Atherosclerosis Flashcards
Define Arteriosclerosis
Thickening of the walls of arteries and arterioles usually as a result of hypertension/diabetes mellitus, often associated with loss of elasticity
What can Arteriosclerosis result in
Poor tissue perfusion
Inelastic/weak vessels (→aneurysm)
Risk of thrombus formation
Define Atherosclerosis
Accumulation of intracellular and extracellular lipid in intima and media of large medium sized arteries
Define Atheroma
Necrotic core of the atherosclerotic plaque. Thickening of arterial walls as a consequence of atherosclerosis
Explain the cellular events and proposed theories that lead to the formation of atherosclerotic lesions
Thrombogenic theory:
Plaques formed by repeated thrombi, lipid derived from thrombi, fibrous cap
Insudation theory: Endothelial→Inflammation→Increased permeability to lipid from plasma
Monoclonal hypothesis:
Each plaque is monoclonal, abnormal smooth muscle proliferation
Reaction to injury hypothesis:
(Chronic inflammatory and healing response of the arterial wall to an endothelial injury)
Plaques form in response to endothelial injury→Increases permeability and allows platelet adhesion→Monocytes penetrate endothelium→Smooth muscle cells proliferate
Outline the components of atherosclerotic plaque
Cells: Endothelial cells, platelets, neutrophils, macrophages, leucocytes, smooth muscle cells
Lipid: Intracellular (FOAM cells) and extracellular (POOLS)
Extracellular matrix: Collagen, elastin, proteoglycans
Describe the roles of these components in atherosclerosis
-Endothelial cells
-Platelets
-Smooth muscle cells
-Macrophages
-Lymphocytes
-Neutrophils
Endothelial cells:
Haemostasis, altered permeability to lipoproteins, production of collagen, stimulation of proliferation & migration of smooth muscle cells
Platelets:
Haemostasis, stimulation & migration of SMC
Smooth muscle cells:
Take up LDL and other lipid to become foam cells, synthesis of collagen & proteoglycans
Macrophages:
Oxidise LDL, Take up lipids to become foam cells, Secrete proteases which modify matrix, Stimulation of proliferation and migration of SMCs
Lymphocytes:
TNF (tumour necrosis factor) may affect lipoprotein metabolism, Stimulation of proliferation & migration of SMCs
Neutrophils:
Secrete proteases leading to local damage and inflammation
Microscopic appearance of atherosclerosis
Fatty streak
-proliferation of SMC
-accumulation of foam cells
-extracellular lipid
Stable plaque
-fibrosis
-necrosis
-cholesterol clefts
-inflammatory cells
Unstable plaque
-disruption of internal elastic lamina
-damage extends into media
-new vessels grow into plaque (from adevntitia
-plaque fissuring (laminar cracking)
Difference between stable and unstable plaque
Unstable has a thinner fibrous cap and more likely to rupture. It has a higher risk of heart attacks and strokes
Macroscopic appearances of atherosclerosis
Check Images
Fatty streaks: yellow, intima
Stable plaque: raised yellow, irregular outline, widely distributed, enlarge and coalesce (come together)
Unstable plaque: yellow&red, irregular, rough, hard, calcified
Complications of Atherosclerosis
Ulceration
Thrombosis
Vasospasm (narrowing brain BV)
Embolisation
Calcification
Haemorrhage
Aneurysm formation
Rupture of atherosclerotic artery
Common sites of Atherosclerosis
Coronary arteries
Carotid arteries
Abdominal arteries→Mesenteric ischaemia, Acute bowel ischaemia, AAA
Peripheral arteries
Renal arteries
Modifiable risks of atherosclerosis
Hyperlipidaemia (high lv. of LDL)
Hypertension
Smoking (predisposition of thrombosis)
Obesity (↑risk of diabetes mellitus, hypertension, hyperlipidaemia)
Non-modifiable risks of atherosclerosis
Age (elderly)
Sex (male) oestrogen is protective of atherosclerosis
Post menopause: sudden drop in oestrogen
Family history: genetic conditions such as hypercholesterolemia
Sign of hypercholesterolaemia
Corneal arcus: deposition of lipid in the outer edges of cornea forming a white ring
Tendon xanthoma: deposition of lipid in tendons which form lumps under skin
Xanthelasma: Deposition of lipid in the skin around the eyelids
Prevention of Atherosclerosis
Decrease total Cholesterol and LDL in diet
Lipid lowering drugs (statin)
Low fat and high fibre diet
Aspirin
Management of Athersclerosis
Statins
Anti-hypertensives
CANTOS: Targeting inflammation, Canakinumab (monoclonal Ab targeting IL-1 Beta)
Exercise
Normal BMI
Non smoker
Alcohol consumption (in moderation)
Balanced diet
Diabetic medication
Glossary of
1. Fatty streak
2. Fibrous cap
3. Foam cells
4. Intima
5. Intima thickening
- The first grossly visible lesion in the development of atherosclerosis (foam cells, tunica intima)
- A layer of fibrous connective tissue in the intima
- Cells in an atheroma that consist of monocyte macrophages containing numerous lipid inclusions rich in cholesterly esters
- The innermost layer of a BV
- Accumulation in the intima of SMCs within a matrix of proteoglycans
Which cells can become foam cells in atherosclerotic plaques
Macrophages
Smooth muscle cells
In which layer of the arterial wall does atheroma build up occur in
Tunica intima
What are the symptoms of Abdominal Aortic Aneurysm
Sudden onset of back/flank pain
Hypotension
Pulsatile abdominal mass
What type of lipoprotein is oxidised leading to atherosclerosis? (reason)
LDL (oxidised and turns macrophages into foam cells
Reason: LDLs have the longest half life and is susceptible to oxidative damage
Define stable plaque
A raised lesion in the arterial wall that begins to occlude the lumen (doesn’t cause symptoms)
