White blood cells and their disorders

1. White blood cells and their disorders Dr K Hampton Haematologist Royal Hallamshire Hospital

2. Normal white cells • Mature cells circulate in blood • Produced from immature precursor cells in the bone marrow, derived from stem cells. • Rate of production under hormonal control by series of growth factors.

3. Neutrophils • Most numerous white cell, lifespan 10 hours • Phagocytose and kill bacteria • Release chemotaxins and cytokines, important in inflammatory response • Lack of number or function results in recurrent bacterial infections

4. Monocytes • Produced in bone marrow, transit through blood for 20 hours and enter tissues as macrophages • Some become dendritic cells that present antigens to the immune system

5. Basophils • Relatively rare in peripheral blood • Migrate to tissues to become mast cells • Contain granules of histamine • Surface IgE • Important in immunity and allergy

6. Eosinophils • Also rare in peripheral blood • Impotant in inflammation and allergic responses • Special role in protection against parasites

7. Lymphocytes • Vital to immunity • Some generate antibodies against specific foreign antigens, eg bacteria, viruses • Other have phenomenon of immunological memory, generates immunity and allow vaccination

8. B lymphocytes • Named after Bone marrow • Differentiate into plasma cells and produce immunoglobulins when stimulated by expose to a foreign antigen

9. T lymphocytes • Named after Thymus • Some are helper cells (CD4) • Some are cytotoxic cells (CD8) • Aid B cells in antibody generation and also responsible for cellular or cell mediated immunity

10. Immunodeficiency • Congential or acquired immunodeficiency very serious condition, often fatal • Congenital immunodeficiency treated with bone marrow transplant or gene therapy • HIV virus causes AIDS due to infecting CD4 lymphocytes and leads to opportunistic infections

11. Bacterial infections • Result in neutrophilia: increase in neutrophils • Engulf and kill bacteria • Failure results in overwhelming infection • Can aid neutrophil response with G-CSF, a specific growth factor for neutrophils

12. Viral infections • Response by lymphocytes • Generate immunoglobulins and memory cells • Usually only have infection once • Severe infections like hepatitis B and Meningococcus C can be prevented by vaccination: generates memory B cells

13. Acute leukaemia • Proliferation of primitive precursor cells usually only found in bone marrow • Proliferation without differentiation • Replaces normal bone marrow cells, leads to: anaemia: palor and lethargy neutropenia: infection thrombocytopenia: bleeding

14. Acute myeloblastic leukaemia (AML) • Malignant proliferation of the precursor myeloblasts in the bone marrow • Disease primarily of adults: 50% survive 5 years • Treatment is with cyclical high dose chemotherapy and possibly bone marrow transplantation

15. Acute lymphocytic leukaemia(ALL) • Malignant proliferation of the lymphoblast precursor cells in the bone marrow • Disease primarily of childhood: 80% cure • Treated with cyclical chemotherapy over 2-3 years, CNS specific treatmentTransplantation only if relapse

16. High grade lymphoma • Classified as Hodgkins disease and Non-Hodgkins lymphoma (NHL) • Disease usually of lymph nodes that spreads to liver, spleen, bone marrow and blood • Needs aggressive curative chemotherapy • Localised disease may be treatable with radiotherapy

17. Chronic leukaemia • Malignant proliferation with differentiation • Overproduction of mature cells, not precursor blast • Untreated has better prognosis, hence called chronic, commoner in older age

18. Chronic lymphocytic leukaemia • Proliferation of mature lymphocytes, usually B lymphocytes • Lymphocytosis in blood, lymphadenopathy, splenomegaly • Prognosis measured in years to decades, treatment with out patient chemotherapy

19. Chronic myeloid leukaemia • Proliferation of mature myeloid cells: neutrophils, also basophils and eosinophils • Philadelphia chromosome, t9:22 specific chromosomal translocation • Can be cured by bone marrow transplantation in younger age group

20. Low grade leukaemia • Chronic proliferation of mature lymphoid cells of lymph node origin • Disease principally of elderly, survival years to decades • Treatment, when necessary, = out patient chemotherapy

21. Multiple myeloma • Malignant proliferation of plasma cells in bone marrow • Plasma cells are B lymphocytes that produce immunoglobulin • Myeloma has monoclonal immunoglobulin in serum and urine

22. Multiple myeloma • Lytic lesions in bones, with pain or pathological fracture • Hypercalcaemia with thirst, polyurea and confusion, due to bone resorption • Hyperviscosity due to immunoglobulin • Renal failure