It has been customary to discuss the body requirements of sodium and chloride together. In view of current knowledge, it would seem desirable to discuss requirement of sodium separately, as well as in terms of salt. The minimum need of sodium is not definitely known but patients have been maintained on diets which furnished 200 to 300 mg. daily for long periods without apparent ill effects. The usual intake of sodium chloride (salt) by adults in the United States is 7 to 15 gm. daily, far more than minimum requirement . This large supply will amply fulfill needs except under conditions of profuse sweating or severe diarrhea or in certain endocrine and metabolic disturbances.
Sodium constitutes the largest fraction of the total base of the blood plasma and extracellular fluids, the normal concentration being 140 mEq/1. The total exchangeable sodium in the body, as determined by dilution techniques using radio-sodium, is about 2500 mEq or 41 mEq/kg. of body weight. Sodium is associated chiefly with chloride and bicarbonate ions and functions with them to maintain the osmotic pressure and ionic equilibrium of the body fluids and tissues (63). When osmotic equilibrium is disturbed, the functional capacity and viability of the cells may be seriously affected.
Cations in the blood other than sodium are calcium, potassium and magnesium; anions include chloride, bi carbonate, protein and small amounts of organic acids. The pH is regulated in large part by the relative amounts of chloride and bicarbonate. The chlorides of the blood constitute about two thirds of the anions, the normal concentration being 104 mEq/1 of serum.
Recent studies indicate that bone functions as an electrolyte reservoir. Skeletal sodium, which comprises 46% of the total body sodium, undoubtedly plays a role in the sodium economy of the body since some 6 to 13% of this sodium can be mobilized in the adult in response to various stimuli. In animals, a loss of bone sodium has been demonstrated with low sodium diets, in hyperchloremic acidosis, after mercurial diuresis and following adrenalectomy. Presumably, similar losses may occur in man under comparable conditions. In view of this, total deficits of sodium may be greater than those found by the usual methods of calculation.
Sodium plays a role, either alone or in conjunction with other extracellular ions, in the conduction of nerve impulses and in muscle contractility. Sodium metabolism is associated closely with that of water, although the mechanisms regulating excretion of these substances are not the same. These mechanisms maintain the concentration and amount of sodium and water in the body relatively constant within wide ranges of intake.
Sodium is excreted in the urine, sweat and feces, urinary excretion being of greatest importance. Losses in sweat are dependent upon the environmental temperature, humidity and body heat. In the unacclimatized person, the salt content of sweat may be 2 to 3 gm. per liter whereas after acclimatization sweat will contain only about 0.5 gm. per liter. Losses of sodium in the stool are small regard-less of intake, in the absence of diarrhea, since the lower small intestine and colon absorb large amounts. The urinary excretion of sodium is controlled principally by the renal tubules which reabsorb sodium according to bodily need; glomerular filtration influences loss to a certain extent. In the normal adult who ingests an average diet, approximately 100 mEq. of sodium is excreted in the urine in 24 hours. In view of the magnitude of glomerular filtration, this means that about 99.6% of the sodium presented to the tubules has been reabsorbed. When dietary sodium is markedly restricted for several days, almost no sodium is lost in the urine. The regulatory mechanism for tubular reabsorption of sodium is con-trolled in large measure by hormones of the adrenal gland. Recent evidence suggests that aldosterone, the recently isolated adrenal hormone, has a major role in salt and water homeostasis. The activity of aldosterone is analagous to that of desoxycorticosterone in its effect on renal sodium and potassium excretion but is about 30 times as great. According to Bartter secretion of this hormone “is controlled by a function of extracellular fluid volume, a function of potassium ions and, less importantly, adrenocorticotropic hormones.”
Sodium Depletion and Retention
Sodium metabolism is deranged in many disease states. Depletion may occur in subjects receiving diets seriously restricted in sodium, such as those used in the therapy of hypertension or in the control of chronic, extensive edema. Sodium deficiency may follow prolonged vomiting, diarrhea, profuse sweating, exudation of fluid from burned or otherwise injured areas and profound diuresis, particularly when low sodium diets have been administered. In adrenal insufficiency, large amounts of sodium are lost in the urine and much of the symptomatology of Addison’s disease may be attributable to sodium depletion.
The loss of sodium in association with chronic nephritis and certain types of acidosis, for example, diabetic acidosis, has long been appreciated.
Excessive retention of sodium is observed in many pathologic conditions including cardiac failure, nephritis, nephrosis, cirrhosis of the liver and hyperfunction of the adrenal cortex. A primary increase in secretion of aldosterone is observed in certain adrenal tumors while a secondary increase in secretion of this hormone has been demonstrated in the other diseases mentioned above in which sodium retention is common.
The diagnosis of sodium depletion is dependent on appreciation of the situations in which it is likely to occur as well as on clinical and laboratory findings. The syndrome is gradual in onset with weakness, lassitude, apathy, and anorexia as early manifestations. Postural faintness and restlessness with anxiety may be observed. It is noteworthy that thirst, a prominent finding in water depletion, is absent. Nausea, vomiting and muscle cramps are noted as the depletion progresses. The patient appears haggard, tissue turgor and elasticity are decreased, and there is loss of weight. The blood pressure falls, the pulse pressure is low, the limbs are pale and cold, and the pulse is rapid. Peripheral circulatory collapse is the mode of death. The concentrations of sodium and chloride in the serum are decreased and excretion of these substances in the urine is very low or absent, except in Addison’s or renal disease. Plasma volume is decreased and, as a con-sequence, levels of serum protein and hemoglobin and the volume of packed erythrocytes are increased. Blood urea nitrogen is elevated, serum potassium may be increased and serum bicarbonate decreased.
Sodium depletion must be differentiated from other syndromes in which hyponatremia is a finding. Causes of hyponatremia other than sodium depletion include depletion of potassium, primary water retention and, possibly, intracellular hypo-osmolarity due to a change in the state of intracellular anions (61f). The signs of primary water retention have been described (p. 67) while those of potassium depletion wil be considered subsequently.
Hyponatremia may be observed in many chronic, serious illnesses and may develop in the presence of a normal, low, or high total body sodium. Clinical assessment of the probable level of body sodium is of primary importance for institution of proper therapy. Edelman, from a consideration of data compiled from the literature, suggested that demonstratable edema is a reliable guide to the quantity of sodium in the body. Total body sodium was found to be increased by essentially the same amount in edematous subjects with cardiac, hepatic or renal disease who were hyponatremic as in those who were eunatremic. Conversely, when total body sodium was de-creased, dehydration rather than edema accompanied hyponatremia. However, findings obtained by Moore and associates (61a) in studies of starvation show that total body sodium may be high in the absence of edema. This may be true in other hyponatremic states.
A type of hyponatremia often seen in patients with chronic illness has been designated “asymptomatic hyponatremia” by Wynn (61c) who has pointed out that this condition is unaffected by treatment with salt and not corrected by water restriction. It may possible be due to a primary lowering of intracellular osmotic pressure. Patients with asymptomatic hyponatremia have no findings relative to the low level of serum sodium per se. They exhibit tissue wasting, progressive loss of weight, normal pulse and blood pressure and, usually, a decrease in hemoglobin, volume of packed erythrocytes and serum proteins.
The prognosis is poor unless these is a response to adequate nutritional intake.
A number of these patients with chronic disease may have a defect similar to that noted in starvation by Moore and associates (61a). In starvation, total body water ex-pressed as per cent of actual body weight is normal, or nearly so, as a result of the balance between marked reduction in intracellular water and marked increase in extracellular fluid. The total exchangeable sodium and chloride are very high, while total exchangeable potassium is low in relation to weight. Low serum sodium and slightly high serum potassium concentration are observed, the depression in serum sodium representing not dehydration but relative overhydration. Moore suggests that these changes may be explained on the basis of insufficient avail-able energy. Enery is required for exclusion of sodium from the cell and retention of potassium within the cell and for maintenance of isotonicity of extracellular fluid by the renal tubule. These mechanisms may break down in the absence of sufficient energy. If this explanation is correct and applicable to certain patients with chronic disease and hyponatremia, the fundamental need of this group of patients may be for energy.
It is obvious from the above that accurate diagnosis of the status of sodium metabolism is not simple and that reliance cannot be placed on any single clinical sign or laboratory test. The whole picture must be carefully evaluated. At times, the more complicated techniques for studying body composition must be applied for clear definition of the situation.
Combined Water and Salt Depletion
Combined water and salt depletion is a syndrome commonly encountered in clinical medicine. Findings are those of both water and salt deficiency: anorexia, weakness, nausea, vomiting, muscle cramps and peripheral circulatory collapse (signs of sodium deficiency), thirst and oliguria (signs of water deficiency). Heat cramps, which occur in persons working in very hot environments, are an example of this syndrome. If only water is ingested, the severity of symptoms is increased.
Hypernatremia appears to be relatively uncommon as judged by the limited number of publications on this sub- . ject. In a recent review, Knowles (61g) cites the following causes: 1) deficient intake of water, 2) excessive out-put of water due to: a) solute diuresis of urea or glucose, b) uncontrolled diabetes insipidus, c) gastroenteritis or d) hyperventilation, and 3) unclassified. Hypernatremia signifies a serum sodium concentration greater than 150 mEq/1. It seems likely that a primary water deficiency precedes and initiates the increase in serum sodium concentration in most instances. The condition is found most often in elderly patients in whom water intake has been limited, or in subjects undergoing solute diuresis from urea or glucose. Unless hypernatremia is severe, there are few or no abnormal symptoms or signs. In severe cases, coma and bizarre neurologic findings may be observed.