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GOOD AFTERNOONLearning Objectives:WBC in health & disease - overview.Classification Disorders of WBCs..Leukopenia:NeutropeniaLymphopenia.PancytopeniaLeucocytosis:NeutrophiliaEosinophiliaLymphocytosis Neoplastic disorders (cancer)Lymphoma Leukemia (AML/ALL,CML/CLL)

Leukamoid reactions.23Normal Blood Cells:

NeutrophilBasophilEosinophilBandLymphocyteMonocytePltNon granular, MononuclearsSpecific ImmunityGranulocytes, PolymorphsNon-Specific Immunity3

The blood-forming population of bone marrow is made up of three types of cells: Self-renewing stem cellsDifferentiated progenitor (parent) cellsFunctional mature blood cellsAll of the blood cell precursors, of the erythrocyte (i.e., red cell), myelocyte (i.e., granulocyte or monocyte), lymphocyte (i.e., T lymphocyte and B lymphocyte), and megakaryocyte (i.e., platelet) series are derived from a small population of primitive cells called the pluripotent stem cells.A committed stem cell that forms a specific type of blood cell is called a colony-forming unit (CFU). Under normal conditions, the numbers and total mass for each type of circulating blood cell remain relatively constant. The blood cells are produced in different numbers according to needs and regulatory factors. The cytokines that stimulate hematopoiesis are called colony-stimulating factors (CSFs), based on their ability to promote the growth of the hematopoietic cell colonies from bone marrow precursors. Lineage-specific CSFs that act on committed progenitor cells include: erythropoietin (EPO)granulocyte-monocyte colony-stimulating factor (GM-CSF)thrombopoietin (TPO)The major sources of the CSFs are lymphocytes and stromal cells of the bone marrow. Other cytokines, such as the interleukins, support the development of lymphocytes and act synergistically to aid the functions of the CSFs.White Blood Cell Count (WBC) 4.1-10.9x103/LDifferential neutrophils(neu) 60-65%lymphocytes (lymp) 20-25% monocytes (mono) 2-12% eosinophils (eos) 0-7% basophils (bas) 0-2%

Normal WBC Production:Left ShiftThis increase in leukocytes (primarily neutrophils) is usually accompanied by a"left shift"in the ratio of immature to mature neutrophils. The proportion of immature leukocytes increases due to proliferation and release of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF."Right shift"in the ratio of immature to matureneutrophilsis considered with reduced count or lack of "young neutrophils" inblood smear, associated with the presence of "giant neutrophils". This fact shows suppression of bone marrow activity, as a hematological sign specific forpernicious anemiaandradiation sickness.Disorders of white blood cellsThe number of leukocytes, or white blood cells, in the peripheral circulation normally ranges from 4000 to 10,000/L of blood. The term leukopenia describes an absolute decrease in white blood cell numbers. The disorder may affect any of the specific types of white blood cells:NeutropeniaLymphopeniaThe term leukocytosis describes an absolute increase in in white blood cell numbers and also may affect any of the specific types of white blood cells:Neutrophilia EosiniphiliaBasophiliaLymphocytosisMonocytosis

Leukopenia:NeutropeniaLymphopenia.PancytopeniaLeucocytosis:NeutrophiliaEosinophiliaLymphocytosis Lymphadenitis.Neoplastic disorders (cancer)Lymphoma Leukemia (AML/ALL,CML/CLL)

WBC Absolute counts in disease:PeniaPhiliaNeutroPeniaPhiliaEosinoPeniacytosisMonoPeniacytosisLymphoLeukopenia: NeutropeniaReduction in granulocytes:Decreased Production Marrow.Increased destruction drugs, immuneWhen severe Agranulocytosis.Clinical features:Infections chills, fever, fatigue, ulcers.

13NeutropeniaNeutropenia refers specifically to a decrease in neutrophils. It commonly is defined as a circulating neutrophil count of less than 1500 cells/L.Agranulocytosis, which denotes a severe neutropenia, is characterized by a circulating neutrophil count of less than 200 cells/L.Neutropenia can be:AcquiredCongenitalKostmanns syndromeIt occurs sporadically as an autosomal recessive disorder, causes severe neutropenia while preserving the erythroid and megakaryocyte cell lineages that result in red blood cell and platelet production. The total white blood cell count may be within normal limits, but the neutrophil count is less than 200/L. Monocyte and eosinophil levels may be elevated (compensatory).Acquired neutropeniaAccelerated removal - removal of neutrophils from the circulation exceeds productionInflammationInfection, viral or bacterialIncreased destruction:Drug-induced granulocytopeniaTreatment of cancer chemotherapy (e.g., alkylating agents, antimetabolites)IrradiationAutoimmune disorders or drug reactions May cause increased and premature destruction of neutrophilsSplenomegalyNeutrophils may be trapped in the spleen along with other blood cellsFeltys syndromeA variant of rheumatoid arthritis, there is increased destruction of neutrophils in the spleenNeoplasms involving bone marrow (e.g., leukemias and lymphomas, myeloma)Acquired neutropeniaAlcoholism In states:Folic acidVitamin B12IronCooperAplastic anemiaAll of the myeloid stem cells are affected, resulting in anemia, thrombocytopenia, and agranulocytosis;Idiopathic neutropenia that occurs in the absence of other disease or provoking influence.

Leukocytosis: NeutrophiliaIncreased granulocytes:Acute inflammation, Bacterial infections.When severe Leukemoid reaction.Clinical features:Infections or Trauma - fever, fatigue.

17NeutrophiliaPhysiological: In newborns PregnancyIn labor Post-partum After exercise Drugs or toxics: Administration of corticosteroids - may increase the release of neutrophils from the bone marrow and reduce their migration into tissues; Acute poisoning with Pb, Hg, some venoms; Reactive neutrophilia - the result of increased release of neutrophils to compensate their high affinity for tissues. It is frequently accompanied by deviation to the left of the leukocyte formula (leukemoid reaction); Metabolic and endocrine diseases: Diabetic ketoacidosisAcute renal failureAcute gout criseIn some malignant hematologic diseases.