What composes plasma?
- Plasma if the yellow/straw coloured liquid portion of blood (non-clotted) - Keeps cells in suspension - 92% water - 7% plasma proteins (albumin, fibrinogen, prothrombin) - 1% other substances - electrolytes, nutrients, hormones, gases, waste products. - Serum is plasma devoid of clotting factors (achieved by drawing blood in the absence of an anti-coagulant).
What is serum?
Serum is centrifuged blood to remove cellular components. Anti-coagulanted blood yields plasma containing fibrinogen and no clotting factors.
Where does haematopoeisis occur most commonly throughout a human lifespan?
- Bone marrow only becomes major producer of RBC about half-way through lifetimes.
- Blood cells regulated by environment by stromal cells.
Which types of white blood cells are found in tissues?
- Mast cells
- Dendritic cells
Macrophages and Dendritic cells come from monocytes.
Memorise the diagramatic overview of all blood cell progenitors.
How is haematopoiesis regulated?
Production of blood and immune cells is tightly controlled by cytokines and growth factors.
EPO - erythropoietin.
TPO - thrombopoeitin
IL - Interlukin
G-CSF - Granulocyte Colony Stimulating Factor
GM-CSF - Granulocyte Macrophage Colony Stimulating Factor
SCF - Stromal Cell Factor
Explain the process of Erythropoiesis
- Erythropoiesis is the process of RBC formation.
- Occurs in the bone marrow.
- Body produces approximately 2.5x10^6 RBC every second.
Hypoxia is detected by kidney cells.
Kidney releases EPO into blood.
Erythropoiesis is regulated by EPO binding to erythropoietin kinase receptor on progenitor cells.
Describe the structure of Haemoglobin (Hb).
- 2 identical alpha chains & 2 identical beta chains. Each chain is associated with a Heme molecule.
- Fe molecule in centre
- Porphyrin ring linked to Iron as a co-factor
- Every RBC has around 280 million haemoglobin molecules and each haemoglobin molecule can carry 4 02.
What is the lifespan of Red Blood Cells?
How are erythrocytes recycled?
- Aged cells are removed by macrophages of the spleen.
- Haemoglobin is seperated into Iron and Porphyrin ring.
- Iron transported to bone marrow via transferrin for new RBC production
- Porphyrin ring excreted via digestive or urinary tract.
(Bilirubin - Urine, Biliverdin - faeces)
What is the lifespan of platelets?
What is the process of platelet production?
- Magakaryocyte (contains 64 copies of DNA)
- Megakaryocytes can produce around 5000 platelets, which occurs through its budding off mechanism. Membrane will extend but platelets will fragment off.
- Thrombocytes are regulated by thrombopoeitein (TPO), produced by the liver and kidneys.
- They secrete PDGF in regulating blood vessels.
What are the five cardinal signs of inflammation?
- Loss of Functioning
What's wierd about natural killer cells?
They are part of the innate immune response despite being part of lymphoid progenitor.
They have a relatively long life (around 14 days). They are essential for killing virally infected cells and comrpomise around 15% of WBCs.
What are the characteristics and functions of Neutrophils?
- Lifespan: 5.4 days
- 60-70% phagocytic
- Initiate inflammatory process.
What are the characteristics and functions of Eosinophils?
Lifespan: 2-5 days
2-5% of WBC
Phagocytic - protection against helminths.
What are the characteristics and functions of Basophils?
- Lifespan: 1-2 days
- 0.2% of WBC
- Involved in allergic reactions
What are the characteristics and functions of monocytes?
Lifespan: 1-7 days
2-10% of WBC phagocytic
What is polycythemia vera and how would you test for it?
Neoplasm in which the bone marrow makes too many red blood cells.
- It may also result in overproduction of white blood cells and platelets.
What is Polycythemia vera and what causes it?
- Increased haemoglobin, PCV and RBC numbers
- 95% of cases due to mutation in the gene encoding the cell signalling Janus Kinase 2 (JAK2)
- Complications of PV include thrombosis and haemorrhage
Mutation in gene V617F (valine to phenylalanine mutation) results in constitutive activation of EPO/TPO receptors even in absence of EPO.
What is essential thrombocythaemia (another type of Polycythaemia)
- Normal Hb and WBC levels but increased platelet counts.
- Complications include thromboembolic events.
- JAK2 mutation present in 50% of all cases.
What is Myelofibrosis/myelosclerosis? (another polycythemia)
- Elevated WBC and platelet count
- 25% of cases preceded by PV
- 50% of cases have a JAK2 mutation.
What treatment options are available for those with Polycythaemia vera?
Aims to maintain normal blood count
Venesection - removal of blood (about a 1 pint)
Chemotherapy can suppress immune system in low doses, maybe that's how it works? Through inhibition of IL-2? Look this shit up?
What are the most common systems for grouping blood?
ABO and Rhesus
What are A and B antigens?
Present on red cell membrane glycoproteins and glycolipids.
The major carriers of A and B on red cells are the abundant N-glycosylated glycoproteins, the anion exchanger (band 3) and the glucose transporter (GLUT1).
Glycosyltransferase structure is encoded by different genes
Type A: N-acetylgalactoaminyltransferase
Type B: galactotransferase
Type O (H): no transferase
What is present on type A red blood cells?
How can Rhesus Disease develop?
Two genes encode this blood group:
- Most important is D
- Why is D antigen important?
- Because it is capabale of resulting in Rhesus disease.
Explain the Rh blood group system
- 5 major Rh antigens - D, C, E, c and e - most immunogenic is D.
- Encoded by two genes: RHD and RHCE
- Individuals can be homozygous for RHD (2 copies) or hemizygous (1 copy).
- All express D antigen on RBC
- Individuals where RHD is deleted have no expression of D antigen.
- Individuals are RhD+ or RhD-
- No anti-D antibodies present in blood
How does Rhesus disease manifest?
- 85% of population
- Range in effect: mild anaemia of newborn to intrauterine death 18 weeks after gestation
- HDN is relatively rare - alleviated through routine antenatal serology and administration of Anti-D therapy
- Anti-D immunoglobulin will bind and neutralise any RhD+ cells preventing the development of maternal antibodies.
Which blood group would make you a universal recipient and a universal donor?
Explain the process of agglutination.
Agglutination is an immune response factilitated by antibody-antigen interactions.
Agglutination is detrimental in vivo.
This is not coagulation
Work out possible blood types of a baby based on mother and father's blood types. (or just memorise this diagram).