Physiological Aspects of Major Cardiovascular Pathologies: Arterial Hypertension Ischemic Heart Disease Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Dept. of Physiology, Faculty of Medicine, Masaryk University Ischemic Heart Disease Coronary Circulation Right coronary Left coronary artery artery a. cor. sinistra (85%) a. cor. dextra Marginal branch epicardial coronary arteries intramuscular arteries plexus of subendocardial arteries Circumflex branch Anterior descending branch Septal branches Marginal branch Posterior descending branch Ganong's Review od Medical Physiology, 23rd edition Epicardial coronary arteries Cardiac muscle j Guyton and Hall. Textbook of Medical Physiology, 11th edition Subendocardial arterial plexus Coronary Circulation • the resting blood flow: 225 ml/min (4-5% of CO) • increases at physical exertion, mental stress, • 02 extraction is almost maximal already at rest, capillaries are open • The only possibility how to increase 02 supply is the coronary vasodilation! • metabolic vasodilation, sympathicus/parasympathicus z oronary Reserve • ability of coronary vessels to adapt blood flow to the actual cardiac work (ergometry) • the maximal blood flow / the resting blood flow • reduction of the coronary reserve: - relative coronary insufficiency (too high resting demands, high resting blood flow cannot be sufficiently increased) - absolute coronary insufficiency (~ ischemic heart disease) (the stenotic arteriosclerotic process) Reduced coronary reserve is a limiting factor of the cardiac output, thus, also of the effort of organism! Ischemic Heart Disease = ischemic heart disease, coronary artery disease • the most often cardiac disease in Western culture • about 1/3 of all deaths • VS. myocardial ischemia (a more general term; anaemia, hypotension, myocardial hypertrophy, thyreotoxicosis) • causes of death: - acute coronary occlusion - ventricular fibrillation - slow, progressive weekening of contractility due to slowly increasing myocardial ischemia (the most often cause of the congestive heart failure) f Y Ischemic Heart Disease pathogenesis: atherosclerotic process of one or more branches of the coronary circulation Hyöirlpdüfflia, ■ ■ypo-lt-Liör. http://www.medecine.unige.ch/recherche/groupes/ b_donnees/sujet_591 _4.html EiyJütwiium Inn iift- C:ni.-;i':J3liJl3r ■:i!'-s arid rtöfMöt Ö6l4 MgiKlKino' PnjgrfHirvc Ekveapmcnl a! ar|»*f«KMrottC piftiqut z Ischemic Heart Disease pathogenesis: atherosclerotic process of one or more branches of the coronary circulation endothelial cells thrombocytes inflammatory cells thrombus rupture of thin fibrous cover smooth y muscle cells lipid core w ~ - . t ' ■ ■. P 100 Mm http://int2.lf1 .cuni.cz/pruvodce-pro-pacienty-pred-katetrizacnim-vysetrenim-srdce http://www.thno.org/v03p0894.htm Ischemic Heart Disease • pathogenesis: atherosclerotic process of one or more branches of the coronary circulation • symptoms (always when blood inflow demands exceed the capacity of stenotic artery): - pain behind the sternum (angina pectoris) - changes of ST segment and T wave on ECG due to sooner repolarization in the ischemic myocardial region, usually in the subendocardium Symptoms are usually provoked by physical exertion, cold, rapid increase of the blood pressure, etc. z Ischemic Heart Disease pathogenesis: atherosclerotic process of one or more branches of the coronary circulation acute coronary occlusion due to: - thrombus (rupture of the plaque) - embolus - local muscular spasm Inf iky Vznik trombu R te ii ve . Lipidov iädro ■2- "V, '^-r .^V- Ischemic Heart Disease Guyton and Hall. Textbook of Medical Physiology, 11th edition pathogenesis: atherosclerotic process of one or more branches of the coronary circulation acute coronary occlusion due to: - thrombus (rupture of the plaque) - embolus - local muscular spasm The degree of damage of the heart muscle is determined to a great extent by the degree of collateral circulation! Ischemic Heart Disease Myocardial infarction = sudden closure of a coronary branch, usually by a thrombus originating on the strength of a rupture of the atherosclerotic plate, changes are irreversible • symptoms: - severe unremitting pain behind sternum - heart failure (in the case of a bigger extent) - on ECG: ST elevation followed by T wave without any decrease to the isoelectric line (the Pardee S Sign) http://www.wikiskripta.eu/ . .. . index.php/Popis_EKG • healing by a scar (a sign of non-conductive tissue remains on ECG - a deep Q wave) z Ischemic Heart Dise Myocardial infarction TQ depression due to depolarization of RMP (accumulation of k* in ect> TQ depression Ischemic Heart Disesi ™ Myocardial infarction TQ depression due to depolarization of RMP (accumulation of k+ in ect) ST elevation due to shortening of AP and delayed depolarization ST elev. TQ depression Ischemic Heart Disease Myocardial infarction Ganong's Review od Medical Physiology, 23rd edition A. Physiological tracing in lead I B. Myocardial infarction - acute phase - hours from infarction. C. Many hours till days from infarction. D. Late pattern - many days till weeks from infarction. E. Very late pattern - months till years from infarction. Ischemic Heart Disease Treatment with drugs - VaSOdilatOry drugs (nitroglycerine, other nitrate drugs) - Beta-blockers (propranolol) Ischemic Heart Disease Surgical treatment Coronary Angioplasty obnovení normálního krevního proudu http ://www. i ke m. cz/www?doci d= 1005912 Aortic-Coronary Bypass Aorta Bypass (štěp z kryté žíly) Closure of a coronary artery http://www.sedmstatecnych.cz/clanek/opr avene-srdce-po-trech-letech/ z Arterial Hypertension Definition and Consequences rtenai nypertension - cnronic increase o blood pressure. Symptoms indistinctive and nonspecific in the first stages of hypertension ->• almost 50% of the hypertensive patients do not know about their hypertension! If not diagnosed in time and adequately treated, arterial hypertension results in: ❖ overload of the left ventricle (hypertrophy, heart failure) ❖ arteriosclerosis increased risk of the myocardial infarction increased risk of the stroke the renal failure, etc. Hypertension significantly shortens the life span. e systemic Definition and Consequences Arterial hypertension - chronic increase of the systemic blood pressure. Table 1 Definitions and classification of blood pressure (BP) levels (mmHg) Category Systolic Diastolic Optimal <120 and <80 Normal High normal Grade 1 hypertension Grade 2 hypertension Grade 3 hypertension Isolated systolic hypertension 120-129 130-139 140-159 160-179 >180 >140 and/or and/or and/or and/or and/or and 80-84 85-89 90-99 100-109 >110 <90 Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462-1536. 24-hours Monitoring of Blood Pressure Definition and Consequences Arterial hypertension - chronic increase of the systemic blood pressure. Table 1 Definitions and classification of blood pressure (BP) levels (mmHg) Category Systolic Diastolic Optimal <120 and <80 Normal . 120-129 . prehypertension „ I High normal M yM 130-139 and/or and/or 80-84 85-89 Grade 1 hypertension Grade 2 hypertension Grade 3 hypertension Isolated systolic hypertension 140-159 160-179 >180 >140 and/or and/or and/or and 90-99 100-109 >110 <90 Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462-1536. Definition and Consequences Arterial hypertension - chronic increase of the systemic blood pressure. Table 1 Definitions and classification of blood pressure (BP) levels (mmHg) Category Systolic Diastolic Optimal Normal High normal Grade 1 hypertension <120 120-129 130-139 140-159 and and/or and/or and/or <80 80-84 85-89 90-99 Grade 2 hypertension Grade 3 hypertension Isolated systolic hypertension 160-179 >180 >140 and/or and/or and 100-109 >110 <90 Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462-1536. Definition and Consequences Stratification of cardiovascular risk Blood pressure (mmHg) Other risk factors, OD or Disease Normal SBP 120-129 or DBP 80-84 High normal SBP 130-139 or DBP 85-89 Grade 1 HT SBP 140-159 or DBP 90-99 Grade 2 HT SBP 160-179 or DBP 100-109 Grade 3 HT SBP>180 or DBP>110 No other risk factors Average risk Average risk Moderate added risk High added risk 1-2 risk factors IVlOderate ffdded risk Moderate added risk Very high added risk 3 or more risk factors, MS, OD or Diabetes Moderate added risk High,*'' aadefl risk High added risk High added risk Very high added risk Established CV or renal disease Very high added risk Very high added risk Very high added risk Very high added risk Very high added risk Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462-1536. Definition and Consequences in children and adolescents - special percentile tables Factors Determining Blood Pressure U = I. R P = CO.TPR arterial pressure cardiac output total peripheral resistance TPR * T Cardiac Output (usually due to T extracellular fluid) —volume-loading (hyperdynamic) hypertension * T total peripheral resistance —> resistance hypertension Factors Determining Blood Pressure U = I. R P = CO.TPR arterial pressure cardiac output total peripheral resistance TPR * T Cardiac Output (usually due to T extracellular fluid) —volume-loading (hyperdynamic) hypertension * T total peripheral resistance —> resistance hypertension C = AV / AP * 4 compliance isolated systolic hypertension kidneys regulation of blood volume heart CO = SV.HR HR is guided by sympathetic and parasympathetic system SV depends on: 1 .venous return (blood volume, tonus of veins) 2.contractilitv 3.peripheral pressure ,— A. Cardiovascular system veins blood reservoire 64% Veins 9* Lungs Heart*" 5% (diastole! g% 7% Capillaries Lesser arteries Greater and arterioles arteries Volume distribution Brain: Q = 13% 47 % Lesser arteries and arterioles 7* 1 i 27* Capillaries 19* Arteries 7* Veins Pulmonary artery Blood pressure: 25,'lOmmHg (mean; 15mmHg) \ J Lungs Low-pressure system (reservoir function) A Coronary ^\ circulation Q = Resistance distribution in systemic circulation Aorta Blood pressure: 120/80 mmHg (mean: 100 mmHg) í Liver and gastrointestinal tract Q =24% Vor 23% Skeletal muscle Q =21% V0 = 27* High-pressure system (suppfy function) Blood flow to organs as * of cardiac output (resting CO 5.6 L.'min at body weight of 70 kg) Skin and other organs Organ CK consumption as % of total O3 consumption f (total at rest- 0.25 U min) / arterioles regulation of TPR kidneys regulation of blood volume also TPR (RAS) heart CO = SV.HR HR is guided by sympathetic and parasympathetic system SV depends on: 1 .venous return (blood volume, tonus of veins) 2.contractilitv 3.peripheral pressure r- A. Cardiovascular system veins blood reservoire B. Vasoconstriction and vasodilatation Pressor area T \ la Neuronal Sympathetic tonus Vessel stretch 2a local Myogenic reaction Pr 02 Endothelin-1 (ETA) - ^ PGF2a, thromboxane ADH (Vi), epinephrine, angiotensin II — E C O u 3a Hormonal 1b Neuronal P = CO . TPR Sympathetic tonus y Parasympathetic system (salivary glands, genitalia) r02v Adenosine, Pcc,2, H\K+ etc. NO PGE2,PGI2y 2b local Bradykinin, kallidin Epinephrine (ß2) Acetylcholine (M), ATP, 3b histamine (Ht), Hormonal endothelin-1 (ETB) Despopoulos; Color Atlas of Physiology © 2003 Thierme aorta and big elastic arteries compliance arterioles regulation of TPR kidneys regulation of blood volume, also TPR (RAS) heart CO = SV.HR HR is guided by sympathetic and parasympathetic system SV depends on: 1 .venous return (blood volume, tonus of veins) 2.contractilitv 3.peripheral pressure ,— A. Cardiovascular system veins blood reservoire heart CO = SV.HR HR is guided by sympathetic and parasympathetic ,— A. Cardiovascular system 64% Veins 9% Lungs Heart"" 5% (diastole) g% J% Capillaries Lesser arteries Greater /f ~T—" and arterioles arteries / ' 7% 47 % Lesser arteries and arterioles P = CO . TPR 27% 19% A-teries 7% Veins aorta and big Pathophysiology of hypertension is very complex, thus, usually hard to be analyzed in a concrete patient! LUII UILJJUIL JJJIL (reservoir function) í Liver and gastrointestinal tract „ Q =24% Skeletal muscle Q = 21* v0 = 27* Blood flow to organs as % of cardiac output (resting CO 5.6 L.'min at body weight of 70 kg) Skin and other organs ■• Organ CK consumption as % of total O3 consumption f (total at rest - 0.25 L/min) arterioles regulation of TPR regulation of blood volume - kidneys - thirst - ADH ^.contractility 3.peripheral pressure veins blood reservoire Classification A. Essential (primary) hypertension • ..hypertension of an unknown origin" • 90-95% B. Secondary (symptomatic) hypertension • symptom of another primary disease with identifiable cause Essential Hypertension ❖ strong hereditary tendency in some patients (polygenic ground - genetic defects, often polymorphisms, causing abnormality/ies in a factor regulating the blood pressure) ❖ provoking factors: • excess weight gain, obesity - account for about 65-70% of the risk for developing of essential hypertension • sedentary lifestyle New clinical guidelines recommend increased physical activity and weight loss as the first step in treating most patients with the essential hypertension. • stress (namely mental) • excessive sodium intake (interpopulation studies -Eskimos vs. people living in the North Japan) Essential Hypertension 40- ^ 30 0) u I 20 C ICH y Northern Japan y y' Bantuovc y y y Jižni Japonsko Austrálie \ Sev Amerika y N Quinea Eskymos i 100 I 200 SCO —I— 400 soo Sodium intake / day mmol/den (Knudsen KD., et al. 1966) Essential Hypertension f~\ 1 ■ ■ ■ Sod ium- oad ing rena function curves Normal Nonsalt-sensitive Salt-sensitive Increased salt intake 6- 5 IS £ 3 = 2 High intake Normal Normal intake Essential hypertension 150 Arterial pressure (mm Hg) Increased extracellular volume Increased arterial pressure Decreased renin and angiotensin Decreased renal retention of salt and water Return of extracellular volume almost to normal Return of arterial pressure almost to normal Definition and Consequences Arterial hypertension - chronic increase of the systemic blood pressure. Table 1 Definitions and classification of blood pressure (BP) levels (mmHg) Category Systolic Diastolic Optimal <120 and <80 Normal 120- 129 and/or 80- 84 High normal 130- ■139 and/or 85- 89 Grade 1 hypertension 140- 159 and/or 90- 99 Grade 2 hypertension 160- ■179 and/or 100- 109 Grade 3 hypertension >180 and/or >110 Isolated systolic > 140 and <90 hypertension Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462-1536. Essential Hypertension soiaie ystoiic i-iypertension t systolic and pulse pressure in the elderly due to: • age-dependent remodelling of the wall of elastic arteries (less elastic and more collagen fibres) ->■ t stiffness, ~| compliance: 1. ->■ J, distension of elastic arteries during the systole (physiologically accommodating the expansion of the volume after ejection of blood from the heart) -» Steeply t arterial systolic pressure + I blood volume (and also pressure) in arteries during the diastole 2. -> t pulse wave velocity Essential Hypertension isoiaiea systolic r-iypertension t pulse wave velocity -> the secondary, reflected pulse wave comes back to the aorta and elastic arteries sooner and, thus, superimposes on the primary pulse wave still during the systolic phase ->■ t systolic pressure and may even I diastolic pressure primary wave + reflected wave resulting wave Systoličky tlak (P1) Diastolický tlak(P3) Augmentacní tlak -ÍP2) *im/v Augmentacní tlak (P2-P1) 1ftň Al(%) = —5— ----100 Pulsni tlak Čas Rosa J, Wídimský J jr. Charakteristika velkých tepen u arteriální hypertenze. Cor Vasa 2011;53:418-422, Essential Hypertension soiate ystoiic Hypertension t systolic and pulse pressure in the elderly due to: • age-dependent remodelling of the wall of elastic arteries (less elastic and more collagen fibres) • endothelial dysfunction (t reactivity on vasoconstrictive mediators, namely the local ones as endothelins, thromboxane A2, ...) Essential Hypertension reatmen New clinical guidelines recommend increased physical activity and weight loss as the first step in treating most patients with EH. Decrease of sodium and increase of potassium intake, relaxation ... vasodilatory drugs | P = CO ■ TPR • i TPR, some of them | renal blood flow as well (ACEI) a. by inhibiting sympathetic nervous system (sympatolytics) b. by directly paralyzing the smooth muscle of the renal vasculature (vasodilatory agents or calcium channel blockers) c. by blocking action of the renin-angiotensin system on the renal blood vessels or tubules (inhibitors of angiotensin l-converting enzyme, ACEI) natriuretic (diuretic) drugs • i renal tubular reabsorption of salt and water -> l CO (by blocking the active transport of sodium through the tubular wall) Classification A. Essential (primary) hypertension • ..hypertension of an unknown origin" • 90-95% B. Secondary (symptomatic) hypertension • symptom of another primary disease with identifiable cause Secondary Hypertension enai nypenension Prerenal causes - Renovascular hypertension Acute and chronic diseases of the renal parenchyma • Postrenal causes (renal vein trombosis, urinary tract obstruction) Renin-producing renal tumor Endocrine hypertension Adrenocortical hyperfunction (Cushing's, Conn's, adrenogenital sy) Sympatoadrenal hyperfunction (pheochromocytoma) • Exogenic hormones (gluko-, mineralocorticoids, sympatomimetics) Hyperthyroidism Acromegaly Coarctation of the aorta Hypertension in preeklampsia Neurogenic hypertension Secondary hypertension Renal hypertension ❖ Circulus vitioSUS in some cases (renal disease can cause hypertension and hypertension can again cause injury to the glomeruli and renal blood vessels) ❖ hypertensive kidney diseases a. lesions j GFR (due to | renal vascular resistance - renovascular hypertension - or | glomerular capillary filtration coefficient - e.g. chronic glomerulonephritis causing thickening of the membranes) b. lesions | tubular reabsorption of sodium (hyperaldosteronism) c. patchy renal damage causing local ischemia (e.g. local arteriosclerosis; changes similar to „two-kidney" Goldblatt hypertension) Once hypertension develops, GFR and urinary excretion rate return to the physiological values (pressure natriuresis and diuresis). ❖ non-hypertensive kidney diseases (loss of whole nephrons) Secondary hypertension enovascular hypertension ❖ experimental „two-kidneys" Goldblatt hypertension (arteficial constriction of one renal artery, the second kidney preserved) (in clinics - e.g. stenosis of one renal artery due to atherosclerosis in the elderly or fibromuscular dysplasia in younger patients) i blood pressure in the kidney on the side of constriction 1. -> j, GFR retention of salt and water in the ischemic kidney 2. -> | secretion of renin in the ischemic kidney -> | angiotensin II -> vasoconstriction + retention of salt and water also in the second, healthy kidney econdary hypertension Henin-producing renal tumor (primary nyperreninism ❖ benign tumor from the juxtaglomerular cells ❖ severe hypertension t secretion of renin -» | angiotensin II 1. vasoconstriction (seconds) -> f TPR 2. retention of salt and water (days) -> | CO Secondary hypertension enai nypenension Prerenal causes - Renovascular hypertension Acute and chronic diseases of the renal parenchyma • Postrenal causes (renal vein trombosis, urinary tract obstruction) Renin-producing renal tumor Endocrine hypertension Adrenocortical hyperfunction (Cushing's, Conn's, adrenogenital sy) Sympatoadrenal hyperfunction (pheochromocytoma) • Exogenic hormones (gluko-, mineralocorticoids, sympatomimetics) Hyperthyroidism Acromegaly Coarctation of the aorta Hypertension in preeklampsia Neurogenic hypertension Secondary hypertension renOCOrllCai nyperTUnCHOn (Cushing's, Conn's, adrenogenital sy) Conn's syndrome R^^^1^S9^^I (primary hyperaldosteronism) IlfH^HI^^ttS^^I • unilateral aldosterone-producing adenoma VC^M^^SS^^^HflMto (less often Ei^l^^H^^^^B^^^I • bilateral hyperplasia of zona glomerulosa -> I absorption of sodium llS^h^ffili^^l -> osmotic absorption of water (eventuallyE^HI^HI IIII^BH t water intake) -> t extracellular fluid -> | i^Hilil llll llul CO -> hypertension -> pressure HSM^^^^^^^^^^^H natriuresis/diuresis + j renin bPNI^^H^R^H^^^I -> I secretion of potassium and H+ ^^SHHRh^H^M -> hypokalemic alkalosis (causing periods Ef'^S^^n^^^H^^^I of muscle weekness/paralysis, nephropathy) IH^MMMBM Secondary hypertension fa t tissue metabolism metabolic vasodilatation + vasodilatation in the skin (f heat elimination) \ blood flow -» t CO (including | HR) t amount and affinity of cardiac (also other) p-receptors -> | sensitivity to their chrono- and inotropic effects -> t expression of a-isoform of MHC (higher ATPase activity than (3-isoform) -> \ heart strength stimulation of the thyroid tissue by autoantibodies (thyroid-stimulating immunoglobulin) - same receptors as TSH thyroid adenoma mean pressure remains physiological but \ pulse pressure (systolic blood pressure - \ by 10 to 15 mmHg, diastolic blood pressure -1) Secondary hypertension enai nypenension Prerenal causes - Renovascular hypertension Acute and chronic diseases of the renal parenchyma • Postrenal causes (renal vein trombosis, urinary tract obstruction) Renin-producing renal tumor Endocrine hypertension Adrenocortical hyperfunction (Cushing's, Conn's, adrenogenital sy) Sympatoadrenal hyperfunction (pheochromocytoma) • Exogenic hormones (gluko-, mineralocorticoids, sympatomimetics) Hyperthyroidism Acromegaly Coarctation of the aorta Hypertension in preeklampsia Neurogenic hypertension Secondary hypertension ypertension in preeklampsia (toxemia of pregnancy ❖ one of the manifestations of the syndrome called preeklampsia which may develop in the last trimester ❖ causes not fully known thickening of the kidney glomerular membranes (autoimmune process?) -> | glomerular filtration rate -> | long-term level of the arterial pressure to preserve the physiological level of formation of urine ❖ salt-sensitive ❖ the most serious type of hypertension during pregnancy considering prognosis for both mother and the fetus ❖ other types of hypertension during pregnancy: • hypertension which began before pregnancy • hypertension which starts in the first months of the pregnancy