1. Anomalous (e.g. aberrant, reduplicated) vessels are principally of interest to surgeons.
2. Berry aneurysms are outpouchings of vessels as a result of congenital focal weakness.
They occur exclusively in cerebral vessels and occasionally rupture catastrophically.
3. Arteriovenous fistula is an abnormal communication between artery and vein.
It may be congenital or secondary to trauma, inflammation, or healed ruptured aneurysm.
Arteriosclerosis denotes thickening and loss of elasticity of arterial walls.
The three types of arteriosclerosis are:
1. Atherosclerosis
2. Monckeberg arteriosclerosis
3. Arteriolosclerosis (primarily associated with hypertension)
Atherosclerosis:
Atherosclerosis is a slowly progressive disease of arteries, marked by elevated fibrofatty, intimal plaques, formed by lipid deposition, smooth muscle cell proliferation, and synthesis of extracellular matrix in the intima.
Lesions initially tend to be focal, only partially involving the vessel circumference, and are patchy along its length.
Atherosclerosis may begin in childhood but typically manifests in middle age or later life either as the vessel lumen is compromised, predisposing to thrombosis, or as the underlying media is thinned, predisposing to aneurysm formation.
Fifty percent of all deaths in the developed world are attributed to atherosclerosis, half resulting from myocardial infarction or sudden death in ischemic heart disease and the remainder from cerebrovascular accidents (stroke), aneurysm rupture, mesenteric occlusion, and gangrene of the extremities.
Arteries involved are large to medium-sized muscular and large elastic arteries, principally in the abdominal aorta, coronary arteries, popliteal arteries, descending thoracic aorta, internal carotid arteries, and circle of Willis (in the descending order of frequency).
Risk factors:
I. Risk of the development of atherosclerosis increases with age, family history, hypertension, cigarette smoking, hypercholesterolemia, and diabetes- the last four often called the major risk factors.
II. Lesser or unquantified risk factors include obesity, sedentary or high-stress life style, type A personality, male gender, postmenopausal estrogen deficiency.
The risk is correlated with the level of serum low-density lipoprotein (LDL), formed from the catabolism of very-low-density lipoprotein (VLDL).
LDL carries 70% of the total serum cholesterol.
The risk is inversely related to high density-lipoprotein (HDL) levels, perhaps because HDL helps clear cholesterol from vessel wall lesions.
Hereditary defects involving the LDL receptor (e.g., in familial hypercholesterolemia) or LDL apoproteins cause elevated LDL, hypercholesterolemia, and accelerated atherosclerosis.
Normal lipid metabolism:
Dietary fat consists of fatty acid and cholesterol. In the intestine fatty acid forms triglyceride and these together (triglyceride and cholesterol) is called chylomicron.
From intestine chylomicron enters via lymphatics into blood.
Very-low-density-lipoproteins (VLDL) and low-density-lipoproteins (LDL) are formed in the liver cells.
High-density-lipoproteins (HDL) are formed by the extrahepatic tissue.
Plasma lipoproteins:
Chylomicron consists of mostly triglyceride and some cholesterol.
Both are increased after meal.
LDL is mostly cholesterol-ester and some triglyceride.
VLDL is mainly triglyceride, synthesized in liver and transports triglyceride from liver to blood.
High Density Lipoprotein:
1. It mobilizes cholesterol from tissue cells to liver for excretion in the bile.
2. It is reverse trasport of cholesterol.
3. Physical exercise and ethanol raise HDL. Smoking and obesity lower it.
Lesions:
The characteristic atheromatous plaque (atheroma) is a raised white-yellow intimal lesion, protruding into the vessel lumen.
Histologically, the typical atheroma (also called fibrofatty plaque) is mainly composed of:
1. Cells- include smooth muscle cells, macrophages and other leukocytes.
2. Connective tissue extracellular matrix- includes collagen, elastic fibers and proteoglycans.
3. Intracellular and extracellular lipid deposits- necrotic core containing dead cells, lipid, cholesterol cleft, lipid-laden foam cells (macrophages and smooth muscle cells), and plasma proteins. In the periphery there is proliferating small blood vessels.
In addition, two common variants are as follows:
1. Fatty streaks: Intimal collections of lipid-laden macrophages and smooth muscle cells, occurring in patients as young as 1 year age.
A causal relationship of fatty streaks to subsequent atheromatous plaques is suspected but has not been proven.
2. Complicated plaques: calcified, hemorrhagic, fissured, or ulcerated atheromas, predisposing to local thrombosis, medial thinning, cholesterol micro-emboli, and aneurismal dilation.
Pathogenesis:
The cause of atherosclerosis remains unknown, but most theories involve some damage to the endothelium or underlying media.
The causes of endothelial cell injury include hyperlipidemia, hemodynamic disturbances (such as disturbed flow), smoking, hypertension, toxins, and potentially infectious agents.
The most important consequences of endothelial injury are increased endothelial permeability, adhesions of white cells and platelets and activation of coagulation.
This is followed by release or activation of chemical mediators, such as growth factors, and migration and subsequent proliferation of smooth muscle cells in the intima to produce atheroma.
The contemporary view of the pathogenesis of atherosclerosis called the response to injury hypothesis, considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by some form of injury to the endothelium.
Central to this thesis are the following:
1. The development of focal regions of chronic endothelial injury, usually subtle, with resultant endothelial dysfunction, such as increased endothelial permeability and increased leukocyte adhesion (via cell adhesion molecules, such as vascular cell adhesion molecule).
2. Adhesion of blood monocytes and other leukocytes to foci of injured endothelium.
3. Migration of monocytes into the intima and their transformation into macrophages, which accumulate lipid and become foam cells.
4. Insudation of lipoproteins into the vessel wall at foci of endothelial injury, mainly LDL with its high cholesterol content and VLDL.
5. Oxidation of such lipoproteins by the accumulated macrophages.
6. Adhesion of platelets to focal areas of endothelial injury or denudation (when present) or to other leukocytes.
7. Release of factors such as platelet-derived growth factors from activated platelets, macrophages, or vascular cells that cause migration of smooth muscle cells from media into the intima.
8. Proliferation of smooth muscle cells in the intima and elaboration of extracellular matrix, leading to accumulation of collagen and proteoglycans.
9. Enhanced accumulation of lipids both within cells (macrophages and smooth muscle cells) and
extracellularly.
Clinical features:
Atherosclerosis is asymptomatic for decades until it causes disease by the following mechanisms:
1. Insidious narrowing of vascular lumen (e.g. gangrene of the lower leg because of stenosing atherosclerosis in the popliteal artery) .
2. Plaque rupture followed by superimposed thrombosis causing sudden occlusion of the lumen (e. g. myocardial infarction precipitated by thrombotic occlusion of disrupted coronary arterial atheroma).
3. Providing a source of embolic debris known as atheroembolism (e.g. renal infarct resulting from cholesterol emboli originating in an ulcerated atherosclerotic aortic plaque).
4. Weakening of the wall of vessel followed by aneurysm formation and possibly rupture (e.g., an abdominal aortic aneurysm).
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