3.3 Ischaemic Heart Disease Flashcards
(35 cards)
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
What are two factors that influence abnormal blood coagulation?
1. Metabolic syn
- insulin resistance
- chronic inflam
- hypercoagulable state (⬆️ clotting factors + ✖️of fibrinolytic pathway)
- AbN vessel wall = endothelial dys
2. Smoking
- procoagulant
What happens when plaque rupture?
- Plaque-fibrin thrombus (clotting profile + binds thrombin)
- Clot retraction
- Red thrombus formation (stable)
What does a white & red thrombus consists of?
White - platelets
Red - fibrin + RC
What are the causes of ischaemia?
1. Coronary artery obstruction
- atheroma
- thrombus
- spasm
- embolus
- microvascular obstruction
- arteritis
- trauma
- syphilis
- ⬇️ supply of O2
- ⬆️ O2 demand
Define angina
Chest discomfort caused by myocardial ischaemia
- it means choking not pain
Nature of anginal pain:
- Retrosternal (middle)
- Burning, pressing, choking
- Pain / merely discomfort
- Precipitated by exercise or emotions
- Spreads to left arm, mandible & throat
- Relief: rest or sublingual nitroglycerin
- Never more than 20min
What is angina precipitated by?
- exercise
- stress
- large meal
- drug therapy terminated
- ⬆️ BP
- cold
- early morning
- heart fail
- rhythm disturbances
Chronic coronary syn (Stable angina pectoris)
- angina caused by stable coronay plaques (static in size / grow very slow)
- lesions = calcified
- ischaemia released before damage
- stable pattern (no ⬆️ frequency or ⬇️ threshold for angina)
- when rupture = unstable / acute coronary syn
Acute coronary syn symptoms
- Angina class 2 or 3
- angina becomes unstable: ⬇️ threshold; ⬆️ frequency, duration, severity
- Crescendo angina - gradual increase in frequency over matter of weeks (not true unstable angina _ no plaque rupture and thrombus form)
- prolonged angina during rest (>20min)
- post-infarc angina (not unstable angina)
