About Patho-physiology in heart failures and the neuro-hormmal activation and compensatory mechanism in heart failure

Mechanism of Heart Failure: Adaptive and maladaptive Mechanisms.

A Number of mechanisms aid the heart faced with an increased hemodynamic burden (such as pressure or volume overload) or one that has sustained loss of myocardium or contractility.

On a short –term basis many of these responses are adaptive. How ever, on a long term basis these responses are often maladaptive.

The Frank

Starling Mechanism operates through an increase in preload. As outlined above, an increase in the end diastolic volume of the ventricle is associated with stretching of the sarcomeres, which increases the interaction between actin and myosin filaments and their sensitivity to there by enhancing contraction.

How ever, ventricular dilation may become maladaptive when it becomes excessive, as may occur in sever valvular regurgitation, dilation increase wall stress through the operation of Laplace’s law and there by reduces shortening .

Compensatory hypertrophy occurs in hemodynamic overload, which in turn restores elevated ventricular wall stress to normal. If the hypertrophy is insufficient to restore wall stress further, leading to a vicious circle. Also, serve ventricular hypertrophy may impair ventricular filling and cause myocardial ischemia .

In ventricular remodeling there are change in the size, mass, and configuration of the ventricle as a consequence of hemodynamic changes following mechanical over load, hypertension, cardiomyopathy, and myocardial infraction.

Remodeling is triggered by myocyte growth, interstitial fibrosis and apoptosis ischemia, vasoactive peptides, and fibrosis. A change to a more spherical shape, which decreases the effectiveness of ejection, is common in the remodeled ventricle.

Redistribution of a subnormal cardiac output away from the skin, skeletal muscle, and kidneys with maintenance of blood flow to the most vital organ, i.e. the brain and the heart, occurs. The vasoconstriction, how ever, may increase after load, thereby reducing cardiac output further.

Reduction in Cardiac Efficiency The common forms of low output systolic HF, secondary to coronary atherosclerosis, Hypertension, cardiomyopathy, and certain valvular and congenital lesions, are characterized by a reduction in the external work performed by the heart.

while myocardial oxygen consumption remains normal or nearly so, there fore the external efficiency i.e. the ratio of external work performed to energy consumed, is often depressed.

Alterations In Energy Metabolism When HF occurs in the presence of acute or chronic ischemia, it can be attributed to reduced supply or oxygen with a resultant reduction of ATP generation.

Severe ventricular hypertrophy and dilatation from any etiology can contribute to ischemia, especially in the subendocardium, and this can impair both ventricular contraction and filling.

In some form of HF with out ischemia, myocardial energy stores in the form of creatine phosphate are decreased, as is the activity of the enzyme creatine kinase required for the shuttling of high energy phosphate between creatine phosphate and ADP,

Suggesting that reductions in myocardial energy reserves may play a role in nonischemic conditions as well.

Abnormal of Excitation Contraction Coupling :

Substantial evidence support the view in may forms of heart failure the delivery of CA2+ to the contractile sites is disturbed, there by impairing cardiac performance.

How ever, the molecular basis of this abnormality in deed of the sub cellular structure involved the sarcolemma, T tubules, and SR has yet to be defined .

There is, however, evidence for a reduction in the activity of the ca2+ release channel in the SR and of messenger RNA’s of the proteins regulating ca2+ channels, and the activity of the SR ca2+ between the SR and the cytoplasm.

Impaired expre3ssion of the genes encoding these proteins can impair both myocardial contraction and relaxation and there by contribute to the development of HF.

Neurohumoral and Cytokine Adjustments: A reduction in cardiac performance evokes a series of Neurohumoral adjustments. Which may at different times be adaptive or maladaptive.

These adjustment are adaptive when they maintain arterial perfusion pressure in the face of a sudden reduction of cardiac output.. However, they are maladaptive when they increase the hemodynamic burden and oxygen required of the failing ventricle and when they exacerbate injury.

The Adrenergic Nervous System : In patients with HF the levels of circulating norepinephrine may be markedly elevated, reflecting the increased activity of the adrenergic nervous system.

This increased activity supports ventricular contractility in acute HF that is intensified when large doses of B- adrenergic blocking agents are administered acutely, providing evidence for the proactive action of adrenergic nervous activation.

However , the chronic adrenergic stimulation that occurs in HF may increase after load by raising vascular resistance, cause cardiac arrhythmias, and may damage myocytes further, perhaps by increasing myocardial energy expenditures and ca2+ overload.

Gradually increasing doses of B Blockers are of benefit in patients with chronic HF. The Renin Angiotensin Aldosterone system When cardiac output declines, the Renin Angiotensin Aldosterone system is activated.

Concentrations of the both circulating angiotensin II and aldoster one are increased, the former contributing to excess vasoconstriction and the latter to the retention of salt and water perhaps to cardiac fibrosis.

The local tissue systems is also activated in HF and angiotensin II exerts a local cardiotoxic effect activates protein kinase C. The latter stimulates cardiac hypertrophy and causes ventricular remodeling .

Patients with HF are usually improved by blocking this system with angiotensim converting enzyme ACM inhibitors, angiotensin II receptor blocked, and Aldosterone antagonists.



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