Abnormal White Blood Cell Count Flashcards
What is the lymphoid lineage?
Lymphoid cells are lymphocytes = T cells, B cells + NK cells
Which 7 cells come under the myeloid lineage?
Erythrocytes Neutrophils Basophils Eosinophils Monocytes Megakaryocytes Dendritic Cells
Describe how the appearance of white cells changes as they develop.
They become smaller + their cytoplasm becomes clearer.
Which factors stimulate the following cell lines:
a. Lymphoid
b. Myeloid
c. Erythroid
Lymphoid: IL-2
Myeloid: G-CSF, M-CSF
Erythroid: Erythropoietin
Define Leukaemia.
A malignant progressive disease in which BM + other blood-forming organs produce increased numbers of immature or abnormal leukocytes.
Leads to suppression of production of other blood cells (erythrocytes + 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.
If mainly in the blood it is leukaemia.
Define Myeloma.
A malignant disease of the BM characterised by >2 of the following criteria:
Excess of abnormal plasma cells in the BM
Typical lytic deposits in the bones on X-ray, giving the appearance of holes
Presence in the serum of abnormal gammaglobulin, usually IgG
Broadly speaking, what can cause an increase in white blood cell count?
Increased white blood cell production
Increased white blood cell survival
What 2 types of disease cause increased white cell production resulting in increased white blood cell count?
Reactive: Infection, inflammation
Malignant: Leukaemia, Myeloproliferative disease
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?
Reactive: only mature WBC’s
Malignant: mature + immature white blood cells present
Where does the mutation occur in chronic myeloid leukaemia?
GM-CFC phase
If there are only immature cells in the blood film with low Hb and low platelets, what would you suspect?
Acute leukaemia
What can cause an elevated lymphocyte count?
Viral infections
Chronic lymphocytic leukaemia
What is the lifespan of a neutrophil?
Hours in peripheral blood
2-3 days in the tissues
What is margination of neutrophils?
~50% of neutrophils in the circulation have marginated meaning that they have stuck to the wall of a damaged vessel (NOT counted in FBC)
Describe the differences in the appearance of neutrophils in infection compared to leukaemia.
Infection: show toxic granulation + vacuoles
Leukaemia: no granules + don’t look toxic. Neutrophils at different stages of maturation, presence of band cells
What would be present in the blood film of someone with leukaemia that would not be present in someone with an infection?
Myeloid precursors
Clonage results in abnormality of 1 particular type of cell e.g. lymphocytes
State 5 causes of neutrophilia.
Infection
Inflammation
Physical stress, adrenaline, corticosteroids
Underlying neoplasia
Malignant neutrophilia: myeloproliferative disorders + CML
What types of infection cause neutrophilia?
Bacterial
Fungal
Certain viral infections
State 3 infections that characteristically do NOT produce neutrophilia.
Brucella
Typhoid
Many viral infections
State 4 reactive causes of eosinophilia.
Parasitic infestation
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
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 + primary haematological disorders TB, brucella, typhoid Viral: CMV, varicella zoster Sarcoidosis Chronic myelomonocytic leukaemia (MDS)
Describe the appearance of chronic lymphocytic leukaemia on a blood film.
Lymphocytes have a big nucleus + little cytoplasm
Mature lymphocytes
This appearance can be present in AI + inflammatory conditions
Describe the appearance of acute lymphocytic leukaemia on a blood film.
Immature lymphoblasts
Much larger than the mature lymphocytes
Visible nucleolus
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 4 causes of reactive lymphocytosis.
Infection (e.g. EBV, toxoplasma, infectious hepatitis, rubella, herpes)
Autoimmune disorders
Neoplasia
Sarcoidosis
What do you see in the blood film of someone with mononucleosis syndrome?
Atypical lymphocytes: similar to immature lymphocytes but not very round + its cytoplasm extends between surrounding cells
Nucleus lacks nucleoli
Typical of glandular fever
So if there is a high WCC + you find these reactive-looking lymphocytes you can suspect that it is a reactive, infection-induced lymphocytosis
What is glandular fever caused by?
Epstein-Barr virus infection of the B-lymphocytes via the CD21 receptor
Infected B-cells proliferate + express EBV associated antigens
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.
Reactive: polyclonal expansion- light chains of antibodies produced by B cells + B cell receptors will have a 50:50 kappa + lambda divide
Malignant: monoclonal expansion- kappa or lambda restriction meaning all the light chains are of 1 type
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?
With primary monoclonal proliferation, all daughter cells carry identical copies of Ig genes or TCR genes
What is haemopoieisis?
production of blood cells in BM
What is the difference between normal and malignant haemopoiesis?
Normal: Polycloncal healthy or reactive
Malignant: Abnormal, clonal e.g. Leukaemia,
Where are immature leukocytes found?
Healthy: Only in BM
When cancer patients are given GCSF + in sepsis: Peripheral blood (Leukoerythroblastic picture)
What causes an increased cell survival resulting in increased white blood cell count?
Failure of apoptosis
e.g. acquired cancer causing mutations in some lymphomas
What causes decreased white cell production resulting in decreased white blood cell count?
Impaired BM function (Vit. B12 or Folate deficiency) BM failure (Aplastic anaemia, post chemo, metastatic cancer)
What causes decreased white cell survival resulting in decreased white blood cell count?
Autoimmune breakdown
Name a common cause of leukocytosis due to lifestyle choices
Smoking
Common to see a reactive neutrophilia or lymphocytosis
What would you suspect if a blood film contained neutrophils, myelocytes and basophils?
Chronic myeloid leukaemia
List 3 reactive causes that stimulate normal (reactive) haemopoiesis
Inflammation
Infection
Increased cytokine production e.g. distant tumour
List 3 malignant causes that stimulate abnormal (malignant) haemopoiesis
Cancers of haemopoietic cells
Leukaemia
Myeloproliferative disorders
How does morphology differ in reactive and malignant eosinophilia?
Reactive: No changes
Malignant: Eosinophils look abnormal, leukoerythroblastic picture in peripheral blood
