3: CVS Flashcards
General patterns of ateriosclerosis
- Arteriosclerosis
○ Hyaline and hyperplastic patterns
○ Affects small arteries/arterioles
○ Seen in severe hypertension/diabetes- Monckeberg’s medial sclerosis
○ Calcifications of medial walls of muscular arteries but do not encroach vessel lumen
○ Often an incidental finding
○ Tends to affect vessels of arms/legs
○ Cause unknown
○ Distinct process or part of atherosclerosis/calcific valve stenosis? - Fibromuscular intimal hyperplasia
○ Muscular arteries – driven by inflammation (transplant-associated arteriopathy) or mechanical injury (e.g. balloon angioplasty)
○ I.e. healing response
○ Cf. fibromuscular dysplasia - Atherosclerosis
○ ‘Gruel’, ‘hardening’
○ Most common, most significant
○ Fat with fibrous cap
○ Underlies coronary artery/cerebrovascular/peripheral vascular disease, causing 50% of all deaths.
- Monckeberg’s medial sclerosis
Define arteriosclerosis
Hardening of arteries - arterial wall thickening and loss of elasticity
Main risk factors for atherosclerosis
- Non-modifiable
○ Family history; strong independent risk factor, polygenic effect
○ Increasing age; atheroma = progressive process (see next slide)
○ Being male (but female protection wanes post-menopause)
○ Genetic abnormalities
§ Mendelian disorders are less common but strongly associated with atherosclerosis (e.g. familial hypercholesterolaemia)- Modifiable
○ Cholesterol
§ Low/high-density lipoprotein (LDL/HDL) -> Statins
○ Obesity
○ Hypertension; IHD RR = 1.6
○ Smoking; IHD RR = 2
○ Diabetes;
§ Increased risk of strokes/MI. 100x risk atherosclerosis-induced lower limb gangrene
○ Inflammation - Other
○ Metabolic syndrome
§ Insulin resistance, hypertension, dyslipidaemia, hypercoagulability, pro-inflammatory state
○ Lipoprotein A
§ Altered form of LDL, high levels associated with increased CV risk
○ Hyperhomocysteinaemia e.g. homocystinuria
○ Factors affecting haemostasis; PAI-1, PDFs, thrombin
○ Lifestyle/personality
- Modifiable
Describe the five progressive stages of atherosclerotic evolution
- ‘Response to injury’ hypothesis – chronic inflammation/healing brought about by endothelial damage
- Endothelial injury causes increased vascular permeability
- Lipoproteins accumulate in vessel wall, monocytes join -> macrophages/foam cells
- Release of factors from platelets/macrophages/vessel cells causes smooth muscle cell proliferation
- ECM proliferation too
- Calcification
Morphological features of atherosclerosis
- Fatty streaks ○ Lipid filled foam cells ○ Small flat yellow macules - Atherosclerotic plaque ○ Intimal thickening ○ Lipid accumulation ○ Yellow tan ○ Raised above surrounding vessel wall ○ Well circumcised ○ Superimposed thrombus - Histology ○ Cells § SMCs, macrophages, T-cells ○ ECM § Collagen, elastic fibres, proteoglycans ○ Lipids § Intracellular/extracellular ○ Calcification
Consequences of atherosclerotic disease
- Rupture and ulceration of surface
- Haemorrhage into the plaque
- Atheroembolism and microemboli
- Aneurysm formation
- Fibrocalcification
- Myocardial infarction
- Stroke
- Aneurysm
- Peripheral vascular disease
How to plaques progress and what factors influence plaque stability?
- Cholesterol deposits causes inflammation; increased collagen degradation and decreased collagen production
- TIMPs vs. MMPs
- Statins have an anti-inflammatory effect
- Adrenergic stimulation
- Emotional stress
- Vasoconstriction
What are the four main clinical presentations of ischaemic heart disease?
- Angina
○ Ischaemia not severe enough to cause infarction
○ Usually associated with intermittent chest pain
○ Stable – occurs when increased demand on the heart and reduces at rest
○ Unstable – occurs at rest
○ Risk of developing MI- MI
○ Ischemia causes frank cardiac necrosis
○ Death of tissue cells
○ Chest pain, nausea, light-headedness, clammy, radiation of pain to shoulder/neck, - Chronic IHD
○ Long term reduced oxygen supply leads to heart failure
○ Breathlessness, dry cough, leg swelling, weight gain and fatigue - Sudden cardiac death
○ Large blockage, wall rupture, ventricular fibrillation
Sudden cardiac arrest
- MI
Pathogenesis of chronic plaque occlusion
○ Hard fixed lesion forms slowly on vessel wall via atherosclerosis
§ 1. Chronic endothelial insult from conditions such as Hyperlipidaemia, hypertension, smoking or from hemodynamic factors result in endothelial dysfunction
§ 2. Lipid droplets, mainly from low density lipoproteins (LDLs), and monocytes cross the endothelium and accumulate in the intima.
§ The lipids become oxidized and the macrophages ingest the lipid. When they do so their cytoplasm appears bubbly microscopically and they are called foam cells.
§ 3. The crowded foam cells cause the endothelium to bulge.. The lesion at this stage is called a fatty streak.
§ Smooth muscle cells migrate into the lesion from the media and start to proliferate
§ 4. The plaque grows as the number of foam cells and smooth muscle cells increases.
§ Some smooth muscle cells will also take up lipid and appear foamy.
§ Some smooth muscle cells will lie over the plaque but beneath the endothelium forming a ‘roof’. This roof is reinforced by collagen, elastin and other matrix proteins and the result is a fibrous cap.
§ As the endothelium stretches over the plaque gaps appear between the endothelial cells. Platelets adhere to the gaps.
§ 5. Cells in the centre of the plaque die and necrosis develops. The dead cells release cholesterol and cholesterol crystals appear in the plaque.
Small blood vessels grow into the plaque from the adventitia and the plaque may undergo calcification
Pathogenesis of acute plaque change
○ Unpredictable conversion of stable atherosclerotic plaque to an unstable and potentially life-threatening atherothrombotic lesion through: § Rupture § Superficial erosion § Ulceration § Fissuring § Deep haemorrhage
Define angina pectoris
- Paroxysmal and usually recurrent attacks of substernal/precordial chest discomfort
- Caused by transient myocardial ischaemia that is insufficient to induce myocyte necrosis
Types of angina pectoris
○ Stable
§ Caused by imbalance of coronary perfusion relative to myocardial demand
§ Does not occur at rest
§ Reliably induced by activities that increase energy requirements of heart
§ Relived by rest or vasodilators
○ Prinzmetal Variant
§ Episodic myocardial ischaemia caused by coronary artery spasm
§ Attacks are unrelated to physical activity, heart rate or blood pressure
§ Can occur at rest
§ Generally respond to vasodilators
○ Unstable
§ Increasingly frequent prolonged or severe angina precepted by progressively lower levels of activity or at rest
§ Associated with plaque disruption and superimposed thrombosis
Patterns of infarction
- Distribution of myocardial necrosis correlates with location and cause of decreased perfusion
- Transmural involve full thickness necrosis
- Subendocardial involve partial thickness necrosis
Morphological features of myocardial infarction over time
- 4-12 hours ○ Gross § Dark mottling ○ Histological § Early coagulative necrosis § Oedema § Haemorrhage § Early neutrophilic infiltrate - 12-24 hours ○ Gross § Dark mottling + pallor ○ Histological § Ongoing coagulative necrosis § Pyknosis of nuclei § Myocyte hypereosinophillia § Marginal contraction band necrosis - 1-3 days ○ Gross § Mottling with yellow-tan infarct centre ○ Histologic § Coagulative necrosis § Loss of nuclei and striations § Heavy infiltrate of neutrophils - 3-7 days ○ Gross § Hyperaemic border § Central yellow-tan softening ○ Microscopic § Beginning disintegration of dead myofibers § Dying neutrophils § Early phagocytosis of dead cells by macrophages at infarct border - 7-10 days ○ Gross § Maximally yellow-tan and soft § Depressed red-tan margins ○ Histologic § Well-developed phagocytosis of dead cell § Granulation tissue at margins - 10-21 days ○ Gross § Maximally yellow and soft § Vascular margins ○ Histologic § Fibrovascular response § Prominent granulation tissue containing capillaries and fibroblasts - 7 weeks + ○ Gross § White fibrosis ○ Microscopic § Fibrosis with dense collagenous connective tissue § No inflammation
Complications following MI
Death Arrhythmia Rupture - 3-7 days Tamponade - 3-7 days Heart failure Valve disease Aneurysm Dressler syndrome Embolism - > 2 weeks Recurrence Regurgitation
