Abnormal white cell counts 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
What are the cell derivatives for lymphocytes and phagocytes? Describe how the appearance of white cells changes as they differentiate and mature
Phagocytes:
myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> granulocytes/monocytes (in peripheral blood)
Lymphocytes:
Lymphoblast -> T/B/NK cell (in peripheral blood)
They become smaller and their cytoplasm becomes clearer.
Which factors stimulate the Erythroid, Myeloid and Lymphoid cell lines? What directs their differentiation and proliferation?
Erythroid - Erythropoietin
Lymphoid - IL-2
Myeloid - G-CSF, M-CSF
DNA directed differentiation and proliferation
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 from lymphatic cells:
- If the disease is mainly in the lymphatic tissue then it is lymphoma (i.e. cancer of the lymph nodes).
- If it is mainly in the blood it is leukaemia.
Define Myeloma. What is it characterised by?
A malignant tumour 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 gamma globulin, usually IgG
Broadly speaking, what two factors can cause an increase in white blood cell count?
Increased white blood cell production
Increased white blood cell survival
What two broad categories of diseases would cause an increase in white blood cell production?
- Reactive - in response to infection or inflammation
2. Malignant (primary) - e.g. Leukemia, myeloproliferative disorders
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
Primary – mature AND immature white blood cells present
What are myelodysplastic syndromes?
Group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells
Where does the mutation occur in chronic myeloid leukaemia? What is the result?
GM-CFC phase (granulocyte-monocyte colony forming cell) => increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood.
If there are only immature cells in the blood film with low haemoglobin and low platelets, what would you suspect?
Acute leukaemia
What are the normal ranges of:
a. Hb
b. Platelets
c. WCC
d. Neutrophils
e. Lymphocytes
f. Monocytes
g. Eosinophils
h. Basophils
Hb; 120-160 g/L Platelets; 150-400 x 10^9/L WCC; 4-11 x 10^9/L Neutrophils; 2.5-7.5 x 10^9/L Lymphocytes; 1.5-3.5 x 10^9/L Monocytes; 0.2-0.8 x 10^9/L Eosinophils; 0.04-0.44 x 10^9/L Basophils; 0.01-0.1 x 10^9/L
What is the lifespan of a neutrophil?
Hours in the peripheral blood
2-3 days in the tissues
Note: also present in BM
What is the margination percentage of neutrophils? What does this mean for a FBC?
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
State some causes of neutrophilia.
Infection Inflammation Physical stress Adrenaline Corticosteroids Underlying neoplasia
Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia)
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 blood film of someone with leukaemia that would not be present in someone with an infection?
Myelocytes and metamyelocytes (precursor cells) – these precursors would not be found in the peripheral blood of someone responding to infection
What types of infection cause neutrophilia?
- Bacterial
- Fungal
- Certain viral infections
Generally, if the neutrophil count is low but there are other features of infection, then you can deduce that it’s a bacterial/viral/fungal infection included neutrophilia
State some infections that characteristically do NOT produce neutrophilia.
Brucella
Typhoid
Many viral infections
State some reactive causes of eosinophilia.
- 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:
- TB, brucella, typhoid
- CMV, varicella zoster
- Sarcoidosis
- Chronic myelomonocytic leukaemia (myelodysplastic syndrome)
Name the type lymphocytosis characterised by increased mature cells. Describe the appearance on the blood film.. What can this appearance also be explained by?
Chronic lymphocytic leukemia
The lymphocytes have a typical appearance – big nucleus + little cytoplasm (mature)
This appearance can also be present in autoimmune and inflammatory conditions
Name the type lymphocytosis characterised by increased immature cells. Describe the appearance on the blood film.
Acute lymphoblastic leukaemia
They are much larger than the mature lymphocytes and you can see the nucleolus (showing that the cell is immature)
State some causes of reactive lymphocytosis.
- Infection (e.g. EBV, toxoplasma, infectious hepatitis, rubella, herpes infections)
- Autoimmune disorders
- Neoplasia
- Sarcoidosis
Describe the difference in the expansion of lymphocytes in secondary (reactive) lymphocytosis compared to primary lymphocytosis.
Secondary lymphocytosis = polyclonal expansion
Primary lymphocytosis = monoclonal expansion
What do you see in the blood film of someone with mononucleosis syndrome (associated with reactive/infection induced lymphocytosis)? What is it typical of?
Atypical lymphocytes
- They look similar to immature lymphocytes but they aren’t very round and its cytoplasm extends between surrounding cells
- The nucleus of the cell lacks nucleoli
This is typical of glandular fever
What is glandular fever caused by? How does it progress?
- 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
- 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, polyclonal expansion of the lymphocytes => light chains of the antigens produced by B cells will kappa and lambda
In primary lymphocytosis, monoclonal expansion => only kappa or only lambda type light chains
Normally, B and T cells will undergo gene rearrangement in the T cell receptor and immunoglobulin genes in a process called affinity maturation. 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
