Abnormal white cell counts Flashcards

1
Q

What is pancytopenia

A

All lineages reduced

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2
Q

What is the types of malignant haemopoeisis

A

Leukaemia (lymphoid, myeloid) = cancer of blood cells
Myelodysplasia = immature cells
Myeloproliferative = too many cells

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3
Q

Where are neutrophils found and how do they develop

A

Found in the peripheral blood

  1. myeloblast
  2. promyelocyte
  3. myelocyte
  4. metamyelocyte
  5. neutrophil (only one in the peripheral blood)
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4
Q

How are cell numbers controlled

A

Different cytokines will increase different cell numbers
Erythroid - Erythropoietin
Lymphoid - IL2
Myeloid - G-CSF, M-CSF

DNA dictates differentiation and proliferation of blood cells
DNA damage can lead to cancer ie leaukaemia, lymphoma (blood cancer of lymphocytes), myeloma (cancer of blood plasma cells)

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5
Q

Which cells are found in the peripheral blood

A

Immunocytes - T, B and NK cells

Phagocytes - granulocytes (neutrophils, eosinophils, basophils) and monocytes

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6
Q

Why may there be an increase WBC production

A

Reactive - infection or inflammation

Malignant - leukaemia or myeloproliferative

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7
Q

Why may there be a decrease in WBC production

A
Impaired bone marrow function
  - Aplastic anaemia 
  - Post chemo
  - Metastatic cancer
  - Haematological cancer
B12 or folate deficiency
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8
Q

Why may there be an increase in cell survival

A

Failure of apoptosis e.g. acquired cancer causing mutation in some lymphomas

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9
Q

Why may there be a decrease in cell survival

A

immune breakdown

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10
Q

What is normal reactive haemopoiesis (eosinophilia) stimulated by

A

Inflammation
Infection
Increased cytokine production (Distant tumour, Haemopoietic or non haemopoietic)

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11
Q

What is abnormal primary (malignant) haemopoiesis (eosinophilia) due to

A

Cancers of haemopoietic cells
Leukaemia (Myeloid or lymphoid, Chronic or acute)
Myeloproliferative disorders

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12
Q

What happens to white blood cells in malignant haematopoeisis (chronic myeloid leukaemia)

A

Increase in myeloid cells
GM-CFC

Granulocutes
Megakaryocytes
Monocytes

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13
Q

How should a raised white cell count be investigate

A

History and examination
Haemoglobin and platelet count
Automated differential
Examine blood film

Abnormality White cells only, or all 3 lineages (red cells/platelets/white cells) ?
White cells 1 cell type only, or all lineages? (e.g. neuts/eos/monocytes/lymphocytes)
Mature cells only or mature and immature cells?

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14
Q

What are the possibilities if only mature cells are present

A

All lineages or just one - reactive/infection

Only lymphocytes - reactive or cancel (chronic lymphocytic leukaemia)

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15
Q

What are the possibilities if both mature and immature cells are present

A

Could be chronic myeloid leukaemia (neutrophils + myelocytes + basophils)

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16
Q

What are the possibilities if only immature cells are present

A

Blasts + low Hb + low platelets = acute leukaemia

17
Q

Describe neutrophil presence in the blood

A

Present in bone marrow, blood and tissues
Life span = 2-3 days in tissues
50% circulating are marginated (stuck to vessels wall)

18
Q

Why may neutrophilia develop according to time span

A

minutes - demargination
hours - early release from BM
days - increased production (x3 in infection)

19
Q

Describe neutrophils in the peripheral blood during infection

A

Neutrophils > 7.5 x 10^9/L
Toxic granulation
Vacuoles

20
Q

Describe neutrophils in the peripheral blood during leukaemia

A

neutrophilia and precursor cells (myelocytes) seen

21
Q

What are the causes of neutrophilia

A

Infection
Tissue inflammation (e.g.colitis, pancreatitis)
Physical stress, adrenaline, corticosteroids
underlying neoplasia

Malignant neutrophilia (myeloproliferative disorders
CML)
22
Q

Describe neutrophilia in infection

A

Localised and systemic infections
acute bacterial, fungal, certain viral infections

Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections.

23
Q

What are the causes of reactive eosinophilia

A

Parasitic infestation
Allergic diseases (e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia)
Neoplasms (esp. Hodgkin’s, T-cell NHL)
Hypereosinophilic syndrome

24
Q

What is a non-reactive cause of eosinophilia

A

Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

25
Q

What is monocytosis

A
Rare but seen in certain chronic infections and primary haematological disorders
TB, brucella, typhoid
Viral; CMV, varicella zoster
Sarcoidosis
Chronic myelomonocytic leukaemia (MDS)
26
Q

What infections can be indicated by reactive elevated phagocyte counts for neutrophils, eosinophils, basophils and monocyte

A

Neutrophils - bacterial
Eosinophils - parasitic
Basophils - pox virus
Monocytes - chronic (TB, brucella)

27
Q

What kind of inflammation can be indicated by reactive elevated phagocyte counts for neutrophils and eosinophils

A

N - Auto-immune tissue necrosis

E - Allergic (asthma, atopy, drug reaction)

28
Q

What may indicate a neoplasia from a reactive elevated phagocyte count

A

N - all types

E - Hodgkins, NHL

29
Q

What may cause lymphocytosis

A

Mature - reactive to infection or a primary disorder (e.g. CLL)

Immature - primary disorder (leukaemia/lymphoma), acute lymphoblastic leukaemia

30
Q

What is the difference between primary and reactive lymphocytosis

A

Secondary (reactive) - polyclonal response to infection, chronic inflammation, or underlying malignancy

Primary - monoclonal lymphoid proliferation e.g. CLL

31
Q

What may reactive lymphocytosis be due to

A

Smoking

Infection

  • EBV, CMV, toxoplasma
  • Infectious hepatitis, rubella, herpes infections

Autoimmune disorders

  • neoplasia
  • sarcoidosis
32
Q

Describe atypical lymphocytes

A

Mononucleosis syndrome/glandular fever

Looks immature but is actually a reactive, infection induced lymphocytosis

33
Q

Describe glandular fever

A

EBV infection of B-lymphocytes via CD21 receptor
Infected B-cell proliferates and expresses EBV associated antigens
Cytotoxic T-lymphocyte response
Acute infection resolved resulting in lifelong sub-clinical infection
Result = lymphocytosis with atypical lymphocytes

34
Q

How can you differentiate between mature lymphocytes and elderly patients with lymphocytosis

A

reactive to underlying auto immune disorder or chronic lymphocytic leukaemia

Morphology
Immunophenotype
Gene re-arrangement

35
Q

How can you evaluate lymphocytosis using light chain restriction

A

Check what light chains the lymphocytes
Kappa and lambda = polyclonal
Only kappa or only lambda = monoclonal (cancer)

36
Q

How can you evaluate lymphocytosis using gene rearrangement

A

Immunoglobulin genes (Ig) and T cell receptor (TCR) genes undergo recombination in antigen stimulated B cells or T cells.

With primary monoclonal proliferation all daughter cells carry identical configuration of Ig, or TCR gene. This can be detected by Southern Blot analysis