CVS: Atheroma and Infarction Flashcards
Describe the key components of atheromatous plaque
- Fibrous cap - Smooth muscle and collagen in dynamic equilibrium
- Cellular layer - Smooth muscle, macrophages, lymphocytes, less connective tissue
- Necrotic corde - Lipid, cholesterol, clefts, fibrin, foam cells, cell debris
Describe atheroma in the proximal left anterior descending coronary artery
- Extracellular lipid forms a confluent core in the muscloelastic layer of eccentric adaptive thickening that is always present in this location
- The region b/w the core and the endothelial surface contains macrophages and macrophage foam cells (fc), but an increase in smooth muscle cells or collagenous fibres is not marked
What are the most common sites of plaque build up?
- Circle of Willis
- Carotid arteries
- Coronary arteries
- Aorta
- Iliac arteries
What are the risk factors for atherosclerois?
- Age
- Male sex (premenopausal women protected)
- Genetics
- Hyperlipidaemia
- Smoking
- Hypertension
- Diabetes mellitus
- Obesity
- Metabolic syndrome
- Alcohol
- Drugs
Describe the initiation phase of atheroma development
- Circulating inflammatory mediators activate endothelial cells which become dysregulated and express cytokines and adhesion molecules (e.g. vascular cell adhesion molecule (VCAM-1)
- Circulating monocytes bind to activated endothelium (rolling hypothesis) and migrate b/w endothelial cells in intimal tissue
- Monocytes differentiate into tissue macrophages and release inflammatory cytokines into intima
Describe the plaque formation of atheroma development
- Macrophages upregulate scavenging receptors, allows uptake of LDL + conversion of macrophages into lipid-laden foam cells
- Further release of proinflammatory mediators stimulates VSMCs to migrate from media into intimal space
- VSMCs release GFs that stimulate cell division and proliferation as well as synthesising collagen and elastin. This is known as the ‘synthetic phenotype’ as VSMCs lose their contractile properties
Describe the maturation of plaque process of atheroma development
- Smooth muscle cells also start to accumulate LDL becoming smooth muscle foam cells
- Both types of foam cell eventually undergo apoptotic cell death releasing pools of lipid that accumulate forming an expanding lipid core within the intimal layer called an atheroma.
- A fibrous plaque of extracellular matrix components elastin and collagen forms layer above atheroma resulting in fibroatheroma
Describe calcification
Calcium deposited by foam cells that hardens atheroma and can be used clinically as a marker of atherosclerosis by imaging techniques
Describe plaque rupture
Lipid core can become necrotic and start to fracture and fragment creating fissures within the core. It can rupture through the endothelial layer causing trauma and exposing subendothelial collagen and tissue factor to blood. This initiates clotting cascade, forming thrombus
What are the consequences of atheroma?
- Occlusive thrombosis
- E.g. MI
- Thromboembolism
- E.g. Ischaemic stroke
- Peripheral vascular disease
- E.g. Critical limb ischaemia
- Aneurysm due to wall weakness
- E.g. Aortic aneurysm
What are causes of chest pain?
- Broken rib
- Collapsed lung
- Nerve infection (shingles)
- ‘Pulled’ muscle
- Infection
- Heart burn (hernia)
- Pericarditis
- Blood clot in lungs (PE)
- Angina
- MI
What causes stable cardiac angina?
Permanent flow limitation
What causes unstable cardiac angina?
Transient thrombosis
What causes myocardial infarction?
Due to complete occlusion
How do ECG and cardiac biomarkers indicate myocardial infarction?
- ST elevated MI: STEMI
- Elevated cardiac troponins e.g. CTnT = necrosis
