Blood Cell Abnormalities Flashcards
What is leukaemia?
Bone marrow disease and overspill of the abnormal cells into the blood, producing white blood.
Leukaemia is a cancer which starts in blood-forming tissue, usually the bone marrow. It leads to the over-production of abnormal white blood cells, the part of the immune system which defends the body against infection.
What are the 2 classifications of leukaemia?
Myeloid - Can include the precursors of monocytes, granulocytes, megakaryocytes and erythroid.
Lymphoid - B, T and NK cells
How does leukaemia differ from many other cancers?
Leukaemia differs from many other cancers in that the abnormal cells circulate in the blood stream and migrate into various tissues. It is difficult to apply the concepts of local invasion and metastasis that are used to describe solid tumours to populations of cells that are normally mobile. The formation of localised tumour masses is also not inevitable in leukaemia, at least not in the earlier stages of the disease. We have to look at other characteristics of this disease to understand that leukaemia is a type of cancer.
What are the differences between acute and chronic?
Acute - if untreated, has profound pathological effects and leads to death in a matter of days, weeks or months.
Chronic - causes less impairment of function of normal tissues and, although it will eventually lead to death, this usually does not occur for a number of years.
Why does leukaemia occur?
Leukaemia results from a number of mutations occurring in a primitive cell that, as a result, has a growth or survival advantage over normal cells that have not undergone mutation. That single cell gives rise to a clone that steadily replaces normal cells.
What are the mutations concerned with leukaemia?
Proto-oncogenes (also known as oncogenes) and sometimes also in tumour suppressor genes.
Mutations in germs cells can be what?
Beneficial
Neutral
Harmful
The process of mutation in a somatic cell may be the result of?
Undetected exposure to mutagens or it may be a random, spontaneous process.
Explain the correlation between age and risk of mutation.
The older a person is the more likely it is that enough spontaneous or induced mutations have accumulated in a single cell for the cell to expand into a clone that replaces normal cells.
List some abnormal behaviours of the leukaemic clone.
Growth occurring without a dependence on GFs
Continued proliferation without maturation.
Failure to undergo normal cell death (apoptosis).
Causes of 4 different leukaemias.
ALL - Usually known, some mutagenic drugs or exposure to irradiation or chemicals in utero; possible delayed exposure to a common pathogen or pathogens.
AML - Usually unknown, sometime irradiation or mutagenic drugs or chemicals (benzene, cigarette smoke).
CML - Usually unknown, rarely irradiation or mutagenic drugs.
CLL - Unknown but some families are predisposed.
What type of leukaemia mainly occurs in infants?
ALL
(Occurs during foetal development. Antigenic stimulation may also be relevant to the development of some forms of ALL. This normally leads to rearrangement of DNA so that antibodies of greater affinity are produced. If the process goes wrong, a lymphoid stem cell may acquire a malignant phenotype.)
What do different types of leukaemia differ in?
Aetiology, nature of mutational events, age of onset, clinical and haematological features and prognosis.
For example, acute lymphoblastic leukaemia (ALL) is particularly a disease of childhood, whereas CLL predominantly affects the elderly.
What do symptoms and signs of leukaemia result from and give examples of each?
Direct effects of the proliferation of leukaemic cell. Examples: bone pain, enlarged liver (hepatomegaly), enlarged spleen (splenomegaly) and swollen lymph nodes (lymphadenopathy, mainly in lymphoid leukaemias)
Indirect effect of leukaemic cell proliferation which leads to: replacement of normal bone marrow cells by leukaemic cells (causing anaemia, thrombocytopenia, neutropenia).
List some general clinical features of leukaemia and their causes.
Bruising and petechiae - thrombocytopenia
Fatigue, lethargy, pallor - anaemia
Fever and infections - neutropenia
Bone pain - bone marrow expansion
Abdominal enlargement - hepatomegaly, splenomegaly
Lumps and swellings - lymphadenopathy
What are the essential investigations for leukaemia?
FBC and blood film.
Also need to characterise the profile of the cell surface markers expressed (e.g. to distinguish T and B lymphoid cells); we do this using a technique called flow cytometry:
We take a sample of bone marrow for examination and perform cytogenetic/molecular analysis on blood and/or bone marrow to look for markers such as the Philadelphia chromosome (9;22).
Main abnormalities seen on a blood film for AML?
Blast cell has large size
Large Nuclei/cytoplasmic ratio
Cytoplasm contains granules consistent with those being myeloblasts.
Platelets and neutrophils notably absent, consistent with replacement of normal haematopoietic cells by leukaemia clone
Symptoms of AML?
Fatigue, pallor (anaemia)
Fever & infections (neutropenia)
Bruising & petechiae (thrombocytopenia)
Bone pain (bone marrow expansion)
Main abnormalities on blood film for CML?
Increase in all granulocytes (neutrophils, eosinophils, basophils) and their precursors - left shift
