ACS, CAD, Angina, PAD: Pathophysiology

What are cardiomyocytes?

Specialized muscle cells in the myocardium that contract and relax rhythmically to pump blood.

What is the role of intercalated discs?

They connect cardiomyocytes and synchronize heart contractions.

What supplies oxygen and nutrients to the myocardium?

Coronary arteries: LAD, circumflex, and right coronary artery.

What causes ischemic heart disease (IHD)?

Imbalance between myocardial oxygen supply and demand.

What increases myocardial oxygen demand?

↑ HR, ↑ contractility, ↑ preload, ↑ afterload, ↑ systolic wall tension.

What decreases myocardial oxygen supply?

↓ coronary blood flow due to atherosclerosis or vasoconstriction.

What is angina pectoris?

Chest pain due to myocardial ischemia.

How does coronary artery calcification affect blood flow?

Progressive narrowing → ischemia → angina.

What causes myocardial infarction (MI)?

Complete stoppage of blood supply → irreversible cell death.

What role does systemic inflammation play in CAD?

Promotes plaque formation and instability.

How do plaque stability and platelet reactivity affect IHD prognosis?

Unstable plaques and reactive platelets increase risk of ACS.

How does vasoconstriction affect coronary blood flow?

It reduces oxygen supply, worsening ischemia.

What causes CAD?

Atherosclerosis of coronary arteries → narrowing/blockage → ischemia/MI.

What initiates plaque formation in CAD?

Endothelial injury → LDL infiltration → foam cell formation.

What is the role of HDL in CAD?

Degrades oxidized lipids, removes cholesterol, inhibits plaque and clot formation.

Why is LDL considered “bad”?

It becomes oxidized and taken up by foam cells, promoting plaque formation.

How does LDL become oxidized?

Exposure to ROS and enzymes like MPO in the arterial wall.

What are “eat me” signals of ox-LDL?

Modified Apo B-100, oxidized lipids, surface markers.

What receptor uptakes ox-LDL?

CD36 scavenger receptor on macrophages.

What is endothelial dysfunction?

Loss of NO production, increased permeability, adhesion molecules, and prothrombotic state.

How does endothelial dysfunction promote CAD?

↑ LDL entry, ↑ leukocyte adhesion, ↓ vasodilation.

What cytokines contribute to plaque instability?

IL-1, IL-6, TNF-α, interferon-γ, CRP.

What causes plaque rupture in ACS?

Inflammation weakens fibrous cap → rupture → thrombosis.

What is the role of prothrombotic systems in CAD?

↑ platelet activation, ↑ thrombin, ↓ fibrinolysis.

What are antithrombotic mechanisms?

NO, PGI2, thrombomodulin, protein C/S, antithrombin III, tPA.

What causes ACS?

Plaque rupture → thrombus formation → reduced coronary blood flow.

What are the types of ACS?

Unstable angina, NSTEMI, STEMI.

How does unstable angina present?

Chest pain at rest, no troponin elevation, no myocardial cell death.

How does NSTEMI present?

ST depression or T-wave inversion, elevated troponin, partial-thickness infarction.

How does STEMI present?

ST elevation, elevated troponin, full-thickness infarction.

What are typical ACS symptoms?

Chest pain at rest, ECG changes, elevated troponin (except UA).

What are complications of ACS?

MI, heart failure, arrhythmias, death.

What ECG findings differentiate ACS types?

UA: normal or ST depression; NSTEMI: ST depression; STEMI: ST elevation.

What is troponin I?

Cardiac-specific protein used to diagnose MI.

Why is troponin normal in unstable angina?

No myocardial cell death occurs.

What is Prinzmetal’s angina?

Vasospastic angina due to transient coronary artery spasm.

What triggers stable angina?

Predictable chest pain with exertion; relieved by rest or nitroglycerin.

What defines unstable angina?

Unpredictable chest pain at rest; >15 min duration.

What is the difference between STEMI and NSTEMI?

STEMI = complete blockage; NSTEMI = partial blockage.

What are angina pain characteristics?

Burning, tightness, substernal, lasts 0.5–30 min, triggered by exertion.

Where is the location(s) of pain associated with angina?

Substernal, occasionally limited to left shoulder, arm, lower jaw.

How does nitroglycerin relieve angina?

Vasodilation → ↓ preload and afterload → improved oxygen supply.

What causes myocardial necrosis in MI?

Prolonged ischemia → irreversible cell death.

How do cardiac biomarkers differentiate MI from angina?

Troponin is elevated in MI, normal in angina.

Why is Prinzmetal’s angina not caused by atherosclerosis?

It’s due to vasospasm, not plaque.

What causes PAD?

Atherosclerosis of peripheral arteries, especially in the legs.

What arteries are commonly affected in PAD?

Femoral, popliteal, tibial arteries.

What is intermittent claudication?

Muscle pain during exertion relieved by rest; hallmark of PAD.

What are major PAD risk factors?

Age >60, diabetes, smoking, hypertension, dyslipidemia, obesity.

How does endothelial dysfunction contribute to PAD?

↓ NO, ↑ adhesion molecules, ↑ permeability.

How does lipid oxidation lead to plaque in PAD?

Oxidized LDL → foam cells → plaque formation.

What is the role of inflammation in PAD?

Foam cells release cytokines → plaque progression.

How does PAD progress?

From mild narrowing to critical limb ischemia and occlusion.

What systemic risks are increased in PAD?

Higher risk of CAD, stroke, and atherothrombotic events.

What are complications of PAD?

Limb amputation, increased morbidity and mortality.