Neutrophilia new version

NEUTROPHILIA Dr Truc Phan University of Medicine and Pharmacy, HCMC Self-renewal Proliferative Differentiation Apoptosis DEFINITION & TERMINOLOGY - Definition: ANC greater than 2SD above the mean value - ≥1 years: 7.5 x 109/L - At birth, mean ANC is 12 x 109/L - Neutrophilia = Neutrophilic leukocytosis = Polymorphonuclear leukocytosis = Granulocytosis - Leukocytosis? - Granulocytosis? - Leukemoid reaction? DIURNAL RYTHYMS - Morning pseudoneutropenia? MECHANISMS OF NEUTROPHILIA Mitotic Pool = Myeloblast + Promyelocyte + Myelocyte Maturation Pool = Metamyelocyte + Band + SN Storage Pool = Mature neutrophil reserve The total blood neutrophil pool (TBNP) = Circulating + Marginal Pool The flow of cells is unidirectional MECHANISMS OF NEUTROPHILIA - Marginal circulating pools: a few minutes, freely exchangeable Marrow blood: a few hours Increases in the production at least a few days Sustained moderate to marked neutrophilia? ACUTE NEUTROPHILIA - Pseudoneutrophilia (Demargination) - shift of cells from the marginal; partially from the spleen; other vascular beds, particularly the pulmonary capillaries - increase heart rate and cardiac output - within a few minutes - account for about a doubling in neutrophil count => ? - distinguishing neutrophilia from the response to infections, protracted stress, or glucocorticoid administration? ACUTE NEUTROPHILIA - Marrow Storage Pool Shift - release of neutrophils from the marrow neutrophil reserves - response to inflammation and infections - The marrow reserve pool consists of SN and bands - Metamyelocytes are not released except under extreme situations - The postmitotic marrow neutrophil pool is #10 times the size of the blood neutrophil pool => ? CHRONIC NEUTROPHILIA - Proliferation of neutrophil precursors - Repeated doses of endotoxin, glucocorticoids, or CSF - Stimulation of cell divisions within the mitotic precursor pool => postmitotic pool size ↑ => M/E? - increases severalfold with chronic infections - Even greater increases? - MPN, AL - Leukemoid reaction - G-CSF > Maximum: week => ? KEY RECOMMENDATIONS FOR PRACTICE Dr Truc Phan University of Medicine and Pharmacy, HCMC Case study A 34-year-old man is brought to the emergency department due to several hours of confusion His wife reports that he has had fever, malaise, and cough for the past days A year ago, the patient required prolonged hospitalization and extensive surgery for multiple gunshot wounds to the abdomen He takes no medications regularly and has no other medical problems The patient does not use tobacco, alcohol, or illicit drugs He has no history of recent travel Temperature is 40.5 C, blood pressure is 80/50 mm Hg, pulse is 110/min, and respirations are 32/min Mucous membranes are moist and no cervical lymphadenopathy is present Dullness to percussion and crackles over the left lower chest are present Cardiovascular examination reveals normal first and second heart sounds and bounding peripheral pulses The abdomen has several well-healed surgical scars Intravenous fluids and broad-spectrum antibiotics are initiated The next day, blood cultures show gram-positive cocci Which of the following is the most likely underlying mechanism leading to this patient’s clinical presentation? A Complement deficiency B Destruction of CD4+ cells C Immunoglobulin A deficiency D Impaired antibody-facilitated phagocytosis E Impaired B cell isotype switching F Impaired chemotaxis G Impaired oxidative burst A 68-year-old woman with a history of chronic leukocytosis was referred for a second opinion She has no significant past medical history She has smoked a pack of cigarettes weekly for the past 30 years She initially presented with a mild neutrophilic leukocytosis, which has been slowly progressive throughout the past 17 years (WBC 13.3-32.7 × 109/L; absolute neutrophil count 26.5 × 109/L at the time of referral) The hemoglobin and platelet count are normal She has remained asymptomatic during this period and does not have palpable lymphadenopathy or hepatosplenomegaly on examination A peripheral blood smear is shown below