Abnormal White Cell Count Flashcards

1
Q

What is pancytopenia?

A

all cell lineages reduced

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2
Q

In normal haemopoiesis, are the cells clonal or polyclonal?

A

polyclonal - different types but there is one original

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3
Q

What are characteristics of malignant haemopoiesis?

A

abnormal and clonal population

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4
Q

Describe the differentiation pathway for T cell and B cell formation?

A

HSC -> Pre T/B -> B/T cell

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5
Q

What regulates haematopoeisis?

A

many cytokines and growth factors

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6
Q

What are the two types of progenitors the HSC can develop into?

A

Common myeloid/lymphoid progenitor

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7
Q

What can a CMP develop into?

A

CMP -> myeloblast, mast cell, erythrocyte, megakarcoyte (-> platelet)

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8
Q

What can a myeloblast become?

A

myeloblast -> basophil, neutrophil, eosinophil, monocyte (-> macrophage)

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9
Q

What is a myeloblast?

A

very large cell with a high nucleus:cytoplasmic ratio – not many granules

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10
Q

During myeloid maturation there are many stages, name some of them

A

myeloblast, promyelocyte, myelocyte, metamyelocyte -> neutrophil for example

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11
Q

What are myeloid cells?

A

Everything that develops from a common myeloid progentior so everything but lymphocytes (includes natural killer cells)

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12
Q

What is a promyelocyte?

A

They are very large cells, with heavy granulation in the cytoplasm

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13
Q

What is a myelocyte?

A

Cells in which the nucleus becomes eccentric and the cytoplasm becomes smaller

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14
Q

In the peripheral blood in a healthy person should differentiating cells be seen?

When may they be seen?

A

no

  1. In septic patients – the bone marrow starts to release very immature cells
  2. In patients receiving chemotherapy – white cell count falls
  3. In chronic myeloid leukaemia -> presence of cells at all stages of myeloid differentiation in the blood
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15
Q

What is seen in septic patients in terms of blood cells?

A
  • We find a leukoerythroblastic picture
  • This described the presence of myeloid precursors with nucleated red cells
  • This shows that the bone marrow is trying to compensate for the peripheral destruction of cells
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16
Q

In patients having chemotherapy, why are immature myeloid cells seen in the blood?

A
  • White cell count falls

- Hence we give these patients the growth factor G-CSF – stimulates bone marrow to release more white cells

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17
Q

What is seen in chronic myeloid leukaemia?

A
  • Presence of cells at all stages of myeloid differentiation in the blood
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18
Q

Which factors mediate the developemt of erythroid, lymphoid and myeloid cells?

A

Erythroid cells -> erythropoietin produced in the kidneys

Lymphoid cells -> IL2, along with other cytokines

Myeloid cells -> G-CSF and M-CSF growth factors

19
Q

Which immature cells should not be seen in peripheral blood and only in bone marrow?

A

lymphoblasts, myeloblasts, promyelocytes, myelocytes and metamyelocytes

20
Q

What can cause abnormal white blood cell production?

A
  1. REACTIVE (you get increased production during infection and inflammation)
  2. MALIGNANT (increased WBC count in leukaemia and can be myeloproliferative)
  3. IMPAIRED BM FUNCTION (reduced WBC count when bone marrow function is impaired)
  4. BM FAILURE (reduced WBC in aplastic anaemia, chemotherapy, metastatic/haematological cancer)
  5. B12 OR FOLATE DEFICIENCY (reduced WBC count
21
Q

What are myeloproliferate neoplasms?

A

A group of rare disorders of the bone marrow that cause an increase in the number of blood cells. Used for both malignant and non cancerous tumours.

22
Q

What can cause abnormal white cell survival?

A
  1. FAILURE OF APOPTOSIS (increased survival in cancer causing mutations in some lymphomas)
  2. IMMUNE BREAKDOWN (decreased survival in autoimmune breakdown of WBCs by antibodies)
23
Q

What are the two main factors that lead to an abnormal white cell count?

A

abnormal white cell production and abnormal white cell sruvival

24
Q

What are the two causes of eosinophilia?

A
  1. REACTIVE CAUSES OF EOSINOPHILIA where haemopoiesis is normal:
    - Inflammation
    - Infection (parasites)
    - Increased cytokine production (due to a distant tumour)
  2. PRIMARY (MALIGNANT) CAUSES OF EOSINOPHILIA where haemopoiesis is abnormal:
    - Cancers of haematopoietic cells
    - Leukaemia
    - Myeloproliferative disorders
25
Q

How should an abnormal white cell count be investigated?

A
  1. History and examination (enlarged spleen, lymph nodes)
  2. Haemoglobin and platelet count (concerning to see someone with high WBC, low Hb and low platelets)
  3. Automated differential (in leukaemia, the machine cannot interpret the blasts)
  4. Examine blood film (easy and cheap to do – look under a microscope at cell morphology)
26
Q

Which factors must be thought about when interpreting a white cell count?

A
  • Need to consider whether the abnormality is seen in all 3 lineages (red cells/white cells/platelets)
  • If its only in white cells, we need to find out if its only one type (neutrophils/eosinophils/lymphocytes)
  • We need to consider whether the abnormality involves only mature cells or immature cells
  • When it only involves mature cells, it is quite reassuring – but could still be a sign of malignancy
  • Seeing immature cells in the peripheral cells can have some non-lethal causes
27
Q

In chronic lymphocytic leukaemia, what is seen?

A

An increased number of B lymphocytes. These cells have a mature nucleus so these are mature cells.

28
Q

In chronic myeloid leukaemia, what is senn?

A

High number of lymphocytes

29
Q

In acute lymphoblastic leukaemia what is seen?

A

An increases number of B cells but they are immature cells

30
Q

What is a common cause of neutrophilia or lymphocytosis?

A

smoking

31
Q

What % of the total nuetrophils are seen in the blood?
What is the life span in tissues and blood?
What % are circulating neutrophils are marginated (not counted in FBC)?

A
  • 10%
  • blood: hours
  • tissues: 2-3 days
  • 50%
32
Q

What is margination?

A

When leukocytes exit the central blood stream - attached to endothelium ready to leave

33
Q

What are some causes of neutrophilia developing in a few minutes, hours and days?

A

Minutes: as a result of demargination

Hours: as a response to inflammation or infection (early release from BM)

Days: increased production (x3 in infection)

34
Q

What are some causes of neutrophilia?

A
  • Infection
  • Tissue inflammation (e.g. colitis, pancreatitis)
  • Physical stress (increased adrenaline), corticosteroids
  • Underlying neoplasia
  • Malignant neutrophilia (myeloproliferative disorders, CML)
35
Q

What can cause eosinophilia?

A

-Parasitic infestation
-Allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
- Neoplasms, especially Hodgkin’s, T-cell NHL
- Hypereosinophilic syndrome
- Malignant Chronic Eosinophilic Leukaemia
syndrome)

36
Q

What is the role of IL5 in eosinophilia (Hodgkin’s and non-Hodgkin’s lymphoma)?

A
  • IL5 stimulates the production of eosinophils
37
Q

What can cause monocytosis (rare)?

A
  • TB, brucella, typhoid (rare)
  • Viral; CMV, varicella zoster
  • Sarcoidosis
  • Chronic myelomonocytic leukaemia
38
Q

When may we see basophilia (rare)?

A
  • cancers

- inflammation

39
Q

If lymphocytosis involved mature cells, what do we need to find out?

A

If it is primary or secondary
- PRIMARY: monoclonal lymphoid proliferation

  • SECONDARY: polyclonal response to infection, chronic inflammation or underlying malignancy
40
Q

What are some reactive causes of lymphocytosis?

A
  • Infection (CMV, EBV, hepatitis, toxoplasma, herpes)
  • Autoimmune
  • Neoplasia
  • Sarcoidosis
41
Q

What is glandular fever?

A
  • EBV infection of B-lymphocytes via CD21 receptor
  • Infected B-cell proliferates and expresses EBV associated antigens
  • This results in a cytotoxic T-lymphocyte response
  • Acute infection is resolved resulting in lifelong sub-clinical infection
42
Q

After the age of 70 it is common to see lymphocytosis, what could cause this?

A

Reactive to underlying autoimmunity or chronic lymphocytic leukaemia

43
Q

How can we distinguish between monoclonal and polyclonal disorders?

A

By looking at the morphology, immunophenotype and gene rearrangement

44
Q

How can a southern blot detect if cells are monoclonal?

A

Immunoglobulin genes 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.