Pathophysiology of Atheroma Flashcards
What is the definition of atherosclerosis?
Formation of focal elevated lesions in intima of large and medium sized arteries
What is narrowing of coronary artery lumen known as?
Ischaemia
What does myocardial ischaemia lead to?
Angina
What is a thromboembolism?
An embolism broken off from a thrombus
What is the pathology of atherosclerosis?
- Not atheromatous
- Age related change in muscular arteries
- Smooth muscle hypertrophy
- Reduplication of internal elastic laminae
- Intimal fibrosis
When are the clinical affects of atherosclerosis most apparent?
- Haemorrhage
- Major surgery
- Infection
- Shock
What is an atheroma?
- Fatty streak
- Seen in young children
- Yellow linear elevation of intimal lining
- Contains lipid laden macrophages
- May disappear
- Can progress to early atheromatous plaque
What is an early atheromatous plaque?
- Young adults onwards
- Smooth yellow patches in intima
- Lipid laden macrophages
- Progresses to established plaques
What is a fully developed atheromatous plaque?
- Central lipid core with fibrous cap
- Covered by arterial epithelium
What does the fibrous cap of a fully developed atheromatous plaque provide?
- Made from collagens
- Provides structural strength
What cells reside in the fibrous cap?
- Macrophages
- T lymphocytes
- Mast cells
What is commonly present to do with the immune system in a fully established plaque?
- Thrombogenic soft ring of “foamy” macrophages
What occurs late in plaque development that will show on an angiogram?
Dystrophic calcification
What can be detected if the calcification occurs at branching points or bifurcations?
Turbulent flow
What is a complicated atheroma?
- A fully established atheroma but
- Haemorrhage into the plaque leading to calcification
- Plaque rupture can occur
- Thrombosis
What is the most important risk factor for atheromatous plaque?
- Hypercholesteraemia
What ways can hypercholesteraemia lead to plaque?
- Causes plaque formation + growth
- LDL cholesterol (lack of cell LDL receptors causes LDL to be deposited
What ratio of caucasians are heterozygous for hypercholesteraemia?
1/500
What ratio of caucasians are homozygous for the condition?
1/million
What will the hetorozygous mutation lead to?
- Loss of function cell LDL receptors
- Elevated plasma LDL
What will the homozygous mutation lead to?
- Much higher cholesterol level
- Patients usually die from a coronary heart atheroma in infancy
What are the two types of major hyperlipidaemia?
- Familial/primary
- Acquired/secondary
What are the evidence on bloods of hyperlipidaemia?
- High LDL
- Low HDL
- High total cholesterol
- Triglycerides
What are the clinical signs of hyperlipidaemia?
- Corneal arcus
- Tendon xanthomota (knuckles/achilles)
- Xanthelasmata
What other risk factors to atheroma are there?
- Smoking
- Hypertension
- Diabetes mellitus
- Male
- Elderly
What are the weaker risk factors?
- Obesity
- Sedentary lifestyle
- Low socio-economic status
- Low birthweight
What is the overall two step process of atheromatous plaque formation?
- Injury to endothelial lining
- Chronic inflammatory and healing response to vascular wall
What do injured endothelial cells usually do?
- Express more cell adhesion molecules (ICAM-1, E-selectin)
- High permeability for LDL
- Increased thrombogenicity
What role do growth factors play in the development of plaques?
- PDGF
- Proliferation of intimal smooth muscle
- Synthesis of collagen, elastin and mucopolysaccharide
What are growth factors secreted by?
- Platelets
- Endothelium (injured)
- Macrophages
- Smooth muscle
Where do microthrombi form?
Areas of a “strip” of plaque surface
What happens to microthrombi?
- Usually healed by the healing process
What does the repetition of formation of microthrombi and healing lead to?
Increased size of atheromatous plaque
What are the clinical consequences of advanced atheroma?
- Stenosis of > 50-75% will critically reduce the blood flow in distal arterial beds
What occurs from stenosed coronary arteries?
- Unstable angina
- Very severe angina at rest
What occurs from stenosed peripheral arteries of the legs?
- Intermittent claudication
- Longstanding tissue ischaemia
What occurs from acute atherothrombotic occlusion?
- Rupture of plaque
- Highly thrombogenic plaque contents released into blood stream triggering coagulation cascade and occluded vessel very quickly
- Total occlusion = irreversible iscaemia
What does irreversible ischaemia lead to?
- Necrosis of tissues
What can a total occlusion lead to?
- Myocardial infarct
- Stroke
- Lower limb gangrene
What is embolisation of the distal arterial bed?
- Small thrombus fragments from thrombosed atheromatous arteries
- Embolise distal plaque
What can embolisation of the distal arterial bed cause?
- Small infarcts in organs
What can a small infarct in the heart lead to?
- Necrosis
- Arrhythmias
What can embolytic plaques of the aorta lead to?
- Cholesterol emboli in kidney, leg, skin
What can carotid artery atheromatous plaques lead to?
Stroke, TIAs
What is the pathology of a ruptured atheromatous abdominal aortic aneurysm?
- Media beneath atheromatous plaques gradually weakened (lipid related inflammation)
- Gradual dilation of vessel
In whom are abdominal aortic aneurysms common?
- Elderly
- Often asymptomatic
What occurs when an aortic aneurysm ruptures?
- Massive retroperitoneal haemorrhage (high mortality)
What size aneurysms have a high rupture chance?
> 5cm
What is a mural thrombus?
A stationary thrombus across the lumen of a vessel
What will arise from a mural thrombus of the aorta?
- Emboli into the legs
- Increase MAP
What features of an atheromatous plaque tend to mean it is close to rupture?
- Thin fibrous cap
- Large lipid core
- Prominent inflammation
- Pronounced inflammatory activity
What is secreted by plaques close to rupture?
- Proteolytic enzymes
- Cytokines
- ROS’s
What personal prevention methods are there for atheroma?
- Smoking cessation
- Control BP
- Weight loss
- Regular exercise (starting off SLOW)
- Dietary changes
What secondary prevention methods exist for atheroma?
- Cholesterol lowering drugs
- Aspirin
- Surgical options
