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ETIOLOGY & CLASSIFICATION

A. Primary Essential Hypertension

“Essential hypertension” is the term applied to the 95% of hypertensive patients in which elevated blood pressure results from complex interactions between multiple genetic and environmental factors. The proportion regarded as "essential" will diminish with improved detection of clearly defined secondary causes and with better understanding of pathophysiology. Blood pressure elevation above 140/90 mm Hg occurs in 10–15% of White adults and 20–30% of Black adults in the United States. The onset is usually between ages 25 and 50 years; it is uncommon before age 20 years. The best understood pathways underlying hypertension include overactivation of the sympathetic nervous and renin-angiotensin-aldosterone systems (RAAS), blunting of the pressure-natriuresis relationship, variation in cardiovascular and renal development, and elevated intracellular sodium and calcium levels.

1. Sympathetic nervous system hyperactivity

This is most apparent in younger persons with hypertension, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor. Insensitivity of the baroreflexes may play a role in the genesis of adrenergic hyperactivity, and polymorphisms in the phosducin gene have been linked to increased blood pressure responses to stress.

2. Abnormal cardiovascular or kidney development

The normal cardiovascular system develops so that elasticity of the great arteries is matched to the resistance in the periphery to optimize large vessel pressure waves. In this way, myocardial oxygen consumption is minimized and coronary flow maximized. Elevated blood pressure later in life could arise from abnormal development of aortic elasticity or reduced development of the microvascular network. This has been postulated as the sequence of events in low birth weight infants, who have an increased risk of hypertension developing in adulthood. Another hypothesis proposes that the association between low birth weight and hypertension arises from reduced nephron number.

3. Renin–angiotensin system activity

Renin, a proteolytic enzyme, is secreted by cells surrounding glomerular afferent arterioles in response to a number of stimuli, including reduced renal perfusion pressure, diminished intravascular volume, circulating catecholamines, increased sympathetic nervous system activity, increased arteriolar stretch, and hypokalemia. Renin acts on angiotensinogen to cleave off the ten-amino-acid peptide angiotensin I. This peptide is then acted upon by angiotensin-converting enzyme (ACE) to create the eight-amino-acid peptide angiotensin II, a potent vasoconstrictor and stimulant of aldosterone secretion. Despite the role of renin in the regulation of blood pressure, it probably does not play a central role in the pathogenesis of most primary (essential) hypertension; only 10% of patients have high renin activity, whereas 60% have normal levels, and 30% have low levels. Black persons with hypertension and older patients tend to have lower plasma renin activity, which may be associated with expanded intravascular volume.

4. Defect in natriuresis

According to the classic Guyton hypothesis, increased ...

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