Porth's Essentials of Pathophysiology, 4e

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Heart Failure and Circulatory Shock

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that heart failure can occur even when the ejection frac- tion is normal or preserved. Persons with symptoms or below normal ejection fractions are classified as hav- ing heart failure with a reduced ejection fraction, while those with a normal or near-normal ejection fraction are classified as having heart failure with a preserved ejection fraction. Pathophysiology of Heart Failure In heart failure, the heart does not adequately pump and/or fill with blood, which results in the inability to meet the metabolic needs of the body. 1 The efficiency of the heart as a pump is determined by the volume of blood that it ejects each minute. The volume of blood ejected is dependent upon the ability of the ventricles to relax and fill. 5,6 The heart has the amazing capacity to adjust its output to meet the varying needs of the body. During sleep, the output declines, and during exercise, it increases markedly. The ability of the heart to increase its output during increased activity is called the cardiac reserve. For example, competitive swimmers and long- distance runners have large cardiac reserves. During exercise, the cardiac output of these athletes rapidly increases to as much as five to six times their resting level. 6 In sharp contrast with healthy athletes, persons with heart failure often use their cardiac reserve at rest. For them, just climbing a flight of stairs or even walking 7 may cause shortness of breath because they exceed their cardiac reserve. Cardiac Performance and Output The cardiac cycle consists of diastole and systole. During diastole, normal filling of the ventricles increases the volume of each to about 110 to 120 mL. 6 Then, as the ventricles contract during systole, blood is ejected from the heart, and the volume decreases by about 70 mL, which is called the stroke volume . The fraction of the end-diastolic volume that is ejected is called the ejection fraction (usually about 60% in a healthy person). 6 Cardiac output, which is the major determinant of cardiac performance, reflects how often the heart beats each minute (heart rate) and how much blood it ejects with each beat (stroke volume). Cardiac output is expressed as the product of the heart rate and stroke volume (i.e., cardiac output = heart rate × stroke vol- ume). The heart rate is regulated by a balance between the activity of the sympathetic nervous system, which produces an increase in heart rate, and the parasympa- thetic nervous system, which slows it down, whereas the stroke volume is a function of preload, afterload, and myocardial contractility. 5,6 Preload and Afterload. The ability of the heart to eject blood that has returned to the ventricles during diastole is determined largely by the loading conditions, or what are called the preload and afterload. Preload reflects the volume of blood that stretches the ventricle at the end of diastole, just before the onset of systole. It is determined by the venous return to the

heart. Also known as the end-diastolic volume, preload increases the length of the myocardial muscle fibers. Within limits, as preload increases, the stroke volume increases in accord with the Frank-Starling mechanism. 6 Afterload represents the force that the contracting heart muscle must generate to eject blood from the filled ventricles. The main components of afterload are the systemic (peripheral) vascular resistance and ventricular wall tension. When the systemic vascular resistance is elevated, as with arterial hypertension, an increased left intraventricular pressure must be generated to first open the aortic valve and then to eject blood out of the ven- tricle and into the systemic circulation. This increased pressure equates to an increase in ventricular wall stress or tension. 6 Myocardial Contractility Myocardial contractility, also known as inotropy, refers to the contractile performance of the heart, or the ability of the contractile elements (actin and myosin filaments) of the heart muscle to interact and shorten against a load 5,6,8 (see Chapter 1, Fig. 1-18). Contractility increases cardiac output independent of preload and afterload. The interaction between the actin and myosin filaments during cardiac muscle contraction (i.e., cross- bridge attachment and detachment) requires the use of energy supplied by the breakdown of adenosine triphos- phate (ATP) and the presence of calcium ions (Ca ++ ). 8 As with skeletal muscle, calcium is released from the sarcoplasmic reticulum of cardiac muscle during an action potential (Fig. 20-1). This calcium, in turn, dif- fuses into the myofibrils and catalyzes the chemical reac- tions that promote the sliding of the actin and myosin filaments along one another to produce muscle shorten- ing. In addition to the calcium released from the sarco- plasmic reticulum at the time of an action potential, a large quantity of extracellular calcium diffuses into the sarcoplasm through voltage-dependent L-type calcium channels located in the T tubules and myocardial cell membrane.Without the extra calcium that enters through the L-type calcium channels, the strength of the cardiac contraction would be considerably weaker. Opening of the L-type calcium channels is facilitated by the second messenger cyclic adenosine monophosphate (cAMP), the formation of which is coupled to β -adrenergic receptors. The catecholamines (norepinephrine and epinephrine) exert their inotropic effects by binding to these adrener- gic receptors. The L-type calcium channel also contains several other types of receptors. Blockade of L-type cal- cium channels by drugs that bind to these receptors (i.e., calcium channel-blocking drugs) results in a selective reduction in cardiac contractility. 9 Another mechanism that can modulate inotropy is the increased activity of the sodium ion (Na + )/Ca ++ exchange pump and the ATPase-dependent Ca ++ pump in the myocardial cell membrane (see Fig. 20-1). These pumps transport calcium out of the cell, thereby preventing the cell from becoming overloaded with calcium. If cal- cium efflux is inhibited, the rise in intracellular calcium produces an increased inotropy. Digitalis and related