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Yr 2 MCD - Haem > 6 - Abnormal White Cell Count > Flashcards

6 - Abnormal White Cell Count Flashcards

1
Q

What is Pancytopenia?

A

Deficiency of all three cellular components of the blood (red cells, white cells, and platelets).

All lineages reduced.

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2
Q

What is Haemopoiesis?

A

Production of blood cells in bone marrow.

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3
Q

What can be the result of malignant haemopoiesis?

A

Leukaemia (lymphoid, myeloid)

Myelodysplasia

Myeloproliferative Neoplasm

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4
Q

What two forms of normal haemopoiesis can occur?

A

Within Normal Marrow

Within Reactive Marrow

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5
Q

How is malignant haemopoiesis characterised?

A

By the presence of an abnormal population of cells in the bone marrow that all derive from the same mother cell

  • clonal haemopoiesis
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6
Q

Why is normal haemopoiesis described as polyclonal?

A

Because the cells in the bone marrow all derive from different lineages.

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7
Q

What is unique about Haemopoietic Stem Cells (HSCs)?

A

They have the ability of self-renewal

- produce daughter cells which have the same characteristics as the mother HSC so generation can continue

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8
Q

What precursors are formed from Haemopoietic Stem Cells (HSCs) and what will the precursors become?

A

Pre-T
- will become T-Cells

Pre-B
- will become B-Cells

BFU-E
- will become RBCs

Meg-CFC
- will become megakaryocytes/platelets

GM-CFC

  • will become granulocytes
  • will become monocytes
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9
Q

What do HSCs produce?

A

Daughter cells the same as the mother HSC

Precursors of other blood cells

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10
Q

Outline the maturation of the myeloid lineage

A

Myeloblast

  • large cell
  • very undifferentiated
  • only way to differentiate from lymphocyte is to see very fine granules in its cytoplasm
  • very high nucleus:cytoplasm ratio

Promyeloblast

  • smaller
  • plenty of granules
  • nucleus becomes smaller
  • nucleus becomes eccentric

Myelocyte
- even smaller

Metamyelocyte
- nucleus starts to fold

Band Cells

Neutrophil (mature)

  • moves into the blood
  • only stage of cell you should see in the blood from this lineage
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11
Q

In what situations would you see non-mature myeloid cells in peripheral blood?

A

Myeloproliferative Disorder

  • e.g. Chronic Myeloid Leukaemia, would see all stages of myeloid maturation
  • e.g. Chemotherapy, neutropenic as a result of the chemotherapy,
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12
Q

In what situations would you see non-mature myeloid cells in peripheral blood?

A

Myeloproliferative Disorder

  • e.g. Chronic Myeloid Leukaemia, would see all stages of myeloid maturation including myeloblasts
  • e.g. Chemotherapy, neutropenic as a result of the chemotherapy, give patient GCSF to boost white cells, see all stages of myeloid maturation except myeloblasts in blood film
    e. g. Sepsis, see some myeloid precursors in peripheral blood but not myeloblasts
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13
Q

What are the associations between nucleated red blood cells and myeloid precursors in peripheral blood known as?

A

Leuko-Erythroblastic Picture

Seen in very few situations such as sepsis or when cancer has infiltrated the bone marrow

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14
Q

What would not want uncontrolled division of RBCs?

A

It would increase the viscosity of the blood

Higher risk of heart attacks, strokes etc.

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15
Q

What chemicals influence cell differentiation and proliferation?

A

Cytokines

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16
Q

Which cytokine influences erythroid differentiation and proliferation?

A

Erythropoietin

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17
Q

Which cytokine influences lymphoid differentiation and proliferation?

A

IL2

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18
Q

Which cytokines influence myeloid differentiation and proliferation?

A

G-CSF

M-CSF

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19
Q

What happens when severe DNA damage occurs?

A

Cancer

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20
Q

Why is M-CSF not used in clinical practice?

A

This is because it increases the proliferation of monocytes, which is not very useful in clinical practice.

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21
Q

Which leucocytes would be found only in bone marrow?

A 
Lymphoblasts
Myeloblasts
Promyelocytes
Myelocytes
Metamyelocytes
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22
Q

What leucocytes would be found only in peripheral blood?

A

IMMUNOCYTES

  • T lymphocytes
  • B lymphocytes
  • NK cells

PHAGOCYTES

  • Granulocytes (neutrophils, eosinophils, basophils)
  • Monocytes
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23
Q

What two overall reasons would cause an abnormal White Blood Cell count?

A

Cell Production problems

Cell Survival problems

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24
Q

What could cause an increased production of WBCs?

A

REACTIVE

  • Infection
  • Inflammation

MALIGNANT

  • Leukaemia
  • Myeloproliferative Neoplasm
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25
Q

Why do WBCs often decrease in sepsis rather than increase?

A

In sepsis, sometimes bone marrow separation occurs causing drop in WBCs and other cells such as platelets. {THROMBOCYTOPENIA]

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26
Q

What could cause an decreased production of WBCs?

A

IMPAIRED BM FUNCTION

  • B12 or Folate deficiency
  • BM Failure
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27
Q

What factors can cause bone marrow failure?

A

Aplastic anaemia
Post chemotherapy
Metastatic cancer into BM
Haematological cancer

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28
Q

What can cause increased WBC survival?

A

Failure of apoptosis

e.g. acquired cancer causing mutations in some lymphomas

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29
Q

What can cause decreased WBC survival?

A

Immune breakdown

30
Q

Is eosinophilia reactive or malignant in most cases?

A

Reactive

  • normally haemopoiesis
  • stimulated by inflammation/infection/increased cytokine production
31
Q

What happens in malignant eosinophilia?

A

Abnormal haemopoiesis (autonomous cell growth)

  • cancers of haemopoietic cells
  • leukaemia (myeloid or lymphoid and chronic or acute)
  • myeloproliferative disorders
32
Q

What occurs from the first differentiation of haemopoietic stem cells in Chronic Myeloid Leukaemia?

A

Haemopoietic Stem Cells

DNA damage occurs

Mechanism to clear DNA damage is not functioning

Permanent mutation acquired at very early stage of stem cell differentiation and maturation (same in all myeloproliferative neoplasms)

Cells that are generated from the mutation will have uncontrolled growth causing increased number of certain cells

In CML, its increased total white cells but especially neutrophilia, eosinophilia and basophilia (granulocytes increased) and lots of myeloid precursors with all stages of myeloid differentiation represented

33
Q

What are the genetics behind Chronic Myeloid Leukaemia?

A

One of the first cancers where a clear genetic abnormality has been identified

Philadelphia Chromosome

  • Created by a translocation between chromosome 9 and chromosome 22
  • Causes a fusion gene to be formed
34
Q

How do you investigate a raised white cell count (WCC)?

A

History and examination

  • recent infection e.g. cough, sore throat
  • smokers often have neutrophilia

Haemoglobin and platelet count
- drop in haemoglobin and platelets in leukaemia

Automated differential
- differentiate between different granulocytes

Examine blood film

35
Q

What are the important factors to consider when investigating a raised white cell count (WCC)?

A

TO CONFIRM REACTIVE OR MALIGNANT?

  • Abnormality: white cells only, or all 3 lineages (red cells/white cells/platelets)?
  • White cells: 1 cell type only or all lineages (e.g. neutrophils/eosinophils/monocytes etc)?
  • Mature cells only or mature + immature cells?
36
Q

What cells are raised in:

  • reactive conditions
  • malignancy?
A

REACTIVE CONDITIONS

  • all lineages affect
  • all mature cells
  • neutrophils, eosinophils, monocytes, lymphocytes

MALIGNANCY

  • increase in one lineage
  • most cells immature
  • exception: Chronic Myeloid Leukaemia, increase in all white cells and mature+immature cells
  • exception: Chronic Lymphocytic Leukaemia, mature and small cells, B lymphocytes, monomorphic cells
37
Q

What is the normal range of Hb?

A

120-160 g/l

38
Q

What is the normal range of platelets?

A

150-400x10^9 /l

39
Q

What is the normal range of white cells?

A

4-11x10^9 /l

40
Q

What is the normal range of neutrophils?

A

2.5-7.5x10^9 /l

41
Q

What is the normal range of lymphocytes?

A

1.5-3.5x10^9 /l

42
Q

What is the normal range of monocytes?

A

0.2-0.8x10^9 /l

43
Q

What is the normal range of eosinophils?

A

0.04-0.44x10^9 /l

44
Q

What is the normal range of basophils?

A

0.01-0.1x10^9 /l

45
Q

Where are neutrophils found in the body?

A

Bone Marrow

Blood

Tissues

46
Q

What is the lifespan of a neutrophil?

A

Lifespan:

2-3 days in tissues
Hours in peripheral blood

47
Q

What percentage of circulating neutrophils are marginated and not counted in a full blood count (FBC)?

A

50% circulating neutrophils

48
Q

What can cause neutrophilia and in what time frames?

A

Demargination = minutes

Early release from Bone Marrow = hours

Increased neutrophil production x3 in infection = days

49
Q

What does margination mean?

A

The process in infection/inflammation when neutrophils leave the bloodstream and attach to the endothelial cells of vessels.

50
Q

What does a peripheral blood film look like in infection?

A

Neutrophilia (>7.5x10^9/l)

Toxic Granulation

Vacuoles

51
Q

What does a peripheral blood film look like in leukaemia?

A

Neutrophilia

Precursor cells (myelocytes)

52
Q

What is Toxic Granulation?

A

Abnormal distribution of granules in cytoplasm of neutrophils.

53
Q

What are the most common causes of Neutrophilia?

A

Infection

Tissue Inflammation

  • e.g. colitis
  • e.g. pancreatitis

Physical Stress

Adrenaline

Corticosteroids

Underlying Neoplasia (cancer)

Malignant Neutrophilia

  • Myeloproliferative Disorders
  • CML
54
Q

How does Neutrophilia present in infection?

A

Can be LOCALISED or SYSTEMIC

Acute bacterial, fungal, certain viral infections

55
Q

Which infections characteristically do not produce a neutrophilia?

A

Brucella

Typhoid

Many viral infections

56
Q

What can cause Reactive or Malignant Eosinophilia?

A

REACTIVE

  • Parasitic Infestation
  • Allergic disease e.g. asthma, rheumatoid, polyarthertisis, pulmonary eosinophilia
  • Neoplasms e.g. Hodgkin’s, T-Cell NHL
  • Hypereosinophilic Syndrome

MALIGNANT

  • Malignant Chronic Eosinophilic Leukaemia
  • Genetic, PDGFR fusion gene
57
Q

What causes Monocytosis?

A

RARE

Seen in certain chronic infections and primary haematological disorders

  • TB, Brucella, Typhoid
  • Viral; CMV, Varicella zoster
  • Sarcoidosis
  • Chronic Myelomonocytic Leukaemia (MDS)
58
Q

What can cause Lymphocytosis with mature lymphocytes?

A

REACTIVE
- due to infection

PRIMARY DISORDER

  • Chronic Lymphocytic Leukaemia (clonal process so all lymphocytes will look the same)
  • Autoimmune/Inflammatory Disease
59
Q

What can cause Lymphocytosis with immature lymphocytes?

A

Primary disorder (leukaemia/lymphoma)

  • lymphoma
  • Acute Lymphoblastic Leukaemia (lymphoblasts with large nuclei)
60
Q

What can cause reactive lymphocytosis?

A

Infection

  • EBV
  • CMV
  • Toxoplasma
  • Infectious hepatitis
  • Rubella,
  • Herpes infections

Autoimmune Disorders

Neoplasia

Sarcoidosis

61
Q

What is Infectious Mononucleosis?

A

EBV infection (Glandular Fever)

Blood film shows atypical lymphocytes

62
Q

What is the mechanism and physiological response to 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

63
Q

By what age have 90% of the population been in contact with EBV?

A

40 years old

64
Q

What are the symptoms of an EBV infection of a person with a high viral load of EBV?

A

Sore throat

Fatigue

65
Q

In which population is lymphocytosis a common finding?

A

The elderly

66
Q

How do distinguish lymphocytosis apart from taking the history and doing a clinical examination?

A

Morphology

Immunophenotype

Gene re-arrangement

67
Q

What is the differential of lymphoctyosis?

A

Reactive to underlying auto immune disorder or Chronic Lymphocytic Leukaemia

68
Q

What is Immunophenotyping/Flow Cytometry?

A

Test that gives ability to distinguish cells depending on molecules they express on their surfaces

69
Q

What is monomorphic lymphocytosis?

A

All the lymphocytes look the same

Clonal process

70
Q

What is pleomorphic lymphocytosis?

A

All the lymphocytes look different (shape/size etc)

Polyclonal process

71
Q

How could you differentiate between monoclonal lymphocytosis and polyclonal lymphocytosis?

A

Look at blood film - look for monomorphism or pleomorphism

Use Light Chain Restriction

  • monoclonal pathological process: only produce one type of light chain (only kappa or only lamda)
  • polyclonal pathological process: equal amounts of kappa and lambda

Yr 2 MCD - Haem (12 decks)

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