The Pathophyiology Of Hypertension Essay
The article I chose bears the title “The Pathophysiology of Hypertension” and is authored by Gareth Beevers, Gregory Y.H. Lip and Eoin O’Brien. It was originally published in the British Medical Journal in April 14, 2001 and was made available in the online version of the journal.
The authors acknowledge that there is no single factor to which hypertension, especially essential hypertension, can be attributed to. In the article, they reviewed all the known physiological mechanisms that work together to maintain blood pressure within a normal range. Then, they presented the possibilities in which failure of these mechanisms may contribute to hypertension.
There are many ways in which the body maintains normal blood pressure. First is through the balance between cardiac output (volume of blood pumped by the heart per minute) and peripheral vascular resistance (Beevers, Lip and O’Brien, 2001). The Pathophyiology Of Hypertension Essay. Majority of hypertensive patients exhibit normal cardiac output but their arterioles register high resistance. The Pathophyiology Of Hypertension Essay. This is because the smooth muscle cells associated with these vessels continuously contract. Hence, the blood vessels are also constantly constricted and begin to thicken, leading to permanent hypertension.
The renin-angiotensin-aldosterone (RAA) system also regulates blood pressure. Renin is released by the kidneys into the bloodstream where it acts upon the protein angiotensinogen. When converted to angiotensin II, it stimulates the adrenal gland to secrete aldosterone. The effect is that more sodium and water are retained in the body contributing to an increase in blood pressure. This, however, does not directly result in hypertension but localized renin in the heart, kidney and blood vessels may facilitate salt sensitive hypertension (Beevers, Lip and O’Brien, 2001).
The autonomic nervous system, in particular the symphathetic component, stimulates the kidneys to produce epinephrine and nor-epinephrine during periods of stress and intense physical activity (Beevers, Lip and O’Brien, 2001). These hormones increase constriction of the arterioles and subsequently, blood pressure. As with the RAA system, this has not been sufficiently proven to result in hypertension although it is established that blocking these hormones significantly lower blood pressure (Beevers, Lip and O’Brien, 2001).
A more significant contributory factor to hypertension is a defect in vascular endothelial cell functioning (Beevers, Lip and O’Brien, 2001). Endothelial cells produce nitric oxide, a vasodilator and endothelin, a vasoconstrictor and a stimulating factor of the RAA system. Malfunction may involve the inability of these cells to produce nitric oxide causing in a decreased capacity for vasodilation contributing to hypertension.
The atrial natriuretic hormone released by the right atrium of the heart is also an important regulator of blood pressure (Beevers, Lip and O’Brien, 2001). It acts to increase the rate in which the body loses water and sodium. This decreases blood volume, effectively lowering blood pressure. If the heart ceases to produce this hormone, the body loses a mechanism response to increases in blood pressure. The Pathophyiology Of Hypertension Essay.
Hypertensive patients usually present with abnormal vessel walls, blood flow and composition which lead to hypercoagulability or blood clotting and increased blood pressure (Beevers, Lip and O’Brien, 2001). Evidence also suggests that genetics also contributes to the condition. Having one or both parents with hypertension increases the chances of their children developing the condition. Studies also reveal that genetic factors are responsible for 30% of the differences in blood pressure. It is also possible that the angiotensinogen gene and angiotensin converting enzyme are related to hypertension while the adducing gene may also contribute to salt sensitive hypertension (Beevers, Lip and O’Brien, 2001).
Hypertension in adolescence and adulthood has also been correlated with birth weight and certain congenital abnormalities (Beevers, Lip and O’Brien, 2001). Persons born with low birth weight have increased chances of developing hypertension than those born with normal birth weight. This is because low birth weight is also associated with metabolic abnormalities which are risk factors for hypertension (Beevers, Lip and O’Brien, 2001).
The clustering of multiple factors such as obesity, hypertension, glucose intolerance, diabetes mellitus and high blood cholesterol in patients who eventually suffer from ireversible hypertension and damage to the blood vessels suggest that all factors may in one way or another contribute towards the development of the condition (Beevers, Lip and O’Brien, 2001). The manner by which this occurs is still subject to research.
The article relates to physiology in that it describes how parts of the body, such as hormones, proteins and organs, normally function together to maintain the normal range of blood pressure. The disruption of normal functioning is shown to result in hypertension.
The article is comprehensive with respect to both known as well as contemplated factors related to the development of hypertension. However, recent updates regarding the progress of research in determining how each factor actually contributes to this condition have to be obtained.The Pathophyiology Of Hypertension Essay. Prior knowledge regarding human anatomy is necessary to better appreciate the information presented. While there were tables, illustrations and graphs, these lacked visual appeal. Nevertheless, it served to deepen my cursory understanding of hypertension as a fairly common but not well understood illness. I recommend its reading to people with a background on anatomy and physiology or health-related subjects and who are interested primarily in contributory factors since the scope of the article did not include a definition of the condition, related diagnostic procedures, complications and management which relate to how normal physiological functioning can be restored in hypertensive patients.
List of References
- Beevers, G., Lip, G.Y.H. and O’Brien, E. (2001). “The Pathophysiology of Hypertension”. British Medical Journal 322(7291): 912-916. Retrieved 14 October 2008 from
There is still much uncertainty about the pathophysiology of hypertension. A small number of patients (between 2% and 5%) have an underlying renal or adrenal disease as the cause for their raised blood pressure. In the remainder, however, no clear single identifiable cause is found and their condition is labelled “essential hypertension”. A number of physiological mechanisms are involved in the maintenance of normal blood pressure, and their derangement may play a part in the development of essential hypertension.
It is probable that a great many interrelated factors contribute to the raised blood pressure in hypertensive patients, and their relative roles may differ between individuals. Among the factors that have been intensively studied are salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. In the past few years, other factors have been evaluated, including genetics, endothelial dysfunction (as manifested by changes in endothelin and nitric oxide), low birth weight and intrauterine nutrition, and neurovascular anomalies.
Cardiac output and peripheral resistance
Maintenance of a normal blood pressure is dependent on the balance between the cardiac output and peripheral vascular resistance. Most patients with essential hypertension have a normal cardiac output but a raised peripheral resistance. Peripheral resistance is determined not by large arteries or the capillaries but by small arterioles, the walls of which contain smooth muscle cells. Contraction of smooth muscle cells is thought to be related to a rise in intracellular calcium concentration, which may explain the vasodilatory effect of drugs that block the calcium channels. Prolonged smooth muscle constriction is thought to induce structural changes with thickening of the arteriolar vessel walls possibly mediated by angiotensin, leading to an irreversible rise in peripheral resistance.
It has been postulated that in very early hypertension the peripheral resistance is not raised and the elevation of the blood pressure is caused by a raised cardiac output, which is related to sympathetic overactivity. The Pathophyiology Of Hypertension Essay. The subsequent rise in peripheral arteriolar resistance might therefore develop in a compensatory manner to prevent the raised pressure being transmitted to the capillary bed where it would substantially affect cell homeostasis.
Renin-angiotensin system
The renin-angiotensin system may be the most important of the endocrine systems that affect the control of blood pressure. Renin is secreted from the juxtaglomerular apparatus of the kidney in response to glomerular underperfusion or a reduced salt intake. It is also released in response to stimulation from the sympathetic nervous system.
Renin is responsible for converting renin substrate (angiotensinogen) to angiotensin I, a physiologically inactive substance which is rapidly converted to angiotensin II in the lungs by angiotensin converting enzyme (ACE). Angiotensin II is a potent vasoconstrictor and thus causes a rise in blood pressure. In addition it stimulates the release of aldosterone from the zona glomerulosa of the adrenal gland, which results in a further rise in blood pressure related to sodium and water retention.
The circulating renin-angiotensin system is not thought to be directly responsible for the rise in blood pressure in essential hypertension. In particular, many hypertensive patients have low levels of renin and angiotensin II (especially elderly and black people), and drugs that block the renin-angiotensin system are not particularly effective.
There is, however, increasing evidence that there are important non-circulating “local” renin-angiotensin epicrine or paracrine systems, which also control blood pressure. The Pathophyiology Of Hypertension Essay. Local renin systems have been reported in the kidney, the heart, and the arterial tree. They may have important roles in regulating regional blood flow.
Autonomic nervous system
Sympathetic nervous system stimulation can cause both arteriolar constriction and arteriolar dilatation. Thus the autonomic nervous system has an important role in maintaining a normal blood pressure. It is also important in the mediation of short term changes in blood pressure in response to stress and physical exercise.
There is, however, little evidence to suggest that epinephrine (adrenaline) and norepinephrine (noradrenaline) have any clear role in the aetiology of hypertension. Nevertheless, their effects are important, not least because drugs that block the sympathetic nervous system do lower blood pressure and have a well established therapeutic role.
It is probable that hypertension is related to an interaction between the autonomic nervous system and the renin-angiotensin system, together with other factors, including sodium, circulating volume, and some of the more recently described hormones.
Endothelial dysfunction
Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent local vasoactive agents, including the vasodilator molecule nitric oxide and the vasoconstrictor peptide endothelin. Dysfunction of the endothelium has been implicated in human essential hypertension.
Modulation of endothelial function is an attractive therapeutic option in attempting to minimise some of the important complications of hypertension. Clinically effective antihypertensive therapy appears to restore impaired production of nitric oxide, but does not seem to restore the impaired endothelium dependent vascular relaxation or vascular response to endothelial agonists. This indicates that such endothelial dysfunction is primary and becomes irreversible once the hypertensive process has become established. The Pathophyiology Of Hypertension Essay.
Vasoactive substances
Many other vasoactive systems and mechanisms affecting sodium transport and vascular tone are involved in the maintenance of a normal blood pressure. It is not clear, however, what part these play in the development of essential hypertension. Bradykinin is a potent vasodilator that is inactivated by angiotensin converting enzyme. Consequently, the ACE inhibitors may exert some of their effect by blocking bradykinin inactivation.
Endothelin is a recently discovered, powerful, vascular, endothelial vasoconstrictor, which may produce a salt sensitive rise in blood pressure. It also activates local renin-angiotensin systems. Endothelial derived relaxant factor, now known to be nitric oxide, is produced by arterial and venous endothelium and diffuses through the vessel wall into the smooth muscle causing vasodilatation.
Atrial natriuretic peptide is a hormone secreted from the atria of the heart in response to increased blood volume. Its effect is to increase sodium and water excretion from the kidney as a sort of natural diuretic. A defect in this system may cause fluid retention and hypertension.
Sodium transport across vascular smooth muscle cell walls is also thought to influence blood pressure via its interrelation with calcium transport. Ouabain may be a naturally occurring steroid-like substance which is thought to interfere with cell sodium and calcium transport, giving rise to vasoconstriction. The Pathophyiology Of Hypertension Essay.
Hypercoagulability
Patients with hypertension demonstrate abnormalities of vessel wall (endothelial dysfunction or damage), the blood constituents (abnormal levels of haemostatic factors, platelet activation, and fibrinolysis), and blood flow (rheology, viscosity, and flow reserve), suggesting that hypertension confers a prothrombotic or hypercoagulable state. These components appear to be related to target organ damage and long term prognosis, and some may be altered by antihypertensive treatment.
Insulin sensitivity
Epidemiologically there is a clustering of several risk factors, including obesity, hypertension, glucose intolerance, diabetes mellitus, and hyperlipidaemia. This has led to the suggestion that these represent a single syndrome (metabolic syndrome X or Reaven’s syndrome), with a final common pathway to cause raised blood pressure and vascular damage. Indeed some hypertensive patients who are not obese display resistance to insulin. There are many objections to this hypothesis, but it may explain why the hazards of cardiovascular risk are synergistic or multiplicative rather than just additive. The Pathophyiology Of Hypertension Essay.
Genetic factors
Although separate genes and genetic factors have been linked to the development of essential hypertension, multiple genes are most likely contribute to the development of the disorder in a particular individual. It is therefore extremely difficult to determine accurately the relative contributions of each of these genes. Nevertheless, hypertension is about twice as common in subjects who have one or two hypertensive parents, and many epidemiological studies suggest that genetic factors account for approximately 30% of the variation in blood pressure in various populations. This figure can be derived from comparisons of parents with their monozygotic and dizygotic twin children, as well as their other children, and with adopted children. Some familial concordance is, however, due to shared lifestyle (chiefly dietary) factors.
Some specific genetic mutations can rarely cause hypertension. Experimental models of genetic hypertension have shown that the inherited tendency to hypertension resides primarily in the kidney. For example, animal and human studies show that a transplanted kidney from a hypertensive donor raises the blood pressure and increases the need for antihypertensive drugs in recipients coming from “normotensive” families. Conversely a kidney from a normotensive donor does not raise the blood pressure in the recipient.
Increased plasma levels of angiotensinogen, the protein substrate acted on by renin to generate angiotensin I, have also been reported in hypertensive subjects and in children of hypertensive parents.
Hypertension is rarely found in rural or “tribal” areas of Africa, but it is very common in African cities and in black populations in Britain and the United States. Whereas the rural/urban differences in Africa are clearly due to lifestyle and dietary factors, the finding that hypertension is commoner in black people compared with white people may have some genetic basis. There is some evidence from salt loading studies in medical students that black Americans are more susceptible to a given salt load than white Americans, and may be more sensitive to the beneficial effects of salt restriction.
Intrauterine influences
There is increasing evidence that fetal influences, particularly birth weight, may be a determinant of blood pressure in adult life. For example, babies who are small at birth are more likely to have higher blood pressure during adolescence and to be hypertensive as adults. Babies who are small for their age are also more likely to have metabolic abnormalities that have been associated with the later development of hypertension and cardiovascular disease, such as insulin resistance, diabetes mellitus, hyperlipidaemia, and abdominal obesity (the “Barker hypothesis”). Insulin resistance almost certainly contributes to the increased prevalence of coronary disease seen in adults of low birth weight.
It is possible, however, that genetic factors influence the Barker hypothesis. Mothers with above average blood pressure in pregnancy give birth to smaller babies who subsequently develop above average blood pressure themselves and eventually hypertension. It is entirely likely that the similarity of blood pressures in mother and child are genetic and, in a modern “healthy” society, unrelated to intrauterine undernutrition. The Pathophyiology Of Hypertension Essay.
Diastolic dysfunction
In hypertensive left ventricular hypertrophy, the ventricle cannot relax normally in diastole. Thus, to produce the necessary increase in ventricular input, especially during exercise, there is an increase in left atrial pressure rather than the normal reduction in ventricular pressure, which produces a suction effect as described above. This can lead to an increase in pulmonary capillary pressure that is sufficient to induce pulmonary congestion. The rise in atrial pressure can also lead to atrial fibrillation, and in hypertrophied ventricles dependent on atrial systole the loss of atrial transport can result in a significant reduction in stroke volume and pulmonary oedema. Exercise induced subendocardial ischaemia can also produce an “exaggerated” impairment of diastolic relaxation of the hypertrophied myocardium.
