Abnormal White Blood Cell Count Flashcards
What is the lymphoid lineage?
Lymphoid cells are lymphocytes = T cells, B cells and NK cells
Which cells come under the myeloid lineage?
Erythrocytes Neutrophils Basophils Eosinophils Monocytes Macrophages Megakaryocytes Dendritic Cells
Describe how the appearance of white cells changes as they develop.
They become smaller and their cytoplasm becomes clearer.
Which factors stimulate the following cell lines:
a. Lymphoid
b. Myeloid
c. Erythroid
a. Lymphoid - IL-2
b. Myeloid - G-CSF, M-CSF
c. Erythroid - Erythropoietin
Define Leukaemia.
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.
Define Lymphoma.
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)
Difference between myeloma, lymphoma and leukaemia
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
Broadly speaking, what can cause an increase in white blood cell count?
Increased white blood cell production
Increased white blood cell survival
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?
Reactive – in response to infection or inflammation
Primary – malignant
slide 9 top left
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)?
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
Where does the mutation occur in chronic myeloid leukaemia?
GM-CFC phase (granulocyte-monocyte colony forming cell)
If there are only immature cells in the blood film with low haemoglobin and low platelets, what would you suspect?
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
What are the normal ranges of:
a. Hb
b. Platelets
c. WCC
d. Neutrophils
e. Lymphocytes
f. Monocytes
g. Eosinophils
h. Basophils
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
What can cause an elevated lymphocyte count?
- Reactive (Viral infections, autoimmune disorder)
- Primary: Chronic lymphocytic leukaemia
slides 15, 33
What is the lifespan of a neutrophil?
Hours in the peripheral blood
2-3 days in the tissues
What is margination of neutrophils?
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)
Describe the differences in the appearance of neutrophils in infection compared to leukaemia.
Neutrophils in infection are granular (show toxic granulation)
Neutrophils in leukaemia do not have granules and do not look toxic.
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
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
State some causes of neutrophilia.
Infection Inflammation Physical stress Adrenaline Corticosteroids Underlying neoplasia Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia)
What types of infection cause neutrophilia?
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
State some infections that characteristically do NOT produce neutrophilia.
Brucella
Typhoid
Many viral infections
State some reactive causes of eosinophilia. (eosinophilia can be also caused be reactive causes or malignant/primary causes)
- Parasitic infection
- Allergic diseases e.g. asthma
- Neoplasms e.g. Hodgkin’s and Non-Hodgkin’s
- Hypereosinophilic syndrome
State a malignant cause of eosinophilia.
Malignant chronic eosinophilic leukaemia (INCREDIBLY RARE)
What would you see in the chest X-ray of someone with Hodgkin’s lymphoma?
Increased mediastinal mass
What can cause monocytosis?
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)
Describe the appearance of chronic lymphocytic leukaemia on a blood film.
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
Describe the appearance of acute lymphoblastic leukaemia on a blood film.
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
Describe the difference in the expansion of lymphocytes in secondary (reactive) lymphocytosis compared to primary lymphocytosis.
Secondary lymphocytosis = polyclonal expansion
Primary lymphocytosis = monoclonal expansion
State some causes of reactive lymphocytosis.
Infection (e.g. EBV, toxoplasma, infectious hepatitis, rubella, herpes infections)
Autoimmune disorders
Neoplasia
Sarcoidosis
What do you see in the blood film of someone with infectious mononucleosis? (aka glandular fever)
What infection causes infectious mononucleosis?
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
What is glandular fever caused by?
- Epstein-Barr virus infection of the B-lymphocytes via the CD21 receptor
- Infected B-cells proliferate and express EBV associated antigen
- Cytotoxic T-lymphocyte response towards infected B cells
- Eventually, acute infection is resolved, leading to life-long sub-clinical infection
What is the usual cause of lymphocytosis in elderly people?
Chronic lymphocytic leukaemia (CLL)
Explain how light chain restriction can be used to distinguish between causes of lymphocytosis.
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)
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?
With primary monoclonal proliferation, all the daughter cells carry identical copies of Ig genes or TCR genes
define reactive
Of antibodies and some allergic and immune illnesses, triggered by an antigen. (foreign or self antigen)
