Pathophysiology of vascular tone. Arterial hypertension. Atherosclerosis.

• Prof. Olha V. Denefil

• Increased blood pressure is found in 15-30 % of the adult population in the world. There are significant differences in this indicator over the world: from 6 % - in Africa to 30-35 % - in the Scandinavian countries, in the USA is 23-31 %, in Ukraine – nearly 40 %.

• Arterial hypertension is a major risk factor of many pathological conditions and diseases of the cardiovascular system:

• atherosclerosis• left ventricular hypertrophy and

heart insufficiency,• ischemic heart disease

(myocardial infarction)• cerebrovascular disease

(ischemic and hemorrhagic brain stroke)

• renal insufficiency

„RULE of HALF”

About 50% of people do not know about an increase

of their blood pressure!!!

Of those who know50% of untreated!!!

Thus, only about 25 % of patients taking medications to

lower blood pressure

Effective antihypertensive therapy have only 12-13 % of

patients

REGULATORY SYSTEM,THAT PROVIDE

STABILITY OF BLOOD PRESSURE

Haemodynamic systems Systems of control

Stable Arterial Pressure

Regulation of arterial pressure (АP)

Systems of AP control

SYSTEMof BRIEFACTION

SYSTEMof LONG TERM

ACTION

Baroreceptors andchemoreceptors of

aortic arch and sinocarotid zones

renin -angiotensin II -

arterioles

angiotensin IIaldosterone

Regulative systems of AP

Regulative systems of AP

Regulative systems of AP

Classification

Arterial hypotension

Arterial hypertension

Acute(collapse)

Chronic

(hypotonic disease, symptomatically)

Secondary (symptomatically)

AP above 139/89 mm Hg

Primary(essential)

AP less than 100/60 mm Hg

Classification

Primary AH (essential, hypertonic disease)

80 % of all increase of AP

Secondary AH (that is happened in 5 - 10 % cases).

It’s a symptom of some disease course

Etiology of AH

Reason is unknown (AH is polyetiological disease).AH arises on the ground of genetically peculiarities of

metabolism. That is possible to have genetically defect of the systems, which

control relaxation of the smooth muscle cells of the arterioles.It is possible to:

1. Hereditary defect of Ca-ATPase (myocyte relaxation of arterioles involves the movement of Ca in the sarcoplasmic

reticulum against the concentration gradient)2. Genetically caused sodium retention in the body

3. The variability of the gene that controls the synthesis of receptors for angiotensin 2

4. Genetically caused by increased activity of ACE5. Lack of endothelial nitric oxide synthesis

Etiology of primary AH Etiology of primary AH

Theories of primary hypertensionTheories of primary hypertension• 1. Recognized the leading role of the nervous system

• Essence: disorders of the nervous regulation of vascular tone

• against failure mechanisms of hormonal regulation of arteriolar tone carried over earlier kidney disease, age-related changes in blood vessels, endocrine disorders during menopause

• 1. Recognized the leading role of the nervous system

• Essence: disorders of the nervous regulation of vascular tone

• against failure mechanisms of hormonal regulation of arteriolar tone carried over earlier kidney disease, age-related changes in blood vessels, endocrine disorders during menopause

• 2. Recognized the leading role of the kidneys

• Essence: imbalance pressor and depressor functions

• Increased vascular tone occurs on the background of exhaustion

depressor of kidneys

• 2. Recognized the leading role of the kidneys

• Essence: imbalance pressor and depressor functions

• Increased vascular tone occurs on the background of exhaustion

depressor of kidneys

Contributing factorsFamily history

Age-related changes in blood pressureHigh salt intake

Stress

Hyperinsulinemia:

causes high activity sympathetic link of ANS and its effect on cardiac output, peripheral vascular resistance and renal sodium retention;

stimulates sodium and calcium transport across the cell membrane of vascular smooth muscle, thereby sensitizing blood vessels to vasopressor stimuli

Obesity (hyperinsulinemia)Excess alcohol consumption

(mechanism in unclear)

Race

(for example: AH isn’t only more prevalent in African Americans than whites, it is also more severe).

Possible explanation: due to evolutionary adaptation to the severe environment (western Africa and Western hemisphere) in condition of salt and water deprivation survival is possible due to retention of sodium and water in organism. That leads to conserve sodium.

There is little information about other racial groups

1. Increased blood volume1. Increased blood volume

Pathogenesis

Causes

NaCl (use of more than 5 g per day) - mountain population of Japan, the

Ukrainian Carpathian and Crimean often suffer from hypertension disease

due to the use of water that contains a lot

of NaCl

NaCl (use of more than 5 g per day) - mountain population of Japan, the

Ukrainian Carpathian and Crimean often suffer from hypertension disease

due to the use of water that contains a lot

of NaCl

Reduced of Na+ excretion by the kidneys(kidney disease)

Reduced of Na+ excretion by the kidneys(kidney disease)

Genetically caused decrease Na excretion by the kidneys

Genetically caused decrease Na excretion by the kidneys

1. Renal (resulted from kidney pathology)

Etiologysecondary АHEtiologysecondary АH

GlomerulonephritisGlomerulonephritis

Kidney damage at collagenosis

Kidney damage at collagenosis

Kidney amiloidosisKidney amiloidosis

Glomerulosclerosis because diabetes mellitus

Glomerulosclerosis because diabetes mellitus

Nephropathy of the pregnant

Nephropathy of the pregnant

Hereditary defect of renal vessels

Hereditary defect of renal vessels

Renal vessels atherosclerosis, embolism or thrombosis

Renal vessels atherosclerosis, embolism or thrombosis

Kidney tumorKidney tumor

Uri stone diseaseUri stone disease

3. Angiogene(is caused by vessels pathology)

2. Renoprive (arises after kidney remove)

Etiologysecondary АHEtiologysecondary АH

Aorta damageAorta damage Arteries carotids damage

Arteries carotids damage

4. Endocrinopathy (develops in the result of endocrine glands pathology)

Etiologysecondary АHEtiologysecondary АH

Cushing's disease (Adrenocorticotropin over production by

the pituitary gland anterior part)

Cushing's disease (Adrenocorticotropin over production by

the pituitary gland anterior part)

Acromegaly (Somatotropin over production by

the pituitary gland anterior part)

Acromegaly (Somatotropin over production by

the pituitary gland anterior part)

Hyperaldosteronism (aldosteron over excretion by suprarenal

glands)

Hyperaldosteronism (aldosteron over excretion by suprarenal

glands)

Menopause(age-depended decrease of female

gonads activity – estrogens excretion decrease)

Possible mechanism – deficit of NO synthesis by endotheliocytes

Menopause(age-depended decrease of female

gonads activity – estrogens excretion decrease)

Possible mechanism – deficit of NO synthesis by endotheliocytes

5. Neurogene (is accompanying to nerves system pathology)

Etiologysecondary АHEtiologysecondary АH

Brain hemorrhageBrain hemorrhage

EncephalitisEncephalitis

Brain tumorBrain tumor

Brain traumaBrain trauma

Brain ischemiaBrain ischemia

7. Drug-induced

6. Cardiac

Etiologysecondary АHEtiologysecondary АH

Heart failureHeart failureHeart defectHeart defect

Drugs, which cause vessels spasm (influent on kidney), hormonal contraceptives

Drugs, which cause vessels spasm (influent on kidney), hormonal contraceptives

Emotional excitement (SNS activation)

Emotional excitement (SNS activation)

Increase of circulative blood volume (CBV)Increase of circulative blood volume (CBV)

Cardiac output (CО) increaseCardiac output (CО) increase

Kidney functions violationKidney functions violation

Peripheral vessels resistance increasePeripheral vessels resistance increase

Pathogenesis

Increase of circulative blood volume (CBV)Increase of circulative blood volume (CBV)

Pathogenesis

Reasons

NaCl (intake more 5 g/day) NaCl (intake more 5 g/day)

Decrease Na excretion by kidney

(kidney diseases)Decrease Na excretion by kidney

(kidney diseases)

1. CBV increase1. CBV increase

Na+ retention in bloodNa+ retention in blood

Blood osmotic pressure increase

Blood osmotic pressure increase

HypervolemiaHypervolemia

Cardiac output increaseCardiac output increase

AP elevationAP elevation

Na accumulation in vessels smooth muscle wall and increase of its

osmotic pressure

Na accumulation in vessels smooth muscle wall and increase of its

osmotic pressure

Vessels wall edemaVessels wall edema

Vessels narrowingVessels narrowing

Peripheral vessels resistance increasePeripheral vessels

resistance increase

Vessels smooth muscle sensitivity to

vasoconstrictive influences increase

(noradrenalin, adrenalin, endotheline, angiotensin)

Vessels smooth muscle sensitivity to

vasoconstrictive influences increase

(noradrenalin, adrenalin, endotheline, angiotensin)

Formula: АP = CO · PRFormula: АP = CO · PR

Pathogenesis

Vessels spasm

Vessels spasm

2. Cardiac output increase (CO)2. Cardiac output increase (CO)

Reasons

Circulative blood volume increase (CBV)

Circulative blood volume increase (CBV)

physical (overload) stress

physical (overload) stress

Emotional stress Emotional stress

HyperthyreosisHyperthyreosis

Pathogenesis

2. Cardiac output increase2. Cardiac output increase

SAS activationSAS activation

Adrenalin excretionAdrenalin excretion

Increase of cardiac contractility force

Increase of cardiac contractility force

Increase of cardiac output

Increase of cardiac output

Increase of heart beats Increase of heart beats

AP elevationAP elevation

Pathogenesis

Formula: АP = CO · PRFormula: АP = CO · PR

3. SAS activation3. SAS activation

Interaction adrenalin and alpha-adrenoreceptors

Interaction adrenalin and alpha-adrenoreceptors

Arterioles smooth muscles spasm

Arterioles smooth muscles spasm

Suprarenal glands activationSuprarenal glands activation

Venues and veins smooth muscles

spasm

Venues and veins smooth muscles

spasm

Increase of circulative blood in big blood

circle

Increase of circulative blood in big blood

circle adrenoreceptors of

heartadrenoreceptors of

heart

АdrenalinАdrenalinNoradrenalinNoradrenalin

Increase of CBVIncrease of CBV

CO increaseCO increase

Arterioles vasoconstriction

Arterioles vasoconstriction

alpha-adrenoreceptors of vessels

alpha-adrenoreceptors of vessels

CO increaseCO increase

AP increaseAP increase

SAS activationSAS activation

Arterioles vasoconstriction

Arterioles vasoconstriction

PR increasePR increase

Pathogenesis

Formula: АP = CO · PRFormula: АP = CO · PR

Production of catecholamineProduction of catecholamine

4. Kidney functions violation4. Kidney functions violation

Long time spasm of kidney’s arteries

Long time spasm of kidney’s arteries

AP increaseAP increase

AP decrease in renal capillaries

AP decrease in renal capillaries

Activation of JGAActivation of JGA

Renin excretionRenin excretion

Angiotensin 2 synthesis

Angiotensin 2 synthesis

Angiotensin 2 effects

• Smooth muscles contraction in the vessels

• Stimulation of the vasoactive center in brain

• Noradrenalin excretion increase• Adrenalin excretion increase from

suprarenal glands• Aldosteron excretion increase from

suprarenal glands (Na retention due to kidney)

• Activation of Na and water reabsorption in the kidney without aldosterone

Angiotensin 2 effects

• Smooth muscles contraction in the vessels

• Stimulation of the vasoactive center in brain

• Noradrenalin excretion increase• Adrenalin excretion increase from

suprarenal glands• Aldosteron excretion increase from

suprarenal glands (Na retention due to kidney)

• Activation of Na and water reabsorption in the kidney without aldosterone

Pathogenesis

Formsof hypertensive

disease

Decrease concentration

of rennin in blood (25-30%)

Increase concentration

of rennin in blood (10-20 %)

Norm concentration of rennin in blood

(55-60 %)

Depressive function of kidney – synthesis of the substances for AP reduce

Depressive function of kidney – synthesis of the substances for AP reduce

PG Е 2PG Е 2

Phospholipids Renin Inhibitor

Phospholipids Renin Inhibitor

AngiotensinaseAngiotensinase

Phosphatydilcholin alkali ethers

Phosphatydilcholin alkali ethers

! ! !

Exhaustion of kidney depressive function

leads to arterial hypertension stabilization

dilates renal arteries, reduces renin synthesis and reduces Na

reabsorbing in kidney

dilates renal arteries, reduces renin synthesis and reduces Na

reabsorbing in kidney

1st period

functional violations

(heart hypertrophy)

2d periodPathological changes in arteries and arterioles (dystrophy):- Arterioles sclerosis

- Arteriole’s wall infiltration by plasma (leads to dystrophy)

- Arterioles necrosis (hypertonic crisis arises in clinic)

- Vein’s wall thickening

Arterial hypertension after-effects

3d period

Secondary changes in organs and systems

Kidney

(nephrosclerosis and chronic kidney insufficiency)

Kidney

(nephrosclerosis and chronic kidney insufficiency)

CNS

– brain hypoxia

– neurons destruction

– apoplexy (because vessels destruction and rupture leads to brain hemorrhages and brain destruction)

CNS

– brain hypoxia

– neurons destruction

– apoplexy (because vessels destruction and rupture leads to brain hemorrhages and brain destruction)

Heart

Decompensate heart failureHeart

Decompensate heart failure

Organs of vision- retinopathy (retina’s vessels injury)- hemorrhages and separation (exfoliation) of

retina, that leads to blindness

Organs of vision- retinopathy (retina’s vessels injury)- hemorrhages and separation (exfoliation) of

retina, that leads to blindness

Endocrine system

Glands atrophy and sclerosisEndocrine system

Glands atrophy and sclerosis

Arterial hypertension after-effects

Pathogenetic principles of treatment

1. Decrease of consumption and increased excretion of fluid and Na+ - decrease of CBV and vascular sensitivity to pressor effects

• 2. Decrease of emotional and physical stress - decrease CNS activity (including sympathoadrenal activity)

• 3. Block of adrenoreceptors - reduce the effects of catecholamine in the heart, i.e. CO

• 4. Block of adrenoreceptors - reduce the effects of catecholamines in the arterioles, i.e. reducing vasomotor arteriolar tone

• 5. Block of ACE - reduce the formation of angiotensin 2 - decrease basal arteriolar tone

• 6. Decrease the effects of angiotensin 2 - blocking receptors for angiotensin 2 - decrease basal arteriolar tone

• 7. Decrease admission of Ca in myocytes of arterioles - decrease basal arteriolar tone

• 8. Increase of depressor kidney function - decrease basal arteriolar tone

• 9. Increase of vasodilator function of blood vessels involving nitric oxide - reducing basal arteriolar tone

1. Decrease of consumption and increased excretion of fluid and Na+ - decrease of CBV and vascular sensitivity to pressor effects

• 2. Decrease of emotional and physical stress - decrease CNS activity (including sympathoadrenal activity)

• 3. Block of adrenoreceptors - reduce the effects of catecholamine in the heart, i.e. CO

• 4. Block of adrenoreceptors - reduce the effects of catecholamines in the arterioles, i.e. reducing vasomotor arteriolar tone

• 5. Block of ACE - reduce the formation of angiotensin 2 - decrease basal arteriolar tone

• 6. Decrease the effects of angiotensin 2 - blocking receptors for angiotensin 2 - decrease basal arteriolar tone

• 7. Decrease admission of Ca in myocytes of arterioles - decrease basal arteriolar tone

• 8. Increase of depressor kidney function - decrease basal arteriolar tone

• 9. Increase of vasodilator function of blood vessels involving nitric oxide - reducing basal arteriolar tone

Thank you for your attention!