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Y2 - HAEM > Abnormal White Cell Count > Flashcards

Abnormal White Cell Count Flashcards

1
Q

Give 3 conditions, including 2 subtypes for one of these, which result in malignant haemopoiesis

A
  1. Leukaemia (lymphoid, myeloid)
  2. Myelodysplasia
  3. Myeloproliferative disorders
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2
Q

Outline the differentiation pathways for the formation of all blood cells (all myeloid and lymphoid except for NK cells) in 2 steps for each, each starting with the HSC (haematopoietic stem cell) as the first step (not included in the 2 steps)

A
  • HSC is initial precursor for all of them
  1. HSC → Pre-T → T-cells
  2. HSC → Pre-B → B-cells
  3. HSC → BFU-E → RBCs
  4. HSC → Meg-CFC → Megakaryocytes / platelets
  5. HSC → GM-CFC → Granulocytes + Monocytes
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3
Q

Outline the steps in the differentiation and maturation pathways for the formation of neutrophils

A

Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Neutrophil

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4
Q

1) In the peripheral blood cells, you only see neutrophils. We should not see any of the cells that are in the differentiating phase, but there are exceptions. List 3 exceptions and then say what you will see in the blood film which contradicts this rule and then, where applicable, mention why or how this is the case
2) What immature cells might you see?

A

1) 1. Septic patients

  • Leukoerythroblastic picture - can see myeloid precursors and nucleated red cells
  • Because the bone marrow is trying to compensate for the peripheral destruction of cells so is churning out cells so you’ll see lots of early stage cells
  1. Chemotherapy
  • Can see immature myeloid cells in the blood
  • Because the WBC count fails due to chemotherapy so we give G-CSF to promote WBC differentiation / proliferation so churn out cells so you’ll see lots of early stage cells too
  1. Chronic Myeloid Leukaemia
    * Can see cells at all stages of myeloid differentiation in the blood

2)

  • Lymphoblasts
  • Myeloblasts
  • Promyelocytes
  • Myelocytes
  • Metamyelocytes
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5
Q

How can you diagnose chronic myeloid leukaemia from a blood film?

A

You can see the presence of myeloid cells at every stage of the differentiation pathway

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6
Q

WBC production fails as a result of chemotherapy, what do we give to patients to remedy this?

A

Give G-CSF - a cytokine which drives WBC production to replace the low WBC count

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7
Q

1) The production of erythroid cells is mediated by ….. produced in the …..
2) The production of lymphoid cells is mediated by ….. (an …..), along with other cytokines
3) The production of myeloid cells is mediated by ….. and ….. growth factors

A

1) The production of erythroid cells is mediated by erythropoietin in the kidneys
2) The production of lymphoid cells is mediated by IL-2 (an interleukin) along with other cytokines
3) The production of myeloid cells is mediated by G-CSF and M-CSF growth factors

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8
Q

What cells would we expect to see in the peripheral blood films normally - essentially what are the cells in the lymphoid and myeloid lineages?

A

Lympoid lineage

  • T-cells
  • B-cells
  • NK cells

Myeloid lineage

  • Granulocytes - basophils, eosinophils, neutrophils
  • Monocytes
  • Erythrocytes

Essentially all the final, mature products of the different lineages in the differentiation pathways

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9
Q

List some cases in which you will have abnormally reduced production of WBC - low WBC

A
  • IMPAIRED BM FUNCTION - DECREASE
  • BM FAILURE - DECREASE: reduced WBC in aplastic anaemia, chemotherapy, metastatic / haematological cancer
  • B12 OR FOLATE DEFICIENCY - DECREASE
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10
Q

List 2 cases in which you will get increase and decrease in WBC survival (1 each)

A
  • FAILURE OF APOPTOSIS - INCREASED SURVIVAL: occurs in cancer causing mutations and lymphomas
  • IMMUNE BREAKDOWN - DECREASED SURVIVAL: autoimmune destruction of WBCs
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11
Q

1) What is eosinophilia?
2) What are the 2 categories for the causes of eosinophilia and outline the causes within these categories?

A

1) Abnormally high production of eosinophils

2)

  1. REACTIVE - where HAEMOPOIESIS IS NORMAL
  • Infection
  • Inflammation
  • Increased cytokine production due to a distant tumour (haematopoietic or non-haematopoietic)
  1. PRIMARY (MALIGNANT) - where HAEMOPOIESIS IS ABNORMAL
  • Cancers of haematopoietic cells
  • Leukaemia (myeloid or lymphoid, chronic or acute)
  • Myeloproliferative disorders (e.g. in chronic myeloid leukaemia)
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12
Q

What WBCs will be elevated in CML (chronic myeloid leukaemia)?

A
  • Granulocytes including basophils, eosinophils and neutrophils
  • Monocytes
  • Megakaryocytes / platelets
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13
Q

4 ways in which to investigate an abnormal white blood cell count?

A
  1. History and examination - splenomegaly, enlarged lymph nodes
  2. Haemoglobin and platelet count - high WBC yet low Hb and platelets is worrying
  3. Automated differential
  4. Examine blood film
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14
Q

What are 3 things we must consider when interpreting an abnormal WBC count?

A
  • Which cell lineages are affected - red cell / white cell / platelets?
  • Which white cell types are affected - basophils, eosinophils, neutrophils, lymphocytes …
  • Whether the cells are mature or immature
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15
Q

In what type of leukaemias will you see lots of mature and in which will you see lots of immature cells?

A
  • Chronic - chronic lymphoblastic / myeloid leukaemia - many mature cells
  • Acute - acute lymphoblastic / myeloid leukaemia - many immature cells
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16
Q

In what case might you see a high number of blasts but a low Hb and platelet count?

A

Acute leukaemia

17
Q

Label the diagram with the causes - these are blocked out

A
18
Q

What is a very common cause for lymphocytosis?

A
  • Smoking
  • Note this effect can persist for a while even after cessation of smoking
19
Q

What is the lifespan of neutrophils in the tissues and then in the peripheral blood?

A
  • 2-3 days in tissues
  • Few hours in the peripheral blood
20
Q

….. of neutrophils are ….. (not counted in the FBC)

A

50% of neutrophils are marginated (not counted in the FBC)

21
Q

Neutrophilia can appear in…

Minutes as a result of …..

Hours as a result of …..

Days as a result of …..

A

Minutes as a result of demargination

Hours as a result of response to infection or inflammation - early release from BM

Days from increased production following infection (much higher now though - x3)

22
Q

List 5 causes of neutrophilia

A
  1. Tissue inflammation (colitis, pancreatitis)
  2. Infection
  3. Physical stress (adrenaline), corticosteroids
  4. Underlying neoplasia
  5. Malignant neutrophilia (myeloproliferative disorders, CML)
23
Q

Which infections lead to neutrophilia, and which do not (including 2 specific examples)?

A
  • ALMOST ALL - localised or systemic - acute viral, fungal and bacterial alike
  • However, some characteristically do not produce neutrophilia: brucella, typhoid, many viral infections
24
Q

What are the 2 main causes of eosinophilia and describe further

A
  1. REACTIVE
  • Parasitic infestation
  • Allergic disease e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
  1. MALIGNANT CHRONIC EOSINOPHILIC LEUKAEMIA (mutation in the PDGR fusion gene)
  • Neoplasms, especially Hodgkin’s, T-cell NHL - IL-5 plays a key role in the hyperproliferation of eosinophils
  • Hypereosinophilic syndrome
25
Q

How to treat hypereosinophilic syndrome due to malignant chronic eosinophilic leukaemia?

A
  • Monoclonal antibody that targets IL-5 which usually results in the hyperproliferation of eosinophils in Hodgkin’s / T-cell NHL
26
Q

1) Monocytosis is mostly caused by infection, what infections could cause monocytosis?
2) Aside from infection, what chronic condition can also lead to monocytosis?

A

1)

  • TB
  • Brucella
  • Typhoid
  • Viral: CMV, varicella zoster
  • Sarcoidosis

2)

  • Chronic myelomonocytic leukaemia
27
Q

Fill in the blanks for the reactive causes for elevated WBC count from the diagram shown

A
28
Q

What might lymphocytosis involving immature cells suggest?

A
  • Acute Lymphoblastic Leukaemia
29
Q

What 2 types of causes might there be that are suggested by lymphocytosis involving mature cells?

A
  1. Primary - monoclonal lymphoid proliferation in CLL
  2. Secondary - polyclonal response to infection, autoimmune disorders, chronic inflammation, underlying malignancy
30
Q

What are the potential reactive causes of lymphocytosis?

A
  • Infection (EBV, CMV, Toxoplasma, Infectious hepatitis, Rubella, Herpes infection)
  • Autoimmune disorders
  • Neoplasia
  • Sarcoidosis
31
Q

What is the pathophysiology of glandular fever causing lymphocytosis?

A
  • EBV infection of B-lymphocytes via CD21 receptor
  • Infected B-lymphocyte proliferates and expresses EBV antigen
  • This elicits a cytotoxic T-lymphocyte response
  • Acute infection is resolved but results in lifelong sub-clinical infection
32
Q

How can differentiate using lab techniques, whether a lymphocytosis is reactive in nature in response to infection or inflammation etc or due instead to a neoplastic process such as CLL / ALL?

A
  • Polyclonal lymphocytes are present as a result of reactive response to infection or response to inflammation whereas monoclonal lymphocyte populations present as a result of neoplastic processes such as CLL / ALL
  • 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
  • Also light chain restriction analysis by peripheral blood immunotype - if there is only kappa present and not lambda for example, we can say that this is not due to a reactive polyclonal response but instead a monoclonal response due to neoplastic processes
33
Q

SEE THE CASE STUDIES IN THE LAST PAGE OF NOTES ON THE LECTURE

A

SEE THE CASE STUDIES IN THE LAST PAGE OF NOTES ON THE LECTURE

Y2 - HAEM (11 decks)

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