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INDIGESTION AS A CAUSE OF NERVOUS DEPRESSION.

T. LAUDER BRUNTON, M. D., F. R. S.

To most men who are engaged in intellectual work, an autumn holiday has become a matter of necessity, and is not to be regarded as a mere luxury. During eleven months of the year many who are engaged in brain-work systematically overtax themselves, trusting to the month's holiday to bring them again into proper working order. Formerly this was not the case. Men seemed to be able to go on, not only month after month, but year after year, without any vacation at all. The circumstances under which they lived were different from those which exist now. The very means which facilitate our holidays—the network of railways which puts us into complete and easy communication with any part of the Continent of Europe, or the quick ocean-steamers which enable us to enjoy half of a six weeks' holiday on the other side of the Atlantic, as well as the telegraphic communications which will warn us in a moment, even at the most distant point of our travels, of any urgent necessity for an immediate return—all these are the very means which increase our labor during the greater part of the year. We live at high pressure; letters and telegrams keep us constantly on the qui vive; express trains hurry us miles away from home in the morning and back again in the evening, and the pressure of competition is so great that few men can afford either to take their work easily or to modify the constant strain of it by breaks of a day or two at a time. Wearied and exhausted, the hard-worked man goes off for his autumn holiday, and, if he can, will spend most of it in the open air, either yachting, walking by the seashore, strolling in the country, shooting on the moors, or climbing the Welsh hills or the Swiss mountains. After a month spent in any of these ways, the brain-worker comes back to town feeling himself a different man. Instead of his work being a slavery to him, as it was before he started, he feels it to be a pleasure; he gets through it with ease, and feels not only that the amount he can accomplish is greatly increased, but that the quality is also improved. Perhaps for a short time after his return he is hardly in a condition to do brain-work at all. He sits down to his desk, but feels cramped in the unaccustomed posture, and he would rather work off the superabundant energy within him in a long walk or a stiff climb than restrain it with difficulty to the simple task of driving a quill. After a week or two he settles down and works steadily along with comfort and ease for a couple of months or more, when he again begins to sink below par. His apprehension is no longer so acute, his power of concentration is diminished, he can no longer fix his attention for any length of time upon one subject without a severe effort. His mental vision becomes less perspicuous, his ideas succeed each other more slowly, and find expression with greater difficulty, so that he communicates his thoughts with less fluency and less clearness than before. His temper, too, undergoes a change. Instead of regarding the daily occurrences of life with equanimity, and making the best of what can not be helped, irritation so slight as to be unfelt at other times provokes him to anger or peevishness, and even when he possesses sufficient self-control to restrain his feelings and prevent them from being manifested outwardly, to the annoyance of his friends or neighbors, the very effort of restraint seems to increase the internal irritation, until at last it either explodes in an ebullition of wrath on some comparatively trivial circumstance, or tells upon the digestion and nervous functions of the individual himself, diminishing the appetite or causing intense muscular weariness. In others, again, we find that along with or taking the place of irritability there is great mental depression. Everything is looked at from a gloomy point of view—himself, his friends, and his surroundings. He does not feel equal to his work; nothing that he does pleases him; he is apt to become distrustful of himself and jealous of others; apt to think that his friends are slighting him, or to fancy that he has offended them. Even when all external circumstances leave nothing to be desired, the unfortunate victim can not enjoy life. His mind is occupied with gloomy forebodings of miseries to come, or he becomes a prey to melancholy and depression without any apparent reason. This melancholy weighs most deeply upon him during the night, and if he happens to wake in the small hours of the morning, as he not unfrequently does, life seems not worth living, but a burden of which he would willingly be quit. Melancholy is at times associated with sleeplessness, and then the two evils react upon and increase each other. For this causeless sorrow has a similar effect to that of real sorrow. As Shakespeare says:

"Sorrow's weight doth heavier grow,

Through debt that bankrupt sleep doth sorrow owe."

At other times instead of sleeplessness there is an abnormal tendency to drowsiness, which sometimes comes on almost irresistibly at the very moment when some important work, requiring all the best powers of the intellect, has to be performed, and rendering its performance either imperfect or completely impossible. As soon as the person goes to bed he falls asleep, and sleeps like a log till morning, when he rises with difficulty, feeling more exhausted than when he went to bed the night before, with perhaps a little tightness or pain over the forehead, eyes, or temples. After breakfast he feels somewhat revived, and will work comfortably for a short time, but about one and a half or two hours after the meal weariness overtakes him, again passing off after it has lasted a variable time. During the day this is repeated, fits of more or less energy alternating with periods of languor and exhaustion. These languid fits may be noticed two or three hours after lunch or dinner, and the sufferer is not unfrequently tempted to have recourse to the decanter of sherry or the brandy-bottle, not only to obtain relief from the feeling of personal discomfort, but to supply the energy which he feels to be necessary to enable him to do the work he has in hand. But this is a ruinous course to adopt, for not only does it pave the way to habits of confirmed drunkenness, and leads to tissue-changes which will ultimately abolish the functional activity of the most important organs of the body, and bring the individual to a premature grave; it enables him to do his work only imperfectly at the time. After an application to the decanter or bottle his powers may seem to himself to be as great as or greater than usual, but this is to a considerable extent a subjective feeling only, as he will probably be able to discover by results.

Now, how is it that such a change has come over the man in a few months, so that he seems to be a different individual from the one who returned, bright and lively, from his autumn holiday? How is it that the even-tempered man has become irritable, the clear-headed man muddled, the active lazy, the sober perhaps a tippler, and the cheerful and buoyant depressed and melancholy; that the brain performs all its functions with difficulty, and the mind is so altered that it does not seem to be that of the same individual? And yet, after all, the man is the same, and the brain is the same, at least in its essential structure, as it was a few months ago, and as it will be in a few months more, after another holiday has again put it in good working order. What has happened to it in the mean time to cause such a dreadful alteration? Not only does the brain seem exhausted, but the whole system appears to be languid and weak; instead of the man being able for a twenty or thirty miles' walk, one of a mile or two will produce fatigue, and sometimes an intense languor is felt without any exertion at all. And yet all this time he may have been trying to keep up his strength. He takes butcher's meat three times a day, perhaps also strong soups, to say nothing of wine, or brandy-and-soda, to pick him up. His tissues ought to be getting sufficient nourishment to enable them to do their work, and yet it is evident that they are not in a condition to do so. The man, and very likely his friends also, wonders at his condition, and when he goes to his medical attendant to describe his case he says, "I take all sorts of strengthening things, and yet I feel so weak." If, instead of using these words, he were to say "Because I take all sorts of strengthening things I feel so weak," he would express a part at least of the truth. He and his friends who wonder with him forget that all the functions of life are more or less processes of combustion, and that they are subject to laws similar to those which regulate the burning of the coal in our fireplaces. Two things are necessary for the combustion, fuel and oxygen; sometimes it is the fuel that fails, but not unfrequently it is the oxygen. Sometimes, no doubt, our fires go out because the fuel is quite exhausted, but this is very rarely the case. It is only under very exceptional circumstances that we find a fire burned away so completely as to leave nothing but ash. Almost invariably some fuel still remains—often, indeed, enough to make up a good fire when properly put together. If we sift the ashes from the grate we generally find a quantity of cinders, sufficient to make a fire, and these have ceased to burn because they were unprovided with oxygen, which was prevented from reaching them by the ashes with which they were covered.

The reason why our fires burn low, or go out altogether, either is that we put on too much coal, or that we allow them to be smothered in ashes. It is the child who pokes the fire from the top to break the coal and make it burn faster; the wise man pokes it from below so as to rake out the ashes and allow free access of oxygen. And so it is with the functions of life, only that, these being less understood, many a man acts in regard to them as the child does to the fire. The man thinks that his brain is not acting because he has not supplied it with sufficient food. He takes meat three times a day, and beef-tea, to supply its wants, as he thinks, and he puts in a poker to stir it up in the shape of a glass of sherry or a nip from the brandy-bottle. And yet, all the time, what his brain is suffering from is not lack of fuel, but accumulation of ash; and the more he continues to cram himself with food, and to supply himself with stimulants, although they may help him for the moment, the worse does he ultimately become, just as the child's breaking the coal may cause a temporary blaze, but allows the fire all the more quickly to become smothered in ashes. It would seem that vital processes are much more readily arrested by the accumulation of waste products within the organs of the body than by the want of nutriment to the organs themselves. In all cases of fasting, whether voluntary or compulsory, life is prolonged to a much greater extent if water be freely supplied. Without water the individual quickly dies, however much other nourishment he may get, but with abundance of water he may live for a considerable time, even if he take no solid nutriment at all. Here it is not that the water acts as a food; it supplies no new energy to the body, for, unlike starch, or sugar, or fat, or proteids, it has already undergone complete combustion. It can not, like them, unite any further with oxygen and thus supply energy.

And yet it is more essential to life than any of them, for without it the products of waste can not be removed from the tissues, and the vital fires, so to speak, are smothered in their own ash. If we take the excised muscle of a frog and stimulate it to repeated contraction, the contractions become feebler and feebler, until at last they cease altogether. But this is not because the fuel which the muscle contains in itself has been so completely burned up that none of it is left to furnish the requisite energy to the muscle; it is because the chemical processes necessary to the contraction of the muscle are arrested by the accumulation of the products of its own waste. If we wash these out of the muscle by sending through its vessels a weak solution of-common salt, which supplies to it no new material, but which removes these waste products, the contractile power of the muscle will be restored.

This restoration takes place still more quickly and thoroughly if we employ a fluid which will supply oxygen, such as a solution of permanganate of potash, instead of a simple solution of salt, which merely washes out the muscular waste. The muscle is like a fire in the grate, which goes out long before the coal is entirely consumed, on account of the ash which smothers it, and just as we can revive the smoldering embers by supplying them with oxygen by the use of bellows, so the muscle revives more quickly when its supply of oxygen is increased. The quicker the fire burns the sooner will it be choked in ash, and the more rapidly the muscle contracts the sooner will it lose its powers.

The same is the case with the heart. The slowly beating heart of a crocodile will pulsate for a day or more after it has been cut out of the body, but the rapidly pulsating heart of a mammal will very soon cease to beat; and, the more rapidly it has been beating before the animal's death, the sooner will it cease to contract afterward. If the vagi are cut in the living animal so that the cardiac pulsations become excessively rapid, the heart's movement ceases almost as soon as the animal dies; but, if during life the vagi are irritated so as to make the heart contract very slowly indeed, it comes to resemble more nearly the heart of the crocodile, and continues to pulsate for a considerable time after the animal's death. The heart, too, resembles voluntary muscles, inasmuch as, if we wash out of it the products of its own waste, it will continue to beat for a much longer time than if we allow them to accumulate. By simply allowing a saline solution to circulate through the heart of a frog it may be kept beating for many hours longer than if it were left to itself. Both voluntary muscles and involuntary ones, such as the heart, cease to act, almost invariably, not by exhaustion of their energy-yielding substance, but by accumulation of the waste products within them; and muscles, both voluntary and involuntary, are much less sensitive to this process of choking than the delicate structures of the nerve-centers. The gastrocnemius, or the heart of a frog, may retain its irritability for very many hours after its sepation from the body, but the spinal cord of the same animal will rarely retain its irritability for a single hour after the circulation through it has been arrested. In warm-blooded animals the spinal cord is much more sensitive than in the frog, and, if the circulation in the lower part of the spinal cord be arrested in a rabbit by the pressure of a thumb upon the aorta for three or four minutes, the hind-legs of the animal will become completely paralyzed. Still more sensitive than the spinal cord is the brain, and if the circulation in the latter organ be arrested, consciousness is almost instantaneously abolished. In the animal body as in the steam-engine, the governing and directing parts are much more sensitive and easily acted upon than the working parts. A single touch of the hand to the steam-valve will set the engine in action or stop its movement, although the power of a thousand men applied to the fly-wheel would avail little or nothing. And in animals the nerve centers are most sensitive and respond most readily to those circumstances which affect the organism. Not only are they exceedingly sensitive to the accumulation within them of the products of their own waste, but they are easily affected by alterations in the blood which circulates through them, and which conveys to them not only the products of muscular and glandular waste formed in other parts of the body, but also substances introduced from without, or absorbed from the intestinal canal. A single whiff of nitrite of amyl is sufficient to dilate the blood-vessels; a fraction of a grain of pilocarpine will stimulate the sweat-glands to the most profuse secretion; and half a drop of pure hydrocyanic acid is enough almost instantaneously to abolish consciousness and destroy the functional activity of the entire nervous system. In the case of the nitrite of amyl, the pilocarpine, or the hydrocyanic acid, we are able to distinguish the relation of cause and effect between the administration of the drug and the resulting changes in the organism. We do this, however, because of our knowledge, obtained by observation and experiment. Sometimes we can not do this. I have seen, for example, a person become aware of a peculiar sensation which, to the patient, was quite unaccountable, but of which I understood the reason, as I knew it to be due to the fumes from a bottle of nitrite of amyl, which the patient could not see. We may notice a similar occurrence in poisoned animals. The poison of the cobra causes paralysis of the spinal cord and nerves, and induces intense weakness, so that the limbs of the animal fail under it, I have seen an animal in this condition attempt to walk, and look round at its legs with a puzzled air, as though it could not understand what was the matter with it. It could not connect the weakness in its limbs with the introduction of the poison some time previously, although the connection between them was to me perfectly clear.

In the same way as the action of the cobra-poison was a mystery to the animal, an epidemic of typhoid fever was formerly to us a mysterious occurrence for which no reason could be assigned, but we now trace it to the absorption into the bodies of the sufferers of typhoid poison introduced from without. We are now completely alive to the important results produced by the absorption from the intestinal canal of poisonous matters, such as typhoid-germs, arsenic, or strychnine introduced into it from without. But perhaps we are not yet sufficiently alive to the important results produced by the absorption from the intestinal canal of substances generated in it by fermentation or imperfect digestion. We recognize the danger of breathing gas from a sewer, but probably we do not sufficiently realize that noxious gases may be produced in the intestine, and, being absorbed from it into the circulation, may produce symptoms of poisoning. And yet we know, from recorded observations, that such is the case, and that one at least of the chief components of sewer-gas, viz., sulphuretted hydrogen, may be produced in the intestine. This gas, which is so readily recognized by its smell resembling rotten eggs, was found by Dumarquay[1] to be very quickly absorbed indeed from the intestine when injected into the rectum, and to be quickly excreted from the lungs, sometimes appearing to produce, during its elimination, some inflammation of the trachea and bronchi. This was especially the case when small quantities were injected, and it seems not improbable that the production of this gas in the intestine may have something to do with the bronchitis which is not unfrequently observed in connection with digestive disturbance. In cases of indigestion this gas seems to be not unfrequently formed, because persons often complain of the taste of rotten eggs in the mouth or in the eructations. Even in such small quantities it is not improbable that it may exert a deleterious influence both upon the nervous system and upon the blood, for it is a powerful poison, in its action somewhat resembling hydrocyanic acid, though not so strong. It destroys ferments, and robs the blood-corpuscles and the seeds and roots of plants of their power to decompose peroxide of hydrogen; and, as this faculty seems to be closely associated with the processes of life, the sulphuretted hydrogen may be regarded as a powerful protoplasmic poison. Upon plants it has a curious action, differing very markedly from sulphurous acid. When plants are exposed to sulphurous acid, the leaves shrivel up, wither, and fall off, but, if the plant be now removed from the noxious influence of the gas and placed under favorable conditions, it will recover and send out fresh shoots. But, if it be exposed to the action of sulphuretted hydrogen, the leaves, instead of shriveling, simply begin to look flaccid, and droop. This seems, at first sight, to be a less deadly action than that of the sulphurous acid, but when the leaves have once begun to droop in this way the plant is dead, and does not recover when removed from the action of the gas. This gas is rarely generated in the intestine in such a quantity as to give rise to symptoms of acute poisoning, but it has sometimes this effect. A case is recorded by [2] in which a strong and previously healthy man became affected with a slight gastro-intestinal catarrh in consequence of some error in his diet, and on the second day afterward he had frequent eructations, smelling strongly of sulphuretted hydrogen. At the same time he suddenly became collapsed, pale, giddy, and with a rapid, small, compressible pulse. This lasted for one and a half to two minutes, and then passed off. The urine which he passed shortly afterward contained sulphuretted hydrogen. On the same day he had a second attack of a similar sort, and then, the bowels having been opened, he recovered completely. Nor is sulphuretted hydrogen the only gas which may be formed in the stomach. Marsh-gas is sometimes formed there too, and, in an exceedingly interesting case recorded by Dr. Ewald,[3] the quantity was so great that it first attracted the patient's attention by taking fire as it issued from his mouth while he was lighting a cigar. In this curious case the formation of gas alternated with the production of a great quantity of acid fluid in the stomach, which led to vomiting, or, as the patient himself expressed it, sometimes his gas factory and sometimes his vinegar-factory was at work. It is possible that this gas may be formed in small quantities in many more cases than has hitherto been suspected, but its absorption does not seem to have anything like the same deleterious action as that of sulphuretted hydrogen. Nor was the acetic acid which was found by chemical analysis to exist in the acid secretion of the stomach in this case likely to be productive of any injurious effects after its absorption. But butyric acid, which is sometimes formed in the stomach in other cases of indigestion, has been shown by O. Weber to be a powerful poison acting chiefly on the nerve-centers.

It seems probable, however, that the substances, both gaseous and solid, formed in the stomach and absorbed from it, are upon the whole less poisonous in cases of indigestion than those which are produced lower down in the intestinal canal. We often find that patients are affected with severe gastric disorder without any affection of the nerve-centers beyond the weakness produced by the inability to digest food, while in many persons the mere omission to evacuate the contents of the bowels at the usual time will lead to a headache in the course of the day. No doubt such a headache as this may be due, to some extent, to the nervous irritation caused by the presence of the fæces in the intestine, but it seems quite possible that it is also due to the absorption of some of the fæcal matter itself. Nor do we at present know what effects are produced by the absorption of the various digestive juices themselves. That such absorption takes place there can be little doubt. It has been demonstrated in the case of the bile, which is absorbed with great rapidity from the intestine and reëxcreted by the liver, so that it does not pass into the general circulation at all. But what becomes of the other digestive fluids, and the ferments they contain? The pepsin finds it way in minute quantities through the liver, and has been discovered in various tissues of the body and in the urine. This, however, matters but little, for it can not act upon the tissues themselves, inasmuch as they possess an alkaline reaction. But the case must be somewhat different with pancreatine, and if pancreatic fluid be absorbed from the intestine and pass through the liver unchanged, we should expect that it would have a very powerful action upon the tissues throughout the body, because there appears to be no reason why it should not act upon them just as it does upon the food in the intestine itself. It seems not at all unlikely, then, that the liver has got another function besides those usually assigned to it, viz., that of preventing the digestive ferments from reaching the general circulation so as to act upon the tissues. Now, we do find in the liver itself and in the bile a ferment having the same diastatic power as the pancreatic juice, but it does not appear in such quantities as one would expect if the whole of the pancreatic ferment were simply reëxcreted by the liver along with the bile, and, as we have no evidence that the ferment is destroyed during its action in the intestine, we are naturally led to think that it may undergo a change in the liver, the converse of that which it undergoes in the pancreatic gland during the process of secretion. In the pancreas itself we have no ready formed ferment, but we have a ferment-forming substance, which has recently become known under the name of zymogen, given to it by Heidenhain, but the writer heard it described by Kühne in his lectures on physiological chemistry delivered at Amsterdam in 1869. I quote verbatim from the notes which I took at the time of his lecture on the pancreas: "Glands which have no action on fibrine can be made active by digesting in very dilute acid and then neutralizing or alkalizing; there seeming to exist a ferment-forming substance in the pancreas." During digestion this ferment-forming substance or zymogen splits up and yields free ferment, and it seems not improbable that it is in the liver that this very ferment, after its digestive work is done, becomes again converted into the ferment-forming substance which may circulate throughout the tissues without doing them any injury.

Whether this be the case or not, however, with regard to the ferments of the gastric, pancreatic, and intestinal juices, all of which must pass through the liver before they reach the general circulation, there can be no doubt that the products of intestinal digestion do undergo very marked changes indeed in the liver, as is shown by the formation from them of very large quantities of a new substance, glycogen—a substance which is not contained in the products of the gastric and intestinal digestion which reach the liver, and yet which is of the highest importance for the nutriment of the body. Under ordinary circumstances, nearly the whole of the sugar formed in the intestine and absorbed from it is arrested in the liver, so that very little passes into the general circulation and appears in the urine, although even in healthy persons traces of sugar are excreted by the kidneys. Under exceptional circumstances, however, sugar may pass through in considerable quantities, as, for example, when the individual takes, on an empty stomach, a large quantity of sirup. However healthy his organs may be, sugar will then appear in the urine. The same is the case in regard to albumen. Usually, the whole albuminous constituents of our food are so transformed in the stomach, intestines, and liver, that no albuminous substances of the kind which can pass through the kidneys get into the general circulation. But, if one takes such a quantity of eggs as to completely overtask the digestive powers, the egg-albumen will pass unchanged into the blood, and be excreted by the kidneys.

Other albuminous substances, the products of intestinal digestion, and peptones also, occasionally make their appearance in the urine, as well as egg-albumen. Even when the processes of assimilation are not so seriously interfered with as in these instances, we observe that products of nitrogenous waste frequently occur in the form of lithates in the urine. An excess of these indicates some pathological condition, even although it may be very trivial. We can not, indeed, say what the exact condition is, because we find lithates appearing in the urine after violent muscular exertion accompanied by profuse sweating, so that they may possibly represent some of the products of muscular waste; but we also find that they occur in large quantities in the urine after slight indiscretions in diet, although no muscular exertion has been undergone, and in these cases we can hardly do otherwise than regard them as products of the imperfect assimilation of nitrogenous matters which ought to have been eliminated, not in the form of urates, but of urea. Now, physiological experiments and observations indicate that the liver is the chief if not the only part of the body in which urea is formed. This at least appears to be the case excepting in febrile conditions, in which, possibly, the urea may also be formed, to a considerable extent, in the muscles. The old notion, then, which connected the appearance of lithates in the urine with disordered function of the liver, is probably in a great measure correct. There is little or no reason to believe that these lithates are formed in the kidneys. They are, probably, simply separated by them from the blood, and their presence in the urine would therefore indicate their presence in the blood and tissues. Now, lithates in themselves do not appear to have any particularly injurious effects, either upon the nervous tissues or the muscles, but, as their presence indicates deficient assimilation, they may be accompanied by other substances which have a much more pernicious action, just as there are many bad smells which, per se, though very disagreeable, have no marked poisonous action, while other very poisonous substances have comparatively little odor.[4] Yet the disagreeable odors which accompany sewer-gas, although perhaps not always dependent upon its poisonous constituents, warn us of the presence of gases which may be intensely poisonous. Nevertheless, just as the poisonous gases may be present without any disagreeable smell, so we may have substances circulating in the blood which have the most injurious effect upon the nerve-centers, without the presence of urates in the urine.

The importance of the functions of the liver in reference to assimilation is now generally recognized, although for a long time this, the largest gland in the body, was considered to have no other office than simply to secrete bile. Although the bile is useful in digestion it is not of primary importance in this process; but its proper secretion is probably associated very closely with the assimilative functions of the liver, and if the biliary secretion does not take place properly we can hardly expect the assimilation to be perfect.

The greatest care appears to have been taken in the construction of the liver to prevent the bile from coming in contact with the blood, the ultimate radicals of the bile-ducts or biliary capillaries being placed as far from the blood capillaries as the structure of the liver will allow. Notwithstanding this care, the distance between the blood and the bile capillaries is small, though it is sufficient, under ordinary circumstances, to prevent the absorption of bile into the blood. But whenever an obstruction takes place to the exit of bile, and the presence of bile in the biliary capillaries increases, an absorption of this secretion occurs. Bile is secreted under very low pressure, and a very slight increase in this is sufficient to cause reabsorption. Such an increase as would not materially affect the secretion of other glands, such as the salivary gland, is sufficient to prevent the exit of bile through the biliary ducts, and cause its reabsorption into the blood. The excretion of bile is greatly aided by the pressure which is exerted upon it by the movements of the diaphragm during respiration, and indeed so low is the pressure under which the bile is secreted that, but for the assistance given by the respiratory movement, it would just barely find its way into the duodenum. Although we are accustomed to say "as bitter as gall," according to my own observations fresh human bile is not bitter. When it is thrown up in consequence of indigestion it is intensely bitter. On one occasion, when making experiments with digitalis, I had taken in the course of two days one grain of the pure alkaloid, and brought on symptoms of poisoning, with intense vomiting. During this I brought up a quantity of bile of a golden-yellow color, and without the least trace of bitterness. This circumstance struck me as being so peculiar that in my published results I hesitated to call it bile, although I did not see what else it could be.[5] But when it remains long in the gall-bladder it undergoes changes, and in some cases of vomiting that I have seen the vomited matters have been of a bright grass-green color. When examined, also, after death, the bile in the gall-bladder is not unfrequently found of a dark color, and the same is probably the case when it is retained in the gall-bladder for any length of time during life. How the Greeks arrived at the notion of giving the name "melancholy," i. e., black bile, to depression of spirits, we do not quite know, but certain it is that depression of spirits is very often associated with indigestion, and, moreover, that the form of indigestion with which we find depression of spirits associated is not so much gastric as intestinal, or, more probably, hepatic. According to Herbert Spencer, we require rapid evolution of nervous energy in order to have exhilaration of the spirits, and depression of nervous energy is associated with melancholy. Now, the effect of bile-acids circulating in the blood, as shown by physiological experiments, is to depress the reflex function of the spinal cord, the functions of the brain also, producing drowsiness ending in coma, and also weakening the circulation by paralyzing the cardiac ganglia.[6] Such a combination of actions is just the one required by Mr. Spencer's hypothesis to produce melancholia, and here we find ancient notions joining hands with modern science.

1 "Comptes Rendus," ix, p. 724.

2 "Berliner klin. Wochenschr.," 1868, No. 24.

3 "Reicherts und Du Bois-Reymond's Archiv.," 1874, p. 217.

4 Brunton and Power, "St. Bartholomew's Hospital Reports," 1877, p. 283.

5 Brunton "On Digitalis," p. 67.

6 Vide Wickham Legge, "Bile, Jaundice, and Bilious Diseases," pp. 207, 216, 217.

But bile is not the only substance which produces a depressing effect upon the circulation when absorbed into it from the portal system. I have already mentioned that certain albuminous products of intestinal digestion and peptones occasionally make their appearance in the urine. Among the former is an albuminous substance, not precipitated by boiling, but by nitric acid in the cold. This constance I have observed in the urine of a healthy man after he had drunk a large quantity of strong beef-tea at a draught upon an empty stomach. My attention was drawn to the urine by the froth remaining upon it for a somewhat unusual time. On examination, this substance was discovered in it. On examining the beef-tea which the person had taken, a similar albuminous substance was found in it, so that there can be little doubt that in this case the albumen was simply absorbed so rapidly from the stomach or intestines that it passed without change through the portal system into the general circulation, and thus reached the kidneys, where it was excreted in much the same way as sugar would have been under similar circumstances. We find only too frequently that both doctors and patients think that the strength is sure to be kept up if a sufficient quantity of beef-tea can only be got down; but this observation, I think, raises the question whether beef-tea may not very frequently be actually injurious, and whether the products of muscular waste which constitute the chief portion of beef-tea or beef essence may not under certain circumstances be actually poisonous. For although there can be no doubt that beef-tea is in many cases a most useful stimulant, one which we find it very hard indeed to do without, and which could hardly be replaced by any other, yet sometimes the administration of beef-tea, like that of alcoholic stimulants, may be overdone, and the patient weakened instead of strengthened. In many cases of nervous depression we find a feeling of weakness and prostration coming on during digestion, and becoming so very marked about the second hour after a meal has been taken, and at the very time when absorption is going on, that we can hardly do otherwise than ascribe it to actual poisoning by digestive products absorbed into the circulation. From the observation of a number of cases I came to the conclusion that the languor and faintness of which many patients complained, and which occurred about eleven and four o'clock, was due to actual poisoning by the products of digestion of breakfast and lunch; but at the time when I arrived at this conclusion I had no experimental data to show that the products of digestion were actually poisonous in themselves, and only within the last few months have I seen the conclusions to which I had arrived by clinical observation confirmed by experiments made in the laboratory. Such experiments have been made by Professor Albertoni, of Genoa, and by Dr. Schmidt-Mühlheim, in Professor Ludwig's laboratory at Leipsic.

Professor Albertoni has found that peptones have a most remarkable action upon the blood, completely destroying its coagulability in dogs, while they have little power in this respect over the blood of rabbits or sheep. The number of species upon which he experimented is limited, so that he can not as yet draw the conclusion with certainty that peptones prevent the coagulation of the blood in carnivora and not in herbivora, although, so far as experiments go, this conclusion seems probable. He and Dr. Schmidt-Mühlheim independently made the discovery that peptones prevented the coagulation of the blood in dogs, and the latter, under Ludwig's direction, has also investigated their action upon the circulation. He finds that, when injected into a vein, they greatly depress the circulation, so that the blood-pressure falls very considerably; and when the quantity injected is large, they produce a soporose condition, complete arrest of the secretion by the kidneys, convulsions, and death. From these experiments it is evident that the normal products of digestion are poisons of no inconsiderable power, and that if they reach the general circulation in large quantities they may produce very alarming, if not dangerous, symptoms.

Such experiments as this open up a new and very wide field of inquiry, which is likely to prove of very great practical importance. We have hitherto been accustomed to reckon all peptones as identical, by whatever digestive ferment they were formed, and to look upon it as a matter of slight moment whether albuminous foods introduced into the digestive canal were dissolved by the stomach or by the pancreas, although it is quite possible that the peptones differ as much from each other as different kinds of sugars. It is a matter of wonder, also, that at the present moment, although the digestive processes have been so carefully investigated, we know very little of the uses of the succus entericus. Notwithstanding the great extent and evident importance of the intestine, and the large quantity of fluid which it is able to secrete, all that we find regarding the action of this secretion in such a book as Foster's "Physiology" is that "the statements with reference to its action are conflicting. Probably it has no direct action on either fats or proteids, but is amylolitic in some animals, though not in all." Succus entericus has also been said to change cane-into grape-sugar, and by a fermentative action to convert cane-sugar into lactic acid, and this again into butyric acid, with an evolution of carbonic acid and free hydrogen. The reason why experiments on the action of intestinal juice have given such an apparently unsatisfactory result is that they have been chiefly tried on such kinds of food as we are accustomed to put into our mouths. Now, the intestinal juice is not intended to act upon such substances: its place is to finish the digestion begun by the other juices; and when experiments with intestinal juice are tried upon foods which have previously been subjected to the action of the other digestive fluids, positive and not negative results are obtained. Thus, for example, it was stated by Kühne, in his lectures at Amsterdam in 1868-'69, that though intestinal juice would dissolve raw albumen and fibrine, it would not act at all upon them if boiled; but if the boiled albumen or fibrine were first subjected to the action of pancreatic juice for a short time, the intestinal juice would afterward dissolve them much more quickly than it would even in a raw condition. The action of digestive ferments is just beginning to find a practical application in medicine, and sometimes, undoubtedly, they are of very great service; but unless their action is investigated more thoroughly than it has been up to the present, it is just possible that we may by and by find that the digestive ferments, like all other powerful agents, may do much harm as well as much good. Hitherto we have been accustomed to regard the phases of digestion, gastric digestion, pancreatic digestion, and intestinal digestion, as almost separate processes, any of which we might increase indefinitely without doing any harm to the patient. We forget the relation which each bears to the other; and yet such a relation undoubtedly exists, for we find that when pepsin is mixed with bile it is precipitated and rendered inert. Further transformation of foods by the gastric juice is thus arrested as soon as the chyme leaves the stomach. And well it is that this should be so, for if the pepsin were not rendered inert it would destroy that pancreatic ferment (trypsin) which acts on albuminous substances, and thus interfere with digestion by it. How far this prolonged peptic digestion and impaired pancreatic digestion of albuminous substances has to do with the production of poisonous digestive products in cases where the quantity of bile poured into the intestine is deficient it is at present impossible to say, but it is a condition which ought to be kept in mind in all cases where there is deficiency of bile in the intestine, and the advisability of nourishing the patient by farinaceous food is constantly considered in these cases.

And now comes the question, How is it that in healthy conditions of the intestine peptones do not pass into the general circulation, and are therefore unable to exert any poisonous action upon the nerve-centers? This question is one which we can not at present answer quite satisfactorily.

Usually the peptones disappear from the portal blood before it reaches the general circulation. Indeed, Ludwig and Schmidt-Mühlheim found that even in the portal blood, before it reaches the liver, very little if any peptone is to be found. They have not succeeded in discovering where the peptone undergoes change. Plósz and Gergyai, and also Drosdorff, have discovered peptone in the blood of the portal vein, and Plósz and Gergyai have been led, by their experiments, to regard the liver as the seat of the transformation of peptones. In consideration of the more recent experiments of Ludwig and Schmidt-Mühlheim, we can not entirely adopt the view of these authors, though it is nevertheless possible that they are to a certain extent right, and that the liver, to some extent at least, serves the purpose of preventing any peptones from getting into the general circulation, which may have escaped transformation in the portal blood before reaching it.[1]

And now, having run over in this cursory manner some points connected with digestion and with the functions of the liver, we come back to the question of why it is that the mental worker becomes depressed, irritable, melancholy, and, it may be, stupid and forgetful, after a few months' work, although every part of his body may be organically healthy, and a month's holiday may be sufficient to restore every organ to perfect functional activity? One reason, no doubt, may be that his systematic overwork may produce a diminution in the energy-yielding substance of his nerve-centers, just as we see that a certain amount of atrophy occasionally occurs in overworked muscles. But this does not seem very probable. It seems much more likely that they cease to act in the normal way because, during each day's activity, a certain amount of waste product is formed which is not perfectly removed during the hours of rest.

All throughout the body we have most elaborate arrangements for removing waste products. In the muscles, for example, we find that the fascia which surrounds them forms a regular pumping arrangement, the two layers of which it consists being separated from each other at each muscular relaxation, and pressed together at each contraction.[2] The lymph and the waste products which it contains are thereby actually pumped out of the muscle at each contraction, and sent onward into the larger lymph-channels, so that the muscular action itself removes the waste products. At the same time we find that the movement of the muscles of the leg, for example, will also pump out the blood from the veins, sending it upward from the feet, and pressing it upward to the body.[3]

Again, we find that in the abdomen and thorax we have pumping arrangements, whereby any excess of the serous fluid which bathes the intestines and lungs is pumped out of the peritoneal pleural cavities by the action of respiration. The two layers of the central tendon of the diaphragm and of the pleura here form pumping arrangements similar to the fascia in the leg.

The brain and spinal cord, being inclosed in rigid cases, have no pumping arrangements in immediate connection with them, but the circulation of the cerebro-spinal fluid in them is probably affected also by the movements of the thorax and abdomen. The cavity of the arachnoid and of the cerebral ventricles is not only continuous with similar cavities in the spinal cord, but also with the lymph-space surrounding the choroid, with the interior chamber of the eye, and even with the lumbar lymphatics; and Professor Schwalbe has succeeded in injecting these parts by a single insertion of the nozzle of his injecting syringe into the arachnoid. His observations have been confirmed and extended by Althann.[4] The experiments of Quincke have shown that during life a current exists in the cerebro-spinal fluid, both from above downward and from below upward.[5] The cause of this current is, in all probability, the respiratory movements. We have, indeed, in the brain and spinal cord, a condition not unlike that which exists in the fascia covering muscles, where the muscular substance during its contraction presses flexibly the inner against the unyielding outer layer of the fascia, and thus produces, in the space between them, a pumping action. The skull and vertebral canal would correspond to the hard outer layer or fascia; and the brain and cord, which, as we know, expand and retract during the movements of respiration, when a part of their bony case is removed, will have a similar pumping action upon the cerebral spinal fluid to that of the muscle upon the lymph in the fascia.

In the case of the brain and the cord there will be, in addition, a pumping action produced by the very circulation of the blood in them, the alternate expansion and dilatation corresponding to the heart's beats, having a similar effect to that produced by the respiratory movements. As stimulation of the brain causes dilatation of its vessels, and increases the flow of blood through them, mental action of itself not only attracts more blood to the brain, but provides to some extent for the removal of waste products. The movements induced by the cardiac pulsations are not so extensive as those caused by the respiratory movements or by muscular exertion, and therefore, when the brain is overworked, and the respiration and muscular movements are underworked, the cerebral nutrition will be diminished by the imperfect removal of waste from its substance. But if, in addition to this, the cerebral cells and fibers are actually poisoned by the circulation within the vessels which supply them, of noxious substances due to imperfect digestion or assimilation, matters will become very much worse,

We have already seen how much the liver has to do with such a condition. Now, while the brain is being taxed to its utmost, the worker generally gets but very little exercise. The consequence of this is, that although the respiratory movements still go on with regularity, and the pressure of the diaphragm upon the liver at each respiration presses the bile more or less out of the liver, yet the pressure thus exerted is very much less than would be the case if the individual were making occasional vigorous efforts during which the breath was held, and the muscles of the abdomen put into action, as, for instance, in springing from bowlder to bowlder on the moraine of a Swiss glacier. So long as the brain-worker is exceedingly careful what he eats, so that no excess of bile is formed, and is fortunate enough to escape duodenal catarrh, so that no impediment, however slight, prevents the flow of bile into the intestine, he may get along perfectly well; but if he be unfortunate enough to get what is commonly known as cold in

the stomach, or unwary enough to irritate the mucous membrane of his stomach or duodenum by wines or spirits, the case is at once altered, for now the swollen mucous membrane of the duodenum tends to close the orifice of the bile-duct, or the congestion may even extend up the duct itself. Thus an impediment, however slight it may be, is opposed to the exit of bile from the liver. The pressure under which the bile is secreted, as I have already said, is very small, and there being no extra pressure put upon the liver by the diaphragm and abdominal muscles, instead of the bile being at once forced out of the bile-capillaries it will remain in them, causing more or less congestion, and now follows a whole series of disagreeable results. The bile, which may be looked upon as a waste product of the liver, not being removed, the other functions of the liver are disturbed. Assimilation becomes imperfect, we find lithates appearing in the urine; the circulation in the liver itself may be altered, and thereby the whole circulation in the stomach and intestines may be impeded, for it must be remembered that all the blood from the stomach and intestines has to pass through the liver before it again reaches the general circulation. Thus the individual becomes troubled with hæmorrhoids, secretion and vermicular movement in the bowels are impaired, so that constipation results; congestion of the stomach, with loss of appetite, impaired digestion, and flatulent eructations ensue, and the brain and nervous system begin to suffer from the accumulation in them of their own waste, or the absorption of abnormal products of assimilation.

Feeling weak, dull, and melancholy, the sufferer now thinks he ought to take meat three times a day, and perhaps, during the intervals of his meals, to take strong beef-tea, or perhaps a glass of wine or a nip of brandy. Yet, in spite of all this, he becomes weaker, more stupid, and more melancholy; and no wonder. He is simply further overtaxing his already overworked digestive organs. He is piling up fuel, instead of removing ash, and choking the vital processes both in his digestive and nervous systems. What he wants is not more nutriment, but a more rapid removal of waste, and the change upon the adoption of a proper system of treatment is in many cases most marked and satisfactory, both to the physician and the patient.

The first thing to be done is to clear out the liver. This may seem to be an unscientific expression, one adapted rather to popular notions than in accordance with ascertained facts. But this is not the case. In a former paper on the action of purgative medicines,[6] I have explained the way in which certain purgatives may be said to have the effect of clearing out the liver, and first among those we must reckon mercurials. In the case which we have just been describing, five grains of blue-pill may be taken every night, or two or three grains of calomel either alone or combined with extract of hyoscyamus or conium, and this should be followed next morning by a saline draught. As a saline we may use sulphate of magnesia, or Friedrichshall, Pullna, Hunyadi Janos, or Carlsbad water; but, whichever saline we may choose, the use of one or other of them should on no account be omitted. One of the best salines is half a drachm of crystallized Carlsbad salts dissolved in a tumbler of hot water and drunk immediately after rising in the morning, and this may be used not merely in the morning after the mercurial, but it may also be employed every morning in cases where the bowels are constipated. The quantity of water is of considerable importance. Half a teaspoonful dissolved in a full tumbler is more efficacious than double the quantity of salt in half the quantity of water. Nor is this to be wondered at, for not only has the larger quantity of liquid greater power to wash out the intestine, but the increased amount of the water tends to increase the quantity of bile secreted, and this increase in bile is especially marked when the water is taken frequently in small quantities, as it is by persons undergoing the cure at Carlsbad, or who take the solution of Carlsbad salts at home by sipping it at intervals while dressing, instead of drinking it all off at once.

Zawilski found that when liquids were taken in this way not only was the bile secreted in greater quantity, but under a greater pressure, so much so that secretion still occurred when such an obstruction was opposed to its exit as would usually have caused the bile which had already been excreted to be reabsorbed.[7]

When the Carlsbad salts are employed after the mercurial, it is, I think, best to take them in single large draughts immediately on rising, but when used by themselves the solution should be sipped at intervals during dressing. When used alone, the Carlsbad water, warmed by standing the tumbler in a basin of hot water or in an ætna, is perhaps even better than the salts, which represent only a part of the normal constituents of the water. After the liver has been thoroughly cleared out in this manner by a mercurial purgative followed by a saline, vegetable cholagogues, such as iridin and euonymin, may be employed to assist the action of the Carlsbad salts, when these are found to be insufficient, even although they are taken with regularity. These cholagogues, the introduction of which into medicine, in this country at least, we owe to Professor Rutherford, are sometimes as useful, perhaps even more so than mercury, but, as a rule, I think the mercurial purgative is the best to begin with. Euonymin is the cholagogue most usually employed, but iridin is really the most powerful one, and is specially recommended by Dr. Rutherford.

Instead of trying to keep up the strength, as it is termed, by loading the stomach with food, the exhausted brain-worker should rather lean toward abstinence from food, and especially toward abstinence from alcoholic liquors. The feeling of muscular weakness and lassitude, which I have already had occasion to mention as frequently coming on about two hours after meals, is not uncommonly met with in persons belonging to the upper classes who are well fed and have little exercise. It is perhaps seen in its most marked form in young women or girls who have left school, and who, having no definite occupation in life, are indisposed to any exercise, either bodily or mental. I am led to look upon this condition as one of poisoning, both on account of the time of its occurrence, during the absorption of digestive products, and by reason of the peculiar symptoms—viz., a curious weight in the legs and arms, the patient describing them as feeling like lumps of lead. These symptoms so much resemble the effect which would be produced by a poison like curare, that one could hardly help attributing them to the action of a depressant or paralyzer of motor nerves or centers. The recent researches of Ludwig and Schmidt-Mühlheim render it exceedingly probable that peptones are the poisonous agents in these cases, and an observation which I have made seems to confirm this conclusion, for I found that the weakness and languor were apparently less after meals consisting of farinaceous food only. My observations, however, are not sufficiently extensive to absolutely convince me that they are entirely absent after meals of this sort, so that possibly the poisoning by peptones, although one cause of the languor, is not to be looked upon as the only cause. A glass of soda water, with or without the juice of a lemon squeezed into it, may be slowly sipped when the feeling of weakness comes on, and a biscuit may be eaten along with it if desired. This will sometimes relieve languor, but if it be found insufficient, a small cup of warm but weak tea or cocoa with a biscuit will act as an efficient stimulant, although they may be less unobjectionable than the soda-water. Heat is one of the most powerful of all cardiac stimulants, and any warm fluid in the stomach will increase its action; a cup of warm water alone will do this, but it is unpleasant to take, and so something must be added to flavor it: a little claret may be used if tea disagrees, or tincture of ginger and sugar, or even some Liebig's extract. It is the local action of the warmth that we want, and in order to obtain it we may sometimes have to put up with the inconvenience of giving substances which will be to some extent injurious after their absorption, such as beef-extract or even whisky. The advice that I have given here, in recommending a glass of cold soda-water or a cup of hot tea, may remind one of the countryman in one of Æsop's Fables who fell into disgrace because he blew upon the fire to heat it, and blew upon his porridge to cool it. And yet the countryman was right, for experience had taught him that the desired result would follow his actions, even though he might not be able to explain the reason why. So we find that a draught of cold water will revive a fainting person, and hot water will have a somewhat similar effect. Both of them give relief by stimulating the circulation, but their modus operandi is different. In the case of the hot water the circulation is stimulated through the heart, which is excited to increased contraction, and thus the tension within the vessels is raised. In the case of the cold, the pressure is also raised, not by stimulation of the heart, but by the contraction of the vessels, especially those of the stomach and intestine. In the case of warmth, more blood is poured into the aorta by the excited heart, and where we apply cold less blood flows out of the aorta into the veins through the intestinal vessels, and thus it is that in both cases the tension is raised and the faintness removed.

At each meal it is well for the patient to begin with the solids before he proceeds to the fluids, and at breakfast, instead of beginning the meal with a cup of tea or coffee, he should finish a slice of dry toast and a piece of fish, egg, or bacon, before he takes any liquid at all. The same rule should be observed at lunch and dinner. The effect of this course is that the patient is less troubled with weight and flatulence after meals. The explanation of the fact probably is that the solids, entering the stomach first, stimulate it to secretion and movement; whereas, if it already contained a quantity of liquid at the time they were ingested, they would not have this effect, and imperfect digestion would be the result. At dinner, wine or beer may be taken if the patient finds them agree, but in all probability he will be better without them. There are some brain-workers who require them and must have them, but it is better for a good many others to avoid either wine or beer, and to take some effervescing water instead. Not unfrequently we hear the complaint that effervescing water is too cold, and where this is felt to be the case ginger ale or zoedone may be substituted, the color of these beverages and their more pungent taste rendering them more grateful both to the eye and the palate of many persons. In some cases weak claret and-water may be used, and if the water be somewhat warm the mixture will be better for the patients, and will not cause the feeling of coldness in the stomach of which they sometimes complain.

A medicine which has long enjoyed a great reputation in disorder of the liver is nitro-muriatic acid, and I think this reputation well deserved. We do not know how it acts, but in some way or another it does tend to improve the digestion. Ten minims of the dilute nitro-hydrochloric acid, either before or immediately after meals, combined with some aromatic and carminative, such as chloroform and cardamoms or orange, and from five to ten minims of tincture of nux vomica, where the nervous depression is great, is a most efficient remedy.

But, even with all this care in food and drink, with all this attention to what is to be taken and what avoided, with medicine morning, noon, and night, how are we to keep the liver in order without exercise? Sometimes the patient may be able to take walking exercise, but when he does it is generally only for a short time during the day, and of so gentle a character that the respiratory movements are but very slightly increased, and the liver is hardly more stimulated by the pressure of the diaphragm and abdominal walls during the walk than it would have been had the patient remained quietly at home. Time is an important element in many cases. Many a hard-worked man has his day so fully occupied that he can not give up more than a quarter or half an hour to exercise, and it is of importance that in this limited period he should get as much exercise as possible, and the best way to employ this brief time is by taking horse-exercise. I believe it is to the late Lord Palmerston that we owe the saying that "the outside of a horse is the best thing for the inside of a man," and it is very near the truth. A brisk trot for fifteen minutes will cause more pressure upon, and stimulation of, the liver than a lazy lounge of an hour or more. The time for this will depend in a great measure upon the engagements of the patient. It should not be taken immediately after a meal, and for most men whose days are fully occupied almost the only time to take it is before breakfast. A cup of milk, or a small cup of tea or coffee, with a piece of bread and butter or a biscuit, may be taken just before starting, and then the regular breakfast will be taken with greater appetite and better digestion after the exercise is over.

By careful attention to the removal of waste products, and to the prevention of absorption of poisonous substances from the intestine, by regulation of the diet, regulation of the bowels, and exercise, in the ways just mentioned, I believe that the nervous exhaustion and depression from which brain-workers suffer may be greatly diminished, even although it may not be entirely prevented.

1 Schmidt-Mühlheim, "Archiv für Anatomie und Physiologie; physiologische Abth.," 1. & 2. Heft, 1880, p. 33. Albertoni, "Centralblatt f. d. medicinischen Wissenschaften," 1880, p. 577.

2 Ludwig and Genersich, p. 53, "Ludwig's Arbeiten," 1870.

3 Braune, "Ber. der sächs. Gesell. d. Wiss.," 1870, p. 251.

4 Althann, vide "Virchow's Jahresbericlit," 1872, p. 156.

5 Several authors, as Abel Key and Retzius ("Nordisk medicinsk Arkiv.," 1870, II, 1, 13-18; "Centralblatt für Medicinischen Wissenschaften," 1871, p. 514); Quincke ("Reichert's und Du Bois-Reymond's Archiv," 1872, 153-177; "Centralblatt für Med. Wissen.," 1872, p. 898).

6 "Practitioner," vol. xii, pp. 342, 403.

7 "Sitzungsber. der wiener Acad.," 1877; mat. nat. Abth., Bd. iv, p. 73.