Hypertension, Pathophysiology, Clinical presentation, Diagnosis & Treatment.

Hypertension 

is defined as persistently elevated arterial blood pressure (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 hypertensive emergency or hypertensive urgency (high BP elevation without acute or progressing target-organ injury).

PATHOPHYSIOLOGY

• 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 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 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. Probability of premature death correlates with the severity of BP elevation.

CLINICAL PRESENTATION

• 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).

DIAGNOSIS

• Elevated BP may be the only sign of primary hypertension on physical examination. Diagnosis should be based on the average of two or more readings taken at each of two or more clinical encounters.

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

• 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.

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

• 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.

TREATMENT

• Goals of Treatment: The overall goal is to reduce morbidity and mortality by the least intrusive means possible. JNC7 guidelines recommend goal BP less than 140/90 mmHg for most patients, less than 140/80 mm Hg for patients with diabetes mellitus, and less than 130/80 mm Hg for patients with CKD who have persistent albuminuria (>30 mg urine albumin excretion per 24 hours).

NONPHARMACOLOGIC THERAPY
• Lifestyle modifications:
(1) weight loss if overweight,
(2) adoption of the Dietary Approaches
(3) restriction of dietary sodium  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.

PHARMACOLOGIC THERAPY

• drug selection depends Initially 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 treat a specific compelling indication or as combination therapy with a first-line antihypertensive agent for patients without a compelling indication .
• stage 1 patients  hypertension should be treated initially with a first-line antihypertensive drug or a two-drug combination.
for patients with stage 2 hypertension Combination therapy is recommended, preferably with two first-line agents.
• There are six compelling indications where specific antihypertensive drug classes provide unique benefits.
• 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 a 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 conversion of angiotensin I to angiotensin II, a potent vasoconstrictor
and stimulator of aldosterone secretion. ACE inhibitors block degradation of bradykinin and stimulate synthesis of vasodilating substances e.g. prostaglandin E2 and prostacyclin.
• Starting doses should be low with slow dose titration. Acute hypotension may occur at the onset of therapy, especially in patients who are sodium- or volume-depleted, in HF exacerbation, very elderly, or on concurrent vasodilators or diuretics. Start administering doses in such patients, using half the normal dose followed by slow dose titration.
• ACE inhibitors decrease aldosterone & can increase serum potassium concentrations. Hyperkalemia occurs in patients with CKD or those also taking potassium supplements, potassium-sparing diuretics, ARBs, or a direct renin inhibitor.
• Acute renal failure is a rare but serious side effect; preexisting kidney disease increases risk. Bilateral renal artery stenosis or unilateral stenosis of a solitary functioning kidney renders patients dependent on the vasoconstrictive effect of angiotensin II on efferent arterioles, making these patients particularly susceptible to acute renal failure.
• GFR declines in patients receiving ACE inhibitors because of inhibition of angiotensin II vasoconstriction on efferent arterioles. Serum creatinine concentrations often increase, but modest elevations (eg, absolute increases <1 mg/dL [88 μmol/L]) do not warrant treatment changes.
Discontinue therapy or reduce dose if larger increases occur.
• Angioedema occurs in fewer than 1% of patients. Drug withdrawal is necessary, and some patients may require drug treatment and/or emergent intubation. An ARB can
generally be used in patients with a history of ACE inhibitor–induced angioedema, with careful monitoring.
• A persistent dry cough occurs in up to 20% of patients and is thought to be due to inhibition of bradykinin breakdown.
• ACE inhibitors (as well as ARBs and direct renin inhibitors) are contraindicated in pregnancy.

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.
• Unlike ACE inhibitors, ARBs do not block bradykinin breakdown. Although this accounts for the lack of cough as a side effect, there may be negative consequences because some of the antihypertensive effect of ACE inhibitors may be due to increased levels of bradykinin.
• All ARBs have similar antihypertensive efficacy and fairly flat dose-response curves. Addition of a CCB or thiazide diuretic significantly increases antihypertensive  efficacy.
• 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 in patients.