Abnormal White Cell Counts Flashcards

1
Q

Where does haematopoiesis occur?

A

bone marrow

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2
Q

When does normal and malignant haematopoiesis occur?

A

normal - normal and reactive situations

malignant - leukaemia, myelodysplasia and myeloproliferation

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3
Q

What happens in normal and abnormal maturation and differentiation?

A

normal

  • first 4 steps of differentiation and maturation occurs in the marrow
  • neutrophil formed in peripheral blood
  • myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> neutrophil

pathology
- cells smaller -> cytoplasm clearer -> multi-lobed nucleus

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4
Q

How is cell differentiation controlled?

A

regulated via cytokines:

  • RBCs – EPO
  • Lymphoid cells – IL-2
  • Myeloid cells – G-CSF, M-CSF
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5
Q

What can cause an abnormal WBC count?

A

Increased WBC count can be due to:

  • Increased cell production – reactive (infection/inflammation) or malignant (leukaemia/myeloproliferative)
  • Increased cell survival (e.g failure of apoptosis)

Decreased WBC count can be due to:

  • Decreased cell production (impaired BM function)
  • Decreased cell survival (immune breakdown)
  • In normal infection, the increased WBC is reactive and mature cells are released. In haematopoietic cancers, immature AND mature cells are released.
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6
Q

What are some causes of eosiniphilia?

A

(raised eosinophil count)

reactive - normal haematopoiesis stimulated by:
- inflammations
- infection
- increased cytokine production (e.g distant tumour)
- Parasitic infection.
- Allergic disease
- Hypereosinophilic syndrome
- Neoplasms – esp Hodgkin’s, T-cell NHL
> Hodgkin’s disease will show up on x-ray with increased mediastinal mass and there will be increased IL-5 secretion (stimulates reactive)
> You can also get a mutation in GM-CFC

malignant (autonomous cell growth)

  • cancers of haematopoietic cells
  • leukaemia (myeloid/lymphoid, chronic/acute)
  • myeloproliferative disorders
  • Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene) – very rare.
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7
Q

What happens in CML?

A

mutation at GM-CFC (after HSC)

chr 9 and 22 -> philadelphia chr -> BCR-ABL

increased WBC - mainly neutrophils, eosinophils and basophils (granulocytes)

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8
Q

How do we investigate a raised WBC count?

A
  • History and examination
  • Hb & platelet count
  • automated differential
  • examine the blood film
  • existence of abnormality in white cells or all cell lineages?
  • WCC raised in one cell type or all cell linages?
  • mature or immature or both cells?
    > Immature cells – think about leukaemia.
    > Immature AND mature cells – think about chronic leukaemia if in the presence of neutrophils and myelocytes.

*Acute leukaemia will present with low Hb and platelets.

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9
Q

What can cause neutrophilia?

A

Present across BM, blood and tissues with a life span of 2-3 days in tissue and hours in PB.
50% of neutrophils are marginated (have stuck onto the wall of a damaged vessel so aren’t in FBC).

Neutrophilia can develop in:

  • Minutes – demargination.
  • Hours – early release from BM – i.e. sepsis.
  • Days – increased production – i.e. x3 in infection.

Causes include –

  • Infection
  • tissue inflammation
  • physical stress
  • adrenaline
  • corticosteroids
  • neoplasia
  • malignant neutrophilia (e.g. myeloproliferative disorders and CML).

*Infection is the normal cause for neutrophilia – occurs in local and systemic infections, acute bacterial, fungal and certain viral infections.

**SOME infections do NOT produce a neutrophilia – e.g. Brucella, typhoid and many viral infections.

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10
Q

What are the differences in the blood films (neutrophils) of someone with an infection and someone with leukaemia?

A

infection

  • toxic granulation
  • vacuoles

leukamia
- neutrophilia and precursor cells (myelocytes)

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11
Q

What are some causes of monocytosis?

A

This is rare but seen in certain chronic infections and primary haematological disorders.

Causes:

  • TB, Brucella, typhoid
  • Viral – CMV, VZV
  • Sarcoidosis
  • Chronic Myelomonocytic Leukaemia (CML)
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12
Q

What are some causes of lymphocytosis?

A
  • Mature cells – either reactive to infection or primary disorder
  • Immature cells – primary disorder only (not reactive)

Causes;
Secondary/reactive – polyclonal response to infection, chronic inflammation or underlying malignancy.
- Infection – e.g. EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes
- Autoimmune
- Neoplasia
- Sarcoidosis

Primary – monoclonal lymphoid proliferation – e.g. CLL

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13
Q

What does acute lymphoblastic leukaemia look like on a blood film?

A

immature lymphoblasts much larger than other cells

visible nucleolus shows immaturity

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14
Q

What is mononucleosis?

A

Shows a reactive-looking lymphocyte that looks like an immature lymphocyte seen in acute lymphoblastic leukaemia BUT these lymphocytes tend to have RBCs clump them and they are jagged and are not self-clumped

High WCC with reactive-looking lymphocytes shows glandular fever

Caused by EBV infection of B lymphocytes via the CD21 receptor.
- Infected B-cell proliferates and expresses EBV-associated antigens causing a cytotoxic T-cell response

Common in the young

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15
Q

What is lymphocytosis in the elderly more likely to be?

A

CLL or autoimmune disorder

you’ll see mature lymphocytes (and smear cells)

This is distinguishable by the – morphology, immunophenotype (what antigens are expressed on the surface) and gene rearrangement

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16
Q

What is the difference between polyclonal and mono clonal expansion?

A

Polyclonal expansion

  • involve more than one mother cell and so the light chains express both kappa and lambda
  • This is indicative of a response to infection

Monoclonal expansion

  • all antibodies are from ONE mother cell
  • this is indicative of a cancer

*Ig genes and TCR genes undergo recombination in antigen stimulated B or T cells.
** With primary monoclonal proliferation, ALL daughter cells carry the IDENTICAL TCR gene arrangement which isn’t normal for infection – indicative of cancer.
 Detected by southern blot analysis