Mechanism of Atheroma and Infarction

• What is an atheroma?

  • A pathological condition characterised by the accumulation of lipid-rich plaques within the intima of arteries, leading to chronic inflammation, endothelial dysfunction and vascular remodelling.
  • Key feature of atherosclerosis and contributes to cardiovascular diseases such as myocardial infarction and stroke.

  
• What are the main stages of atheroma formation?

  1. Endothelial Dysfunction
  2. Fatty Streak Formation
  3. Fibrous Plaque Formation
  4. Plaque Rupture and Complications
• What causes endothelial dysfunction in atheroma formation?

  
  

  Injury to the endothelium due to:

  • Hypertension (increased mechanical stress on the endothelium)
  • Hyperlipidaemia (high levels of LDL cholesterol)
  • Smoking (oxidative damage and inflammation)
  • Diabetes (glycation of endothelial proteins)
  • Inflammation (cytokine-mediated damage)
• What are the consequences of endothelial cell damage in atheroma formation?

  Lose their ability to regulate:

  • Vascular tone
  • Permeability
  • Anti-thrombotic properties leading to increased inflammation, LDL infiltration, and platelet adhesion, which contribute to atheroma development.
• What role does LDL cholesterol play in atheroma formation?

  • Low-Density Lipoprotein (LDL) cholesterol penetrates the damaged endothelium and becomes trapped in the intima.
  • LDL is oxidised by free radicals, forming oxidised LDL (oxLDL), which is pro-inflammatory and attracts immune cells.
• How do monocytes contribute to atheroma formation?

  • Monocytes adhere to the damaged endothelium and migrate into the intima.
  • They differentiate into macrophages, which engulf oxidised LDL via scavenger receptors.
  • This leads to the formation of foam cells, which accumulate to form a fatty streak—the earliest visible sign of atheroma.
•  What is a fatty streak?

  An early stage of atheroma formation, composed of lipid-laden foam cells within the intima. It is initially asymptomatic but can progress to a more advanced lesion if risk factors persist.
• How does a fatty streak develop into a fibrous plaque?

  • Smooth muscle cells (SMCs) from the tunica media migrate into the intima.
  • They proliferate and secrete extracellular matrix (ECM) components such as collagen and elastin, forming a fibrous cap.
  • This stabilises the lesion but also contributes to arterial narrowing, leading to reduced blood flow.
• What is the significance of the fibrous cap in atheroma?

  • The fibrous cap covers the lipid core and helps prevent plaque rupture.
  • A thick fibrous cap is more stable, while a thin fibrous cap is prone to rupture, increasing the risk of thrombus formation and infarction.
• What happens when an atheromatous plaque ruptures?

  • Exposure of the lipid core and collagen activates platelets, leading to thrombus formation.
  • This can partially or completely occlude the artery, causing ischemia and potentially leading to myocardial infarction or stroke.
• What are the complications of atheroma?

  1. Plaque Rupture → Thrombosis → Myocardial Infarction or Stroke
  2. Progressive Narrowing → Ischemia → Angina or Peripheral Artery Disease
  3. Aneurysm Formation due to weakened arterial walls
  4. Embolism if a thrombus dislodges and blocks smaller arteries
• What is occlusive thrombosis?

  • The formation of a thrombus (blood clot) that completely blocks the lumen of a blood vessel, leading to ischemia (restricted blood supply) and potentially infarction (tissue death).
  • Often associated with advanced atherosclerosis, where ruptured atheromatous plaques trigger the coagulation cascade.
• What are the key steps in the formation of occlusive thrombosis?

  1. Endothelial Injury – Atherosclerotic plaque rupture exposes subendothelial collagen and tissue factor.
  2. Platelet Activation and Aggregation – Platelets adhere, get activated, and release pro-thrombotic factors.
  3. Coagulation Cascade Activation – Fibrin mesh forms, stabilizing the thrombus.
  4. Lumen Occlusion – The clot enlarges, blocking blood flow.
  5. Ischemia & Infarction – Tissue distal to the occlusion suffers from oxygen deprivation, leading to necrosis.
•  What are the common sites of occlusive thrombosis?

  • Coronary arteries → Myocardial infarction
  • Cerebral arteries → Ischemic stroke
  • Peripheral arteries → Gangrene (e.g., in diabetes)
•  What is thromboembolism?

  When a thrombus (blood clot) dislodges from its original site and travels through the bloodstream, potentially obstructing smaller distal vessels and causing ischemia or infarction.
•  What are the major types of thromboembolism?

  1. Pulmonary Embolism (PE) – A deep vein thrombosis (DVT) dislodges and blocks pulmonary arteries.
  2. Systemic Embolism – An arterial thrombus travels to the brain (causing stroke), limbs, or organs.
  3. Paradoxical Embolism – A venous embolus bypasses the lungs via a heart defect (e.g., patent foramen ovale) and enters systemic circulation.
• How does thromboembolism lead to infarction?

  • Embolus lodges in a distal artery.
  • Blood supply to dependent tissue is blocked.
  • Ischemia develops, leading to necrosis if prolonged.
• What is an aneurysm?

  • An abnormal, localised dilation of a blood vessel due to weakened arterial walls, often caused by chronic hypertension and atherosclerosis.
  • Increases the risk of rupture, leading to life-threatening haemorrhage.
• What are the common types of aneurysms?

  1. Saccular Aneurysm – A bulging, sac-like outpouching (e.g., Berry aneurysm in the brain).
  2. Fusiform Aneurysm – A uniform, spindle-shaped dilation along an artery.
  3. Dissecting Aneurysm – Blood enters the arterial wall layers, forming a false lumen (e.g., aortic dissection).
• What are the complications of aneurysms?

  • Rupture → Haemorrhage (e.g., subarachnoid haemorrhage in Berry aneurysm).
  • Thrombosis & Embolism – Clot formation inside an aneurysm may embolise.
  • Compression of Adjacent Structures – Large aneurysms may press on nerves/organs.
• What are the key risk factors contributing to atherosclerosis development?

  A: Arterial hypertension

  T: Tobacco

  H: Hereditary

  E: Endocrine

  R: Reduced physical activity

  O: Obesity

  M: Male gender

  A: Age
• Describe how an atheromatous plaque can cause infarction

  1. Plaque Rupture – Mechanical stress and inflammation weaken the fibrous cap, leading to rupture.
  2. Thrombosis Formation – Exposure of thrombogenic material (e.g., collagen, tissue factor) activates platelets and coagulation pathways.
  3. Arterial Occlusion – Thrombus formation partially or fully blocks the affected artery, reducing blood supply.
  4. Ischaemia & Tissue Death – Reduced oxygen delivery causes irreversible cell damage and infarction, leading to myocardial infarction (heart) or stroke (brain).
•  Explain the role of inflammation in atheroma development and rupture

  Inflammation is a central driver of atheroma progression:

  • Monocytes & Macrophages – Recruited to the intima, they engulf oxidised LDL, becoming foam cells.
  • Cytokines (e.g., TNF-α, IL-1, IL-6) – Promote vascular dysfunction and smooth muscle proliferation.
  • Matrix Metalloproteinases (MMPs) – Degrade the fibrous cap, increasing the likelihood of rupture.
  • Chronic Inflammation – Conditions like diabetes and obesity sustain an inflammatory state, worsening plaque instability.
• List the possible outcomes of infarction due to atheroma

  • Myocardial Infarction (Heart Attack): Occlusion of coronary arteries leading to ischaemic heart disease and heart failure.
  • Cerebral Infarction (Stroke): Blockage of cerebral arteries causing neurological deficits.
  • Peripheral Arterial Disease (PAD): Reduced blood supply to limbs, leading to claudication and ulceration.
  • Aneurysm Formation: Chronic arterial wall weakening, increasing rupture risk.
• How can atheroma progression and infarction be prevented?

  Lifestyle Modifications:

  • Diet: Low saturated fat, high fibre, Mediterranean-style diet.
  • Exercise: Regular aerobic activity improves lipid profile and vascular function.
  • Smoking Cessation: Reduces oxidative stress and endothelial injury.

  Pharmacological Approaches:

  • Statins: Lower LDL cholesterol and stabilise plaques.
  • Antihypertensives: Reduce arterial stress and endothelial dysfunction.
  • Antiplatelets (e.g., Aspirin, Clopidogrel): Reduce thrombotic risk.
• What is arterial occlusion?

  • The complete or partial blockage of an artery, usually due to atherosclerosis, thrombosis, or embolism.
  • Leads to ischaemia (restricted blood supply), which can cause tissue hypoxia and infarction if prolonged.
• What is venous occlusion?

  • Occurs when a vein is blocked, often by thrombosis.
  • Leads to increased hydrostatic pressure, congestion, and oedema.
  • Severe cases, it can cause ischaemia and infarction due to impaired venous return.
• How does arterial occlusion cause infarction?

  Arterial occlusion reduces or stops blood flow to downstream tissues, depriving them of oxygen and nutrients. This leads to:

  1. Ischaemia – Oxygen deprivation triggers anaerobic metabolism, increasing lactic acid and causing cell damage.
  2. Hypoxia – Cells die if oxygen supply is not restored.
  3. Necrosis (Infarction) – Tissue death occurs, typically in organs with single arterial supply (e.g., heart, brain, kidney).
• What are the consequences of arterial occlusion?

  1. Ischaemia – Reduced oxygen supply leads to metabolic dysfunction.
  2. Infarction – Irreversible tissue necrosis if prolonged.
  3. Loss of function – Affected organ/tissue loses normal function (e.g., myocardial infarction → impaired heart contraction).
  4. Inflammation and repair – Dead tissue is replaced by fibrosis or scarring.
• What is the most common cause of arterial occlusion?

  Atherosclerosis is the primary cause. It involves lipid accumulation, endothelial dysfunction, inflammation, and plaque formation, leading to thrombosis and arterial narrowing/blockage.
• How does venous occlusion cause infarction?

  Venous occlusion prevents proper blood drainage, leading to:

  1. Increased hydrostatic pressure – Blood accumulates in capillaries.
  2. Congestion and oedema – Fluid leaks into tissues, impairing oxygen diffusion.
  3. Hypoxia – Prolonged oxygen deprivation damages cells.
  4. Haemorrhagic infarction – Tissues become necrotic due to trapped, deoxygenated blood (common in organs with dual blood supply, e.g., lungs, intestines).
• What are the consequences of venous occlusion?

  1. Oedema – Fluid buildup due to increased venous pressure.
  2. Congestion – Accumulation of deoxygenated blood.
  3. Haemorrhagic infarction – Tissue death with bleeding into necrotic areas.
  4. Organ dysfunction – Impaired function due to prolonged hypoxia.
• How does arterial infarction differ from venous infarction?

  1. Arterial infarction:

  • Caused by ischaemia due to arterial blockage.
  • Pale (anaemic) infarct due to lack of blood supply.
  • Common in heart, kidneys, spleen (single arterial supply).

  1. Venous infarction:

  • Caused by venous congestion.
  • Haemorrhagic infarct due to trapped deoxygenated blood.
  • Common in lungs, intestines (dual blood supply).
• Why are some infarcts haemorrhagic and others pale?

  • Pale (anaemic) infarcts occur in organs with single arterial supply (e.g., heart, kidneys, spleen) where arterial occlusion leads to no blood flow.
  • Haemorrhagic infarcts occur in organs with dual blood supply (e.g., lungs, intestines), where venous occlusion or reperfusion causes blood to leak into necrotic tissue.
• What factors influence infarct severity?

  1. Nature of vascular supply – Dual supply (e.g., lungs) reduces infarct severity.
  2. Rate of occlusion – Slow occlusions allow collateral circulation to develop.
  3. Tissue vulnerability – Neurons are highly sensitive, whereas skeletal muscle is more resistant.
  4. Oxygen content of blood – Anaemia or respiratory disease worsens infarction.
• What is myocardial infarction (MI)?

  • Commonly known as a heart attack, occurs when there is a sudden blockage in one of the coronary arteries, leading to the interruption of blood flow to a part of the heart muscle (myocardium).
  • Results in tissue death (necrosis) due to lack of oxygen and nutrients.
• What causes myocardial infarction (MI)?

  • Often caused by atherosclerosis, a condition where fatty deposits (atheromas) build up in the walls of the coronary arteries.
  • These plaques can rupture, triggering the formation of a thrombus (blood clot). The thrombus can completely block blood flow, leading to myocardial ischemia and infarction.
• What is the mechanism of myocardial infarction due to a ruptured atheroma?

  • An atheroma in the coronary artery wall becomes unstable and ruptures.
  • The rupture exposes the underlying thrombogenic core to the bloodstream.
  • Platelets adhere to the exposed area and release clotting factors, initiating the coagulation cascade.
  • A thrombus forms and occludes the coronary artery, reducing or completely blocking blood flow to the heart muscle.
  • The ischemic area becomes hypoxic, and myocardial cells begin to die.
• What are the immediate consequences of myocardial infarction?

  • Cell death: Myocardial cells undergo necrosis within 20–40 minutes of ischemia.
  • Tissue damage: The affected region of the heart muscle suffers irreversible damage.
  • Inflammatory response: Inflammation occurs as immune cells clear dead cells and tissue debris.
  • Loss of contractility: The damaged heart muscle loses its ability to contract effectively, leading to decreased cardiac output.
• What are the long-term consequences of myocardial infarction?

  • Heart failure
  • Arrhythmias
  • Cardiac remodelling
  • Increased risk of future infarctions