血液循环障碍英文课件：PATHOPHYSIOLOGY OFHEARTFAILURE

1、PATHOPHYSIOLOGY OF HEART FAILURE,Jianzhong Sheng MD PhD,Notes to heart physiology,Essential functions of the heart,to cover metabolic needs of body tissue (oxygen, substrates) by adequate blood supply,to receive all blood coming back from the tissue to the heart,Essential conditions for fulfilling t

2、hese functions,normal structure and functions of the heart,adequate filling of the heart by blood,Essential functions of the heart are secured by integration of electrical and mechanical functions of the heart,Cardiac output (CO) = heart rate (HR) x stroke vol.(SV),- changes of the heart rate,- chan

3、ges of stroke volume,Control of HR:,- autonomic nervous system,- hormonal(humoral) control,Control of SV:,- preload,- contractility,- afterload,Adaptive mechanisms of the heart to increased load Frank - Starling mechanism Ventricular hypertrophy increased mass of contractile elements strength of con

4、traction Increased sympathetic adrenergic activity increased HR, increased contractility Incresed activity of RAA system,Causes leading to changes of number and size of cardiomyocytes,Preload,Stretching the myocardial fibers during diastole by increasing end-diastolic volume force of contraction dur

5、ing systole = Starlings law,preload = diastolic muscle sarcomere length leading to increased tension in muscle before its contraction (Fig. 2,3),venous return to the heart is important end-diastolic volume is influenced,stretching of the sarcomere maximises the number of actin-myosin bridges respons

6、ible for development of force,- optimal sarcomere length 2.2 m,Myocardial contractility,Contractility of myocardium Changes in ability of myocardium to develop the force by contraction that occur independently on the changes in myocardial fibre length,Mechanisms involved in changes of contractility,

7、 amount of created cross-bridges in the sarcomere by of Ca +i concentration,- catecholamines Ca+i contractility,- inotropic drugs Ca+i contractility, contractility shifting the entire ventricular function curve upward and to the left, contractility shiffting the entire ventricular function curve (hy

8、poxia, acidosis) downward and to the right,The pressure volume loop, It is the relation between ventricular volume and pressure This loop provides a convenient framework for understanding the response of individual left ventricular contractions to alterations in preload, afterload, and contractility

9、, It is composed of 4 phases: - filling of the ventricle - isovolumic contraction of ventricle - isotonic contraction of ventricle(ejection of blood) - isovolumic relaxation of ventricle,Pressure volume loops recorded under different conditions,It is expressed as tension which must be developed in t

10、he wall of ventricles during systole to open the semilunar valves and eject blood to aorta/pulmunary artery,Laplace law:,intraventricular pressure x radius of ventricle wall tension = - 2 x ventricular wall thickness, afterload: due to - elevation of arterial resistance - ventricular size - myocardi

11、al hypotrophy, afterload: due to - arterial resistance - myocardial hypertrophy - ventricular size,Afterload,Heart failure,Definition It is the pathophysiological process in which the heart as a pump is unable to meet the metabolic requirements of the tissue for oxygen and substrates despite the ven

12、ous return to heart is either normal or increased,Explanation of the terms,Myocardial failure = abnormalities reside in the myocardium and lead to inability of myocardium to fulfilling its function,Circulatory failure = any abnormality of the circulation responsible for the inadequacy in body tissue

13、 perfusion, e.g. decreased blood volume, changes of vascular tone, heart functiones disorders,Congestive heart failure = clinical syndrome which is developed due to accumulation of the blood in front of the left or right parts of the heart,General pathomechanisms involved in heart failure developmen

14、t,Cardiac mechanical dysfunction can develop as a consequence in preload, contractility and afterload disorders,Disorders of preload, preload length of sarcomere is more than optimal strength of contraction, preload length of sarcomere is well below the optimal strength of contraction,Important: fai

15、ling ventricle requires higher end-diastolic volume to achieve the same improvement of CO that normal ventricle achieves with lower ventricular volumes,Disorders of contractility,In the most forms of heart failure the contractility of myocardium is decreased (ischemia, hypoxia, acidosis, inflammatio

16、n, toxins, metabolic disorders. ),Disorders of afterload due to:,fluid retention in the body, arterial resistance,valvular heart diseases ( stenosis ),Characteristic features of systolic dysfunction (systolic failure) ventricular dilatation reducing ventricular contractility (either generalized or l

17、ocalized) diminished ejection fraction (i.e., that fraction of end-diastolic blood volume ejected from the ventricle during each systolic contraction les then 45%) in failing hearts, the LV end-diastolic volume (or pressure) may increse as the stroke volume (or CO) decreases,Characteristic features

18、of diastolic dysfunctions (diastolic failure) ventricular cavity size is normal or small myocardial contractility is normal or hyperdynamic ejection fraction is normal (50%) or supranormal ventricle is usually hypertrophied ventricle is filling slowly in early diastole (during the period of passive

19、filling) end-diastolic ventricular pressure is increased,Causes of heart pump failure,A. MECHANICAL ABNORMALITIES,1. Increased pressure load, central (aortic stenosis, aortic coarctation.), peripheral (systemic hypertension),2. Increased volume load, valvular regurgitation hypervolemia,3. Obstructio

20、n to ventricular filling, valvular stenosis, pericardial restriction,B. MYOCARDIAL DAMAGE,1. Primary,a) cardiomyopathy,b) myocarditis,c) toxicity (e.g. alcohol),d) metabolic abnormalities (e.g. hyperthyroidism),2. Secondary,a) oxygen deprivation (e.g. coronary heart disease),b) inflammation (e.g. in

21、creased metabolic demands),c) chronic obstructive lung disease,C. ALTERED CARDIAC RHYTHM,1. ventricular flutter and fibrilation,2. extreme tachycardias,3. extreme bradycardias,Pathomechanisms involved in heart failure,A. Pathomechanisms involved in myocardial failure,Damage of cardiomyocytes contrac

22、tility, compliance,Consequences:, defect in ATP production and utilisation, changes in contractile proteins, uncoupling of excitation contraction process, number of cardiomyocytes,impairment of relaxation of cardiomyocytes with decrease compliance of myocardium,impaired of sympato-adrenal system (SA

23、S) number of 1-adrenergic receptors on the surface of cardiomycytes,2. Changes of neurohumoral control of the heart function,Physiology: SNS contractility HR activity of physiologic pacemakers,Mechanism: sympathetic activity cAMP Ca +i contractility sympathetic activity influence of parasympathetic

24、system on the heart, Pathophysiology: normal neurohumoral control is changed and creation of pathologic neurohumoral mechanisms are present,Chronic heart failure (CHF) is characterized by an imbalance of neurohumoral adaptive mechanisms with a net results of excessive vasoconstriction and salt and w

25、ater retention,Catecholamines : - concentration in blood :,norepinephrin 2-3x higher at the rest than in healthy subjects,- circulating norepinephrin is increased much more during equal load in patients suffering from CHF than in healthy subject, number of beta 1 adrenergic receptors sensitivity of

26、cardiomyocytes to catecholamines contractility,System rennin angiotensin aldosteron,heart failure CO kidney perfusion stim. Of RAA system,Important:,Catecholamines and system RAA = compensatory mechanisms, heart function and arterial BP,The role of angiotensin II in development of heart failure, vas

27、oconstriction ( in resistant vesels), retention of Na blood volume, releasing of arginin vasopresin peptide (AVP ) from neurohypophysis, sensitivity of vessel wall to norepinephrine,mitogenic effect on smooth muscles in vessels and on cardiomyocytes hypertrophy, constriction of vas efferens ( in glo

28、merulus ), sensation of thirst, secretion of aldosteron from adrenal gland, mesangial conctraction glomerular filtration rate,facilitation of norepinephrine releasing from sympathetic nerve endings,Pathophysiology of diastolic heart failure,systolic heart failure = failure of ejecting function of th

29、e heart,diastolic heart failure = failure of filling the ventricles, resistance to filling of ventricles,But, which of the cardiac cycle is real diastole ?,Diastolic failure is a widely recognized clinical entity,Definition of diastolic heart failure,It is pathophysiological process characterized by

30、 symptoms and signs of congestive heart failure, which is caused by increased filling resistance of ventricles and increased intraventricular diastolic pressure,Primary diastolic heart failure,no signs and symptoms of systolic dysfunction is present - ! up to 40% of patients suffering from heart fai

31、lure!,Secondary diastolic heart failure,- diastolic dysfunction is the consequence of primary systolic dysfunction,Main causes and pathomechanisms of diastolic heart failure,1. structural disorders passive chamber stiffness,intramyocardial e.g. myocardial fibrosis, amyloidosis, hypertrophy, myocardi

32、al ischemia.,b) extramyocardial e.g. constrictive pericarditis,2. functional disorders relaxation of chambers e. g. myocardial ischemia, advanced hypertrophy of ventricles, failing myocardium, asynchrony in heart functions,Causes and mechanism participating on impaired ventricular relaxation,a) phys

33、iological changes in chamber relaxation due to: prolonged ventricular contraction Relaxation of ventricles is not impaired !,b) pathological changes in chamber relaxation due to: Impaired relaxation process, delayed relaxation (retarded), incomplete (slowed) relaxation, Consequences of impaired vent

34、ricular relaxation,filling of ventricles is more dependent on diastasis and on the systole of atrias than in healthy subjects,Symptoms and signs:, exercise intolerance = early sign of diastolic failure, coronary blood flow during diastole, Causes and mechanisms involved in development of ventricular

35、 stiffness, ventricular compliance = passive property of ventricle,Source of compliance: cardiomyocytes and other heart tissue to stretching, Ventricular compliance is caused by structural abnormalities localized in myocardium and in extramyocardial tissue,a) Intramyocardial causes : myocardial fibr

36、osis, hypertrophy of ventricular wall, restrictive cardiomyopathy,b. Extramyocardial causes : constrictive pericarditis,The role of myocardial remodelling in genesis of heart failure, adaptive remodelling of the heart, pathologic remodelling of the heart,Main causes and mechanisms involved in pathological remodelation of the heart,1. Increased amount and size of myocytes = hypertrophy,Due to: - volume and/or pressure load (excentric, concentric hypertrophy),- hormo