Heart and blood vessels- atheroma Flashcards
Atheroma
build-up of fatty material on the inside wall of an artery
Atherosclerosis
the progressive narrowing and hardening within an artery potentially resulting in a complete blockage
Where does atheroma affect?
Lower abdominal aorta, coronary arteries, popliteal arteries, internal carotid arteries and vessels of circle of Willis
Pathogenesis
Initiated by chronic injury to the endothelium (response to injury hypothesis) resulting in chronic inflammation
Causes of injury
Hyperlipidaemia, disturbed flow, smoking, hypertension
Progresses as white cells, fat and blood constituents infiltrate injury
Pathogenesis- Stages of atheroma
Type I: Initial lesion Isolated macrophage foam cells
Type II: Fatty streak lesion Mainly intracellular accumulation
Type III: Intermediate lesion Type II changes with small extracellular lipid pools
Type IV: Atheroma lesion Type II changes and core of EC lipid
Type V: Fibroatheroma lesion Lipid core and fibrotic layers, or mainly calcific, or mainly fibrotic
Type VI: Complicated lesion Surface defect, hematoma-hemorrhage, thrombus
Clinical manifestation of Atheroma
Can occur in any artery:
Coronary artery- heart attacks/angina(ischaemic heart disease
Aorta- aneurysm due to weakening of the wall
Carotid- narrowing causing strokes
Peripheral vascular disease
Atherosclerotic plaques
Atherosclerotic plaques develop slowly over decades but may acutely cause symptoms due to: Aneurysm and Rupture Thrombosis Haematoma formation Embolisation Development of critical stenosis
Plaque rupture, thrombosis, and healing - Arterial remodeling during atherogenesis
A. Arterial remodeling during atherogenesis. During the initial part of the life history of an atheroma, growth is often outward, preserving the caliber of lumen. This phenomenon of “compensatory enlargement” accounts in part for the tendency of coronary arteriography to underestimate the degree of atherosclerosis.
Plaque rupture, thrombosis, and healing - Rupture of the plaque’s fibrous cap
B. Rupture of the plaque’s fibrous cap causes thrombosis. Physical disruption of the atherosclerotic plaque commonly causes arterial thrombosis by allowing blood coagulant factors to contact thrombogenic collagen found in the arterial extracellular matrix and tissue factor produced by macrophage-derived foam cells in the lipid core of lesions. In this manner, sites of plaque rupture form the nidus for thrombi. The normal artery wall possesses several fibrinolytic or antithrombotic mechanisms that tend to resist thrombosis and lyse clots that begin to form in situ. Such antithrombotic or thrombolytic molecules include thrombomodulin, tissue and urokinase-type plasminogen activators, heparan sulfate proteoglycans, prostacyclin, and nitric oxide.
Plaque rupture, thrombosis, and healing - Endogenous fibrinolytic mechanisms
C. When the clot overwhelms the endogenous fibrinolytic mechanisms, it may propagate and lead to arterial occlusion. The consequences of this occlusion depend on the degree of existing collateral vessels. In a patient with chronic multivessel, occlusive coronary artery disease, collateral channels have often formed. In such circumstances, even a total arterial occlusion may not lead to myocardial infarction, or it may produce an unexpectedly modest or a non-ST segment elevation infarct because of collateral flow. In the patient with less advanced disease and without substantial stenotic lesions to provide a stimulus to collateral vessel formation, sudden plaque rupture and arterial occlusion commonly produces ST-segment elevation infarction. These are the types of patients who may present with myocardial infarction or sudden death as a first manifestation of coronary atherosclerosis. In some cases, the thrombus may lyse or organize into a mural thrombus without occluding the vessel. Such instances may be clinically silent.
Plaque rupture, thrombosis, and healing - Fibroproliferative response
D. The subsequent thrombin-induced fibrosis and healing causes a fibroproliferative response that can lead to a more fibrous lesion, one that can produce an eccentric plaque that causes a hemodynamically significant stenosis. In this way, a nonocclusive mural thrombus, even if clinically silent or causing unstable angina rather than infarction, can provoke a healing response that can promote lesion fibrosis and luminal encroachment. Such a sequence of events may convert a “vulnerable” atheroma with a thin fibrous cap prone to rupture into a more “stable” fibrous plaque with a reinforced cap. Angioplasty of unstable coronary lesions may “stabilize” the lesions by a similar mechanism, producing a wound followed by healing.
Treatment for Atheroma
Revascularization
Secondary prevention
Ischaemic Heart Disease
Imbalance between supply (perfusion) and demand of the heart for oxygenated blood
Important:
Not only ↓ oxygen but also ↓ nutrient substrates and inadequate removal of metabolites
Causes of Ischemic Heart Disease
> 90% are caused by atherosclerotic obstruction of coronary arteries, coronary artery disease
Reduced/no flow of oxygenated blood –> Atheroma, Embolism & Spasm
increased demand for oxygenated blood –> Thyrotoxicosis, Myocardial hypertrophy (hypertension)
Risk Factors for Ischemic Heart Disease
Positive family history Male Age Genetic (ACE gene deletion) Hyperlipidaemia cigarette smoking Hypertension Diabetes Lack of exercise obesity Heavy alcohol consumption
