Blood hematopoiesis bone marrow TB Dr David Dora

Blood, hematopoiesis, bone marrow TB Dr. David Dora Assistant professor 2020. February

Blood primary functions • Supplies oxygen for tissues (bound to hemoglobin, in red blood cells, (RBC)) • Supplies nutrients such as glucose, amino acids, and fatty acids (dissolved in the blood or bound to plasma proteins) • Removal of waste such as carbon dioxide, urea, and lactic acid • Immunological functions, including circulation of white blood cells, and detection of foreign material by antibodies • Coagulation, blood clotting: part of the body's self-repair mechanism • Messenger function, including the transport of hormones and a variety of molecular mediators • Regulation of body p. H • Regulation of core body temperature

Composition of blood CELLULAR COMPONENTS Red blood cells (erythrocytes) 99% of the cells Gas transport (O 2, CO 2) White blood cells (leukocytes) Internal defense Platelets (thrombocytes) blood clotting PLASMA 55 % of the blood’s volume - Water - Electrolytes - Proteins: - Albumin, fibrinogen, globulins - Transported molecules: - Nutrients, vitamins, hormones, trace elements, metabolic products, fatty substances Plasma without fibrinogen is called serum

Blood smear and May-Grünwald Giemsa staining to study the morphology of blood cells

Red blood cells (erythrocytes)

Red blood cells (erythrocytes) - no cell nucleus - Erythrocytes are flexible, biconcave discs that are packed with hemoglobin (special cytoskeleton with actin, spectrin, ankyrin molecules high elasticity) - O 2 and CO 2 transport - lifespan: 120 days, processed in the spleen and in the liver (iron: stored, reused) - Covered by extensive glycocalix ABO blood groups

Hemoglobin Almost 99% of the O 2 in human blood is transported as oxyhemoglobin (Hb. O 2) Hemoglobin is a group of compounds that have an iron-porphyrin (heme) group bound to a protein (globin)

Platelets (thrombocytes) - cytoplasm fragments which derives from megakaryocytes (giant cells in the bone marrow) - lifespan: 5 -10 days - 250 -300 000/ml - 2 -3 µm - blood clotting: forming the platelet-plug

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White blood cells (leukocytes) Granulocytes Agranulocytes (polymorphonuclear leukocytes) MPS PMNS neutrophils (neutrophil granulocytes) eosinophils (eosinophil granulocytes) basophils (basophil granulocytes) Monocytes Lymphocytes B-cells T-cells NK-cells

Neutrophil granulocyte - size: 10 -15 µm - segmented nucleus (3 -5 lobes), small granules in the cytoplasm (neutrophil=no colour) - 60 -70% of white blood cells - Main function: phagocytosis - Innate immune system

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Eosinophil granulocyte - size: 10 -15 µm - bilobed nucleus - eosinophilic granules containing histamin, crystals can be detected by EM - 1 -6% of white blood cells - In allergic reactions inactivation of excess histamine (from mast cells or basophils) - Anti-parasitic defense (Major basic protein, MBP)

Basophil granulocyte - size: 10 -15 µm - bilobed nucleus (not seen because of the granules) - many, large, basophil cytoplasmic granules (heparin, histamine). - 0 -1% of white blood cells - effector cells in allergy, immediate hypersensitivity

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Monocytes - size: 15 -20 µm (largest WBC!) - ovale or kidney-shaped nucleus, numerous lysosomes in the cytoplasm - precursors of tissue macrophages - 2 -6 % of white blood cells - coordination of cellular and humoral immune response, phagocytosis

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Lymphocytes - size: 8 -10 µm round-shaped nucleus, organellum rich citoplasm 20 -40 % of white blood cells of the specific (humoral and cellular) immunity Inactive B-cells, T-cells and NK-cells are indiscernable on MGG staining

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Hematopoiesis and the bone marrow What are stem cells? • Stem cells are unspecialized cells that have two defining properties: the ability to differentiate into other cells and the ability to self-regenerate. • The three broad categories of stem cells are: • Embryonic stem cells, derived from blastocysts, • Adult stem cells, which are found in adult tissues • Fetal stem cells, which are found in the umbilical cord. • Stem cells of the adult tissues are tissue specific (hemopoetic, nervous, muscle stem cells)

Primitive, yolk sac Definitive, hepatolienal Definitive, myeloid, BM

The hemangioblast vasculogenesis and hematopoiesis Yolk sac primitive hematopoesis

Intraembryonic hematopoesis AGM region

Bone marrow Red bone marrow • (spongy bone, long bone) • stroma (reticulum cells, adipocytes, macrophages) • cells of hematopoesis • sinusoid (discontinuous endothel) • Megakaryocytes Defragmenting thrombocytes

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Diapedesis, TEM image

Hematopoiesis TB

Thank you for your attention! Dr. David Dora 2020. February