Cards (49)

  • Blood is made up of cells and liquid
  • Plasma
    • Clear, straw-coloured liquid portion of blood that remains after cellular components are removed
    • 90% water
    • Transport medium for blood cells
    • Also contains salts, enzymes, antibodies, and other proteins
  • Serum
    Fluid left after blood clots = plasma without fibrinogen
  • Red blood cells (Erythrocytes)
    • Diameter: 6-8um
    • Lifespan: 120 days
    • Number: Male – 4.5-6.5 x 10^12/L, Female – 3.9 – 5.6 x 10^12/L
    • Function: Oxygen and carbon dioxide transport
    • 'Biconcave disc'
    • No nucleus
  • Platelets
    • Diameter: 0.5-3um
    • Lifespan: 10 days
    • Number: 140 – 400 x 10^9/L
    • Function: Haemostasis
    • Contain fine granules
    • Should be dispersed
  • White blood cells (Leucocytes)
    • Polymorphonuclear
    • Neutrophils
    • Eosinophils
    • Basophils
    • Mononuclear
    • Lymphocytes
    • B cell
    • T cell
    • Monocytes
  • Neutrophil
    • Diameter: 12-15 um
    • Lifespan: 6-10 hrs
    • Number: 1.8-7.5 x 10^9/L
    • Function: Protection from bacteria and fungi
    • Fine granules in cytoplasm
    • Nucleus divided into 2-5 distinct lobes
  • Eosinophil
    • Diameter: 12-15um
    • Lifespan: days
    • Number: 0.04-0.44 x 10^9/L
    • Function: Protection against parasites
    • Bi-lobed nucleus
    • Cytoplasm packed with large reddish-orange granules
  • Basophil
    • Diameter: 12-15um
    • Lifespan: days
    • Number: 0.01-0.1 x 10^9/L
    • Function: Allergic reactions
    • Nucleus obscured by purple-black granules
  • Lymphocytes
    • B cells (10-15%) and T cells (80%)
    • Diameter: 7-9 um (resting); 12-20 um (active)
    • Lifespan: Weeks or years
    • Number: 1.5-3.5 x 10^9/L
    • Function: B cells – immunoglobulin synthesis; T cells – protection against viruses
    • Round or slightly indented nucleus
    • Scanty cytoplasm
    • Small ones are circular; larger ones may have an irregular outline
  • Monocyte
    • Diameter: 12-20um (largest)
    • Lifespan: 20-40 hrs
    • Number: 0.2-0.8 x 10^9/L
    • Function: Protection from bacteria and fungi
    • Irregular lobulated nucleus
    • Greyish-blue cytoplasm
    • Cytoplasm may contain vacuoles
  • Venepuncture
    The process of drawing blood from a vein
  • EDTA
    A type of anticoagulant used in blood tests
  • Methods of investigating blood
    • Venepuncture
    • Automated full blood count
    • Blood film
    • Bone marrow biopsy
  • Steps in automated full blood count
    • Whole blood in EDTA
    • Platelet count and size
    • Red cell count and size
    • Lysis of red cells
    • Flow cytometry to obtain white blood cell differential
  • Coulter Principle
    A method of counting cells using electrical impedance
  • Steps in Coulter Principle
    • Whole blood passed between 2 electrodes through single cell aperture
    • EI changes as a cell passes through the aperture
    • Change in impedance is proportional to cell volume, resulting in a cell count and measure of volume
  • Flow cytometry
    A method of analysing cells by passing them in single file in front of a laser
  • Measurements taken by flow cytometry
    • Passage of cells in single file in front of a laser
    • The degree to which the laser is interrupted forward (FSC) and obliquely (SSC) tells us the size and granularity of the cell
  • CD Molecules
    Cluster of differentiation molecules, which are cell surface proteins that can differentiate one cell type from another
  • Components of a blood film
    • Commonest stain in UK: May-Grunwald
    • Giemsa (MGG)
  • Haemopoiesis
    Blood cell formation
  • Erythropoiesis
    Red cell formation
  • Myelopoiesis
    White cell formation
  • Thrombopoiesis
    Platelet formation
  • Site of haemopoiesis
    1. First few weeks of gestation: yolk sac
    2. From 6 weeks until 6-7 months of fetal life: liver and spleen (until 2 weeks after birth)
    3. 6-7 months onwards: bone marrow
  • Site of haemopoeisis
    1. Infancy: all the bone marrow is haemopoietic
    2. Childhood: progressive fatty replacement
    3. Adult: confined to central skeleton and proximal ends of femurs and humeri
    4. 50% fat even in these areas
    5. Capable of reverting to haemopoiesis
    6. Liver and spleen can resume fetal haemopoietic role (‘extramedullary haemopoiesis’)
  • Haemopoietic stem cells (HSC)
    • Asymmetric cell division allows self-renewal and pluripotency
    • Rare - 1 in every 20 million nucleated cells
    • Many are dormant, only entering the cell cycle ~every 20 weeks
    • Exact phenotype unknown: CD34+CD38- and negative for lineage markers
    • Look like a small lymphocyte
    • Located in ‘niches’: either endosteal (lined by osteoblasts) or vascular (lined by endothelium)
  • Bone marrow microenvironment
    Stromal cells secrete molecules to form the extracellular matrix and growth factors for stem cell survival
  • Haemopoietic progenitors
    • Lost capacity for self-renewal
    • Irreversibly committed to a specific lineage
    • Earliest recognised: colony-forming unit (CFU)
    • Lab tissue culture work: progenitor cell is identified by culture in a semi-solid medium by the type of colony they form
  • Abbreviations
    • BFU: burst-forming unit; CFU: colony-forming unit; E: erythroid; Eo: eosinophil; GEMM: granulocyte, erythroid, monocyte and megakaryocyte; GM: granulocyte, monocyte; Meg: magakaryocyte; NK: natural killer
  • How is lineage determined?
    1. Expression of transcription factors
    2. External signals such as growth factors
  • Haemopoietic Growth Factors
    • Source: stromal cells (except erythropoietin – kidney and thrombopoietin – liver)
    • Glycoproteins that act at very low concentrations
    • Act hierarchically
    • Usually produced by many cell types
    • Usually affect more than one lineage
    • Usually active on stem/progenitor cells
  • GATA-1 and FOG-1
    • Roles in erythropoietic and megakaryocytic differentiation
  • External signals such as growth factors
    • Source: stromal cells (except erythropoietin – kidney and thrombopoietin – liver)
    • Glycoproteins that act at very low concentrations
    • Act hierarchically
    • Usually produced by many cell types
    • Usually affect more than one lineage
    • Usually active on stem/progenitor cells AND differentiated cells
    • Usually show synergistic or additive interactions with other growth factors
  • Erythropoiesiscell forms
    Proerythroblast, Early erythroblast, Late erythroblast, Reticulocyte
  • Myelopoiesis cell forms
    Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte
  • Thrombopoiesis
    Megakaryocytes undergo endoreduplication – replication of the nuclear genome without undergoing mitosis leading to elevated nuclear gene content and polyploidy
  • Haemopoietic Growth Factors
    • Act on stromal cells: IL-1, TNF
    • Act on pluripotent stem cells: SCF, FLT3-L, VEGF
    • Act on multiple progenitor cells: IL-3, GM-CSF, IL-6, G-CSF, Thrombopoietin
    • Act on committed progenitor cells: G-CSF, M-CSF, IL-5, erythropoietin, thrombopoietin
  • Erythropoietin comes from the kidney