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61 Cards in this Set
- Front
- Back
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What cell is the first definitive precursor to neutrophils?
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Promyelocyte
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What are the four different kind of myeloid cells?
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Neutrophils
Eosinophils Monocytes Basophils |
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What is counted in the WBC?
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Circulating pool of myeloid and lymphoid cells
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What are the steps of neutrophil life cycle?
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Proliferation phase (marrow)
Maturation (marrow) Intravascular Tissues |
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Describe the proliferation phase of the neutrophil life cycle.
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25% of all neutrophils are in this stage
Lasts 6-7 days Starts with myelocytes, then promyelocytes, then myelocytes |
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Describe the maturation phase of the neutrophil life cycle.
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65% of neutrophils
Lasts 6-7 days Starts with metamyelocytes, then bands, then neutrophils |
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How long are neutrophils in blood vessels or tissues?
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Intravascular (12h)
Tissues (12h) |
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What is the normal neutrophil range?
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1,500 - 8,000/uL
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What are the different levels of neutropenia and what is the infection risk?
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Mild: 1000-1500/uL - no significant increased risk of infection
Moderate: 500-1000/uL - slight increase in risk Severe: 0-500/uL - significant increase in risk of bone marrow reserve is not robust |
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How do you calculate the absolute neutrophil count (ANC)?
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Add neutrophils and bands (immediate neutrophil precursor) together
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When should you suspect neutropenia?
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Acute, severe bacterial infection
History of recurrent or rare infections Prolonged or recurrent fevers Recurrent mouth ulcers, CHRONIC GINGIVITIS, cellulitis Findings associated with malignancy or immunodeficiency |
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What should you especially not on the physical exam of someone who might be neutropenic?
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Height (often short)
Temperature (fever) Oral cavity (gingivitis/gums) Skin assessment (pigmentation, warts, folliculitis, cellulitis, dystrophic nails) Palpation (lymphadenopathy and splenomegaly) |
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Describe the oral cavity in neutropenic patients.
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RED ALL OVER THE PLACE
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What are the types of acquired neutropenia?
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Infection (most often secondary to a viral infection)
Drug-induced (commonly anticonvulsants/psychotics and antibiotics such as bactrim) Immune-based |
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What are the types of immune-based acquired neutropenia?
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Alloimmune neutropenia of infancy (similar to Rh and PLA1, mom's IgGs against paternal antigens in fetus crossing placenta)
Autoimmune neutropenia of infancy (appears around 12th month, most have spontaneous remission; don't need prophylatic antibiotics or G-CSF) Autoimmune neutropenia as part of larger immune problem (SLE, ALPS, CVID) |
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What are some categories of inherited neutropenia?
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Primary disorders of myelopoiesis (severe congenital neutropenia, cyclic neutropenia)
Disorders of ribosomal function Disorders of granule sorting/trafficking (Chediak-Higashi syndrome) Disorders of metabolism Neutropenia in disorders of immune function (WHIM syndrome) |
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What is severe congenital neutropenia?
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Arrest in myeloid maturation at the promyelocyte stage
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How do patients with severe congenital neutropenia present?
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In 1st year of life with recurrent and/or severe infections
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How do you diagnose severe congenital neutropenia?
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Three ANC values < 500 over a 1 month period
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What is the most common genetic mutation in severe congenital neutropenia? What kind of inheritance?
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ELANE gene (autosomal dominant)
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How do you treat severe congenital neutropenia?
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G-CSF and sometimes marrow transplant
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Do patients with severe congenital neutropenia need to have their marrows monitored?
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Yes, they are at risk for transformation to myelodysplastic syndrome/acute myeloid leukemia
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What is cyclic neutropenia?
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Disorder characterized by regular, periodic oscillations in the ANC
When neutropenic, often have reciprocal MONOCYTOSIS |
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How do cyclic neutropenia patients present?
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1st year of life with recurrent fevers, malaise, oral ulcers, and occasionally serious infections (especially CLOSTRIDIUM)
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What gene is responsible in cyclic neutropenia?
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Often ELANE (again!)
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Do cyclic neutropenia patients need marrow monitoring?
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Generally no, because they have no increased risk for progression to MDS/AML
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What is neutrophilia?
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Abnormally high neutrophil count
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What are some general causes of neutrophilia?
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Acute shift of neutrophils from marginating pool to circulating pool (steroid treatment, exercise, epi, hypoxia, seizures)
Chronic stimulation with excess cytokines increasing proliferative pool (infection, medications [G-CSF], pregnancy, trisomy 21, chemotherapy recovery, MPD/leukemia) |
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What are the 8 stages of neutrophil killing and what diseases are associated with them?
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1. Mobilization (WHIM syndrome)
2. Chemotaxis (LAD) 3. Recognition/opsinization 4. ingestion 5. degranulation (Chediak-Higashi syndrome) 6. peroxidation (MPO deficiency, CGD 7. killing and digestion 8. net formation (MPO deficiency, CGD) |
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What is WHIM syndrome?
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Also called myelokathexis
Defect in CXCR4 chemokine receptor that causes abnormal apoptosis and retention of neutrophils in the bone marrow |
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What are the clinical characteristics of WHIM syndrome?
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Warts
Hypogammglobulinemia Infections Myelokathexis |
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How do you treat WHIM syndrome?
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G-CSF and/or CXCR4 antagonist (plexifor)
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What is the general process of neutrophil migration into tissues, and what diseases are associated with the various parts?
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Rolling (LAD2)
Firm adhesion to endothelium (LAD1) Migration |
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What is LAD2?
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Leukocyte adhesion deficiency in which neutrophils have deficient or absent SLex expression
SLex on neutrophils binds to E-selectin on endothelium to initiate rolling behavior |
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What is LAD1
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Leukocyte adhesion deficiency in which neutrophils have deficient or absent CD18 expression
CD11/CD18 is necessary to bind to integrins on endothelium and allow for firm adhesion before diapedesis |
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What is the general problem and clinical presentation of leukocyte adhesion deficiencies?
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Leukocytes (esp. neutrophils) cannot leave vasculature
Clinically, neutrophilia, infections (peridontitis), absence of pus formation, impaired wound healing |
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What is Chediak-Higashi syndrome (CHS)?
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Defect in formation and trafficking of granules in neutrophils (and platelets and melanin-containing cells)
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What are some symptoms of CHS?
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Immunodeficiency (neutrophils, NK, T)
Partial oculo-cutaneous albinism (clumped melanosomes) Bleeding diathesis (decreased dense granules in platelets) Progressive neurologic deterioration |
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What is diagnostic of CHS?
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Giant, coalesced granules in neutrophils
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A defect in what gene is response for CHS?
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CHS1/LYST gene which is responsible for lysosomal trafficking
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How do you treat CHS?
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Antibiotics, G-CSF, and bone marrow transplant (BMT)
BMT cures hematologic and immunodeficiency, but NOT albinism or neurologic features of disease |
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What is MPO?
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Myeloperoxidase, found in azurophilic granules and plays a key role in amplifying toxicity from hydrogen peroxide from RESPIRATORY BURST
Needed for rapid killing of microbes (especially Candida), but is not absolutely required |
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How does MPO deficiency present?
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95% asymptomatic
DM patients have increased Candida problems |
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How do you diagnose MPO deficiency?
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Histochemical staining for MPO in neutrophils
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How do you treat MPO deficiency?
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Observe, tight glucose control, and aggressive management of fungal disease
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What is CGD?
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Defect in NADPH oxidase in phagocytes that is NECESSARY to destroy catalase-positive organisms through super-oxide destruction
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Which is worse, MPO deficiency or CGD?
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CGD by far
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What bugs go HAM on CGD patients?
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Staph aureus, aspergillus, burkholderia, serratia, nocardia, (E. coli)
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What are the two common mutations in CGD and what do they code for? How are the inherited?
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NADPH oxidase
gp91phox - most common, X-linked p47phox - second most common, autosomal recessive |
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How do you diagnose CGD?
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Screen for neutrophil superoxide production using DHR testing
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How does DHR testing work?
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Non-fluorescent DHR dye is taken up by phagocytes and oxidized to a green fluorescent dye by NADPH oxidase
Can detect carriers as well |
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How do you treat CGD?
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Antimicrobial prophylaxis (bactrim, itraconazole)
Immune modulation (interferon gamma) Aggressive treatment of infections Bone marrow transplant is only cure |
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What is net formation?
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Post-apoptosis, neutrophils can shoot out their DNA to trap bacteria, but this is dependent on hydrogen peroxide production, so CGD and MPO deficiency patients can't do this
This is not bactericidal, but aids other phagocytes |
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What is the relation of monocytes to macrophages?
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Monocytes are circulating macrophage precursors
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What is the average circulating monocyte count?
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300/uL
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Which is more dangerous: eosinopenia or eosinophilia?
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Eosinophilia
Eosinopenia is usually transient and not associated with risk of infection |
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What does the eosinophil count have to be to be eosinophilia?
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> 500/uL
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What are some secondary causes of eosinophilia?
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Neoplasms, allergies, asthma, collagen vascular disease, and parasitic infections
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What is idiopathic hypereosinophilic syndrome?
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Elevated eosinophil count (>1500/uL) for 6 months without identifiable cause
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How does idiopathic hypereosinophilic syndrome present?
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Organ infiltration by eosinophils leads to dysfunction of heart, CNS, kidneys, liver, GI, lungs, and skin (toxicity in part due to eosinophil degranulation and release of major basic protein)
Can progress to chronic eosinophilic leukemia (CEL), which is more likely in children |
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What do basophils do?
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Unsure, perhaps role against certain parasites
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