Flashcards in 0513 - Thrombosis and embolism - CS Deck (12):
What is haemostasis?
The physiological sealing of blood vessel defects - initiated by platelet adhesion and fibrin deposition. It is the first stage of wound healing. The opposite of hemostasis is haemorrhage. Results in either a blood clot (good) or a thrombus (bad).
What is thrombosis?
The pathological occlusion of blood vessels - in response to endothelial damage, stasis, procoagulants. Eg. a clot can form on the inside of vessel without an obvious injury and does not dissolve naturally
Briefly describe the physiology of coagulation, from initiation to clot formation
-Blood vessel is injured, exposing subendothelial structures and collagen-Vasoconstriction slows blood flow-Von Willebrand factor is released leading to platelet activation and aggregation at site of injury - forming a platelet plug.-Tissue factor (a membrane bound protein) is released leading to activation of the coagulation cascade-The coagulation cascade has two interlinked pathways (extrinsic and intrinsic) - they are a series of reactions involving zygomen “factors” being activated (they are previously produced by the liver and circulate in the bloodstream in inactive form)-End result is cleaving fibrinogen to fibrin-The fibrinolytic system is activated - fibrin monomers bind to each other and become permanently cross-linked forming a solid clot or thrombus.
List some of the functions of thrombin in the haemostasis process
-Thrombin feedback leads to positive feedback and amplification of coagulation cascade-Thrombin activates platelets, coagulation inhibitors and fibrinolysis-Thrombin cleaves fibrinogen to fibrinthere are many others...
Discuss the physiological regulation of thrombosis
The coagulation cascade pathways get amplified by positive feedback.In order to maintain homeostasis and stop coagulation from continuing indefinitely, the body also has coagulation inhibition processes:1- Thrombin also activates Protein C and its cofactor, protein S. Protein C and Protein S together cleave the activation factors V and VIII - switching them off2- Antithrombin binds to thrombin in the presence of heparin3- Tissue factor pathway inhibitor binds to tissue factor and Xa
Describe the differences between clot formation in arterial and the venous systems
Venous clot formationCombination of stasis and hypercoagulability plays a more important role than in arterial clots.Mainly constituted by fibrin and red blood cells and less by platelets - appear redInflammation, lipids and the immune system are less importantThrombus predominates Arterial clotsEndothelial damage due to shear stress plays a more important rolePlatelet rich - appear “white”Inflammation, lipids and the immune system play an important role
What is Virchow’s triad?
Describes the pathological conditions under which Virchow’s triad occurs1 - vessel wall injury2 - blood flow (stasis or turbulence)3 - blood constituents (hypercoaglability)
What is atherosclerosis?
-Formation of inflammatory fatty plaques (with a central lipid rich core) within artery walls-Primarily affects elastic arteries and medium to large muscular arteries-Multifocal
Describe how atherosclerosis forms
1. Triggered by an irritant (eg toxin from cigarette smoke, droplets of LDL in hyperlipidemia, hypertension cauing haemodynamic disturbance). Adhesion molecules are expressed2. Endothelial cells become disfunctional (in the inside layer of the arterial wall - the tunica intima). Endothelial cells start breaking down3. LDL starts to enter the tunica intima (arterial wall)4. Monocytes and T cells are recruited. Leads to chronic inflammation and accumulation of oxidised LDL which is a potent chemo-attractant for monocytes.5. Macrophages enter the vessel wall and start eating the LDL that has become embedded in vessel walls. Macrophages full of the LDL they have been endocytosing die and become ‘foam cells’ - forming fatty streaks in vessels6. Cytokines lead to the migration of smooth muscle cells into the tunica intima7. Smooth muscle cells make a fibrous cap over the fatty streak and start to lay down calcium deposits .. so the vessel narrows and becomes more stiff, less flexible and blood pressure increases
What is an embolism?
- A detached intravascular mass (gas, liquid or solid) carried by the blood to a site distant from the point of origin- Usually thrombosis but air (chest injuries, decompression sickness), amniotic fluid or fat embolism may occur- Occlusion of small vessels leads to infarction (cell death) of distal tissues- May originate from arterial, cardiac or venous location
What is arterial thrombosis and list some of the serious outcomes it can cause
Often triggered by atherosclerosis. Occurs when fatty plaque haemorrhages and ruptures. Clots form (as per haemostasis) and travel to distal sites in the body (a type of embolism)May cause:- stroke- myocardial infarction or unstable angina- femoral artery occlusion- peripheral vascular disease- mesenteric artery thrombosis- mural thrombi (MI, AF) (see diagram)