3.3 Ischaemic Heart Disease Flashcards
Define Atherosclerosis
- degenetrative disease of large & med sized ateries
- elevated lesions in intima (plaque)
life-threatening - thrombus forms on disrupted plaque (atherothrombosis)
Atherosclerosis aetiology
- maultifactoral
Major RF:
- Hypercholesterolaemia (can cause plaque formation & growth in absence of other RF)
- smoking
- hypertention (uncontrolled)
- DM (uncontrolled)
- Male
- increase age
Minor RF:
- Obesity
- low social economic status
- high carbohydrate intake
- oral contraceptives
- stress
- chlamydia pneumoniae
Atherosclerosis pathogenesis
Development 2 step process:
1. Endothelial damage
- ⬆️ express of cell adhesion for monocytes (ICAM-I, E-selection)
- high permeability for macromol (LDL)
- ⬆️ thromogenicity
2. Tissue response of vascular wall to injurious agents
- macrophages & T-cells accum in plaque tissue
- Lipid-laden macrohages (foam cells) die through apoptosis -> lipid spilled into enlarging lipid core
- inflam reaction + tissue repair (GF, collagen, elastin, mucopolysaccharide) -> fibrous cap
Haemorrhage:
- important mech of plaque growth
- from rupture or leak of microvessels
- large haemorrhage cause rapid expansion of plagues
Atherosclerosis morphology of lesion
3 different types
1. Fatty streak
- earliest lesion
- yellow linear elevation of intimal lining
- lipid-laden macrophages
- no clinical significance
- mostly at branches of bone (turbulent flow)
2. Fully developed plaque
- central lipid core
- fibrous cap
- covered: endothelium
- infam cells (macrophages, T-, mast cells)
3. Atheromatous lesion
- rich in cellular lipids and debris
- soft, semi-fluid
- highly thrombogenic
- bordered by foam cells
Atherosclerosis clinical manifestation
1. Progressive lumen narrowing due to plaque stenosis
- ⬇️ in blood flow to distal arterial bed
- reversible tissue ischaemia (effort)
2. Acute atherothrombotic occlusion
- plaque rupture expose thrombogenic components (collagen, lipid debris) to blood stream -> coagulation cascade
- total occlusion = irreversible ischaemia
3. Embolisation of distal aterial bed
- small infarctions in organs
- common: carotid atery -> stroke
4. Ruptured abdom atherosclerotic aneurysm
- causes retroperitoneal haemorrhage -> death
Does ischaemia lead to cell death?
No not prolonged enough, only leads to cell dysfunction
What is “stunning”?
If restore blood flow to ischaemic area; the muscle remains dysfunc for few hours
What is Ischaemic preconditioning?
Repeated brief episodes of ischaemia protect muscle from subsequent longer occlusion
What are the main causes of ischaemia?
- atherosclerotic flow-limiting stenoses -> chronic stable angina
- coronary artery spasm -> vasospastic angina
- coronary thrombus superimposed on atherosclerotic plaque -> acute coronary syn
- coronary microvascular dys
What % of coronary flow resistance is from epicardial arteries?
5%
What is the effects of ischaemia?
- energy met: aerobic -> anaerobic (without O2)
- cells become acidotic
- phosphates (source of ATP) deplete
Define Infarction
- longer occlusion -> myocardial cell death (>20min)
- irreversible
- cell necrosis (contents in blood stream)
What is the microscopic finding with MI?
- Early - necrosis
- 12-24hrs - eosinophil + neutrophil
- 10-14 days - macrophages + fibroblasts
- 4 weeks - collagen laden scar
What are the 3 predisposing factors to thrombus formation according to Virhow triad?
- Abnorm vessel wall
- Abnorm blood coagulation
- Turbulent blood flow
What are 3 triggers for thrombus formation leading to infarction?
- Plaque rupture
- Plaque erosion
- Calcium nodules eroding
Leads to disruption of vessel wall
