Intro to haematology Flashcards
Define haematology?
Biology and pathology of the cells that normally circulate in the blood
What is meant by haemapoiesis/haematapoiesis?
The physiological developmental process that gives rise to the cellular components of the blood - a single haematopoietic stem cell can divide and differentiate to form different cell lineages that will populate the blood
What are the 4 directions a haemapoietic stem cell can take in its first division, how does each affect the stem cell pool?
1) Symmetric self renewal - 2 stem cells formed (increase in stem cell pool)
2) Assymetric self renewal - 1 stem cell and progenitor formed (maintenance of stem cell pool)
3) Lack of self renewal to form 2 progenitors (depletion of stem cell pool)
4) Lack of self renewal - no division (maintenance of stem cell pool)
What 2 different cells can a haemapoietic cell divide to form in its first cell division?
1) Another stem cell
2) Progenitor (daughter cell which has undergone an element of differentiation and lost self renewal capacity, can go on to differentiate into any blood cell)
What are the 4 properties of a haemapoietic stem cell?
1) Differentiation potential for all lineages
2) High proliferative potential
3) Long term activity throughout the life span of the individual
4) Self renewal ability
What are the 2 main haemapoietic lineages?
1) Myeloid
2) Lymphoid
What 3 main types of cell does the myeloid line give rise to?
1) Granulocytes (WBCs)
2) Erythrocytes
3) Platelets
What 3 main cell types does the lymphoid line give rise to?
1) B lymphocytes
2) T lymphocytes
3) Natural Killer cells
What 4 stages of cells are involved in haemapoiesis?
1) Multipotential stem cell
2) Pluripotential stem cell (either moved to myeloid or lymphoid lineage at this point)
3) Committed cells (form 1 type of cell)
4) Mature cells
On which day and where in embryogenesis is any sign of haemapoiesis first seen, is this the beginning of haemapoiesis?
Seen in trophoblast at 9 days
Erythroid cells from yolk sac area
This is the first sign of haemapoiesis but is a false start and not the beginning
Where does haemapoiesis fully begin in the foetas on what day of embryogenesis?
Starts at day 27
In the aorta gonad mesonephros area
On which day of embryogenesis does haemapoiesis at the AGM expand rapidly?
Day 35
What happens to haemapoietic activity at the AGM on day 40 of embryogenesis?
Haemapoiesis rapidly disappears from the AGM
Haemapoietic stem cells migrate through the wall of the aorta into the bloodstream and travel to the liver which then becomes the subsequent sight of haemapoiesis
What are the 4 roles of blood cells?
1) Oxygen transport
2) Coagulation
3) Immune response to infection
4) Immune response to abnormal cells (senescent, malignant)
What is the shape and life span of erythrocytes?
Bi-concave discs (7.5micrometers in diameter)
120 days in blood
How many RBCs can be found in the body?
333,200 x 10^6
What is the term for reduced red cells?
Anaemia
What is the term for raised red cells?
Polycythaemia
What is relative polycythaemia?
Red cell count is not abnormally raised but as plasma volume is reduced the red cell count is raised in comparison
What are the 3 types of leukocytes (WBCs)?
1) Granulocytes
2) Lymphocytes
3) Monocytes
What are the 3 types of granulocytes, what is distinctive about granulocytes?
Have cytoplasmic granules
1) Neutrophils
2) Eosinophils
3) Basophils
What is the main action of neutrophils?
Phagocytic cells
What is the most common white cell in adult blood?
Neutrophils
What is the term for increased numbers of neutrophils?
Neutrophilia
In which 2 common situations is neutrophilia likely to occur?
1) Bacterial infection
2) Inflammation
What is the life span of neutrophils?
Only a few hours in the blood
What is the term for reduced numbers of neutrophils, when might this occur?
Neutropenia
May occur as a side effect of drugs
What is the term for increased numbers of eoisinophils?
Eosinophilia
In which 2 situations is eoisinophilia likely to occur?
1) Parasitic infection
2) Allergies
Are basophils abundant in the blood?
No they are a rare cell
What is the term for increased numbers of basophils, when may this occur?
Basophilia
Occur in chronic myeloid leukaemia
What are the 2 roles of monocytes?
1) Phagocytic cells
2) Antigen presenting cells
What are monocytes identified as once they leave the blood and enter the tissues?
Macrophages or histiocytes
Monocytes which migrate into the liver tissue become what?
Kupffer cells in liver
Monocytes which migrate into the skin become what?
Langerhans cells in the skin
What is the term for increased numbers of monocytes, in which disease specifically would this occur?
Monocytosis
Tuberculosis
Are natural killer cells a part of the innate or adaptive immune system?
Innate
What type of cell are natural killer cells?
Large granular lymphocytes
What is the role of natural killer cells, what do they identify?
Recognise non self - ie abnormal tissue or virus infected cells
What is the main function of B lymphocytes, why are they considered part of the adaptive immune system?
Humoral immunity - attack particles within the blood not contained within cells such as bacteria
Produce Ag
Adaptive as they modify immunoglobulin genes to enable antigen specific antibody production
What is the main role of T cells, what 3 roles specifically does this entail?
Cell mediated immunity
1) Target specific cytotoxicity
2) Interact with B cells and macrophages
3) Regulate immune response
What is the term for increased numbers of lymphocytes?
Lymphocytosis
What is term for reduced numbers of lymphocytes?
Lymphopenia
Why are T lymphocytes considered part of the adaptive immune system?
They can rearrange the genes for the T cell receptor to produce an antigen specific receptor
In which 2 situations would lymphocytosis occur?
1) Chronic lymphocytic leukaemia
2) Glandular fever (infective mononucleosis) - get atypical lymphocytes
Give an example of a situation where lymphopenia may occur?
Post bone marrow transplant
What is the term for increased plasma cells (mature B cells), in which 2 situations may it occur?
Plasmacytosis
1) Infection
2) Myeloma - malignant overproduction of plasma cells
Platelets are derived from which cells?
Bone marrow megakaryocytes
Where does haemapoiesis occur?
Bone marrow - mature cells then enter blood
What are the 4 main subdivisions of haematology in clinical practise?
1) Coagulation
2) Malignant
3) Non malignant eg anaemia, sickle cell disease
4) Transfusion
What are the 4 main types of diagnostic tests in haematology?
1) FBC
2) Blood film (or smear)
3) Coagulation screen
What are the 5 main aspects of a FBC?
1) Haemaglobin concentration Red cell parameters: 2) Mean cell volume (MCV) 3) Mean cell Hb (MCH) 4) White cell count (WCC) 5) Platelet count
What is a blood film?
Drop of blood placed on film and smeared to create a monolayer of cells which is viewed down a microscope
What is a coagulation screen?
test which measures the time take for a clot to form when plasma is mixed with specified reagents
What are the 3 main coagulation screen tests?
1) Prothrombin time
2) Activated partial thromboplastin time
3) Thrombin time
How is a bone marrow aspirate performed?
Under local anaesthetic bone marrow is aspirated from the posterior iliac crest of the pelvis and a trephine core biopsy is then taken with a hollow needle
For what 3 reasons can test results vary in a healthy person?
1) Technical failure (eg. clotted sample or variation in reagents)
2) Normal but abnormal due to intra-individual variation (eg. diurnal variation of cortisol levels)
3) Normal but abnormal due to inter-individual variation (eg. platelet count can differ between people)
What 3 consideration are relevant in establishing a reference range for what is normal in terms of FBC?
1) Define the reference population - should be relevant to the test population
2) Consider if separate ranges are required for adults versus children, men versus women etc.
3) Determine the expected range of inter individual variation
What defines the reference rang?
The set of values for a given test which incorporates 95% of the normal population - determined by collecting data from vast numbers of lab test
In tests of healthy and diseases subjects which 2 types of results overlap?
1) False negatives
2) False positive
What is sensitivity?
Proportion of abnormal results correctly classified as abnormal by the test - expresses the ability to detect true abnormality
What is specificity?
Proportion of normal results correctly classified as normal by the test
What is the normal range of Hb in g/L for men and women?
Men = 135-180 Women = 115-160
What is the normal range of WBC (same for men and women)?
4.00-11.00
What is the normal range for platelets (same for men and women)?
150-400
What is the normal range for MCV (Same for men and women)?
78-100
What is the normal range for MCH (Same for men and women)?
27-32`
What would it be necessary to do if you noticed an unexpectedly abnormal result in a patients blood test eg. thrombocytopenia?
Consider technical problems - this may be a real problem, may be an artefact. Could contact the lab to ask if thinks its an artefact
Abnormal results may be totally appropriate for the given situation - give 2 situations when an abnormal lymphocyte count would be appropriate?
1) Post splenectomy mild lymphocytosis
2) 3 months post bone marrow transplant lymphopenia
How is microcytic hypochromic anaemia classified?
Low mean cell volume
MCV
Give 4 causes of microcytic hypochromic anaemia?
1) Iron deficiency
2) Thalassaemia
3) Anaemia of chronic disease (some)
4) Lead poisoning
5) Sideroblastic anaemia (some cases)
What is sideroblastic anaemia?
Sideroblastic anemia or sideroachrestic anemia is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells
How is normocytic anaemia classified?
Reduced numbers of erythrocytes Normal mean cell volume MCV - 80-95 fl Normal mean cell Hb MHC - greater than or equal to 27 pg
Give 6 causes of normocytic anaemia?
1) Many haemolytic anaemias
2) Anaemia of chronic disease
3) After acute blood loss
4) Renal disease
5) Mixed deficiencies - folic acid, B12 & iron
6) Bone marrow failure (eg. post chemo, infiltration by carcinoma etc.)
How is macrocytic anaemia classified?
Reduced erythrocytes
Increased mean cell volume
MCV = >95 fl
What is the commonest cause of macrocytic anaemia?
Alcohol abuse
What are the 2 types of macrocytic anaemia, what is the difference?
Megaloblastic and non megaloblastic
Megaloblastic is due to inhibition of DNA synthesis in haemapoiesis
Give the 2 main causes of megaloblastic macrocytic anaemia?
Vitamin B12 deficiency
Folate deficiency
Give the 4 main causes of non-megaloblastic macrocytic anaemia?
1) Alcohol abuse
2) Liver disease
3) Myelodisplasia
4) Aplastic anaemia
How would iron deficiency anaemia appear histologically?
Small, pale red cells with variable size and shape eg. long thin ‘pencil cells’
How would Vitamin B12 deficiencies appear histiologically?
Larger cells
Presence of hypersegmented neutrophils (more than 7 nuclear lobes) and oval macrophages
Hypersegmented neutrophils are characteristic of macrocytic anaemia due to what 2 causes?
Vitamin B12 and folic acid deficiency
