Abnormal White Cell count Flashcards
What does neutro-cytopenia/cytosis mean?
- reduced/raised cell counts
what does pancytopenia mean?
all cell lines reduced
where does normal haemopoiesis occur? when is it is normal/malignant?
- occurs in bone marrow
- normal haemopoiesis can occur in normal situations and in reactive situations
- malignant happens in leukaemia, myelodysplasia and myeloproliferative
haematopoeitic stem cells can differentiate into many cell lines, including BFU-E. what are they?
blast forming unit erythrocyte
normally where do the steps of differentiation and maturation occur?
- normally first 4 steps of differentiation and mature occur within bone marrow
- neutrophil is formed in peripheral blood
what happens in pathology?
this changes
cell becomes smaller –> cytoplasm clearer –> multi-lobed nucleus
how is cell differentiation controlled?
via cytokines
- RBCs by EPO
- lymphoid cells by IL-2
- myeloid cells by G-CSF, M-CSF
what does DNA damage in cancer do?
affect these regulating signals and lead to cancer proliferation
define leukaemia, lymphoma/leukaemia, myeloma
leukaemia: malignant process in primary lymphoid organs
lymphoma: lymphatic cell tumours in tissue/blood
- myeloma: disease of bone marrow
what can inc. WBC count be due to?
- inc. cell production (reactive or malignant)
- inc. cell survival
name the reactive reasons
- inflammation
- infection
name the malignant reasons
- leukaemia
- myeloproliferative
what causes inc. cell survival?
failure of apoptosis (e.g. acquired cancer causing mutations in some lymphomas)
what can decreased WBC count be due to?
- dec. cell production
- dec. cell survival
what causes dec. cell production?
- impaired BM function
- B12 or folate def
- BM failure: aplastic anaemia, post chemotherapy, metastatic cancer, haematological cancer
what causes dec. cell survival?
immune breakdown
what is the difference between the WBC in normal infection and cancer?
- normal infection: inc. WBC is reactive and mature cells released
- haematopoietic cancers, immature and mature cells released
what are the 2 causes of inc. number of eosinophilia?
- reactive: infection/inflammation
- primary: malignant
give an example of a malignany haematopoiesis?
CML
mutation occurs at GM-CFC
how do you investigate a raised WCC?
- history
- exam
- Hb and platelet count
- blood film
- abnormalities in white ells or all cell lineages
what do you think about if there are immature cells?
think about leukaemia
what do you think about when there are immature AND mature cells?
chronic leukaemia if in presence of neutrophils and myelocytes
how does acute leukaemia present?
low Hb and platelets
where are neutrophilia found?
- present across BM, blood and tissues
- life span of 2-3 days in tissues and hours in PB
- 50% are marginalised (have stuck onto wall of a damaged vessel so aren’t in FBC)
how long does it take neutrophilia to develop?
- minutes: demargination
- hours: early release from BM i.e. sepsis
- days: inc. production - i.e. in infection
what are the causes of neutrophilia?
- infection
- tissue inflammation
- physical stress
- adrenaline
- corticosteroids
- neoplasia
- malignant neutrophilia
what is the normal cause of neutrophilia?
- infection (local and systemic, acute bacterial, fungal, certain viral infections)
- some infections do NOT produce neutrophila (e.g. Brucella, typhoid)
what are the reactive causes of eosinophilia?
- parasitic infection
- allergic disease
- neoplasms - esp Hodgkin’s
- hypereosinophilic syndrome
when is monocytosis seen? what are the causes?
- rare but seen in certain chronic infections and primary haematological disorders causes: - TB, brucella, typhoid - Viral - CMV, VZV - Sarcoidosis - CML
when are mature lymphocytes seen?
either reactive to infection or primary disorder
when are immature lymphocytes seen?
primary disorder only
not reactive
what are the secondary/reactive causes of lymphocytosis?
polyclonal response to infection, chronic inflammation or underlying malignancy
- infection
- AI
- neoplasia
- sarcoidosis
what are the causes of primary lymphocytosis?
monoclonal lymphoid proliferation e.g. CLL
what is seen in mononucleosis?
- reactive looking lymphocyte
- looks like immature lymphocyte seen in ALL
- but these lymphocytes tend to have RBCs clump them
- they are jagged and not self clumped
what does a high WCC with reactive looking lymphocytes show?
glandular fever
what causes glandular infection?
- caused by EBV infection of B lymphocytes via CD21 receptor
- infected B cell proliferates and expresses EBV-associated antigens
- causes a cytotxic T- cell response
what are the causes of lymphocytosis in the elderly?
- more often going to be CLL or an AI disorder
- will see mature lymphocytes
what is lymphocytosis in the elderly distinguishable by?
- morphology
- immunophenotype
- gene rearrangement
when evaluating lymphocytosis, what is polyclonal expansion?
- involves more than 1 mother cell
- so light chains express both kappa and lambda
- indicative of a response to infection
when evaluating lymphocytosis, what is monoclonal expansion?
all antibodies are from ONE mother cell
indicative of cancer
what happens in primary monoclonal proliferation?
all daughter cells carry IDENTICAL TCR gene arrangement
isn’t normal for infection, indicative of cancer