Consultant Hematologist White Blood Cells Dr. Mansour Aljabry Assistant Professor & Consultant Hematologist

Hematopoiesis Hematopoiesis is the process of life long production, multiplication & specialization of blood cells in the bone marrow. It begins with the most basic blood cell, the stem cell or “pluripotent hematopoietic stem cell” (PHSC). Differentiation Proliferation HSC (mother)

Hematopoietic stem cell Megakaryocytic –Erythroid Progenitors Lymphoid Progenitor Hematopoietic stem cell Granulocytic-Monocytic Progenitors Monocytes Myeloid Progenitor Erythroid Progenitor Megakaryocytic –Erythroid Progenitors

Hematopoietic growth factors : Hormones that regulate the proliferation and differentiation of HCS. Can be administered clinically to stimulate the hematopoiesis : -G-CSF in severe neutropenia -EPO in Sever anemia

Hematopoietic stem cell Megakaryocytic –Erythroid Progenitors PAX-5 Lymphoid Progenitor T-bet Hematopoietic stem cell G-CSF SCF FLT3-L Granulocytic-Monocytic Progenitors M-CSF Monocytes EPO Myeloid Progenitor Erythroid Progenitor Megakaryocytic –Erythroid Progenitors Thrombopoietin

Normal ranges WBC count 4-11 x 109/L Absolute count (x109/L) Differential count % Cells 1.5-6.5 50-70 Neutrophils 1.2-3.4 20-44 Lymphocyte 0.1-0.6 2-9 Monocytes 0-0.7 0-6 Bands 0-0.5 0-5 Eosinophils 0-0.2 0-2 Basophils

Neutrophil Phagocytic cell contain a nucleus divided into 2–5 lobes with pale granulated cytoplasm. stain a neutral pink (Basophils dark blue while eosinophil is bright red). They are short lived(≈6 days) and highly motile.

Chemotaxis: Migration toward sites of infection or inflammation through detection of IL-8 ,TNFγ &C5a  Neutrophil extracellular traps(NETs): are web-like structures of DNA and fiber that trap and kill microbes extracellularly Superoxide Hydrogen peroxide Lysozyme  NADPH oxidase Myeloproxidase (MPO)

Neutrophil

Neutrophilia Marginal pool (tissues) Circulating pool (blood)

Causes of neutrophilia Neoplastic Benign Chronic Myeloid leukemia Bacterial infection (Pyeogenic) Polycythemia vera,Essential Thrombocythemia Inflammation and tissue necrosis Chronic Myelomonocytic Leukemia Acute hemorrage or hemolysis Non hematological Neoplasms Steroid therapy (inhibits margination) G-CSF treatment Rare inherited disorders Aspleni

Leukemoid reaction Leukocytosis(mainly neutrophilia with left shift) due to physiological response to stress or infection. Common with : sever or chronic infection ,sever hemolysis & metastatic cancers. Associated with: Toxic granulation ,Vaculation & Dohle bodies.

Left shift Vaculation Döhle bodies Toxic gran. S. neutrophil

Neutropenia Lower limit of normal is 1.5 × 10⁹/L Sever neutropenia : ≤0.5 × 10⁹/L Part of general pancytopenia Selective neutropenia Bone marrow failure Congenital : - Kostmann syndrome - Benign neutropenia , - Cyclical neutropenia Chemotherapy Drug induced Acute Leukemia Autoimmune (SLE) Lymphoma Viral infection (hepatitis ,HIV) Metastatic carcinoma Some Bacterial infections(Typhoid)

Lymphocytes Small WBC having spherical nucleus surrounded by a thin layer of non granular cytoplasm. Fundamental importance in the immune system (Innate &Adaptive)

Lymphocyte (B or T) NK Lymphocyte Reactive looking Atypical looking

Lymphocytosis 1- Viral infection : Infectious mononucleosis ,cytomegalovirus ,rubella, hepatitis, adenoviruses, varicella…. 2- Some bacterial infection: (Pertussis ,brucellosis …) 3- Other conditions: Allergic drug reactions, splenectomy, dermatitis ,hyperthyroidism metastatic carcinoma….) 4- Chronic lymphocytic leukemia (CLL) 5-Other lymphomas: Mantle cell lymphoma ,Hodgkin lymphoma…

Lymphocytopenia Part of general pancytopenia Selective Lymphocytopenia Bone marrow failure Bacterial or fungal sepses Chemotherapy or radiotherapy Post operative state Acute Leukemia Post steroid therapy Lymphoma Immunodeficiency (congenital or acquired) Metastatic carcinoma Autoimmune disorders (SLE..)

Monocytes Large, phagocytic WBC, having a single well-defined nucleus and very fine granulation in the cytoplasm. Represents about 2-9% of WBC Matures into different types of macrophages at different anatomical locations (skin, spleen, liver …..)

Monocytes Monocytosis Monocytopenia (TB , Brucellosis..) 1- Chronic infection : (TB , Brucellosis..) 2-Autoimmune :SLE.. 3-Chronic neutropenia 4-Acute leukemia (AML M5) 5-Chronic Myelomonocytic leukemia Hairy cell leukemia Selective monocytopenia:

Eosinophil Granular leukocyte having a nucleus with two lobes and cytoplasm containing bright red coarse and round granules . Major functions : 1-Antiparasitic and bactericidal activity, 2-Participating in immediate allergic reactions, 3-Modulating inflammatory responses. 

Eosinophilia Causes: C H I N A Helminthic parasitic infections Connective tissue diseases Helminthic parasitic infections Idiopathic: Hypereosinophilic syndrome Neoplasia: eosinophilic leukaemia, lymphoma or MPN Allergy 23 23

Basophil Phagocytic leukocyte of characterized by numerous coarse bluish-black granules of variable size. Mature to tissue mast cells. Functions of Basophils - Major role in immediate allergic reaction (IgE) - Anticoagulant activity (Heparin) - Vasodilatation (Histamine)

Basophilia 1-Neoplasia (CML, mastocytosis, basophilic leukaemia, MPN) 2-Hypothyroidism 3-Some viral infections (Chickenpox) 4-Inflammatory conditions 5-Drugs (IL3, oestrogen) 6-Hyperlipidaemia 25 25

leukoerythroblastic picture Bone marrow response in which nucleated red blood cells and immature leukocytes are released in the blood Causes: Metastatic neoplasm Primary Myelofibrosis Severe hemolysis (Thalassemia major) Severe infection ( Miliary TB)

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