Chronic hypertension pathophysiology

Hypertension Main page
Overview
Causes
Classification Primary Hypertension Secondary Hypertension Hypertensive Emergency Hypertensive Urgency
Screening

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.

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

Hypertension is highly heritable and polygenic (caused by more than one gene) and a few candidate genes have been postulated in the etiology of this condition.

Salt sensitivity

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.

Mechanisms

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.

Role of 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 over-ride 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.

Genetics

Hypertension is one of the most common complex disorders, with genetic heritability averaging 30%. Data supporting this view emerge from animal studies as well as in population studies in humans. Most of these studies support the concept that the inheritance is probably multifactorial or that a number of different genetic defects each have an elevated blood pressure as one of their phenotypic expressions.

More than 50 genes have been examined in association studies with hypertension, and the number is constantly growing.

Diet

The North American diet that is high in fat and salt has been proven to exacerbate hypertension. A study in the U.S. found that patients placed on a strict vegetarian diet showed a significant benefit to their condition over the one year. Certain medications, especially NSAIDS (Motrin/ibuprofen) and steroids can cause hypertension. Imported licorice (Glycyrrhiza glabra) inhibits the 11-hydroxysteroid hydrogenase enzyme (catalyzes the reaction of cortisol to cortison) which allows cortisol to stimulate the Mineralocorticoid Receptor (MR) which will lead to effects similar to hyperaldosteronism, which itself is a cause of hypertension.

Age

Over time, the number of collagen fibers in artery and arteriole walls increases, making blood vessels stiffer. With the reduced elasticity comes a smaller cross-sectional area in systole, and so a raised mean arterial blood pressure.