Chronic hypertension pathophysiology

Hypertension Main page
Overview
Causes
Classification Primary Hypertension Secondary Hypertension Hypertensive Emergency Hypertensive Urgency
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor-In-Chief: Taylor Palmieri

Overview

While the mechanisms underlying secondary hypertension are well understood, the mechanisms underlying primary or essential hypertension are poorly understood. It has been postulated that polygenic influences, increased arterial collagen with aging, salt consumption and sensitivity, hyperinsulinemia as part of the metabolic syndrome and renin may all play a role.

Time Dependence of Pathophysiology

• Cardiac output is raised early in the disease course, while total peripheral resistance (TPR) is normal.
• Over time cardiac output drops to normal levels but TPR is increased. Three theories have been proposed to explain this:

1. Inability of the kidneys to excrete sodium, resulting in natriuretic factors such as Atrial Natriuretic Factor being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
2. An overactive renin / angiotension system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension.
3. An overactive sympathetic nervous system, leading to increased stress responses.

Genetics

Genetics account for approximately 30% of the expression of the disorder. Hypertension is heritable and polygenic (caused by more than one gene) and a few candidate genes have been identified.

Salt Sensitivity and Diet

Sodium is the environmental factor that has received the greatest attention. Approximately 60% of the essential hypertension population is responsive to sodium intake. This is due to the fact that increasing amounts of salt in a person's bloodstream causes the body to draw in more water, increasing the pressure on the blood vessel walls. In addition to sodium, choride plays an important role as it causes volume expansion thereby increasing blood pressure. It is notable that sodium, when combined with other anions, does not increase blood pressure. It is only when sodium is combined with chloride does the blood pressure rise. Salt sensitivity itself is associated with increasing age, obesity, African american race, and the metabolic syndrome.

The proposed mechanism for salt-sensitvity is increased salt intake over a long period of time leads to impaired excretion of salt which causes hypertension. There may be several other pathways involved in the pathophysiology of salt-sensitivity leading to hypertension. Salt-sensitive patients are known to have a dysregulated renin-angiotensin pathway and patients show an abnormal vascular response to angiotensin II. Increased sodium re absorption, though not well understood, is mostly related abnormalities across Na-H proximal tubule channels, Na-K-Cl co-transporter across the thick ascending limb, Na-Cl distal tubule co-transporter and epithelial Na channels. Dietary deficiency in potassium is also known to trigger increased sodium sensitivity in patients in particular African-Americans, but the mechanism is not well understood.

Renin

Renin is a hormone secreted by the juxtaglomerular cells of the kidney and linked with aldosterone in a negative feedback loop. The range of renin activity observed in hypertensive subjects tends to be broader than in normotensive individuals. As a consequence, some hypertensive patients have been defined as having low-renin and others as having essential hypertension. Low-renin hypertension is more common in African Americans than Caucasians and may explain why African Americans tend to respond better to diuretic therapy than drugs that interfere with the renin-angiotensin system.

High Renin levels may predispose to hypertension through the following sequence of events: Increased Renin --> Increased Angiotensin II --> Increased Vasoconstriction, Thirst/ADH and Aldosterone --> Increased Sodium Reabsorption in the Kidneys (DCT and CD) --> Increased Blood Pressure.

Insulin resistance

Insulin is a polypeptide hormone secreted by the pancreas. Its main purpose is to regulate the levels of glucose in the body antagonistically with glucagon through negative feedback loops. Insulin also exhibits vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic activity without elevating mean arterial pressure. However, in more extreme conditions such as that of the metabolic syndrome, the increased sympathetic neural activity may override the vasodilatory effects of insulin. Insulin resistance and/or hyperinsulinemia have been suggested as being responsible for the increased arterial pressure in some patients with hypertension. This feature is now widely recognized as part of syndrome X, or the metabolic syndrome.

Age

As a patient ages, the number of collagen fibers in artery and arteriole walls increases, making blood vessels stiffer, and blood pressure higher for any given stroke volume.