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
Symptoms of CML?
Abdominal discomfort (hepatomegaly, splenomegaly)
Main abnormalities seen on blood film for patients with CLL?
4 mature CLL lymphocytes and a squashed CLL lymphocyte (smear)
Symptoms of CLL?
Lumps and swellings (lymphadenopathy)
Fatigue, lethargy, pallor (anaemia)
Main abnormalities seen on blood film for ALL?
Blast cells recognised by large size
High nuclei:cytoplasmic
Open chromatin pattern of nuclei and prominent nucleoli
Cytoplasm has no granules
Platelets and neutrophils are notably absent, consistent with replacement of normal haematopoietic cells by leukaemic clone
Symptoms of ALL?
Lumps and swelling (lymphadenopathy) Lethargy, pallor (anaemia) Fever & infections (neutropenia) Bruising and petechiae (thrombocytopenia) Bone pain (bone marrow expansion)
Define anaemia?
Reduction in the haemoglobin concentration (Hb) in the circulating blood below what is normal for a healthy person of the same age and gender as the individual.
List mechanisms that cause anaemia.
Reduced production of red cells by the bone marrow
Loss of blood from the body
Reduced survival of red cells in the circulation (haemolysis)
Increased pooling of red cells in an enlarged spleen
Describe a red blood cell seen on a blood film for a patient with microcytic anaemia.
Microcytic (smaller) - low MCV
Usually hypochromic → appear pale when looked at with a microscope → low MCHC
Common causes of microcytic anaemia?
Iron deficiency
ACD
Thalassaemia
What are the causes of IDA?
Increased blood loss: Commonest in adults
Hookworm is commonest cause worldwide.
Menstrual (menorrhagia)
Insufficient intake: Dietary (veg) OR Malabsorption due to Coeliac disease (gluten-induced enteropathy) and H. pylori gastritis
Increased requirements - Physiological, pregnancy and infancy.
What are the 3 stages of iron depletion?
Iron depletion - Storage iron reduced or absent
Iron deficiency - Low serum iron and transferrin saturation
Iron deficiency anaemia - Low Hb and Hct
Clinical features of IDA?
Pallor, fatigue, breathlessness
Failure to thrive
Koilonychia, angular stomatitis, glossitis
Define ACD.
Anaemia in patients who are unwell; usually an inflammatory aspect to the underlying disease.
Common causes of ACD.
- Rheumatoid arthritis
- Autoimmune disease
- Malignancy
- Infections such as TB or HIV
- Kidney disease
What are some laboratory clues that a patient has ACD?
- Erythrocyte sedimentation rate (ESR) is high (unlike iron deficiency)
- C-reactive protein is high (unlike iron deficiency)
- Ferritin is high
- Transferrin is low
- Acute phase proteins increase
Why is important to department what the cause of microcytic anaemia is?
As patients with anaemia of chronic disease have plenty of storage iron, treating with iron replacement therapy (as you would for patients with iron deficiency anaemia) will not help and should be avoided.
Compare each of these diagnostic perimeters for a patient with ACD and IDA: Hb MCV Serum iron Ferritin Transferrin
Hb:
IDA - Low
ACD - Low
MCV:
IDA - Low
ACD - Low
Serum iron:
IDA - Low
ACD - Low
Ferritin:
IDA - Low
ACD - High
Transferrin:
IDA - High
ACD - Low
What value is usually elevated in macrocytic anaemia?
Elevated MCV
What does macrocytic anaemia usually result from?
Abnormal haemopoiesis so that red cell precursors continue to synthesise haemoglobin and other cellular proteins, but fail to divide normally.
What is megaloblastic erythropoiesis?
Delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow.
Megaloblasts generally seen in bone marrow, not the blood film.
What is megaloblast erythropoiesis caused by?
Lack of VB12 or folic acid
It is possible to suspect MA from peripheral blood features, but to be sure?
Do a bone marrow examination
What are some common causes of macrocytic anaemia?
Lack of VB12 or folic acid (megaloblastic anaemia)
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Recent major blood loss with adequate iron stores (reticulocytes increased)
Haemolytic anaemia (reticulocytes increased)
What are the mechanisms that can lead to noromocytic anaemia?
Recent blood loss
Pooling of red cells in the spleen
Failure of production of red cells
List some examples of causes to normocytic anaemia.
Bone marrow failure or suppression (e.g. chemotherapy)
Early stages of iron deficiency
GI haemorrhage, trauma
Hypersplenism (e.g. liver cirrhosis)
Splenic sequestration in SCA
Bone marrow infiltration (e.g. leukaemia)
What does measuring reticulocyte count involve?
Exposing red cells to a new methylene blue that stains higher RNA content of young red blood cells so that they can be counted.
What is polychromasia?
That cells have a blue tinge, caused by the ribosomal RNA in young red cells, in addition to the pink colour of the haemoglobin.
What is increased reticulocyte count seen as a response to?
Haemolytic anaemia
Recent blood loss
Response to treatment with iron, vitamin B12 or folic acid.
When is a reduced reticulocyte count seen?
When there is reduced output of red cells from the bone marrow.
