Disorders of Granulocyte Number (complete)

Question 1

Identify the basic morphologic features of neutrophils. Explain production, distribution and turnover.

Answer 1

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)

Question 2

Identify the basic morphologic features of eosinophils. Explain production, distribution and turnover.

Answer 2

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

Question 3

Identify the basic morphologic features of basophils. Explain production, distribution and turnover.

Answer 3

M: Blue/purple cytoplasm, bi-lobe nucleus

P: in BM

D: released into peripheral blood in frequently, then tissues

T: ?

Question 4

Identify the basic morphologic features of monocytes/macrophages. Explain production, distribution and turnover.

Answer 4

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)

Question 5

Define neutropenia

Answer 5

Decrease in absolute neutrophil count (abnormal)

Varies w/ age, ethnicity, altitude

Neutrophil levels: <1500 (child/adult)

Question 6

Describe the clinical consequences of neutropenia.

Answer 6

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)

Question 7

Major causes of neutropenia can be divided into 2 categories. What are they?

Answer 7

1) Decreased BM production

2) Increased turnover in BM production (normal reserve however)

Question 8

What are the primary causes of decreased BM production in neutropenia?

Answer 8

1) Kostmann syndrome
2) Shwachman Diamond syndrome
3) Cyclic neutropenia

Question 9

What are the secondary causes of decreased BM production in neutropenia?

Answer 9

1) Drug-induced
2) Viral infection
3) Nutritional deficiencies
4) Chemotherapy

Question 10

Define leukocytosis.

Answer 10

An increase in total # of WBCs beyond normal

Question 11

Why is there a high WBC count with leukocytosis?

Answer 11

1) Infection
2) Inflammation
3) non-specific physiologic stress
4) malignancy

Question 12

Describe the term “left shift”. What does it indicate?

Answer 12

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

Question 13

Define eosinophilia

Answer 13

An abnormal absolute count >350/microL

Causes:

1) Allergies/allergic disorders
2) parasitic infections
3) drug reactions

Question 14

Define basophilia

Answer 14

Increase in peripheral basophils

Causes:

1) drug/food hypersensitivity
2) urticaria
3) infection
4) inflammation
5) myeloproliferative diseases

Question 15

Define monocytosis

Answer 15

Newborns: >1000/microL
Children/adults: >500/microL

Causes:

1) hematologic (pre)malignancies
2) collagen vascular diseases
3) granulomatous diseases
4) infections
5) carcinoma

Question 16

What are the 2 categories of increased turnover of neutrophils in neutropenia?

Answer 16

1) Immune

2) Non-immune

Question 17

What are the 3 immune causes of increased turnover of neutrophils in neutropenia?

Answer 17

1) Chronic benign neutropenia of childhood
2) Autoimmune neutropenia
3) Alloimmune neutropenia

Question 18

What are the 3 non-immune causes of increased turnover of neutrophils in neutropenia?

Answer 18

1) Infection
2) Splenomegaly and hypersplenism
3) Pseudoneutropenia

Question 19

Describe autoimmune neutropenia

Answer 19

Mech: Abs to specific determinants on neutrophils —Abs to RBCs, platelets, coags

Oftentimes w/ lupus, Evan’s synd., Felty’s synd

Question 20

Describe alloimmune neutropenia

Answer 20

• 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

Question 21

How do you treat neutropenia?

Answer 21

• 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

Question 22

What is the purpose of G-CSF?

Answer 22

• normalizes neutrophil production
• increases # of neutrophils in all compartments and delivery to tissues
• prevents infection

Question 23

Describe Kostmann’s Syndrome

Answer 23

• 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!

Question 24

Describe cyclic neutropenia

Answer 24

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

Question 25

Shwachman-Diamond Syndrome

Answer 25

• Defect in SBDS gene
• Multisystem disease: neutropenia, pancreatic insufficiency
• Recurrent infections

Treatment: G-CSF, aggressive antibiotic therapy, supportive care for infection