Glenn E. Cullen

HEAT STROKE: CLINICAL AND CHEMICAL OBSERVATIONS ON 44 CASES

The problem of heat diseases has long been an important one in the tropics, in certain industries and occupations requiring exposure of individuals to high temperatures, and during periods of excessively hot weather in the cities of the United States. In spite of the voluminous literature on the subject, there is no unanimity of opinion regarding the predisposing and precipitating factors which bring about such reactions. Three fairly distinct clinical syndromes may occur as the result of an excessively high environmental temperature. These are heat cramps, heat exhaustion, and heat stroke. The syndrome of heat cramps has long been known among workers in hot environments. In addition to severe muscular cramps, these patients sweat profusely and have a normal temperature. The work of Edsall (1), Moss (2), Haldane (3), Glover (4), Talbott and his coworkers (5, 6), and others (7) suggests that this syndrome results primarily from an excessive loss of electrolytes, namely sodium chloride, in the sweat. The symptoms can be relieved or prevented by the administration of sodium chloride, and the mortality is negligible. The syndrome of heat exhaustion is characterized by profuse perspiration, pallor of the skin and low blood pressure-manifestations of peripheral circulatory collapse. The temperature may be subnormal, normal, or slightly elevated. The symptoms are of a syncopal nature, namely, weakness, dizziness, and sometimes fainting. Nausea and vomiting may occur. As a rule, heat exhaustion is not a serious condition. Recovery is rapid and the mortality low. Heat stroke, on the other hand, is a most serious condition, having a mor-

Hydrogen ion concentration of the blood in health and disease

Relation of [H+] to buffer effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 The acid base balance of the blood. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 Alkali reserve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . COZ absorption curves. . . . . . . . . . . . . . . . . . . . . . . . . . . 282 Influence of salts and proteins on the acid base equilibrium. . . . . . . . . . . . 283 Relation between p H of blood and serum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 pH of blood cell.. . . . . . . . . . . . . . . . . . . . . . 284 Relation between [BHCOz] o . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 pHof serumorplasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.5 Regulation of pH of blood. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Relation between [H+] and gram equivalent normality of acid concentration. . . . 279

The nature and detection of diabetic acidosis

Simultaneous determinations by the following three methods were made on diabetics in various stages of acidosis. 1. The alveolar carbon dioxide, by Fredericias method. 2. The carbon dioxide capacity of the oxalate plasma. The plasma is shaken with air containing 6 per cent. CO2, and the CO2 content of the plasma is then determined. A simple apparatus was devised which permits, in three or four minutes, a determination of the CO2 content, with an accuracy within one per cent. It consists essentially of a 50 c.c. pipette, provided with three-way stopcocks at the top and bottom, and connected with a mercury bulb. The pipette being full of mercury, 1 c.c. of plasma, washed in with 1 c.c. of water and 0.5 c.c. of N/1 acid, is introduced through the upper cock. The mercury is then drawn out from below by lowering the mercury bulb until a Torricellian vacuum is obtained in the pipette. The carbon dioxide escapes from the solution as the result of a few seconds shaking, and the water solution is drawn out of the pipette at the bottom. The mercury is then let in again through the other entrance of the 3-way cock at the bottom, and the volume of the carbon dioxide is read in the upper stem of the pipette, which is calibrated in 0.02 c.c. divisions. Normal serum binds about 75 per cent. of its volume of CO2. In acidosis we have seen the figure as low as 20 per cent. 3. The H+ concentration of the plasma after addition of known amounts of HCZ. The H+ concentration of the untreated plasma itself is about the same in normal condition and in acidosis. In the latter condition, however, as follows from the reasoning of L. J. Henderson, the ability of the blood to maintain its reaction when treated with acid must be lowered.

The formation of urea in the liver

In dogs etherized and operated at various intervals after feeding, we have found the urea content of blood from the hepatic vein to be from 3 to 20 per cent. higher than the portal blood. A similar increase in the urea content during passage of the blood through the muscle tissue of etherized dogs did not occur.

Changes in blood alkalinity during digestion

It has been noticed by former observers that the alveolar carbon dioxide tension usually rises after a meal. Two diametrically opposite explanations have been possible: (1) Acid digestion products displace carbon dioxide from the blood, and during the displacement the rate at which carbon dioxide passes from blood to lungs is increased. (2) The blood becomes more alkaline, as the result of secretion of gastric hydrochloric acid, or absorption of alkaline digestion products. Consequently the carbon dioxide capacity of the blood is increased, and in equilibrium with it the carbon dioxide tension of the alveolar air rises. We have determined on each of a number of subjects, in conditions of approximate digestive rest and of digestive activity, the following data: (1) Alveolar carbon dioxide tension; (2) Alkaline reserve of the plasma as indicated by its ability to maintain its alkalinity after addition of acid; (3) Alkaline reserve of the plasma as indicated by the amount of carbon dioxide with which it can combine. The results show that the reserve alkalinity of the plasma increases during digestion, the alveolar carbon dioxide increasing simultaneously. The second of the above explanations is therefore correct. The cause of the increase in alkaline reserve is being further studied.

Blood changes in ether anesthesia

During light ether anesthesia the bicarbonate content of the arterial blood falls, the carbon dioxide tension (determined directly by the tonometric method on the blood) rises, as does the hydrogen ion concentration. These phenomena indicate a state of uncompensated acidosis. The oxygen saturation increases, indicating that ventilation is accelerated in response to the stimulus of increased carbon dioxide tension. The acceleration does not, however, as under normal conditions, reach the height necessary to keep CO2 tension and hydrogen ion concentration down to normal limits. It therefore appears that even in light etherization the respiratory center is markedly deadened. In deep etherization the carbon dioxide tension rises still higher (over 80 mm. has been observed) and the PH may fall to below 7.2. Respiration not only fails to be accelerated in response to the increased CO2 tension but may even be so retarded that the oxygen saturation of the arterial blood falls below that normally found in venous. The blood tends to become concentrated. Conductivity and chloride determinations on the serum indicate only minute changes. The only striking electrolyte changes appear to be the increase in hydrogen ions and the replacement of part of the bicarbonate HCO3 anions by the anions of acids as yet unidentified.

On the deterioration of crystalline strophanthin in aqueous solution

For clinical use, crystalline strophanthin is commonly dissolved in normal salt solution or water and marketed in glass ampules. Sterilization is accomplished by autoclaving after the ampules have been filled and sealed. In making biologic assays, by the cat method of Hatcher and Brody, of several lots of a commercial preparation of “ouabain” (g-strophanthin) wide variations in potency were found. On adding a drop of indicator, phenol red, to the contents of those ampules showing low potency, it was observed that they were decidedly alkaline in reaction, whereas freshly prepared, aqueous solutions of the drug are neutral or slightly acid. Experiments were undertaken to ascertain the cause of the deterioration in relation to the altered hydrogen ion concentration and to devise a method for preparing a stable solution for therapeutic purposes. Doubly distilled water, pH 6.0, was autoclaved in various types of glass bottles and flasks, chosen at random from the laboratory supply. Immediately after autoclaving, the reaction of the water in the cheaper and softer varieties of container had become quite alkaline, the pH ranging from 6.3 to 9.0. In the hard glass flasks (Pyrex) no significant alteration in reaction occurred. A similar experiment was done with sixteen types of glass ampules, obtained from a number of pharmaceutical firms, and used by them in marketing their products. The distilled water autoclaved in these ampules in every instance showed a change in pH, which now ranged, in different lots, from 6.2 to 9.0. In order to titrate back to neutrality (pH 7.0) the most alkaline solution in the series, 2.6 C.C. of NJ5o HCl per IOO C.C. of water were required. Next, a 2 per cent. solution of strophanthin was made in standard M/20 phosphate mixtures with pH 7.0, pH 8.6 and pH 5.0.

Improved methods for the quantitative determination of plasma proteins

The blood is drawn into a tube containing an amount of potassium oxalate sufficient to make 0.2 or 0.3 per cent. oxalate solution, and is centrifuged twenty minutes. Fibrin.—5 c.c. of plasma are run into a beaker containing 100-150 c.c. 0.8 per cent. NaCl and 2-5 c.c. of a 2.5 per cent. CaCl2 solution. The CaCl2 may be in amounts from 2-25 equivalents of the oxalate, but about five equivalents are best. When coagulation is complete, the fibrin is filtered, the clot washed with 0.8 per cent. NaCl, and the nitrogen determined by Kjeldahl. The above is an adaptation of Howells method for determining the activity of thrombin. 1 The filtrate from the clot may be tested for complete precipitation by addition of a solution containing thromboplastic substances. Albumin and Globulin are calculated from the following three determinations: Total nitrogen is determined on a 1-2 c.c. sample. Non-protein nitrogen is determined in the filtrate obtained after precipitating the plasma with nine volumes of trichloracetic acid. Nitrogen of Globulin Filtrate:—Globulin and fibrin are precipitated by adding to 5 c.c. of plasma 20 c.c. of H2O and 25 c.c. of saturated ammonium sulfate solution. 20 c.c. of the filtrate are mixed in a Kjeldahl flask with 3 gm. MgO “Mercks Reagent” and 350 c.c. of 50 per cent. alcohol. The solution is distilled until the distillate gives a negative test to red litmus. This takes about one hour and reduces the volume to about 20 c.c. The nitrogen, representing albumin plus non-protein nitrogen, is then determined by Kjeldahl, using 25 c.c. H2SO4. When the digestion mass becomes light brown, the sides of the flask are washed down with a few c.c. of water and ten more c.c. H2SO4 added.

The mode of action of urease. II

The action of the generated ammonium carbonate in retarding the action of urease is due to the alkalinity of the carbonate. When the solution is kept neutral by a proper phosphate mixture the products have no effect on the velocity of the reaction. Elimination of the effect of the products makes urease a particularly favorable enzyme with which to study the reaction between enzyme and substrate. The results indicate that the action consists of two successive reactions: combination of enzyme and substrate in definite proportions; and decomposition of the compound, the urea being thrown off as ammonium carbonate; each of the two reactions consuming a definite portion of the total time. Formulation of these relations leads to the equation representing the time required for the decomposition of x amount of the initial substrate amount, a; c is a constant representing the velocity of combination of enzyme and substrate, d representing the velocity of decomposition of the complex. The values of c and d can be determined independently, and one can thereby determine whether changes in conditions affect the combination reaction, or that of decomposition. Neutral salts retard the combination. Alkaline reaction hastens it, but retards the decomposition. Slightly acid reaction greatly retards the combination, affecting the other reaction but little. The independent variation of the two phases of the process of enzyme action explains some previously obscure facts in regard to the effect of alkalies, acids, and other substances on enzyme action.