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Atherosclerosis is thickening of the artery resulting from deposition of specific atheromatous lesions. “arteriosclerosis” is a nonspecific term that denotes thickening and loss of elasticity (“hardening”) of the Arteries from Any Cause. Changes Associated with Aging and Hypertension Often Lead to Arteriosclerosis.
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Atherosclerosis is the main cause of ischemic heart disease and cerebrovascular disease, and it is the major primary cause of death in most developed countries. The incidence of deaths due to atherosclerotic arterial disease increased in the United States until the mid 1960s, when it leveled off and began to decline. By 1986, death rates from atherosclerotic coronary and cerebral arterial disease had decreased over 50% when compared with death rates in 1968. The cause of this highly desirable trend is uncertain, although it is probably related to changes in diet and exercise habits and better control of hypertension. In North America and Europe, some degree of atherosclerosis is almost invariably present in the aorta and muscular arteries after age 30 years. The incidence and severity are generally less in South America, Africa, and Asia.
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The basic abnormality in atherosclerosis is the deposition of complex lipids in the intima. The cause is uncertain. Numerous risk factors have been identified (Table 20-1). The major controllable risk factors are discussed here.
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Hypertension is the most important risk factor in people over 45 years of age. Ischemic heart disease is five times more common in an individual whose blood pressure is > 160/95 mm Hg than in one who is normotensive (blood pressure < 140/90 mm Hg). The risk is diminished when high blood pressure is controlled with drugs.
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People who smoke more than 10 cigarettes per day have a threefold increase in risk. The risk declines to normal 1 year after cessation of smoking. The association of smoking with atherosclerosis is thought to be related to the presence of factors such as carbon monoxide that may cause endothelial cell injury.
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All diabetics who have had the disease for more than 10 years are likely to have significant atherosclerosis. Part of the risk in diabetes is due to the coexistence of other risk factors such as obesity, hypertension, and hyperlipidemia. Other suggested reasons for increased risk are (1) increased glycosylation of collagen, which increases LDL binding to collagen in atheromatous lesions; and (2) the fact that glycosylated high-density lipoprotein (HDL) is more easily degraded than is normal HDL. Because the latter two mechanisms are dependent on glycosylation, which is dependent on elevated blood glucose, it may explain how rigid control of diabetes can reduce the risk of atherosclerosis.
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(Table 20-2.) The presence of hyperlipidemia is the strongest risk factor for atherosclerosis in patients under age 45. Both primary and secondary hyperlipidemias increase the risk. Lipoproteins associated with endogenous lipid metabolism such as low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL) are much greater risk factors than chylomicrons associated with exogenous lipid metabolism (Figure 20-4). Increased levels of the following components of plasma lipids have been identified as associated with increased risk:
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Total Serum Cholesterol
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A level of > 240 mg/dL (> 6 mmol/L) imposes a high risk; 200–239 mg/dL (5.2–6.0 mmol/dL) is borderline; < 200 mg/dL (< 5.2 mmol/L) is desirable.
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Low Density Lipoprotein Cholesterol (LDL-C)
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A level of > 160 mg/dL (> 4.2 mmol/L) imposes a high risk; 130–159 mg/dL (3.4–4.1 mmol/L) is borderline; < 130 mg/dL (< 3.4 mmol/L) is desirable. The LDL-C serum level is determined by the following formula after direct measurement of plasma levels of total cholesterol (C), cholesterol associated with high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG):
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LDL-C levels are greatly elevated in familial hypercholesterolemia, which is caused by a mutation in the gene coding for the LDL receptor on the cell surface. Lack (in homozygotes) or decrease (in heterozygotes) of LDL-C receptor leads to failure of clearing of plasma LDL-C by cells and a subsequent increase in plasma LDL-C. There is also an increased production of LDL in these patients, due to failure of metabolism of intermediate density lipoproteins (IDL) by the liver. (IDL also uses the LDL receptor for uptake into the liver cell, and when this fails, IDL is converted to LDL [Figure 20-4].) As LDL accumulates in the plasma, it is taken up by tissues that do not depend on the presence of LDL receptors—macrophages (resulting in xanthomas in the skin and connective tissues) and probably the arterial intima. Homozygotes have extremely high LDL-C levels and develop severe atherosclerotic disease in their teens. Heterozygotes are common (1:500 people in the population), have a twofold to threefold elevation of plasma cholesterol, and develop premature atherosclerosis. Heterozygous familial hypercholesterolemia is found in 3–6% of survivors of myocardial infarction.
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Total Plasma Triglyceride
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A level > 250 mg/dL (> 2.8 mmol/L) imposes a high risk. Accurate risk evaluation for triglycerides has been difficult because of the associated changes in the more significant cholesterol levels.
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Patients who have high-risk lipid levels should be treated to reduce these levels because reduction has a protective effect and may even cause some regression of atherosclerosis. Patients with borderline levels should be treated if they have two or more of the highly significant risk factors other than hyperlipidemia listed in Table 20-1.
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The risk of athero-sclerosis bears an inverse relationship to plasma level of cholesterol associated with high-density lipoprotein (HDL-C). An HDL-C level < 35 mg/dL (< 0.9 mmol/L) imposes a high risk. Low HDL-C levels occur more commonly in (1) males, (2) cigarette smokers, (3) diabetics, (4) inactive people who do not exercise regularly, and (5) patients with high triglyceride levels. Regular exercise and a small daily intake of alcohol have been shown to increase plasma HDL-C levels.
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High-density lipoproteins are believed to remove cholesterol liberated from cell turnover. It is possible that HDL also removes cholesterol from atheromatous plaques as part of this function, explaining its protective effect in atherosclerosis.
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Apoproteins are proteins that are associated with lipid to form lipoproteins and are genetically determined. Different apoprotein types are associated with different lipoproteins (Table 20-3; Figure 20-4). In addition to being structural components of the lipoprotein molecule, apoproteins function (1) as ligands that interact with cell receptors which bind lipoproteins, and (2) as cofactors of enzymes of lipid metabolism. The following abnormalities of apoproteins, which are inherited, are associated with an increased risk of atherosclerosis:
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Familial Type III Hyperlipoproteinemia,
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which is associated with an increased plasma level of intermediate-density lipoproteins (IDL) and accelerated atherosclerosis. IDL is normally derived from very-low-density lipoproteins (VLDL), which cleaves off triglyceride and leaves the cholesteryl ester-rich IDL (Figure 20-4). IDL is associated with apoproteins B100 and E and is either taken up by the liver cell for recycling into VLDL or metabolized into LDL. Hepatic uptake of IDL is dependent on recognition of IDL by the same receptor that recognizes LDL. The binding of IDL to the receptor is dependent on the presence of apoprotein E. Patients with familial type III hyperlipoproteinemia inherit an abnormal apoprotein E, resulting in failure of IDL uptake by the liver, increased IDL in the plasma, and atherosclerosis.
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Abnormal HDL-Associated Apoproteins
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High-density lipoproteins are believed to remove excess cholesterol from cells and tissues (probably including atheromatous lesions, explaining their protective effect). HDL is associated with several apoproteins, three of which (A1, C3, and A4) are encoded by genes clustered on chromosome 11. Inherited abnormalities of these apoproteins lead to a defect in HDL function and have been associated with atherosclerosis. The best-understood component is defective Apo-AI. Normally, Apo-AI serves as a cofactor for the enzyme lecithin-cholesterol acyltransferase (LCAT), which is necessary for the metabolism and removal of cholesterol taken up by HDL. With defective Apo-AI, this reaction fails, interfering with the normal protective function of HDL.
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Increased Lipoprotein (a)
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Lipoprotein (a) [Lp(a)] is associated with an increased risk. Lp(a) is a variant of LDL in which the normal LDL apoprotein (B100) is linked by disulfide bridges to a distinct apoprotein (a) which is encoded by a single gene. Plasma levels of Lp(a) are determined by the amount of apoprotein(a) that is produced. Apo(a) has structural similarity to plasminogen (it contains 37 copies of kringle 4, which is part of the plasminogen molecule that normally binds to fibrin during fibrinolysis). It is known that microthrombi are frequently formed in relation to atherosclerotic lesions. If these are normally removed by plasminogen, the presence of Apo(a) in the lesions can inhibit this process by competing with plasminogen for kringle 4 receptors on the fibrin molecule.
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The mechanism responsible for lipid deposition in the intima and formation of the atheromatous lesion is unknown. The following hypotheses of the pathogenesis of atherosclerosis are not mutually exclusive.
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Reaction to Endothelial Injury
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The primary event of atherosclerosis according to this hypothesis is endothelial injury. Nondenuding endothelial injury is believed to lead to adherence of blood monocytes, which are activated, imbibe LDL and actively enter the intima, and become macrophages. Active macrophages release free radicals that oxidize LDL. Oxidized LDL is toxic to endothelium, causing endothelial loss and exposure of subendothelial connective tissue to blood components. This leads to platelet adhesion and aggregation and to fibrin deposition, forming microthrombi. Platelets release various factors—one of which has been identified as being mitogenic—causing migration of smooth muscle into the intima and proliferation therein. The activated macrophages and smooth muscle cells secrete numerous cytokines that can be found in the early lesion. These include platelet-derived growth factor (PDGF), tumor necrosis factor (TNF), fibroblast growth factor (FGF), and interleukin-1, some of which may also have mitogenic capability.
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The smooth muscle cells, macrophages, and matrix accumulate LDL from the plasma, a process that is enhanced by the presence of increased LDL in the blood. Smooth muscle cells and endothelial cells have LDL receptors on their surfaces, and macrophages are capable of taking up LDL—facts that would explain the high association of LDL with lesions. This sets up a cycle of changes that involves macrophage activation, LDL oxidation, and endothelial damage that cause progression of the atheromatous lesion.
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The nature of the initial endothelial injury is unknown. Physical shear injuries are maximal at sites of arterial branching, which are the sites most involved in atherosclerosis, and hypertension would aggravate these injuries. There may be a toxic effect of hypercholesterolemia itself, and exogenous toxins such as carbon monoxide are present in the serum of cigarette smokers. Homocysteine-induced endothelial injury is believed to be responsible for the premature atherosclerosis seen in patients with homocystinuria.
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Thrombus Encrustation
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According to this hypothesis, the primary event is thrombosis. The thrombus becomes incorporated into the intima and then undergoes lipid degeneration to initiate the lesion. Thrombosis is now thought not to be the initial event, but it probably plays a role in the development and enlargement of the lesion. Lipoprotein(a) promotes development of atherosclerosis by virtue of its inhibition of plasminogen activity, which suggests that removal of fibrin is important in preventing progression of the atheromatous lesion.
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Monoclonal Hypothesis
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The smooth muscle cell proliferation in the lesion was shown, at least in some cases, to be monoclonal. This suggested that mitogen-induced smooth muscle proliferation was the primary event. This is unlikely, as it has been shown that monoclonality of the smooth muscle cells is not a constant feature. However, mitogen-induced smooth muscle proliferation is still thought to be important in the development of the atheromatous lesion.
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The lesions associated with atherosclerosis are the fatty streak, the fibrous atheromatous plaque, and the complicated lesion. The latter two are definitely pathologic and are responsible for clinically significant disease.
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Fatty streaks are thin, flat, yellow streaks in the intima. They consist of macrophages and smooth muscle cells the cytoplasm of which has become distended with lipid (to form foam cells). Fatty streaks occur maximally around the aortic valve ring and thoracic aorta. They are present very early in life, often in the first year, and are seen all over the world irrespective of sex, race, or environment. They increase in number until about age 20 years and then remain static or decrease. There is controversy about whether some fatty streaks progress into fibrous atheromatous plaques or whether they are independent of atherosclerosis.
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The Fibrous Atheromatous Plaque
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This is the basic lesion of clinical atherosclerosis. It consists of three zones: (1) A fibrous cap under the endothelium, consisting of dense collagen and scattered smooth muscle cells and macrophages; (2) the lipid zone, which consists of foam cells (lipid-laden macrophages and smooth muscle cells) and extracellular lipid and debris; and (3) the basal zone, composed of proliferated smooth muscle cells and connective tissue. Different plaques contain varying amounts of these three layers; some are mainly fibrous, and others are predominantly fatty.
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The fibrous atheromatous plaque appears grossly as a yellow-white elevation on the intimal surface of the artery (Figure 20-5). In cut section, the center of the plaque consists of semisolid yellow material (Gk ather- = porridge). Microscopically, the three zones are recognizable and are of varying thickness in different plaques (Figure 20-6). Needle-shaped cholesterol crystals are commonly present in the lipid zone.
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Fibrous atheromatous plaques are present in the aorta in most cases, with maximal change most commonly in the abdominal aorta (Figure 20-5). Involvement of muscular arteries such as the coronary, carotid, vertebrobasilar, mesenteric, renal, and iliofemoral arteries is associated with luminal stenosis. This is common and is responsible for many of the clinical manifestations of atherosclerosis (Table 20-4). Plaques tend to be most prominent at points of branching of the major arteries. In severe disease, plaques become confluent, involving much of the intimal surface (Figure 20-5).
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The Complicated Plaque
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(Figure 20-7.) Thrombosis is the most important complication of atherosclerosis because it may cause complete occlusion of the artery. Thrombosis is caused by (1) slowing and turbulence of blood in the artery in the region of the plaque and (2) ulceration of the plaque.
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Dystrophic calcification is very common and occurs in the lipid zone of the plaque. Severely affected vessels (including the aorta) may become converted into calcific tubes. Ulceration of the endothelium overlying the plaque may cause the lipid contents of the plaque to be discharged into the circulation as cholesterol emboli (Chapter 9: Abnormalities of Blood Supply). Ulceration of the plaque may also precipitate arterial thrombosis at the site. Vascularization of the plaque occurs by ingrowth of poorly supported vessels from the medial aspect. These may rupture, leading to hemorrhage into the plaque, which may then expand sufficiently to occlude the lumen of the artery. Hemorrhage may also cause ulceration and thrombosis. Aneurysms may develop in arteries weakened by extensive plaque formation; the abdominal aorta is the favored site of atherosclerotic aneurysms.
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Narrowing of Affected Arteries
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Ischemia from arterial narrowing is responsible for most of the clinical effects of atherosclerosis (Figure 20-8). A decrease in blood flow usually occurs only with severe (> 70%) narrowing of the vessel. Aortic narrowing is almost never sufficient to cause symptoms. However, narrowing of coronary, cerebral, renal, mesenteric, and iliofemoral vessels often causes ischemic changes in the organs and tissues supplied. Superimposed thrombotic occlusion of these arteries may cause infarction.
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Ulceration of the atheromatous plaque may result in embolization of the lipid contents of the plaque (Figure 20-7). This is important in the cerebral circulation, where small emboli produce transient ischemic attacks. Emboli can sometimes be visualized in the retinal arteries on funduscopic examination.
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(Figure 20-9.) In severe athero-sclerotic involvement of the aorta, the wall may be weakened to an extent that leads to dilation or aneurysm formation. Atherosclerotic aneurysms occur mainly in the lower abdominal aorta and may appear as a fusiform dilation of the whole vessel circumference or a saccular bulge on one side of it.
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Systemic Hypertension
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Hypertension is defined as sustained elevation of systemic arterial blood pressure. While the concept is clear, the exact pressure that constitutes hypertension is an arbitrary determination based on pressures associated with a statistical risk of developing diseases associated with hypertension. In adults, a diastolic pressure below 85 mm Hg is normal; 85–89 mm Hg is high normal; 90–99 mm Hg is mild hypertension; 100–109 mm Hg is moderate hypertension; 110–119 mm Hg is severe hypertension; and >120 mm Hg is very severe hypertension. In a person with a diastolic pressure of < 90 mm Hg, a systolic pressure < 140 mm Hg is normal; 140–159 mm Hg is borderline isolated systolic hypertension; and >160 mm Hg is isolated systolic hypertension. Both diastolic and isolated systolic hypertension are associated with increased risk of cardiovascular complications.
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About 15–20% of adults in the United States have blood pressures over 160/95 mm Hg, and nearly 50% have pressures over 140/90 mm Hg. The incidence is higher in African-Americans than in whites, Asians, and Hispanic-Americans. Hypertensive individuals have increased mortality rates related to associated atherosclerotic arterial disease in direct proportion to the severity of the hypertension. Control of blood pressure decreases the risk of cardiovascular morbidity.
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Etiology & Pathogenesis
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Essential Hypertension
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Essential hypertension occurs as a primary phenomenon without known cause. It is the most common type of hypertension, usually occurring after age 40 years, with a familial incidence suggestive of polygenic inheritance upon which environmental factors are superimposed.
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The pathogenesis is uncertain. No constant changes have been identified in plasma levels of angiotensin, renin, aldosterone, or catecholamines—or in the activity of the sympathetic nervous system or baroreceptors—that could account for the elevated blood pressure. Some hypertensive individuals have elevated levels of plasma angiotensin, which has been related to the finding of a variant angiotensin gene. Inhibitors of angiotensin-converting enzyme are effective antihypertensive drugs.
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The currently favored hypothesis is that essential hypertension is due to high dietary intake of sodium in a genetically predisposed individual. There may be associated failure of excretion by the kidney in the face of a prolonged high sodium load. Sodium retention results in an increase in circulating natriutretic factors. One of these inhibits membrane Na+–K+ ATPase, thereby leading to intracellular accumulation of Ca2+. Cytosol Ca2+ is increased in essential hypertension; in vascular smooth muscle, increased cytosol Ca2+ enhances reactivity and tends to cause vasoconstriction. This effect of Ca2+ is inhibited by calcium channel-blocking drugs, which are effective antihypertensive agents.
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Endothelium derived factors such as nitrous oxide are produced in response to shear forces, intraluminal pressure, circulating hormones, and platelet factors. Nitrous oxide acts on the underlying smooth muscle cells, causing vasodilation. An abnormality in the nitrous oxide system has been suggested as causing hypertension. Nitrous oxide donors such as nitroprusside are effective antihypertensive agents.
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Secondary Hypertension
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Secondary hypertension is that due to a preceding defined disease process (Table 20-5). Even though an underlying cause can be identified in less than 10% of cases of hypertension, this group of patients is important because many of their diseases can be treated. Secondary hypertension must be strongly suspected in a patient under 40 years of age who develops hypertension.
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Secondary hypertension results from accentuation of one of the many factors (renin, aldosterone, renal sodium reabsorption, catecholamines, sympathetic stimulation) that may increase cardiac output or peripheral resistance (Figure 20-10 and Table 20-5).
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In the earliest phase of hypertension, vasoconstriction is produced by smooth muscle contraction and there are no microscopic changes in blood vessels. Following sustained vasoconstriction, there is thickening of the media due to muscle hypertrophy, progressing to hyaline degeneration and intimal fibrosis. These changes are known as hyaline arteriolosclerosis and are found with longstanding hypertension of mild to moderate degree (benign hypertension). The tissues supplied by affected vessels may show changes of chronic ischemia.
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Malignant Hypertension
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Malignant hypertension is characterized by papilledema (which defines the entity), retinal hemorrhages and exudates, and blood pressures usually > 200/140 mm Hg. It is characterized pathologically by the occurrence of fibrinoid necrosis of the media with marked intimal fibrosis and extreme narrowing of the arteriole (Figure 20-11). The tissues supplied by affected vessels show acute ischemia with microinfarcts and hemorrhages. Malignant hypertension is frequently associated with elevated serum renin levels, establishing a vicious cycle that tends toward further elevation of the blood pressure.
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The early phase of hypertension is asymptomatic, and the diagnosis can be made only by detecting the elevation of blood pressure.
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Hypertensive Heart Disease
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Systemic hypertension results in increased work for the left ventricular muscle, which undergoes hypertrophy, thereby maintaining cardiac output. With severe hypertension, particularly in the malignant phase, left ventricular failure occurs.
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Hypertension is a major risk factor for coronary atherosclerosis and ischemic heart disease. Ischemia is aggravated by the increased oxygen demand of the hypertrophied myocardium.
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Hypertensive Renal Disease
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Changes in renal arterioles occur in most cases of hypertension, resulting in decreased glomerular filtration rate, progressive fibrosis, and loss of nephrons in the kidneys. Renal ischemia resulting from these changes sets up a vicious cycle (falling glomerular filtration rate, renin release, angiotensin production, salt retention) that aggravates the hypertension.
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Renal failure with elevation of serum creatinine usually occurs only in patients with malignant hypertension. Fibrinoid necrosis is present in renal arterioles (Figure 20-11). Hematuria occurs, and marked reduction in glomerular filtration rate may progress to acute renal failure.
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Hypertensive Cerebral Disease
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Hypertensive patients have a greatly increased incidence of cerebrovascular disease, both thrombosis and hemorrhage (strokes). Cerebral thrombosis is the result of atherosclerosis; cerebral hemorrhages result from rupture of microaneurysms in small intracerebral perforating arteries.
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Hypertensive encephalopathy is due to spasm of small arteries in the brain induced by very high blood pressures. The temporary spasm, though insufficient to cause infarction, leads to cerebral edema, which produces headache and transient cerebral dysfunction.
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Hypertensive Retinal Disease
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The retinal arterioles show all the changes of hypertension on funduscopic examination (hypertensive retinopathy). Narrow, irregular arteries with thickened walls characterize mild to moderate hypertension. Malignant hypertension leads to papilledema, retinal hemorrhages, and fluffy exudates (cotton wool spots)—ill-defined areas of edema and repair resulting from ischemia (Figure 20-12).
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Diagnosis, Treatment, & Prognosis
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The blood pressure should be measured several times over a period of several weeks to make certain that hypertension is sustained. It is important to look for clinical effects due to hypertension and for treatable causes, especially in patients under 40 years, because essential hypertension is uncommon in this age group.
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When a treatable cause of hypertension such as renal artery stenosis or an adrenal neoplasm is present, surgery is curative. Patients with essential hypertension must receive lifelong treatment with antihypertensive drugs. The prognosis for patients with essential hypertension depends on how well the blood pressure is controlled. With modern effective drugs, the prognosis is good. Without control of blood pressure, even patients with mild hypertension develop significant complications after 7–10 years. Untreated hypertension shortens life by 10–20 years, usually by increasing the rate of atherosclerosis.
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Medial Calcification (Monckeberg's Sclerosis)
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Medial calcification is a clinically unimportant but very common degenerative change affecting muscular arteries such as the femoral, radial, and uterine arteries. The tunica media shows extensive calcification. There is no luminal narrowing or endothelial damage. Medial calcification does not produce any clinical abnormality—it is seen in elderly persons and is regarded as an aging change.
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Aortic Dissection (Dissecting Aneurysm of the Aorta)
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In aortic dissection, there is disruption of the media of the aorta by entry of blood under high pressure through an intimal tear. Hypertension is present in 70% of patients and is the most important factor, causing tearing of the endothelium and intima and permitting entry of blood at high pressure into the weakened media. Myxomatous degeneration of the media (Erdheim's cystic medial degeneration) is present in 20% of cases.
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Aortic dissection is associated with an intimal tear, usually just above the aortic valve or immediately distal to the ligamentum arteriosum. Blood enters the media at this intimal tear and dissects between the layers of smooth muscle in the media. Cystic medial degeneration, when present, facilitates dissection (Figures 20-13 and 20-14).
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Cystic medial degeneration appears microscopically as ill-defined mucoid lakes with associated patchy loss of elastin fibers and smooth muscle. Cystic medial degeneration and aortic dissection are more common in patients with Marfan's syndrome.
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Lathyrism is a similar condition induced experimentally in animals by feeding a diet of sweet peas. The high content of β-aminopropionitriles in sweet peas interferes with collagen synthesis, causing myxomatous degeneration of the media.
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The clinical effects of aortic dissection depend upon its site and extent. Dissection of the media produces sudden severe pain, which is usually retrosternal and mimics the pain of myocardial infarction. Arteries taking origin from the aorta may become occluded, or rupture may occur leading to massive hemorrhage (Figure 20-13). Thirty percent of patients die within 24 hours. In those who survive, treatment with antihypertensive drugs and surgery has greatly improved survival.
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Abnormally dilated and tortuous veins occur in several sites—in the legs, rectum (hemorrhoids), esophagus (varices in portal hypertension), or spermatic cord (varicocele). They are associated with increased pressure in the affected vessels, obstruction to adequate venous drainage, or increased blood flow in the affected vessels.
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In the legs, varicose veins involve the superficial saphenous venous system and result (1) from obstruction to the deep veins of the leg, with the superficial varicose veins representing the collateral venous drainage; or (2) from incompetence of the valves in the saphenous veins and in the perforating veins that normally prevent flow of blood from the deep to the superficial veins. The latter mechanism involving valve incompetence is responsible for most cases of varicose veins. The cause of valve incompetence is unknown but is probably a degenerative phenomenon.
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Varicose veins are visible in the leg as markedly dilated tortuous veins (Figure 20-15) whose distribution depends upon which valves are incompetent. They are associated with obesity and pregnancy, and there may be a familial predisposition.
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Varicose veins produce adverse cosmetic effects and chronic aching and swelling, and they serve as sites for recurrent thrombophlebitis, stasis dermatitis, and skin ulceration. Stasis ulcers typically occur in the region of the ankle.
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Treatment consists of surgical removal of the varicose superficial leg veins or, for small varices, local injection of sclerosing agents. Before such treatment is undertaken, deep venous occlusion must be excluded; otherwise, the venous drainage of the entire leg may be compromised.