Vascular Pathologies: Atherosclerosis and Congenital Anomalies
Consequences of Pathological Changes in Vessels
- Stenosis and obstruction of the vessel.
- Weakening of vessel walls.
- Production of thrombotic deposits.
Congenital Anomalies
- Abnormal blood vessels
- Strawberry aneurysm
- Arteriovenous fistulas (causing increased venous return and high risk of cardiac insufficiency)
Atherosclerosis
Atherosclerosis is a chronic inflammatory response of the arterial wall to some form of injury from the endothelial cells (EC). It commonly occurs in the abdominal aorta, coronary arteries, popliteal arteries, descending thoracic aorta, and internal carotid arteries.
Characteristics: Raised yellowish-white fibrofatty atheromatous plaques based on the intima, composed of superficial fibrous layers, smooth muscle cells, leukocytes, and extracellular matrix of dense connective tissue. Above the necrotic center are dead cells, cholesterol clefts, foam cells, and plasma proteins. Lesions can be circumferential and longitudinal. At the interface of the media and intima, vessels proliferate.
Fatty streak: Composed of macrophages, lipids, and smooth muscle cells in young patients as early as 1 year of age.
Complicated plaques: Calcified atheroma, bleeding, or ulcerated fissures, which predispose to local thrombosis, decreased average cholesterol, microemboli, and aneurysmal dilation.
Risk Factors:
- Positive: Age, family history, hypertension, smoking, hypercholesterolemia, and diabetes.
- Negative: Obesity, sedentary lifestyle, stress, type A personality.
Major irrigation increases low-density lipoprotein (LDL, which transports 70% of cholesterol) and decreases the level of HDL (which removes cholesterol from the wall lesions).
Causes of Endothelial Injury: Hyperlipidemia, hemodynamic alterations, smoking, hypertension, toxins, and infectious agents.
“Response to Injury” Hypothesis
Endothelial injury (EI) increases the permeability of the endothelial cells, leading to leukocyte and platelet adhesion and activation of coagulation. It induces the release of chemical mediators and the recruitment and proliferation of smooth muscle cells (SMCs) in the intima to produce atheroma.
Focal EC injury causes endothelial dysfunction, increased permeability, and the expression of adhesion molecules on leukocytes. Monocytes and other blood cells adhere to the altered EC. Monocytes migrate to the intima and transform into macrophages, accumulating lipids to become foam cells. Lipoproteins (serum LDL with high cholesterol and VLDL) penetrate the vessel walls at sites of EC injury. Macrophages oxidize lipoproteins. Platelets adhere to sites of EC injury or to leukocytes. Activated platelets, macrophages, or vascular wall cells release factors (e.g., PDGF) that cause SMCs to migrate to the intima. SMCs proliferate in the intima, and the release of ECM leads to the accumulation of collagen and proteoglycans. Lipids accumulate both in cells (macrophages and SMCs) and extracellularly.
Although monocyte recruitment and foam cell formation are initially protective, macrophages produce cytokines that further recruit monocytes and T cells into the intima, induce the production of growth factors (smooth muscle cell proliferation), and induce the synthesis of reactive oxygen species (which can oxidize LDL). The interaction of macrophages and T cells also produces a characteristic immune cell activation state of chronic inflammation.
Manifestations
Atherosclerosis manifests through the following mechanisms:
- Insidious narrowing of vascular lumens.
- Plaque rupture or superficial erosion, leading to the formation of a thrombus that causes sudden stenosis.
- Weakening of the wall, followed by the formation and possible rupture of an aneurysm.
- Providing a source of emboli (atheroembolism) that causes distal organ injury.
Atherosclerosis is responsible for approximately one-third of deaths in the U.S., due to myocardial infarction, sudden death, stroke, ruptured aneurysms, mesenteric occlusion, or gangrene of the extremities.