12 - Leukocytic Disorders

Normal WBC range in microliters

4k-11k

2 pools of blood neutrophils

1. Circulating and free pool, the one that shows up in lab reports

2. Marginal pool, WBCs that are bound to vascular beds and not flowing freely

How do catecholamines, released in stress/exercise, affect neutrophils in the marginal pool?

• They shake them off blood vessels and make them join the circulating pool

How do pathological causes like infection, inflammation, tumor, or necrosis impact neutrophils?

• They cause a real, neutrophil response by triggering more proliferation in the bone marrow

If there is an infection with neutropenia, that indicates…

• Severe infection with possibility for sepsis

Left shift

• What is it and what does it indicate generally

• How far does it go?

• Increased release of young WBC forms into the peripheral blood, indicating an increased marrow response

• It goes as far as metamyelocytes

Myelophthisis

• Meaning

• What is it

• phthisis: “Wasting away”

• Invasion of the bone marrow by something like metastatic cancer cells or fibrosis

Agranulocytosis

• Absolute neutrophil count(ANC) of <500 cells/microliter

Leukemoid reaction vs CML

• Cause

• Splenomegaly

• Basophilia

• LAP

• Ph chromosome

• Cause: Leukemoid reaction is an identifiable reaction to something like a disease, while CML is due to a HSC mutating and proliferating non-stop, with no external trigger

• Splenomegaly: Not present vs present

• Basophilia: Not present in leukemoid reaction because a leukemoid reaction increases only neutrophils for the purpose of fighting infection while CML is a HSC mutation that will give rise to all cells downstream

• LAP: High in leukemoid reaction, low in CML

• Ph chromosome: None because Ph chromosome is the CML mutation

Congenital morphologic disorders

1. Pelger Huet: Bilobed neutrophil, normal function

2. May Hegglin: Harmless blue inclusion bodies

3. Chediak-Higashi syndrome: Autosomal recessive disorder where granules fuse into dysfunctional clumps that are visible in smear, and can’t kill bacteria

How to spot Chediak-Higashi syndrome

• A child with recurrent bacterial infections

Explain

• Toxic granulations

• Vacuoles

• Dohle bodies

• Granulations that are made under inflammatory stimulus

• A space left after phagocytosis

• Blue-gray patches found at the edge of the cell, they are actually rER remnants that weren’t cleared due to accelerated growth

Pseudo-Pelger Huet anamoly

• The normal anomaly is a benign bi lobed neutrophil, but these can also be found in a patient with myelodysplastic syndrome, where the bone marrow is making abnormal cells, leading to cytopenias. So if we see a patient with low blood counts and other abnormal looking cells and see bilobed nuclei, it’s probably pseudo-pelger huet.

Atypical lymphocyte

• What is it

• Found in what

• Tell me a typical patient

• A larger lymphocyte with clumped chromatin and deep blue cytoplasm

• Found in patients with viruses like EBV virus where T cells are activated to kill infected B cells

• A patient with sore throat, fatigue, and swollen lymph nodes

Chronic Granulomatous Disease

• What is it

• Presentation

• NADPH oxidase turns NADPH to superoxide, allowing them to kill the bacteria the neutrophil just engulfed, but in CGD, NADH is nonfunctional, we can’t clear that bacteria so instead it gets turned into a granuloma

• Think of patients sick constantly with catalase positive bacteria like S. aureus