Granulocyte production kinetics and function

Question 1

What are the functions of G-CSF?

Answer 1

1. Stimulates proliferation and differentiation of neutrophil precursors and neutrophils
2. Stimulates release from bone marrow
3. delays apoptosis in neutrophils

Question 2

When is there a propensity to infection in neutropenia?

Answer 2

• propensity for infection related to adequacy of marrow reserve pool and not to the Absolute neutrophil count (ANC)
• ANC reflects propensity for infection only in case of marrow failure
• in immune or destructive neutropenia, theren’s no relation between ANC and propensity to infection
• must determine if neutropenia is causing infection or if its a secondary result of another global inflammatory process
• Isolated neutropenia is almost never due to malignancy

Question 3

How does neutrophilia or neutropenia present?

Answer 3

• usually is unexpected finding on a CBC done routinely or in course of eval of febrile or anemic child or adult
• or as part of eval of child with recurrent infection

Question 4

How do neutrophils get from the blood to site of infection?

Answer 4

1. margination
2. Diapedesis
3. chemotaxis
4. phagocytosis
5. killing

Question 5

How do neutrophils kill bacteria?

Answer 5

Oxygen-independent
-proteases and hydrolyses in granules
-antimicrobial peptides: defensins, azurocidin, properdin, cathelicidins
Oxygen dependent
-respiratory burst: production of superoxide anion upon phagocytosis or stimuli
-forms hydrogen peroxide

Question 6

What is chronic granulomatous disease?

Answer 6

-presentation: recurrent infections at epithelial surface in contact with environment, e.g. skin abscesses
-complications: pneumonia, lymphodenitis, osteomyelitis, liver abscesses, subcut abscesses
Diagnosis: NBT test-nitroblue-tetrazolium-does not turn blue in CGD
-Mechanism: in ability of phagocytes to produce superoxide anion and to kill bacteria/fungi
-mostly x linked but also autosomal

Question 7

What is myeloperoxidase?

Answer 7

• abundant in neutrophils
• produces HOCl and Cl- from H2O2 during respiratory burst, used to kill bacteria
• MPO deficiency results in impairment in host defense to Candida, but not to S. Aureus
• susceptible to abdominal infection after cecal ligation and puncture