Abnormal white cell count- tricky Flashcards
What does lymphoid mean?
Relating to or denoting the tissue responsible for producing lymphocytes (T cells, B cells and NK cells)
In the bone marrow, what sort of cells do you start haematopoiesis with ?
Haematopoietic stem cells
What happens to haematopoietic stem cells?
They become committed to different lineages such as pre T, pre B, Meg-CFC, GM-CFC etc
What are Meg-CFC?
Megakaryocyte colony forming cells
What are GM-CFC?
Granulocyte macrophage colony forming cells
As a myeloblast matures into a neutrophil, what happens?
Cell becomes smaller and smaller
Cytoplasm becomes clearer
Multi-lobed nuclei form
What regulates haematopoiesis?
Cytokines
Chemokines
Hormones
What factors stimulate haematopoiesis in myeloid, lymphoid and erythroid?
Myeloid: G-CSF and M-CSF
Lymphoid: IL2
Erythroid: Erythropoietin
What can DNA damage during differentiation cause?
These cells can stop being regulated and will have a survival advantage so stops being regulated by cytokines and starts replicating uncontrollably causing cancer
What is leukaemia?
A malignant progressive disease in which bone marrow and the blood-forming organ produce increased numbers of immature or abnormal leukocytes, this leads to suppression of production of other blood cells such as erythrocytes, granulocytes and platelets
What is lymphoma?
Any group of blood cell tumours that develop from lymphatic cells. If it is mainly in the lympathic tissue then it is lymphoma, if it is mainly in the blood then it is leukaemia
What is myeloma?
A malignant disease of the bone marrow characterised by two or more of the following criteria:
Presence of an excess of abnormal malignant plasma cells in the bone marrow
Typical lytic deposits in the bones on X-ray, giving the appearance of holes
The presence in the serum of an abnormal gammaglobulins, usually IgG
What causes increased white cell production?
Reactive: -Infection I-nflammation Malignant: -Leukaemia -Myeloproliferative
What causes decreased white cell production?
Impaired bone marrow function B12 or folate deficiency Bone marrow failure: -Aplastic anaemia -Post chemotherapy -Metastatic cancer -Haematological cancer
What causes increased white cell survival?
Failure of apoptosis (acquired in cancer)
What causes decreased white cell survival?
Immune breakdown
What is the difference between the cells that will be released in response to infection and in cancer?
In response to infection - mature cells
Cancer- immature and mature
In chronic myeloid leukaemia, where does the mutation occur?
GM-CFC
What effect does the GM-CFC have?
Massive proliferation of the myeloid cells beyond this point
How do you investigate a raised white cell count?
History and examination
Haemoglobin and platelet count
Automated differential
Examine blood film
What is a key sign in the blood film of leukaemia?
Immature cells
What is the normal range for blood Hb?
120-160g/l
What is the normal range for platelets?
150-400 x 10^9/l
What is the normal range for WCC?
4-11 x 10^9/l
What is the normal range for neutrophils?
2.5-7.5 x 10^9/l
What is the normal range for lymphocytes?
1.5-3.5 x 10^9/l
What is the normal range for monocytes?
0.2-0.8 x 10^9/l
What is the normal range for eosinophils?
0.04-0.44 x 10^9/l
What is the normal range for basophils?
0.01-0.1 x 10^9/l
Where are neutrophils found?
Bone marrow, blood and tissues
How long do neutrophils survive in tissues and blood?
2-3 days in tissue
Hours in blood
50% of circulating neutrophils are marginated, what does this mean?
They have stuck onto the wall of a damaged vessel (not counted in FBC)
Explain causes for neutrophilia developing in minutes, hours and days
Minutes- Demargination
Hours- Early release from bone marrow
Days- Increased production
How can you tell the difference between infection and leukaemia?
Infection will have high WCC and granular neutrophils
Leukaemia will have neutrophils but not granular ones, also myelocytes and metamyelocytes will be present which aren’t in response to infection
What causes neutrophilia?
Infection
Tissue inflammation
Physical stress- adrenaline and corticosteroids
Underlying neoplasia
Malignant neutrophilia- myeloproliferative disorders and CML
What type of infections does neutrophilia occur in?
Local and systemic
Acute bacteria, fungal and certain viral infections
If you had a low neutrophil count but other features of infection, what can you deduce?
Viral infection
What infections characteristically don’t produce neutrophilia?
Brucella, typhoid, many viral ones
What causes eosinophilia?
Reactive: -Parasitic infection -Allergic diseases e.g. asthma -Neoplasms -Hypereosinophilic syndrome Malignant Chronic Eosinophilic Leukaemia (PDGFR)- Rare Hodgkin's disease
How can you tell if someone has Hodgkin’s disease?
Increased mediastinal mass on chest X-ray
When is monocytosis seen?
Rare but seen in certain chronic infections and primary haematological disorders e.g: TB, brucella and typhoid Viral: CMV Sarcoidosis CML
What would the blood film of someone with CLL or autoimmune/inflammatory disease be like?
Cells very similar to each other
Typical appearance of mature lymphocyte with big nucleus and little cytoplasm
What would the blood film of someone with acute lymphoblastic leukaemia?
Immature lymphocytes- much larger than mature ones and you can see nucleolus
What causes reactive lymphocytosis?
Infection EBV, CMV, toxoplasma Infectious, hepatitis, rubella and herpes infections Autoimmune disorders Neoplasia Sarcoidosis
What do you see in mononucleosis syndrome?
An atypical reactive looking lymphocyte- it isn’t round like normal lymphocytes and it extends between red cells and the nucleus looks weird because it lacks nucleoli
What is mononucleosis syndrome typical of?
Glandular fever
What is glandular fever?
EBV infection of B lymphocytes via CD21 receptor which proliferate and express EBV associated antigens
How does the body respond to glandular fever?
Cytotoxic T-lymphocyte response and the acute infection is resolved resulting in lifelong sub-clinical infection
What is the most likely cause of lymphocytosis in elderly?
Chronic lymphocytic leukaemia (mature lymphocytes and maybe smear cells)
Your differential diagnosis is reactive to underlying autoimmune disorder or chronic lymphocytic leukaemia, how can you distinguish?
Morphology
Immunophenotype
Gene rearrangement
What sort of response will you get to an infection?
Polyclonal
