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Leukocytes

Leukocytes. Leukocytes, or white blood cells, are found within the bone marrow (BM ),the peripheral blood, and the tissues .

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Leukocytes

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  1. Leukocytes Leukocytes, or white blood cells, are found within the bone marrow (BM),the peripheral blood, and the tissues. Leukocytes are among the essential elements of the hematopoietic-lymphoreticular-immune system, which functions to protect the human body from nonself cells (infection) and altered-self cells (cancer).

  2. NoNNeopLasticDisorDers • Quantative evaluation • Qualitative evaluation

  3. Neutrophilia • Mechanisms: (1) the rate of inflow of cells from the BM (2) the proportion of neutrophils in the marginal granulocyte pool (MGP) and the circulating granulocyte pool (CGP) of the blood (3) the rate of outflow of neutrophilsfrom the blood. • Determinants: • Certain host factors • Microorganisms factors • Drugs

  4. Neutrophilia • Physiologic • Pathologic

  5. Neutrophilia with a left shift can be seen in response to infection or inflammation

  6. Neutropenia Neutropeniais a reduction in the absolute neutrophil count (ANC) below ˜1.5–2 × 10*9/L for white adults and below ˜1.2–1.3 × 10*9/L for black adults. • Mechanisms: (1) the rate of inflow of cells from the BM (2) the proportion of neutrophils in the marginal granulocyte pool (MGP) and the circulating granulocyte pool (CGP) of the blood (3) the rate of outflow of neutrophils from the blood.

  7. Causes of Neutropenia • Drugs • Radiation

  8. Causes of Neutropenia • Intrinsic defects • myeloid hypoplasia or a proliferation defect • Fanconi’s anemia (FA) • Kostmann’ssyndrome • Schwachman-Diamond syndrome • cyclic neutropenia 2. maturation defects • myelokathexis • Chédiak-Higashi syndrome.

  9. Kostmann’s syndrome • The peripheral smear confirmed the leukopenia and almost complete absence of neuutrophils. • A touch preparation done on the marrow biopsy shows a marked increase in myeloid precursors without evidence of maturation PMN

  10. Myelokathexis WHIM:warts, hypogammaglobulinemia, infectionsandmyelokathexis

  11. Causes of Neutropenia • Immune-mediated: RA • Hematologic: megaloblasticanemia, myelodysplasia, marrow failure, marrow replacement • Infectious: any overwhelming infection • Others: starvation, hypersplenism

  12. Pseudoneutropenia • Pseudoneutropenia may be caused by increased margination of neutrophils in some individuals, without a decrease in total granulocyte count. • Small doses of endotoxin will cause a shift of neutrophils into the MGP from the CGP, giving an apparent neutropenia, before causing leukocytosis.

  13. Morphologic Alterations in Neutrophils

  14. Functional Disorders of Neutrophils • alterations in both morphology and function: • Chédiak-Higashi syndrome • specific granule deficiency (SGD) • functional disorders with essentially normal morphology on Wright’s- and Giemsastained films: • Chronic granulomatous disease (CGD) • Myeloperoxidase deficiency(MYD) • Leukocyte adhesion deficiency (LAD)

  15. Chronic Granulomatous Disease (CGD)

  16. Myeloperoxidase Deficiency(MYD) • Myeloperoxidase (MPO) is present in neutrophils (in azurophil/primary granules) and monocytes (in lysosomes) but is not present in promonocytes and tissue macrophages. • (H2O2 + Cl- → H2O + ClO-)

  17. Leukocyte Adhesion Deficiency (LAD) • LAD-I: a mutation in the ß2-subunit (of CD18) • LAD-II: mutation affecting fucose transport, leading to the impaired expression of selectinligands on leukocytes (CD15a or sialyl Lewis X) • LAD-III: defect in integrin activation (via endothelial chemokines) caused by a mutation in leukocyte-expressed G protein–coupled receptors (GPCRs)

  18. Specific Granule Deficiency (SGD) • present with multiple bacterial infections, atypical bilobed nuclei within neutrophils, and lack of secondary/specific cytoplasmic granules within neutrophils on Wright’sstained peripheral blood films. • SGD also affects eosinophils. • granule deficiencies , impaired bactericidal activity, neutrophils are defective in chemotaxis, receptor upregulation, and disaggregation. • A mutation in a myeloid transcription factor gene (C/EBPe) appears to play a role in this disease.

  19. Keep Smiling

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