Ischemic Heart Disease (IHD), also known as coronary artery disease (CAD), arises when there is an imbalance between myocardial oxygen supply and demand, leading to myocardial ischemia. Understanding the pathophysiology of IHD is essential for clinicians to recognize the underlying mechanisms, identify high-risk patients, and implement preventive and therapeutic strategies. This post provides a comprehensive overview of the coronary artery anatomy, the development of atherosclerosis, endothelial dysfunction, thrombosis, and mechanisms of acute versus chronic ischemia.
1. Coronary Artery Anatomy
1.1 Overview
The coronary arteries are the primary vessels supplying oxygenated blood to the myocardium. Their structure and branching patterns are crucial in understanding regional ischemia and infarction.
- Left Coronary Artery (LCA): Arises from the left aortic sinus and branches into:
- Left anterior descending (LAD) artery: Supplies the anterior wall, anterior septum, and apex.
- Left circumflex (LCx) artery: Supplies the lateral and posterior walls of the left ventricle.
- Right Coronary Artery (RCA): Arises from the right aortic sinus and supplies:
- Right atrium, right ventricle, inferior wall of the left ventricle, and posterior descending artery in most individuals.
1.2 Functional Significance
- Coronary blood flow occurs mainly during diastole, especially in the left ventricle due to high systolic pressures.
- Collateral circulation can partially compensate for blocked arteries.
- Anatomical variations influence clinical manifestations of IHD:
- LAD occlusion → anterior wall infarction.
- RCA occlusion → inferior wall infarction.
- LCx occlusion → lateral wall infarction.
1.3 Coronary Circulation Zones
- Epicardial arteries: Main conduits, often the site of atherosclerotic plaque formation.
- Intramyocardial arteries: Penetrate the myocardium, supplying subendocardial layers.
- Subendocardium: Most susceptible to ischemia due to higher oxygen demand and compression during systole.
2. Atherosclerosis and Plaque Formation
Atherosclerosis is the primary cause of ischemic heart disease, characterized by progressive narrowing of coronary arteries due to lipid deposition, inflammation, and fibrosis.
2.1 Initiation of Atherosclerosis
- Endothelial Injury:
- Triggered by hypertension, smoking, diabetes, dyslipidemia, and oxidative stress.
- Leads to increased permeability to lipids and leukocyte adhesion.
- Lipoprotein Retention:
- Low-density lipoprotein (LDL) cholesterol infiltrates the intima.
- LDL is oxidized by reactive oxygen species, triggering inflammation.
2.2 Inflammatory Response
- Oxidized LDL attracts monocytes, which differentiate into macrophages.
- Macrophages engulf LDL → foam cell formation, creating fatty streaks, the earliest lesion in atherosclerosis.
- T-lymphocytes secrete pro-inflammatory cytokines, amplifying the response.
2.3 Plaque Progression
- Smooth muscle cells migrate from the media to the intima.
- Fibrous tissue forms a cap over the lipid core, producing a fibroatheromatous plaque.
- Plaques can be:
- Stable plaques: Thick fibrous cap, minimal inflammation, less prone to rupture.
- Vulnerable plaques: Thin fibrous cap, large lipid core, high inflammation, prone to rupture → acute coronary syndromes.
2.4 Calcification and Advanced Lesions
- Chronic inflammation leads to plaque calcification, detectable on imaging.
- Plaques may narrow the lumen gradually (chronic ischemia) or rupture suddenly (acute ischemia).
3. Endothelial Dysfunction and Thrombosis
The endothelium is critical in regulating vascular tone, platelet activity, and coagulation. Dysfunction of this layer is central to IHD.
3.1 Endothelial Dysfunction
- Normal endothelium: Produces nitric oxide (NO) → vasodilation, inhibits platelet aggregation, reduces smooth muscle proliferation.
- Dysfunctional endothelium: Reduced NO, increased endothelin, and pro-thrombotic factors.
- Consequences:
- Impaired vasodilation → increased coronary resistance.
- Promotes inflammation and atherosclerosis progression.
- Facilitates thrombus formation after plaque rupture.
3.2 Thrombosis
- Plaque rupture exposes subendothelial collagen and tissue factor, activating platelets and coagulation cascades.
- Thrombus may be:
- Occlusive: Complete blockage → STEMI.
- Non-occlusive: Partial blockage → unstable angina or NSTEMI.
- Platelet aggregation and thrombus propagation amplify myocardial ischemia.
3.3 Role of Inflammation
- Chronic inflammation destabilizes plaques and enhances thrombogenicity.
- Biomarkers like C-reactive protein (CRP) predict risk of acute events.
4. Acute vs Chronic Ischemia Mechanisms
4.1 Acute Ischemia
Acute ischemia typically results from sudden reduction in coronary blood flow, often due to plaque rupture and thrombosis.
Mechanisms:
- Plaque Rupture: Thin-capped fibroatheroma ruptures, exposing lipid core.
- Thrombus Formation: Platelet aggregation → acute lumen obstruction.
- Vasospasm: Local release of vasoconstrictors (e.g., thromboxane) → further narrowing.
- Outcome: If ischemia is prolonged → myocardial necrosis (STEMI); transient → unstable angina.
Clinical Features:
- Severe chest pain, often at rest.
- ECG: ST-segment elevation (STEMI) or depression/T-wave inversion (NSTEMI).
- Biomarkers: Troponin elevation in infarction.
4.2 Chronic Ischemia
Chronic ischemia results from gradual narrowing of coronary arteries due to progressive plaque growth.
Mechanisms:
- Fixed Atherosclerotic Stenosis: Reduces maximal blood flow, particularly during exertion.
- Collateral Circulation: Slow development of alternative vessels partially compensates.
- Subendocardial Vulnerability: Inner myocardial layers are more susceptible to reduced perfusion.
- Outcome: Stable angina during exertion, silent ischemia in some cases.
Clinical Features:
- Exertional chest pain relieved by rest (stable angina).
- May be asymptomatic (silent ischemia), especially in diabetics.
- ECG: May show ST depression during stress, normal at rest.
4.3 Differences Between Acute and Chronic Ischemia
| Feature | Acute Ischemia | Chronic Ischemia |
|---|---|---|
| Onset | Sudden | Gradual |
| Cause | Plaque rupture, thrombosis | Fixed stenosis, atherosclerosis |
| Symptoms | Severe, prolonged | Exertional angina, transient |
| ECG | ST elevation or depression | Often normal at rest |
| Biomarkers | Elevated troponins | Usually normal |
| Outcome | Myocardial infarction possible | Stable ischemia, compensated by collaterals |
5. Cellular and Molecular Responses to Ischemia
5.1 Myocardial Oxygen Supply and Demand
- Supply depends on coronary perfusion pressure, coronary artery diameter, and oxygen-carrying capacity.
- Demand depends on heart rate, contractility, wall stress.
- Ischemia occurs when demand exceeds supply, leading to metabolic and functional impairment.
5.2 Metabolic Consequences
- ATP depletion: Impairs myocyte contraction and ion pump function.
- Anaerobic metabolism: Lactate accumulation → acidosis.
- Electrolyte imbalances: Potassium and calcium disturbances → arrhythmias.
5.3 Functional Consequences
- Myocardial stunning: Temporary post-ischemic dysfunction even after reperfusion.
- Hibernating myocardium: Chronic low perfusion causes downregulated metabolism to preserve viability.
- Infarction: Irreversible necrosis with replacement by scar tissue.
6. Factors Modifying Ischemia Severity
- Coronary Anatomy: Single-vessel vs multi-vessel disease.
- Collateral Circulation: Well-developed collaterals reduce infarct size.
- Heart Rate: Tachycardia increases oxygen demand.
- Blood Pressure: Hypotension reduces coronary perfusion.
- Left Ventricular Hypertrophy: Increases myocardial oxygen demand.
- Systemic Conditions: Anemia, hypoxemia, or sepsis exacerbate ischemia.
7. Summary
Ischemic heart disease results from coronary atherosclerosis leading to reduced myocardial blood flow, creating an imbalance between oxygen supply and demand. Key points include:
- Coronary Artery Anatomy: LCA and RCA supply different myocardial regions; collateral circulation may mitigate ischemia.
- Atherosclerosis: Lipid deposition, inflammation, and plaque formation gradually narrow arteries.
- Endothelial Dysfunction and Thrombosis: Loss of nitric oxide, increased platelet aggregation, and thrombus formation precipitate acute events.
- Acute vs Chronic Ischemia: Acute ischemia arises from sudden plaque rupture and thrombosis, while chronic ischemia results from progressive arterial narrowing.
- Cellular Effects: ATP depletion, anaerobic metabolism, arrhythmogenic potential, and myocardial stunning or infarction.
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