This document discusses leukopenia, neutropenia, and agranulocytosis. It defines them as abnormally low white blood cell counts, specifically a reduction in granulocytes or neutrophils. Neutropenia is classified as mild, moderate, or severe based on neutrophil counts. Agranulocytosis is a marked reduction or absence of neutrophils in the blood and bone marrow. The causes include ineffective granulopoiesis, accelerated removal/destruction of neutrophils, and most commonly drug toxicity from chemotherapy agents, antipsychotics, antibiotics, and others. Signs and symptoms relate to increased risk of infection. Treatment involves antibiotics, growth factors, and withdrawing the causal drug.

1. LEUKOPENIAAbnormally LOW WBC

2. NEUTROPENIA, AGRANULOCYTOSIS

3. NEUTROPENIAReduction in the number of granulocytes in PBS (peripheral blood smear)< 2000/uLMild 1000-2000/uLModerate 500-1000/uLSevere (agranulocytosis) <500/uLDEFINITION:

4. AGRANULOCYTOSISMarked reduction in neutrophil countDisappearance of neutrophil precursors in the bone marrowAbsence or less than 500/uL of pmns

5. PATHOGENESIS:1. INEFFECTIVE GRANULOPOIESIS 2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS

6. Multipotent ProgenitorsCommited PrecursorsLate PrecurosorsMature Form

7. INEFFECTIVE GRANULOPOIESISSuppression of hematopoietic stem cellsAplastic anemiaInfiltrative d/oSuppression of committed granulocytic precursors Alkylating drugs – generalized effectIdiosyncratic reaction – Chloramphenicol

8. Defective precursor cells susceptible to death while in BMMegaloblastic anemiaGenetic defect  impaired granulocytic differentiation : Kostmann syndromeINEFFECTIVE GRANULOPOIESIS

9. Immune mediatedIdiopathic AutoimmuneDrugsSplenic sequestration20 to enlargement of spleenIncreased peripheral utilizationOverwhelming infectionACCELERATED REMOVAL/DESTRUCTION

10. Most common cause is DRUG TOXICITYAlkylating drugs/ Anti-metabolitesGeneralized suppresion of BM  AgranulocytosisPredictableDose relatedChlorpromazine/ PhenothiaxinesToxinc effect on granulocytic precursors in BMThiouracil/Sulfonamides/ AminopyrineAntobody mediated destruction of mature neutrophilsAutoantibodies against neutrophil specific antigens Suppression of marrow granulocytic progenitors by products of neoplastic cell Agranulocytosis:

11. S/S Related to infectionMalaise, chills, feverMarked weakness & fatigueDeath in severe agranulocytosisNeutrophil count < 500/mm3 CLINICAL COURSE:

12. Broad spectrum antibioticG-CSF , a growth factor that stimulates production of granulocytes from BMGiven following chemotxWithdrawing or tapering dose of drugTreatment:

13. LEUKOCYTOSISINCREASE IN NUMBER OF WBC REACTIVE

14. FIRST SIGN OF NEOPLASTIC GROWTH OF WBC Pathogenesis

18. CAUSES:

19. CAUSES:

20. ACUTE NONSPECIFIC LYMPHADENITIS

21. Reactive changes to:Microbe , Cell debris, Foreign matterLocalized – Regional LNGeneralized LymphadenopathySystemic Viral infection – ChildrenBacteremiaProminence of Lymphoid Follicles with Large germinal center, Debris, Macrophages, Necrosis, SuppurationFeatures:

22. Enlarged Tender to touchFluctuant if (+) abscessDraining sinuses to skin Suppurative necrosisClincal Presentation:

23. CHRONIC NONSPECIFIC LYMPHADENITISMORPHOLOGIC TYPES

24. Activation of Humoral responseRheumatoid arthritisEarly stage of HIVMust be differentiated from Follicular LymphomaGerminal center B-cells are (+) for BCL2 stain FOLLICULAR HYPERPLASIA

25. Morphology

26. Trigger the Cellular Immune responsesReactive changes in T cell region of LNPARACORTICAL AREA EXPANSIONEFFACED THR FOLLICLESDrugs – DilantinAcute viral infxnIMViral VaccinePARACORTICAL LYMPHOID HYPERPLASIA

27. PARACORTICAL LYMPHOID HYPERPLASIA

28. Distention of lymphatic sinusoids Non-specificParticularly prominent in LN draining cancersRepresent host immune reaction to cancerSinus Histiocytosis

29. Sinus Histiocytosis