In the absorption of proteid products, their passage from the intestine by way of the portal circulation insures exposure to the action of the hepatic cells, before they are distributed by the general circulation throughout the body. It is only under conditions of an excessive intake of proteid foods that their products are absorbed by way of the lymphatics. These points are clearly established, and there is every ground for believing that substantial reasons exist to account for this single line of departure. Just what the liver does, however, is uncertain. In fact, as already indicated, there is lack of definite knowledge as to how far the proteid foods are broken down in digestion, prior to absorption. The combined action of pepsin, trypsin, and erepsin, if sufficiently long continued, can accomplish a complete disruption of the proteid molecule. We are inclined to assume in a general way that the “proteids taken as food cannot find a place in the economy of the animal body till they have been, as it were, melted down and recast.”[14] How far this melting down or disruption extends in normal digestion, we do not at present know. As already stated, neither proteoses and peptones, nor the amino-acids, are found in the blood stream in sufficient amounts, or with that frequency, to suggest absorption in these forms. Possibly, as some physiologists have suggested, the amount of any of these products to be found at any one time in a given quantity of blood is too small for certain recognition, yet in the twenty-four hours the amount passing from intestine to liver might be sufficiently large to equal the total proteid absorbed. We can, however, at present only conjecture, and must rest content with the simple statement that in the digestion of the proteid foodstuffs, proteoses, peptones, and amino-acids are formed, and that by transformation or total reconstruction of these products, special types of proteid are manufactured either in the epithelial cells of the intestinal walls during absorption, or elsewhere in the body after absorption. If this latter is the case, the liver might readily be regarded as a likely spot for the synthesis to occur.
Bearing in mind what has been said regarding the production of specific types of proteid by every species of animal, we can the more readily conceive of a synthesis “out of fragments of the original molecules rearranged and put together in new combinations, by processes in which the intestine can hardly be supposed to play a part.” This, the liver might well be assumed as capable of accomplishing, and if we were disposed to accept this view we might use as an argument the fact that the products of proteid digestion are taken directly to this organ, before being cast loose in the tissues and organs of the body. There is perhaps as good ground for assuming that a synthesis or reconstruction of proteid takes place all over the body; that, as suggested by Leathes, “the synthesis of proteids is a function of every cell in the body, each one for itself, and that the material out of which all proteids in the body are made is not proteid in any form, but the fragments derived from proteids by hydrolysis, probably the amido-acids, which in different combinations and different proportions are found in all proteids, and into which they are all resolved by the processes, autolytic or digestive, which can be carried out in every cell in the body.” It is certainly a reasonable hypothesis, and since we lack positive knowledge it cannot at present be disproved. All that we can affirm in the light of established fact is that the products of proteid digestion are absorbed from the intestine by way of the portal circulation, and that either in their passage through the intestinal wall, or later on in the liver or elsewhere, there is a construction of new proteid to meet the wants of the body. The liver, indeed, may be effective in both construction and destruction of proteid, but there is no way of telling at present just how far it acts in either direction.
Regarding the absorption of fats, a single statement will suffice, in addition to what has already been said. Fats gain access to the general circulation by passing from the intestine into the lacteal radicles, thence into the lymphatics, whence they move onward into the thoracic duct, and from there are emptied into the great veins at the neck. A small amount is apparently absorbed in the form of soap by the portal circulation, but by far the larger amount of fat gains access to the blood stream without going through the liver.
In these ways, the blood and lymph are continually supplied with proteid, fat, and carbohydrate from the ingested food, and as these fluids surround and permeate the organized elements of the tissues, the latter are enabled to gain what they need to maintain their nutritive balance. Living matter is essentially unstable; it is the seat of chemical changes of various kinds, anabolic or constructive, and katabolic or destructive. The more comprehensive term “metabolic” is applied to all of these changes that take place in living matter. In anabolism, the dead, inert proteids, fats, and carbohydrates are more or less assimilated and made a part of the living matter of the tissue cells, while at the same time a certain amount of the food material, probably the larger amount, is simply stored as such, or left to circulate in the blood and lymph, without being raised to the higher level of living protoplasm. In katabolism, this accumulated material, and in some degree the living substance itself, is broken down or disintegrated with liberation of the stored-up energy, which manifests itself in the form of heat and mechanical work. At times, the anabolic processes predominate and there is a relatively large accumulation of stored-up materials; while at other times, katabolism, with its attendant chemical decompositions, predominates, and the body loses correspondingly. The point to be emphasized here is that the living body, with its multitude of living cells, is the seat of incessant change. Construction and destruction are continually going forward side by side; sometimes the one and sometimes the other predominating, according to existing conditions. The living protoplasm with its attendant storage material is, under ordinary conditions, constantly being made good from the assimilated food, a part of which is raised to the dignity of living matter and becomes an integral part of the living cells, while the larger portion is simply stored for future uses, or circulates in the blood and lymph which bathe them. Doubtless, this storage or circulating material is the main source of the energy which constantly flows from the cells in the form of heat and of work, as a result of the disruptive changes that constitute katabolism.
Worthy of special notice is the fact that cell protoplasm is essentially proteid in nature; water and proteid make up the larger part of its substance, to which are added small proportions of carbohydrate, fat, and mineral matter. Proteid is the basis of cell protoplasm; it is the chemical nucleus of living matter, and owing to the large size of its molecule, with its large number of contained atoms, is capable of many combinations and many alterations. Most of the reactions characteristic of katabolism centre around this proteid, but the disruptive changes that occur undoubtedly involve more largely the circulating materials present in the blood and lymph, and which bathe the cells, rather than the so-called fixed, or organ proteid, of the cell substance itself. Still, while the circulating blood and lymph furnish largely the substances which are made to undergo disintegration in katabolism, the living protoplasmic cell is the controlling power which regulates the extent and character of the decompositions, and proteid matter is the chemical basis of protoplasm. From these statements, we again have suggested the significant importance of the proteid foods in nutrition, since they alone can furnish the material which constitutes the chemical basis of living cells. The human body, which represents the highest form of animal life, is merely, as stated by another, “literally a nation of cells derived from a single cell called the ovum, living together, but dividing the work, transformed variously into tissues and organs, and variously surrounded by protoplasm products” (Waller).
The processes involved in metabolism are not easily unravelled. The word itself is simple, but it is employed to designate that complex of “chemical changes in living organisms which constitute their life, the changes by which their food is assimilated and becomes part of them, the changes which it undergoes while it shares their life, and finally those by which it is returned to the condition of inanimate matter. Gathered together under this one phrase are some of the most intricate and inaccessible of natural phenomena. It implies also, and gently insists on the idea, that all the phenomena of life are at bottom chemical reactions” (Leathes). Regarding the processes of anabolism, as in the construction of living protoplasm out of inert food materials, we can say nothing. This is altogether beyond our ken at present, and doubtless will remain so, since it involves a chemical alteration, or change, akin to that of bringing the dead to life. With the processes of katabolism, however, we may hope for more satisfactory results; and, indeed, to-day we have considerable information of value as to some of the methods, at least, which are the cause of this phase of nutrition. This knowledge, however, has been slow of attainment.
In the earlier years of the sixteenth century, when anatomy and physiology were beginning to make progress, the savants of that day, hampered as they were by grave misconceptions and by the lack of any understanding of chemical phenomena, could not take advantage, naturally, of the suggestion that as wood burns or oxidizes in the air with liberation of heat, so might the food substances, absorbed by the body, undergo oxidation in the tissues and thus give rise to animal heat. Such suggestions were at that time as a closed book, and so we find Vesalius, in 1543, teaching the Galenic doctrines in physiology then prevalent. The conception of heat production, as it existed at that time, may be inferred from the following quotation:[15] “The parts of the food absorbed from the alimentary canal are carried by the portal blood to the liver, and by the influence of that great organ are converted into blood. The blood thus enriched by the food is by the same great organ endued with the nutritive properties summed up in the phrase ‘natural spirits.’ But blood thus endowed with natural spirits is still crude blood, unfitted for the higher purposes of the blood in the body. Carried from the liver by the vena cava to the right side of the heart, some of it passes from the right ventricle through innumerable invisible pores in the septum to the left ventricle. As the heart expands it draws from the lungs through the vein-like artery air into the left ventricle. And in that left cavity, the blood which has come through the septum is mixed with the air thus drawn in, and by the help of that heat, which is innate in the heart, which was placed there as the source of the heat of the body by God in the beginning of life, and which remains there until death, is imbued with further qualities, is laden with ‘vital spirits,’ and so fitted for its higher duties. The air thus drawn into the left heart by the pulmonary vein, at the same time tempers the innate heat of the heart and prevents it from becoming excessive.” In other words, heat was considered as a divine gift, and as can readily be seen, there was an utter lack of appreciation of the use of air in breathing. Even van Helmont, who lived in 1577–1644, and was in a sense an alchemist, still gave credence to the spirits, viz., that the food absorbed from the stomach and intestine is in the liver endued with natural spirits, while in the heart the natural spirits are converted into vital spirits, and in the brain the vital spirits are transformed into animal spirits.[16] Later, Malpighi discovered the true structure of the lungs, and Borelli, in 1680, exposed the erroneous views then prevalent regarding the purpose of breathing. It is not true, says Borelli, that the use of breathing is to cool the excessive heat of the heart or to ventilate the vital flame, but we must believe that this great machinery of the lungs, with their accompanying blood vessels, is for some grand purpose. In a long and vigorous argument, he contends that the “air taken in by breathing is the chief cause of the life of animals, far more essential than the working of the heart and the circulation of the blood.” He quotes the experiments of Boyle, who showed in 1660 “that even in a partial vacuum brought about by his air pump, flame was extinguished and life soon came to an end; the candle went out and the mouse or the sparrow died.”
At this time, and for long afterwards, the belief was prevalent that the air taken up by the blood in the lungs was the air of the atmosphere in its entirety. No one appears to have thought of the possibility of only a part of the air being used, for at that time there was no suspicion that air was a mixture of substances. Mayow, however, in 1668, showed that it was not the whole air which was employed for respiration, but a particular part only. At this time, great attention was being given to a study of nitre or saltpetre; its wonderful properties in combustion were being recognized, and Mayow, who was a chemist of repute, claimed that it had its origin partly in the air and partly in the earth. The air “which surrounds us, and which, since by its tenuity escapes the sharpness of our eyes, seems to those who think about it to be an empty space, is impregnated with a certain universal salt, of a nitro-saline nature, that is to say, with a vital, fiery, and in the highest degree fermentative spirit,” to which the name of “igneo-aereus” was applied. Nitre was shown to be composed of a sal fixum or sal alkali,—potash as it is now called,—and was obviously derived from the earth, while the other part of nitre was made up of the spiritus acidus, or nitric acid. For a time it was supposed that the whole of this spiritus acidus was contained in the atmosphere, but it was soon recognized that this could not be the case, since nitric acid was found to be a corrosive liquid, destructive to life and quite incapable of supporting combustion. Hence, Mayow concluded that only a part of the acid exists in the atmosphere, viz., that part which he termed spiritus nitro-aereus. In combustion, there is something in the air which is necessary for the burning of every flame, unless perchance igneo-aereal particles should pre-exist in the thing to be burnt. These igneo-aereal particles form “the more active and subtle part of air which is thus necessary for combustion, exist in nitre and indeed constitute its ‘more active and fiery part.’” Mayow fully recognized that burning and breathing involved in a measure the same process; both consisted in the consumption of the igneo-aereal particles present in the air. “If a small animal and a lighted candle be shut up in the same vessel, the entrance into which of air from without be prevented, you will see in a short time the candle go out, nor will the animal long survive its funeral torch. Indeed, [says Mayow] I have found by observation that an animal shut up in a flask together with a candle will continue to breathe for not much more than half the time than it otherwise would, that is, without the candle.” Something contained in the air, necessary alike for supporting combustion and for sustaining life, passes from the air into the blood. Mayow expressed his thoughts in these words: “And indeed it is very probable that certain particles of a nitro-saline nature, and those very subtle, nimble, and of very great fermentative power, are separated from the air by the aid of the lungs and introduced into the mass of the blood. And so necessary for life of every kind is that aereal salt (constituent) that not even plants can grow in earth the access of air to which is shut off. But if that same earth be exposed to air and so forthwith impregnated with that fecundating salt, it at once becomes fit again for growing.”[17] Mayow fully appreciated the importance of his nitro-aereal particles in the processes of life; he had indeed a fairly accurate conception of a sound theory of animal heat; he saw that they were equally necessary for burning, or combustion, and for respiration, and so was enabled to draw a parallelism between the two processes; he pointed out that they were essential for the ordinary activity of the muscles of the body, that as muscle work was increased more particles from the air were required; indeed, he clearly foresaw the need which the body had for these igneo-aereal particles in all the chemical processes of life. And thus was foreshadowed a conception of oxidation, a hundred years before Priestley evolved his phlogiston theories and Lavoisier discovered oxygen.
The discoveries of Lavoisier, published in 1789, led to a clear understanding of combustion as a process of oxidation, and paved the way for a fuller knowledge of the part played by the oxygen of the air in the chemical reactions going on in the animal body. Lavoisier showed that the oxygen drawn into the lungs with the air breathed was used in the body for the oxidation of certain substances, carbon being transformed thereby into carbon dioxide, and hydrogen into water. Further, he noted that these oxidations were carried forward on a large scale, and he emphasized the importance of oxygen as being the true cause of the varied decompositions taking place in the living body. The larger the amount of oxygen inspired, the more extensive the oxidation, and consequently the rate of respiration as modifying the intake of oxygen served in his opinion as a regulator to control the extent of the oxidative processes. He pointed out that a definite relationship existed between the amount of work done by the body and the oxygen consumed; greater muscular activity, lower temperature of the surrounding air, the activities attending the digestive functions, all seemed to be associated with a greater utilization of oxygen. Oxidation was the pivot around which all the chemical reactions of the body seemed to centre. Lavoisier, however, was not a physiologist, and he was, quite naturally perhaps, led into some errors. For example, he considered that the process of combustion or oxidation took place in the lungs, certain fluids rich in carbon and hydrogen formed in the different organs of the body being brought there for exposure to the inspired oxygen. Further, his views implied a simple and complete combustion, in which complex substances rich in carbon were directly and completely oxidized to carbon dioxide and water, in much the same manner as combustion occurs outside the body. Again, he assumed that the amount of oxygen taken into the lungs determined the extent of oxidation, just as the use of the bellows, by increasing the draft of air, causes the fire to burn more brightly.
To Liebig (1842) the next great advance was due. This phenomenally clear-minded man, while recognizing at their full value the fundamental theories advanced by Lavoisier, saw and fully appreciated their incompleteness, and he likewise understood their failure to explain many of the phenomena of life more familiar to the physiological mind than to that of a simple chemist like Lavoisier. Liebig had made a special study of the chemical composition of foodstuffs, and likewise of the tissues and organs of the body. He had, moreover, given great attention to the decomposition products formed in the body, especially the nitrogenous substances excreted through the kidneys, as well as the carbon dioxide and water passed out through the lungs and skin. It was not strange, therefore, that he should take exception to Lavoisier’s view that oxidation in the body consisted in the combustion of a fluid, rich in carbon and hydrogen, which was brought to the lungs. On the contrary, Liebig contended that it was the organic compounds, proteids, fats, and carbohydrates, that underwent oxidation, and not necessarily in the lungs, but all over the body, wherever organs and tissues were active. Especially noteworthy was the view advanced by Liebig, and upheld for many years, that of these three classes of compounds the proteids alone served for the construction of organized tissues, like muscle, and that in the activity of this tissue, as in muscle contraction or muscle work, the energy for the work was derived solely from the breaking down or oxidation of this organized proteid. On this ground he termed the proteid foodstuffs “plastic,” or tissue-building foods. Liebig further pointed out that the substances of the body have the power of combining with and holding on to the inspired oxygen, and that fats and carbohydrates, i. e., the non-nitrogenous compounds, easily undergo oxidation or combustion, and thereby furnish the heat of the body. For this reason he termed the corresponding foodstuffs “respiratory” foods. Proteids, on the other hand, according to Liebig’s view, are capable of combustion only in slight degree. The cause of the decomposition of proteid substances in the body was to be traced solely to muscle work, i. e., the energy of muscle contraction, or muscle work, was derived from the breaking down of the proteids of the muscle tissue, and work was the stimulus which brought about proteid decomposition. Non-nitrogenous substances played no part in these reactions; muscle work was without influence on these compounds, oxygen being the sole stimulus which led to their combustion, and heat was the sole product of the combustion.