1. Pathophysiology of vascular tone. Arterial hypertension Ph. D., M D. Nataliya Potikha

2. Regulation of arterial pressure (АP) Formula: АP = CO · PR CO – cardiac output PR – peripheral resistance (depended to arterioles tone) CO leads to PR and АP normalizes finally PR leads to CO and АP normalizes finally AP normal range: Systolic – 100 - 125 (equilibration 100 - 139) mm Hg Diastolic – 70 - 80 (equilibration 60 - 89) mm Hg

4. Regulative systems 1. Barroreceptors of aorta arch and sinus caroticus Barroreceptors of the vessels Medulla oblongata (vessel’s active center) Afferent impulses Heart (CO increase at decreased АP) Arterioles (spasm) Еfferent і impulses

5. Regulative systems 2. Renin–angiotensin system АP Activation of kidney JGA (juxta glomerular apparatus) Excretion of the RENIN (it is enzyme) Conversation angiotensin 1 into angiotensin 2 Conversation angiotensinogen into angiotensin 1 Angiotensin converting enzyme (АCE)

6. Regulative systems 3. Renin–angiotensin-aldosteron system ReninActination of suprarenal glangs (cortical layer) Na reabsorbtion in kidney increase Angiotensin 2 Aldosteron excretion Na concentration in blood increase, blood osmotic pressure increase Move of extravascular fluid inside the vessels Increase of circulative blood volume (CBV) CО increase

7. Classification Arterial hypotension Arterial hypertension Acute Chronic Secondary AP above 139/89 mm Hg Primary AP less than 100/60 mm Hg

8. AP elevation (value above 139/89 mm Hg), which is resulted from rising of peripheral vessels resistance (one of the most common cardiovascular disorders) Arterial hypertension (АH)

9. Classification Primary AH (essential, hypertonic disease) Secondary AH (that is happened in 5 - 10 % cases). It’s a symptom of some disease course

10. 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. Etiology (primary AH)

11. 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 (because 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

12. 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

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

14. 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

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

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

17. 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

18. 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)

19. 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, endothelin, angiotensin) Formula: АP = CO · PR Pathogenesis Vessels spasm

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

21. 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

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

23. 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) 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) Pathogenesis

24. Depressive function of kidney – synthesis of the substances for AP reduce PG Е 2 Phospholipid 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

25. 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

26. 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

28. Retinopathy