Abnormal white cell count

Question 1

Be aware of the ways to describe raised/reduced cell counts:

Answer 1

o Neutro-cytopenia/cytosis (reduced/raised). 
o Pancytopenia (all cell lines reduced

Question 2

where does haemopoiesis occur?

Answer 2

production of blood cells in marrow

Question 3

what can HSCs can differentiate into many cell lines?

Answer 3

BFU-E = Blast Forming Unit Erythrocyte.

Question 4

what is normal haemopoiesis?

Answer 4

(polyclonal healthy/ reactive)

• Normal marrow
• Reactive marrow

Question 5

what is malignant haemopoiesis?

Answer 5

(abnormal/clonal)

-Leukaemia (lymphoid,myeloid), myelodysplasia, myeloproliferative

Question 6

describe the process of differentiation and maturation of

Answer 6

Normally the first 4 steps of differentiation and maturation occur within the bone marrow and the neutrophil is formed in the peripheral blood but in pathology, this can change – cell becomes smaller -> cytoplasm clearer -> multi-lobed nucleus.

Question 7

what can be used for controlling cell differentiation?

Answer 7

§ Regulation is via cytokines:
o RBCs – EPO.
o Lymphoid cells – IL-2.
o Myeloid cells – G-CSF, M-CSF

Question 8

give examples of how DNA damage in cancer can affect the regulating signals and lead to cancer proliferation

Answer 8

o Leukaemia – malignant process in primary lymphoid organs.
o Lymphoma/Leukaemia – lymphatic cell tumours in tissue/blood.
o Myeloma – disease of bone marrow.

Question 9

what can increased WBC count be due to?

Answer 9

o Increased cell production – reactive or malignant. (reactive = infection/inflammation)
o Increased cell survival.

Question 10

what can decreased WBC count be due to?

Answer 10

o Decreased cell production – impaired BM function.

o Decreased cell survival.

Question 11

what is the difference between the WBCs released in normal infection and cancer?

Answer 11

In normal infection, the increased WBC is reactive and mature cells are released. In haematopoietic cancers, immature AND mature cells are released.

Question 12

give an example of increased WBC number

Answer 12

eosinophilia

Question 13

give an example of malignant haematopoiesis

Answer 13

CML – mutation occurs at GM-CFC.

Question 14

how can you investigate a raised WCC?

Answer 14

History, examination, Hb & platelet count, automated differential, examine the blood film, existence of abnormality in white cells or all cell lineages, WCC raised in one cell type or all cell linages.

Question 15

what conditions would you think of if you saw:
elevated immature cells
immature and mature cells

Answer 15

§ Immature cells – think about leukaemia.
§ Immature AND mature cells – think about chronic leukaemia if in the presence of neutrophils and myelocytes.
o Acute leukaemia will present with low Hb and platelets.

Question 16

what can abnormal WCC be caused by?

Answer 16

o Phagocytes – neutrophils, eosinophils and monocytes.

o Immune cells – lymphocytes (infection or CML).

Question 17

what is neutrophilia?

Answer 17

neutrophils are present across BM, blood, tissues with a life span of 2-3 days in tissue and hours in PB.

50% of neutrophils are marginated (have stuck onto the wall of a damaged vessel so aren’t in FBC).

Question 18

neutrophilia, time of onset and what does that mean?

• minutes
• hours
• days

Answer 18

o Minutes – demargination.
o Hours – early release from BM – i.e. sepsis.
o Days – increased production – i.e. x3 in infection

Question 19

what are the causes of neutrophilia?

Answer 19

Causes include – Infection, tissue inflammation, physical stress, adrenaline, corticosteroids, neoplasia, malignant neutrophilia (e.g. myeloproliferative disorders and CML).

Infection is the normal cause for neutrophilia – occurs in local and systemic infections, acute bacterial, fungal and certain viral infections.

Question 20

which viral infections do not produce a neutrophilia?

Answer 20

e.g. Brucella, typhoid and many viral infections.

Question 21

what are the potential causes of eosinophilia?

Answer 21

Eosinophilia – Causes:

§ Reactive:
o Parasitic infection.
o Allergic disease.
o Neoplasms – esp. Hodgkin’s, T-cell NHL.
§ Hodgkin’s disease will show up on x-ray with increased mediastinal mass and there will be increased IL-5 secretion (stimulates reactive).
§ You can also get a mutation in GM-CFC.
o Hypereosinophilic syndrome.

§ Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene) – very rare.

Question 22

what is monocytosis?

Answer 22

Monocytosis is an increase in the number of monocytes circulating in the blood.

Question 23

what are potential causes of monocytosis?

Answer 23

§ This is rare but seen in certain chronic infections and primary haematological disorders.

Causes: 
o TB, Brucella, typhoid. 
o Viral – CMV, VZV. 
o Sarcoidosis. 
o Chronic Myelomonocytic Leukaemia (CML).

Question 24

why do you get lymphocytosis?

-mature cells

Answer 24

either reactive to infection or primary disorder.

eg. CLL or autoimmune conditions

Question 25

why do you get lymphocytosis?

-immature cells

Answer 25

primary disorder only (not reactive).

eg. acute lymphoblastic leukaemia

Question 26

what are the causes of secondary/reactive lymphocytosis?

Answer 26

Secondary/reactive – polyclonal response to infection, chronic inflammation or underlying malignancy.
o Infection – e.g. EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes.
o Autoimmune.
o Neoplasia.
o Sarcoidosis.

Question 27

what are the primary causes of lymphocytosis?

Answer 27

Primary – monoclonal lymphoid proliferation – e.g. CLL

Question 28

what is monoculeosis and what does it show?

Answer 28

§ Shows a reactive-looking lymphocyte that looks like an immature lymphocyte seen in acute lymphoblastic leukaemia BUT these lymphocytes tend to have RBCs clump them and they are jagged and are not self-clumped.
§ High WCC with reactive-looking lymphocytes shows glandular fever.
§ Caused by EBV infection of B lymphocytes via the CD21 receptor.
o Infected B-cell proliferates and expresses EBV-associated antigens causing a cytotoxic T-cell response.
§ Common in the young.

Question 29

what is lymphocytosis in the elderly?

Answer 29

§ Lymphocytosis in the elderly is more often going to be Chronic Lymphocytic Leukaemia (CLL) or an autoimmune disorder.
§ You will see mature lymphocytes (and smear cells).
§ This is distinguishable by the – morphology, immunophenotype (what antigens are expressed on the surface) and gene rearrangement.

Question 30

what does polyclonal expansion mean?

Answer 30

– involve more than one mother cell and so the light chains express both kappa and lambda.
o This is indicative of a response to infection.

Question 31

what is monoclonal expansion?

Answer 31

Monoclonal expansion – all antibodies are from ONE mother cell and this is indicative of a cancer.

Question 32

evaluating lymphocytosis

Answer 32

§ Ig genes and TCR genes undergo recombination in antigen stimulated B or T cells.
§ With primary monoclonal proliferation, ALL daughter cells carry the IDENTICAL TCR gene arrangement which isn’t normal for infection – indicative of cancer.
§ Detected by southern blot analysis.