Abnormal White Blood Cell Count

Question 1

What is the lymphoid lineage?

Answer 1

Lymphoid cells are lymphocytes = T cells, B cells and NK cells

Question 2

Which cells come under the myeloid lineage?

Answer 2

Erythrocytes  
Neutrophils 
Basophils  
Eosinophils 
Monocytes 
Macrophages  
Megakaryocytes  
Dendritic Cells

Question 3

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

Answer 3

They become smaller and their cytoplasm becomes clearer.

Question 4

Which factors stimulate the following cell lines:

a. Lymphoid
b. Myeloid
c. Erythroid

Answer 4

a. Lymphoid - IL-2
b. Myeloid - G-CSF, M-CSF
c. Erythroid - Erythropoietin

Question 5

Define Leukaemia.

Answer 5

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 6

Define Lymphoma.

Answer 6

A group of blood cell tumours that develop in lymphatic tissues and normally involve lymphocytes.
Both lymphoma and leukaemia are increased proliferation of WBCs but if the disease is mainly in the lymphatic tissue then it is lymphoma.
If it is mainly in the blood it is leukaemia. (you can have e.g acute lymphoblastic leukaemia which is leukaemia with lymphocytes)

Question 7

Difference between myeloma, lymphoma and leukaemia

Answer 7

In leukemia, the cancerous cells are discovered circulating in
the blood and bone marrow, while in lymphoma, the cells tend to aggregate and form masses, or tumors, in lymphatic tissues. Myeloma is a tumor of the bone marrow, and
involves a specific subset of white blood cells (B cells) that produce a distinctive protein.

The difference between leukemia and lymphoma is NOT really in the cell type, lymphocytes can be involved in both. However, lymphoma specifically refers to the location of the cancer being in lymphatic tissues and this also is where lymphocytes are and hence it is cancer of lymphocytes, but not the ONLY cancer of lymphocytes

Question 8

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

Answer 8

Increased white blood cell production

Increased white blood cell survival

Question 9

Increased WBC count can be due to increased cell production or cell survival. Under increased WBC production, what 2 subcategories can cause this increased WBC production and hence increased WBC count?

Answer 9

Reactive – in response to infection or inflammation
Primary – malignant
slide 9 top left

Question 10

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 10

Reactive – only MATURE white blood cells present in peripheral blood to respond to infection

Primary – mature AND immature white blood cells present in peripheral blood as the cancer is causing BM to spit out immature cells as well

Question 11

Where does the mutation occur in chronic myeloid leukaemia?

Answer 11

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

Question 12

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

Answer 12

Acute leukaemia

Acute leukaemia develops quickly. Chronic develops over a longer period of time e.g you will experience symptoms for years before being diagnosed in a routine blood film

Question 13

What are the normal ranges of:

a. Hb
b. Platelets
c. WCC
d. Neutrophils
e. Lymphocytes
f. Monocytes
g. Eosinophils
h. Basophils

Answer 13

a. Hb 120-160 g/L
b. Platelets 150-400 x 10^9/L
c. WCC 4-11 x 10^9/L
d. Neutrophils 2.5-7.5 x 10^9/L
e. Lymphocytes 1.5-3.5 x 10^9/L
f. Monocytes 0.2-0.8 x 10^9/L
g. Eosinophils 0.04-0.44 x 10^9/L
h. Basophils 0.01-0.1 x 10^9/L

Question 14

What can cause an elevated lymphocyte count?

Answer 14

1. Reactive (Viral infections, autoimmune disorder)
2. Primary: Chronic lymphocytic leukaemia

slides 15, 33

Question 15

What is the lifespan of a neutrophil?

Answer 15

Hours in the peripheral blood

2-3 days in the tissues

Question 16

What is margination of neutrophils?

Answer 16

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

Question 17

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

Answer 17

Neutrophils in infection are granular (show toxic granulation)
Neutrophils in leukaemia do not have granules and do not look toxic.

Question 18

What else would be present in the peripheral blood film of someone with leukaemia that would not be present in someone with an infection?
slude 19

Answer 18

PRECURSOR CELLS Myelocytes and metamyelocytes – these precursors would not be found in the peripheral blood of someone responding to infection

https://en.wikipedia.org/wiki/Myelocyte#/media/File:Hematopoiesis_(human)_diagram_en.svg

Question 19

State some causes of neutrophilia.

Answer 19

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

Question 20

What types of infection cause neutrophilia?

Answer 20

Acute Bacterial , Fungal and
some viral infections

NB Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections do not cause raised neutrophil level

Generally: if the neutrophil count is low but there are other features of infection, then you can deduce that it’s a viral infection

Question 21

State some infections that characteristically do NOT produce neutrophilia.

Answer 21

Brucella
Typhoid
Many viral infections

Question 22

State some reactive causes of eosinophilia. (eosinophilia can be also caused be reactive causes or malignant/primary causes)

Answer 22

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

Question 23

State a malignant cause of eosinophilia.

Answer 23

Malignant chronic eosinophilic leukaemia (INCREDIBLY RARE)

Question 24

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

Answer 24

Increased mediastinal mass

Question 25

What can cause monocytosis?

Answer 25

RARE but it is seen in certain chronic infections and primary haematological disorders 
Reactive causes: 
TB, brucella, typhoid  
CMV, varicella zoster 
Sarcoidosis  

Primary:
Chronic myelomonocytic leukaemia (similar to MDS – myelodysplastic syndrome)

Question 26

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

Answer 26

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

slide 28

Question 27

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

Answer 27

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)

slide 28

Question 28

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

Answer 28

Secondary lymphocytosis = polyclonal expansion

Primary lymphocytosis = monoclonal expansion

Question 29

State some causes of reactive lymphocytosis.

Answer 29

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

Question 30

What do you see in the blood film of someone with infectious mononucleosis? (aka glandular fever)

What infection causes infectious mononucleosis?

Answer 30

ATYPICAL LYMPHOCYTES
slide 31,32

atypical lymphocyte:

• larger than normal due to more cytoplasm
• have nucleoli in nuclei
• cytoplasm extends to space between the surrounding RBCs see pic on slide 31

Caused by EBV infection most of the time

Question 31

What is glandular fever caused by?

Answer 31

1. Epstein-Barr virus infection of the B-lymphocytes via the CD21 receptor
2. Infected B-cells proliferate and express EBV associated antigen
3. Cytotoxic T-lymphocyte response towards infected B cells
4. Eventually, acute infection is resolved, leading to life-long sub-clinical infection

Question 32

What is the usual cause of lymphocytosis in elderly people?

Answer 32

Chronic lymphocytic leukaemia (CLL)

Question 33

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

Answer 33

In reactive lymphocytosis, there will be polyclonal expansion of the lymphocytes meaning that the light chains of the antibodies and BCR produced by B cells will have a 50:50 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 (either kappa or lambda)

Question 34

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

Answer 34

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

Question 35

define reactive

Answer 35

Of antibodies and some allergic and immune illnesses, triggered by an antigen. (foreign or self antigen)