Blood 2016 PDF

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Summary of Blood Hematopoiesis Page 1 of 9 BLOOD AND HEMATOPOIESIS 1. Know the normal range of values for an adult complete blood count 2. Describe the structure (nucleus type) and functions of each mature circulating blood cell. 3. Pluripotent stem cells of the hematopoietic lineage give rise to th...

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Summary of Blood & Hematopoiesis Page 1 of 9 BLOOD AND HEMATOPOIESIS

1. Know the normal range of values for an adult complete blood count

2. Describe the structure (nucleus shape/granule type) and functions of each mature circulating blood cell.

3. Pluripotent stem cells of the hematopoietic lineage give rise to the mature blood cells. Know the progenitor and precursor cell that lead to each mature cell as well as the colony-forming unit from which each mature cell arises.

4. Describe the structural characteristics of both erythrocyte differentiation and granulocyte maturation.

5. Describe how platelets are formed

Summary of Blood & Hematopoiesis Page 2 of 9 Whole blood: Cells –erythrocytes, leukocytes, thrombocytes and their precursors Hematocrit -percentage of blood volume that is erythrocytes (40-50% in men; 3545% in women) Leukocytes – ‘buffy coat’; ~1% of blood volume Serum – fluid remaining when blood clots Plasma – water, plasma proteins (i.e., albumin, immunoglobulins, fibrinogen), inorganic salts, organic compounds Anemia = low hematocrit; common causes are blood loss, reduced production of erythrocytes or accelerated destruction of erythrocytes Polycythemia = increased number of erythrocytes (examples – low oxygen environments, dehydration, myeloproliferative disorders)

Erythrocytes (red blood cells) -fully mature cell -anucleate and without organelles -biconcave disks which are extremely flexible (facilitates travel in capillary) -7-8 micrometers in diameter; serves as a ‘histological ruler’ -120 day lifespan; phagocytosed by macrophages in spleen Leukocytes (White blood cells) Two classifications depending on whether or not specific granules are present: Granulocytes -neutrophils, eosinophils, basophils -have nuclei with 2 or more lobes

Summary of Blood & Hematopoiesis Page 3 of 9 -have specific granules which contain various enzymes (differ among granulocytes) and azurophilic granules (predominantly lysosomes) Agranulocytes -lymphocytes and monocytes -have azurophilic granules but no specific granules

Neutrophils (often called polymorphonuclear leukocytes, PMNs) -60-70% of leukocytes -act as defense against bacteria -multi-lobed (2-5) nucleus linked by chromatin -number of lobes is indicative of cell age -newly formed neutrophils have horseshoe shaped nucleus (band cell) -Barr body forms a drumstick-like appendage in females -short lifespan (1-4 days); inactive in the circulation -express P-selectin ligands on cell surface which interact with vasculature to slow travel through vasculature -enter connective tissue at post-capillary venules (diapedesis)

Neutrophil Kinetics

1)

Medullary formation compartment (7 days) -Cells form and mature

2)

Medullary storage compartment (4 days) -Cells accumulate and wait for release

3)

Circulating compartment/Marginating compartment (6-7 hours) -In active circulation or trapped in capillaries

4)

Connective tissue (1-4 days) -enter via diapedesis; attach to endothelial cells via surface receptors and then push through intercellular junctions and move through connective tissue via chemotaxis;, do their job (phagocytosis), then die via apoptosis

Summary of Blood & Hematopoiesis Page 4 of 9

Eosinophils -2-4% of leukocytes -bilobed nucleus -large specific granules (highly eosinophilic) -key protein in the specific granules is major basic protein (kills parasites) -high concentrations at sites of potential inflammation (e.g. intestinal tract)

Basophils -about 0.5% of leukocytes -irregularly lobed nucleus which is often masked in histological slides by the granules -key proteins in specific granules are heparin and histamine -function much like a mast cell (mediator of inflammation) Agranulocytes Monocytes -originate in bone marrow and enter circulation as mature cell -circulate for ~8 hours and then go into connective tissue and become macrophage (ie, microglia in CNS; osteoclasts in bone) -nucleus is oval, horseshoe, or kidney shaped; is typically ‘eccentric’ Lymphocytes -all lymphocytes originate from bone marrow as lymphoblast and prolymphocyte - B lymphocytes fully differentiate in the bone marrow and then migrate to peripheral organs where they multiply; T lymphocytes go from marrow to the thymus where they mature -about 28% of total leukocytes

Summary of Blood & Hematopoiesis Page 5 of 9 -small, medium and large in size with small being most prominent; small lymphocytes have almost no visible cytoplasm. -characteristics are based on function, not size -T cells = cell-mediated immunity -B cells = recognize antigens -Natural Killer (NK) cells = attack virus-infected cells and some tumor cells -histological differentiation of different lymphocytes necessitates immunohistochemical staining

Thrombocytes (Platelets) -from megakaryocytes in marrow -no nucleus -granules containing clotting factors (i.e. fibrinogen, platelet-derived growth factor)

Summary of Blood & Hematopoiesis Page 6 of 9 Hematopoiesis Begins in yolk sac mesoderm and then transitions to the liver/spleen/marrow in fetus. Eventually, after birth, 100% of hematopoiesis occurs in bone marrow. All blood cells arise from pluripotential stem cells (comprises ~ 0.05% of all marrow cells) which are self-renewing. Pluripotential stem cells become either multipotential lymphoid cells or multipotential myeloid stem cells which then differentiate into unipotential/multipotential cells termed progenitor cells. Collections of each type of progenitor cell are contained within colony forming units (CFUs) -examples are erythrocyte units (CFU-E) and Granulocytemonocyte units (CFU-GM) -CFUs influenced by colony stimulating factors (CSFs) (see Table 13-1) -each CFU produces one cell lineage (except for the CFU-GM) Progenitor cells within CFU differentiate into unipotent or bipotent cells (termed precursor cells or ‘blast cells). Precursor cells are the first stage where histological distinction can be made. Precursor cells go through various stages of maturation and eventually become a terminal cell within the lineage. Bone Marrow: -Red (hematogenous) = 100% of marrow in newborns; transition to yellow marrow with age -stroma = network of reticular cells & fibers, type I & III collagen; hemonectin -hematopoietic cords = site of blood cell formation; contain CFUs -sinusoidal capillaries = formed by endothelial cells -Yellow (fatty) = inactive, majority of marrow in adults; comprised of adipocytes; can revert to red marrow

Summary of Blood & Hematopoiesis Page 7 of 9 Erythrocytes (red blood cells) Erythroblastic islands -macrophages in medullary cords promote erythrocyte differentiation -erythropoietin (from kidney) stimulates macrophages

Differentiation (3-5 cell divisions and ~ 7 days): -proerythroblast = large with clearly visible nucleoli -basophilic erythroblast = basophilic cytoplastm, condensed nucleus, mitotic cell -polychromatophilic erythroblast = mitotic cell -orthochromatophilic erythroblast = not mitotic, still has nucleus -reticulocytes = no nucleus, some polyribosomes

Maturational process is associated with progressive changes: -Decreased cell volume -Decreased nuclear diameter -Increased chromatin density (until extruded) -Decreased polyribosomes and mitochondria -Increased hemoglobin

Summary of Blood & Hematopoiesis Page 8 of 9

Granulocytes Granulopoiesis -main feature is accumulation of proteins and packaging of them into granules -azurophilic granules made first, then specific granules -All granulocytes go through similar stages of maturation -Myeloblast = most immature recognizable cells in series -Promyeloblast = multi-potential stem cell, has azurophilic granules -Myelocyte = precursor to each lineage, acquire specific granules -Metamyelocyte = prominent granulation

Thrombopoiesis -Maturation of megakaryoblasts to megakaryocytes (thrombopoietin) -Large cells, lobulated nucleus -Proplatelets – cytoplasm processes that extend from megakaryocte body; penetrate into sinusoidal capillaries; ends of proplatelets are pinched off to form platelets (up to 8000 per cell); demarcation membranes within megakaryocte are invagniations of the plasma membrane that serve as a reservoir for growing prolatelets.

Summary of Blood & Hematopoiesis Page 9 of 9...