Bodily changes in pain, hunger, fear, and rage

THE INCREASE OF BLOOD SUGAR IN PAIN AND GREAT EMOTION

Sugar is the form in which carbohydrate material is transported in organisms; starch is the storage form. In the bodies of animals that have been well fed the liver contains an abundance of glycogen or “animal starch,” which may be called upon in times of need. At such times the glycogen is changed, and set free in the blood as sugar. Ordinarily there is a small percentage of sugar in the blood—from 0.06 to 0.1 per cent. When only this small amount is present the kidneys are capable of preventing its escape in any noteworthy amount. If the percentage rises to the neighborhood of 0.2–0.3 per cent, however, the sugar passes the obstacle set up by the kidneys, and is readily demonstrable in the urine by ordinary tests. The condition of “glycosuria,” therefore, may properly be considered, in certain circumstances, as evidence of increased sugar in the blood. The injection of adrenin can liberate sugar from the liver to such an extent that glycosuria results. Does the adrenal secretion discharged in pain and strong emotional excitement play a rôle in producing glycosuria under such conditions?

In clinical literature scattered suggestions are to be found that conditions giving rise to emotional states may be the occasion also of more or less permanent glycosuria. Great grief and prolonged anxiety during a momentous crisis have been regarded as causes of individual instances of diabetes, and anger or fright has been followed by an increase in the sugar excreted by persons who already have the disease. Kleen[1] cites the instance of a German officer whose diabetes and whose Iron Cross for valor both came from a stressful experience in the Franco-Prussian War. The onset of the disease in a man directly after his wife was discovered in adultery is described by Naunyn;[2] and this author also mentions two cases in his own practice—one started during the bombardment of Strassburg (1870), the other started a few days after a companion had shot himself. In cases of mental disease, also, states of depression have been described accompanied by sugar in the urine. Schultze[3] has reported that in these cases the amount of glycosuria is dependent on the degree of depression, and that the greatest excretion of sugar occurs in the fear-psychoses. Raimann[4] has reported that in both melancholia and mania the assimilation limit of sugar may be lowered. Similar results in the insane have recently been presented by Mita,[5] and by Folin and Denis.[6] The latter investigators found glycosuria in 12 per cent of 192 insane patients, most of whom suffered from depression, apprehension, or excitement. And Arndt[7] has observed glycosuria appearing and disappearing as alcoholic delirium appeared and disappeared in his patients.

Although clinical evidence thus indicates an emotional origin of some cases of diabetes and glycosuria, the intricacies of existence and the complications of disease in human beings throw some doubt on the value of that evidence. Both Naunyn[8] and Hirschfeld, although mentioning instances of diabetes apparently due to an emotional experience, urge a skeptical attitude toward such statements. It is desirable, therefore, that the question of an emotional glycosuria be tested under simpler and more controllable conditions. “Emotional glycosuria” in experimental animals has indeed been referred to by Waterman and Smit[9] and more recently by Henderson and Underhill.[10] Both these references, however, are based on the work of Böhm and Hoffmann,[11] reported in 1878.

Glycosuria From Pain

Böhm and Hoffmann found that cats, when bound to an operating board, a tube inserted into the trachea (without anesthesia), and in some instances a catheter inserted into the urethra through an opening above the pubis, had in about half an hour an abundance of sugar in the urine. In three determinations sugar in the blood proved slightly above “normal” so long as sugar was appearing in the urine, but returned to “normal” as the glycosuria disappeared. Since they were able to produce the phenomenon by simply binding animals to the holder, they called it “Fesselungsdiabetes.”

As possible causes of this glycosuria in bound animals, they considered opening the trachea, cooling, and pain. The first two they readily eliminated, and still they found sugar excreted. Pain they could not obviate, and since, without binding the animals, they caused glycosuria by merely stimulating the sciatic nerves, they concluded that painful confinement was itself a sufficient cause. Other factors, however, such as cooling and circulatory disturbances, probably coöperated with pain, they believed, to produce the result. Their observations on cats have been proved true also of rabbits;[12] and recently it has been shown that an operation involving some pain increases blood sugar in dogs.[13] Temporary glycosuria has likewise been noted in association with intense pain in human beings.

Inasmuch as Böhm and Hoffmann did not mention the emotional element in discussing their results, and inasmuch as they admitted that they could not obviate from their experimental procedure pain, which they themselves proved was effective in causing glycosuria, designating what they called “Fesselungsdiabetes” as “emotional glycosuria” is not justified.

Emotional Glycosuria

The discovery that during strong emotion adrenal secretion is increased, and the fact that injection of adrenin gives rise to glycosuria, suggested that glycosuria might be called forth by emotional excitement, and then that even without the painful element of Böhm and Hoffmann’s experiments, sugar might be found in the urine. The testing of this possibility was undertaken by A. T. Shohl, W. S. Wright and myself in 1911.

Our first procedure was a repetition of Böhm and Hoffmann’s experiments, freed from the factor of pain. The animals (cats) were bound to a comfortable holder, which left the head unfastened. This holder I had used hundreds of times in X-ray studies of digestion, with many different animals, without causing any signs of even so much as uneasiness. Just as in observations on the movements of the alimentary canal, however, so here, the animals reacted differently to the experience of being confined. Young males usually became quite frantic, and with eyes wide, pupils dilated, pulse accelerated, hairs of the tail more or less erect, they struggled, snarling and growling, to free themselves. Females, on the contrary, especially if elderly, were as a rule much more calm, and resignedly accepted the novel situation.

According to differences in reaction the animals were left in the holder for periods varying in length from thirty minutes to five hours. In order to insure prompt urination, considerable quantities of water were given by stomach tube at the beginning of the experiment and in some cases again later. Arrangements were made for draining the urine promptly, when the animal was on the holder or when afterwards in a metal metabolism cage, into a glass receiver containing a few drops of chloroform to prevent fermentation. The diet in all cases consisted of customary raw meat and milk. In every instance the urine was proved free from sugar before the animal was excited.

In our series of observations twelve cats were used, and in every one a well-marked glycosuria was developed. The shortest periods of confinement to the holder which were effective were thirty and forty minutes; the longest we employed, five hours. The average time required to bring about a glycosuria was less than an hour and a half; the average in seven of the twelve cases was less than forty minutes. In all cases no sugar was found in the urine passed on the day after the excitement.

The promptness with which the glycosuria developed was directly related to the emotional state of the animal. Sugar was found early in animals which early showed signs of being frightened or in a rage, and much later in animals which took the experience more calmly.

As cooling may result in increased sugar in the blood, and consequent glycosuria, the rectal temperature was observed from time to time, and it was found to vary so slightly that in these experiments it was a wholly negligible factor. In one cat the rectal temperature fell to 36° C. while the animal was bound and placed in a cold room (about 2° C.) for fifty minutes, but no sugar appeared in the urine.

Further evidence that the appearance of sugar in the urine may arise purely from emotional excitement was obtained from three cats which gave negative results when bound in the holder for varying periods up to four hours. It was noteworthy that these animals remained calm and passive in their confinement. When, however, they were placed, separately, in a small wire cage, and were barked at by an energetic little dog, that jumped at them and made signs of attack, the cats became much excited, they showed their teeth, humped their backs, and growled defiance. This sham fight was permitted to continue for a half hour in each of the three cases. In each case the animal, which after four hours of bondage had exhibited no glycosuria, now had sugar in the urine. Pain, cooling, and bondage were not factors in these experiments. The animal was either frightened or enraged by the barking dog, and that excitement was attended by glycosuria.

The sugar excreted in the twenty-four hours which included the period of excitement was determined by the Bertrand method.[14] It ranged from 0.024 gram to 1.93 grams, or from 0.008 gram to 0.62 gram per kilo body weight, for the twenty-four hours’ quantity.

The presence of sugar in the urine may be used as an indication of increased sugar in the blood, for unless injury has been done to the cells of the kidneys, they do not permit sugar to escape until the percentage in the blood has risen to a considerable degree. Thus, though testing the urine reveals the instances of a high content of blood sugar, it does not show the fine variations that appear when the blood itself is examined. Recently Scott[15] has concluded a thorough investigation of the variations of blood sugar in cats, and has found that merely incidental conditions, producing even mild excitement, as indicated by crying or otherwise, result in a noticeable rise in the amount. Indeed, so sensitive is the sugar-liberating mechanism that all the early determinations of the “normal” content of sugar in blood which has been drawn from an artery or vein in the absence of anesthesia, are of very doubtful value. Certainly when care is taken to obtain blood suddenly from a tranquil animal, the percentage (0.069, Scott; 0.088, Pavy) is much less than when the blood is drawn without anesthesia (0.15, Böhm and Hoffmann), or after light narcosis (0.282, Rona and Takahashi[16]).

Our observations on cats have since been found valid for rabbits. Rolly and Oppermann, Jacobsen, and Hirsch and Reinbach[17] have recently recorded that the mere handling of a rabbit preparatory to operating on it will increase the percentage of blood sugar (in some cases from 0.10 to 0.23 and 0.27 per cent). Dogs are said to be much less likely to be disturbed by the nature of their surroundings than are rabbits and cats. Nevertheless, pain and excitement are such fundamental experiences in animals that without much doubt the same mechanism is operative in all when these experiences occur. Probably, just as the digestion of dogs is disturbed by strong emotion, the blood sugar likewise is increased, for sympathetic impulses occasion both changes.[*] Gib has given an account of a bitch that became much agitated when shut up, and after such enforced seclusion, but never otherwise, she excreted small quantities of sugar in the urine.[18]

The results noted in these lower animals have been confirmed in human beings. One of my former students, W. G. Smillie, found that four of nine medical students, all normally without sugar in their urine, had glycosuria after a hard examination, and only one of the nine had glycosuria after an easier examination. The tests, which were positive with Fehling’s solution, Nylander’s reagent, and also with phenyl-hydrazine, were made on the first urine passed after the examination. Furthermore, C. H. Fiske and I examined the urine of twenty-five members of the Harvard University football squad immediately after the final and most exciting contest of the season of 1913, and found sugar in twelve cases. Five of these positive cases were among substitutes not called upon to enter the game. The only excited spectator of the Harvard victory whose urine was examined also had a marked glycosuria, which on the following day had disappeared.

Other tests made on students before and after important scholastic examinations have been published by Folin, Denis and Smillie.[19] Of thirty-four second-year medical students tested, one had sugar before the examination as well as afterwards. Of the remaining thirty-three, six, or 18 per cent, had small but unmistakable traces of sugar in the urine passed directly following the ordeal. A similar study was made on second-year students at a women’s college. Of thirty-six students who had no sugar in the urine on the day before, six, or 17 per cent, eliminated sugar with the urine passed immediately after the examination.

From the foregoing results it is reasonable to conclude that just as in the cat, dog, and rabbit, so also in man, emotional excitement produces temporary increase of blood sugar.

The Rôle of the Adrenal Glands in Emotional Glycosuria

Since artificial stimulation of the splanchnic nerves produces glycosuria,[20] and since major emotions, such as rage and fright, are attended by nervous discharges along splanchnic pathways, glycosuria as an accompaniment of emotional excitement would naturally be expected to occur. To what extent the adrenal glands which, as already mentioned, are stimulated to increased secretion by excitement, might play a part in this process, has been in dispute. Removal of these glands or cutting of the nerve fibres supplying them, according to some observers,[21] prevents glycosuria after puncture of the fourth ventricle of the brain (the “sugar puncture,” which typically induces glycosuria) and also after stimulation of the splanchnics.[22] On the other hand, Wertheimer and Battez[23] have stated that removal of the glands does not abolish the effects of sugar puncture in the cat. It was questionable, therefore, whether removal of the adrenal glands would affect emotional glycosuria.

Evidence on this point I secured with Shohl and Wright in observations on three animals in which the adrenals were removed aseptically under ether. The animals selected had all become quickly excited on being bound to the holder, and had manifested glycosuria after about an hour of confinement. In the operation, to avoid discharge of adrenin by handling, the adrenal veins were first tied, and then the glands freed from their attachments and removed as quickly and with as little manipulation as possible. In one cat the entire operation was finished in twenty minutes. In two of the cats a small catheter was introduced into the urethra through an incision, so that the bladder could be emptied at any time.

In all three cases urine that was free from sugar was obtained soon after the operation. Although the animals deprived of their adrenals manifested a general lessening of muscular tone, they still displayed much of their former rage or excitement when bound. Indeed, one was more excited after removal of the adrenals than before. That the animals might not be excessively cooled they were kept warm with coverings or an electric heating pad. Although they were now bound for periods from two to three times as long as the periods required formerly to cause glycosuria, no trace of sugar was found in the urine in any instance. The evidence thus secured tends, therefore, to support the view that the adrenal glands perform an important contributory rôle in the glycosuria resulting from splanchnic stimulation.

Possibly the emotional element is in part accountable for the glycosuria observed after painful stimulation, but conditions causing pain alone will reasonably explain it. As we have already seen, strong stimulation of sensory fibres causes the discharge of impulses along the splanchnic nerves, and incidentally calls forth an increased secretion of the adrenal glands. In glycosuria resulting from painful stimulation, as well as in emotional glycosuria, the adrenal glands may be essential factors.

Later the evidence will be given that sugar is the optimum source of muscular energy. In passing, we may note that the liberation of sugar at a time when great muscular exertion is likely to be demanded of the organism may be interpreted as a highly interesting instance of biological adaptation.

REFERENCES