Disorders of Granulocyte Number (complete) Flashcards
Identify the basic morphologic features of neutrophils. Explain production, distribution and turnover.
M: Red cytoplasm, seg nucleus
P: In BM. Activated by M-CSF
D: Remains in BM storage (10-14 days); released into peripheral blood (6hr), then tissues
T:1-2 days (once in tissue)
Identify the basic morphologic features of eosinophils. Explain production, distribution and turnover.
M: Pink cytoplasm, bi-lobe nucleus
P: in BM, under IL-5 influence
D: Released into peripheral blood, move to external surfaces (trach, GI tract)
T: Survive for weeks
Identify the basic morphologic features of basophils. Explain production, distribution and turnover.
M: Blue/purple cytoplasm, bi-lobe nucleus
P: in BM
D: released into peripheral blood in frequently, then tissues
T: ?
Identify the basic morphologic features of monocytes/macrophages. Explain production, distribution and turnover.
M: Gray cytoplasm, kidney shaped nucleus; changes in tissues
P: in BM (7 days)
D: Released after last mitotic division, move to intravascular areas (3-5 days), then tissues
T: days-months (in tissue)
Define neutropenia
Decrease in absolute neutrophil count (abnormal)
Varies w/ age, ethnicity, altitude
Neutrophil levels: <1500 (child/adult)
Describe the clinical consequences of neutropenia.
May reflect a decrease in marrow myeloid pools
Affects neutrophil delivery to infected tissues is decreased — bugs win!
<250 (severe), 250-500 (moderate/severe), 500-1000 (mild)
Major causes of neutropenia can be divided into 2 categories. What are they?
1) Decreased BM production
2) Increased turnover in BM production (normal reserve however)
What are the primary causes of decreased BM production in neutropenia?
1) Kostmann syndrome
2) Shwachman Diamond syndrome
3) Cyclic neutropenia
What are the secondary causes of decreased BM production in neutropenia?
1) Drug-induced
2) Viral infection
3) Nutritional deficiencies
4) Chemotherapy
Define leukocytosis.
An increase in total # of WBCs beyond normal
Why is there a high WBC count with leukocytosis?
1) Infection
2) Inflammation
3) non-specific physiologic stress
4) malignancy
Describe the term “left shift”. What does it indicate?
Refers to changes in white cell differential w/ an increase in segs, bands and some immature myeloid precursors (metamyelocytes and myelocytes) — a bacterial infection?
Specifics depend on which cell line increased
Define eosinophilia
An abnormal absolute count >350/microL
Causes:
1) Allergies/allergic disorders
2) parasitic infections
3) drug reactions
Define basophilia
Increase in peripheral basophils
Causes:
1) drug/food hypersensitivity
2) urticaria
3) infection
4) inflammation
5) myeloproliferative diseases
Define monocytosis
Newborns: >1000/microL
Children/adults: >500/microL
Causes:
1) hematologic (pre)malignancies
2) collagen vascular diseases
3) granulomatous diseases
4) infections
5) carcinoma
What are the 2 categories of increased turnover of neutrophils in neutropenia?
1) Immune
2) Non-immune
What are the 3 immune causes of increased turnover of neutrophils in neutropenia?
1) Chronic benign neutropenia of childhood
2) Autoimmune neutropenia
3) Alloimmune neutropenia
What are the 3 non-immune causes of increased turnover of neutrophils in neutropenia?
1) Infection
2) Splenomegaly and hypersplenism
3) Pseudoneutropenia
Describe autoimmune neutropenia
Mech: Abs to specific determinants on neutrophils —Abs to RBCs, platelets, coags
Oftentimes w/ lupus, Evan’s synd., Felty’s synd
Describe alloimmune neutropenia
- Passive xfer of Ab from mom’s circulation attacking baby’s cells
- Due to neonat cells xfer to maternal circulation — mom creates Abs against this Ag b/c it seems foreign
How do you treat neutropenia?
- Figure out the cause — what is the infected site? which organisms are involved?
1) G-CSF given at 3-5 microg/kg
2) Intravenous gamma-globulin
What is the purpose of G-CSF?
- normalizes neutrophil production
- increases # of neutrophils in all compartments and delivery to tissues
- prevents infection
Describe Kostmann’s Syndrome
- Apoptosis of myeloid precursors
- B/c of elastase (ELA-2) or HAX-1 gene mutations
- Severe neutropenia
- Monocytosis, eosinophilia
Treat w/ G-SCF, and infection fighting things!
Describe cyclic neutropenia
ELA-2 mutations —» apoptosis of precursors
- Myeloid hypoplasia, arrest at myelocyte level
- ANC, platelet and retic count cycle up and down every 3 weeks or so
- Treatment: antibiotic/supportive care for infection
Shwachman-Diamond Syndrome
- Defect in SBDS gene
- Multisystem disease: neutropenia, pancreatic insufficiency
- Recurrent infections
Treatment: G-CSF, aggressive antibiotic therapy, supportive care for infection
