Cardiac Pathophysiology II

1. Cardiac Pathophysiology II

2. 1. Cardiac failure – a survey • 2. Pathological overload of the heart • 2.1 Volume overload • 2.2 Pressure overload • 3. Systolic and diastolic dysfunction • 3.1 Systolic dysfunction • 3.2 Diastolic dysfunction • 4. Compensation mechanisms of the failing heart • 5. Frank-Starling mechanism • 6. Neurohumoral activation • 7. Wall stress and hypertrophy • 8. Hypertrophy  dilation and manifest failure • 9. Cellular and molecular mechanisms • 10. Neurohumoral hypothesis and vitious circles • 11. Organismic consequencies of the heart failure

3. Cardiac failure – a survey Definition: Pathophysiologic: Condition in which the heart is not able to pump blood adaquately to the metabolic needs of the body under normal filling pressures Clinical: Syndroma in which a ventricular dysfunction is connected with lowered capacity to cope with physical loading, encompassing dyspnea, venostatic edema, hepato- megaly, jugulary venous distention, pulmonary rales The term „congestive“ is too restricted and should be avoided

4. Types: latent, manifest („cardiac decompensation“) chronic, acute (sudden, abrupt – more consequential) Forwards Backwards Systolic dysfunction unable to enhance filling able to enhance filling pressures pressures Diastolic dysfunction (unable to enhance filling able to enhance filling pressures) pressures (nearly synonymous) The failure „forwards“ and „backwards“ are connected vessels – ability/unability to enhance filling pressures is decisive in both conditions Etiology – Fig. 1

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6. Pathogenesis – Fig 2: A survey of some interconnections among the components of cardiac failure.  = wall stress, Ø = Frank-Starling mechanism ceases to work 2

7. Systolic and diastolic dysfunction represent an early stage of later manifest failure and its immediate hemodynamic mechanism • Neural and endocrine compensatory reactions are originally useful • physiological feedback reactions; their effectivity, however, pre- • supposes the functioning „regulatory organ“ = heart and vessels. • If the regulatory organ is not able to respond properly the SAS and • RAS reactions overshoot and become detrimental: • peripheral resistance & fluid retention & myocardial hypertrophy • vicious circles  pathological reversal  myocardial dysfunction •  SAS RAS

8. Both dysfunction and compensatory reactions are stretched in time just from the action of etiological factors to the definitive failure. The role of compensatory reactions is, however, different in different phases: compensatory and advantageous at the beginning, overshoot- ing and detrimental later (vicious circles)

9. 2. Pathological overload of the heart 1/3 of all failures • 2.1 Pathological volume overload • Causes see Fig. 1 • Stages: • - acute volume overload, F-S  end-systolic volume maintained • - slippage of myocardial fibers compliance of myocardium • (not dilation) • - excentric hypertrophy • - (lasting overload  and hypertrophy)  internal • irreversible changes of the myocardium systolic and • diastolic function (Fig. 3) • ESV, ejection fraction = emptying • EDV , coronary perfusion  ischemia  • fibrotization active relaxation (diastolic dysfunction) • Disruption of aortal valve in endocarditis, mitral regurgitation with • disruption of papillary muscle  acute volume overload  no • compliance  acute pulmonary edema

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12. 2.2 Pathological pressure overload • Stroke volume declines linearly with the afterload (Fig. 4) • Systolic work, effectivity (Fig. 5) • Causes see Fig. 1 • aortic or pulmonary stenosis, coarctation of aorta, hypertrophic • cardiomyopathy, systemic or pulmonary hypertension • right ventricle: persisting ductus arteriosus, mitral stenosis • Stages: • - acute pressure overload: Anrep´s phenomenon + F-S  • maintaining of stroke volume (SV) • - sympaticus contractility (Fig. 6) • - concentric hypertrophy • - hypertrophy compliance  systolic and diastolic • dysfunction (Fig. 7)

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18. 3. Systolic and diastolic dysfunction 8% of population: asymptomatic left ventricle dysfunction and manifest failure (1:1) cardiac failure from inherent cause • 2.3 Systolic dysfunction Systolic dysfunctioncontractility Etiology see Fig. 1 Overload  hypertrophy contractility (mechanisms known only partially) Working diagram: Fig. 3 Failure forwards: tissue perfusion (calm and sticky skin), renal perfusion (oliguria), cerebral perfusion (confusion) Failure backwards: pressure in pulmonary veins (left v.) or in systemic veins (right v.)

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21. What should be known in a particular case: - preload (EDV or EDP) - afterload (arterial pressure) - contractility (SV and EF) A compromise between forward and backward failure (Fig. 7) Therapy see Fig. 8  preload by volume expansion (cave pulmonary congestion and edema!)  afterload by vasodilators (cave hypotension!) arteriolar (hydralazine) „balanced“ (IACE) contractility by inotropic drugs (cave arrhythmias and other side-effects!)

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24. 2.4 Diastolic dysfunction Diastolic dysfunction compliance Etiology see Fig. 1 Pressure overload  mainly diastolic dysfunction (possibly with intact systolic function) Working diagram: Fig. 3 Although the pathogenesis of systolic and diastolic dysfunction is different, the consequences for the pumping function (and for the patient) are the same – forward or backward failure Moreover, EDP pressure gradient ventricle – aorta  coronary perfusion  ischemia

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27. 3. Compensation mechanisms of the failing heart Fig. 2

28. 3.1 Frank-Starling mechanism Volume or pressure overload utilization of F-S = of diastolic reserve diastolic reserve: the work which the heart is able to perform beyond that required under the ordinary circumstances of daily life, depending upon the degree to which the cardiac muscle fibers can be stretched by the incoming blood during diastole contractility utilization of F-S Dilation utilization of F-S (strongly limited)

29. 3.2 Neurohumoral activation Fig. 9 – regulation of blood pressure Cardiac failure CO  lowered pressure is indicated  sympatoadrenal system  generalized vasoconstriction  venous return  F-S (stops later)  maintaining of blood pressure (and cutting off kidneys, skin, GI etc.)

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31. Fig. 10 – a simple scheme of volume regulation Already before manifest cardiac failure, plasma norepinephrine and atrial natriuretic factor levels are enhanced – physiological reactions merge smoothly into pathological ones

32. 3.3 Wall stress and hypertrophy Definition of cardiac hypertrophy:left ventricle muscular mass per unit of the body surface Presupposes protein synthesis (dilation not so!) Pathogenesis: wall stress () Important compensatory mechanism normalizing the wall stress. Risiko factor of morbidity and mortality at the same time Fig. 12 muscle mass, but contractility/gram of tissue not changed There probably is a qualitative difference between physiological and pathological hypertrophy (Tab. 1) A „fine“ must be paid for hypertrophy: EDP unsufficient adaptation of vessel and capillary bed  coronary reserve compliance and contractility

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