1. Pathophysiology of vascular tone. Arterial hypertension. Atherosclerosis. Prof. Olha V. Denefil

2. 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 %.

3. 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

4. „RULE of HALF” About 50% of people do not know about an increase of their blood pressure!!! Of those who know 50% of untreated !!! Thus, only about 25 % of patients taking medications to lower blood pressure Effective antihypertensiv e therapy have only 12-13 % of patients

5. REGULATORY SYSTEM, THAT PROVIDE STABILITY OF BLOOD PRESSURE Haemodynamic systems Systems of control Stable Arterial Pressure

6. Regulation of arterial pressure (АP)

8. Systems of AP control SYSTEM of BRIEF ACTION SYSTEM of LONG TERM ACTION Baroreceptors and chemoreceptors of aortic arch and sinocarotid zones renin - angiotensin II - arterioles angiotensin II aldosterone

12. Regulative systems of AP

16. 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

17. 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

18. Etiology of AH

19. 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 ACE 5. Lack of endothelial nitric oxide synthesis Etiology of primary AH

20. Theories 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

21. Contributing factors Family history Age-related changes in blood pressure High 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

22. 1. 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 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

23. 1.Renal (resulted from kidney pathology) Etiology secondary АH Glomerulonephritis Kidney damage at collagenosis Kidney amiloidosis Glomerulosclerosis because diabetes mellitus Nephropathy of the pregnant Hereditary defect of renal vessels Renal vessels atherosclerosis, embolism or thrombosis Kidney tumor Uri stone disease

24. 3. Angiogene (is caused by vessels pathology) 2. Renoprive (arises after kidney remove) Etiology secondary АH Aorta damage Arteries carotids damage

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

26. 5. Neurogene (is accompanying to nerves system pathology) Etiology secondary АH Brain hemorrhage Encephalitis Brain tumor Brain trauma Brain ischemia

27. 7. Drug-induced 6. Cardiac Etiology secondary АH Heart failure Heart defect Drugs, which cause vessels spasm (influent on kidney), hormonal contraceptives

28. Emotional excitement (SNS activation) Emotional excitement (SNS activation) Increase of circulative blood volume (CBV) Cardiac output (CО) increase Kidney functions violation Peripheral vessels resistance increase Pathogenesis

29. Increase of circulative blood volume (CBV) Pathogenesis Reasons NaCl (intake more 5 g/day) Decrease Na excretion by kidney (kidney diseases) Decrease Na excretion by kidney (kidney diseases)

30. 1. CBV increase Na + retention in blood Blood osmotic pressure increase Hypervolemia Cardiac output increase AP elevation Na accumulation in vessels smooth muscle wall and increase of its osmotic pressure Vessels wall edema Vessels narrowing Peripheral vessels resistance increase Vessels smooth muscle sensitivity to vasoconstrictive influences increase (noradrenalin, adrenalin, endotheline, angiotensin) Formula: АP = CO · PR Pathogenesis Vessels spasm

31. 2. Cardiac output increase (CO) Reasons Circulative blood volume increase (CBV) physical (overload) stress Emotional stress Hyperthyreosis Pathogenesis

32. 2. Cardiac output increase SAS activation Adrenalin excretion Increase of cardiac contractility force Increase of cardiac output Increase of heart beats AP elevation Pathogenesis Formula: АP = CO · PR

33. 3. SAS activation Interaction adrenalin and alpha-adrenoreceptors Arterioles smooth muscles spasm Suprarenal glands activation Venues and veins smooth muscles spasm Increase of circulative blood in big blood circle adrenoreceptors of heart Аdrenalin Noradrenalin Increase of CBV CO increase Arterioles vasoconstriction alpha-adrenoreceptors of vessels CO increase AP increase SAS activation Arterioles vasoconstriction PR increase Pathogenesis Formula: АP = CO · PR Production of catecholamine

34. 4. Kidney functions violation Long time spasm of kidney’s arteries AP increase AP decrease in renal capillaries Activation of JGA Renin excretion 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

35. Forms of 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 %)

36. Depressive function of kidney – synthesis of the substances for AP reduce PG Е 2 Phospholipids Renin Inhibitor Angiotensinase 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

37. 1st period functional violations (heart hypertrophy) 2d period Pathological 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

38. 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 failure Heart 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 sclerosis Endocrine system Glands atrophy and sclerosis Arterial hypertension after-effects

39. 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

43. Thank you for your attention!