Table 93 Causes Of Hypertension

Essential hypertension (90% to 95%)

• Unknown causes

- increased blood volume

- increased systemic vascular resistance (vascular disease)

• Associated with:

- heredity

- abnormal response to stress

- diabetes and obesity

- age, race, and socioeconomic status Secondary hypertension (5% to10%)

• Renal artery stenosis

• Renal disease

• Hyperaldosteronism (primary)

• Pheochromocytoma (catecholamine-secreting tumor)

• Aortic coarctation

• Pregnancy (preeclampsia)

• Hyperthyroidism

• Cushing's syndrome (excessive glucocorticoid secretion)

has led some investigators to suggest that the basic underlying defect in hypertensive patients is an inability of the kidneys to adequately handle sodium. Increased sodium retention could account for the increase in blood volume. Indeed, many excellent experimental studies as well as clinical observations have shown that impaired renal natriuresis (sodium excretion) can lead to chronic hypertension.

Besides the renal involvement in hypertension, it is well known that vascular changes can contribute to hypertensive states, especially in the presence of impaired renal function. For example, essential hypertension is usually associated with increased systemic vascular resistance caused by a thickening of the walls of resistance vessels and by a reduction in lumen diameters. In some forms of hypertension, this is mediated by enhanced sympathetic activity or by increased circulating levels of an-giotensin II, causing smooth muscle contrac tion and vascular hypertrophy. In recent years, experimental studies have suggested that changes in vascular endothelial function may cause these vascular changes. For example, in hypertensive patients, the vascular endothe-lium produces less nitric oxide. Nitric oxide, besides being a powerful vasodilator, inhibits vascular hypertrophy. Increased endothelin-1 production may enhance vascular tone and induce hypertrophy. Evidence suggests that hy-perinsulinemia and hyperglycemia in type 2 diabetes (non-insulin-dependent diabetes) cause endothelial dysfunction through increased formation of reactive oxygen species and decreased nitric oxide bioavailability, both of which may contribute to the abnormal vascular function and hypertension often associated with diabetes.

Essential hypertension is related to heredity, age, race, and socioeconomic status. The strong hereditary correlation may be related to genetic abnormalities in renal function and neurohumoral control mechanisms. The incidence of essential hypertension increases with age, and people of African descent are more likely to develop hypertension than are Caucasians. Hypertension is more prevalent among lower socioeconomic groups.

Some patients with essential hypertension are more strongly influenced by stressful conditions than are normotensive individuals. Stress not only leads to acute elevations in arterial pressure, but it can also lead to chronic elevations in pressure. Stress activates the sympathetic nervous system, which increases cardiac output and systemic vascular resistance. Furthermore, stress causes the adrenal medulla to secrete more catecholamines (epi-nephrine and norepinephrine) than normal. Sympathetic activation increases circulating angiotensin II, aldosterone, and vasopressin, which together can increase systemic vascular resistance and, through their renal effects, increase sodium and water retention. In addition, prolonged elevation of angiotensin II and catecholamines leads to vascular and cardiac hypertrophy.

Secondary Hypertension

Secondary hypertension accounts for 5% to 10% of hypertensive cases. This form of hypertension has identifiable causes that often can be remedied. Regardless of the underlying cause, arterial pressure becomes elevated owing to an increase in cardiac output, an increase in systemic vascular resistance, or both. When cardiac output is elevated, it is often related to increased blood volume and neurohumoral activation of the heart. Several causes of secondary hypertension are summarized in Table 9-3 and discussed below.

Renal artery stenosis occurs when the renal artery becomes narrowed (stenotic) owing to atherosclerotic or fibromuscular lesions. This reduces the pressure at the afferent arte-riole, which stimulates the release of renin by the kidney (see Chapter 6). Increased plasma renin activity increases circulating angiotensin II and aldosterone. Angiotensin II causes vasoconstriction by binding to vascular AT: receptors and by augmenting sympathetic influ ences. Furthermore, angiotensin II along with aldosterone increases renal sodium and water reabsorption. The net effect of the renal actions is an increase in blood volume that augments cardiac output by the Frank-Starling mechanism. In addition, chronic elevation of angiotensin II promotes cardiac and vascular hypertrophy. Therefore, hypertension caused by renal artery stenosis is associated with increases in cardiac output and systemic vascular resistance.

Renal disease (e.g., diabetic nephropathy, glomerulonephritis) damages nephrons in the kidney. When this occurs, the kidney cannot excrete normal amounts of sodium, which leads to sodium and water retention, increased blood volume, and increased cardiac output. Renal disease may increase the release of renin, leading to a renin-dependent form of hypertension. The elevation in arterial pressure secondary to renal disease can be viewed as an attempt by the kidney to increase renal perfusion, thereby restoring normal glomerular filtration and sodium excretion.

Primary hyperaldosteronism is increased secretion of aldosterone by an adrenal adenoma or adrenal hyperplasia. This condition causes renal retention of sodium and water, thereby increasing blood volume and arterial pressure. Aldosterone acts upon the distal convoluted tubule and cortical collecting duct of the kidney to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are excreted in the urine. Plasma renin levels generally are decreased as the body attempts to suppress the renin-angiotensin system. In addition, hypokalemia is associated with the high levels of aldosterone.

A pheochromocytoma (a catecholamine-secreting tumor, usually in the adrenal medulla) can cause high levels of circulating catecholamines (both epinephrine and norepinephrine). A pheochromocytoma is diagnosed by measuring plasma or urine cate-cholamine levels and their metabolites (vanillylmandelic acid and metanephrine). This condition leads to a-adrenoceptor-medi-ated systemic vasoconstriction and pradreno-ceptor-mediated cardiac stimulation that can cause substantial elevations in arterial pres sure. Although arterial pressure rises to very high levels, tachycardia still occurs because of the direct effects of the catecholamines on the heart and vasculature. Excessive p:-adreno-ceptor stimulation in the heart often leads to arrhythmias in addition to the hypertension.

Aortic coarctation is a narrowing of the aortic arch usually just distal to the left subclavian artery. It is a congenital defect that obstructs aortic outflow, leading to elevated pressures proximal to the coarctation (i.e., elevated arterial pressures in the head and arms). Distal pressures, however, are not necessarily reduced as would be expected from the hemodynamics associated with a stenosis. The reason for this is that reduced systemic blood flow, and in particular reduced renal blood flow, leads to an increase in the release of renin and an activation of the renin-angiotensin-aldosterone system. This in turn elevates blood volume and arterial pressure. Although the aortic arch and carotid sinus baroreceptors are exposed to higher-than-nor-mal pressures, the baroreceptor reflex is blunted owing to structural changes in the walls of vessels where the baroreceptors are located. Furthermore, baroreceptors become desensitized to chronic elevation in pressure and become "reset" to the higher pressure.

Preeclampsia is a type of hypertension that occurs in about 5% of pregnancies during the third trimester. Preeclampsia differs from less severe forms of pregnancy-induced hypertension in that preeclampsia causes a loss of albumin in the urine because of renal damage, and it is accompanied by significant systemic edema. Preeclampsia results from increased blood volume and tachycardia, as well as increased vascular responsiveness to vasoconstrictors, which can lead to vasospasm. It is unclear why some women develop this condition during pregnancy; however, it usually disappears after parturition unless an underlying hypertensive condition exists.

Hyperthyroidism induces systemic vasoconstriction, an increase in blood volume, and increased cardiac activity, all of which can lead to hypertension. It is less clear why some patients with hypothyroidism also develop hypertension, but it may be related to decreased tissue metabolism reducing the release of vasodilator metabolites, thereby producing vasoconstriction and increased systemic vascular resistance.

Cushing's syndrome, which results from excessive glucocorticoid secretion, can lead to hypertension. Glucocorticoids such as cortisol, which are secreted by the adrenal cortex, share some of the same physiologic properties as aldosterone, a mineralocorticoid also secreted by the adrenal cortex. Therefore, excessive glucocorticoids can lead to volume expansion and hypertension.

Physiologic Basis for Therapeutic Intervention

If a person has secondary hypertension, it is sometimes possible to correct the underlying cause. For example, renal artery stenosis can be corrected by placing a wire stent within the renal artery to maintain vessel patency; aortic coarctation can be surgically corrected; a pheochromocytoma can be removed. However, for the majority of people who have essential hypertension, the cause is unknown so it cannot be targeted for correction. Therefore, the therapeutic approach for these patients involves modifying the factors that determine arterial pressure by using drugs.

Because hypertension results from an increase in cardiac output and increased systemic vascular resistance, these are the two physiologic mechanisms that are targeted in drug therapy. In most hypertensive patients, altered renal function causes sodium and water retention. This increases blood volume, cardiac output, and arterial pressure. Therefore, the most common treatment for hypertension is the use of a diuretic to stimulate renal excretion of sodium and water. This reduces blood volume and arterial pressure very effectively in most patients. In addition to a diuretic, most hypertensive patients are given at least one other drug. This is because decreasing blood volume with a diuretic leads to activation of the renin-angiotensin-aldo-sterone system, which counteracts the effects of the diuretic. Therefore, many patients are given an angiotensin-converting enzyme

(ACE) inhibitor or angiotensin receptor blocker (ARB) as well.

In addition to using diuretics, cardiac output can be reduced using p-blockers and the more cardiac-selective calcium-channel blockers (e.g., verapamil). Beta-blockers are particularly useful in patients who may have excessive sympathetic stimulation owing to emotional stress, and these drugs also inhibit sympathetic-mediated release of renin.

In combination with a diuretic, some hypertensive patients can be effectively treated with an a-adrenoceptor antagonist, which dilates resistance vessels and reduces systemic vascular resistance. Other drugs that reduce systemic vascular resistance include ACE inhibitors, angiotensin receptor blockers, calcium-channel blockers (especially dihy-dropyridines), and direct-acting arterial dilators such as hydralazine.

Although pharmacologic intervention is an important therapeutic modality in treating hypertension, improved diet and exercise have been shown to be effective in reducing arterial pressure in many patients. A proper, balanced diet that includes sodium restriction can prevent the progressive of, and in some cases reverse, cardiovascular changes associated with hypertension. Regular exercise, especially aerobic exercise, reduces arterial pressure and has beneficial effects on vascular function.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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