Physiology and pathology of clotting Flashcards
What is the equation to find the haematocrit?
Haematocrit = Height of RBC’s / Total height
What is the composition blood?
Plasma
Erythrocytes
Leukocytes
Platelets
What is the composition of plasma ?
Electrolytes
Plasma proteins
Carbohydrates
Lipids
What process are principal protein separated from plasma?
Electrophoresis
What are 3 major principal proteins?
Albumin
Fibrinogen
Globulins
What is the most abundant element in haemotcrit?
Erythrocytes
Structure of an erythrocyte
Non-nucleated biconcave discs
How is the cytoskeleton of an erythrocyte anchored to the plasma membrane?
Glycophorin
Band 3 Cl- HCO3 exchanger
What are the 3 major functions of erythrocytes?
O2 carriage from lungs to systemic system
CO2 carriage from tissue to lungs
Buffering of acids/bases
What are the 2 classification of white blood cells?
Granulocytes
Non-granular
Role of a neutrophil?
Phagocytose bacteria
Is a neutrophil a granulocyte or non-granular wbc?
Granulocyte
Function of Eosinophil?
Combat parasites and viruses
Is an eosinophil a granulocyte or non-granular?
Granulocyte
Function of a basophil?
Release IL-4, histamine, heparin and peroxidase
Is a basophil a granulocyte or non-granular?
Granulocyte
Function of a lymphocyte?
Mature into T cells and B cells (plasma cells)
Is a lymphocyte a granulocyte or non-granular?
Non granular
What is a monocyte?
- Non granular wbc
Macrophage
Dendritic cell
Where are platelets formed?
Megakaryocytes in bone marrow
What is the feedback mechanism for platelet production?
Platelet receptor for TPO ->
Abundant platelets bind TPO ->
So megakaryocytes are not generated ->
Meaning no platelets are produced -?
So receptors no longer bind TPO ->
TPO stimulates megakaryocyte production ->
So platelets are produced
Describe the composition of a platelet?
Nucleus free fragments -
- Mitochondria
Lysosomes
Peroxisomes
Alpha granules
Dense core granules
What do alpha granules in platelets contain?
Von Willebrand factor
Clotting factor 5
What is the external coat of a platelet covered in?
Platelet receptors
Describe the structure of the inner skeleton of a platelet
Circumferential band of tubulin microtubules
What is the relationship between blood flow and haematocrit?
Blood flow decreases with increasing haematocrit
Describe viscosity in terms of blood flow.
Resistance to sliding of shearing fluid layers
What is blood viscosity dependent on?
Haematocrit
Fibrinogen plasma conc
Vessel radius
Linear velocity
Temperature
What is a concentric cylinder in terms of blood flow?
Different velocities of blood flowing through different layers of the blood vessel at different velocities
What happens to velocity as you get closer to the centre of the blood vessel?
The velocity increases
- Each concentric layer gets faster than the prior layer
Where is concentration of rbc highest in a blood vessel?
In the centre
Describe plasma skimming
Plasma layer around the branching vessel
- Due to no rbc on the outer layer of the vessel
- Lower haematocrit in this region
How is skimming prevented?
Via arterial cushioning
Describe tank treading.
Membrane of vessel rolls like a tank tread
Helps achieve plasma spin
What are lamina layers limited to?
The width of the rbc
What happens to rbc in vessels smaller than the rbc?
Rbc are deformed and the viscosity falls
When does laminar blood flow turn to turbulence?
When blood flow is above a critical velocity
What happens to the parabolic profile in turbulence?
The parabolic profile becomes blunted
What is local stenosis?
A restriction
What combination of factors will cause turbulent flow?
Large radius
High velocity
Local stenosis
How would you identify turbulence?
Produces a murmur whereas laminar is silent
What are the 4 methods for haemostasis? (prevention of haemorrhage)
Vasoconstriction
Increased tissue pressure
Platelet plug
Coagulation
What factors are involved in vasoconstriction?
Thromboxane A
Serotonin
Thrombin
Endothelin -1
How does increasing tissue pressure prevent haemorrhage?
Decreases transmural pressure
- Difference between intravascular pressure and tissue pressure
What are the steps involved in a platelet plug?
Adhesion
Activation
Aggregation
Describe platelet adhesion
Mediated by platelet receptors bound to ligands
- Von Willebrand factor is released and binds to collagen and platelets
What is the release of Von Willebrand factor triggered by?
High shear forces
Cytokines
Hypoxia
What does breach of endothelium expose?
Collage
Fibronectin
Laminin
Describe platelet activation.
Ligand binding leads to conformational change ->
Intracellular signalling cascade ->
Release reaction/exocytosis of dense storage granules or ->
Cytoskeletal changes (lamellipodium and filopodia)
Describe platelet aggregation
Activation leads to conformational change in the receptor ->
Allowing it to bind to fibrinogen, forming molecular bridges between platelets
What is a blood clot composed of?
A semisolid mass of :
Erythrocytes
Leukocyte
Serum
Mesh of fibrin
What is thrombus?
An intravascular clot
What are the 2 clotting pathways?
Intrinsic pathway- surface contact activation on activated platelet membrane
Extrinsic pathway - membrane bound tissue factor activation, from blood contact with material from damaged cell membrane
What do the 2 clotting pathways end in?
Common pathway that generates Thrombin and stable fibrin
What are the blood clot preventions?
Homeostatic mechanisms
Paracrine factors
Anticoagulant factors
Name 2 paracrine factors which prevent clotting
NO (platelet adhesion)
Prostacyclin (promotes vasodilation)
Name 2 anticoagulant factors which prevent clotting
Tissue factor pathway inhibitors
Antithrombin
Describe the mechanism of TFPI
Maintain antithrombic surface
Bind and inhibit the pathway
Prevent the downstream cascade when binding to a complex
Describe the mechanism of antithrombin
Stops activation of various factors
Modulators of clotting to prevent when no injury has occured
What is a thrombus?
An intravascular blood clot
What is venous stasis?
Valves of the vasculature aren’t working properly
What is hypercoaguability?
Coagulation at a higher rate
When does arterial thrombosis occur?
Following the erosion or rupture of atherosclerotic plaque
