Hypertension is a condition in which the individual’s blood pressure rises to an abnormal level. In this condition, the systolic blood pressure is persistently above 140 mm of Hg and/or the diastolic blood is persistently above 90 mm of Hg. The quantity of blood pumped by the heart, and the size of the blood determine the blood pressure (blood pressure = cardiac output * peripheral vascular resistance). Besides this, the quantity of water present in the body, the salt levels, kidneys, nervous system, hormone levels, etc, also play a very important role in determining the blood pressure (Najafian, N., 2006).
The blood pressure tends to increase with age, and is about 160/95 at the age of 50 years. There may several causes related to hypertension. However, in 95 % of the cases a single underlying cause is not found, which may be due to interplay of several factors. This type of hypertension is known as ‘essential hypertension’. In more than 70 % of such individual, a pattern of inheritance is observed.
Several ethnic groups such as Jews, African-American and Japanese, develop hypertension more often (Mayo Clinic. 2006).
Studies have demonstrated that the important cause for essential hypertension is an increase in the peripheral resistance of the blood vessels. This disorder can develop due to sympathetic nervous activity or from narrowing of the blood vessels. The remaining 5% of the cases are caused due to certain disorders such as cardiac disorder (corarctation of the aorta), renal disorders (glomerulonephritis and chronic pyelonrphritis), endocrinal disorders (such as pheochromocytoma, primary aldosteronism, Cushing’ syndrome), drug usage (such as corticosteroids, certain birth control pills) and sometimes during pregnancy.
Excessive hormones are released in pheochromocytoma, which cause an increase in the cardiac output and rise in the peripheral vascular resistance. In the renal disorder, the kidneys do not function efficiently, resulting in sodium retention in the body. In some conditions, excessive rennin is produced by the kidney resulting in activation of the angiotensin II (that has great vasoconstrictor action). Angiotensin II encourages release of aldosterone which causes sodium retention. In primary aldosteronism, the mineral sodium is retained in the body, along with changes in the vascular smooth muscles of the blood vessels (Boon, N.A. and Fox, K.A.A. 1996).
In individuals with essential hypertension, the large arteries experience changes in the vessel wall. The inner elastic lamina gets thickened; the smooth muscles increase in size and fibrous tissues gets deposited. In an effort to normalise the blood flow, the arteries dilate and become tortuous. In such circumstances, due to the damage of the inner-lining tissues of the blood vessels (endothelium), the deposition and retention of lipoproteins in the sub-epithelial wall develops. Along with this, other substances such as connective tissue matrix, smooth muscles, the mineral calcium, inflammatory cells and newly-developed blood vessels are formed. (Shah, P.K., 2001). Smaller blood vessels get narrowed, and aneurysms are formed.
Due to these anatomical changes in the blood vessels, the blood flow and the peripheral vascular resistance is increased. The process of atheroma is also hastened. If the blood supply to the kidney is affected with the narrowing of the blood vessels, rennin and angiotensin are activated, and sodium and water are retained. Sometimes the associated narrowing of the blood vessels to the organs are so severe that the organs began to function abnormally. The kidneys produce proteinuria and microscopic haematuria. Besides, the blood supply to the brain is also affected as the arteries begin to narrow (Boon, N.A. and Fox, K.A.A. 1996).
In the body, multiple mechanisms may be involved in elevating the blood pressure. In arterial hypertension, the relationship between cardiac output and the total vascular peripheral resistance is distorted. Blood pressure is affected by several variables including genetic, environmental and demographic, which affect both the cardiac output and peripheral vascular resistance (includes age, sex, gender, body mass index, etc). Cardiac output has an effect on the blood volume which is influenced by sodium levels in the body. The peripheral vascular resistance is affected by hormonal and neuronal factors. Vasoconstrictors that reduce the lumen for blood flow include Angiotensin II, catecholamines and the endothelium.
The vasodilatation factors include kinin and prostoglandins. Several auto-regulatory mechanisms also take part in regulating the peripheral vascular resistance. They automatically increase the blood flow when vasoconstriction occurs. The local factors that adjust the blood pressure include pH, hypoxia, alpha and beta-adrenergic mechanisms that affect cardiac contraction, vascular tone, heart beat, etc. The kidneys adjust the blood pressure in several ways. The rennin-angiotensin system (RAS) affects the metabolism of sodium and peripheral vascular resistance.
Renin is released by the juxtaglomerular cells that transform angiotensinogen present in the blood to angiotensin 1. This is later transformed to angiotensin II by the angiotensin converting enzyme (ACE). Angiotensin increases the blood pressure by inducing vasoconstriction (action on the smooth muscles present in the blood vessels) and increasing the blood volume (by encouraging aldosterone release). The kidneys also increase the blood pressure by reabsorbing sodium from the proximal tubules. In this way the sodium levels increases in the body and thereby there is an increase in the blood volume (Schoen, F. J. 2002).
The kidneys manage about 170 litres of blood filtration every day. This amount of blood contains about 23 moles of salt. More than 99.5% of this is reabsorbed back into the blood through ionic channels, exchange and transporter, etc. Certain changes in the proteins that involve sodium reabsorption may be expressed through genetic defects. This condition is known as ‘Liddle’s syndrome’. Likewise, several other components of the RAS system are affected by genetic defects. The kidneys may release reduced amounts of sodium leading to increased blood volume and increased cardiac output, leading to a rise in the blood pressure (Schoen, F. J. 2002).
The blood vessel wall may be directly stimulated by chronic vasoconstriction. This can lead to thickening of the blood vessel wall, which further narrows the lumen and raises the peripheral vascular resistance. Large and medium-sized blood vessels have associated changes in the blood vessel wall. Aortic dissection and haemorrhage can occur due to increased vascular resistance. In small blood vessels, hyaline arteriosclerosis and hyperplasic arteriosclerosis can result (Schoen, F. J. 2002).
Genetic defects can cause rare forms of hypertension. Deficiency in enzymes of aldosterone metabolism leads to increased release of aldosterone, and increased salt and water reabsorbtion (Schoen, F. J. 2002).
Aldosterone is present in the cells of adrenal zona gloemerulosa. Angiotensin II helps to activate it through the RAS system. When the sodium levels decrease, and the blood pressure drops, the alodsterone gets activated. Angiotensongen is combined with renin. Angiotensin I is formed which is converted to Angiotensin II by the ACE enzyme present on the surface of endothelial cells located in the kidneys and the lungs. Aminopeptidase converts Angiotensin II to Angiotensin III by the enzyme aminopeptidase (Schmidt, T.J. Et al. 2006).
Several enzymes such as caboxypeptidases and aminopeptidases produce a number of subtacnes related to angiotensin such as angiotensin I, II, III, IV, etc. Each has their own physiological function. Several alternative pathways may be present mainly associated with angiotensin II production. Angiotensin I can be converted to another form known as ‘Angiotensin-(1-9) by the enzyme carboxypeptidase (associated with ACE). This later gets converted to Angiotensin II. Further studies need to be conducted on the exact mechanism by this conversion takes place. Clinically, ACE and angiotensin I receptor are significant, although a lot has to be studied about these alternate pathways (Kramkowski, K. Et al. 2006).
The diagnosis of hypertension is made based on the history, symptoms, signs, and the results of several diagnostic tests such as urine tests, blood tests, Electrocardiogram (ECG), chest X-rays, etc. Urine tests are required to determine the level of proteins, glucose, and the presence of blood in the urine. Blood tests are required to determine the level of urea, creatinine, cholesterol, triglycerides and hormones in the blood. Chest X-rays, angiograms and MRI scans of the heart are required to determine the activity of the heart and the lungs.
ECG is required to determine the electrical activity of the heart and abnormalities such as ischemia and left ventricular hypertrophy. The National Heart, Lung and Blood Institute (2003) have classified hypertension based on the severity of the blood pressure. These include normal blood pressure (120/80 mm), pre-hypertension (120-139/80-89 mm), stage 1 (140-159/90-99 mm), and stage 2 (>150/>100 mm). In pheochomocytoma a specialised test to determine the 24 hour urinary cathecholamine output may be performed. In Conn’s syndrome the blood rennin and aldosterone activity is determined (Boon, N.A. and Fox, K.A.A. 1996).
The main aim of treatment is to relieve the symptoms, reduce the effects of the disease process and prevent further complications. Once hypertension is detected, the individual has to take care and follow certain measures in diet, lifestyle, physical activity and consume certain medications. Studies have demonstrated that timely and appropriate treatment can help reduce the occurrence of several complications such as stroke, renal failure and others. Besides, the fatalities due to cardiovascular events are significantly reduced (Boon, N.A. and Fox, K.A.A. 1996).
The individual has to consume a low-sodium diet, and reduce consumption of alcohol. Individuals, who smoke, may gain significantly if they stop the habit. Exercises can also be very beneficial to hypertensive individuals, and can drastically help reduce the blood pressure. Regular consumption of medications has ensured that the individual’s blood pressure is within normal limits. Drugs are administered as a single or a combination therapy. The problem in hypertensive individuals is that they tend to stop the medications once the symptoms reduce. However, the disease can remain silent, and the individual may experience the complications, later.
Hence, it would be advisable to continue the medications as prescribed, with appropriate control of the side-effects. Several agents such as beta-blockers, angiotensin II receptor blockers, ACE inhibitors, thiazide diuretics, calcium channel blockers, vasodilators are available which are administered appropriately. The first-line drugs use varies from one individual to another depending on the severity of the condition.
Combination therapy is also available to treat refractory cases (or when hypertension cannot be controlled by drug doses at which side-effects do not develop). During emergency treatment of hypertension, the blood pressure should not be brought rapidly down as it can lead to brain damage, cardiac insufficiency and renal problems. The blood pressure has to be brought down to 150/90 level over a period of one hour to ninety minutes. In an emergency situation, sodium nitroprusside is mode ideal bring down the blood pressure. Labetalol, oral nifedipine and hydralazine are also ideal to bring to bring down the blood pressure reduced (Boon, N.A. and Fox, K.A.A. 1996).
Boon, N.A. and Fox, K.A.A. 1996, “Diseases of the Cardiovascular System.” In: Edwards, C.R.W., Bouchier, I.A.D. and Haslett, C., Davidson’s Principles and Practice of Medicine, 17th ed, Churchill Livingstone, Edinburgh. 191-311.
Kramkowski, K., Mogielnicki, A. and Buczko, W. 2006. “The physiological significance of the alternative pathways of angiotensin II production.” J Physiol Pharmacol, vol. 57, no. 4, pp. 529-539.
Mayo Clinic Staff. 2006, High blood pressure (hypertension). [Online], Available: http://www.mayoclinic.com/health/high-blood-pressure/DS00100/DSECTION=1, [Accessed: 2007, January, 30].
Schmidt, T.J. and Litwack, G. 2006, Biochemistry of Hormones, in: Devlin, T.M., Textbook of Biochemistry with Clinical Correlations, Wiley-Less, New jersey. 895-946.
Schoen, F.J. 2002, Blood Vessels, in: Kumar, V., Abbas, A.K., Fausto, N. (eds), Robins and Cotran: Pathologic Basis of Disease, 6th ed, Saunders, Philadelphia. 2002. 423-444.
Shah, P.K. 2001, Pathogenesis of arthrosclerosis, in: Rosendorff, C., Essential Cardiology: Principles and Practice, W.B. Saunders Company., Philadelphia.
Tweedie, D. (2006). The Pathology of Hypertension (Heart/Circulation). [Online], Available: http://18.104.22.168/search?q=cache:izxWLiHy3tUJ:www.uwo.ca/pathol/MedsII/Notes/CVS-Hypertension.rtf+hypertension+pathology&hl=en&ct=clnk&cd=4, [Accessed: 2007, January, 30].