Abnormal White Cell Counts Flashcards
Where does haematopoiesis occur?
bone marrow
When does normal and malignant haematopoiesis occur?
normal - normal and reactive situations
malignant - leukaemia, myelodysplasia and myeloproliferation
What happens in normal and abnormal maturation and differentiation?
normal
- first 4 steps of differentiation and maturation occurs in the marrow
- neutrophil formed in peripheral blood
- myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> neutrophil
pathology
- cells smaller -> cytoplasm clearer -> multi-lobed nucleus
How is cell differentiation controlled?
regulated via cytokines:
- RBCs – EPO
- Lymphoid cells – IL-2
- Myeloid cells – G-CSF, M-CSF
What can cause an abnormal WBC count?
Increased WBC count can be due to:
- Increased cell production – reactive (infection/inflammation) or malignant (leukaemia/myeloproliferative)
- Increased cell survival (e.g failure of apoptosis)
Decreased WBC count can be due to:
- Decreased cell production (impaired BM function)
- Decreased cell survival (immune breakdown)
- In normal infection, the increased WBC is reactive and mature cells are released. In haematopoietic cancers, immature AND mature cells are released.
What are some causes of eosiniphilia?
(raised eosinophil count)
reactive - normal haematopoiesis stimulated by:
- inflammations
- infection
- increased cytokine production (e.g distant tumour)
- Parasitic infection.
- Allergic disease
- Hypereosinophilic syndrome
- Neoplasms – esp Hodgkin’s, T-cell NHL
> Hodgkin’s disease will show up on x-ray with increased mediastinal mass and there will be increased IL-5 secretion (stimulates reactive)
> You can also get a mutation in GM-CFC
malignant (autonomous cell growth)
- cancers of haematopoietic cells
- leukaemia (myeloid/lymphoid, chronic/acute)
- myeloproliferative disorders
- Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene) – very rare.
What happens in CML?
mutation at GM-CFC (after HSC)
chr 9 and 22 -> philadelphia chr -> BCR-ABL
increased WBC - mainly neutrophils, eosinophils and basophils (granulocytes)
How do we investigate a raised WBC count?
- History and examination
- Hb & platelet count
- automated differential
- examine the blood film
- existence of abnormality in white cells or all cell lineages?
- WCC raised in one cell type or all cell linages?
- mature or immature or both cells?
> Immature cells – think about leukaemia.
> Immature AND mature cells – think about chronic leukaemia if in the presence of neutrophils and myelocytes.
*Acute leukaemia will present with low Hb and platelets.
What can cause neutrophilia?
Present across BM, blood and tissues with a life span of 2-3 days in tissue and hours in PB.
50% of neutrophils are marginated (have stuck onto the wall of a damaged vessel so aren’t in FBC).
Neutrophilia can develop in:
- Minutes – demargination.
- Hours – early release from BM – i.e. sepsis.
- Days – increased production – i.e. x3 in infection.
Causes include –
- Infection
- tissue inflammation
- physical stress
- adrenaline
- corticosteroids
- neoplasia
- malignant neutrophilia (e.g. myeloproliferative disorders and CML).
*Infection is the normal cause for neutrophilia – occurs in local and systemic infections, acute bacterial, fungal and certain viral infections.
**SOME infections do NOT produce a neutrophilia – e.g. Brucella, typhoid and many viral infections.
What are the differences in the blood films (neutrophils) of someone with an infection and someone with leukaemia?
infection
- toxic granulation
- vacuoles
leukamia
- neutrophilia and precursor cells (myelocytes)
What are some causes of monocytosis?
This is rare but seen in certain chronic infections and primary haematological disorders.
Causes:
- TB, Brucella, typhoid
- Viral – CMV, VZV
- Sarcoidosis
- Chronic Myelomonocytic Leukaemia (CML)
What are some causes of lymphocytosis?
- Mature cells – either reactive to infection or primary disorder
- Immature cells – primary disorder only (not reactive)
Causes;
Secondary/reactive – polyclonal response to infection, chronic inflammation or underlying malignancy.
- Infection – e.g. EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes
- Autoimmune
- Neoplasia
- Sarcoidosis
Primary – monoclonal lymphoid proliferation – e.g. CLL
What does acute lymphoblastic leukaemia look like on a blood film?
immature lymphoblasts much larger than other cells
visible nucleolus shows immaturity
What is mononucleosis?
Shows a reactive-looking lymphocyte that looks like an immature lymphocyte seen in acute lymphoblastic leukaemia BUT these lymphocytes tend to have RBCs clump them and they are jagged and are not self-clumped
High WCC with reactive-looking lymphocytes shows glandular fever
Caused by EBV infection of B lymphocytes via the CD21 receptor.
- Infected B-cell proliferates and expresses EBV-associated antigens causing a cytotoxic T-cell response
Common in the young
What is lymphocytosis in the elderly more likely to be?
CLL or autoimmune disorder
you’ll see mature lymphocytes (and smear cells)
This is distinguishable by the – morphology, immunophenotype (what antigens are expressed on the surface) and gene rearrangement
