Introduction to Haematology Flashcards
What are the 2 main blood groups that you need to know about?
- ABO
- RhD
What are the 4 blood types in the ABO blood type system? What
Type A - A antigens on surface
Type B - B antigens on surface
Type AB - mixture
Type O - no A or B antigens on surface and nothing to make up for these
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What are the ABO antigens?
They are sugars
- The ABO gene encodes glycosyltransferase which then adds glycans to proteins or lipids on RBCs
- A and B genes code for transferase enzymes
- A antigen is N-acetyl-galactosamine
- B antigen is galactose
- ‘O’ gene is non-functional allele
- So A and B are (co-)dominant and O is recessive
Which antibodies are produced if you have…
- A antigen on the surface of your RBCs?
- B antigen on the surface of your RBCs?
- O antigen on the surface of your RBCs?
- AB antigen on the surface of your RBCs?
- Antibodies against B
- Antibodies against A
- Antibodies against A and B
- No antibodies against either A and B
What is immune tolerance?
- Immune tolerance is the state of unresponsiveness of the immune system to antigens that have the potential to induce an immune response.
- Self tolerance to an individual’s own antigens is achieved through both central tolerance and peripheral tolerance mechanisms.
- You have active immune tolerance from birth
- If you are blood group A then you will not develop antibodies against A unless you develop some form of autoimmune haemolytic anaemia
If you were to centrifuge blood what does it split into? (3)
- Plasma 55%- contains clotting/coagulation factors, albumin and antibodies
- Buffy coat <1% - contains platelets, WBCs or leukocytes
- Red Blood Cells 45%
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What are the 3 main functions of blood?
-
Transport
- In RBCs
- Gases - O2 and CO2
- In Plasma
- Nutrients
- Waste
- Messages
- In RBCs
-
Maintenance of Vascular Integrity
- Prevention of leaks - platelets and clotting factors
- Prevention of blockages - anticoagulants and fibrinolytics
-
Protection from pathogens
- Phagocytosis and killing - granulocytes/monocytes
- Antigen recognition and antibody formation - lymphocytes
Diagram showing the development of different blood cells from the haematopoietic stem cell to mature cells (haematopoiesis)
- All cellular blood components are derived from pluripotent haematopoietic stem cells which reside in the medulla of the bone in bone marrow.
- HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs, so the pool of stem cells is not depleted (assymetric division)
- The other daughters of HSCs (myeloid and lymphoid progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell, but cannot renew themselves.
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What are the 3 lineages that all blood cells are divided into?
- Erythrocytes - functional and are released into the blood. The number of reticulocytes (immature red blood cells) gives an estimate of the rate of erythropoiesis.
- Lymphoid - lymphocytes are the cornerstone of the adaptive immune system. The lymphoid lineage is composed of T-cells, B-cells and natural killer cells.
- Myeloid - which include granunlocytes, megakarocytes and macrophages - these are involved in such diverse roles as innate immunity and blood clotting.
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Where are mature cells released into within bone marrow?
Into sinusoids (blood vessels)
Erythroid differentiation
Erythroblast –> reitculocyte –> erythrocyte
What is Erythropoietin and where is it made?
- A hormone that governs RBC and platelet production
- It is made in the kidney in response to hypoxia
What can be measured to determine the rate of red cell production?
Reticulocyte count
Very generally, what is Polycythaemia?
Too many RBCs
Very generally, what is Anaemia?
RBC count is lower than normal / low
Anaemia causes poor gas transfer and commonly causes which symptoms as a result?
SOB and fatigue
Common causes of Anaemia
- Decreased production of iron, folate and vitamin B12 which are crucial for RBC production
- Congenital - thalassaemias - low or absent haemoglobin
- Increased blood loss through bleeding or haemolysis (RBC destruction)
Lifespan of platelets?
7 days
What is Thrombocytosis?
Thrombocytosis occurs if there is an excessive number of platelets in the blood
Platelet levels increase:
- Acute inflammatory response
- Myeloproliferative diseases i.e some myeloiod malignancies cause this
An increase in platelets causes spontaneous thrombosis
What is Thrombocytopenia and what are some common symptoms of this condition?
Abnormally low levels of platelets (thrombocytes) in the blood.
Results in:
- Excessive bleeding
- Superficial bleeding into the skin which appears as petechial rash
- Bruising
- Blood in urine or stools
Causes of Thrombocytopenia (3)
- Failure of production (bone marrow failure - infiltration by leukaemia of some sort)
- Immune destruction (autoantibodies against platelets)
- Altered function - drugs such as aspirin, clopidogrel (anti-platelets)
What is G-CSF?
Granulocyte colony-stimulating factor
It stimulates bone marrow to produce granulocytes and stem cells and release them into the bloodstream - this can be used therapeutically for Neutropenia and mobilisation of stem cells
Causes of Neutropenia
- Decreased production - Drugs or Marrow failure
- Increased consumption - Sepsis (body can’t keep up with demands of infected tissues) or Autoimmune
- Altered function - eg chronic granulomatous disease
What regulates the production of neutrophils/levels of neutrophils in the blood?
Granulocyte-colony stimulating factor (G-CSF)
What can cause Neutrophilia?
- Infection - left shift, toxic granulation
- Inflammation e.g after an MI, post-operative, rheumatoid arthritis
Neutrophil development
Myeloblast –> Promyelocyte –> Neutrophilic myelocyte –> Neutrophilic metamyelocyte –> Band neutrophil –> Segmented/mature neutrophil
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What is a ‘left shift’ in terms of neutrophil level?
A left shift = a shift towards immaturity
In normal steady state only segmented/mature neutrophils should be in blood but during infection/inflammation etc there can be a so called ‘left shift’ where more immature cells are in the blood
- What is the reticuloendothelial system (RES)?
- Which cells make up RES?
- RES consists of cells descending from monocytes which migrate into tissues and become macrophages or dendritic cells, performing phagocytosis of foreign materials and particles.
- 90% of the RES are located in the liver.
- Monocytes (dendritic cells and macrophages)
- Their function is to ingest and destroy pathogens (like neutrophils) but they are specialised to present these to lymphocytes
Types of myeloid cells (6)
Neutrophils
Monocytes (present in blood)
Eosinophils
Basophils
Erythrocytes (RBCs)
Macrophages (present in different tissues)
Types of lymphoid cells
Lymphoid stem cell –> Lymphoblast –> natural killer cell, T cells and B cells
- B cell –> plasma cell
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Diagnostic tools in blood disorders (6)
- Full blood count + blood film
- Clotting times for clotting factors and platelets
- Chemical assays - iron, B12 or folate
- Marrow aspirate and trephine biopsy
- Lymph node biopsy or other organ biopsy
- Imaging