Daniel C. Darrow

The retention of electrolyte during recovery fromsevere dehydration due to diarrhea

Summary Balances of nitrogen, sodium, chloride, potassium, phosphorus, and calcium are reported during recovery from dehydration due to severe diarrhea. The balances are correlated with each other to bring into view the disturbances in composition of the intracellular as well as the extracellular fluids. Diarrhea led to a decrease in extracellular water owing to loss of sodium andchloride in extracellular fluid. In some cases, a large part of the loss of extracellular sodium was explained by transfer of sodium from the extracellular to the intracellular fluids. Such a transfer of sodium explained the acidosis in one case. In other cases, sodium was lost from the intracellular as well as extracellular fluids. Loss of intracellular potassium was a prominent feature of all cases and was equivalent in two cases to about one-fourth of the estimated normal potassium content of the baby. This loss of potassium is in excess of the loss which would be expected from loss of nitrogen. No great disturbance in the relative concentration of intracellular phosphorus was demonstrated. The usual replacement therapy of fasting and the parenteral administration of solutions containing sodium chloride, sodium lactate, and glucose corrected the extracellular concentrations. However, considerable sodium entered the cells in two cases and loss of potassium was aggrevated. Replacement of intracellular potassium was obtained by adding 1 to 2 Gm. of potassium chloride to submaintenance feeding. One observation indicated that replacement of intracellular potassium is not likely to occur if the diarrhea continues and submaintenance milk feedings without added potassium chloride are given. The data indicate that the usual milk mixtures contain sufficient potassium to replenish the tissues if these mixtures can be taken in the amounts necessary for growth. During the period of fasting, retention of intracellular potassium can beproduced by adding potassium chloride to solutions containing sodium chloride and sodium lactate. Such a treatment restores extracellular concentrations and replaces the deficit of potassium in part. Accompanying this replenishment of both intracellular and extracellular electrolyte, the babies looked better than after the usual type of treatment and recovered from attacks of diarrhea that would usually be fatal. The significance of a deficit of potassium is discussed.

Congenital alkalosis with diarrhea

Summary A report is made of a new syndrome. The patient showed intractable watery diarrhea from birth to the age of 2 years, 11 months (the time of this report). The stools were acid, contained considerable amounts of sodium, chloride and, at times, potassium. The alkaline urine contained no chloride, little sodium, and variable amounts of potassium. Stool chloride was always greater than stool sodium and stool water greater than urine water. Absorption of nitrogen, fat, carbohydrate, phosphorus, and calcium were essentially normal. As a result of these disturbances, the boy grew slowly, and was subject to frequent exacerbations of the diarrhea accompanied by signs and symptoms of dehydration. The blood serum showed extreme alkalosis, the maximal changes being pH 7.73; bicarbonate, 47 mM per liter; chloride 45 mM per liter; sodium, 118 mM per liter. Occasionally, serum potassium was low (1.5 mM per liter) but usually normal. Usually no signs of tetany were present but tetanic convulsions occurred once and carpopedal spasm, occasionally. Metabolic data are presented which show that as chloride is lost more rapidly than sodium, extracellular sodium is transferred into intracellular fluids and approximately equivalent amounts of potassium are released from the cells and excreted. Similarly when dehydration is treated with sodium chloride and potassium chloride, insufficient sodium is retained to account for the expansion of extracellular chloride but retention of potassium accounts for the release of sufficient sodium from cells to replace the deficit of extracellular sodium and to explain the changes in concentration of extracellular electrolytes. The alkalosis and low serum chloride are accompanied by no evidence of change in the blood-brain barrier. The displacement of muscle potassium by sodium is discussed.

THE PRODUCTION OF CARDIAC LESIONS BY REPEATED INJECTIONS OF DESOXYCORTICOSTERONE ACETATE

Desoxycorticosterone acetate prolongs the lives and restores many of the functions of patients suffering from Addisons disease and of adrenalectomized animals (1 to 5). The beneficial effects are related to the action on the kidneys which leads to excretion of potassium and retention of sodium (1, 5). Clinical observations have suggested that injurious results due to the steroid may appear along with the beneficial effects. While receiving desoxycorticosterone acetate, certain patients develop edema which has been attributed to excessive nephrogenic retention of sodium chloride and water (3, 5). Furthermore, a number of these patients have developed cardiac symptoms, including advanced congestive failure and enlargement of the heart by roentgenogram (2 to 8). In some cases the cardiac decompensation was regarded as a manifestation of previously existing disease of the heart which was aggravated by a return of the blood pressure to normal or high values (3). Certain authors have attributed cardiac failure to the added burden brought about by the increased volume of circulating fluids which retention of sodium chloride by the kidneys has caused (5). McGavack (6) pointed out that continued treatment leads to low concentration of potassium in serum and that this abnormality may account for the heart failure. Since it is recognized that desoxycorticosterone acetate exerts little or none of the glycogenic function of the adrenal cortex, disturbances in carbohydrate metabolism might be anticipated in Addisonian patients treated with the synthetic hormone (9). Hypoglycemia has been observed but does not seem to be an important factor except during pro-

The use of potassium chloride in the treatment of the dehydration of diarrhea in infants

Summary A new plan for the treatment of diarrhea in infants is described. Thevarious procedures which have been employed during the past twenty years are followed except that replenishment of body electrolyte is accomplished by adding potassium chloride to the solutions containing sodium chloride, sodium lactate, and glucose. In all severely ill patients, blood or plasma infusions are also carried out. The results obtained with the new treatment in the last half of the diarrhea season are compared with the results obtained with the old treatment during the first half of the diarrhea season. The two series of cases were of comparable severity. With the new treatment 3 of 50 patients died; with the conventional treatment 17 of 53 patients died. The decrease in mortality was not accompanied by a shortening of the duration or a decrease in intensity of the diarrhea. Administration of potassium chloride in conjunction with the other established procedures enables the babies to recover from some attacks of diarrhea that would otherwise be fatal. Two complications of the new treatment were encountered: (1) Potassium intoxication with complete heart block developed once, but recovery followed treatment. (2) Five patients developed intense erythema followed, by desquamation. While this complication did not otherwise alter the course, it is probably a consequence of the new treatment. The precautions necessary for the prevention of potassium intoxication are briefly discussed.

The role of potassium in the prevention of alkalosis

Abstract 1.1. Loads of sodium bicarbonate were administered to normal rats in drinking water along with known amounts of potassium and chloride. Alkalosis did not develop after two weeks as long as potassium chloride intake exceeded 0.5 mM/kg./day even though sodium bicarbonate intake amounted to 10 to 30 mM/ kg./day. It was not possible to produce alkalosis in this way in the absence of potassium deficiency, as demonstrated by muscle analysis. 2.2. Sodium bicarbonate, 15 mM per kg., was injected into normal and potassium-deficient rats, and urine was collected for the subsequent twelve hours. Serum and muscle analyses were obtained at the end of that time also. Normal animals excreted 10 mEq. of sodium and 5 mEq. of potassium per kg. of body weight in the twelve-hour period following loading. Essentially no chloride was excreted and alkalosis was not present after twelve hours. Potassiumdeficient animals excreted only 6 mEq. of sodium per kg. and no potassium. Almost 1 mEq. of chloride per kg. of body weight was excreted by the potassium-deficient animals and severe hypochloremic alkalosis was present twelve hours after loading. 3.3. Potassium bicarbonate, 3 mM per kg., was injected twice a day into potassium-deficient rats with hypochloremic alkalosis. No sodium or chloride was administered. After 24 mM per kg. of potassium bicarbonate had been administered, serum bicarbonate concentration fell to normal and serum chloride concentration rose to normal. This correction was associated with relatively little increase in bicarbonate excretion and with essentially no change in urinary pH or titratable acidity. Cation was excreted with organic anion, a large part of which was shown to be citrate.These results suggest that citrate may be substituted for chloride in the renal defense against alkalosis so that sodium is excreted without chloride and without change in urinary pH. Potassium would seem to be essential for the maximal conservation of chloride in this way. 4.4. These findings suggest that potassium deficiency may alter the ratio in which sodium and chloride are reabsorbed from glomerular filtrate. Such an alteration leads to changes not only in extracellular concentrations but also in extracellular volume.

The serum albumin and globulin of newborn, premature and normal infants

Summary The serum concentration of total protein, albumin, and globulin was determined in 20 newborn infants, 14 normal infants, aged about five months, and 26 permature infants. Similar studies in full-term and premature infants suffering from various diseases were made. The total protein is decreased in all infants, the decrease being due chiefly to low globulin. The diminution in globulin is greatest in premature infants. Postmortem serum of small fetuses shows essentially the same albumin-globulin ratio as that of full-term infants. Both premature and normal infants may show an increase in globulin during infection. It is suggested that the low globulin in infants may indicate the lack of the usual stimuli that give rise to globulin production in adults.

Retention of water and electrolyte during recovery in a patient with diabetic acidosis.

Summary The retentions during recovery in apatient with severe diabetic acidosis were 114 Gm. of water, 9 meq. of chloride, 13 meq. of sodium, and 6 meq. of potassium per kilogram of body weight. In the light of this and previousstudies, the significance of losses of water and electrolytes was discussed. It is pointed out that the acidosis is due in large part to accumulation of organic acids and that the loss of Na in relation to chloride is little if any in excess of their ratio in extracellular fluids. The magnitude of the deficits of Na, Cl, and water indicate that about 80 c.c. per kilogram of a fluid containing Na and Cl in the ratio found in extracellular fluids suffices to replace most of the deficits of water and all the deficits of Na and Cl. As long as all fluids are given parenterally, provision for water without electrolyte in glucose solutions must be given to cover the obligatory expenditure of water in urine and as insensible loss. Although potassium deficits are moderate, the effects of insulin are likely to produce a rapid and dangerous decrease in serum potassium concentration. Potassium should therefore be administered as soon as insulin begins to reduce blood sugar (two to six hours). The amount to be given is apparently 2 to 4 meq. per kilogram during the first twenty-four hours.

Effect of Low Potassium Diet and Desoxycorticosterone on the Rat Heart.

Summary A diet low in potassium when accompanied by injections of desoxycorticosterone acetate produces in 4 days loss of potassium and gain in sodium in the rat heart. Lessions are induced within a week by this treatment.

The importance of deficit of sodium and chloride in dehydration

Summary The case of a patient with severe burn is reported. Two episodes of symptoms of dehydration developed in which loss of sodium chloride without loss of water was produced by placing the boy in a continuous tub containing hypotonic salt solution. Symptoms of dehydration were due to loss of extracellular electrolyte without loss of body water. Metabolic studies are reported on a patient with infantile diarrhea, which show that the symptoms of intestinal intoxication were brought about by loss of sodium and chloride without deficit of body water. Therapeutic procedures for the treatment of dehydration are discussed in the light of recent concepts of the nature of dehydration.

Cardiac Necrosis Accompanying Potassium Deficiency and Administration of Corticosteroids

Rats were given distilled water or subjected to a load of 50 mM of either NaH2PO4 or Na2HPO4/liter in drinking water while on a diet low in sodium, potassium, and chloride for 12 to 14 days. The drinking water was modified by addition of either 20 mM of potassium chloride, 20 mM of sodium chloride or 20 mEq of magnesium chloride/liter or a combination of the salts. The effects of hydro-cortisone, desoxycorticosterone and 2 alpha methyl 9 alpha fluorocortisol were also tested. Serum, muscle, and heart were analyzed for electrolytes. Both Na2HPO4 and NaH2PO4 induced met-abolic alkalosis, decrease in muscle potassium, increase of intracellular sodium and slight decrease in heart potassium. Necrosis of heart muscle was associated with metabolic alkalosis, loss of muscle potassium and high intracellular sodium. The lesions and tissue changes are aggravated by the mineral ocorticoids but not hydrocortisone. Adding potassium chloride but not magnesium chloride decreased or prevented the lesions and changes in tissue composition.