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LEUKOPENIA Abnormally LOW WBC
NEUTROPENIA, AGRANULOCYTOSIS
NEUTROPENIA Reduction in the number of granulocytes in PBS    (peripheral blood smear) < 2000/uL Mild 1000-2000/uL Moderate 500-1000/uL Severe (agranulocytosis) <500/uL DEFINITION:
AGRANULOCYTOSIS Marked reduction in neutrophil count Disappearance of neutrophil precursors in the bone marrow Absence or less than 500/uL of pmns
PATHOGENESIS: 1. INEFFECTIVE GRANULOPOIESIS  2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS
Multipotent Progenitors Commited Precursors Late  Precurosors Mature  Form
INEFFECTIVE GRANULOPOIESIS Suppression of hematopoietic stem cells Aplastic anemia Infiltrative d/o Suppression of committed granulocytic precursors  Alkylating drugs – generalized effect Idiosyncratic reaction – Chloramphenicol
Defective precursor cells susceptible to death while in BM Megaloblastic anemia Genetic defect  impaired granulocytic differentiation :  Kostmann syndrome INEFFECTIVE GRANULOPOIESIS
Immune mediated Idiopathic  Autoimmune Drugs Splenic sequestration 20 to enlargement of spleen Increased peripheral utilization Overwhelming infection ACCELERATED REMOVAL/DESTRUCTION
Most common cause is DRUG TOXICITY Alkylating drugs/ Anti-metabolites Generalized suppresion of BM  Agranulocytosis Predictable Dose related Chlorpromazine/ Phenothiaxines Toxinc effect on granulocytic precursors in BM Thiouracil/Sulfonamides/ Aminopyrine Antobody mediated destruction of mature neutrophils Autoantibodies against neutrophil specific antigens  Suppression of marrow granulocytic progenitors by products of neoplastic cell  Agranulocytosis:
S/S  Related to infection Malaise, chills, fever Marked weakness & fatigue Death in severe agranulocytosis Neutrophil count < 500/mm3   			 CLINICAL COURSE:
Broad spectrum antibiotic G-CSF , a growth factor that stimulates production of granulocytes from BM Given following chemotx Withdrawing or tapering dose of drug Treatment:
LEUKOCYTOSIS INCREASE IN NUMBER OF WBC  ,[object Object]
FIRST SIGN OF NEOPLASTIC GROWTH	 OF  WBC ,[object Object]
CAUSES:
CAUSES:
ACUTE NONSPECIFIC LYMPHADENITIS
Reactive changes to: Microbe , Cell debris, Foreign matter Localized – Regional LN Generalized Lymphadenopathy Systemic Viral infection – Children Bacteremia Prominence of Lymphoid Follicles with Large germinal center, Debris, Macrophages, Necrosis, Suppuration Features:
Enlarged  Tender to touch Fluctuant if (+) abscess Draining sinuses to skin  Suppurative necrosis Clincal Presentation:
CHRONIC NONSPECIFIC LYMPHADENITIS MORPHOLOGIC TYPES
Activation of Humoral response Rheumatoid arthritis Early stage of HIV Must be differentiated from Follicular Lymphoma Germinal center B-cells are (+) for BCL2 stain  FOLLICULAR HYPERPLASIA
Morphology
Trigger the Cellular Immune responses Reactive changes in T cell region of LN PARACORTICAL AREA EXPANSION EFFACED THR FOLLICLES Drugs – Dilantin Acute viral infxn IM Viral Vaccine PARACORTICAL LYMPHOID HYPERPLASIA
PARACORTICAL LYMPHOID HYPERPLASIA
Distention of lymphatic sinusoids  Non-specific Particularly prominent in LN draining cancers Represent host immune reaction to cancer Sinus Histiocytosis
Sinus Histiocytosis

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Neutropenia, Agranulocytosis

  • 3. NEUTROPENIA Reduction in the number of granulocytes in PBS (peripheral blood smear) < 2000/uL Mild 1000-2000/uL Moderate 500-1000/uL Severe (agranulocytosis) <500/uL DEFINITION:
  • 4. AGRANULOCYTOSIS Marked reduction in neutrophil count Disappearance of neutrophil precursors in the bone marrow Absence or less than 500/uL of pmns
  • 5. PATHOGENESIS: 1. INEFFECTIVE GRANULOPOIESIS 2. ACCELERATED REMOVAL OR DESTRUCTION OF NEUTROPHILS
  • 6. Multipotent Progenitors Commited Precursors Late Precurosors Mature Form
  • 7. INEFFECTIVE GRANULOPOIESIS Suppression of hematopoietic stem cells Aplastic anemia Infiltrative d/o Suppression of committed granulocytic precursors Alkylating drugs – generalized effect Idiosyncratic reaction – Chloramphenicol
  • 8. Defective precursor cells susceptible to death while in BM Megaloblastic anemia Genetic defect  impaired granulocytic differentiation : Kostmann syndrome INEFFECTIVE GRANULOPOIESIS
  • 9. Immune mediated Idiopathic Autoimmune Drugs Splenic sequestration 20 to enlargement of spleen Increased peripheral utilization Overwhelming infection ACCELERATED REMOVAL/DESTRUCTION
  • 10. Most common cause is DRUG TOXICITY Alkylating drugs/ Anti-metabolites Generalized suppresion of BM  Agranulocytosis Predictable Dose related Chlorpromazine/ Phenothiaxines Toxinc effect on granulocytic precursors in BM Thiouracil/Sulfonamides/ Aminopyrine Antobody mediated destruction of mature neutrophils Autoantibodies against neutrophil specific antigens Suppression of marrow granulocytic progenitors by products of neoplastic cell Agranulocytosis:
  • 11. S/S Related to infection Malaise, chills, fever Marked weakness & fatigue Death in severe agranulocytosis Neutrophil count < 500/mm3 CLINICAL COURSE:
  • 12. Broad spectrum antibiotic G-CSF , a growth factor that stimulates production of granulocytes from BM Given following chemotx Withdrawing or tapering dose of drug Treatment:
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  • 21. Reactive changes to: Microbe , Cell debris, Foreign matter Localized – Regional LN Generalized Lymphadenopathy Systemic Viral infection – Children Bacteremia Prominence of Lymphoid Follicles with Large germinal center, Debris, Macrophages, Necrosis, Suppuration Features:
  • 22. Enlarged Tender to touch Fluctuant if (+) abscess Draining sinuses to skin Suppurative necrosis Clincal Presentation:
  • 24. Activation of Humoral response Rheumatoid arthritis Early stage of HIV Must be differentiated from Follicular Lymphoma Germinal center B-cells are (+) for BCL2 stain FOLLICULAR HYPERPLASIA
  • 26. Trigger the Cellular Immune responses Reactive changes in T cell region of LN PARACORTICAL AREA EXPANSION EFFACED THR FOLLICLES Drugs – Dilantin Acute viral infxn IM Viral Vaccine PARACORTICAL LYMPHOID HYPERPLASIA
  • 28. Distention of lymphatic sinusoids Non-specific Particularly prominent in LN draining cancers Represent host immune reaction to cancer Sinus Histiocytosis