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Year 2: MCD > Haem 6 - Abnormal white cell count > Flashcards

Haem 6 - Abnormal white cell count Flashcards

1
Q

Define haematopoiesis

A

Production of BC in the bone marrow

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2
Q

Describe normal haemopoiesis

A

Polyclonal healthy/reactive

  • Normal marrow
  • Reactive marrow (during infection)
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3
Q

Describe malignant haemopoiesis

A

Abnormal/clonal

- Leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative

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4
Q

Draw the diagram for normal haematopoiesis

A

See diagram

Myeloid stem cells - maturation only occurs in the bone marrow.

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5
Q

Describe the differentiation & maturation of a neutrophil?

A

See diagram

Bone marrow

1) Myeloblast
2) Promyelocyte
3) Myelocyte
4) Metamyelocyte

Pheripheral blood
5) Neutophil

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6
Q

What cytokines control the cell numbers for erythroid, lymphoid and myeloid cells

A

Erythroid - Erythropoietin
Lymphoid - IL-2
Myeloid - G-CSF, M-CSF

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7
Q

What do cytokines do in terms of haematopoiesis?

A

Influences differentiation and proliferation.

If it is DNA directed differentiation and proliferation = DNA damage –> cancer (leukaemia/lymphoma/myeloma)

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8
Q

What two classes of WBC fall under leucocytes?

A

lymphocytes and phagocytes

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9
Q

What do lymphoblasts differentiate to?

A

T lymphocytes
B lymphocytes
NK cells

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10
Q

What do phagocytes differentiate to?

A

Granulocytes - Neutrophils, Eosinophils, basophils

Monocytes

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11
Q

What is the basis of abnormal WBC?

A

Its the balance between cell production and cell survival

See diagram

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12
Q

What would cause an increase in WBC production?

A

Reactive

  • Infection
  • Inflammation

Malignant

  • Leukaemia (haematopoeitic cancer)
  • myeloproliferative
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13
Q

What would cause a decrease in WBC production?

A

Impaired BM function
- B12 or Folate deficiency

  • BM failure
    1) Aplastic anaemia
    2) Post chemotherapy
    3) Metastatic cancer
    4) Haematological cancer
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14
Q

What would cause an increase in WBC survival?

A

Failure of apoptosis (e.g acquired cancer causing mutations in some lymphomas)

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15
Q

What would cause a decrease in WBC survival?

A

Immune breakdown

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16
Q

Describe what happens during haemopoietic cancers?

A 
Haemopoietic cancers (leukaemia) produce immature and mature cells which go into the peripheral blood.
In normal WBC proliferation and differentiation immature cells proliferate and differentiate from stem cells in the bone marrow. Then the mature cells are released into the peripheral blood that respond to infection.
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17
Q

What are two causes of Eosinophilia?

A

Reactive (parasitic infection)

Primary (malignant - myeloproliferative disorder)

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18
Q

What is normal haematopoiesis stimulated by?

A

1) Inflammation
2) Infection
3) Increased cytokine production
- Distant tumour
- Haemopoietic or non haemopoietic

19
Q

What can cause abnormal haematopoiesis?

A

(autonomic cell growth)

1) Cancers of haematopoietic cells
2) Leukaemia
- Myeloid or lymphoid
- Chronic or acute
3) Myeloproliferative disorders

20
Q

Describe Malignant haemoatopoiesis?

A

See diagram

21
Q

How do you investigate a raised WCC?

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?

22
Q

If there are elevated levels of immature WBC what can that suggest?

A

Blastocytes + low Hb + low platelets –> Acute leukamia

23
Q

If there are elevated levels of mature + immature WBC what can that suggest?

A

Neutrophils + Myelocytes + basophils –> Chronic myeloid leukaemia

24
Q

If there are elevated levels of mature cells what can that suggest?

A

All lineages or only one (neuts, eos, baso) –> reactive/infection

Lymphocytes –> reactive (viral) or primary (chronic lymphocytic leukaemia)

25
Q

What are the normal FBC?

A 
Hb 			120-160g/l
Platelets		150-400 x 10^9/l
WCC		4-11 x 10^9/l
Neutrophils	2.5-7.5 x 10^9/l
Lymphocytes	1.5-3.5 x 10^9/l
Monocytes	0.2-0.8 x 10^9/l
Eosinophils	0.04-0.44 x 10^9/l
Basophils	0.01-0.1 x 10^9/l
26
Q

List the types of phagocytes?

A

Neutrophils
Basophils
Eosinophils

27
Q

List the type of immune cells?

A

Lymphocytes

28
Q

Describe neutrophils

A

Present in BM, blood and tissues
Life span 2-3 days in tissues (hours in PB)
50% circulating neutrophils are marginated (not counted in FBC)

Neutrophilia can develop in:
minutes > demargination (process of neutrophils entering the peripheral circulation from areas of intravascular marginated polymorphonuclear cell pools)
hours > early release from BM
days > increased production (x3 in infection)

29
Q

Describe the content of neutrophils in the peripheral blood during infection

A

Neutrophilia >7.5x109/l
toxic granulation
vacuoles

30
Q

What malignant conditions feature neutrophlia

A

PB in leukaemia

Chronic leukaemia
Chronic myeloid leukaemia
Neutrophilia and
Precursor cells (myelocytes)

31
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
32
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.

33
Q

What are the causes of Eosinophilia?

A

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

2) Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

34
Q

Eosinophilia and malignant disease slide

A

See slide

35
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)
36
Q

Draw the table showing the reactive elevated phagocyte count?

A

See diagram

37
Q

What are the causes of lymphocytosis?

A

Mature or immature cells:

If mature it is:

1) reactive to infection (autoimmune/inflammatory disease)
2) primary disorder (Chronic Lymphocytic Leukaemia)

If immature it is:
1) primary disorder (leukaemia/lymphoma). If you see immature lymphoblasts it suggests acute lymphoblastic leukaemia.

38
Q

Describe lymphocytosis of mature cells

A

Primary or reactive?

Secondary (reactive); polyclonal response to infection, chronic inflammation, or underlying malignancy.
Primary; monoclonal lymphoid proliferation e.g. CLL

39
Q

What are some causes of reactive lymphocytosis?

A

Infection

  • EBV, CMV, Toxoplasma
  • infectious hepatitis, rubella, herpes infections

Autoimmune disorders

  • neoplasia
  • sarcoidosis
40
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.

41
Q

Lymphocytosis slide

A

Slide 32

42
Q

How do you evaluate lymphocytosis?

A

Evaluate light chain restriction -

polyclonal = kappa and lambda
Monoclonal (a group cell deriving from one mother cell) = kappa only or lambda only

43
Q

Describe the evaluation of lymphocytosis in terms of gene rearrangement

A

Imuunoglobulin 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

Year 2: MCD (40 decks)

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