Systemic+Hypertension


 * Systemic Hypertension**
 * Arterial Pressure**
 * Hypertension Categories**
 * Causes of Hypertension**
 * Antihypertensive Drugs**


 * Hypertension - Introduction**

High blood pressure, termed "hypertension," is a condition that afflicts more than 50 million Americans and is a leading cause of morbidity and mortality. Hypertension is much more than a "cardiovascular disease" because it affects other organ systems of the body such as kidney, brain, and eye. Tens of millions of Americans are not even aware of being hypertensive because it is usually asymptomatic until the damaging effects of hypertension (such as stroke, myocardial infarction, renal dysfunction, etc.) are observed. //**Definition of hypertension.**// The term "hypertension" can apply to elevations in [|mean arterial pressure], [|diastolic pressure], or [|systolic pressure]. According to the latest U.S. national guidelines (JNC 7 Report), the following categories of hypertension have been defined: Elevations in either diastolic or systolic pressure represent a significant risk factor to a patient for coronary artery disease, stroke and renal disease. Mean arterial pressure is usually not discussed in the context of hypertension because it is not normally measured in a patient. However, changes in either cardiac output or systemic vascular resistance will increase not only diastolic and systolic pressures, but also mean arterial pressure. The term "[|mean arterial pressure]" is usually spoken in the context of the arterial pressure that is responsible for organ perfusion. //**Two classes of of hypertension.**// In 90-95% of patients presenting with hypertension, the cause is unknown. This condition is called __[|primary (or essential) hypertension]__. The remaining 5-10% of hypertensive patients have hypertension that results secondarily from renal disease, endocrine disorders, or other identifiable causes. This form of hypertension is called __[|secondary hypertension]__. //**Hemodynamic basis of hypertension.**// Regardless of the origin of hypertension, the actual increase in arterial blood pressure is caused by either an increase in [|__systemic vascular resistance__] (SVR) or an increase in [|__cardiac output__] (CO). The former is determined by the [|vascular tone] (i.e., state of constriction) of systemic resistance vessels, whereas the latter is determined by [|heart rate] and [|stroke volume]. Therefore, in order to understand how arterial blood pressure can become elevated, it is necessary to understand the mechanisms that regulate both SVR and CO.
 * Classification || Systolic (mmHg) || Diastolic (mmHg) ||
 * Normal || <120 || <80 ||
 * Prehypertension || 120-139 || 80-89 ||
 * Stage 1 || 140-159 || 90-99 ||
 * Stage 2 || >160 || >100 ||

//**Treatment of hypertension.**// Most people with hypertension are treated with **antihypertensive medications**. In most forms of hypertension, the hypertensive state is maintained by an elevation in [|blood volume], which in turn increases cardiac output by the [|Frank-Starling relationship]. **Diuretic drugs**, which enhance the removal of sodium and water by the kidneys and thereby decrease blood volume, are very effective in the treatment of hypertension. Hypertension is also commonly treated with drugs that decrease cardiac output. These **cardioinhibitory drugs** either block beta-adrenoceptors on the heart (i.e., **beta-blockers)** or L-type calcium channels (i.e., calcium-channel blockers), which decreases cardiac output by decreasing [|heart rate] and [|contractility (inotropy)]. **Vasodilator drugs**, which decrease systemic vascular resistance, are also used to treat hypertension. Included in these drugs are alpha-adrenoceptor antagonists (**alpha-blockers),** **direct-acting vasodilators**, **angiotensin-converting enzyme inhibitors** and **angiotensin receptor blockers**.

__**Arterial Pressure**__ Arterial blood pressure is generated by the left ventricle ejecting blood into the systemic vasculature, which acts as a resistance to cardiac output. With each ejection of blood (ventricular systole), the aortic blood volume increases, which stretches the wall of the aorta. As the heart relaxes (ventricular diastole), blood flows from the aorta into distributing arteries that transport the blood to the various organs. Within the organs, the arterial vasculature undergoes extensive branching and the vessel diameters decrease. The smaller arteries and arterioles serve as the chief resistance vessels, and through changes in their diameter, serve to regulate systemic vascular resistance and organ blood flow. In hemodynamic terms, the mean arterial pressure (MAP) can be described by //Equation 1:// **MAP = (CO x SVR) + CVP** where CO =cardiac output, SVR= systemic vascular resistance, and CVP = central venous pressure. Therefore, increases in CO, SVR or CVP will lead to increases in MAP. While MAP is an important hemodynamic parameter and is required for calculating SVR, it is generally not measured in clinical practice unless a person's arterial pressure is being monitored with an indwelling catheter. The most common method for measuring arterial pressure is by use of a sphygmomanometer, which gives systolic and diastolic pressure values in mmHg. The systolic pressure is the peak arterial pressure that occurs during ventricular systole, whereas the diastolic pressure is the minimal aortic pressure just before the ventricle ejects blood into the aortic. At normal heart rates, MAP can be estimated from the systolic (Psys) and diastolic (Pdias) values according to the following equation: //Equation 2:// **MAP = 1/3 (Psys - Pdias) + Pdias** This equation is useful for estimating MAP from systolic and diastolic pressure values; however, this equation does not describe the hemodynamic variables that determine MAP. The hemodynamic variables that determine MAP are found in Equation 1.

__**Hypertension Categories**__ According to the latest U.S. national guidelines ([|JNC 7 Report]), the following categories of hypertension have been defined: It is important to note that a hypertensive state may defined as an abnormal elevation of either systolic or diastolic pressure. In past years, the diastolic value was emphasized in determining whether or not a person was hypertensive. However, elevations in systolic pressure ("systolic hypertension") are also associated with increased incidence of coronary and cerebrovascular disease (e.g., stroke). Therefore, we now recognize that both systolic and diastolic pressure values are important to note.
 * Classification || Systolic (mmHg) || Diastolic (mmHg) ||
 * Normal* || <120 || <80 ||
 * Prehypertension || 120-139 || 80-89 ||
 * Stage 1 || 140-159 || 90-99 ||
 * Stage 2 || >160 || >100 ||
 * Arterial pressures less than 90/60 mmHg are considered hypotension, and therefore not normal.

__**Causes of Hypertension**__ The are two basic types of hypertension: [|primary (essential) hypertension] and [|secondary hypertension]. The vast majority of patients (90-95%) have essential hypertension, which is a form with no identifiable underlying cause. This form of hypertension is commonly treated with drugs in addition to lifestyle changes (e.g., exercise, proper nutrition, weight reduction, stress reduction). A smaller number of patients (5-10%) have secondary hypertension that is caused by an identifiable underlying condition such as renal artery disease, thyroid disease, primary hyperaldosteronism, pregnancy, etc. Some causes of secondary hypertension are listed below: [|artery stenosis|Renal artery stenosis] [|renal disease|Chronic renal disease] [|hyperaldosteronism|Primary hyperaldosteronism] [|Stress] [|Apnea|Sleep apnea] [|Pheochromocytoma] [|Preeclampsia] [|coarctation|Aortic coarctation] (renovascular disease)** Renal artery disease can cause of narrowing of the vessel lumen ([|stenosis]). The reduced lumen diameter increases the pressure drop along the length of the diseased artery, which reduces the pressure at the afferent arteriole in the kidney. Reduced arteriolar pressure and reduced renal perfusion stimulate [|renin] release by the kidney. This increases circulating [|angiotensin II] (AII) and [|aldosterone]. These hormones increase blood volume by enhancing renal reabsorption of sodium and water. Increased AII causes systemic vasoconstriction and enhances sympathetic activity. Chronic elevation of AII promotes cardiac and vascular hypertrophy. The net effect of these renal mechanisms is an increase in [|blood volume] that augments cardiac output by the [|Frank-Starling mechanism]. Therefore, hypertension caused by renal artery stenosis results from both an increase in systemic vascular resistance and an increase in cardiac output.  Any number of pathologic processes (e.g., diabetic nephropathy, glomerulonephritis) can damage 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 by the [|Frank-Starling mechanism]. Renal disease may also result in increased 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 and restore glomerular filtration.  Increased secretion of aldosterone generally results from adrenal adenoma or adrenal hyperplasia. Increased circulating [|aldosterone] causes renal retention of sodium and water, so [|blood volume] and arterial pressure increase. Plasma [|renin] levels are generally decreased as the body attempts to suppress the renin-angiotensin system; there is also hypokalemia associated with the high levels of aldosterone.  Emotional stress leads to activation of the [|sympathetic nervous system], which causes increased release of norepinephrine from sympathetic nerves in the heart and blood vessels, leading to increased cardiac output and increased systemic vascular resistance. Furthermore, the adrenal medulla secretes more [|catecholamines] (epinephrine and norepinephrine). Activation of the sympathetic nervous system increases circulating [|angiotensin II], [|aldosterone], and [|vasopressin], which can increase systemic vascular resistance. Prolonged elevation of angiotensin II and catecholamines can lead to cardiac and vascular hypertrophy, both of which can contribute to a sustained increase in blood pressure.  Sleep apnea is a disorder in which people repeatedly stop breathing for short periods of time (10-30 seconds) during their sleep. This condition is often associated with obesity, although it can have other causes such as airway obstruction or disorders of the central nervous system. These individuals have a higher incidence of hypertension. The mechanism of hypertension may be related to sympathetic activation and hormonal changes associated with repeated periods of apnea-induced hypoxia and hypercapnea, and from stress associated with the loss of sleep.  Excessive thyroid hormone 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 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.  Catecholamine secreting tumors in the adrenal medulla can lead to very high levels of circulating [|catecholamines] (both epinephrine and norepinephrine). This leads to [|alpha-adrenoceptor] mediated systemic vasoconstriction and [|beta-adrenoceptor] mediated cardiac stimulation, both of which contribute to significant elevations in arterial pressure.. Despite the elevation in arterial pressure, tachycardia occurs because of the direct effects of the catecholamines on the heart and vasculature. Excessive beta-adrenoceptor stimulation in the heart often leads to [|arrhythmias]. The pheochromocytoma is diagnosed by measuring plasma or urine catecholamine levels and their metabolites (vanillylmandelic acid and metanephrine).  This is a condition that sometimes develops during the third trimester of pregnancy that causes hypertension due to increased [|blood volume] and tachycardia. The former increases cardiac output by the [|Frank-Starling mechanism].  Coarctation, or narrowing of the aorta (typically just distal to the left subclavian artery), 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 normal pressures, the baroreceptor reflex in blunted due to structural changes in the walls of vessels where the baroreceptors are located. Also, baroreceptors become desensitized to chronic elevation in pressure and become "reset" to the higher pressure.
 * Hyper- or hypothyroidism]]**
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