Abnormal Chite Cell Count Flashcards
1
Q
Pancytopenia
A
all lineages reduced
2
Q
When might myeloid precursors be found in the blood?
A
- in sepsis
- in patient that are given G-CSF
3
Q
How is the production of RBCs, lymphoid and myeloid cells controlled?
A
RBC - erythropoietin
lymphoid - IL2
myeloid: G-CSF or M-CSF
4
Q
Eosinophilia
A
- very common in general population
-
5
Q
Normal / reactive eosinophilia
A
- stimulated by: inflammation, infection (e.g. parasitic), increased cytokine production (distant tumor, paraneoplastic syndrome, haematopoietic to non-haematopoietic)
6
Q
How does leukaemia usually present with regards to cell amounts?
A
- leukocytosis
- anemia and thrombopenia
7
Q
How does leukaemia usually present with regards to cell amounts?
A
- leukocytosis
- anemia and thrombopenia
8
Q
Causes of Neutrophilia
A
- Infection
- Tissue inflammation (e.g.colitis, pancreatitis)
- Physical stress, adrenaline, corticosteroids
- underlying neoplasia
- Malignant neutrophilia: myeloproliferative disorders or
CML
9
Q
Neutrophilia in infections
A
- Localised and systemic infections
- acute bacterial, fungal, certain viral infections
- Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections
10
Q
Causes of reactive eosinophilia
A
- Parasitic infestation
- Allergic diseases e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia.
- Neoplasms, esp. Hodgkin’s, T-cell NHL
- Hypereosinophilic syndrome
11
Q
Causes of malignant eosinophilia
A
- Malignant chronic eosinophilic Leukemia (PDGFR fusion gene)
12
Q
When would a patient present with Monocytosis?
A
Rare but seen in certain chronic infections and primary haematological disorders TB, brucella, typhoid Viral; CMV, varicella zoster Sarcoidosis Chronic myelomonocytic leukaemia (MDS)
13
Q
Causes of reactive lymphocytosis
A
- Infection
- > EBV, CMV, Toxoplasma
- > infectious hepatitis, rubella, herpes infections
- smokers can have lymphocytosis
- Autoimmune disorders
- neoplasia
- sarcoidosis
14
Q
Causes of reactive lymphocytosis
A
- Infection
- > EBV, CMV, Toxoplasma
- > infectious hepatitis, rubella, herpes infections
- smokers can have lymphocytosis
- Autoimmune disorders (but might also haven lymphopenia)
- neoplasia
- sarcoidosis
15
Q
Glandular fever
A
- EBV infection of B-lymphocytes via CD21 receptor
- Infected B-cell proliferates and expresses EBV associated antigens
- Cytotoxic T-lymphocyte response
- acute infection resolved resulting in lifelong sub-clinical infection.
16
Q
Normal haematopoiesis
A
Polyclonal healthy / reactive
- normal marrow
- reactive marrow
17
Q
Malignant haematopoiesis
A
Abnormal / clonal
- leukemia (l/m), myelodysplasia, myeloproliferative
18
Q
Which cells are normally found in the marrow?
A
- lymphoblasts
- myeloblasts
- promyelocytes
- myelocytes
- metamyelocytes
19
Q
Which cells are normally found in the peripheral blood?
A
- T-lymphocytes
- B- lymphocytes
- NK-cells
- Granulocytes (E, B, N)
- monocytes
20
Q
What mechanisms cause leukocytosis?
A
Increased Cell Production:
- Reactive (Infection, Inflammation)
- Malignant (Leukaemia, myeloproliferative)
Increased Cell Survival:
- Failure of apoptosis (eg acquired cancer causing mutations in some lymphomas)
21
Q
What mechanisms cause Leukipenia?
A
Decreased Cell Production:
- Impaired BM function (B12 or folate deficiency -> sometimes vegans have lower levels of Leuks due to deficiencies)
- BM failure (aplastic anaemia, post chemotherapy, metastatic cancer, haematological cancer)
Decreased Cell Survival:
- immune breakdown
22
Q
malignant (primary) eosinophilia
A
- cancers of haematopoietic cells
- leukemia (m or l, a or c)
- myeloproliferative disorders)
23
Q
What would you expect the result of a blood film to be in CML?
A
- very high WBC count
- film would show every stage of white cell maturation
24
Q
How to investigate a raised WCC? (1)
A
- History and examination
- Hb and platelet count
- Automated differential
- Examine blood film
25
How to investigate a raised WCC? (2)
- Abnormality White cells only, or all 3 lineages (red cells/platelets/white cells) ?
- White cells 1 cell type only, or all lineages? (e.g. neuts/eos/monocytes/lymphocytes)
- Mature cells only or mature and immature cells?
26
What usually differentiates cancer from a reactive condition?
- Usually: in cancer there will be clones identical to mother cell, abnormality of 1 particular cell type.
All types suggests a reactive condiiton.
- also in cancer you would probably have thrombopenia and anaemia / erythropenia
27
Neutrophils - location, lifespan, circulation
- Present in BM, blood and tissues
- Life span 2-3 days in tissues (hours in PB)
- 50% circulating neutrophils are marginated (not counted in FBC)
28
How fast can neutrophilia develop?
- minutes > demargination
- hours > early release from BM
- days > increased production (x3 in infection)
29
What is margination of neutrophils?
Margination refers to the prolonged transit of neutrophils through specific organs, which results in discrete intravascular (marginated) pools; these can be found within the spleen, liver, bone marrow and, more controversially, the lung.
30
How can you differentiate between reactive and malignant eosinophilia?
reactive: no changes in the eosinophil
malignant: abnormalities in granule distribution, cells look abnormal; also look for the PDGFR mutation
31
Monocytosis
- Rare but seen in certain chronic infections and primary haematological disorders
- TB, brucella, typhoid
- Viral; CMV, varicella zoster
Sarcoidosis
- Chronic myelomonocytic leukaemia (MDS)
32
Lymphocytosis
Mature cells:
- reactive to onfection
- primary disorder
Immature cells:
- primary disorder (leukemia/lymphoma)
33
How do mature and immature lymphocytes differ in appearance?
M: small cell with a high nucleus to cytoplasm ratio, compact and dark chromatin
-> CLL or autoimmune/inflammatory disease
IM: high nucleocytoplasmic ratio but more cytopplasm than mature cells, larger cells, nucleolus in the nucleus -> blasts, immature cells.
-> ALL
34
How to see if lymphocytosis of mature cells is primary or reactive?
=> thorough examination of the blood film
- Secondary (reactive); polyclonal response to infection, chronic inflammation, or underlying malignancy.
- Primary; monoclonal lymphoid proliferation e.g. CLL
35
When would you expect to see a reactive lymphocytosis?
Infection:
- EBV, CMV, Toxoplasma
- infectious hepatitis, rubella, herpes infections
Autoimmune disorders
neoplasia
sarcoidosis
36
Mononucleosis syndrome
- abnormal lymphocytes
- Very big lymohocytes with a blastic appearance,
- Secondary to EBV: other cell linneages are not affected
- In leukemia you would have anaemia and throbocytopenia
37
What key points would you look at to distinguish causes of lymphocytosis?
Morphology
Immunophenotype
Gene re-arragement
38
Light chains in normal conditions and in malignancy?
Normal: similar amount of kappa and lambda
Malignant lymohocytosis: the malignant clone will have only one type of light chains.
39
Evaluating lymphocytosis through gene rearrangement
Imuunoglobulin genes (Ig) and T cell receptor (TCR) genes undergo recombination in antigen stimulated B cells or T cells.
With primary monoclonal proliferation all daughter cells carry identical configuration of Ig, or TCR gene. This can be detected by Southern Blot analysis
40
Look at PP and patient cases in presentation slides
:)
