Pathology Blood vessels

• Principal mechanisms underlying vascular disease:

  • Narrowing or stenosis of the blood vessel leading to partial or complete obstruction of the vessel lumen
  • Weakening of the vessel wall leading to abnormal dilatation of the vessel, known as an aneurysm
• Vascular wall response to injury:

  • Endothelial activation: response to injurious agents causing trauma or injury to the endothelium
  • Intimal thickening: involves thickening of the Tunica Intima due to activation of the endothelium
• Endothelial activation:

  • Normal endothelium is non-adhesive and non-thrombogenic
  • In response to injurious agents, there is release of chemical mediators for inflammation, increased expression of procoagulants, adhesion molecules, and proinflammatory factors, leading to a thrombogenic endothelium
• Intimal thickening:

  • Tunica Intima is the thinnest layer of the blood vessel
  • Thickening results from smooth muscle cell recruitment and proliferation, ECM synthesis, and regulation by chemical mediators released by the inflammatory process
• Hypertensive vascular disease features:

  • Sustained BP >139/89 mmHg increases the risk of atherosclerotic disease, cardiac hypertrophy, and heart failure
  • Malignant hypertension is characterized by severe hypertension, renal failure, retinal hemorrhages, and exudates
• Classification of hypertension:

  • Essential hypertension: no organic pathology or underlying systemic disease responsible for hypertension
  • Secondary hypertension: due to an underlying disease
• Pathogenesis of essential hypertension:

  • Related to multiple small changes in renal sodium homeostasis and changes in vessel wall tone or structure
  • Multifactorial condition affected by genetic factors, reduced renal Na+ excretion, environmental factors, and vasoconstrictive influences
• Pathogenesis of secondary hypertension:

  • Renovascular hypertension: renal artery stenosis leading to activation of RAAS
  • Single-gene disorders affecting aldosterone secretion and sodium reabsorption in response to aldosterone
• Vascular pathology in hypertension:

  • Effects of long-term hypertension on blood vessels include accelerated atherogenesis, degenerative wall changes in large and medium arteries, and small blood vessel diseases like hyaline and hyperplastic arteriolosclerosis
• Narrowing of the lumen can result from the deposition of pink, homogenous hyaline material composed of plasma proteins that leak across injured endothelial cells and smooth muscle cell ECM
• This narrowing can lead to nephrosclerosis in the kidneys, which can ultimately result in renal failure
• Hyperplastic arteriolosclerosis is associated with severe or malignant hypertension
• In hyperplastic arteriolosclerosis, concentric, laminated wall thickening with an "onion skin appearance" leads to luminal narrowing
• Atherosclerosis is characterized by arterial wall thickening and loss of elasticity
• Arteriosclerosis includes arteriolosclerosis, Monckeberg medial sclerosis, and atherosclerosis
• Atheromas or atheromatous plaques in atherosclerosis can obstruct, rupture, or weaken vessel walls
• Major risk factors for atherosclerosis include genetic abnormalities, hyperlipidemia, family history, hypertension, increasing age, smoking, male gender, diabetes, and inflammation
• Cholesterol and cholesterol esters are deposited in atherosclerosis, mainly low-density lipoproteins (LDL)
• Hyperlipidemia, particularly hypercholesterolemia, is a significant risk factor for atherosclerosis
• Hypertension is a major risk factor for atherosclerosis, affecting both systolic and diastolic levels
• Cigarette smoking is a well-established risk factor for atherosclerosis, leading to vasoconstriction
• Diabetes mellitus increases the risk of atherosclerosis and related complications like myocardial infarction and stroke
• Inflammation is a crucial factor in all stages of atherosclerosis development
• The pathogenesis of atherosclerosis involves chronic inflammatory and healing responses to arterial wall endothelial injury
• Chronic hyperlipidemia leads to increased production of reactive oxygen species (ROS) in atherosclerosis
• Endothelial dysfunction in atherosclerosis results in the accumulation of lipid-laden macrophages, triggering inflammation
• The accumulation of lipid-laden macrophages constitutes the earliest lesion in atherosclerosis, known as a fatty streak
• Smooth muscle cell proliferation and extracellular matrix deposition convert a fatty streak into a mature atheroma in atherosclerosis
• Growth factors like PDGF, FGF, and TGF-α play a role in smooth muscle cell proliferation in atherosclerosis
• The earliest lesion in atherosclerosis, the fatty streak, is composed of foam cells and multiple minute flat yellow spots that can coalesce into elongated streaks
• Fatty streaks can be seen in the aorta of some infants and in virtually all adolescents
• Common locations for atheromatous plaques include the lower abdominal aorta, coronary arteries, popliteal arteries, internal carotid artery, and Circle of Willis vessels
• Atheromatous plaques consist of smooth muscle cells, macrophages, T cells, ECM, collagen, elastic fibers, and proteoglycans
• Three principal components of atheromatous plaque are:

  • Smooth Muscle Cells, Macrophages, and T Cells
  • ECM (Collagen, Elastic Fibers, Proteoglycans)
  • Intracellular and Extracellular Lipid
• Mild atherosclerosis is composed of fibrous plaques, while severe atherosclerosis includes diffuse and complicated lesions like an ulcerated plaque and a lesion with overlying thrombus
• Fibrous cap consists of smooth muscle cells and dense collagen, while the necrotic core contains cholesterol, debris from dead cells, foam cells, fibrin, and variably organized thrombus
• Foam cells are lipid-laden macrophages with abundant foamy cytoplasm and small nuclei
• Acute plaque changes can include rupture/fissuring, erosion/ulceration, and hemorrhage into the atheroma, leading to thrombosis and vessel occlusion
• Rupture, ulceration, or erosion in atherosclerotic plaques can expose highly thrombogenic substances, leading to thrombosis and vessel occlusion
• Plaque rupture can lead to intraplaque hemorrhage, plaque expansion, or atheroembolism