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Year 2 Collin > Haem 6 - Abnormal white cell counts > Flashcards

Haem 6 - Abnormal white cell counts Flashcards

1
Q

Explain how neutrophil differentiation and maturation occurs

A

Myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band cells –> neutrophil

Myeloid precursors are not normally seen in peripheral blood

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2
Q

When is it not uncommon to see myeloid precursors?

A

In sepsis patients

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3
Q

How are cell numbers controlled in haematopoiesis

A

Cytokines influence differentiation and proliferation.

Erythroid - controlled by erythropoietin

Lymphoid - controlled by IL-2

Myeloid - controlled by G-CSF and M-CSF

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4
Q

What are the causes of abnormal WBC

A

Increased WBC:

  1. Increased cell production - Reactive (infection/inflammation), Malignant (leukaemia/myeloproliferative)
  2. Increased cell survival - failure of apoptosis

Decreased WBC:
1. Decreased cell production - impaired bone marrow function, B12/Folate deficiency, bone marrow failure (aplastic anaemia/post chemo/metastatic cancer/haematological cancer)

  1. Decreased cell survival - immune breakdown
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5
Q

What happens when there are haematopoietic cancers

A

Immature and mature cells are released into the circulation

Normally, should just be mature cells

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6
Q

What are the 2 causes of eosinophilia

A
  1. Reactive - normal haemopoiesis. Stimulated by inflammation, infection, increased cytokine production (as a result of a distant tumour, e.g.)
  2. Primary (malignant) - abnormal haemopoiesis (autonomous cell growth). Caused by cancers of haemopoietic cells, leukaemia (myeloid / lymphoid, both chronic and acute), myeloproliferative disorders
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7
Q

In chronic myeloid leukaemia, where does the mutation occur?

A

Mutation occurs at the GM-CFC phase - causes massive proliferation of myeloid cells beyond this point

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8
Q

How to investigate a raised WCC?

A
  1. History and examination
  2. Hb and platelet count
  3. Automated differential
  4. Examine blood film
  5. Are all 3 lineages (RBC, WBC, platelet) affected or just WBC?
  6. Is it only one type of WBC affected?
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9
Q

How to suspect leukaemia and acute leukaemia?

A

If immature cells in the blood film

If ONLY immature cells with low Hb and low platelets - acute leukaemia

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10
Q

Why might lymphocytes be elevated?

A
  1. Viral infections
  2. Chronic lymphocytic leukaemia

In leukaemia, neutrophils don’t have granules (whereas there are granular neutrophils In infection)

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11
Q

Describe neutrophils

A
  1. Present in bone marrow, blood and tissues
  2. Lifespan of 2-3 days in tissues
  3. 50% neutrophils - marginated - stuck onto wall of damaged vessel (hence not counted in RBC)
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12
Q

Give 3 instances when neutrophilia can develop

A

Minutes - demmargination

Hours - early release from bone marrow

Days - increased production

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13
Q

What are the causes of neutrophilia

A
  1. Infection
  2. Tissue inflammation
  3. Physical stress
  4. Adrenaline
  5. Corticosteroids
  6. Underlying neoplasia
  7. Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia)
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14
Q

How can we deduce a viral infection

A

Low neutrophil count but other features of infection

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15
Q

What are some reactive causes of eosinophilia

A
  1. Parasitic infection
  2. Allergic disease (e.g. asthma, RA, polyarteritis, pulmonary eosinophilia)
  3. Neoplasms (e.g. Hodgkins, non-hodgkins lymphoma)
  4. Hypereosinophilic syndrome
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16
Q

Give a genetic cause of eosinophilia

A

Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

  • very rare
  • can be detected by FISH (fluorescent)
17
Q

Hodgkins disease can cause eosinophilia - how can you tell if someone has Hodgkins disease?

A
  1. Increased mediastinal mass on CXR

2. IL-5 secretion - stimulating reactive eosinophilia

18
Q

When is monocytosis seen

A

Rare - seen in certain chronic infections and primary haematological disorders

e.g. TB, Brucella, typhoid

Viral - cmv, Varicella zoster

Sarcoidosis, chronic myelomonocytic leukaemia (MDS- myelodysplastic syndrome)

19
Q

How can we distinguish lymphocytosis types

A

If mature cells - reactive to infection, primary disorder

If immature cells - primary disorder (leukaemia/lymphoma)

20
Q

What is a typical blood film of Chronic lymphoid leukaemia

cells may look similar if autoimmune / inflammatory conditions

A

Mature lymphocytes - big nucleus with little cytoplasm

Oligo

21
Q

Describe the appearance of immature lymphoblasts

A

Immature lymphoblasts = much larger than mature lymphoblasts. Can also see nucleolus in immature lymphoblasts.

Can be seen in acute lymphoblastic leukaemia

22
Q

What is secondary (reactive) cause of lymphocytosis

A

Polyclonal response to infection, chronic inflammation or underlying malignancy

23
Q

What is a primary cause of lymphocytosis

A

Monoclonal lymphoid proliferation - all cells will look the same - mutated cell expanding and making clones of itself

e.g. CLL

24
Q

Name some causes of reactive lymphocytosis

A
  1. Infection (e.g. EBV, CMV, toxoplasma, etc)
  2. Autoimmune disorders
  3. Neoplasia
  4. Sarcoidosis
25
Q

Describe mononucleosis syndrome

A

“Atypical lymphocyte” - reactive looking lymphocyte

26
Q

Mononucleosis syndrome is typical of?

A

Glandular fever

27
Q

If you see a high White cell count, and find reactive looking lymphocytes, you can be reassured that it is a?

A

Reactive, infection-induced lymphocytosis

28
Q

Describe glandular fever

A
  1. EBV infection of B lymphocytes via CD21 receptor
  2. Infected B cell proliferates and expresses EBV associated antigens
  3. Cytotoxic T-lymphocyte response
  4. Acute infection resolved - results in lifelong sub-clinical infection
  5. Glandular fever - more common in young people
29
Q

Lymphocytosis in elderly is more likely to be caused by?

A

Chronic lymphocytic leukaemia - mature lymphocytes (and maybe smear cells).

30
Q

When responding to infection, you get a polyclonal response. Lightchains in antibody can be which ?

A

Kappa or lambda

If polyclonal expansion in B cells, 50/50 split in kappa and lambda

But if monoclonal expansion - you get Light chain restriction - B cells produce only kappa or only lambda

So if MONOCLONAL - kappa/lambda restriction - NOT response to infection

31
Q

Explain gene rearrangement in lymphocytosis

A

Immunoglobulin genes (Ig) and T cell receptors (TCR) genes undergo recombination in antigen stimulated B/T cells

In PRIMARY MONOCLONAL Proliferation - all daughter cells carry identical configuration of Immunoglobulin gene, or TCR gene - can be detected by southern blot analysis

32
Q

2 likely causes of eosinophilia?

A
  1. Parasitic infection - schistosomiasis
  2. Underlying lymphoma (Hodgkins / NHL)
  3. Allergic autoimmune disorder
33
Q

If kappa / lambda restriction, what should I do

A

To distinguish further - test light chain restriction or test for T cell receptor arrangement

If K/L restriction present, most likely to be chronic lymphocytic leukaemia

34
Q

Blood film features of CML

A
  1. Myelocyte precursors (shouldn’t be present normally)
  2. No toxic granules present in neutrophils (would be present in infection)
  3. Basophil seen
  4. Expansion of myeloid cells

Year 2 Collin (114 decks)

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