ELECTROLYTE DISTURBANCES IN CONGESTIVE HEART FAILURE*

Transcription

1 ELECTROLYTE DISTURBANCES IN CONGESTIVE HEART FAILURE* DAVID P. B.AUMANN, M.D. Department of Medicine, University of Arkansas School of Medicine, Little Rock, Arkansas The retention of salt and water secondary to altered renal hemodynamics is generally accepted as a most important process in the pathologic physiology of congestive heart failure. The actual mechanism and anatomy of this process is known only in part. It w r as postulated and, later, clearly demonstrated that there is a marked decrease in renal plasma flow and rate of glomerular filtration. 13 These changes can be expressed quantitatively, and the values given in one recent study 7 will be used in the following discussion. The renal plasma flow as measured withparaminohippurate was decreased from a mean control of 603 ml. per minute to a mean of 190 ml. per minute in patients in congestive failure. When cardiac compensation was reestablished, the effective renal plasma flow- increased by 57 per cent. The mean mannitol glomerular nitration rate was 103 ml. per minute in control subjects as compared with a mean of 75 ml. per minute in patients having cardiac decompensation. The mean maximal tubular excretory capacity as determined with paraminohippurate (Tm, pah) in 7 normal subjects w r as 80.3 mg. per minute. The mean Tm, pah of the group in congestive failure w r as 44.2 mg. per minute. The mean filtration fraction, which is an expression of the glomerular filtration in relation to the renal plasma flow (G:F./R.P.F.) showed a definite increase from the normal of 17.4 per cent to 40.5 per cent in decompensated patients. This increase in the filtration fraction has been explained in the current concept as being a result of efferent arteriolar constriction, which, by increasing the hydrostatic pressure within the glomerular capillaries, would force a greater filtration from the blood during its flow through these structures. 4 That there may be impairment of tubular function is suggested by a measurable decrease in the tubular excretory capacity. Normally, sodium is believed to be reabsorbed from the tubules in 2 phases: (1) an obligatory phase in the proximal tubule and (2) a facultative phase in the distal tubule. The former accounts for reabsorption of approximately 85 per cent of the filtered sodium. 6 With decreased glomerular filtration in congestive heart failure there is a great reduction in tubular sodium load. This apparently results in increased reabsorption of sodium in the obligatory phase, either because of the decreased sodium load or because of malfunction of the tubular apparatus. Some observers believe that increased tubular reabsorption occurs in the distal tubule, also, and contributes further to the total retention of sodium. Other factors in the mechanism of sodium and water retention remain to be evaluated. There is increasing evidence that the pituitary and adrenal glands * Presented at the Thirtieth Annual Meeting of the American Society of Clinical Pathologists, in Chicago, October 18, Received for publication, February 7,

2 ELECTROLYTES IN HEART FAILURE 617 may play a major role. It is of particular interest that an antidiuretic substance has been detected in the urine of patients with congestive heart failure. 3 One can only speculate at the present time on the possible effect of increased plasma volume and altered circulatory dynamics on the production of the salt-andwater-retaining hormones of the adrenal cortex. Whatever the etiology may be, the retention of sodium appears to be the keystone in the development of edema. Its fluid-retaining effect depends upon its position as the principal osmotically active base in the extracellular fluid compartment. With the retention of this ion in congestive failure, one might expect increased plasma sodium concentration. Our present concept assumes the existence of an osmotic equilibrium between the extracellular and intracellular fluid compartments that allows the movement of water and possibly sodium across the cell wall. With sodium retention there is movement of water from cells to the extracellular space resulting in a proportionate increase of plasma volume. This is further amplified by a decreased excretion of water. Thus, sodium retention is reflected as an over-all gain in weight (fluid weight or edema) while a normal value of serum sodium concentration is usually obtained. Schroeder 16 has shown that patients in congestive failure are unable to excrete efficiently relatively small amounts of chloride, whether given by mouth or by vein. This was demonstrated in a group of decompensated patients to whom sodium chloride was administered. There was a subsequent depression of urinary chloride, and the urine volume was also occasionally lowered. One,observer" has recently noted low serum sodium values in patients having cardiac decompensation (Fig. 1), and has commented on similar findings from 3 other laboratories. During the recovery of his patients, a larger volume of water was excreted than would be expected from the measured amount of sodium chloride lost at the same time. It was suggested that the edema of heart failure was initiated primarily by retention of water rather than retention of salt. In Schroeder's study there appeared,to be a disturbance of water balance in many patients not wholly dependent on a specific retention of salt. Diuresis in many was not accompanied by an amount of chloride sufficient to explain the loss of weight, if this were due simply to the excretion of edema fluid containing physiologic concentrations of salt. Other considerations of electrolytes in congestive heart failure are related to the existence of complicating factors. Patients in whom diffuse pulmonary disease is present are unable to maintain adequate ventilation. This results in an initial respiratory acidosis with increase in the CO2 partial pressure. As a compensatory process, there is an increased excretion of chlorides by the kidneys and a metabolic alkalosis may be produced. The net result as can be observed by clinical laboratory procedures is a rise in plasma bicarbonate concentration and a decrease in plasma chloride. Renal disease, preexistent and possibly associated with cardiac decompensation, may occasionally produce what is known as a "sodium wasting nephritis" in which there is marked loss of fixed base, especially sodium. A decrease in bicarbonate and chloride levels may be expected to overshadow all other findings.

3 618 BAUMANN With hyperventilation, occurring not infrequently in patients with heart failure, respiratory alkalosis may ensue. The plasma C0 2 content is decreased, and there is a rise in ph of the blood. With the usual renal compensatory process, sodium and bicarbonate are excreted but chlorides retained. Here, the net result is found to be a low plasma bicarbonate and increased plasma chlorides. In patients with congestive failure who are treated by drastic restriction of fluid intake, the specific gravity of the urine may rise to or higher. Hypertonic dehydration of the. blood appears, attended eventually by a rise in the HC03~ 27 HCO, 3 18 HC NA CL" 103 NA CL~ 88 NA CL" 88 R" 25 B + 13 R~ 25 B + 13 R" 25 I _ NORMAL 2-HYPONATREMIA 3-HYPOCHLOREMIC ALKALOSIS FIG. 1. Composition of plasma electrolytes: 1. Normal composition of plasma electrolytes. These values are the usual picture in untreated congestive heart failure. 2. True low sodium syndrome with depression of both plasma sodium and plasma chloride levels. 3. Hypochloremic alkalosis is a result of vigorous mercurial diuresis. The plasma sodium is essentially unchanged. blood urea nitrogen and of sodium and chloride. If uncorrected, this dehydration produces refractory heart failure, which is relieved only by increase of fluid intake, principally water. Newburgh 12 has emphasized that a salt-poor diet exerts a severe, strain on tubular cellular function and may require work that the tubules are incapable of performing. This actually occurs in extensive and prolonged sodium restriction with a daily intake of 0.5 gram or less. The tubular sodium loss continues, dehydration appears, azotemia becomes pronounced and the patient appears to be in uremia or shock. This sequence of.events is quite common if there is preexisting renal disease. The favorable action of digitalis by increasing the cardiac output in patients

4 ELECTROLYTES IN HEART FAILURE 619 with congestive failure may produce water diuresis with increased excretion of both sodium and chloride. The effect on the blood electrolyte pattern, however, is minimal. Oxygen therapy with consequent decrease in ventilation results in a rise of CO2 in the blood. 1 The blood ph shows little change. 2 When diuresis occurs with oxygen thei'apy, there is an increased excretion of urinaiy chlorides and a fall of serum chlorides to a'low normal level. Following the administration of ammonium chloride in adequate amounts, an increase in the chloride concentration of plasma and of edema fluid has been shown. There is a marked increase in the urinary chlorides. This is accompanied by considerable amounts of body base, especially sodium, with potassium and calcium in lesser amounts. Appreciable quantities of extracellular fluid with smaller amounts of intracellular fluid are excreted as indicated by the electrolyte pattern of the urine. A decrease in plasma volume occurs with hemoconcentration and a rise in the plasma protein level. It appears that the kidneys after a period of several days begin to produce sufficient quantities of ammonia to prohibit further loss of fixed base. Thus, the effect of ammonium chloride administration is not appreciable after about 96 hours. It has been shown that large amounts of ammonium chloride will lower the level of plasma bicarbonate and also the plasma ph. 9 In the presence of renal disease and impairment of the normal mechanism for conservation of base, loss of sodium in the urine may be excessive. Continuous administration of ammonium chloride to patients with reduced glomerular filtration can result in chloride retention and ultimately "chloride acidosis." The frequent and vigorous use of mercurial diuretics can produce severe and often unrecognized changes in electrolyte distribution. The clinical picture is that of a patient with chronic congestive failure who, despite the intensive use of mercurials, shows no demonstrable improvement. The volume of urine decreases progressively; edema may persist or even increase. The symptoms are characteristically those of increasing weakness, apathy and muscular pains. Disorientation progressing to coma may occur. This particular sequence of events has been called the "low sodium syndrome" but, perhaps, erroneously so. Numerous studies have shown that mercurials, when administered as the sole diuretic, produce primarily an increase in excretion of chloride but stimulate to less extent the loss of sodium. 8 Griggs and Johns 6 have demonstrated in a recent study of 9 patients with congestive heart failure on a low-sodium diet, that the injection of mercurial diuretic produced these same characteristic changes in the urine. The total excretion of sodium increased fourfold, while the total excretion of chloride increased more than sixfold. This marked excretion of chlorides not infrequently produces a profound hypochloremia. It is more pronounced in those patients with large collections of edema. Simultaneously there is often a rise in plasma bicarbonate while the plasma sodium usually remains unchanged. As the chlorides continue to drop with repeated administration of mercurial diuretic, the diuretic response progressively diminishes. When the chloride level falls below 86 meq per liter, the individual tends to become refractory to the drug. 16 A slight rise in potassium

5 620 BAUMANN may occur but, apparently, this is not often observed until such a time as there is almost complete urinary suppression. The excretion of protein catabolic products is diminished, and a precipitous rise in nonprotein nitrogen is observed. With this apparent lack of response, the physician may increase the frequency or amount of mercurial diuretic, may impose a more rigid sodium restriction and thus produce the clinical picture previously described in a vicious cycle of events. This state of hypochloremic alkalosis will usually respond to adminisstration of ammonium chloride either orally or parenterally. With the simultaneous administration of ammonium chloride and the mercurials, the depression of chloride levels is prevented and the state of hypochloremic alkalosis avoided. 9 An alternate sequence to that just presented has been described as the loss of bicarbonate during the alkalosis with secondary excretion of sodium. Depletion of sodium may thus occur with subsequent severe dehydration. The urine becomes acid although the patient is in alkalosis. This circumstance has been called "paradoxical aciduria." 14 In the presence of preexisting renal disease, the combination of rigid sodium restriction with the frequent use of mercurial diuretics may result in the loss of sodium as well as chloride because of the apparent inability of the damaged tubules to reabsorb the cation. This is accompanied by hypotonic dehydration with acidosis and elevated urea nitrogen in the blood. Symptoms similar to water intoxication may appear. It is this picture, then, that may more appropriately be termed the "low sodium syndrome." If sodium chloride is given to such a patient, edema may reappear although there may be a marked subjective improvement. After correction of the hyponatremia and hypochloremia, mercurial diuretics may again be given with satisfactory, response. 16 The clinical appearance may be almost identical, but it is important to differentiate the "low salt syndrome" from hypochloremic alkalosis in patients who have become resistant to mercurial diuretics. Guesswork may result in improper therapy and disastrous consequences. It is only by use of the clinical laboratory with frequent determinations of the blood electrolyte pattern that proper management of the problem patient can be securely maintained. REFERENCES 1. BARACH, A. L.: Therapeutic use of oxygen in heart disease. Ann. Int. Med., 5: , BARACH, A. L., AND RICHARDS, D. W., JR. : Effects of treatment with oxygen in cardiac failure. Arch. Int. Med., 48: , BERCU, B. A., ROKAW, S. N., AND MASSIE, E.: Antidiuretic action of the urine of patients in cardiac failure. Circulation, 2: , BURCH, G. E., AND RAY, C. T.: A consideration of the mechanism of congestive heart failube. Am. Heart J., 41: , CORCORAN, A. D., AND PAGE, I. H.: Hypertensive cardiovascular disease. Arch. Int. Med., 87: , GRIGGS, D. E., AND JOHNS, V. J.: Influence of mercurial diuretics on the excretion of sodium, potassium, and chlorides. California Med., 69: , HELLER, B. I., AND JACOBSON, W. E.: Renal hemodynamics in heart disease. Am. Heart J., 39: , HERRMANN, G., AND DECHERD, G. M., JR.: Further studies on mechanism of diuresis with especial reference to action of some newer diuretics. J. Lab. & Clin. Med., 22: , JUDSON, W. E.: Present day treatment of congestive heart failure. M. Clin. North America, pp , (Sept.) 1951.

6 ELECTROLYTES IN HEART FAILURE MERRILL, A. J.: Edema and decreased renal blood flow in patients with chronic congestive heart failure: Evidence of forward failure as primary cause of edema. J. Clin. Investigation, 25: 3S9-400, MILLER, G. E.: Water and electrolyte metabolism in congestive heart failure. Circulation, 4: , NEWBUROH, L. H.: Renal tubule work: Its significance for the clinician. Bull. New York Acad. Mod., 24: , PITTS, R. F., AND DUOGAN, J. J.: Studies on diuretics: II. The relationship between glomerular filtration rate, proximal tubular reabsorption of sodium, and diuretic efficacy of mercurials. J. Clin. Investigation, 29: , RELMAN, A. S., AND SCHWARTZ, W. B.: The recognition and management of sodium depletion. M. Clin. North America, pp , (Sept.) SCHROEDER, H. A.: Studies on congestive circulatory failure: III. Relation of edema to urinary chlorides. Circulation, 1: , SOLOFF, L. A.: Some clinical aspects of refractory heart failure. Mod. Concepts Cardiovas. Dis., 19: No. 8, (Aug.) 1950.