Cardiovascular Pathophysiology-Hypertension

1. Cardiovascular Pathophysiology
Hypertension
Dr. Vishal Balakrushna Jadhav
Assistant Professor (Pharmacology)
School of Pharmaceutical Sciences (SOPS), SUN
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2. Content
 Definition of Hypertension
 JNC-WHO/ISH Clinical Classification of Hypertension
 General Classification of Hypertension
 Etiopathogenesis of Hypertension
 Pathological Changes
 Clinical Features
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3. Definition of Hypertension
 Arterial or systemic hypertension in patient is defined clinically
as borderline- if systolic/diastolic B.P. > 140/90 mm Hg. It is
sometime refer to as mild or borderline hypertension.
 Hypertensive or moderate hypertension is defined clinically if
systolic/diastolic B.P. > 160/100 mm Hg.
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4. JNC-WHO/ISH Clinical Classification of Hypertension
Sr. No. Category
B.P. in mm Hg
Systolic B.P. Diastolic B.P.
1 Normal < 130 < 85
2 High normal 130-139 85-89
3 Hypertension
3a Mild, stage- I 140-159 90-99
3b Moderate, Stage- II 160-179 100-109
3c Severe, Stage- III 180-209 110-119
3d Very severe, Stage- IV ≥ 210 ≥ 120
4 Malignant > 200 ≥ 140
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5. General Classification of Hypertension
 Primary or essential (Idiopathic) hypertension- It is the type of
hypertension in which the cause of an increased B.P. is unknown. It
constitutes about 90-95% patients of hypertension.
 Secondary hypertension- It generally caused by disease of kidneys,
endocrines and some other organs. It comprises about 5-10% cases.
According to clinical course, the primary and secondary hypertension may be-
benign- characterized by moderate elevation of B.P. and rise is slow over the
years, and malignant, characterized by marked and rapid rise of B.P. to
systolic/diastolic B.P. 200/140 mm Hg.
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6. Etiopathogenesis of Hypertension
 Etiopathogenesis of secondary hypertension is well known, but primary one
remains unclear.
 Cardiac output (CO) and total peripheral resistance (TPR) regulates BP. Any
alteration in CO and TPR leads to hypertension.
 Anti-diuretic hormone (ADH) and renin- angiotensin- aldosterone system
(RAAS) of kidneys catalyzes long term regulation of B.P.
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7. Primary or essential hypertension
 Unidentified cause
 Factors responsible-
a. Genetic factors- Suspected role of heredity in etiology of hypertension.
Evidences which supports their involvement are-
 Familial aggregation,
 Occurrence of hypertension in the twins,
 Epidemiological data,
 Experimental animal studies,
 Identification of hypertensive susceptible gene (angiotensinogen gene)
b. Racial and environmental factors-
 Blacks are more prone than whites.
 Salt intake, obesity, skilled occupation, higher living standards, and high stress are
environmental factors.
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8. c. Risk factors modifying the cause of essential; hypertension are-
 Age- Hypertension is noted mostly in young. If untreated, decreases their life
expectancy.
 Sex- Females are more prone towards hypertension then males.
 Accelerated atherosclerosis- due to cigarette smoking, elevated serum cholesterol,
glucose intolerance and obesity etc.
 Other risk factors like smoking, excessive alcohol consumption, diabetes mellitus,
persistent high diastolic B.P. > 115 mm Hg and evidence of end organ damage
(heart, eyes, kidneys, nervous system).
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9. Pathogenesis of primary or essential hypertension-
 High plasma concentration of catecholamines (adrenal medullary
hormones- adrenaline and nor-adrenaline),
 Increased blood volume (arterial overfilling- volume hypertension and
arteriolar constriction- vasoconstrictor hypertension),
 Increased cardiac output (CO),
 Low renin secretion (as a leading cause in 20% of essential hypertensive
patients), and
 High renin secretion (as a leading cause in 15% of patients, shows
decrease adrenal responsiveness to angiotensin-II, AT-II)
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10. Secondary hypertension
 Well identified cause
 On the basis of etiology, it includes-
1) Renal hypertension,
2) Endocrine hypertension,
3) Coarctation of aorta, and
4) Neurogenic hypertension.
 Renal hypertension The most prominent form of secondary
hypertension.
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11. Renal hypertension
 Caused by renal diseases, characterized by renal vascular hypertension
and renal parenchymal hypertension.
a) Renal vascular hypertension
seen in major renal artery occlusion, pre-eclampsia, eclampsia, polyarteritis nodosa, and
fibromuscular dysplasia of renal artery.
b) Renal parenchymal hypertension
seen in various types of glomerulonephritis, pyelonephritis, interstitial nephritis, diabetic
nephropathy, amyloidosis, polycystic kidney disease, and renin secretory tumours.
 Mechanisms causing a or b
 Activation of RAAS,
 Sodium (Na+) and water (H2O) retention, and
 Release of vasodepressor materials 11

12.  Activation of RAAS
 Trigger stimuli like sympathetic overactivity, renal ischaemia, depressed Na+
concentration, fluid depletion, decreased K+ intake stimulates the granules of
Juxtaglomerular cells to release of renin, a proteolytic enzyme.
 Released renin then transported to the liver via blood circulation which
converts angiotensinogen, plasma α2 globulin (synthesized in liver) into
angiotensin I (AT-I, an inactive decapeptide).
 ACE converts AT-I into angiotensin II (AT-II, an active octapeptide having
vasoconstrictor action).
 Vasoconstrictor AT-II induces peripheral arteriolar constriction, stimulates
adrenal cortex, leads to the release of aldosterone which induces reabsorption
of sodium (Na+) and water (H2O), increase secretion of K+ and H+ into the
urine, increases blood volume and BP, and thereby develops hypertension. 12

13.  Sodium (Na+) and water (H2O) retention
Blood volume and cardiac output (CO) are regulated mainly by blood level of Na+.
Mechanisms that regulate blood concentration of Na+ ions are-
 Release of aldosterone from activation of RAAS,
 Reduction in GFR due to reduced blood flow as seen in reduced renal mass and
renal artery stenosis, and
 Release of atriopeptin or atrial natriuretic peptide (ANP), the hormone secreted
from atria of the heart in response to stretching of the atrial wall. It decreases
reabsorption of Na+ and H2O from the proximal convoluted tubules and
collecting ducts.
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14.  Release of vasodepressor materials
 Vasodepressors causes fall in blood pressure by reducing peripheral resistance.
 Both the vasodepressor and antihypertensives counterbalance the vasoconstrictor
response of AT-II.
 These vasodepressors includes-
a) Prostaglandins released from interstitial medullary cells,
b) Urinary kallikrein-kinin system, and
c) Platelet activating factor (PAF).
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15. Endocrine hypertension
 Hyperactivity of endocrine hormones induced hypertension.
 Adrenal glands releases aldosterone, e.g. in primary aldosteronism,
Cushing syndrome, adrenal virilism and pheochromocytoma,
 Parathyroid gland secretes parathyroid hormone (PTH), e.g. in
hypercalcaemia, and in hyperparathyroidism,
 Oral contraceptives- Estrogen component of oral contraceptive mainly
stimulate hepatic synthesis of renin substrate (angiotensinogen).
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16. Coarctation of aorta
 It causes systolic hypertension in upper part of the body due to
constriction itself.
 Diastolic hypertension results due to change in circulation.
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17. Neurogenic hypertension
 The uncommon causes of secondary neurogenic hypertension are-
 Psychogenic/ psychological cause,
 polyneuritis,
 increased cranial pressure, and
 section of spinal cord.
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18. Pathological changes
 Cardiovascular changes-
Heart-
Grossly Concentric hypertrophy of left ventricular wall, increased
thickness and increased heart weight, intact pericardium, myocardium, and
heart valves, and dilatation of left ventricular wall in left ventricular failure.
Microscopically Enlarged myocytes with increased transverse diameter,
marked disorganization of myocytes, regressive alterations with loss of
myofibrils, disruption of Z-bands, loss of linear array of sarcomeres with
sharp angulations of myocytes, random cell atrophy and death, and increased
interstitial fibrosis.
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19. Blood vessels-
Grossly thickening and fibrosis of blood vessels wall along with narrowing
of lumina.
Microscopically
 Primary hypertension causes arteriolar hyalinisation, reduplication of
elastic lamina and fibroelastic hyperplasia in median of vessels,
 Secondary hypertension causes fibrinoid necrosis of arteries (necrotizing
arteriolitis) and hyperplastic arteriolitis that is onion skinning of arterioles
with marked narrowing of lumen.
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20. Renal changes-
Benign nephrosclerosis in primary hypertension and malignant
nephrosclerosis in secondary hypertension.
 Benign nephrosclerosis
Grossly Normal or moderately reduced size of kidney, presence of fine
granules on cortical surface, and cut section shows loss of mass due to
cortical narrowing.
Microscopically the changes are predominantly vascular.
Other changes are tubercular atrophy and intestinal fibrosis, glomerular
alterations like collapse of glomerular basement membrane, deposition of
collagen within the Bowman’s capsule, periglomerular fibrosis and total
sclerosis of the glomeruli.
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21.  Malignant nephrosclerosis
Grossly Variation in kidney size is due to severity in hypertension. The
cortical surface shows the presence of small pinpoint patechial hemorrhages.
Microscopically the changes are predominantly vascular.
Other changes are ischaemic atrophy and infarction due to vascular changes.
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22. Clinical Features
 Primary hypertension-
Gradual or insidious onset, usually detected many years or decades after
its onset. Sometimes the patients presents with the complications like
IHD, MI, cerebrovascular accidents, LVF or chronic renal failure.
Complications may cause morbidity or mortality.
 Secondary hypertension-
Clinically characterized by diastolic pressure >130 mm Hg. Papilloedema,
encephalopathy, cardiovascular abnormalities and renal failure are the
major clinical features. Patients may suffer from hypertensive crisis and
increased intracranial pressure. Death in malignant hypertension is caused
by uraemia (in 90% of cases) and cerebral hemorrhage or cardiac failure.
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