Pathophysiology of Atheroma Flashcards
What is an atheroma?
A focal elevated lesion in the intima of large and medium sized arteries
What happens when an atheromatous plaque forms in the coronary arteries?
The lumen becomes narrowed and the heart becomes ischaemic
What cause angina
An atheroma in a coronary artery causing ischaemia
List the constituents of a normal artery wall
- Intima (made of endothelium and internal elastic lamina)
- Media (made of elastic tissue)
- Adventitial (made of the external elastic lamina)
What is the most important risk factor associated with atheroma?
Hypercholesterolaemia
describe the pathogenesis of the genetic mutation which causes hypercholesterolaemia
A lack of adequate LDL receptors on the surface of cells means that LDL remains in the blood
Describe the major clinical signs of hyperlipidaemia
- Corneal arcus (premature)
- Tendon xanthomata (knuckles, Achilles)
- Xanthelasmata
Other than hypercholesteraemia, list 5 significant risk factors for atheroma
- Smoking
- Hypertension
- Diabetes mellitus
- Male
- Elderly
Describe the three steps of atheroma development
- Development of a fatty streak in young children
- Development of an early atheromatous plaque in young adults
- Fully developed atheromatous plaque
What does the fatty streak and the early atheromatous plaque comprise?
masses of lipid laden macrophages
Describe the structure of a fully developed atheromatous plaque
a central lipid core with a fibrous tissue cap. The whole structure will be covered by the arterial endothelium.
What 2 constituents make up the fibrous cap of atheromas and where do they come from?
Collagens produced by smooth muscle cells Inflammatory cells (macrophages, T-lymphocytes and mast cells) recruited from the arterial endothelium
What is the lipid core of an atheroma made of?
Cellular lipids/debris derived from the lipid laden macrophages which died in the plaque
What is the lipid core surrounded by (underneath the fibrous cap)?
a rim of foamy macrophages
Why are the macrophages foamy?
they are “foamy” due to the uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor
What happens to the plaque structure later in developement?
It is subject to extensive dystrophic calcification
What can be used as a marker for atheromas in angiograms/CT scans?
Dystrophic calcification
Where in a blood vessel network do atheromas form and why?
They form at arterial branching points/bifurcations due to the turbulent nature of the blood flow in these regions
Which three events can result in a complicated atheroma?
- Haemorrhage into the plaque
- Plaque rupture
- Fissuring and thrombosis
List the 2 steps in the process os atheromatic plaque development (with regards to the vessel wall)
- Injury to the endothelial lining of an artery occurs (accumulation of LDL in the vessel wall, monocyte adhesion to the endothelium and migration into the intima and transformation into foamy macrophages)
- Chronic inflammation and healing response of the vascular wall causes further injury (Platelet adhesion, a factor released from activated platelets and macrophages cases smooth muscle cell recruitment and proliferation, extracellular matrix production and T cell recruitment. lipids accumulate)
Name the two main causes of endothelial injury (the fist step in the development of an atheromatic plaque)
- haemodynamic disturbance (e.g. turbulent flow)
2. Hypercholesteraemia
Explain how hypercholesteraemia causes endothelial injury
Chronic hypercholesterolaemia can directly impair endothelial cell function by increasing local production of reactive oxygen species.
lipoproteins aggregate in the intima and are modified by the free radicals produced by inflammatory cells. The modified low density lipoprotein is then accumulated by macrophages but not completely degraded which results in foamy macrophages. These foamy macrophages are toxic to endothelial cells and release of growth factors & cytokines
Explain the process by which injured endothelial cells become highly permeable to LDL
Injured endothelial cells are functionally altered which results in them producing an abnormally high quantity of cell adhesion molecules (ICAM-1, E-selectin), which makes the endothelia highly permeable to LDL and increases thrombogenicity
Explain the process by which an atheromatic plaque increases in size over time
Small areas of endothelial loss cause microthrombi to form at the denuded areas of the plaque surface
This happens over and over again which slowly increases the size of the plaque
List the 4 pathologies caused by atheromous plaques which have serious clinical consequences
- Progressive lumen narrowing (stenosis)
- Acute atherothrombotic occlusion
- Embolisation of the distal arterial bed
- Ruptured atheromatous abdominal aortic aneurysm
Carotid artery atheromatous debris is a common cause of ______
Stroke
Aneurysms > ____cm diameter are considered to be at high risk of rupture
5cm
What is a mural thrombus and where can it embolise to?
Mural thrombus = thrombi that attach to the wall of a blood vessel and cardiac chamber
can embolise to the legs
Name the three features of an atheromatous plaque that is vulnerable to rupture
- Thin fibrous cap
- Large lipid core
- Prominent inflammation
List the ways in which an atheromatous plaque can be prevented
- Stop smoking
- Control blood pressure
- Weight loss
- Regular exercise
- Dietary modification
- Cholesterol lowering drugs
- Aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)
- Surgical management (removal or bypass of atheromatous vessels)
