Leucocytes Benign Disorders
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LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS DrDr AdelAdel MM AbuzenadahAbuzenadah LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative Change in number TerminologyTerminology Cytosis / philia Increase in number Cytopenia Decrease in number QualitativeQualitative Morphologic changes Functional changes LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS Quantitative changes RelativeRelative vsvs AbsoluteAbsolute valuesvalues TotalTotal whitewhite bloodblood cellcell countcount DifferentialDifferential countcount AbsoluteAbsolute countcount DifferentialDifferential givesgives thethe relativerelative percentagepercentage ofof eacheach WBCWBC AbsoluteAbsolute valuevalue givesgives thethe actualactual numbernumber ofof eacheach WBC/mmWBC/mm3 ofof bloodblood Calculation:Calculation: absoluteabsolute count=count= TotalTotal WBCWBC xx percentpercent LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS Quantitative changes RegulationRegulation ofof cellcell productionproduction RegulatoryRegulatory mechanismsmechanisms mustmust operateoperate inin closeclose controlledcontrolled wayway HaemopoieticHaemopoietic growthgrowth factorsfactors TheThe controlcontrol ofof cellcell deathdeath InhibitorsInhibitors ofof cellcell proliferationproliferation StromalStromal cellcell factorsfactors (cell(cell--cellcell andand cellcell--matrixmatrix interaction)interaction) LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS Quantitative changes (LEUCOCYTOSIS) LeucocytesLeucocytes PhagocytesPhagocytes Granulocytes Neutrophils Eosinophils Basophils Mononuclear phagocytic cells Monocytes Macrophage and denderetic cells LymphocytesLymphocytes B-cells T-cells LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS Quantitative changes (LEUCOCYTOSIS) DefinitionDefinition RaisedRaised TWBCTWBC duedue toto elevationelevation ofof anyany ofof aa singlesingle lineage.lineage. Note: elevation of the minor cell populations can occur without a rise in the total white cell count. NormalNormal referencereference rangerange (adult(adult 2121 years)years) 4.5 -- 11.0 x 109/L LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (LEUCOPENIA)(LEUCOPENIA) DefinitionDefinition TWBCTWBC lowerlower thanthan thethe referencereference rangerange forfor thethe ageage isis defineddefined asas leucopenialeucopenia LeucopeniaLeucopenia maymay affectaffect oneone oror moremore lineageslineages andand itit isis possiblepossible toto bebe severelyseverely neutropenicneutropenic oror lymphopeniclymphopenic withoutwithout aa reductionreduction inin totaltotal whitewhite cellcell count.count. LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (contd.)(contd.) GranulocytosisGranulocytosis IncreaseIncrease inin thethe countcount ofof allall oror oneone ofof thethe granulocyticgranulocytic componentcomponent Neutrophils Basophils Eosinophils AgranulocytosisAgranulocytosis DecreaseDecrease inin thethe countcount ofof allall oror oneone granulocyticgranulocytic componentcomponent WBCWBC Histogram:Histogram: NeutrophilsNeutrophils CountCount 2.52.5 -- 7.57.5 xx 10109/l/l GranularGranular cytoplasmcytoplasm TransientTransient staystay inin bloodblood MajorMajor phagocyticphagocytic rolerole BacterialBacterial killingkilling 33--55 lobeslobes ofof nucleusnucleus LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPHILIA)(NEUTROPHILIA) DefinitionDefinition Increase in the number of neutrophils and / or its precursors In adults count >7.5 x 109/L but the counts are age dependent Increase may results from alteration in the normal steady state of Production Increased progenitor cell proliferation Increased frequency of cell division of committed neutrophil precursors Transit Impaired transit to tissutissuee Migration Destruction LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPHILIA)(NEUTROPHILIA) contd.contd. CausesCauses ofof NeutrophiliaNeutrophilia Infection Bacterial Inflammatory conditions Autoimmune disorders Gout Neoplasia Metabolic conditions Uraemia Acidosis Haemorhage Corticosteroids Marrow infiltration/fibrosis Myeloproliferative disorders LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPHILIA)(NEUTROPHILIA) contd.contd. AcuteAcute NeutrophiliaNeutrophilia MobilizedMobilized rapidlyrapidly byby stress,stress, suggestedsuggested byby adrenalineadrenaline stressstress test;test; duedue toto reducedreduced neutrophilneutrophil adhesionadhesion Bacterial infection Stress Exercise SlowerSlower riserise whenwhen cellscells areare releasedreleased fromfrom thethe bonebone marrowmarrow storagestorage poolpool Steroid Infections (reactive changes; left shift, toxic granulation, high NAP score and Dohle bodies. SteroidsSteroids alsoalso reducesreduces thethe passagepassage toto thethe tissuestissues LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPHILIA)(NEUTROPHILIA) contd.contd. ChronicChronic neutrophilianeutrophilia Long term corticosteroid therapy Chronic inflammatory reactions Infections or chronic blood loss Infections Less common organisms e.g poliomyelitis Leukemoid reactions Applied to chronic neutrophilia with marked leucocytosis (>20 x 109/L) The usual feature is the shift to the left of myeloid cells Causes include Infections Marrow infiltration Systemic disease (Acute liver failure) LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPENIA)(NEUTROPENIA) contd.contd. NeutropeniaNeutropenia isis anan absoluteabsolute reductionreduction inin thethe numbernumber ofof circulatingcirculating neutrophilsneutrophils Mild (1- 1.5 x 109/L) Moderate (0.5 – 1 x 109/L) Severe (<0.5 x 109/L) Symptoms are rare with the neutrophil count above 1 x 109/L Bacterial infections are the commonest Fungal, viral and parasitic infection are relatively uncommon LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPENIA)(NEUTROPENIA) contd.contd. Causes of Neutropenia Racial Congenital Cyclical neutropenia Marrow aplasia MarMarrowrow infiltration Megaloblastic anemia Acute infections Typhoid, Miliary TB, viral hepatitis Drugs Irradiation exposure Immune disorders HIV SLE Felty’s syndrome Neonatal isoimmune and autoimmune neutropenia Hyperslplenism LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (NEUTROPENIA)(NEUTROPENIA) contd.contd. ManagementManagement ofof NeutropeniaNeutropenia Remove the cause if possible Treat any infection aggressively Role of Growth factors Splenectomy CyclicalCyclical neutropenianeutropenia Regular recurring episodes ofof severesevere neutropenianeutropenia (<0.2(<0.2 xx 10109/L) usually lasting for 3-6 days Can be familial & inherited with maturation arrest Three suggested mechanisms for cyclical neutropenia Stem cell defect & altered response to growth factors Defect in humoral or cellular stem cell control Periodic accumulation of an inhibitor EosinophilsEosinophils CountCount 0.20.2 –– 0.80.8 xx 10109/l/l BilobedBilobed nucleusnucleus PhagocyticPhagocytic activityactivity isis lowlow ModulationModulation ofof hypersensitivityhypersensitivity andand allergicallergic reactionsreactions LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (EOSINOPHILIA)(EOSINOPHILIA) IncreaseIncrease inin thethe eosinophileosinophil countcount mustmust promptprompt forfor furtherfurther investigationinvestigation (>0.6(>0.6 xx 10109/L)/L) TheThe causescauses ofof eosinophiliaeosinophilia cancan bebe consideredconsidered underunder followingfollowing headingsheadings Allergy Atopic, drug sensitivity and pulmonary eosinophilia Infection ParasitesParasites,, recovery from infections Malignancy Hodgkin’s disease, NHL and myeloprolifmyeloproliferativeerative disorders Drugs Skin disorders Gastrointestinal disorders Hypereosinophilic syndrome LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (EOSINOPHILIA)(EOSINOPHILIA) Contd.Contd. HypereosinophilicHypereosinophilic syndromesyndrome CriteriaCriteria ofof diagnosisdiagnosis Peripheral blood eosinophil >1.5 x 109/L Persistence of counts more than 6 months End organ damage Absence of any obvious cause for eosinophilia OrganOrgan mostmost commonlycommonly involvedinvolved Heart Lung Skin Neurological MonocytesMonocytes CountCount isis 0.20.2--0.80.8 xx 10109/l/l FunctionsFunctions Antigen presentation Cytokine production Phagocytosis LEUCOCYTESLEUCOCYTES BENIGNBENIGN DISORDERSDISORDERS QuantitativeQuantitative changeschanges (MONOCYTOSIS)(MONOCYTOSIS) AbsoluteAbsolute monocytemonocyte countcount isis ageage dependentdependent CountCount rarelyrarely exceedsexceeds >1.0>1.0 xx 10109/L/L HaveHave nono marrowmarrow reservesreserves UsefulUseful harbingerharbinger ofof engraftmentengraftment CausesCauses ofof monocytosismonocytosis cancan bebe groupedgrouped asas Infections Chronic infection (TB, typhoid fever, infective endocarditis) Recovery ffromrom acute infection Malignant disease MDS, AML, HD, NHL Connective tissue disorders Ulcerative colitis, Sarcoidosis, Crohn’s disease Post splenectomy BasophilsBasophils CountCount 0.10.1 –– 0.20.2 xx