Week 3 - Blood and Haemostasis Flashcards
What is another word for red blood cells
Erythrocytes
Shape of RBCs
Biconcave discs
What is different about erythrocyte cell structure
Lacking organelle such as nucleus, mitochondria, ribosomes etc
They do have a cell membrane however
What does blood typing categorise individuals based on
Antigens found on the surface of red blood cells
3 components of red blood cell antigens
Proteins
Glycoproteins
Glycolipids
Describe the structure of haemoglobin
Tetrameric heterodimer composed of 2 alpha globin chains and 2 beta globin chains which each contain a haem group
(A1+B1) (A2,B2)
How is haem connected to the globulin chain
Histidine
Reversible binding occurs between oxygen and which atom, that composes haem?
Fe2+
Which secondary protein structures support the haem group?
Alpha helices
During oxygenation and deoxygenation of haemoglobin what structural change occurs?
Allosteric conformational change (change in protein structure due to binding of a molecule at an allosteric site)
Describe how cooperative binding affects oxygenation of haemoglobin
As oxygen binds to one of the haem groups, the affinity that haem has for bonding of subsequent oxygen molecules increases
Haemoglobin develops where 2-6 weeks after fertilisation?
Yolk sac of embryo
Haemoglobin develops where 6-30 weeks after fertilisation?
In the liver/spleen/(lymph nodes)
Haemoglobin develops where 30 weeks after fertilisation?
Bone marrow
Describe the composition of haemoglobin
97% HbA (adult haemoglobin)
1% HbF (fetal haemoglobin)
2% HbA2 (minor adult haemoglobin)
How many molecules of oxygen bind to each molecule of haemoglobin
4
2 roles of haemoglobin
Carries oxygen from the lungs to the peripheral tissues AND carries carbon dioxide back from peripheral tissues to the lungs
Has a buffering function (i.e keeps pH within erythrocyte stable)
What is the approximate lifespan of erythrocytes
120 days
What happens to erythrocytes at the end of their lifespan
They are targeted for phagocytosis by the macrophages of the reticuloendothelial system
What is the reaction that occurs when erythrocytes catalyse reaction between water and carbon dixoide
Carbon dioxide + water –> carbonic acid
CO2 + H2O –> H2CO3
What is the hormone that triggers erythrocyte production
Erythropoietin
Describe the composition of the blood and give percentages
Plasmin (55%) -
* Amino acids
* Electrocytes
* Gases
* Nitrogenous waste
* Nutrients – fat and glucose particles
* Proteins – albumin, globulins, enzymes, clotting factors like fibrinogen
Buffy coat (<1%) -
* Leukocytes
* Thrombocytes
Erythrocytes (45%)
5 stages to blood clotting mechanism
- Vasoconstriction
- Formation of platelet plug
- Formation of blood clot
- Eventual growth of fibrous tissue in the blood clot to close the hole permanently
- Clot lysis
Describe the mechanism of platelet plug formation
Platelets contact exposed collagen on vascular wall, swell and produce pseudopodial projections
Swelling causes release of active factors causing them to become sticky and adhere to collagen and Von Willebrand factor
Willebrand factor leaves circulation and enters tissue causing production of ADP and activated thromboxane
ADP and activated thromboxane attact and activate nearby platelets which adhere to the original activated platelets
Where is thromboxane produced
In enzymes found in the platelets
Is the intrinsic or extrinsic pathway faster?
Extrinsic is faster
What initiates the extrinsic pathway
Blood vessel tissue trauma
What initiates the intrinsic pathway
Activated blood platelets
What is the common product of the intrinsic and extrinsic pathway
Prothrombin activator
How long until blood clotting starts after major trauma
15-20 seconds
How long until blood clotting starts after minor trauma
1-2 minutes
Where is prothrombin produced
Continually in the liver
Which vitamin is required for production of prothrombin
Vitamin K
What is the first structural change thrombin makes to fibrinogen
It removes 4 low molecular weight peptides forming a fibrin monomer
What does fibrin-stabilising factor do
It creates covalent bonds between the fibrin monomers as well as cross linkages between adjacent fibrin fibres
Which factors cause the cross linking of adjacent fibrin strands
Factor VIIIa
Once the blood clot is formed what molecules does it trap
Red blood cells
Plasma
Platelets
Other than to other fibrin polymers, where else do fibrin fibres adhere to
Damaged surfaces of blood vessels
Which factor causes the conversion of plasminogen to plasmin
tPA
What causes clot lysis
Plasmin
Once clot has been produced, what further tightens the damaged perforation
The blood clot expresses most of its fluid within 20-60 minutes
What is the name of the fluid that is expressed from the blood clot and how does this differ from plasma
Serum - lacks fibrinogen and other clotting factors
Describe the positive feedback action of thrombin
Further breaks down prothrombin to produce more thrombin
Intrinsic and extrinsic pathways are further stimulated
This positive feedback continues until blood leakage seizes
Describe the action of heparin
ANTICOAGULANT
Enhances the natural effect of antithrombin
Describe the action of antithrombin
ANTICOAGULANT
Natural anticoagulant found in the liver that inhibits thrombin, Xa and IXa.
Describe the action of low-molecular-weight-heparin
Chemically splits heparin into pieces about 1/3 of original size. There are fewer side effects and more predicable results when compared to heparin
Describe the mechanism of warfarin
A vitamin K antagonist. Works since vitamin K is required to produce a lot of clotting factors. Takes a few days to work since residual factors must be cleared first.
What are drugs that target specific factors called
Direct oral anticoagulants
Name 2 drugs that prevent the breaking up of blood clots
Transexamic acid
Aprotinin
How does transexamic acid work
It inhibits the activation of plasminogen to plasmin as a non-competitive inhibitor
How does aprotinin work
Inhibits plasmin alongside. other enzymes such as trypsin and chemotrypsin
What is the name for drugs that prevent the breaking down of blood clots
Antifibrinolytic drugs
Which test is a measure of the time it takes for fibrin to form via the extrinsic pathway
Prothrombin time (PT)
Which test is a measure of time it takes for fibrin to form via the intrinsic pathway
Activated partial thromboplastin time
What is a normal PT
9-12 seconds
What is a normal APTT
23-38 seconds
Which factor is affected in haemophilia A
VIII
Which factor is affected in haemophilia B
IX
Why do patients with Von Willebrand disease have lots of bruises/excessive bleeding
Von Willebrand factor is required for platelets to stick together - patients with the disease have low levels of VW factor
Which cell do platelets originate from
Megakaryocytes
Which cells eliminate platelets
Macrophage
Which molecules in platelets are required for formation of projections
Actin and myosin
What causes platelets to adhere to damaged sections of vessel walls and not normal endothelium
Glycoprotein
What do you call the process of blood cell formation
Haematopoiesis
What is extra-medullary haematopoiesis
production of blood cells in the liver, lymph node and spleen
What are progenitor cells called that are involved in extra-medullary haematopoiesis
Common lymphoid progenitor
What are the progenitor cells called that are involved in medullary haematopoiesis
Common myeloid progenitor
Where does the majority of haematopoiesis happen during fetal development
In the liver and spleen
What causes an increase in blood cells in the liver/spleen after birth?
Infection or onset of a disease since they have to work extra hard to produce immune cells for example
What is a clinical sign of infection relating to extra medullary haematopoesis
Swelling of liver/spleen/lymph nodes
Haematopoiesis is regulated by which what, and what are two examples of these?
Cytokines
- interleukins (IL)
- stimulating factors
What do cytokines control in the context of haematopoiesis
Proliferation
Differentiation
Death
(of progenitor cells)
What initiates the production of blood cells
Progenitor cells develop surface receptors for a specific stimulating factor and when stimulating factors bind, they lose their potency and remain committed to producing that certain cell type
3 examples of cytokines that influence haematopoiesis
Erythropoietin (EP) - erythrocyte production
Colony-stimulating factors (CSFs) - granulocyte and macrophage production
Thrombopoietin (TPO) - megakaryocyte production which produce platelets
Why is sodium citrate used in blood transfusion
Chelates calcium ions, preventing blood clot formation for some time. Sodium citrate is easily metabolised by the body as well, so calcium ions are made available in vivo
What is an example of a Zymogen
Fibrinogen
