Heart Failure, Part 5. Mechanisms, Compensatory Mechanisms and Their Adverse Effects

When I finished writing this part, I found it too long, but I decided to post it anyway: on Tuesday and Thursday Semester 4 students will have PACE sessions and after that they will definitely loose any interest in Cardiovascular Pathology. So, before that happened, please read the last part of Heart Failure.

There are three primary physiologic mechanisms that regulate stroke volume: preload, afterload and contractility, which have been (thoroughly?) explained in the previous posts. We have learnt that cardiac failure, as an inability of the heart to maintain stroke volume, can develop either through reduced preload, or increased afterload, or impaired contractility. Each of these factors has its own causes, ways of development, and mechanisms of compensation. It is important to understand that both physiologic mechanisms of heart activity and compensatory mechanisms have their own limits, which, if overwhelmed, may produce adverse effects on cardiac function and structure. Let’s talk again about preload, afterload and contractility but now in terms of heart failure development and compensation.

Preload. Reduced preload of the ventricles (e.g., mitral stenosis, hypertophic or restrictive cardiomyopathy) will automatically lead to decreased stroke volume and subsequently, to ventricular failure. Few physiologic mechanisms can compensate this phenomenon:
1) When the ventricles cannot accommodate all required blood, it will stay in the atria with their distension (preload increase) and activation of Frank Starling mechanism.
   a. We always keep in mind limitations of Frank-Starling mechanisms: after a certain point, an increase in EDV will lead to a fall in SV.
2) Sympathetic activation will enhance force of atrial contraction and tone of venous compartment of systemic circulation with augmented venous return to the heart (=increased preload)
   a. An increment in sympathetic tone will induce a considerable amount of adverse effects:
      i. Increased heart rate that is not always good, e.g., tachycardia will reduce preload
      ii. Calcium influx with possible arrhythmia and ischemia
      iii. Too much venous return will overwhelm the pulmonary circuit with possible development of pulmonary edema
      iv. A raise in arteriolar resistance will increase afterload and ca cause multisystem organ ischemia
3) Activation of renin-angiotensin system as well as synthesis and secretion of antidiuretic hormone with water and salt retention count for a great deal in cases of cardiac failure caused by hypovolemia
   a. Adverse effects of renin and ADH surplus:
      i. An excess in EDV – a fall in SV (see above)
      ii. Activation of myocardial fibrosis
      iii. An increase in arteriolar tone with elevation in afterload

Afterload. Increased afterload is always bad: pressure or volume overload, or thinning of the heart wall always have unfavorable effects on cardiac function. Pressure and volume overload induce the following compensatory mechanisms:
1) An increase in preload
   a. See the adverse effects of preload above
2) Myocardial hypertrophy with augemented force of contraction and reduction of overall afterload (see LaPlace law)
   a. Adverse effects of myocardial hypertrophy:
      i. Growth of cardimyocytes is always accompanied by production of extracellular matrix with subsequent myocardiosclerosis
      ii. Inadequate growth of blood vessels with diminished oxygen and nutrient supply
      iii. Changed geometry of cardimyocytes: larger diameter – less surface/volume ratio with insufficient metabolite transport through the sarcolemma.
3) Release of natriuretic peptides with reduction in arteriolar tone and volume of circulating blood (inhibition of sodium reabsorption).

Contractility. Impaired contractility often becomes a cause of heart failure, for example in patients with acute MI or chronic ischemic heart disease. Affected contractility can be partially compensated by
1) An increase in preload
2) Activation of adrenergic nervous system
3) Medications, e.g., beta-adrenoceptor agonists or phosphodiesterase inhibitors.
Adverse effects of too high preload and activated sympathetic nervous system have been covered above. About side effects of the mentioned drugs, please refer to Dr. Babbini’s lectures.

With this post I finish my talk about heart failure and I truly hope that my work helped you a little to understand this pathology. Going through my posts you had chances to appreciate this problem in all its complexity, and I believed it would influence in good way your approach in diagnosis and management of heart failure, a very serious medical problem in the modern world.

Very soon I will start to work on respiratory failure, I guess, I have a few words to say about it.

Good luck,

Dr. Y.