Hypertension

Definition: Hypertension is that level of sustained

systemic arterial pressure which results over

time in end-organ damage, most commonly in

the eyes, the brain, the heart, the kidneys and

the vasculature.

Incidence in US:- among induvidualis over the age of 35

years : 20-25%

- over 60 years: 35-40%

Clinical Classification of Blood Pressurea

Blood Pressure Category

(mm Hg)

Diastolic <85 Normal

85-89 High normal

90-104 Mild hypertension

105-114 Moderate hypertension

115 Severe hypertension

Systolicb <140 Normal

140-159 Borderline isolated systolic hypertension

160 Isolated systolic hypertension

a Modified from The 1988 Report of the Joint National Committee on Detection.

Evaluation and Treatment of High Blood Pressure. Arch Int Med 148: 1023-1038, 1988b When diastolic blood pressure <90 mm Hg.

Etiology

90-95% of hypertension in adults has

no indentifiable

cause: primary or essential

5-10% Secondary

Principal Causes of Hypertension I.

1. Idiopathic (essential, primary)

2. Renal

A. Renovascular stenosis

1. Fibromuscular dysplasia

2. Atherosclerotic

B. Renal parenchymal disease

C. Obstructive nephropathy

Principal Causes of Hypertension II.

Adrenal

A. Medullary-pheochromocytoma

B. Cortical

1. Primary aldosteronism

a. Adrenal adenoma

b. Bilateral adrenal hyperplasia

2. Cushing’s disease

Principal Causes of Hypertension III.

Exogenous agents

A. Oral contraceptives

B. Sympathetic amines ( decongestants )

C. Nonsteroidal anti-infammatory drugs

D. High dose corticosteroid administration

E. Disorders simulating mineralocorticoid

excess

1. Licorice

2. Chewing tobacco

Principal Causes of Hypertension IV.

Miscellaneous

A. Coarctation of aorta

B. Acute stress

Determinant of normal blood pressure

Myocardial Plasma Humoral Adrenergic Arteriolar

function volume factors activity muscle tone

Heart rate Na+ balance catecholamines α-constriction autoregulation

contractility aldosterone angiotensin II. β- dilatation cell Ca 2+

stroke volume kinins

prostagladins

CARDIAC PERIPHERAL VASCULAR

OUTPUT RESISTANCE

BLOOD PRESSURE

Pathogenetic Mechanisms in Secondary Hypertension

Disorder Mediators Pathophysiologic Mechanisms

Pheochromocytoma Catecholamines Vasocontriction

Cardiac output

Primary aldosteronism Aldosterone Na+ retention

Renal artery stenosis Renin a Vasoconstriction

Aldosterone Na+ retention

Renal insufficiency GFR Na+ retention

Renin a Vasoconstriction

Cushing’s syndrome Cortisol Na+ retention

Renin substrate Vasoconstriction

Oral contraceptives Renin substrate Vasoconstriction

Estrogen Na+ retention

Aortic coarctation Renin Vasoconstriction

Aldosterone Na+ retentiona A minority of cases.

Essential Hypertension ( EH )

Thirty years ago, Page coined the term hypertension „mosaic”; his notion regarding the heterogeneity of hypertension remains highly relevant today.

Factors contributing to the development of EH:

1. Systemic hemodynamics

2. Plasma volume

3. Renin-angiotensin system

4. Sympathetic nervous system

5. Kidney

6. Dietary factors

sodium, calcium, potassium, obesity, alcohol

7. Heredity

8. Race

Effect of volume expansion on mean arterial pressure, cardiac output, and systemic vascular resistance in an anephric 22-year-old women

From T. G. Coleman, H. J. Granger, and A. C. Guyton, Circ. Res., 28 (suppl. 2): 76, 1971

Inverse relationship between plasma volume (in: milliliters per centimeter of height) and diastolic blood pressure in untreated men with essential

hypertension

From H. P. Dustan, R. C. Tarazi, E. L. Bravo, and R. A. Dart, Circ. Res., 32 (suppl. 1): 73, 1973.

Direct relationship between diastolic blood pressure and plasma volume in 11 essential hypertensive patients during chronic diuretic treatment

From H. P. Dustan, E. L. Bravo, and R. C. Tarazi, Am. J. Cardiol, 31:606, 1973.

Hemodynamic effects of the renin-angiotensin-aldosterone system

Renal hypoperfusion

Afferentarteriolar stretch

NaCl deliveryto macula densa

Renin release Sympathetic neural tone

Renin substrate Angiotensin I

Angiotensin II.

Converting enzyme

Aldosterone secretion

Renal Na+ reabsorption

Extracellular volume expansion

Systemic blood pressure

Renin release

HypotensionHypovolemia

Hemodynamic effects of the sympathetic nervous system

Effectivve circulating volume

Venous return

Cerdiac output

Blood pressure

Baroreceptor stimulation

Sympathetic tone

Venous

construction

Cardiac

contractility

Arterial

construction

Renin

secretion

Tubular Na+

reabsorption

Venous

returnHeart rate

+Vascular

resistance

Angiotensin II

formation

Cardiacoutput

Blood pressureAldosterone

secretion Effective

circulating volume

Relationship between arterial blood pressure and urinary sodium chloride and water excretion in normal subjects and in patients with hypertension

From A. C. Guyton, T. G. Colerman, a. W. Cowley, Jr. K. W. Scheel, R. D. Manning, Jr., and R. A. Norman, Jr., Am. J. Med., 52:584, 1972.

Effect of angiotensin II infusion in a dog in which renal artery pressure was initially servo-controlled at the baseline level

Frrom J. E. Hall, J. P. Granger, R. L. Hester, T. G. Coleman, M. J. Smith, Jr., and R. B. Cross, Am. J. Physiol., 246:F627, 1984.

Action of plasma membrane Na+-K+-ATPase in the renal tubule and arteriolar smooth muscle

Correlation between mean arterial pressure and intracellular free calcium concentration in platelets

From P. Erne, P. Bolli, E. Burgisser, and F. R. Buhler, N. Engl. J. Med., 310:1084, 1984.

Calcium

The prevalence of EH appears to inversaly relates to dietary calcium intake with the risk rising two to three times as daily Ca intake falls from 1200 to less than 300 mg.

There is, however, a direct correlation between mean arterial pressure and intracellular free calcium.

Mechanism (?): Contradiction: extracellular Ca++

intracellular Ca++

Hypocalcemia could promote intracellular Ca cummulation (?)

Potasium

In humans with EH K supplementation has been shown to produce a moderate fall in BP averaging 5 to 6 mmHg.

Mechanism(?): - it acts mainly in Na sensitive patients

- it may act in part by enhancing urinary

sodium excretion

Obesity

The incidence of hypertension is increased in obese patients

- increase in plasma volume

- sympathetic activity enhanced

- SVR higher

- insulin resistance increased Na retention

( insulin increase Na-K-ATP ase activity,

increased insulin resistance and secretion Na-K-

ATP ase )

Alcohol

1 or 2 drink a day 1.5 to 2 times as likely to become hypertensive

Mechanism: plasma volume ; NE ; renin ;

Na-excretion

Others

Smoking, coffeine (?)

Heredity and Race

70-80 % of patients with EH have a positive family history

Correlation's within families

between parents and children's medium,

identical twins, (high) adopted children (low)