6 - abnormal white blood cell count

Question 1

Define polcythaemia

Answer 1

increased conc of haemoglobin

Question 2

Define thrombocytopenia

Answer 2

deficiency of platelets in the blood

Question 3

Define thrombocytosis

Answer 3

presence of high platelet (thrombocyte) counts in the blood
can be either primary (also termed essential thrombocythemia, and caused by a myeloproliferative disease) or secondary (also termed reactive).

Question 4

Define neutropenia

Answer 4

an abnormally low level of neutrophils

Question 5

Define neutrophilia

Answer 5

(leukocytosis of neutrophils)

a high number of neutrophil granulocytes in the blood.

Question 6

What is the term used to describe a reduction in the number of white cells in the blood?

Answer 6

leucopenia

Question 7

What is the term used to describe an increase in the number of white cells in the blood?

Answer 7

leukocytosis

Question 8

What is the term used to describe reduction of all cell lines?
(deficiency of all three cellular components of the blood (red cells, white cells, and platelets))

Answer 8

pancytopenia

Question 9

What is the difference between normal and malignant haematopoiesis?

Answer 9

normal - occurs in normal and in reactive bone marrow

malignant - occurs in leukaemia, myelodysplasia and myeloproliferative

Question 10

Define lymphoid lineage

Answer 10

relating to or denoting the tissue responsible for producing lymphocytes (T cells, B cells and NK cells)

Question 11

Which cells come under the myeloid lineage?

Answer 11

o	Monocytes 
o	Macrophages 
o	Neutrophils 
o	Basophils 
o	Eosinophils 
o	Erythrocytes
o	Dendritic Cells 
o	Megakaryocytess

Question 12

Describe how the appearance of white cells changes as they develop.

Answer 12

They become smaller and their cytoplasm becomes clearer. A multi lobed nucleus develops

Question 13

Where do the stages of differentiation and maturation of a neutrophil occur?

Answer 13

normally, first 4 stages occur in bone marrow and only the fully differentiated neutrophils should be found in the blood

Question 14

How is cell differentiation controlled?

Name the cytokines that stimulate the different cell lineages

Answer 14

via cytokines
o Myeloid = G-CSF and M-CSF
o Lymphoid = IL2
o Erythroid = Erythropoietin

Question 15

Define Leukaemia.

Answer 15

malignant process in primary lymphoid organs
A malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. This leads to suppression of the production of other blood cells such as erythrocytes, granulocytes and platelets.

Question 16

Define Lymphoma.

Answer 16

lymphatic cell tumours in tissue/blood
A group of blood cell tumours that develop from lymphatic cells. If the disease is mainly in the lymphatic tissue then it is lymphoma, if it is mainly in the blood it is leukaemia.

Question 17

Define Myeloma.

Answer 17

disease of bone marrow
A malignant disease of the bone marrow characterised by two or more of the following criteria:
• The presence of an excess of abnormal plasma cells in the bone marrow
• Typical lytic deposits in the bones on X-ray, giving the appearance of holes
• The presence in the serum of abnormal gammaglobulin, usually IgG

Question 18

Broadly speaking, what are the two mechanisms by which white blood cell count can increase?

Answer 18

Increased white blood cell production - reactive or malignant
Increased white blood cell survival

Question 19

Broadly speaking, what can cause an decrease in white blood cell count?

Answer 19

Decreased white blood cell production - impaired bone marrow function
Decreased white blood cell survival

Question 20

What two broad categories of diseases can cause an increase in white blood cell count?

Answer 20

Reactive – in response to infection or inflammation

Primary – malignant

Question 21

What is the difference in the type of white blood cell seen in the peripheral blood of someone with an infection/inflammation (reactive) and someone with a malignancy (primary)?

Answer 21

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

Question 22

Where does the mutation occur in chronic myeloid leukaemia?

Answer 22

GM-CFC phase (granulocyte-monocyte colony forming cell)

Question 23

Is there are immature cells, what can you suspect?

Answer 23

leukaemia

Question 24

If there are only immature cells in the blood film with low haemoglobin and low platelets, what would you suspect?

Answer 24

Acute leukaemia

Question 25

If there are mature and immature cells present, what can you begin to suspect?

Answer 25

chronic leukaemia | but only if in the presence of neutrophils and myelocytes

Question 26

What can cause an elevated lymphocyte count?

Answer 26

Viral infections | Chronic lymphocytic leukaemia

Question 27

What is the lifespan of a neutrophil?

Answer 27

Hours in the peripheral blood | 2-3 days in the tissues

Question 28

What is margination of neutrophils?

Answer 28

Around 50% of neutrophils in the circulation have marginated meaning that they have stuck to the wall of a damaged vessel (this means that they are NOT counted in the full blood count)

Question 29

Describe the differences in the appearance of neutrophils in infection compared to leukaemia.

Answer 29

Neutrophils in infection are granular (show toxic granulation) Neutrophils in leukaemia do not have granules and do not look toxic. NOTE: myelocytes (precursors) may also be present in someone with leukaemia

Question 30

State some causes of neutrophilia.

Answer 30

``` Infection Inflammation Physical stress Adrenaline Corticosteroids Underlying neoplasia Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia) ```

Question 31

State some infections that characteristically do NOT produce neutrophilia.

Answer 31

Brucella Typhoid Many viral infections

Question 32

State some reactive causes of eosinophilia.

Answer 32

Parasitic infection Allergic diseases e.g. asthma Neoplasms e.g. Hodgkin’s and Non-Hodgkin’s Hypereosinophilic syndrome

Question 33

State a malignant cause of eosinophilia.

Answer 33

Malignant chronic eosinophilic leukaemia (INCREDIBLY RARE)

Question 34

What would you see in the chest X-ray of someone with Hodgkin’s lymphoma?

Answer 34

Increased mediastinal mass

Question 35

What can cause monocytosis?

Answer 35

RARE but it is seen in certain chronic infections and primary haematological disorders TB, brucella, typhoid CMV, varicella zoster Sarcoidosis Chronic myelomonocytic leukaemia (MDS – myelodysplastic syndrome)

Question 36

Describe the appearance of chronic lymphocytic leukaemia on a blood film.

Answer 36

The lymphocytes have a typical appearance – big nucleus + little cytoplasm They are mature lymphocytes This appearance can also be present in autoimmune and inflammatory conditions

Question 37

Describe the appearance of acute lymphoblastic leukaemia on a blood film.

Answer 37

There are immature lymphoblasts They are much larger than the mature lymphocytes Within the large nucleus you can see the nucleolus (showing that the cell is immature)

Question 38

Describe the difference in the expansion of lymphocytes in secondary (reactive) lymphocytosis compared to primary lymphocytosis.

Answer 38

Secondary lymphocytosis = polyclonal expansion | Primary lymphocytosis = monoclonal expansion

Question 39

State some causes of reactive/secondary lymphocytosis.

Answer 39

Infection (e.g. EBV, toxoplasma, infectious hepatitis, rubella, herpes infections) Autoimmune disorders Neoplasia Sarcoidosis

Question 40

What do you see in the blood film of someone with mononucleosis syndrome?

Answer 40

Atypical lymphocytes They look similar to immature lymphocytes but they aren’t very round as its cytoplasm extends between surrounding cells The nucleus of the cell lacks nucleoli This is typical of glandular fever So high WCC and reactive-looking lymphocytes can indicate reactive, infection-induced lymphocytosis

Question 41

What is glandular fever caused by?

Answer 41

Epstein-Barr virus infection of the B-lymphocytes via the CD21 receptor Infected B-cells proliferate and express EBV associated antigen There is a cytotoxic T-lymphocyte response

Question 42

What is the usual cause of lymphocytosis in elderly people?

Answer 42

Chronic lymphocytic leukaemia (CLL) | or autoimmune disorders

Question 43

Explain how light chain restriction can be used to distinguish between causes of lymphocytosis.

Answer 43

In reactive lymphocytosis, there will be polyclonal expansion of the lymphocytes meaning that the light chains of the antigens produced will have equal kappa and lambda divide. In primary lymphocytosis, there will be a monoclonal expansion so you will get kappa or lambda restriction meaning that all the light chains are of one type

Question 44

Normally, B and T cells will undergo gene rearrangement in the TCR and Ig genes in a process called affinity maturation. How is this different in primary monoclonal proliferation of B and T cells?

Answer 44

With primary monoclonal proliferation, all the daughter cells carry identical copies of Ig genes or TCR genes