Term
| Myeloid Cell Maturation - Role of CSFs |
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Definition
• GM-CSF – granulocyte-m-phage col. stim. factor; myeloid stem cell (myeloblast)/(immature monocyte)
• G-CSF – granulocyte colony stimulating factor; stimulates myeloblasts N. promyelocyte
• Use as drugs – both GM and GCSF are in use as drugs to cause differentiation in neutropenias |
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Term
| WBC counts vs. PMN and lymphocytes in infant, child, adult |
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Definition
• WBC Measurement – uses automated counter, reflects circulating pool of myeloid/lymphoid cells
• Relative/Absolute Amounts – each WBC type indicated by relative (%) and absolute (% * WBC)
• Infant WBC – usually very high WBC (fighting infections), high PMN compared to lymphocytes
• Child WBC – also somewhat high WBC (developing immunity), high lymphocytes compared to PMNs
• Adult WBC – has a lower WBC (mature immune system), high PMN compared to lymphocytes |
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Term
| Disease states affecting WBC |
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Definition
• Disease States – can also affect WBC:
o Bacterial infection – huge increase in WBC, high PMN % and left-shift (band cells)
o Steroid therapy – actually increases WBC, due to high PMN % (marginating effect)
o Splenectomy – also increases WBC, due to putting more into active circulation, less sequestered
o Viral infection – actually decreases WBC, due to suppressive effect of virus on bone marrow
o Chemotherapy – has huge decrease in WBC, although monocyte increase after recovery |
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Term
| neutrophil proliferation and maturation |
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Definition
• Proliferation – involves myeloblast N. promyelocyte N. myelocyte in bone marrow (6-7 days, 25%)
• Maturation – longest, involves N. myelocyte N. metamyelocyte N. band PMN in marrow (6-7 days, 65%)
• Intravascular/Tissues – about 10% of neutrophils finish development here, N. band PMN |
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Term
| Neutrophilia - definition, acute shift vs. chronic stimulation |
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Definition
• Neutrophilia – an abnormally high PMN count (>7700), often involving a left-shift (more bands/precursors)
• Types – either an acute shift or a chronic stimulation:
o Acute shift – a sudden shift of PMNs from marginating circulating pool, (not a total WBC ↑)
Causes – include steroids, exercise, epinephrine, hypoxia, seizures, stress
o Chronic stimulation – excess cytokines stimulating proliferative pool; a real WBC ↑
Causes – include infection, pregnancy/eclampsia, chemo recovery
Disorders – causes are Down’s syndrome, myeloproliferative dz., marrow metastases |
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Term
| Neutropenia - def, acute shift, decreased production, increased destruction |
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Definition
• Neutropenia – an abnormally low PMN count (<1500), with risk of infection
o 500-1000 – infection from exposure
o <500 – infection from host organisms
o AfAm – lower normal n’phil counts (1000-1200)
• Types – include decreased production, increased destruction, or shift to marginating pool
o Acute shift – a sudden shift of PMNs from circulating marginating pool (not a real WBC ↓)
Infection – a severe infection (penetrates to tissues), endotoxin release will cause
Medical procedures – artificial circulations, such as hemodialysis, cardiopulm. bypass
o Decreased production – fewer PMNs produced in bone marrow
Immunosuppression – some medications, chemotherapy, antibiotics will cause
o Increased destruction – more PMNs destroyed in peripheral circulation
Autoimmune diseases – such as RA, SLE will cause |
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Term
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Definition
• Management – any time patient has fever + neutropenia (F+N), good reason to hospitalize
o Medications – many medications have neutropenia as a known SE; look through these
o Bone marrow – look for malignancies in bone marrow which indicate myeloproliferative disorder
o Cyclic neutropenia – inherited disorder (auto dom) where every 3 weeks patient has neutropenia (fever, mouth ulcers); treat w/ G-CSF, usually improves after puberty
o Congenital neutropenia – PMN maturation arrest; freq. infections, mouth sores, leukemia risk
Tx – give artificial G-CSF, bone marrow transplant (BMT) |
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Term
| Normal PMN response to damaged tissue |
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Definition
• Response Process – when tissue is damaged, chemotactic factors released which induce PMN response:
1) Rolling & attachment – PMNs stick to endothelial cell wall due to chemotactic interactions
2) Adhesion – integrins allow for tight adhesion of PMN to vessel wall
3) Diapedesis – margination of PMN across endothelial cell wall
4) Phagocytosis – PMN phagocytosis offending organism, contains within lysosomal vesicle
5) Granule release – granules, along with peroxide & superoxide released to kill organism |
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Term
| PMN disorders: Sialyl Lewis, LAD-1, Chediak-Higashi Syndrome, Chronic Granulomatous Disease (cat +/-), Myeloperoxidase Deficiency |
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Definition
1) Sialyl LewisX – PMNs lack protein needed for rolling/attachment, => neutrophilia – you keep on making but not go away.
2) LAD-1 – a leukocytic adhesion protein (integrin) defect (Type 1), PMNs can’t adhere and can’t migrate
3) --
4) --
5) Chediak-Higashi Syndrome (CHS)– defect in granule formation (too large); associated w/ oculocutaneous albinsim, neuropathy, frequent infxn; treat w/ bone marrow x-plant
Chronic Granulomatrous Disease – defect in peroxide/superoxide formation
Catalase (–): CGD can kill Cat (–) bacteria (strep B), since they produce own peroxide
Catalase (+): CGD can’t kill Cat (+) bacteria (E. coli), since they break down peroxide
Myeloperoxidase Deficiency – more common, defect in hyperchlorous acid (HOCl), usually
clinically silent, although bacterial killing takes longer than norm |
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Term
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Definition
| low monocyte count, can occur with steroids or stress |
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Term
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Definition
| high monocyte count, can occur with tumor, infection, CGD, marrow recovery and a number of infections (malaria, TB, RMSF, leshmaniasis, brucellosis, mononucleosis) |
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Term
| Monocytes/Macrophages (RES, maturation, function, defects) |
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Definition
• RES – the reticuloendothelial system is the monocyte/macrophage system
• Maturation – again involves proliferation, maturation (shorter), and intravascular/tissue (longer)
• Function – can phagocytose foreign particles after nphils arrive at site and release cytokines to attract them
o Destruction – can destroy phagocytosed particles (innate immunity)
o T-cell presentation – APCs can also present phagocytosed particles to T-cells (adaptive)
• Defects – defects of PMNs also affect monocytes (LAD, CHS, CGD) |
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Term
| Eosinophils = Maturation, function, eosinophilia, idiopathic hypereosinophilia |
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Definition
• Maturation – also have a faster maturation than PMNs
• Function – bright red granules with IgE on surface (unlike PMNs); key role in killing parasites
• Eosinophila – elevated eosinophils (<400), “NAACP” conditions:
o Neoplasm – hodgkin’s disease, lymphoma, other tumor
o Allergies – induced by environment, drugs
o Asthma – has elevated eosinophils too
o Collagen vascular disease – includes vasculitis
o Parasite – infection of parasite
• Idiopathic Hypereosinophilia – too high eosinophil count organ dysfxn; Tx immunosuppress, antihist |
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Term
| Basophils/Mast cells: maturation, function, low count, high count |
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Definition
• Maturation – basophil like PMN, mast cell very quick
• Function – largely unknown, possible defense against parasites
• Low Basophil count – from steroids, hypersensitivity
• High Basophil count – from allergies, infection, endocrinopathies, myeloproliferative dz (CML)¸ systemic mastocytosis (symptoms due to excess histamine release) |
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