Granulocytes Flashcards
Myeloid Lineage
- Myeloid Precursor –> CFU - GEMM
- GMP (granulocytes - monocyte)
- MEP (megakaryocyte-erythroid)
What are the 6 stages of granulocyte production?
- Mitotic Pool
- 1- Myeloblast - nucleoli, scant granules or cytoplasm, fine chromatin
- 2- Promyelocyte - larger, similar nucleus, primary granules (lysozymes, myeloperoxidase, defensins, bactericidal permeability inducing factor, acid hydrolases)
- 3- Myelocyte - nucleoli disappear, chromatin more clumped, secondary granules (lactoferrin, B12 binding proteins, parts of NADPH oxidase)
- Maturation Pool
- 1- Metamyelocyte - indented coarse chromatin
- 2- Band Cells - smaller, non-segmented horseshoe nucleus
- 3- PMNs (polymorphonuclear) - 2 to 5 segments of nucleus
Neutropenia Grading System
- 1 - ANC 2000-1500
- 2- ANC 1500 - 1000 mild (risk of infection starts inc)
- 3- ANC 500-1000 moderate
- 4- ANC 0-500 severe (major risk of infection)
Causes of Neutropenia (categories)
- Ethnicity - American and S African blacks, Yemenite and Ethiopian Jews, Black Bedouins
- Immune - Related
- Primary neutropenia
- Secondary to others - SLE, RA, Felty’s syndrome
- Infectious
- Meds
- Abx
- Cardiac
- Anti-convulsants
- Psych
- Anti-inflammatory
- Hypoglycemics
- Antineoplastic
- Malignancy
- Acute leukemia
- Myelodysplastic syndrome
- Myelophthisis
- Large granulocytic lymphocyte leukemia
- Mechanical - splenomegaly
- Nutritional Def - B12, copper, folic acid
- Hyper/hypothyroidism
- Congenital
Felty’s Syndrome
longstanding RA –> splenomegaly, ANC < 500
2 Broad Categories of Neutrophilia
(inc # neutrophils)
1- Reactive (secondary to something)
- Acute infection, chronic infection (inc marrow - tb, fungus, abscess)
- Chronic inflammation
- Smoking
- Stress
- Drug-induced (corticosteroids, beta-agonists, lithium, adhesion inhibitors, recombinant cytokines)
- Non-heme malignancy - cytokine sec tumor or myelo mets
- Marrow stim - hemolytic anemia, recombinant cytokines, recovery from suppression
- Post-splenectomy
2- Malignant / Primary Heme Problem
- Congenital neutrophilia - Hereditary neutrophilia, DS, LAD I and II
- Acute Myelogenous Leukemia
- Myeloproliferative Neoplasms
3 General Types of Functional Granulocyte Disorders
Problem w/ respiratory burst
Abnormal phagocyte adhesion
Defect in granule structure or function
Chronic Granulomatous Disease
- mutation in any 4 subunits of NADPH oxidase –> bac and fungal infections w/ granulomas b/c no oxidative burst; pneumonia most common
- Tx - pro abx and gamma interferon to inc non-oxidative killing
- Abnormal NBT test - tests ability to make ROS
- X-linked Carriers- risk of discoid lupus, polyarthritis, Raynauds, some infections AND women may inactive normal X –> cgd
Deficiency in glutathione reductase v glutathione synthetase
- Def in glutathione reductase –> resp burst stops prematurely b/c oxidant damage to NADPH oxidase enzyme; but sufficient killing happens first; no problem w/ infections
- Def glutathione synthetase –> normal burst but severe acidosis, intermittent neutropenia, oxidative hemolysis and mild problems w/ infections
LAD I
repeated bac or fungal infections w/o pus despite elevated neutrophils in blood
dx by flow cytometry for CD11b integrin on neutrophils
HIES
hyperimmunoglobulin E syndrome
- inc IgE; dermatitis, boils, staph infections, dental/bone problems; T cell dysfunction –> neutrophil chemotactic defect
Chediak Syndrome
- Rare, auto recessive
- Large granules w/o anti-microbials –> delayed/incomplete degranulation –> dec killing / recurrent infections
- Similar problems in macrophages and lymphocytes and platelet deficiency
- Hypopigmentation of skin, eyes, hair; prolonged bleeding; peripheral neuropathy
Specific Granule Deficiency
- Rare, recurrent skin ear and lung infections
- Bi-lobe nuclei and absence of specific granule and specific granule proteins in neutrophils
MPO Deficiency
auto rec def in myeloperoxidase
MPO is in granules of neutrophils and monocytes to catalyze hypochlorous acid prod
usually asymptomatic b/c acid not necessary for killing
