Download - Pathophysiology of vascular tone. Arterial hypertension. Atherosclerosis. Prof. Olha V. Denefil
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!