Pathophysiology of atheroma Flashcards
What is the definition of an atheroma
Formation of Localised accumulation of lipid and fibrous tissue (plaques) in intima of arteries
What is arteriosclerosis
No atheromatous, thickening and hardening of the walls of the arteries, occurring typically in old age
What is the pathophysiology of arteriosclerosis
Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae, intimal fibrosis → decrease in vessel diameter
When do the clinical effect of arteriosclerosis become more apparent
when CVS further stressed by haemorrhage, major surgery, infection, shock
What would you see in the development of early atheroma plague with no clinical significance
Fatty streaks - Smooth yellow patches in inner most coating of the arteries and Lipid-laden macrophages are present
What can be seen in full developed atheromatous plague
Central lipid core with fibrous tissue cap , covered by arterial endothelium
What is present in fibrous tissue cap
Collagen (produced by smooth muscle cells)
Inflammatory cells - macrophages, T-lymphocytes, mast cells (recruited from material endothelium)
What is present in the central lipid core in developed atheromatous plague
Central lipid core rich in cellular lipids
and debris derived from macrophages that died in the plague
What is the structure of the central lipid core
Soft,
highly thrombogenic,
often rim of “foamy” macrophages
(due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor)
What occurs in late plague development that leads to atherosclerosis
Dystrophic calcification extensive
Atheroma from arterial branching points as plague are merge together and cover large areas
What is the investigations for atheroma development - what can be seen
angiograms/CT
calcification of coronary arteries
What is the out come of Haemorrhage of plague
The plague ruptures, and travels though the blood vessels then causes a blockage - thrombosis
What is the most important risk factor in atheroma and why
Hypercholesterolaemia
- Causes plaque formation and growth in absence of other known risk factors
What is the signs of major Hypercholesterolaemia
Corneal arcus (premature) - cholesterol deposit in the iris
Tendon xanthomata - yellow patches caused by deposition of lipid on the knuckles and Achilles
Xanthelasmata - sharply demarcated yellowish deposit of fat underneath the skin, usually on or around the eyelids
What is the biochemistry of Hypercholesterolaemia
LDL, HDL, total cholesterol, triglycerides
What clinical history can show signs of Hypercholesterolaemia
Risk factors
Family history of MI/ atheroma
What is the major risk factors for atheroma
Smoking Hypertension Diabetes mellitus Male Elderly Accelerate process of plaque formation driven by lipids Hypercholesterolaemia Obesity
What is the process of atheromatous plaque development
- injury to endothelial lining of artery
- chronic inflammatory and healing response of vascular wall to agent causing injury
- Chronic exposure of arterial wall to these processes results in the formation of atheromatous plaques
In more detail what is the pathogenesis of atheromatous plaques
Damaged Arterial endothelium leads to an:
inflammatory response in a process of tissue repair
- Growth factors, cause proliferation of smooth muscle, synthesis more collagen, elastin and mucopolysaccharide as well as platelets, and macrophages
- Platelet adhesion and smooth muscle proliferation results int the further recruitment of white blood cells and lipids
- Monocyte adhesion to artery wall and transforms into foamy macrophage
- T cell recruitment
- Accumulation of LDL to the vessel wall due to extracellular (high permeability because of damage) and also the foamy macrophages
This chronic process resulting in thickened artery wall and proliferated intimal of smooth muscle therefore creating an atheromatous plaque
What is the possible aetiologies of endothelial injury that leads on to atheroma
haemodynamic disturbances which result in a turbulent flow of blood
Hypercholesterolaemia
Endothelial loss -
What is the characteristics of injured endothelia lining
Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
High permeability for LDL
Increased thrombogenicity
Trigger inflammatory cells and lipids which deposit In the inner material layer and cause plaques
What is the clinical manifestations of atheroma plaque formation
Progressive lumen narrowing due to high grade plaque stenosis
Embolisation of the distal arterial bed - blood clotting
When atheroma is located in the coronary arteries, the clinical manifestation of atheromatous plaques results in what conditions
Myocardial Ischaemia
stable angina
Unstable angina with sever stenosis
Myocardial infarction
What can, femoral and popliteal artery stenosis result in
intermittent claudication (peripheral arterial disease)
Cramping in leg induced by exercise
Why is the rupture of the plaque a major complication
Leads on to an acute event as rupture exposes highly thrombogenic plaque contents to blood stream,
This activities coagulation of cascade and thrombotic occlusion in very short time - closing blood vessels
Acute atherothrombotic occlusion can then cause irreversible ischaemia and infarction
Where is examples of places where infarction can occur as a result of ruptured in the plaque
- stroke (carotid, cerebral artery)
- Myocardial infarction (coronary artery)
- lower limb gangrene (ileal, femoral, popliteal artery)
Due to the small foci of necrosis in the heart what can embolisation cause
life-threatening arrhythmias
What happens in ruptured atheromatous abdominal aortic aneurysm and what is the characteristics
Excessive swelling (aneurysm) present and the media beneath atheromatous plaques becomes gradually weakened causing gradual dilatation of vessel, this can then cause a Sudden rupture → massive retroperitoneal haemorrhage
Slow but progressive, seen in elderly, often asymptomatic
what size of aneurysm gives you a higher risk of rupturing
> 5cm
What is the Preventative and therapeutic approaches to embolism
Stop smoking Control blood pressure Weight-loss Regular exercise Dietary modifications
What is the secondary prevention
Cholesterol lowering drugs, aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)
What is a final approach to embolism
surgery
What is an atheroma in the aorta cause
aneurysm
