Leukocyte kinetics

• Leukocytes


  White blood cells, relatively colorless compared to RBCs
• Types of leukocytes


  • Granulocytes (Neutrophils, Eosinophils, Basophils)
  • Agranulocytes (Monocytes, Lymphocytes)
• Reference range for leukocytes

  4.5 to 11.5 x 10^9/L
• Functions of leukocytes


  • Immunity through nonspecific (phagocytosis by neutrophils) and adaptive (production of antibodies by lymphocytes and plasma cells)
• Leukocyte kinetics


  Movement of cells through developmental stages, into the circulation, and from the circulation to the tissues, including the time spent in each phase
• Leukocyte maturation series


  1. Myeloblast

  2. Promyelocyte

  3. Myelocyte

  4. Metamyelocyte

  5. Bands or Juvenile

  6. Mature Granulocytes (Segmented Neutrophils, Eosinophils, & Basophils)
• Myeloblast


  • 0-3% of nucleated cells in the bone marrow, 14 to 20 um in diameter, N:C ratio of 8:1 to 4:1
• Promyelocyte


  • 16 to 25 um in diameter, a paranuclear halo or hof is usually seen in normal promyelocytes, primary (azurophilic) granules are produced, eosinophilic promyelocytes can be identified by Charcot-Layden crystal protein in their primary granules
• Myelocyte


  • 6-7% of nucleated cells in the bone marrow, begins to manufacture secondary (specific) granules and ceases to produce primary granules
• Metamyelocyte


  • 3% to 20% of nucleated marrow cells, nucleus is indented (kidney bean shaped or peanut shaped), synthesis of tertiary granules (aka gelatinase granules) begin
• Bands or Juvenile


  • 9 to 32% of nucleated marrow cells and 0 to 5% of the nucleated peripheral blood cells, elevated in patients with infection
• Segmented Neutrophils


  • 7 to 30% of nucleated cells in the bone marrow, presence of 2-5 nuclear lobes connected by thread-like filaments, comprise 50% to 70% of leukocytes (2.3 to 8.2 x 10^9/L), function is phagocytosis and destruction of foreign material and microorganisms via chemotaxis and diapedesis
• Neutrophil granules


  • Primary (Azurophilic) Granules
  • Secondary (Specific) Granules
  • Tertiary Granules
• Eosinophils


  • 1 to 3% of nucleated cells in the bone marrow, account for 1 to 3% of peripheral blood leukocytes, with an absolute number of up to 0.4 x 10^9/L, function is immune regulation (release of MBP to cause mast cell degranulation) and destruction of tissue-invading helminths through secretion of MBP and eosinophil cationic protein, hallmark of allergic reactions
• Eosinophil granules


  • Primary Granules
  • Secondary Granules
• Basophils


  • Least numerous of all WBCs, 0-2% of circulating leukocytes and less than 1% of nucleated cells in the bone marrow, function is initiating allergic inflammation through release of preformed cytokines and playing a role in angiogenesis through expression of vascular endothelial growth factor and its receptors
• Basophil granules


  • Secondary Granules
• Monocytes


  • Make up between 2% and 11% of circulating leukocytes, with an absolute number of up to 1.3x10^9/L, influenced by M-CSF, the major cytokine responsible for the growth and differentiation of monocytes, differentiate into macrophages
• Monocyte destinations


  • Differentiation into macrophages in the liver, lung, skin, serous cavities, and other tissues
  • Innate immunity through pattern recognition receptors
  • Adaptive immunity by degrading antigen and presenting antigen fragments
  • Housekeeping functions like removal of debris and dead cells, destruction of senescent red blood cells, and maintenance of a storage pool of iron for erythropoiesis
• Lymphocytes


  • Different from other leukocytes in that they are not end cells, they recirculate from blood to tissues and back, they can rearrange antigen receptor gene segments, and early progenitors originate in the bone marrow while T and NK cells develop and mature outside the bone marrow
• Lymphocyte functions


  • Cellular immunity (T cells and NK cells)
  • Humoral immunity (B cells)
• 1. lymphocyte development


  1. Pro-B cells

  2. Pre-B cells

  3. Immature B cells

  4. Mature B cells
• 1. lymphocyte development


  1. Pre-T cells in the bone marrow

  2. Migrate to the thymus (cortex)

  3. Mature in the thymus (medulla)
• 1. lymphocyte functions


  • CD4+ T cells (T1, T2, T17, regulatory T cells) mediate immune responses against intracellular pathogens, extracellular parasites, and maintain self-tolerance
  • CD8+ (cytotoxic T cells) kill target cells via secretion of granzymes and perforins
  • NK cells kill certain tumor cells and virus-infected cells without prior sensitization
• Platelets


  Play a central and immediate role in the response to vessel injury, 2-3 um in diameter with a mean platelet volume of 8 to 10 fL, produced from the cytoplasm of bone marrow megakaryocytes
• Megakaryocyte maturation series


  1. Megakaryoblast

  2. Promegakaryocyte

  3. Megakaryocyte

  4. Metamegakaryocyte
• Megakaryoblast


  • 20 to 50 um in diameter, cytoplasm in varying shades of blue, N/C ratio is about 10:1, fine chromatin pattern, multiple nucleoli
• Promegakaryocyte


  • 20 to 60 um in diameter, N/C ratio is 4:1 to 7:1, irregularly shaped nucleus, may show slight lobulation, chromatin becomes more coarse, multiple nucleoli
• Megakaryocyte


  • 30 to 90 um in diameter, very fine and diffusely granular cytoplasm, N/C ratio is 2:1 to 1:1, multiple nuclei may be visible or the nucleus may show multi-lobulation, no nucleoli are visible
• Metamegakaryocyte


  • 40 to 120 um in diameter, contains coarse clumps of granules aggregating into little bundles, which bud off from the periphery to become platelets, N/C ratio is less than 1:1, multiple nuclei are present
• Platelets


  • 2-3 um in diameter with a mean platelet volume of 8 to 10 fL, two-thirds in circulation and one-third sequestered in the spleen, function is adhesion, secretion, and aggregation at the site of vessel injury
• Beticulated platelets, aka stress platelets, appear in compensation for thrombocytopenia and are larger than ordinary mature platelets
• Platelet lifespan


  9 to 10 days (according to Steininger) or 10 to 12 days (according to Harmening and Brown)