WBC

• Myeloid tissues


  Bone marrow and cells derived from it

  
• Lymphoid tissues


  Thymus, lymph nodes and spleen
• Development and maintenance of hematopoietic tissues

  1. Blood cell progenitors first appear during third week of development

  2. Hematopoietic stem cells arise several week later in the mesoderm of the intraembryonic aorta / gonad / mesonephros region

  3. Liver becomes the chief site of hematopoiesis from the third month and shortly before birth

  4. HSC also resides in the placenta and at the fourth month occurs at the bone marrow

  5. At birth, the marrow serves as the chief site of hematopoiesis until puberty, where it only occur at the axial skeleton

  
• Formed elements of blood

  Have a common origin from HSCs, the pluripotent cells that sit at the apex of a hierarchy of bone marrow progenitors

  
• Colony forming units


  Produce colonies composed of specific kinds of mature cells when grown in culture
• Pluripotency and capacity for self-renewal


  • Essential properties of HSCs for maintenance of hematopoiesis
• Marrow response to short-term physiologic needs

  Regulated by hematopoietic growth factors through the effects on committed progenitors

  
• Multipotent progenitors


  More proliferative than HSCs but have a lesser capacity for self-renewal
• Stem cell factor (KIT ligand), FLT3-ligand

  Act through receptors expressed in very early committed progenitors
• Erythropoietin, GM-CSF, G-CSF and thrombopoietin

  Act through receptors of restricted committed progenitors
• Primary tumors of hematopoietic cells are the most important disease the interfere marrow function

  
• Tumors of hematopoietic origin are often associated with mutations that block progenitor cell maturation or abrogate growth factor dependence

  
• Disorders of white cells

  • Proliferative disorders - expansion of leukocytes
  • Reactive proliferations - in the setting of infections or inflammation
  • Neoplastic proliferations - less frequent, more important clinically
  • Leukopenias - deficiency of leukocytes

  
• Leukopenia


  An abnormally low WBC count that results from reduced numbers of neutrophils (neutropenia, granulocytopenia)
• Lymphopenia


  Less common, but can be congenital or acquired, commonly observed in HIV infection, drug therapy, autoimmune disorders, malnutrition and acute viral infections
• Granulocytopenia


  More common and often associated with diminished granulocyte function
• Neutropenia


  The reduction in the number of neutrophils in the blood
• Agranulocytosis


  The clinically significant reduction in neutrophils which makes the individual susceptible for bacterial and fungal infections
• Pathogenesis of neutropenia/agranulocytosis


  1. Inadequate or ineffective granulopoiesis

  2. Accelerated destruction or sequestration of neutrophils
• Causes of inadequate or ineffective granulopoiesis


  • Suppression of HSCs - occurring in aplastic anemia and infiltrative marrow disorders
  • Suppression of committed granulocytic precursors - exposure to drugs
  • Ineffective hematopoiesis - defective precursors die in the marrow as seen in megaloblastic anemia and myelodysplastic syndromes
  • Rare congenital conditions - defects in genes as seen in Kostmann syndrome

  
• Causes of accelerated destruction or sequestration of neutrophils

  • Immunologically mediated injury - can be idiopathic, seen in SLE or drug exposure
  • Splenomegaly - leads to modest neutropenia, associated with anemia and thrombocytopenia
  • Increased peripheral utilization - bacterial, fungal or rickettsial infections
• Causes of drug-induced agranulocytosis

  • Generalized suppression of hematopoiesis due to alkylating agents and anti-metabolites used in cancer treatment
  • Idiosyncratic reaction caused by aminopyrine, chloramphenicol, sulfonamides, thiouracil, chlorpromazine and phenylbutazone
  • Chlorpromazine and phenylbutazone produces a toxic effect on granulocytic precursors on the marrow
  • Sulfonamides, aminopyrine, thiouracil and antibodies induce immune destruction of mature PMNs
• Monoclonal proliferations of large granular lymphocytes (LGL leukemia)


  Can also produce severe neutropenia
• Alterations on the bone marrow vary with the etiology of neutropenia/agranulocytosis

  
• Infections are common consequences of agranulocytosis
• Severe and life threatening infections occur in the lungs, urinary tract and kidneys
• Increased risk for fungal infections caused by Candida and Aspergillus
• Site of infection has little WBC response and cause an inflamed or enlarged regional lymph node
• Ulcerating necrotizing lesions of the oral cavity (agranulocytic angina) can occur
• Agranulocytosic infections


  May cause death within hours to days
• Most serious infections present <500 per mm3 PMNs while <1,000 per mm3 is quite worrisome
• 1. CSF


  Stimulates the production of granulocytes from marrow precursor and is given for myelosuppresive chemotherapy

  
• Leukocytosis


  Increase in the number of WBC in the blood
• Leukocytosis is a common reaction to a variety of inflammatory stress
• Factors that influence blood leukocyte count

  1. Size of myeloid and lymphoid precursor and storage cell pools in the marrow, thymus, circulation and peripheral tissues

  2. Rate of release of cells to the circulation

  3. Proportion of cells adherent to vessel walls at any time (marginal pool)

  4. Rate of extravasation of cells into the tissue

  
• Factors that cause leukocytosis

  • Neutrophilic leukocytosis
  • Eosinophilic leukocytosis (eosinophilia)
  • Basophilic leukocytosis (basophilia)
  • Monocytosis
  • Lymphocytosis
• In sepsis or severe inflammatory disorders, leukocytosis is accompanied by toxic granules, Dohle bodies, and cytoplasmic vacuoles
• Leukemoid reaction


  The increase in granulocytes in blood due to severe infections
• Lymphadenitis


  Activation of resident immune cells leads to morphological changes in lymph nodes
• Changes in lymph nodes during lymphadenitis


  1. Primary follicles enlarge and develop pale staining germinal centers

  2. Paracortical T-cell zones may also undergo hyperplasia