Balancing Diuretic Therapy in Heart Failure: Loop Diuretics, Thiazides, and Aldosterone Antagonists

Sara Paul, RN, MSN, FNP


CHF. 2002;8(6) 

In This Article

Sodium Retention and Edema in Heart Failure

Some fundamental features of extracellular volume overload in heart failure have been known and well documented in medical literature for decades. At the turn of the century, Starling[1] noted that blood volume was more than likely to be increased in patients with edema. Over 50 years ago, Starr et al.[2,3] showed that edema occurs only when venous pressure is elevated, and Warren and Stead[4] made the observation that an increase in weight precedes an increase in venous pressure. In 1946, Merrill[5,6] noted that weight gain in patients with congestive heart failure (CHF) was the result of salt and water retention by the kidney due to low renal blood flow.

The physiology behind these observations remains the same today. In normal subjects, intravascular volume (plasma volume) and interstitial space, which together constitute the extracellular volume (ECV), remain constant, despite altered sodium and water intake. Since sodium constitutes more than 90% of the total cations of the extracellular fluid, the body content of sodium is the primary determinant of ECV. Control of ECV is dependent upon sodium balance, which is controlled by the kidneys. If ECV is increased in a normal person, the kidneys excrete extra salt and water. In CHF, however, sodium is retained by the kidneys despite increases in ECV.

Sodium and water retention is not necessarily due to decreased cardiac output, since there are high output states that also cause edema, such as severe anemia, thyrotoxicosis, chronic arteriovenous fistula, Paget's disease, and beriberi.[7] Furthermore, sodium retention is not caused by decreased blood volume, since blood volume is increased with CHF, not decreased. It is clear, however, that salt and water retention in CHF is at least in part due to the body's attempt to maintain a normal arterial blood pressure.

Data from a group of patients with untreated severe left ventricular dysfunction gave insight into the physiology of edema in CHF. As would be expected, these patients had resting tachycardia and increased right- and left-sided filling pressures.[8] Despite a 50% reduction in cardiac output, arterial blood pressure was normal due to increased systemic vascular resistance. Total body water was increased 16% above normal, almost all of which was in the extracellular space. Plasma volume increased by 34% and total body exchangeable sodium increased 37%. Effective renal plasma flow was severely decreased to 30% of normal due to severe renal vasoconstriction. Glomerular filtration rate was reduced to a lesser extent, suggesting greater efferent than afferent arteriolar vasoconstriction. Plasma norepinephrine was increased more than six times above normal and plasma renin activity was nine times normal. Aldosterone was increased six times above normal and plasma atrial natriuretic peptide was increased to 15 times normal. It appears, therefore, that the sodium-retaining effects of the catecholamines and the renin-angiotensin system prevail over the natriuretic effects of atrial natriuretic peptide in advanced CHF. It is noteworthy that the marked increase in plasma volume did not mitigate the ongoing activation of neurohormonal sodium-retaining mechanisms.

Diminished renal blood flow is thought to be the stimulus for activation of renin secretion in heart failure, which culminates in the production of angiotensin II, causing vasoconstriction and aldosterone secretion. Angiotensin II and aldosterone synergistically produce an increase in tubular reabsorption of sodium and water. Angiotensin II and aldosterone exert direct myocardial effects, leading to ventricular hypertrophy and cardiac fibrosis.