This conception of the kinetic system has stood a crucial test by making possible the shockless operation. It has offered a plausible explanation of the cause and the treatment of Graves' disease. Will the kinetic theory stand also the clinical test of controlling that protean disease bred in the midst of the stress of our present-day life? Present-day life, in which one must ever have one hand on the sword and the other on the throttle, is a constant stimulus of the kinetic system. The force of these kinetic stimuli may be lessened at the cerebral link by intelligent control—a protective control is empirically attained by many of the most successful men. The force of the kinetic stimuli may be broken at the thyroid link by dividing the nerve supply, reducing the blood supply, or by partial excision; or if the adrenals feel the strain, the stimulating force may be broken by dividing their nerve supply, reducing the blood supply, or by partial excision. No theory is worth more than its yield in practice, but already we have the shockless operation, the surgical treatment of Graves' disease, and the control of shock and of the acute infections by overwhelming morphinization (Figs. 62, 72, and 73).

Conclusions

To become adapted to their environment animals are transformers of energy. This adaptation to environment is made by means of a system of organs evolved for the purpose of converting potential energy into heat and motion. The principal organs and tissues of this system are the brain, the adrenals, the thyroid, the muscles, and the liver. Each is a vital link, each plays its particular role, and one cannot compensate for the other. A change in any link of the kinetic chain modifies proportionately the entire kinetic system which is no stronger than its weakest link.

In this conception we find a possible explanation of many diseases one which may point the way to new and more effective therapeutic measures than those now at our command.



ALKALESCENCE, ACIDITY, ANESTHESIA—A THEORY OF ANESTHESIA[*]

[*] Paper delivered before the Virginia Medical Association, Washington, D. C., October 29, 1914.

Alkalis and bases compose the greater part of the food of man and animals, the blood in both man and animals under normal conditions being slightly alkaline or rather potentially alkaline; that is, although in circulating blood the concentration of the OH-ions— upon which the degree of alkalinity depends—is but little more than in distilled water, yet blood has the power of neutralizing a considerable amount of acid (Starling, Wells). At the time of death, whatever its cause, the concentration of H-ions in the blood increases,— the concentration of H-ions being a measure of acidity,—that is, the potential or actual alkalinity decreases and the blood becomes actually neutral or acid.

To determine what conditions tend to diminish the normal alkalinity of the blood, many observations were made for me in my laboratory by Dr. M. L. Menten to determine by electric measurements the H-ion concentration of the blood under certain pathologic and physiologic conditions.

As a result of these researches we are able to state that the H-ion concentration of the blood—its acidity—is increased by excessive muscular activity; excessive emotional excitation; surgical shock; in the late stages of infection; by asphyxia; by strychnin convulsions; by inhalation anesthetics; after excision of the pancreas, and in the late stages of life after excision of the liver and excision of the adrenals. Morphin and decapitation cause no change in the H-ion concentration. Ether, nitrous oxid, and alcohol produce an increased acidity of the blood which is proportional to the depth of anesthesia.

Many of the cases studied were near death, as would be expected, since it is well known that a certain degree of acidity is incompatible with life.

Since alkalis and bases preponderate in ingested food; since alkalinity of the blood is diminished by bodily activity; and since at the point of death the blood is always acid, we may infer that some mechanism or mechanisms of the body were evolved for the purpose of changing bases into acids that thus energy might be liberated.

These observations lead naturally to the question, May not acidity of itself be the actual final cause of death? We believe that it may be so from the facts that—(1) The intravenous injection of certain acids causes death quickly, but that convulsions do not occur, since the voluntary muscles lose their power of contraction; and (2) the intravenous injection of acids causes extensive histologic changes in the brain, the adrenals, and the liver which resemble the changes invariably caused by activation of the kinetic system (Figs. 74 and 75). In view of these facts may we not find that anesthesia and many instances of unconsciousness are merely phenomena of acidity?

As has been stated already, we have found that the H-ion concentration of the blood—its acidity—is increased by alcohol, by ether, and by nitrous oxid. In addition our tests have shown that under ether the increase of the H-ion concentration—acidity—is more gradual than under nitrous oxid, an observation which accords well with the fact that nitrous oxid more quickly induces anesthesia than does ether.

Further striking testimony in favor of the hypothesis that the production of acidity by inhalation anesthetics is the method by which anesthesia itself is produced is found in the fact that although lethal doses of acid cause muscular paralysis, yet this paralysis may be mitigated by adrenalin—which is alkaline. This observation may explain in part the remarkable success of the method of resuscitation devised by me, in which animals "killed" by anesthetics and asphyxia are revived by the use of adrenalin.

In animals under inhalation anesthesia Williams found that no nerve-current could be detected by the Einthoven string galvanometer, a fact which might be explained by postulating that nerve-currents can flow from the brain to the muscles and glands only when there is a difference of potential. Any variation from the normal alkalinity of the body must change the difference in potential. Since the nerve-currents in animals under anesthesia are not demonstrable by any apparatus at our command, and since anesthesia produces acidity, then we may infer that acidity reduces the difference in potential. As long as there is life, a galvanometer of sufficient delicacy would perforce detect, a nerve-current until the acidity increased to such a point as to reduce the difference in potential to zero— the point of death. If at this point a suitable alkali— adrenalin solution—can be introduced quickly enough, the vital difference in potential may be restored and the life processes will be renewed. Bearing especially on this point is the fact that if adrenalin in sufficient quantities be administered simultaneously with an acid, it will not only prevent the fall in blood-pressure usually caused by the acid, but will also prevent the histologic changes in the brain, adrenals, and liver which are usually caused by the intravenous injection of acids.

This hypothesis regarding the cause of anesthesia and unconsciousness explains and harmonizes many facts. It explains how asphyxia, overwhelming emotion, and excessive muscular exertion, by causing acidity, may produce unconsciousness. It explains the acidosis which results from starvation, from uremia, from diabetes, from Bright's disease, and supplies a reason for the use of intravenous infusions of sodium bicarbonate to overcome the coma of diabetes and uremia (Fig. 76). It may explain the quick death from chloroform and nitrous oxid; and may perhaps show why unconsciousness is so commonly the immediate precursor of death.

One of the most noticeable immediate effects of the administration of an inhalation anesthetic is a marked increase in the rapidity and force of the respiration. The respiratory center has evidently been evolved to act with an increase of vigor which is proportional— within certain limits—to the increase in the H-ion concentration, whereas the centers governing the voluntary muscles are inhibited. In this antithetic reaction of the higher cortical centers and the lower centers in the medulla to acidity we find a remarkable adaptation which prevents the animal from killing itself by the further increase in acidity which would be produced by muscular activity. That is, as the acidity produced by muscular action increases and threatens life, the respiratory action, by which carbon dioxid is eliminated and oxygen supplied, is increased, while the driving power of the brain, which produces acidity, is diminished or even inhibited entirely; that is, the state of unconsciousness or anesthesia is reached. We conclude first that, without this life-saving regulation, animals under stress would inevitably commit suicide; and, second, that it is probable that the remarkable phenomenon of anesthesia— the coincident existence of unconsciousness and life—is due to this antithetic action of the cortex and the medulla.

In the human, as in the animal, the degree of acidity parallels the depth of inhalation anesthesia.

Within a few seconds after beginning nitrous oxid anesthesia the acidity of the blood is increased. This rapid acidulation is synchronous with almost instantaneous unconsciousness and increased respiration. If the oxygen in the inhaled mixture be increased, a decrease in acidity is again synchronous with lighter anesthesia and a decrease in the respiratory rate.

If these premises be sound, we are justified in asserting that the state of anesthesia is due to an induced acidity of the blood. If the acidity is slight, then the anesthesia is slight and the force of the nerve impulses is lessened, but the patient is still conscious of them. As the acidity increases associative memory is lost, and the patient is said to be unconscious: the centers governing the voluntary muscles are not inhibited, however, and cutting the skin causes movements. If the acidity is further increased, there is loss of muscular tone and even the strong contact ceptor stimuli of a surgical operation do not cause any muscular response, and, finally, the acidity may be increased to the point at which the respiratory and circulatory centers can no longer respond by increased effort, and anesthetic death— that is, ACID death—follows.

Certain clinical phenomena are clarified by this theory and serve to substantiate it. For example, it is well known that inhalation anesthesia precipitates the impending acidosis which results from starvation, from extreme Graves' disease, from great exhaustion, from surgical shock, and from hemorrhage, and which is present when death from any cause is imminent.

We see, therefore, that anesthesia is made possible, first, by the fact that inhalation anesthetics cause acidity, and, second, by the antithetic adaptation of the higher centers in the brain and of the centers governing respiration and circulation.

In deep contrast to the action of inhalation anesthetics is that of narcotics. Deep narcotization with morphin and scopolamin is induced slowly; the respiratory and pulse-rate are progressively lessened— and there is no acidity.

By our researches we have established in what consists the generic difference between inhalation anesthetics and narcotics. In our experiments no increase in the H-ion concentration was produced by morphin or by scopolamin, no matter how deep the narcotization. In animals already narcotized by morphin the production of acid by any of the acid-producing stimuli was delayed or prevented. On the other hand, in animals in which an acidity had already been produced by ether, by shock, by anger, or by fear, the later administration of morphin delayed or inhibited entirely the neutralization of the acidity. In other words, morphin interferes with the normal mechanism by which acidity is neutralized possibly because its inhibiting action on the respiratory center is sufficient to overcome the stimulating action of acidity on that center, for, as we have stated, the neutralization of acidity is in large measure accomplished by the increased respiration induced by the acidity itself.

SUMMARY

Acidity inhibits the functions of the cerebral cortex, but stimulates those of the medulla. This antithetic reaction to the stimulus of increased H-ion concentration is an adaptation to prevent animals from committing suicide by over-activity, for the mechanism for the initiation and control of the transformation of energy is in the higher centers of the brain, while an essential part of the mechanism for the neutralization of acidity—the centers governing circulation and respiration— is in the medulla. This explains many clinical phenomena— why excessive acidity causes paralysis, why there is great thirst after inhalation anesthesia, after excessive muscular activity, excessive emotion—after all those activities which we have found to be acid-producing, for water, like air, neutralizes acids. The excessive use of alcohol, anesthetics, excessive work, intense emotion, all produce lesions of the kidney and of the liver. The explanation is found in the fact that all these stimuli increase the acidity of the blood. and that, if long continued, the neutralizing mechanism must be broken down and so the end-products of metabolism are insufficiently prepared for elimination.

In view of these considerations we may well conclude that the maintenance of the normal potential alkalinity of the blood is to be estimated as the keystone of the foundation of life itself.



INDEX

ABDOMEN, diseases of, phylogenetic association and, 44 Acidity, 227 Adaptive energy, 176 variation in rate of energy discharge, 177 Adrenalin, Cannon's test for, 134, 196 injection of, changes in brain-cells from, 186 Adrenals, 196 brain and, relation of, 1.98 diseases of, effect of, on output of energy, 216 functional study of, 196 histologic study of, 198 Alcohol, changes in brain-cells from, 116 Alkalescence, 227 Anemia, pain of, 77 Anesthesia, 2, 227 anoci-association and, differentiation, 34 effect of trauma under, upon brain that remains awake, 3 inhalation, cause of exhaustion of brain-cells as result of trauma under, 8 theory of, 227 Anger, 63, 70 Anoci-association, 34 anesthesia and, differentiation, 34 Graves' disease and, 36 prevention of shock by application of principle of, 36 Aristotle, 127 Asher, :37 Associational centers, dulled, 47 Austin, 2, 55, 173

BASS, 159 Beebe, 213 Benedict, 212 Biologic consideration of adaptive variation in amounts of energy stored in various animals, 176 Brain, adrenals and, relation of, 198 diseases of, effect of, on output of energy, 216 effect of trauma under anesthesia oil, 3 functions, physical state of brain-cells and, relation between, 111 influence of fear on, 64 Brain-cells, cause of exhaustion of as result of trauma under inhalation anesthesia, 8 changes in, from alcohol, 116 from drugs, 113 from fatigue, 112 from fear, 112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform, 116 from strychnin, 113 in Graves' disease, 116 in infections, 116 in insanity, 120 in insomnia, 119 histologic changes in, in relation to maintenance of consciousness and to production of emotions, muscular activity, and fever, 182 physical state, brain functions and, relation between, 111

CANNON, 57, 64, 68, 73, 133, 138, 196, 202 Cannon's test for adrenalin, 134, 196 Cells, brain-, cause of exhaustion of, as result of trauma under inhalation anesthesia, 8 changes in, from alcohol, 116 from drugs, 113 from fatigue, 112 from fear, 112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform, 116 from strychnin, 113 in Graves' disease, 116 in infections, 116 in insanity, 120 in insomnia, 119 histologic changes in, in relation to maintenance of consciousness and to production of emotions, muscular activity, and fever, 182 physical state, brain functions and, relation between, Ill Chemical noci-association in infections, 48 Cold pain, 83 sweat, 27 Contact pain, special, 78 Crying, 90 in exophthalmic goiter, 106

DARWIN, 12, 26, 30, 91, 127, 153 on phenomena of fear, 26 Disease, mechanistic theory of, 157 Distance receptors, discharge of energy through stimulation of, 25 Dog, spinal, 4 Dolley, 2, 10 Drugs, changes in brain-cells from, 113

ELIOT, 1 Elliott, 202 Energy, adaptive, 176 Energy, discharge, rate of, adaptive variation in, 177 nervous, cause of discharge of, 12 as result of trauma under inhalation anesthesia, 12 discharge of, role of summation in, 30 through representation of injury, 25 through stimulation of distance receptors, 25 psychic discharge, 25 output of, effect of diseases of adrenals on, 216 of brain on, 216 of liver on, 216 of muscles on, 216 of thyroid on, 217 rate of out put, influences that cause variation in, 177 Environment, 128, 130 Evacuation pain, 77 Exophthalmic goiter, 66 crying in, 106 fear and, resemblance between, 68 laughing in, 106

FATIGUE, changes in brain-cells from, 112 Fear, 26, 52, 55 changes in brain-cells from, 112 Darwin on phenomena of, 26 Graves' disease and, resemblance between, 68 influence of, on brain, 61 phenomena of, 56 Fly-trap, Venus', 151 Frankel, 68 Frazier, 82 Functional study of adrenals, 196

GOITER, exophthalmic, 66 crying in, 106 Goiter, exophthalmic, fear and, resemblance between, 68 laughter in, 106 Graves' disease, 66 anoci-association and, 36 changes in brain-cells in, 116 crying in, 106 fear and, resemblance between, 68 laughter in, 106

HARVEY, 1,57 Headache, 80 Heat pain, 77 production in infections, purpose and mechanism, 180 Hemorrhage, changes in brain-cells from, 113 Hippocrates, 127 Histologic changes in liver, 205 study of adrenals, 198 Hitchings, 173 Hodge, 10 Hornaday, 26 Hydrogen ion concentration in activation of kinetic system, 217 Hyperthyroidism, 42

INFECTIONS, changes in brain-Cells in, 116 chemical noci-association in, 48 heat production in, purpose and mechanism, 180 pain of, 79 Inhalation anesthesia, cause of exhaustion of brain-cells as result of trauma under, 8 trauma under, cause of discharge of nervous energy as result of, 12 Insanity, changes in brain-cells in, 120 Insomnia, changes in brain-cells in, 119 effect of, 205

Iodoform, changes in brain-cells from, 116

KINETIC diseases, 219 reaction, 93 system, 173

LABOR pains, 79 Laughter, 90 causes of, 91 in exophthalmic goiter, 106 Law, Sherrington's, 24 Light pain, 77 Liver, diseases of, effect of, on output of energy, 216 histologic changes in, 205 Livingstone, 148 Lower, 42

MALARIA, 159 McKenzie, 162 Mechanistic theory of disease, 157 view of psychology, 127 Medical problems, phylogenetic association in relation to, 1 Menten, 2, 55, 173, 218, 227 Muscles, diseases of, effect of, on output of energy, 216

NAGGING, 46 Nausea pains, 78 Nervous energy, cause of discharge of, 12 as result of trauma under inhalation anesthesia, 12 discharge of, role of summation in, 30 through representation of injury, 25 through stimulation of distance receptors, 25 psychic discharge, 25 Neurasthenia, sexual, 43 Neuroses, postoperative, 46 traumatic, 46 Noci-association, chemical, in infections, 48 Nociceptors, 14 diseases and injuries of regions not endowed with, 47

PAIN, 77, 107, 144, 158 cold, 83 contact, special, 78 evacuation, 77 heat, 77 labor, 78 light, 77 nausea, 78 of anemia, 77 of infection, 79 pleasure, 78 post-operative, 89 site of, 83 traumatic, 89 Personality, 47 Phylogenetic association, diseases of abdomen and, 44 in relation to certain medical problems, 1 to emotions, 55 Pleasure pains, 78 Postoperative neuroses, 46 pain, 89 Propagation of species, 152 Psychic discharge of energy, 25 Psychology, mechanistic view, 127

REACTION, kinetic, 93 Receptors, distance, discharge of energy through stimulation of, 25 sexual, 53 ticklish, 19

SELF-PRESERVATION, 152 Sexual neurasthenia, 43 Sexual receptors, 53 Sherrington, 12, 13, 14, 24, 25, 48, 52, 132, 136, 158 Sherrington's law, 24 Shock, prevention of, by application of principle of anoci-association, 36 Sloan, 2, 14, .55, 173 Spinal dog, 4 Starling, 195, 227 Strychnin, changes in brain-cells from, 113 Summation, role of, in discharge of nervous energy, 30 Sweat, cold, 27

TEST, Cannon's, for adrenalin, 134, 196 Thyroid gland, 213 diseases of, effect of, on output of energy, 217 Ticklish receptors, 19 Trauma, cause of exhaustion of brain-cells as result of, under inhalation anesthesia, 8 effect of, under anesthesia, upon brain that remains awake, 3 under inhalation anesthesia, cause of discharge of nervous energy as result of, 12 Traumatic neuroses, 46 pain, 89

VAUGHAN, 180 Venus' fly-trap, 149, 151

WEEPING, 90 Welch, 1 Wells, 227 Williams, 231 Worry, 74

THE END