Atherosclerosis Flashcards
What is arteriosclerosis?
Arteriosclerosis is a thickening and loss of elasticity in arteries, of which there are two main types - arteriolosclerosis and atherosclerosis.
What is arteriolosclerosis?
Arteriolosclerosis is a thickening in the small arteries and arterioles causing a decrease in the lumen size related to systemic hypertension and diabetes.
What is atherosclerosis?
Atherosclerosis is a progressive, inflammatory disease of medium-large sized arteries due to endothelial injury.
What are the stages of atherosclerosis?
- Endothelial dysfunction
- Formation of a fatty streak
- Development of a lipid plaque
- Advanced plaque
Explain: Stage 1, Endothelial Dysfunction?
- damage to endothelium due to smoking / high LDL
- upregulation of inflammatory adhesion molecules such as ICAD-1
- ICAD-1 causes monocyte and platelet adhesion to endothelium
- damage causes increased permeability to lipids and LDL and they accumulate in the intima
Explain: Stage 2, Formation of a fatty streak?
- LDL and lipids accumulate in intima, and LDL becomes oxidised
- Oxidised LDL chemotactic for monocyte and they migrate into intima, take up LDL and become foam cells
- PDGF release from macrophages, platelets and endothelium
- PDGF causes smooth muscle cell migration from media into intima
Explain: Stage 3, Development of a lipid plaque?
- Dying foam cells release lipids to create lipid pools in intima
- Internal elastic lamina is disrupted (later to be replaced with collagen)
- Collagen deposition begins to occur in intima
- Smooth muscle proliferation and macrophage migration into intima continues
Explain: Stage 4, Advanced Plaques?
- consists of rich lipid core and fibrous cap
- core consists of free lipid, macrophages, smooth muscle cells and cellular debris
- cap composed of collagen and sits underneath endothelium
What is Glagovian Remodelling?
Remodelling of media allowing a vessel to increase its diameter to accomodate a plaque without compromising the vessels lumen.
In normal vessels, the lumen size is reduced due to the plaque and hence blood flow is altered or reduced.
In Glagovian vessels, the plaque grows towards the endothelium rather than the lumen, and the lumen diameter expands allowing for compensation for the plaque to hence gain normal blood flow.
What are the risk factors for atherosclerosis?
Modifiable
- diabetes mellitus (type 2 diabetes)
- hypertension
- smoking
- hyperlipidaemia (high LDL/low HDL)
- obesity
- sedentary lifestyle
- diet high in saturated fat
Non-modifiable
- genetic predisposition ( family history)
- age (older)
- sex (men more likely due to protective oestrogen until menopause)
What drugs can lower cholesterol?
Statins
Bile acid resins
Absorption inhibitors
What drugs lower triglycerides?
Niacin
Fibrates
Examples of Statins and how they work?
- Simvastatin
- Atorvastatin
Statins are HMG CoA reductase enzyme inhibitors. They work by inhibiting the HMG CoA reductase enzyme which reduces acetyl CoA into cholesterol (and is the rate limiting step of cholesterol). By reducing the synthesis of cholesterol, this reduces the level of cholesterol (and LDL) in the blood
Examples of Bile Acid Resins and how they work?
- Colestipol
- Colestyramine
Bile acid resins work by binding to bile acid to make an insoluble complex, meaning bile acids cannot be reused like the usually do and have to be synthesised again. As cholesterol is a main factor of bile acid, this continual synthesis of new bile acid means a reduction of cholesterol (and LDL) in the blood.
Examples of Absorption Inhibitors and how they work?
- Ezetimibe
Ezetimibe, and other cholesterol absorption inhibitors, stop the absorption of cholesterol through the NPC1L1 receptor in enterocytes in the lumen, hence reducing the uptake and absorption and therefore reducing the plasma levels of dietary cholesterol.
