Abnormal White Cell count

Question 1

What does neutro-cytopenia/cytosis mean?

Answer 1

• reduced/raised cell counts

Question 2

what does pancytopenia mean?

Answer 2

all cell lines reduced

Question 3

where does normal haemopoiesis occur? when is it is normal/malignant?

Answer 3

• occurs in bone marrow
• normal haemopoiesis can occur in normal situations and in reactive situations
• malignant happens in leukaemia, myelodysplasia and myeloproliferative

Question 4

haematopoeitic stem cells can differentiate into many cell lines, including BFU-E. what are they?

Answer 4

blast forming unit erythrocyte

Question 5

normally where do the steps of differentiation and maturation occur?

Answer 5

• normally first 4 steps of differentiation and mature occur within bone marrow
• neutrophil is formed in peripheral blood

Question 6

what happens in pathology?

Answer 6

this changes

cell becomes smaller –> cytoplasm clearer –> multi-lobed nucleus

Question 7

how is cell differentiation controlled?

Answer 7

via cytokines

• RBCs by EPO
• lymphoid cells by IL-2
• myeloid cells by G-CSF, M-CSF

Question 8

what does DNA damage in cancer do?

Answer 8

affect these regulating signals and lead to cancer proliferation

Question 9

define leukaemia, lymphoma/leukaemia, myeloma

Answer 9

leukaemia: malignant process in primary lymphoid organs
lymphoma: lymphatic cell tumours in tissue/blood
- myeloma: disease of bone marrow

Question 10

what can inc. WBC count be due to?

Answer 10

• inc. cell production (reactive or malignant)

- inc. cell survival

Question 11

name the reactive reasons

Answer 11

• inflammation

- infection

Question 12

name the malignant reasons

Answer 12

• leukaemia

- myeloproliferative

Question 13

what causes inc. cell survival?

Answer 13

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

Question 14

what can decreased WBC count be due to?

Answer 14

• dec. cell production

- dec. cell survival

Question 15

what causes dec. cell production?

Answer 15

• impaired BM function
• B12 or folate def
• BM failure: aplastic anaemia, post chemotherapy, metastatic cancer, haematological cancer

Question 16

what causes dec. cell survival?

Answer 16

immune breakdown

Question 17

what is the difference between the WBC in normal infection and cancer?

Answer 17

• normal infection: inc. WBC is reactive and mature cells released
• haematopoietic cancers, immature and mature cells released

Question 18

what are the 2 causes of inc. number of eosinophilia?

Answer 18

• reactive: infection/inflammation

- primary: malignant

Question 19

give an example of a malignany haematopoiesis?

Answer 19

CML

mutation occurs at GM-CFC

Question 20

how do you investigate a raised WCC?

Answer 20

• history
• exam
• Hb and platelet count
• blood film
• abnormalities in white ells or all cell lineages

Question 21

what do you think about if there are immature cells?

Answer 21

think about leukaemia

Question 22

what do you think about when there are immature AND mature cells?

Answer 22

chronic leukaemia if in presence of neutrophils and myelocytes

Question 23

how does acute leukaemia present?

Answer 23

low Hb and platelets

Question 24

where are neutrophilia found?

Answer 24

• present across BM, blood and tissues
• life span of 2-3 days in tissues and hours in PB
• 50% are marginalised (have stuck onto wall of a damaged vessel so aren’t in FBC)

Question 25

how long does it take neutrophilia to develop?

Answer 25

- minutes: demargination - hours: early release from BM i.e. sepsis - days: inc. production - i.e. in infection

Question 26

what are the causes of neutrophilia?

Answer 26

- infection - tissue inflammation - physical stress - adrenaline - corticosteroids - neoplasia - malignant neutrophilia

Question 27

what is the normal cause of neutrophilia?

Answer 27

- infection (local and systemic, acute bacterial, fungal, certain viral infections) - some infections do NOT produce neutrophila (e.g. Brucella, typhoid)

Question 28

what are the reactive causes of eosinophilia?

Answer 28

- parasitic infection - allergic disease - neoplasms - esp Hodgkin's - hypereosinophilic syndrome

Question 29

when is monocytosis seen? what are the causes?

Answer 29

``` - rare but seen in certain chronic infections and primary haematological disorders causes: - TB, brucella, typhoid - Viral - CMV, VZV - Sarcoidosis - CML ```

Question 30

when are mature lymphocytes seen?

Answer 30

either reactive to infection or primary disorder

Question 31

when are immature lymphocytes seen?

Answer 31

primary disorder only | not reactive

Question 32

what are the secondary/reactive causes of lymphocytosis?

Answer 32

polyclonal response to infection, chronic inflammation or underlying malignancy - infection - AI - neoplasia - sarcoidosis

Question 33

what are the causes of primary lymphocytosis?

Answer 33

monoclonal lymphoid proliferation e.g. CLL

Question 34

what is seen in mononucleosis?

Answer 34

- reactive looking lymphocyte - looks like immature lymphocyte seen in ALL - but these lymphocytes tend to have RBCs clump them - they are jagged and not self clumped

Question 35

what does a high WCC with reactive looking lymphocytes show?

Answer 35

glandular fever

Question 36

what causes glandular infection?

Answer 36

- caused by EBV infection of B lymphocytes via CD21 receptor - infected B cell proliferates and expresses EBV-associated antigens - causes a cytotxic T- cell response

Question 37

what are the causes of lymphocytosis in the elderly?

Answer 37

- more often going to be CLL or an AI disorder | - will see mature lymphocytes

Question 38

what is lymphocytosis in the elderly distinguishable by?

Answer 38

- morphology - immunophenotype - gene rearrangement

Question 39

when evaluating lymphocytosis, what is polyclonal expansion?

Answer 39

- involves more than 1 mother cell - so light chains express both kappa and lambda - indicative of a response to infection

Question 40

when evaluating lymphocytosis, what is monoclonal expansion?

Answer 40

all antibodies are from ONE mother cell | indicative of cancer

Question 41

what happens in primary monoclonal proliferation?

Answer 41

all daughter cells carry IDENTICAL TCR gene arrangement | isn't normal for infection, indicative of cancer