What is tissue ischaemia and what can it be due to?
Reduced blood flow to an organ or tissue due to:
- lack if O2 and nutrients supply
- lack of washout of metabolic
Describe Myocardial ischaemia.
- Reduced blood flow to the heart.
- Ischaemia as an imbalance between myocardial demand and supply.
- Concept of exertional demand and ischaemia and non-exertional supply ischaemia.
Define CHD
Pathological conditions and characterised by a reduced or inadequate blood flow to the heart.
Usually due to an obstructive/constrictive disease of coronary arteries
What are the characteristic of CHD?
- Incurable
- High morbidity and mortality
- Highly dependent on environmental and cultural factors.
- Preventable
Describe the process of CHD.
- Coronary artery obstruction or constriction.
- Reduced regional blood flow to the heart
- Oxygen and nutrient deprivation and accumulation of toxic waste.
- Leading to: metabolic and contractile dysfunction, electrical instability and myocardial cell death (infarction).
What are the clinical manifestations of CHD?
- Angina pectoris - stable, variant and microvascular.
- Immediate or sudden cardiac death.
- Acute coronary syndromes (ACS) - unstable angina, acute myocardial infraction (NSTEMI, STEMI).
What are the pathological factors of CHD?
- Atherosclerosis
- Coronary thrombosis
- Coronary artery spam
- Coronary microvascular dysfunction
Define Atherosclerosis.
A progressive, degenerative arterial disease characterised by asymmetric deposition of lipids and fibrous tissue on the inside wall of arteries
Describe the disease process of Atherosclerosis.
- LDL deposition in sub-endothelial space.
- LDL oxidation + monocyte recruitment into sub-endothelial space.
- Macrophage differentiation + uptake of oxidised LDL.
- Foam cell formation
- SMC migration, proliferation and de-differentiation.
- Fibrous plaque or atheroma
What are the consequences of Atheroclerosis?
Impact on coronary function:
- Partial coronary occlusion - stable angina
- Endothelial/ vascular dysfunction - coronary artery spasm.
- Ulceration/ rupture - coronary thrombosis
Define Coronary Thrombosis.
Unwanted formation of a haemostatic plug or thrombus or blood clot within coronary arteries
What is the disease process of Coronary thrombosis?
- Rupture or ulceration of atherosclerotic plaque.
- Contact of blood elements with collagen and tissue factor.
- Platelet adhesion and activation - platelet aggregation - thrombus/ clot.
Activation of coagulation cascade - fibrin formation and deposition - thrombus/clot
What are the consequences of Coronary Thrombosis?
Impact on coronary function:
- Complete and permanent occlusion of coronary artery - ACS (STEMI).
- Subtotal or intermittent occlusion of coronary artery- ACS (UA/NSTEMI).
- Thromboembolism in a distal artery
Define Coronary artery spasm.
A transient, spontaneous coronary vasoconstriction.
- May occur in normal coronary arteries
- May occur at mildly atherosclerotic sites or during ongoing coronary thrombosis.
- The underlying cause of variant angina.
What are the disease mechanisms coronary artery spasm?
- Local endothelial injury - increase reactivity to vasoconstriction.
- Abnormal release of vasoconstrictors or local imbalance in release of vasodilators and constrictors.
- Smooth muscle cell hyper-contraction/ hyper-reactivity
What are the consequences of Coronary artery spasm?
impact on coronary function:
- subtotal or intermittent occlusion of coronary artery
- complete focal occlusion of coronary artery
Define Coronary microvascular dysfunction.
Damage to the inner walls of the small coronary blood vessels of the heart, leading microvascular spasm, decreased blood flow of the heart muscle and reduced coronary flow reserve.
What is the are disease mechanisms for Coronary microvascular dysfunction?
- Microvascular remodelling - luminal narrowing of the intramural arterioles and capillaries - microvascular obstruction.
- Endothelial dysfunction - impaired vasodilator response and reduced coronary blood during exercise or stress.
- Functional abnormalities of smooth muscle cells that regulate arteriolar tone.
What are the consequences of Coronary microvascular dysfunction?
Reduced coronary flow reserve and increased risk of myocardial ischaemia - INOCA (microvascular angina) or MINOCA (myocardial infraction with no obstructive coronary artery disease)
What are the medical and modifiable risk factors for coronary atheroma and CHD?
- High blood cholesterol
- Hypertension
- Diabetes
- Obesity
- Poor diet
- Cigarette smoking
- Physical inactivity
