Abnormal White Blood Cell Count Flashcards
How to describe raised/reduced cell counts?
Reduced - cytopenia/penia
Raised - cytosis/philia
What is it called when ALL cell lineages are reduced?
Pancytopenia
What is haemopoiesis and how can it occur?
Production of blood cells in the bone marrow
o Normal haemopoiesis (polyclonal healthy/reactive)
- normal marrow
- reactive marrow
o Malignant haemopoiesis (abnormal/cloncal)
- leukaemia (lymphoid, myeloid)
- myelodysplasia
- myeloproliferative
What cell starts haematopoiesis?
HSC - haemopoeitic stem cells
Can differentiate into many cell lines
BFU-E (blast forming unit erythrocyte) goes on to form RBCs
Explain differentiation and maturation in haematopoiesis in the myeloid lineage
ONENOTE!!
Myeloid lineage go on to form granulocytes!!
Normally the FIRST 4 STEPS occur within the bone marrow
AND
The neutrophil is formed in the peripheral blood
BUT in pathology this can change
e. g. after chemotherapy see myeoblasts iin blood
e. g. in sepsis see meyoblasts in the blood and nucleated RBCs
How do you control cell numbers? What are the specifics for each type?
Regulation is via. CYTOKINES
o RBCs = EPO
o Lymphoid cells = IL-2
o Myeloid cells = G-CSF, M-CSF
What can affect the regulating signals in controlling cell number?
DNA damage in cancer can affect the regulating signals leading to cancer proliferation
o Leukaemia - malignant process in 1o lymphoid process
o Lymphoma/leukaemia - lymphatic cell tumours in blood/tissues
o Myeloma - disease of bone marrow
What can increase WBC count?
Leukocytosis
o Increased cell production
- REACTIVE e.g. infection/inflammation
- MALIGNANT e.g. leukaemia/myeloproliferative
o Increased cell survival
- failure of apoptosis (e.g. acquired cancer causing mutations in some lymphomas)
What can decrease WBC count?
Leukopaenia
o Decreased cell production
- Impaired BM function
- B12 or folate deficiency
- BM failure (aplastic anaemia, post chemotherapy, metastatic ca, haematological ca)
o Decreased cell survival
- Immune breakdown
Difference between normal infections and haematopoietic cancers
In normal infections
- increased WBC is reactive
- mature cells are released
In haematopoietic cancers
- immature AND mature cells are released
Example of an increase in cell number?
Eosinophilia - 2 causes!
- Reactive (infection/inflammation)
i.e. Normal haemopoiesis - stimulated by
o inflammation/infection/increased cytokine production
- Primary (malignant)
i.e. Abnormal haemopoiesis o autonomous cell growth o cancers of haemopoietic cells o Leukaemia (myeloid OR lymphoid/ chronic OR acute) o myeloproliferative disorders
Exampel of malignant haematopoiesis?
Chronic myeloid leukaemia
o Mutation occurs at GM-CFC (onenote!)
o Instead of cellular death, have an overun proliferation
How would you investigate a raised WBCC?
History, examination, Hb & platelet count, automated differential, examine blood film
What indications should make you think further when investigating a rasied WBCC?
If see IMMATURE cells in blood film
- think about LEUKAEMIA
- in a normal reactive response you would not see this in peripheral blood
If see IMMATURE & MATURE cells
- think about CHRONIC LEUKAEMIA if in the presence on neutrophils & myelocytes
o Acute leukaemia will present w. LOW Hb & LOW platelets
Normal FBC NR?
Hb = 120-160g/L
Platelet = 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
Common causes of abnormal WCC in terms of the FBC?
- Phagocytes
- neutrophils
- eosinophils
- monocytes - Immune cells
- lymphocytes
Neutrophils properties?
Present in BM, blood and tissues
Life span 2-3days in tissues (hours in PB)
50% circulating neutrophils are marginated (NOT counted in FBC)
PB = peripheral blood
Neutrophilia?
INCREASE
Can develop in:
o minutes - demargination
o hours - early release from BM
o days - increased production (x3 in infection)
Blood film of PB in infection?
o Neutrophilia
o Toxic granulation
o Vacuoles
Blood film of PB in leukaemia?
Shows neutrophilia & myelocytes
NOTE - the absence of granules in leukaemia (NO toxic granulation)
When does neutrophilia normally present?
Causes include:
o INFECTION
o Tissue inflammation
o physical stress, adrenaline, corticosteroids
o underlying neoplasia
o malignant neutrophilia (myeloproliferative disorders, CML)
Main cause of neutrophilia?
INFECTION
o localised and systemic infections
e.g. acute bacterial, fungal, certain viral infections
SOME infections do NOT produce a neutrophilia e.g. tyhpoid, many viral infections, Brucella
Causes of REACTIVE Eosinophilia?
o Parastitic infection
o Allergic disease
o Neoplasms e.g. Hodgkin’s, T-cell NHL
- Hodgkins will show on x-ray with increased mediastinal mass and an increase in IL-5 secretion
- can also get a mutation in GM-CFC
o Hypereosinophilic syndrome
Causes of MALIGNANT Eosinophilia?
Malignant Chronic Eosinohpilic Leukaemia (PDGFR fusion gene)
RARE!
Monocytosis?
INCREASE!
Rare BUT seen in certain
o chronic infections
AND
o primary haematological disorders
Causes of monocytosis?
o TB, brucella, typhoid
o Viral - CMV, VZV
o Sarcoidosis
o CML (M=muelomonocytic)
Summary of reactive elevated phagocyte count?
ONENOTE!!
Lymphocytosis?
INCREASE
Is it:
o Mature cells?
- either reactive to infection OR 1o disorder
o Immature cells?
- 1o disorder ONLY (not reactive)
Mature vs. Immature cells in Lymphocytosis?
o Mature lymphocytes
- cells are LIKE each other i.e. oligoclonal expansion
- could be CLL OR autoimmune/inflammatory disease
o Immature lymphoblasts
- Much larger
- Can see a nuclelous = shows immaturity
- due to ACUTE LYMPHOBLASTIC LEUKAEMIA
Causes of primary vs. secondary (reactive) lymphocytosis?
Is it 1o or reactive (2o)?
Secondary/Reactive
- POLYCLONAL response to infection
- chronic inflammation OR underlying malignancy
Primary
- MONOCLONAL lymhpoid proliferation
- e.g. CLL - all cells look the same as mutated cell making clones of itself
Causes of reactive lymphocytosis?
o Infection e.g. EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes
o Smoking
o Autoimmune
o Neoplasia
o Sarcoidosis
Explain Mononucleosis Syndrome on a blood film
Shows a reactive-looking lymphocyte
- looks like an immature lymphocyte seen in ALL
BUT
These lymphocytes tend to have RBCs clump them
- they are jagged
- and are NOT self-clumped
Glandular Fever?
High WCC with reactive-looking lymphocytes
Causes by an EBV infection
- of B-lymphocytes via. CD21 receptor
- infected B-cell proliferated and expresses EBV-associated antigens
- causes a CYTOTOXIC T-CELL response
Common in the young!
Lymphocytosis in the elderly and how to identify?
Most often going to be caused by
o CLL
OR
o an autoimmune disorder
Will see MATURE lymphocytes (& smear cells)
How can you distinguish between the different causes of lymphocytosis in the elderly?
o Morphology
o Immunophenotype (what antigens are expressed on the surface)
o Gene rearrangement
How can you evaluate lymphocytosis?
Light chain restriction
OR
Gene rearrangement
Evaluating lymphocytosis with light chain restriction?
POLYCLONCAL expansion
o invovles MORE than one mother cell o SO the light chain expresses BOTH - kappa - lambda o this is indicative of a response to INFECTION
MONOCLONAL expansion
o ALL Abs from ONE mother cell o SO light chain EITHER - kappa OR - lambda o indicative of a cancer
Evaluating lymphocytosis with gene rearrangement?
Ig genes and T-cell R genes undero recombination in antigen stimulated B or T-cells
With 1o monoclonal proliferation
o ALL daughter cells carry IDENTICAL TCR gene arrangement
o this is NOT normal for infection
o SO idicative of cancer
Detect via. Southern Blot Analysis
Cases?
4 CASES in ONENOTE!!
DO THEM!!
