3. Benign Disorders of WBCs TEST ONLY.docx

Benign Disorders of WBCs Leukopenia: Decrease in # of WBCs Types: Neutropenia Lymphocytopenia Neutropenia: Decrease in circulating neutrophils Mild (1000-1500/mm) Mod (500-1000/mm) Severe (<500mm): risk of serious infection increases as absolute neutrophil count (ANC) drops severely Agranulocytos...

Benign Disorders of WBCs Leukopenia: Decrease in # of WBCs Types: Neutropenia Lymphocytopenia Neutropenia: Decrease in circulating neutrophils Mild (1000-1500/mm) Mod (500-1000/mm) Severe (<500mm): risk of serious infection increases as absolute neutrophil count (ANC) drops severely Agranulocytosis: ANC <100 Absence of neutrophils in peripheral blood Granulocytopenia: Reduced number of blood granulocytes (neutrophils, eosinophils, basophils) Etiology: Reduced production Increased destruction Increased peripheral utilization Congenital Treatment Antibiotics Colony stimulating factor Granulocyte transfusion Splenectomy for Felty Syndrome (combination of rheumatoid arthritis, splenomegaly, and neutropenia) and neutropenia w recurrent bacteria infection, systemic lupus w autoimmune agranulocytosis Chediak-Higashi Syndrome: Autosomal recessive Lysosomal storage disorder Signs: Recurrent bacterial infections Abnormal NK function Hypopigmentation of skin, eyes, hair Pathogenesis: Mutation of LYST/CHS1 Defective lysosome functions Delayed fusion of phagosomes with lysosomes Decreased cytotoxicity of NK cell and T cell Clinical Features: Nonpigmented/hypopigmented skin Gingivitis Lab Findings: Reduced/absent NK cytotoxicity Larger and irregular lysosomes Autoimmune Neutropenia Most common in children Occurs due to neutrophil antibodies include IgG against: CD 16b (most common) HNA1 (most common) HNA4 (less common) Shwachman-Diamond Syndrome Autosomal recessive Associated with mutations in the SBDS gene Characterized by: Exocrine pancreatic insufficiency Bone marrow dysfunction (defect in bone marrow stroma and stem cell) Skeletal abnormalities Leukocytosis Increase in WBC Reaction to physiological or pathological process Left shift: Release of stored leukocytes and increase in immature leukocytes in circulation Leukemoid rxn: á immature cells, particularly more myelocytes than in left shift á leukocyte alkaline phosphatase score than leukemia Leucoerythroblastic rxn: leukemoid rxn + nucleated red blood cells common in myelofibrosis Diagnosis is confirmed via blood smear: Myeloid Increased blasts Lymphocytosis Neutrophils Made in bone marrow Immobilize or kill pathogens through releasing neutrophil extracellular traps (NETs) Neutrophilia: Higher than normal # of neutrophils Shift neutrophilia: Shift of marginal to circulating, NO left shift True Neutrophilia: left shift present NO leukocytosis in certain infections, such as typhoid fever, paratyphoid fever, mumps, measles and TB Drugs: Cortical steroid Eosinophils: Participates in: Antiparasitic and bactericidal activity Immediate allergic reactions Eosinophilia: Parasite infections Allergic reactions Neoplasms Basophils: Irregular bilobed nuclei Contain histamines (vasodilation) and heparin (anticoagulant) Basophilia: Occasionally seen in allergic reactions Most commonly associated with neoplastic disorders especially myelogenous leukemia Monocytes: Kidney or C-shaped nuclei Migrate to tissue transformed into macrophages Monocyte-macrophage system (single functional unit) consisting of: Kupffer cells in liver Microglia in CNS Osteoclasts in bone Increased in infections, autoimmune disorders, and neoplasms Reduced in marrow failure, AIDS and hairy cell leukemia Monocytosis: Associated with neoplastic lesions especially myeloproliferative disorders Lymphocytes: T cells, B cells or NK cells B cells: from bone marrow (responsible for humoral immunity) T cells: from bone marrow but mature in thymus (responsible for cell-mediated immunity) Lymphocytosis: Absolute count gets high Reactive: Polyclonal Clonal: Monoclonal B cell lymphocytosis Morphological Abnormality of White Cells Toxic Granulation: Seen in severe infection/inflammatory states Dohle Bodies: Remnants of Rough ER Hypersegmentation: Defined as increased lobes: 3 cells have 5 lobes or a single cell with 6 lobes Benign Disorders of Lymph Nodes Acute Lymphadenitis Most commonly due to S. aureus infection Also associated with cat-scratch disease, IV drug use Usually superficial lymph nodes Enlarged lymph nodes that are soft and tender Overlying skin red and edematous Histologically granulocytes are seen Chronic Lymphadenitis Painless enlargement of lymph nodes Tingible-body macrophages commonly present Diagnosis: Flow cytometry to rule out monoclonal lymphocytic proliferation Splenomegaly: Hyperfunction of spleen Etiology: RBC destruction: Hereditary spherocytosis, thalassemia Ectopic hematopoiesis: Myeloproliferative neoplasm, etc Clinical Features: Nucleated red cells Teardrop red cell shape Hyposplenism: Reduced spleen Due to congenital abnormalities Peripheral blood abnormalities Howell-Jolly bodies Pappenheimer bodies Target cells