Haemostasis and Atherosclerosis Flashcards
What is an atheroma?
- Abnormal accumulation of material in the inner layer of the wall of an artery
- Material consists of macrophages, debris, lipids, fibrous material
Describe the process of atherogenesis
- White blood cells attach to damaged endothelial cells which express adhesion molecules - diapedesis occurs (monocyte enters intima)
- Cholesterol accumulates and oxidises causing an inflammatory response in the tunica intima
- Monocytes enter the artery turning to macrophages and then foam cells once they digest cholesterol
- Foam cells degenerate releasing there contents which are engulfed by other macrophages
- This process produces an area with a lipid core that forms a plaque which endothelial cells cover
- The plaque grows and accumulates more lipids, dead cells and calcium salts, additionally, SM cells proliferate and produce collagen
- If endothelial cells are compromised blood clots can form on vessel wall (thrombus), these may break off
What is arteriosclerosis?
The process by which blood vessels become thick and stiff - often restricting blood flow
What are foam cells?
- Type of macrophages that localise to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins.
What cells are contained in the tunica media?
Smooth muscle cells
What is the tunica adventitia/externa made up of?
Connective tissue (mainly collagen)
What is the process called by which monocytes enter the tunica intima?
Diapedesis
What causes LDLs to become oxidised in the tunica intima?
Dysfunctional endothelial cells release reactive oxygen species (ROS) and metallo-proteases
- Oxidation means the LDLs become trapped in the tunica intima
What triggers endothelial cells to express adhesion molecules for WBCs? (there are 2 main factors)
- Dysfunctional endothelium (due to damage) and subsequently the:
- Oxidised LDL
What do foam cells release to attract more macrophages?
Chemokines
What do foam cells release which cause SMCs to migrate and proliferate?
IGF-1
What can cause inflammation within the tunica intima?
- Foam cells can release DNA material which attracts neutrophils
- Foam cells can release proinflammatory cytokines and ROS
- T cells bind to adhesion receptors on endothelial cells and enter plaque area, release IF-y after activation by macrophages
What is the blood supply called that supplies larger vessles?
Vasa vasorum (when a plaque is formed this blood supply increases)
What substance do endothelial cells release when injured to cause smooth muscle contraction?
Endothelin
What is protein C activated by?
Thrombin
What does protein C degrade?
factors V and VIII
What does ATIII (Antithrombin 3) degrade?
Factors II, IX, X
What does heparin sulphate (glycosaminoglycan) bind to to activate?
ATIII (antithrombin 3)
What receptor on the platelet binds to VWF?
GPIb
What does the binding of GPIb to VWF cause the platelet to release?
- ADP
- TxA2
- Serotonin
What receptors on the platelets bind together to create a platelet plug?
GPIIb/GPIIIa
What do TxA2 and ADP cause?
Platelets to aggregate at the site of the injury
What does TXA2 and 5HT do?
Cause vasoconstriction
What are the 3 factors in vascular spasm?
- Endothelin release, activating SM contraction
- Myogenic mechanism by SM (due to contact)
- Inflammatory molecules stimulating nociceptors which initiate constriction of blood vessels
