29-09-22 – Ischaemic heart disease Flashcards
Learning outcomes
- Describe the causes of ischaemic heart disease
- Describe the macroscopic features of coronary artery atheroma
- Describe the clinical and pathological features of acute myocardial infarction
- Describe the complications of acute myocardial infarction
- Describe the clinico-pathological features of chronic ischaemic heart disease
What is ischaemic heart disease?
What does it lead to?
What are 3 different names for Ischaemic heart disease (IHD)?
What are 4 the main cardiac effects of Ischaemic heart disease?
- Ischaemic heart disease is where the blood vessels supplying the heart (coronary vessels) are narrowed or blocked
- This results in a mismatch of blood supply (coronary blood flow) to demand (myocardial oxygen consumption)
- Ischaemic heart disease (IHD) is also known as:
1) Atherosclerotic heart disease
2) Coronary heart disease
3) Coronary artery disease - Main cardiac effects of Ischaemic heart disease:
1) Chronic coronary insufficiency
* Causes Angina - this is the pain of myocardial ischemia.
* IHD usually becomes symptomatic only when the luminal cross-sectional area of the affected vessel is reduced by more than 75%, leading to coronary insufficiency
2) Unstable coronary disease (likely due to clot of plaque)
* Can lead to:
* Myocardial infarction
* Sudden ischemic coronary death
3) Heart Failure
* Contractile impairment in these people is due to irreversible loss of myocardium (previous infarcts) and hypoperfusion of surviving muscle, which leads to chronic ventricular dysfunction
4) Arrhythmia
* Due to acute ischaemia
* Scar related
What is the epicardium?
What is the endocardium?
What is the subendocardial space?
Why is it relevant in IHD?
What is the main cause of angina?
What are the main epicardial coronary branches?
- Epicardium = outer surface of the heart (consistent with visceral layer of serous pericardium)
- Endocardium = inner surface of the heart
- Subendocardial space is the area beneath the endocardium or between the endocardium and myocardium
- The subendocardial space is the water-shed area of perfusion and first to become ischaemic
- Subendocardial ischaemia due to epicardial coronary artery stenosis and is the main cause of angina
- The main epicardial coronary arteries are the left and right coronary arteries and their branches
What are the 3 main imaging techniques used for coronary artery imaging?
- Main imaging techniques used for coronary artery imaging:
1) Coronary Angiography
2) CT
3) MR imaging
What are 7 risk factors of IHD?
- Risk factors of IHD:
1) Age
2) Hypertension
3) Hypercholesterolaemia
4) Smoking
5) Diabetes
6) Obesity
7) Physical inactivity
What is hypercholesterolaemia?
How does this affect endothelial function?
Where does LDL accumulate in this condition?
What does this cause?
What happens when Macrophages ingest LDL?
What are these chemotactic for?
What happens to the motility of macrophages?
What does this stimulate the release of?
How do these effect endothelial and smooth muscle cells?
- Hypercholesterolaemia is a form of hyperlipidaemia, where there is too much bad LDL cholesterol in the blood
- This impairs endothelial function
- In this condition, LDL cholesterol accumulates in the tunica intima, which causes oxidative modification of LDL
- When macrophages in the tunica intima ingest oxidised LDL cholesterol via scavenger receptors, they become foam cells
- These foam cells are very chemotactic for monocytes, which come into the tunica intima and become macrophages
- Ingesting the LDL cholesterol will inhibit motility in the macrophages
- This stimulates the release of cytokines, which are cytotoxic to endothelial and smooth muscle cells
What are the 3 roles of macrophages in the development of atherosclerosis?
- Role of macrophages in development of atherosclerosis:
1) Macrophages engulf oxidised LDL to from Foam cells
2) They secret various factors, such as Interleukin 1 and Growth factors, which will be chemotactic for more monocytes
3) Macrophages can form a fatty streak, which is the first grossly visible (to the naked eye) lesion in the development of atherosclerosis
Role of smooth muscles in the development atherosclerosis.
What does the fatty streak mature into?
What 3 steps is this done in?
- The fatty streak matures into fibrofatty atheroma
- Steps of this process:
1) The smooth muscle enters the tunica intima, which help in formation of collagen on the surface of fibrous tissue, causing a fibrous cap
2) In the centre of the atheroma, foam cells will eventually die, the LDL cholesterol will crystalise and will group together in the centre forming a lipid necrotic debris
3) It is now a full formed fibrofatty atheroma
What is morphology?
What is the morphology of atherosclerosis?
What are the 6 sites atheromas can occur from most likely to least likely?
What are 5 complications that can rise due to atheroma?
- Morphology is the visual study of anomalies caused by diseases
- Morphology of atherosclerosis is an atheromatous (fibrofatty, fibro-lipid) Plaque which:
1) Is patchy and raised white to yellow 0.3-1.5cm
2) Has a core of lipid
3) Has a fibrous cap - 6 sites atheromas can occur from most likely to least likely:
1) Abdominal aorta
2) Coronary arteries
3) Popliteal arteries
4) Descending thoracic aorta
5) Internal carotid arteries
6) Vessels of the circle of Willis - 5 complications that can rise due to atheroma:
- Calcification
- Rupture or ulceration
- Haemorrhage
- Thrombosis
- Aneurysmal dilation (when the ascending aortic diameter reaches or exceeds 1.5 times the expected normal diameter)
Distinguish between stenosis and occlusion of an artery.
How is total occlusion of left anterior descending artery compensated for by the body?
- Stenosis is a narrowing of a vessel
- Occlusion is a complete or partial blockage/closure of a blood vessel
- Total occlusion of left anterior descending artery compensated for by filling from the collaterals of the Right Coronary Artery
What is the main cause of angina?
How does an ECG with angina present differently?
What is ischaemia?
What proportion of narrowing of the lumen diameter signifies limitation of max blood supply?
What other factors, besides degree of narrowing, affect blood flow?
- Subendocardial ischaemia due to epicardial coronary artery stenosis is the main cause of angina
- ECGs with angina have an ST depression
- Ischaemia is Insufficient supply of blood to an organ, usually due to a blocked artery.
- 50% of narrowing of the lumen diameter usually signifies limitation of maximal flow.
- Length of narrowing can also significantly affect blood flow
Do organs auto-regulate blood flow?
How do organs auto-regulate blood flow?
What 2 intrinsic ways can we maintain safe blood flow when blood pressure increases?
- Organs auto-regulate blood flow independent of innervation/hormonal control, despite the central decision about where we constrict vasculature to modify total peripheral resistance
- Organs auto-regulate blood flow through Active and reactive hyperaemia
- 2 intrinsic ways we can maintain safe blood flow when blood pressure increases:
1) Myogenic theory (acute flow auto-regulation) - Stretch induces vascular depolarisation of smooth muscle due to increase in arterial pressure
- This limits the blood flow that can move through the vessel, preventing damage to the vessels
- This is a myogenic response, where stretch activated Ca2+ channels trigger the process of contraction
2) Metabolic theory (acute flow autoregulation)
* An increase in arterial pressure increases O2 and washes out local factors e.g Breakdown of ATP to ADP and AMP, which can be converted to adenosine in the blood
* High degree of oxygen delivery to smooth muscle is likely to trigger constriction mediated effects in the vasculature, leading to an occlusion of the blood supply downstream, as there is enough oxygen present
* This constriction can reduce flow and protect the vessel walls from being damages
How does exercise effect cardiac blood flow and total body oxygen consumption?
What accounts for most of the increase in cardiac blood flow?
What is O2 extraction fraction (OEF)?
How does this change during exercise?
- Cardiac blood flow can rise up to five-fold (400 ml/min/100g) during exericse
- This is to accommodate a 20-fold increase in total body O2 consumption
- Vasodilation accounts for most of the increase in cardiac blood flow (Increase in HR where per beat CBF is constant accounts for about 1/3rd of the increase in cardiac blood flow)
- Oxygen extraction fraction (OEF) is defined as the ratio of blood oxygen that a tissue takes from the blood flow to maintain function and morphological integrity
- During heavy exercise, approximately 70–80% of the oxygen delivered to the active muscles may be extracted.
- This demonstrates that there is a reserve of oxygen in the blood that can be utilized immediately to meet the needs of the contracting muscles at the onset of exercise.
What is coronary flow reserve?
How does degree of stenosis affect coronary flow reserve?
- Coronary flow reserve is the maximum increase in blood flow through the coronary arteries above the normal resting volume (difference between autoregulated flow and flow with maximum vasodilation)
- Greater stenosis will lead to a decreased coronary flow reserve
What are 5 factors that determine myocardial oxygen consumption?
- Factors that determine myocardial oxygen consumption:
1) Mass of tissue
* Ventricular hypertrophy increases mass of tissue
- Factors which are variable per unit mass of tissue:
2) Tension development
* Higher tension means higher maximum force of contraction through Frank Starling mechanism.
* A stronger maximum force of contraction requires more oxygen
3) Contractility
* A stronger maximum force of contraction requires more oxygen
* Positive inotropes will increase myocardial oxygen consumption
4) HR
- Factor which is fixed per unit mass of tissue:
5) Basal activity
* heart accounts for 10-20% of oxygen consumption at rest
Is coronary flow reserve constant?
How is this linked to variant angina?
Does the collateral circulation have fixed or variable coronary reserve?
- Coronary flow reserve is not constant and may change from time to time (especially for smaller vessels, less than 200 microns)
- This underpins the cause of variant angina, where coronary artery spasms (vasospasms) can cause supply ischaemia to the heart
- Collateral circulation has variable coronary reserve, because they’re small vessels (less than 200 microns)
How does the appearance of angina differ between fixed stenosis with variable coronary flow reserve and fixed stenosis with fixed coronary flow reserve?
- If fixed stenosis occurs with fixed coronary flow reserve, the same intensity of exercise will always either cause pain or not
- If fixed stenosis occurs with variable coronary flow reserve, the same intensity of exercise can sometimes cause angina, and sometimes not
What are the 3 different types of treatment options for angina?
What is the aim of each option?
What vessel are used for CABG?
- 3 different types of treatment options for angina and aims of each treatment:
1) Drugs
* Reduce Myocardial Oxygen consumption
* Reduce variability of coronary flow reserve (e.g. vasodilators)
2) Percutaneous Coronary Intervention (stents and balloons)
* Improve coronary flow reserve
3) Coronary Artery Bypass Grafting (CABG)
* Improve coronary flow reserve
* For the Right coronary artery (RCA), the saphenous vein is used
* For the Left anterior descending artery (LAD), the left internal mammary artery is used (LIMA)
What are 6 primary coronary causes of MI?
How does coronary occlusion occur from plaque rupture?
- 6 primary coronary causes of MI:
1) Plaque rupture –
* Rupture is the disruption of a fibrous cap over a lipid core.
* The overlying thrombus is in continuity with the lipid core
2) Plaque erosion –
* Superficial disruption of a fibromuscular plaque without a core.
* An acute thrombus in direct contact with the intima in an area of denuded endothelium
3) Coronary embolism
4) Coronary artery spasm/drug
5) Coronary anomaly
6) Spontaneous coronary dissection
- How coronary occlusion occurs from plaque rupture:
- Atherosclerotic plaque ruptures, contents leak out, resulting in platelet aggregation and arterial thrombosis.
- Platelets express prothrombinase complex leads to more thrombi forming, which can totally occlude a coronary artery
What are 3 ways we can classify myocardial infarctions?
- 3 ways we can classify myocardial infarctions:
1) By site of infraction (pathology)
* Full thickness, transmural (occurring across entire surface of heart) - A transmural myocardial infarction refers to a myocardial infarction that involves the full thickness of the myocardium
* Sub endocardial - A subendocardial infarct results in necrosis exclusively involving the innermost aspect of the myocardium.
2) By ECG (clinical)
* ST Elevation myocardial infarction (STEMI) – implies full thickness, transmural MI
* Non-ST elevation myocardial infarction (non- STEMI / NSTEMI) - NSTEMI will include subendocardial infraction but does not exclude transmural infarctions in regions remote from ECG (e.g; back of the heart)
3) By cause
* Type 1-5
1) Type 1:
* spontaneous MI related to ischemia due to primary coronary event (e.g. plaque erosion, rupture, fissuring, dissection)
1) Type 2:
* MI secondary to ischemia due to increase oxygen demand or decreased supply
2) Type 3:
* Sudden unexpected cardiac death with symptoms suggestive of myocardial ischemia
3) Type 4:
* MI associated with percutaneous coronary intervention or stent thrombosis
4) Type 5:
* MI associated with cardiac surgery
