya pathak Md Ashik billa baidya

2. WBC:INTRODUCTION In 1843 Gabriel Andral & William A ddison ,reported the first description of leucocytes. White blood cells (WBCs) or leukocytes are the colorless and nucleated formed elements of blood (leukos = white).  WBC is made in the bone marrow and found in the blood and lymph tissue. 

3. General features of WBC: Color- Colorless Number- less 4000-11000/cu mm Size- maximum diameter of 18 micron Shape- Irregular Hb - Absent Nucleus- present Types- many Lifespan- Shorter ½ to 15 days Function – Defence & immunity

4. CLASSIFICATION OF WBC:

5. LIFESPAN & FUNCTIONS OF WBC:

6. LEUKOPOIESIS: The process of development and maturation of leukocytes(WBC), is called leukopoiesis.

7. Cont. STEM CELLS: Stem cells are the primary cells capable of self-renewal and differentiating into specialised cells. Committed pluripotent stem cell gives rise to leukocytes through various stages.

8. STEM CELLS

9. STAGES OF LEUKOPOIESIS:

10. GROWTH FACTORS NECESSARY FOR LEUKOPOIESIS: Leukopoiesis is influenced by- haemopoietic growth factors. colony stimulating factors. Cont.

11. Haemopoietic growth factors Hematopoietic growth factors or growth inducers are the interleukins and stem cell factors . these factors induced the proliferation of PHSCs. Interleukins (IL) are glycoproteins, which belongs to the cytokines family. T cells > IL-3 T cells,endothelial cells & macrophages > IL-6 Osteoblast > IL-11 Cont.

12. Colony stimulating factors Colony-stimulating factors(CSFs) are proteins which promote the formation of colony forming blastocystes. TYPES: Monocytes & endothelial cells > Granulocyte-CSF( G-CSF ) Monocytes, endothelial cells and t lymphocytes > granulocyte monocyte CSF ( GM-CSF ) Monocytes & endothelial cells> Monocyte-CSF( M - CSF ) Cont.

13. SCF=  Stem cell factor ; Tpo =  Thrombopoietin ; IL=  Interleukin ; GM-CSF=  Granulocyte Macrophage-colony stimulating factor ; Epo =  Erythropoietin ; M-CSF=  Macrophage-colony stimulating factor ; G-CSF=  Granulocyte-colony stimulating factor ; SDF-1=  Stromal cell-derived factor-1 ; FLT-3 ligand = FMS-like tyrosine kinase 3 ligand ; TNF-a =  Tumour necrosis factor-alpha ; TGF β =  Transforming growth factor  beta

14. CLINICAL IMPORTANCE

15. INFECTIOUS MONONUCLEOSIS Epstein-Barr virus (EBV)  is the most common cause of infectious mononucleosis, but other viruses can also cause this disease. It is common among teenagers and young adults CLINICAL FEATURES: Fatigue. Sore throat Hepatitis lymphadenopathy Swollen tonsils. Encephalitis Meningitis Pneumonitis Skin rash

16. MYELOID LEUKAEMOID REACTION: 1.Infections e.g. staphylococcal pneumonia, disseminated tuberculosis, meningitis, diphtheria, sepsis, endocarditis, plague, infected abortions etc. 2. Intoxication e.g. eclampsia , mercury poisoning, severe burns. 3. Malignant diseases e.g. multiple myeloma, myelofibrosis, Hodgkin’s disease, bone metastases. 4. Severe haemorrhage and severe haemolysis .

17. MYELOID NEOPLASMS : MYELOPROLIFERATIVE NEOPLASMS(MPN) This is a group of neoplastic proliferation of multipotent haematopoietic stem cells. Besides their common stem cell origin, these disorders are closely related, occasionally leading to evolution of one entity into another during the course of the disease.

18. WHO CLSSIFICATION OF MYELOPROLIFERATIVE NEOPLASMS(MPN): The WHO classification of myeloproliferative disorders includes 9 types.(a/c WHO 2016 Classifi.) 1.Chronic myeloid leukemia (CML) 2.Chronic neutrophilic leukemia (CNL) 3.Polycythemia vera (PV) 4.Primary myelofibrosis (PMF) 5.prefibrotic/early stage PMF 6.overt fibrotic stage Essential thrombocythemia (ET) 7.Chronic eosinophilic leukemia,not otherwise specified(NOS) 8.Mastocytosis 9.MPN, unclassifiable

19. ACUTE MYELOID LEUKAEMIA(AML): WHO CLASSIFICATION Recent WHO classification for AML differs from revised FAB classification in the following ways: 1. AML with recurrent genetic abnormalities. 2.AML with myelodysplasia related changes. 3. Therapy related AML. 4. AML, not otherwise categorised. 5. Myeloid sarcoma. 6. Myeloid proliferations related to Down’s syndrome. 7. Blastic plasmacytoid dentritic cell neoplasm.

20. Clinical manifestations of AML: Clinical manifestations of AML are divided into 2 groups: 1.those due to bone marrow failure: Anaemia, Bleeding manifestations, Infections of mouth,throat, skin, respiratory, perianal and other sites. 2.those due to organ infiltration : Pain and tenderness of bones, Lymphadenopathy, Splenomegaly, Hepatomegaly , Gum hypertrophy, Chloroma or granulocytic sarcoma etc.

21. MYELODYSPLASTIC SYNDROMES(MDS): Myelodysplastic syndromes (MDS) are a heterogeneous group of haematopoietic clonal stem cell disorders having abnormal development of different marrow elements (i.e. dysmyelopoiesis), cytopenias,cellular marrow and ineffective blood cell formation. These conditions are, therefore, also termed as preleukaemic syndromes or dysmyelopoietic syndromes .

22. WHO CLASSIFICATION OF MDS(2016 revised) 1.MDS with single lineage dysplasia ( MDS-SLD) 2.MDS with multilineage dysplasia ( MDS-MLD ) 3.MDS with ring sideroblasts ( MDS-RS ) 4.MDS with excess blasts( MDS-EB ) 5.MDS with isolated del(5q) 6.MDS, unclassifiable 7.Refractory cytopenia of childhood. 8.Myeloid neoplasms with germ line predisposition.

23. CLINICAL FEATURES OF MDS: 1. Anaemia appreciated by pallor, fatigue and weakness. 2. Fever. 3. Weight loss. 4. Sweet syndrome (having neutrophilic dermatosis seen in some cases). 5. Splenomegaly ( een in 20% cases of MDS).

24. Thank you.