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Hypertension : pathophysiology, sign&symptoms, diagnosis, treatment

Hypertension |etiopathogenesis |sign&symptoms| diagnosis| treatment


 Hypertension is defined as persistently elevated arterial blood pressure (BP). The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) classifies adult BP as shown below-
classification of BP
Isolated systolic hypertension is diastolic blood pressure (DBP) values less than 90 mm Hg and systolic blood pressure (SBP) values of 140 mm Hg or more.

 Hypertensive crisis (BP >180/120 mm Hg) may be categorized as a hypertensive emergency (extreme BP elevation with acute or progressing target-organ damage) or hypertensive urgency (high BP elevation without acute or progressing target-organ injury).


Hypertension may result from a specific cause (secondary hypertension) or from an unknown etiology (primary or essential hypertension). Secondary hypertension (<10% of cases) is usually caused by chronic kidney disease (CKD) or renovascular disease. Other conditions are Cushing syndrome, coarctation of the aorta, obstructive sleep apnea, hyperparathyroidism, pheochromocytoma, primary aldosteronism, and hyperthyroidism. 

Some drugs that may increase BP include corticosteroids, estrogens, nonsteroidal anti-inflammatory drugs (NSAIDs), amphetamines, sibutramine, cyclosporine, tacrolimus, erythropoietin, and venlafaxine.

Factors contributing to the development of primary hypertension include:
✓ Humoral abnormalities involving the renin–angiotensin–aldosterone system (RAAS), natriuretic hormone, or insulin resistance and hyperinsulinemia;
✓ Disturbance in the CNS, autonomic nerve fibers, adrenergic receptors, or baroreceptors;
✓ Abnormalities in renal or tissue autoregulatory processes for sodium excretion, plasma volume, and arteriolar constriction;
✓ Deficiency in the synthesis of vasodilating substances in vascular endothelium (prostacyclin, bradykinin, and nitric oxide) or excess vasoconstricting substances (angiotensin II, endothelin I);
✓ High sodium intake or lack of dietary calcium.

Main causes of death are cerebrovascular accidents, cardiovascular (CV) events, and renal failure. The probability of premature death correlates with the severity of BP elevation.

Sign & symptoms 

Patients with uncomplicated primary hypertension are usually asymptomatic initially. Patients with secondary hypertension may have symptoms of the underlying disorder. Patients with pheochromocytoma may have headaches, sweating, tachycardia, palpitations, and orthostatic hypotension. In primary aldosteronism, hypokalemic symptoms of muscle cramps and weakness may be present. Patients with Cushing syndrome may have weight gain, polyuria, edema, menstrual irregularities, recurrent acne, or muscular weakness in addition to classic features (moon face, buffalo hump, and hirsutism). if you have this types of symptoms consult with your doctor immediately.


Measurements of BP

• Elevated BP may be the only sign of primary hypertension on physical examination. BP measure by using sphygmomanometer and compare the reading with normal BP.

• Signs of end-organ damage occur primarily in the eye, brain, heart, kidneys, and peripheral blood vessels.

• The funduscopic examination may reveal arteriolar narrowing, focal arteriolar constrictions,
arteriovenous nicking, retinal hemorrhages and exudates, and disk edema. Presence of papilledema usually indicates a hypertensive emergency requiring rapid treatment.

• The cardiopulmonary examination may reveal abnormal heart rate or rhythm, left ventricular(LV) hypertrophy, coronary heart disease, or heart failure (HF).

• The peripheral vascular examination may reveal aortic or abdominal bruits, distended veins, diminished or absent peripheral pulses, or lower extremity edema.

• Patients with renal artery stenosis may have an abdominal systolic-diastolic bruit.

• Baseline hypokalemia may suggest mineralocorticoid-induced hypertension. Protein, blood cells, and casts in the urine may indicate renovascular disease.

• Laboratory tests: Blood urea nitrogen (BUN)/serum creatinine, fasting lipid panel, fasting blood glucose, serum electrolytes (sodium and potassium), spot urine albumin-to-creatinine ratio, and estimated glomerular filtration rate (GFR, using the Modification of Diet in Renal Disease [MDRD] equation). A 12-lead electrocardiogram (ECG) should also be obtained.

• Laboratory tests to diagnose secondary hypertension: Plasma norepinephrine and urinary metanephrine levels for pheochromocytoma, plasma, and urinary aldosterone concentrations for primary aldosteronism, plasma renin activity, captopril stimulation test, renal vein renin, and renal artery angiography for renovascular disease.


Non-pharmacological treatment

• Lifestyle modifications: (1) weight loss if overweight, (2) adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan, (3) dietary sodium restriction ideally to 1.5 g/day (3.8 g/day sodium chloride), (4) regular aerobic physical activity, (5) moderate alcohol consumption (two or fewer drinks per day), and (6) smoking cessation.

• Lifestyle modification alone is sufficient for most patients with prehypertension but inadequate for patients with hypertension and additional CV risk factors or hypertension-associated target-organ damage.

Pharmacological treatment

• Initial drug selection depends on the degree of BP elevation and presence of compelling indications for selected drugs.

• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide diuretics are acceptable first-line options.

• β-Blockers are used to either treat a specific compelling indication or as combination therapy with a first-line antihypertensive agent for patients without a compelling indication.

• Most patients with stage 1 hypertension should be treated initially with a first-line antihypertensive drug or a two-drug combination. Combination therapy is recommended for patients with stage 2 hypertension, preferably with two first-line agents.

• There are six compelling indications where specific antihypertensive drug classes provide unique benefits are given below-
compelling indication in hypertension
compelling indication in hypertension
• Other antihypertensive drug classes (α1-blockers, direct renin inhibitors, central α2-agonists, peripheral adrenergic antagonists, and direct arterial vasodilators) are alternatives that may be used for select patients after first-line agents.

Angiotensin-Converting Enzyme Inhibitors

ACE inhibitors are the first-line option, and if they are not the first agent used, they should be the second agent tried in most patients.

• ACE inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block degradation of bradykinin and stimulate synthesis of other vasodilating substances, including prostaglandin E2 and prostacyclin.
eg:-Benazepril (Lotensin), Captopril (Capoten), Enalapril (Vasotec), Fosinopril (Monopril), Lisinopril (Prinivil, Zestril).

Angiotensin II Receptor Blockers

• Angiotensin II is generated by the renin-angiotensin pathway (which involves ACE) and an alternative pathway that uses other enzymes such as chymases. ACE inhibitors block only the renin-angiotensin pathway, whereas ARBs antagonize angiotensin II generated by either pathway. The ARBs directly block the angiotensin II type 1 receptor that mediates the effects of angiotensin II.
eg:-Irbesartan (Avapro), Losartan (Cozaar), Olmesartan (Benicar), Telmisartan (Micardis), Valsartan (Diovan).

• ARBs have a low incidence of side effects. Like ACE inhibitors, they may cause renal
insufficiency, hyperkalemia, and orthostatic hypotension. ARBs are contraindicated
in pregnancy.

Calcium Channel Blockers

• Calcium channel blockers (CCBs) cause relaxation of cardiac and smooth muscle by blocking voltage-sensitive calcium channels, thereby reducing entry of extracellular calcium into cells. This leads to vasodilation and a corresponding reduction in BP. Dihydropyridine calcium channel antagonists may cause reflex sympathetic activation, and all agents (except amlodipine and felodipine) may have negative inotropic effects.

• Verapamil decreases heart rate, slows atrioventricular (AV) nodal conduction, and produces a negative inotropic effect that may precipitate HF(heart failure) in patients with borderline cardiac reserve. Diltiazem decreases AV conduction and heart rate to a lesser extent than verapamil.

• Diltiazem and verapamil can cause cardiac conduction abnormalities such as bradycardia, AV block, and HF. Both can cause anorexia, nausea, peripheral edema, and hypotension. Verapamil causes constipation in ~7% of patients.


• Acutely, diuretics lower BP by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and BP. The initial drop in cardiac output causes a compensatory increase in peripheral vascular resistance. With chronic therapy, extracellular fluid volume and plasma volume return to near pretreatment levels, and peripheral vascular resistance fall below the baseline. Reduced peripheral vascular resistance is responsible for the long-term hypotensive effects.

• Thiazide diuretics are the preferred type of diuretic for most hypertensive patients. They mobilize sodium and water from arteriolar walls, which may contribute to decreased peripheral vascular resistance and lowered BP.

• Loop diuretics are more potent for inducing diuresis but are not ideal antihypertensives unless relief of edema is also needed. Loops are often preferred over thiazides in patients with CKD when estimated GFR is less than 30 mL/min/1.73 m2.

• Potassium-sparing diuretics are weak antihypertensives when used alone and provide minimal additive effect when combined with a thiazide or loop diuretic. Their primary use is in combination with another diuretic to counteract potassium-wasting properties.

• Aldosterone antagonists (spironolactone and eplerenone) are also potassium-sparing diuretics but are more potent antihypertensives with a slow onset of action (up to 6 weeks with spironolactone).

α1-Receptor Blockers

• Prazosin, terazosin, and doxazosin are selective α1-receptor blockers that inhibit catecholamine uptake in smooth muscle cells of peripheral vasculature, resulting in vasodilation.

• A first-dose phenomenon characterized by orthostatic hypotension accompanied by transient dizziness or faintness, palpitations, and even syncope may occur within 1 to 3 hours of the first dose or after later dosage increases. The patient should take the first dose (and subsequent first increased doses) at bedtime. Occasionally, orthostatic dizziness persists with chronic administration.

• Sodium and water retention can occur; these agents are most effective when given with a diuretic to maintain antihypertensive efficacy and minimize edema.

Direct Renin Inhibitor

Aliskiren blocks the RAAS at its point of activation, resulting in reduced plasma renin activity and BP. BP reductions are comparable to an ACE inhibitor, ARB, or CCB. Aliskiren is approved for monotherapy or in combination with other agents. It should not be used in combination with an ACE inhibitor or an ARB because of a higher risk of adverse effects without the additional reduction in CV events.

• Many of the cautions and adverse effects were seen with ACE inhibitors and ARBs apply to aliskiren. It is contraindicated in pregnancy.

• Use aliskiren only as an alternative therapy because of lack of long-term studies evaluating CV event reduction and its significant cost compared with generic agents that have outcomes data.

Central α2-Agonists

• Clonidine, guanabenz, guanfacine, and methyldopa lower BP primarily by stimulating α2-adrenergic receptors in the brain, which reduces the sympathetic outflow from the vasomotor center and increases vagal tone. Stimulation of presynaptic α2-receptors peripherally may contribute to reduced sympathetic tone. Consequently, there may be decreases in heart rate, cardiac output, total peripheral resistance, plasma renin activity, and baroreceptor reflexes.

• Chronic use results in sodium and fluid retention. Other side effects include depression, orthostatic hypotension, dizziness, and anticholinergic effects.


Reserpine depletes norepinephrine from sympathetic nerve endings and blocks transport of norepinephrine into storage granules. When the nerve is stimulated, less than the usual amount of norepinephrine is released into the synapse. This reduces sympathetic tone, decreasing peripheral vascular resistance and BP.

Direct Arterial Vasodilators

• Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in the increased sympathetic outflow from the vasomotor center, increasing heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic.

• Patients taking these drugs for long-term hypertension therapy should first receive both a diuretic and a β-blocker. The diuretic minimizes the side effect of sodium and water retention.

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