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• Normal Anatomy & Histology: Basic Components Of The Wall Of Blood Vessels Are Endothelial Cells (Ecs), Smooth Muscle Cells (Smcs), and Extracellular Matrix (Ecm)

  
• Layers of blood vessel wall (from lumen to outside)

  • Intima: Single layer of endothelial cells
  • Media: Smooth muscle cells
  • Adventitia: Connective tissue, Vasa Vasorum, Nerve Fibers

  
• Classification of arteries by size and structure

  • Large or elastic arteries: Aorta, major branches of aorta, pulmonary arteries (elastic fiber rich media)
  • Medium-sized or muscular arteries: Smaller branches of aorta like coronary and renal arteries (media composed predominantly of SMC)
  • Small arteries (≤2mm) and arterioles (20-100μm): Media of smooth muscle, control blood pressure

  
• Vascular disorders are responsible for more morbidity and mortality than any other category of human diseases
• Two main mechanisms underlying vascular disease

  • Narrowing (stenosis) or obstruction of vessel lumens (e.g. atherosclerosis, thrombosis, embolism)
  • Weakening of vessel walls, leading to dilation or rupture

  
• Arteriosclerosis


  Thickening and loss of elasticity of arterial walls, leading to hardening
• Variants of arteriosclerosis

  • Atherosclerosis
  • Monckeberg medial calcific sclerosis
  • Arteriolosclerosis
  • Fibromuscular intimal hyperplasia

  
• Atherosclerosis is the most frequent and important form of arteriosclerosis

  
• Risk factors for atherosclerosis


  • Non-modifiable: Genetic abnormalities, Increasing age, Male gender
  • Modifiable: Hyperlipidemia, Hypertension, Cigarette smoking, Diabetes mellitus, Metabolic syndrome, Physical inactivity, Stressful lifestyle, Lipoprotein (a), Hyperhomocystinemia
• Atherosclerosis

  Thickening or hardening of arteries caused by buildup of atheromatous plaque in the inner lining

  
• Atherosclerosis is responsible for more deaths and serious complications than any other disorder, as it targets vital arteries like coronaries, cerebral arteries, and aorta

  
• Atherosclerotic plaque (atheroma)


  • Complex interplay of cells and extracellular materials, intimal-based process

  
• Pathogenesis of atherosclerosis (response to injury hypothesis)


  1. Chronic injury to endothelium

  2. Increased endothelial permeability, blood monocyte and platelet adhesion

  3. Accumulation of oxidized LDL in vessel wall

  4. Monocyte transformation to macrophages, foam cell formation

  5. SMC migration, proliferation, ECM production, T cell recruitment

  
• Three most important causes of endothelial injury are hemodynamic disturbances, hypercholesterolemia, and inflammation

  
• Oxidized LDL is considered atherogenic as it induces foam cell formation, is chemotactic to monocytes, and cytotoxic to endothelial cells
• Antioxidants like vitamin E and β-carotene may prevent atherosclerosis by reducing LDL oxidation
• Morphological features of atherosclerosis


  • Fatty streaks
  • Atheromatous plaques (atheroma)

  
• Fatty streaks


  Composed of lipid-laden macrophages (foam cells), precursor to atheromatous plaques
• Atheromatous plaques (atheroma)


  Consist of a soft, yellow core of cholesterol and cholesterol esters, and a firm, white fibrous cap

  
• Atherosclerotic lesions are patchy and rarely circumferential, usually involving only a portion of the arterial wall

  
• Arteries most heavily involved by atherosclerosis (in descending order)


  • Lower abdominal aorta
  • Iliac arteries
  • Coronary arteries
  • Popliteal arteries
  • Internal carotid arteries
  • Vessels of the circle of Willis

  
• Vessels of the upper extremities, mesenteric arteries, and renal arteries (except at their ostia) are usually relatively spared from atherosclerosis

  
• Consequences/complications of atherosclerosis


  • Plaque rupture, ulceration, or erosion leading to thrombosis
  • Organization of thrombus
  • Intraplaque hemorrhage
  • Atheroembolism
  • Aneurysm formation

  
• Stable atherosclerotic plaques have a dense fibrous cap, minimal lipid accumulation and little inflammation, whereas "vulnerable" unstable plaques have thin caps, large lipid cores, and dense inflammatory infiltrates

  
• Monckeberg's arteriosclerosis (medial calcific sclerosis)


  Characterized by ring-like calcifications within the media of muscular arteries, does not narrow the lumen and is of little clinical significance