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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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 treatment Transplantation only if relapse

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

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

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

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

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

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

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