Introduction to Haematology Flashcards
What is the definition of haematology?
Biology and pathology of the cells that normally circulate in the blood 🩸
What is the definition of haemopoiesis?
The physiological developmental process that gives rise to the cellular components of the blood
a single multipotent haemopoietic stem cell can divide and differentiate to form different cell lineages that will populate the blood
What is the difference between symmetrical and asymmetrical division when the haemopoietic stem cell undergoes differentiation and/or self-renewal?
Symmetrical division:
- may yield two identical stem cells
- or two daughter cells that have undergone a degree of differentiation and concomitant loss of self-renewal capacity
Aysmmetrical division:
- both a stem cell and a daughter cell are generated
What are the 2 different types of symmetrical division?
Symmetric self-renewal:
- increase stem cell pool
- no generation of differentiated progeny
Lack of self-renewal:
- depletion of stem cell pool
- generation of differentiated progeny ONLY
What is meant by aysmmetric self-renewal and lack of self-renewal?
Asymmetric self-renewal:
- maintains the stem cell pool
- generation of differentiated progeny
Lack of self-renewal:
- maintain the stem cell pool
- no differentiated progeny
What are the characteristics of the haemopoietic stem cell?
- Self-renewal
- High proliferative potential
- Differentiation potential for all lineages
- Long term activity throughout the lifespan of the individual
What is an example that gives experimental proof of the properties of the haemopoietic stem cell?
- Stem cells transplanted from one mouse to another over several generations
- bone marrow transplantation in humans
What are the 2 different haemopoietic lineages with examples?
Myeloid:
- granulocytes (white blood cells)
- erythrocytes (red blood cells)
- platelets
Lymphoid:
- B-lymphocytes
- T-lymphocytes
How do stem cells help to maintain the cellular content of the blood?
Stem cells give rise to sufficient numbers of committed haemopoietic progenitors to maintain the cellular content of the blood throughout the lifespan of the individual
What are the stages shown in haemopoiesis?
What is the lifespan of an erythrocyte and neutrophil like?
Mature blood cells all have a finite life
an erythrocyte has a lifespan of about 120 days
a neutrophil only lasts for 6-10 hours in the bloodstream
What is the difference between pluripotent and committed stem cells?
Pluripotent stem cells:
- develop into cells and tissues of the three primary germ layers
- can develop into any type of cell in the body
Committed stem cell:
- cells that have been committed to a particular pathway of differentiation
Label the components of the trophoblast at 9 days
Extra-embryonic coelom is the chorionic cavity
this is a fluid-filled area formed from trophoblast and extra-embryonic mesoderm that forms the placenta
What is the morula?
An early-stage embryo consisting of 16 cells (called blastomeres) in a solid ball contained within the zona pellucida
it goes on to form the blastula
trophoblasts are cells forming the outer layer of the blastocyst
When does haematopoiesis start?
Where does this occur?
Haemopoiesis starts at day 27 in the aorto-gonado-mesonephros
this expands rapidly at day 35, and then disappears at day 40
What happens when the aorto-gonado-mesonephros disappears at day 40?
The disappearance correlates with the migration of the haemopoietic stem cells to the foetal liver
this becomes the subsequent site of haemopoiesis
What are the 4 main functions of blood cells?
- Oxygen transport
- coagulation (haemostasis)
- immune response to infection
- immune response to abnormal cells (senescent, malignant, etc.)
What are the properties of erythrocytes?
How many are present in the body?
Biconcave discs that are 7.5 um in diameter
lifespan of 120 days in the blood
contain haemoglobin
there are 333,200 x 106 red cells in the blood
What is it called when there are reduced and raised red cells?
Anaemia occurs when there are reduced red cells
polycythaemia occurs when there are raised red cells
What is relative polycythaemia?
The number of red blood cells has not changed but the plasma volume has been reduced
What are the functions of white blood cells (leukocytes)?
What are the 3 different types?
They have functions in immunity and host defence
granulocytes:
- have cytoplasmic granules
- neutrophils, eosinophils, basophils
monocytes
lymphocytes
How many neutrophils are present in the blood usually?
They are phagocytes and the most common white cell in adult blood
10 x 109 per litre
they live for only a few hours in the blood
What is it called when there are increased and decreased numbers of neutrophils in the blood?
Why might this occur?
Neutrophilia:
- increased numbers of neutrophils
- occurs in bacterial infection and inflammation
Neutropenia:
- decreased numbers of neutrophils
- occurs as a side effect of some drugs
When might there be increased numbers of eosinophils?
Eosinophilia is an increase in the number of eosinophils
this occurs in allergies and parasitic infection
What is the role of basophils?
When may there be an increase in basophils and what is this called?
Basophils are rare cells that are part of the primitive immune system
basophilia is an increase in the number of basophils
this occurs in chronic myeloid leukaemia
What are the roles of monocytes?
Where do they migrate to?
They are phagocytic and act as antigen-presenting cells
they migrate to tissues and are then identified as macrophages and histiocytes
e.g. Kupffer cells in the liver, Langerhans cells in the skin
When may there be an increase in monocytes?
Monocytosis
this is an increase in the number of monocytes
occurs in tuberculosis
What is it called when there is an increase or decrease in lymphocytes?
Why might this occur?
Lymphocytosis:
- increase in number of lymphocytes
- occurs in chronic lymphocytic leukaemia
- atypical lymphocytes of glandular fever (infectious mononucleosis)
lymphopenia:
- decrease in the number of lymphocytes
- e.g. post bone marrow transplant
What are the role of natural killer lymphocytes?
They are large granular lymphocytes that are part of the innate immune system
they recognise “non-self” - cells / viruses
What are the roles of T-lymphocytes?
Part of the adaptive immune system
- involved in cell-mediated immunity
- target-specific cytotoxicity
- interact with B cells and macrophages
- regulate immune responses
What are the roles of B-lymphocytes?
part of the adaptive immune system
- rearrange immunoglobulin genes to enable antigen-specific antibody production
- involved in humoral immunity
What is plasmacytosis?
When may it occur?
An increase in the number of plasma cells (produced from B-lymphocytes)
occurs in infection and myeloma
What are platelets formed from?
How many are present in the blood?
Platelets are derived from bone marrow megakaryocytes
there are 200 x 109 per litre
What are the roles of platelets?
Together with soluble plasma clotting factors and endothelial cells, they form part of the blood clotting system
they aggregate to plug holes in damaged blood vessels
What are the four main subdivisions of haematology clinical practice?
- Coagulation
- malignant
- non-malignant
- transfusion
What diagnostic tests are used in haematology?
- Full blood count
- blood film (or “smear”)
- coagulation screen
What is involved in a full blood count?
- Haemoglobin concentration
- red cell parameters:
MCV - mean cell volume
MCH - mean cell Hb
- white cell count (WCC)
- platelet count
What is a blood film?
A thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically
What is a coagulation screen?
Tests that measure the time taken for a clot to form when plasma is mixed with specific reagents
various parts of the coagulation cascade can be assayed
What types of things are looked at when a coagulation screen is performed?
- Prothrombin time
- activated partial thromboplastin time
- thrombin time
What is involved in a bone marrow aspirate & trephine?
Under local anaesthetic, liquid marrow is aspirated from the posterior iliac crest of the pelvis
a trephine core biopsy is then taken with a hollow needle
What is a trephine?
A hole saw used in surgery to remove a circle of tissue or bone
What is involved in obtaining a blood specimen?
An accurate FBC and correct interpretation of a blood film
- need an appropriate sample from the patient
- collect into EDTA anticoagulated blood
this should be mixed well and [K2EDTA] = 1.5 - 2.2 mg / ml
blood should be filled to the line on the tube
- Samples should get to the lab promptly since EDTA artefact can affect the results
What is EDTA and what does it do?
It is a chemical that binds and holds onto minerals and metals
e.g. Iron, lead, mercury, copper, magnesium, etc.
when they are bound, they cannot have any effects on the body and are removed from the body
Why may test results vary?
Technical failure:
- e.g. clotted sample or variation in reagents
normal variation:
- intra-individual variation e.g. diurnal variation of cortisol levels
- inter-individual variation e.g. platelet count
abnormal results
How is a reference range established?
* Define the reference population
- reference population should be relevant to the test population
- consider if separate ranges are required for adults v children, men v women etc.
- determine the expected range of inter individual variation
What is meant by a reference range?
The set of values for a given test that incorporates 95% of the normal population
this is determined by collecting data from vast numbers of laboratory tests
95% of results should fall within the reference range
What is shown in this image?
The distribution of test results for healthy and diseased subjects
TN - true negative
TP - true positive
FN - false negative
FP - false positive
What is meant by sensitivity?
How is it calculated?
The proportion of abnormal results correctly classified by the test
expresses the ability to detect a true abnormality
sensitivity = TP / (TP + FN )
What is the definition of specificity?
How is it calculated?
The proportion of normal results correctly classified by the test
expresses the ability to exclude an abnormal result in a healthy person
specificity = TN / (TN + FP )
When interpreting full blood count, what is it important to keep in mind?
Be alert to technical problems:
- e.g. thrombocytopenia is sometimes real and sometimes artefact
abnormal results:
- will be flagged by the laboratory but may trigger additional tests e.g. blood film
serious urgent abnormalities:
- laboratory staff will alert the on-call doctors e.g. new leukaemia
Why is it important to know clinical details of patients when interpreting a full blood count?
FBC may fall outside the “normal range” but the results may be appropriate for the given clinical situation
e.g. Abnormal lymphocyte count
post-splenectomy mild lymphocytosis or 3 months post bone marrow transplant lymphopenia
What are MCV and MCH in microcytic anaemia?
What are examples of microcytic anaemias?
MCV < 80 fl & MCH < 27 pg
- iron deficiency
- thalassaemia
- anaemia of chronic disease (some)
- lead poisoning
- sideroblastic anaemia (some cases)
What is meant by microcytic anaemia?
The presence of small, often hypochromic, red blood cells
What are the MCV and MCH in normocytic normochromic anaemia?
What are examples of anaemias in this category?
MCV 80-95 fl & MCH >/= 27 pg
- many haemolytic anaemias
- anaemia of chronic disease (some cases)
- after acute blood loss
- renal disease
- mixed deficiencies
- bone marrow failure (e.g. post-chemotherapy, infiltration by carcinoma)
What is meant by normocytic normochromic anaemia?
Anaemia in which the average size and haemoglobin content of the red blood cells are within normal limits
under the microscope, the cells resemble normal erythrocytes
What is MCV in macrocytic anaemia?
What are the 2 different types?
MCV > 95 fl
megaloblastic:
- vitamin B12 or folate deficiency
non-megaloblastic:
- alcohol
- liver disease
- myelodysplasia
- aplastic anaemia
What is meant by macrocytic anaemia?
A type of anaemia that causes unusually large red blood cells
the red blood cells have low levels of haemoglobin
What type of anaemias is shown here?
Iron deficiency anaemia
small, pale red cells (low MCV and MCH)
variable shape and size with long thin “pencil” cells
What feature is visible in anaemia caused by vitamin B12 deficiency?
Hypersegmented neutrophils and oval macrocytes
