Pathophysiology of Atheroma Flashcards
What is atheroma?
Formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries
What is arteriosclerosis?
Age related changes in muscular arteries - smooth muscle hypertrophy and apparent reduplication of the internal elastic laminae(not atheromatous)
What is a fatty streak?
The earliest significant lesion which is comprised of masses of lipid laden macrophages
When do early atheromatous plaques develop?
Early adulthood onwards
What is the structure of a fully developed atheromatous plaque?
A central lipid core with a fibrous cap covered by arterial endothelium
What type of cells reside in the fibrous cap of an atheromatous plaque?
Inflammatory cells such as macrophages, T-lymphocytes and mast cells
What is the central lipid core of an atheromatous plaque made up of?
Cellular lipids and debris derived from macrophages
Where do fully developed atheromatous plaques form?
At arterial branching points/bifurcations
What features make an atheroma complicated?
Haemorrhage into the plaque (calcification), plaque rupture/fissuring and thrombosis
What is the most important risk factor of atheroma?
Hypercholesterolaemia
Why does high cholesterol levels increase the risk of atheroma?
It causes plaque formation and growth in the absence of other known risk factors
What are the signs of major lipidaemia?
Biochemical evidence: LDL, HDL, total cholesterol and triglycerides, corneal arcus, tendon xanthomata, xanthelasmata and risk/family history of MI/atheroma
Besides Hypercholesterolaemia, what are the risk factors for atheroma?
Smoking, hypertension, diabetes mellitus, male, elderly and an accelerate process of plaque formation driven by lipids
What are the less strong risk factors?
Obesity, sedentary lifestyle, low socio-economic status and low birthweight
What are the two steps in the development of atheromatous plaques?
Injury to the endothelial lining and chronic inflammation and healing of vascular wall to the agent causing the injury
What role do monocytes play in the development of plaques?
They adhere to the endothelium and migrate into the intima where they transform into foamy macrophages
What do the factors released from the platelets and macrophages in plaque formation do?
Recruit smooth muscle which results in smooth muscle cell proliferation
What are the causes of endothelial injury?
Haemodynamic disturbances (turbulent flow) and hypercholesterolaemia
What effect does injury to the endothelial cells have on their function?
Enhanced expression of cell adhesion molecules, high permeability for LDL and increased thrombogenecity
What effect does stenosis of 50-75% have on the vessel lumen?
It causes critical reduction of blood flow in the distal arterial bed which causes reversible tissue ischaemia
What are the major complications of atheroma?
Rupture of the plaque - leads to thrombotic occlusion, which if it causes total occlusion could lead to MI, stroke or lower limb gangrene.
Embolism of the distal arterial bed - can lead to small infarcts, life-threatening arrhythmias, cholesterol emboli in the kidneys and sin etc. or cerebral infarct/TIA
Abdominal aortic aneurysm - sudden rupture or emboli to the legs
What are the features of vulnerable plaques?
Thin fibrous cap, large lipid core and prominent inflammation
What are the non-pharmacological preventative and therapeutic approaches?
Smoking cessation, control of blood pressure, weight loss, regular exercise and dietary modifications
What are the pharmacological approaches?
Cholesterol lowering drugs and aspirin (inhibits platelet aggregation)
