Compensatory mechanisms in heart failure

By | 2013-08-07

The normal physiological mechanisms regulating the cardiovascular system are primarily concerned with the maintenance of arterial blood pressure which is adequate for cerebral perfusion. A fall in cardiac output and therefore arterial blood pressure will activate the following neurohormonal systems:

  1. 1. The sympathetic nervous system
  2. 2. The renin-angiotensin-aidosterone system
  3. 3. The renal body fluid system

The resultant effects of these neurohormonal systems are as follows.

  • Blood vessels constrict, reducing the capacitance of the circulation and mobilizing blood from the venous side thereby increasing cardiac chamber filling pressures and, via the Frank-Starling mechanism, the force with which the heart muscle contracts. In addition, constriction of the arterioles diverts blood away from so called non-essential tissues towards the heart and the brain.
  • The heart beats more forcefully and at a faster rate.
  • The extracellular fluid volume increases which increases cardiac filling pressure.

The neuroendocrine systems listed above all interact to produce the compensatory effects which maintain cardiac output at a reasonable level to match tissue requirements. Central to this interaction is the renin-angiotensin-aldosterone system (RAAS) as shown in site.

The sympathetic nervous system stimulates contraction of arterial and venous smooth muscle, an effect mediated by alpha adrenoceptors (primarily of the alpha1 subtype). The cardiac effects of sympathetic stimulation are an increase in heart rate and force of cardiac muscle contraction, effects which are mediated primarily by beta1-adrenoceptors. The increase in noradrenaline levels in dogs with congestive heart failure (congestive heart failure) correlates with the clinical severity, and dogs with dilated cardiomyopathy tend to have higher noradrenaline levels than those with chronic mitral valve disease (endocardiosis). There appears to be no correlation, however, between noradrenaline concentrations and myocardial function as measured by the end-systolic volume index.

In addition to the above, an increase in sympathetic tone via renal sympathetic nerves increases rerun secretion by the juxtaglomerular apparatus of the kidney resulting in activation of the RAAS. Renin metabolizes angiotensinogen to produce angiotensin I which in turn is converted by angiotensin converting enzyme (present in many tissues) to produce the active hormone, angiotensin II. Angiotensin II also causes vasoconstriction, particularly of arterial smooth muscle and has a negative feedback effect on the production of renin. In addition, it increases release of noradrenaline from sympathetic nerve endings, thus potentiating the vascular and cardiac effects of the sympathetic system. Angiotensin II itself also has direct effects on cardiac muscle which result in increases in the rate and force of contraction and in cardiac muscle hypertrophy. Indeed, there is now good evidence for local production of renin and angiotensin II in a number of tissues, including the myocardium where up-regulation of the system is thought to occur with increased ventricular wall stress. There are also direct renal effects of angiotensin II. In the proximal convoluted tubule, angiotensin II increases the absorption of salt and water. Angiotensin II stimulates the adrenal cortex to secrete aldosccrone which acts on the distal convoluted tubule of the kidney to enhance sodium retention. Salt and water homeostasis is also affected by the effects of angiotensin II in the brain where it is thought to increase thirst (possibly via a direct action on the hypothalamic thirst centres), salt appetite and the secretion of antidiurettc hormone (ADH), another potent vasoconstrictor.

The RAAS is also activated by decreased renal perfusion. The kidney senses poor perfusion both by a decrease in flow of tubular fluid, detected by the macula densa of the juxtaglomerular apparatus, and by reduced pressure in the afferent artcrioles. Both are signals for increased renin secretion and therefore activation of the RAAS. Reduced renal blood flow therefore results in increased aldosterone secretion and enhanced salt and water retention by the kidney. Glomerular filtration rate is sustained at a normal level by angiotensin II constricting the efferent arteriole more than the afferent arteriole. The fractional amount of renal plasma flow which is filtered therefore rises, leaving perirubular capillary hydrostatic pressure low and oncotic pressure high. Both these factors favour enhanced aidosteronc-induced reabsorption of tubular fluid, that is, salt and water retention.

It has been shown that the progressive increase in plasma aldosterone concentration which occurs in dogs with heart failure correlates with the clinical status of the animal.

As stated above, all these compensatory factors increase the work load for the heart by raising circulating volume> increasing venous return and thereby increasing the filling pressure of the heart. The effect of this increase in preload is to stretch the heart muscle and increase the end-diastolic length of the muscle which, by Starling’s law, results in a greater contractile force. Stretching of the heart muscle, by Laplace’s law, means that the amount of energy required to raise the pressure within the ventricle during the isovolumetric phase of contraction increases since the radius of the ventricle has increased and the wall thickness has decreased. In addition, the increase in artcriolar tone (i.e. peripheral vasoconstriction mediated by catecholamines, angiotensin II, ADH and other vasoactive peptides) also increases the isometric wall tension which must be attained before the aortic valve opens and the ejection phase of systole can commence (i.e. the resistance to cardiac output has increased). Both of these factors contribute to the increased cardiac afterload and a reduction in stroke volume.