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The series of phenomena which are called the symptoms of disease appear at first sight to be of such malignant and whimsical and illogical character that it is no wonder that in earlier times, and even to this day in some circles, people consider diseases as entities, as if they were wild beasts seeking whom they might devour. There is something ferocious in the attitude of the symptoms of sudden illness, and there is no blame to the ignorant person, who, seeing only the superficial aspect of the suffering patient, thinks of the disease as a cruel entity, to be propitiated or conquered.
With such a viewpoint, drug therapy is almost inevitable. If diseases are entities, if they have certain powers, if they perform certain malicious actions, then the rational thing to do is to expel, or kill, or counteract the disease, the creature which is making the mischief. Witchcraft sought to expel diseases, modern drug and serum therapy seeks to kill or counteract them. If diseases are malicious entities, and their symptoms are evidences of their presence, as the odor of an animal might betray its presence, then drugs of the most poisonous nature are rational enough, and the only question to be raised is one of the efficiency and expediency of these methods. They are, for the most part, found entirely wanting, even from this standpoint, according to the statements of those who have used them longest. But the standpoint is an untrue one, if there be no diseases as entities. It is true that certain groups of symptoms, usually found co-existant, have been studied and named, and our knowledge of these conditions has been greatly increased thereby, but it is not true that there is any real thing which may be called a disease. The researches into physiological problems during the last few years indicate the utter fallacy of regarding diseases as entities. Disease symptoms are efforts, not at the destruction of the body by some more or less personal malignancy, but at the maintenance of existence under changing and abnormal conditions. Health is not an entity, either; both health and disease are abstract terms applied to conditions of metabolism. Health is merely the condition of an organism which is perfectly adapted to its environment; disease is the condition of an organism which is not well adapted to its environment. When any organism is subjected to the influence of abnormal conditions, its metabolism is affected in various manners. The nature of the changes in the metabolism of the organism depends only in part upon the nature of the external influences; the character of the cells affected is a factor of equal importance. The activities of normal cells vary considerably under normal conditions, and are subject to great variations under abnormal conditions. Hence the nature of the effects produced upon the cells by any given abnormality in their surroundings may differ very widely at different stages of physiological activity.
Loeb has shown that some of the simpler animals reverse their reaction to light under the influence of temperature changes. H. S. Jennings and Ada Watterson Yerkes have shown that among the unicellular organisms and the simpler multicellular organisms the character of the reaction to any stimulus depends in large part upon the character of the stimuli previously received. The behavior of these organisms is then said to be “modifiable.” The nature of the reactions of these organisms is modified by the occurrence of previous stimulations. It would almost seem that the phenomena observed in these cases indicates a sort of education of the cell, if the expression may be employed without involving any considerations of consciousness on the part of these simple structures.
The nature of the living molecule may be considered for a moment. The ultimate division of living proteid matter that retains a semblance of life is too small to be seen with the microscope. That is, the very smallest bits of protoplasm that can be seen display signs of life, and it is probable that still smaller bits also live for a time. It is hardly likely that the limits of our present vision should coincide with the limits of the size of the proteid molecule. But the smallest bit of protoplasm that displays the powers of nutrition and reproduction must be quite large. It must include both nucleus and protoplasm in a certain amount. Although the living proteid molecule is ultra-microscopic, it is known that the chemical configuration of the molecule is continually changing, and yet retains its individuality throughout its life time. This apparent anomaly becomes conceivable when the activity of the living cell is compared to a water-fall. Here, in a crude manner, is illustrated the phenomenon of continual change with retention of identity. In a far more complex manner, yet perhaps in some ways comparable to this, the cell retains its identity and its characteristics through changes almost inconceivably rapid and exhaustive. The central portion of this living molecule may be considered as fairly stable. Attached to this rather stable center are side-chains of very variable structure. There are certainly chains containing certain fatty acids, some containing carbohydrates; some apparently contain simple sugars, others hold oxygen in unstable combination and facilitate oxidation processes, and many are very complex nitrogenous side chains. The character of the foods that are taken up by the living proteid molecule depends upon the affinities of these side chains. The nature of the reaction of the cell to external stimulation depends upon the essential structure of the molecule and upon its position in the rhythm of its series of chemical changes. As illustrative of the first of these factors, we note that a muscle cell contracts and a gland cell secretes under the influence of identical stimuli; while as an instance of the second factor, we note the occurrence of the “latent period” of muscle and neuron.
Overton has studied the permeability of cells under different conditions. He finds that the substances that are soluble in water and also in organic solvents, -- Oil, ethyl-ether, the higher alcohols, etc., penetrate cells very easily. But the more the solubility of any substances in water exceeds its solubility in the organic solvents, the more slowly does it penetrate living cells. Overton suggests that the limiting layers of the protoplasm are impregnated with a fatty substance,--a mixture of lecithin and cholesterin, and that the elective solvent power of this mixture for different substances governs the pure osmotic permeability of the cells. If this be a justifiable conclusion , the accumulation of the products of katabolism might affect the permeability of the limiting membrane and thus affect the permeability of the limiting membrane and thus affect the reaction of the cells to subsequent stimulation. The immunity of some cells to certain poisons, and the great susceptibility of others may be in part due to the nature of this “elective solvent power” and in part due to the affinities of the open side chains at the moment of the stimulation. The variations of the reactions to the same stimulus at different times may be accounted for in this way, perhaps.
Many of these variations in the metabolism of the cells, or of animals or plants of higher development, form a part of their normal life or race history. These are not to be considered abnormal manifestations. The phenomena of metabolism are normal so long as the cell is able to reply to its environal changes in an efficient and logical manner; the phenomena of metabolism become abnormal when the cell is unable to give a logical reply to the changes in its environment. Or, in other words, the cell, or group of cells, is normal when it is able to secure from its environal changes the energy necessary to the perpetuation of its characteristic metabolism; it is abnormal and displays phenomena which we call the symptoms of disease when it is not able to make use of the energy supplied by its environment, in a degree sufficient to maintain its characteristic series of chemical reactions, or when the environment itself is abnormal.
Because of this possibility of variation in cell metabolism, the cells (and cell groups) are able to endure certain changes in their environment. If the changes be slowly made, and if it be not destructive in its effect upon the cell structure, the cells may become adapted to the new environment, which thus becomes the normal. During this period of adaptation, the cell metabolism is not that which is characteristic either of the cells in the old environment, or of the acclimated cell. During this period of adjustment, the cell is not to be considered quite normal. It is more susceptible to the ill effects of temperature changes, is more erratic in its reactions to unusual stimulation. In the case of the higher animals, the cells are more easily fatigued, more liable to injury, and more susceptible to bacterial invasion. Ultimately, under such conditions, either adaptation is secured, and the new environment becomes the normal one, or the cells and organisms perish, as is the case with the manifestly unfit.
Cells are unable to make rational reply to the changes in their environment under two conditions: The cell structure may be abnormal or its environment may be abnormal. The cell structure may be abnormal from its first existence as an individual. The influence of heredity in maintaining peculiarities of structure is not doubted by thoughtful persons. This influence is not absolute, however, but is subject to modification by environal conditions.
The influence of heredity is to perpetuate the best of the race, for the most part. By varying combinations, and the tendency of those with unworthy characteristics to die young, the normal and sane characters leave greater effects of their lives upon the race than do the abnormal or insane, unless the abnormal conditions be perpetuated by continuous inbreeding. There is an inheritance of cell structure as well as of gross structure, as is shown by the occurrence in families of nutritional or metabolic traits. In the last analysis, these tendencies must be transmitted as peculiarities of structure, only in the one case it is a peculiarity of gross, and in the other of molecular, structure. Given the faulty inheritance, the occurrence of disease symptoms is almost inevitable, under conditions of unusual stress, at any rate. It is true that the weakling may live a fairly normal life provided his environment remains fairly normal. The normal person is able to maintain normal conditions of metabolism under unfavorable conditions. The weakling fails in time of extra demands. The only thing to do for the person of faulty inheritance is to give him the environment that secures for him the best strength of body and mind of which he is capable. This varies with all individuals. The gross structure of the body may be rendered abnormal by accident. This aspect of the subject has been discussed in Chapter I. The
structure of the body may be rendered abnormal through faulty function.
By this is meant that the environal changes may make excessive or unusual
demands upon the powers of the cells or the cell groups, and the cells
be finally injured, or the environment may not afford the available energy
needful to the metabolism of the cell.
The older theories of pathology rested with the discovery of the abnormal structure of the cells of the organ whose malfunction was being investigated. The later investigations seek to penetrate further into the causes of the lack of cellular integrity. The osteopathic theories of pathology differ from those commonly accepted in this urgent demand for the causes of malfunction. The view that the normal cell may act in an abnormal manner unless it is affected by some abnormal factor in its environment is unscientific and primitive. Every rational theory of disease or therapeutics must recognize as a biological necessity that there is an efficient cause for malfunction,--that every symptom of disease is the manifestation of a changed metabolism of the cells of the body in reply to some abnormal donations in their environment or structure.
The cells of bodies so complex as ours have as their environment the other cells of the body, and the fluids formed by other cells. Thus, any malfunction of any cell may affect almost any other cell in the whole body. For this reason, the symptoms of disease may be grouped as the phenomena displayed by cells in their reactions to their environment; the phenomena displayed by cell groups, or organs in their reaction to their environment; and the phenomena displayed by the body as a whole in its reaction to its environment. These reactions are theoretically separate. Actually, the reaction of one cell group, or one organ, affects the reactions of others and of the body as a whole. For convenicence, however, the simple classification may be retained here. The effects of changes in the environment of the cells may be considered in some detail. It
is not desirable that every possible factor in the environment should be
considered in this connection. The study of the significance of the
symptoms resulting from a few of the changes in the environment of cells,
organs and the body as a whole will serve to illustrate some of the principles
underlying all disease processes.
The phenomena of starvation have been studied from the condition of starving cells and from the condition of certain organs of the body when their nutrition is interfered with. The starving paramecium was studied by Wallengren. According to his observations, the food masses and the food vacuoles disappear first. Small granules, probably deutoplasm, disappear next, and the living substance of the endoplasm is then used as a source of energy. The cilia keep on waving, and the contractile vacuole maintains its pulsation at the expense of these structures until they are exhausted. The endoplasm becomes vacuolated, and just before all signs of life fail the cilia are absorbed, then the macronucleus, and the micronucleus persists longest of all the cell structures. All that remains of the cell becomes granulated and the granules fall apart. Nothing is left but a mass of granular debris. This description of the starving paramoecium resembles the vivid pictures which Berkeley gives of the neuron which dies of old age.
Organs of the body which have failed to secure sufficient nourishment, or nerve fibers which have been severed from their cell bodies, or cells which have been poisoned, or which have been subjected to abnormal pressure, may undergo what is called “fatty degeneration.” These conditions are probably all due to failing nutrition, in their ultimate nature. The occurrence of fat in these starved cells appears at first sight to be rather an anomaly. Leathes and his predecessors have found that much of the fat found in these tissues is derived from other less essential organs of the body. Another part of the fat found in starvation is accounted for in another way. The living proteid molecule contains at least one and probably several side chains built upon the plan of the fatty acid radical. There is reason to believe that a partial disintegration of the living molecule sets the fat free. Leathes shows, in this relation, that the heart, the cerebral cortex, and degenerating nerve fibers contain actually less fat, by careful analysis, than do these tissues under normal conditions. Under normal conditions, these side chains do not give the micro-chemical reactions characteristic of fats in general, because they are in chemical union with the other parts of the living molecule. But it is possible to break them off, and to extract and estimate them as fats. By the action of the autolytic enzymes during bad nutritional conditions, these side chains are set free from their feeble union with the rest of the living molecule, and they then give the micro-chemical reactions of the fats. Hence the old absurd idea that the fatty degeneration is a cause of disease.
There also occurs a form of starvation not commonly considered as such, -- oxygen starvation. Organisms of simple structure may live upon the oxygen derived from the disintegration of oxygen-containing compounds, but higher animals require this gas to be supplied to them free from “entangling alliances.” Such complex bodies as our own require that the oxygen shall be brought to the cells in a very continuous stream. Oxygen starvation is sometimes characterized by an excessive storing of fat. The abnormal fatty accumulations found in persons suffering from cardiac lesions are due to the faulty oxidation. The condition is in no way different in its nature from the excessive deposit of fat which accompanies deficient hemoglobin percentages.
The low hemoglobin percentages are often due to faulty nutrition, and this condition may be due to bad habits of eating, as well as to some digestive ailment. Ordinarily, starvation causes emaciation, but a lack of oxygen, either in the air, or in the blood and lymph, or because of a lack of the iron and phosphorus containing foods, may be accompanied by obesity. It is perhaps needless to point out the fallacy of suggesting starvation diet to the obese person who lacks hemoglobin enough to carry the oxygen requisite to the proper oxidation of the food materials, or whose heart is incapable of sending the aerated blood to the tissues in sufficient quantity to oxidize the food substances, or to carry away the waste products of cell metabolism.
The cells of all forms of life are very susceptible to changes in the osmotic tension of the fluids which surround them. The change in osmotic tension is not the only factor in modifying their metabolism when different quantities of salts are added to their environment, as is shown by the exhaustive work of Loeb and many other investigators into the physiological effects of ions in solutions. Though not the only factor, variations in osmotic tension are very effective agents in modifying the activities of cells. The structure of the cell is changed by variations in the osmotic tension either within its walls, or in its surrounding fluids. It absorbs water, perhaps until it bursts, or it yields its own fluids to its denser medium, until it becomes shrunken and dead.
Under normal conditions the number of molecules within the cell is just sufficient to maintain a normal circulation of liquid into and out of the cell, in connection with the series of chemical changes which are devoted to the same end. If the function of the cell be subjected to serious interference, its very complex molecules become broken down into simpler compounds. This occurs normally under conditions of increased katabolism, but the rebuilding proceeds as fast, or almost as fast, as the breaking down. Abnormally, the anabolism fails in a certain degree. Under abnormal conditions, then, the molecules within the cell are simpler and smaller than normal, there are thus more of them from the numerical standpoint. Since the osmotic tension of any fluid varies according to the number of molecules present, without regard to their size, if the complex molecules are divided into simpler molecules of half the atomic weight, the osmotic tension is doubled. In a cell which has been injured, the molecules are simple and therefore greater in number. Therefore, the abnormal cell, however it may be injured, invariably swells first. The simpler molecules, being more diffusible than the larger ones, are slowly dissolved out of the cell, and the cell shrinks. This sequence of swelling and shrinking is present under almost every manifestation of disease of cells, either those living an independent existence, or those associated with millions of others, as in our own bodies.
Changes in temperature exert a marked difference upon the metabolism of all living things. A slight increase in the temperature of the environment increases the mobility of many unicellular organisms. This increased motility causes their escape from the harmful neighborhood. In like manner, probably, the cells of higher animals react to slight increase of temperature by increased metabolism. In animals with nervous systems of considerable complexity, the increased metabolism of different organs following increased temperature is coordinated in such a manner that the loss of heat from the body is facilitated, and the body temperature kept normal. Higher degrees of temperature are fatal. The resistance of some spores and seeds to high temperatures is very remarkable. Many of them remain alive even after having been boiled for more than half an hour. Variations in the lethal temperature of the various living things depend upon the nature of their more complex globulins. The work of Brodie and Haliburton indicates that the lethal temperature of any animal depends upon the temperature at which its most complex globulins are precipitated. The frog is accustomed to a low body temperature, and dies if kept very long in a temperature above 34 degrees C. Even in glass, the extract from a frog’s muscle forms a coagulum at a temperature of 34.5 degrees C. The extract from the brain or muscle of most mammals does not give a precipitate until a temperature of 42 degrees C. is reached. Extracts from the brain or muscles of birds require even higher temperatures before the first coagulum is formed. This is in accordance with the facts of the resistance of these animals to heat. Birds endure temperatures disastrous to human beings; mammals endure temperatures fatal to frogs. These temperature figures apply to the temperature within the body itself, and takes no account of thermogenic and thermolytic regulation through nervous activity.
Goildscheider and Flatau have studied the nature of the effects of heat upon the neurons. Small animals, rabbits and guinea-pigs, I believe, were kept in a warming chamber at a temperature of 42-44 degrees C. for several hours. After they became apparently moribund, they were removed. Some were killed at once, others at various intervals during their recovery. Not all of them did recover, but some were able to regain their normal condition within periods varying from a few hours to several days, according to the animals, the length of time spent in the warming chamber, and other factors. The brains and cords of those killed at once upon removal from the warming chamber were prepared after the method of Nissl. Their neurons showed that the cell structure had become greatly changed. The tigroid substance had almost or quite disappeared. Its place was taken by light brown opaque masses and small granules. The whole cell was enlarged and the dentrites much swollen. The animals which began to recover were killed at varying intervals. Their neurons displayed various stages in the return to the normal structure. The opaque masses were slowly absorbed, and the tigroid substance was formed again. The function of the neurons returned before the tigroid substance was replaced. This is in harmony with the view that the tigroid substance represents a store-house of potential energy, rather than an essential part of the cell structure, and that deutoplasmic granules may be of more complex molecular structure than the living proteid. According to Halliburton and Brodie, if an extract be made of the brains of animals dying from excessive heat, it does not produce a precipitate at 42 degrees C. as do extracts of normal brains. The difference is clearly due to the fact that these have been precipitated before death, or at the time of death. The globulins of muscles, glands, nerve cells and other active structures of the body give the first precipitate at about the same temperature. (It is commonly known that there are several globulins present in all living structures, some of which are only distinguishable by differences in their coagulibility.)
The significance of the mental symptoms observed in fever are easily explained in the light of these experiments. The temperature of the body cavities is certainly higher than the mouth temperature. The temperature within the brain must exceed the coagulation temperature of the tigroid substance before death. But a quite advanced degree of chromatolysis is not incompatible with ultimate recovery. Death, or permanent disability, is inevitable after the coagulation of the globulins which form an essential part of the cell structure. During very high temperatures, there is no mental activity whatever; under less increase of temperature, the mental activity is abnormal but intense. After recovery from high fever, the mental activity is decreased until the partly precipitated complex globulins representing the reserves of potential energy are again rebuilt by the cell. In some cases, some of the cells may have yielded to the effects of the high temperature sooner than others, and these may have been injured in their essential structure. Recovery is not possible for these, and the patient never does recover his old measure of mental efficiency, unless embryonic cells may be developed to take the place of those injured. Delirium is due to the stimulating action of the high temperature upon the neurons; torpor is due in part to exhaustion, in part to the presence of toxins, and, more seriously, in part to the partial precipitation of the deutoplasmic globulins in the neurons.
The fatigue phenomena display two well marked series of disease symptoms. The symptoms commonly called fatigue are really conditions of poisoning from the retention of the waste products of metabolism. Very similar to this condition are the phenomena observed in the action of ferments. These act with celerity upon the class of substances to which they are adapted, but after certain changes are produced, the accumulation of the products of the ferment action hinders further action until these substances are removed. Cells are unable to maintain their normal metabolism in the presence of their own waste products, even though their food and oxygen supply remain normal, and every other factor is such as to facilitate metabolism. The cells of more complexly organized beings are also unable to perform their functions normally in the presence of their own waste products. The more active the metabolism of any organ, the more rapidly are its waste products formed and the more essential is their rapid removal. The psychoses and neuroses which are usually considered due to exhaustion are in reality due more to auto-intoxication than to an actual exhaustion of the cells. It is true that there are conditions of real exhaustion underlying some of these neuroses, but by far the larger number of these are merely due to the retention of the wastes of metabolism within the system, or to some other form of poisoning, as, for example, the use of stimulating drugs. The ordinary sensations of fatigue are due altogether to the accumulation of the katabolic products within the blood and lymph streams. Under normal conditions, there is rarely a possibility of exhaustion, in the literal sense of the word.
There are some instances, however of true exhaustion, or of what seems to be true exhaustion. This occurs in the muscles as a result of long continued strain under excitement or the stress of some unusual circumstances. The muscle atrophies afterward, and only rarely recover, though the maintenance of the normal nerve and blood supply seems to facilitate recovery in some cases. In the case of the nerves, cases presenting the symptoms of exhaustion are more frequently found. In these cases, the rational treatment should include rest, and plentiful food, and the correction of all conditions which might interfere with the normal anabolic processes. In the cases mentioned in connection with fatigue, such a treatment would be disastrous. Here there is needed the increased elimination of the waste products, the rather slim diet, the increase of the oxygen supply, often the increase of exercise, and the correction of all factors which prevent the free elimination of the katabolic wastes. These cases present about the same subjective symptoms, but the treatment advised the one might be very inefficient for the other. If any cell, or any organ of a complex body, does not perform its duties in a normal manner, it is because there is some reason for its malfunction. The use of certain stimulants may cause a further evolution of energy, and thus secure the appearance of the normal function, but this evolution of energy must be at the expense of the cell structure. The experiments which have been performed upon cells show this beyond question, in the case of simpler animals, and there are post-mortem findings which verify the conclusion in human beings. The onset of starvation may be very greatly facilitated by increasing abnormally, by stimulants, the activity of the organism subjected to experiment. The fallacy of trying to increase the activity of over worked, poorly nourished structures by any form of stimulation, is apparent. It would be just as rational to try to stimulate an engine to run while the fire box is empty. In the other cases, where the fatigue symptoms are due to the accumulation of the wastes, an effort to secure a return to health by increased feeding would be as sensible as an effort to make a fire burn while the stove is full of ashes. These considerations apply in a certain degree to the reactions of organs of the body to abnormal factors in their environment. Among the simpler forms of life the injury or destruction of any organ is followed by the regeneration of the lost part. This process may be repeated for a number of times which varies for the species, but which has not been found unlimited for any. With the appearance of the complex and efficient nervous system such as vertebrates possess, the possibility of regeneration decreases. It has not yet disappeared, for even we ourselves grow new skin daily. For the most part, however, regeneration has been superseded by compensation. The nervous system has so perfectly unified the various and diverse organs of the body that the injury of one is shared by all, and the strength of one is shared by all. The nervous system regulates this matter very largely, though there are other factors concerned in compensation. The nerve relations concerned in compensation are discussed in Chapters VII and VIII. The reaction of the body as a whole to its environment is for the most part a matter of conscious action. In the case of the unicellular organisms, we consider that certain phenomena are significant of life, and that the absence of these phenomena denotes death. So, in the case of people, there are certain mental attitudes which are characteristic of life, and there are certain other conditions which indicate the presence of some abnormality either of structure or environment. The normal person experiences pleasure in living. His circumstances may affect him unpleasantly at times,--he is not normal if he is able to enjoy, or to look with indifference upon anything which occasions pain to any one, or which has a disastrous effect upon his neighbors in any way. Yet, on the whole, the normal person enjoys life, and likes to help others also to enjoy it. A gloomy outlook indicates an abnormal condition of the cortical neurons. There are some diseases, notably tuberculosis, in which there is a tendency to an abnormal, because baseless, cheerfulness. The occurrence of this cheerfulness is not to be considered as indicative of a favorable prognosis in this disease, but if the dyspeptic should become cheerful the prognosis becomes bright almost at once. Motion is characteristic of life. In the same way, expression is significant of the normal mental condition. The normal brain transfers the sensory impulses which reach it into some form of activity. The cell derives energy from its environment; it is not normal if it does not do so, or, if it does not use that energy for the good of itself and its race. The person of normal mentality derives energy from his environment and uses that energy for the good of himself and his race. He is not normal if he does not do so. The person whose cortical neurons are starved or poisoned is not capable of doing the best work, of living the best life, of attaining the highest pleasure, of enjoying or of expressing in any effectual degree those generous and altruistic instincts which make for the highest and finest development of human life. In short, the person of normal brain works and enjoys work, lives and enjoys life, and bases all his efforts upon a rational appreciation of his environment, and of his own place in the midst of things. Mental conditions not in harmony with these factors are not normal and are significant of some interference with the structure or the nutrition of the neurons, or with the environment of the individual. Note A.—According to Plato, “No man is voluntarily bad; but the bad becomes bad by reason of ill disposition of the body and bad education, things which are hateful to every man and happen to him against his will.”
Diffusion and Osmosis, in Howell’s Physiology, p. 881, Edition of 1906. The Assimilation and Synthesis of Fat, in Leathes’ Problems of Animal Metabolism. |