# 1911 Encyclopædia Britannica/Nutrition

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​NUTRITION. The physiology of nutrition involves the study of the way in which the tissues of the body, and more especially the great master tissues, muscle and nerve, obtain the material for growth and repair and the energy for mechanical work and heat production, and of the mode in which they get rid of the waste products of their activity. The study is therefore very largely a study of the history of the food of the body, since it is in the food that the necessary matter and energy are supplied. Under Dietetics the composition and special importance of various foods and the laws which regulate the supply of food under different conditions of the body are separately dealt with. Here the mode of digestion, the utilization and the elimination of the end products of the three great constituents, proteins, carbohydrates and fats, are alone considered. They are treated under the following heads: I. The Chemistry of Digestion; II. The Mode of Formation of the Digestive Secretions; III. The Mechanism by which the Food is passed along the Alimentary Canal; IV. The Absorption of Food; V. Metabolism; VI. Excretion.
I. Chemistry of Digestion
The essential step which prepares the ordinary food for utilization in the body, for the change into living matter, is digestion, a process which the food undergoes under the influence of the ferments or enzymes present in the gastro-intestinal tract. By this process it is broken down into simpler substances, which can be utilized by the body tissues for conversion into protoplasm and as the supply of energy. That part which is unsuited for use in the body is either passed as faeces or absorbed and excreted in the urine.
1. Enzyme Action generally.—The substances which bring about this change are known as ferments, enzymes or zymins. Formerly it was believed that there were two distinct classes ​ of enzymes, those which were living or associated with living cells, and those which were non-living. In 1897, however, E. Buchner and M. Hahn showed that from living cells (yeast) a ferment could be obtained which acted quite as well extracellularly as when it was bound up within the cell. Subsequent work has shown that other organisms act by the enzymes they contain, so that it is now recognized that there is no essential difference between the living or organized ferment and the non-living or unorganized ferment. All ferments probably act as catalysators or catalysts. Catalysis is the process by which reactions are either initiated or accelerated by the mere presence of certain substances which remain unchanged during the process; to these substances the name of catalysators has been given. As an example of such catalytic action the acceleration of the decomposition of hydrogen peroxide (H$_2$O$_2$) into water (H$_2$O) and oxygen (O) by the action of a colloidal solution of platinum may be given. C. Oppenheimer defines an enzyme as a substance produced by living cells, which acts by catalysis. E. Fischer has shown that the action of ferments is specific, that is, the ferment only exerts its action on definite substances or substrates of definite structural arrangement. He has compared the relation of ferment to substrate to that of a key to its lock. Ferments which bring about the breakdown of proteins are without influence on fats and carbohydrates; those which decompose fats leave proteins and carbohydrates untouched, and so on.
The chemical composition of enzymes is unknown. It has been assumed that they are protein in nature, but this is mainly because it has been found that when they are extracted from tissues they are apparently in combination with proteins. In all probability the protein is there as an impurity owing to incomplete separation.
As regards the general properties of enzymes, most of them can be precipitated from their solutions by means of alcohol. They can also be carried down by fine precipitates of certain inorganic salts or by protein precipitation, e.g. when a precipitate of casein is produced by acidifying a casein solution with acetic acid. Most of the ferments are soluble in water or saline solutions, and in glycerin and water. The ferments are found to have an optimum temperature of action. This temperature in most cases ranges from 37° to 40° C. All true ferments are thermolabile, being destroyed at about 70° C. Ferments are hindered in their action to some extent by the general protoplasmic poisons, such as salicylic acid, chloroform, &c. The action of many of them is retarded when the products of their action are allowed to accumulate. Just as when a chemical reaction is set up its rate tends to decrease and finally comes to a standstill before the reaction is completed—an equilibrium being established—so the reactions set up by enzymes also tend to come to an equilibrium before the complete conversion of the original substance. In the case of certain enzymes at least this equilibrium may be reached from either side; thus the enzyme maltase may either bring about the breakdown of the sugar maltose to dextrose or cause a synthesis of dextrose to maltose.
A number of the body ferments have now been shown to exist in the tissues in an inactive form. This condition is known as the proferment or zymogen state, and before any action can be exerted it must be activated, usually by some specific substance, as in the case of the activation of trypsinogen by means of enterokinase. The following table gives a list of the principal ferments concerned in the digestion and metabolism of food-stuffs:—
Certain oxydases, catalases and de-amidizing enzymes are found in the tissues generally and play an important part in the various metabolic processes.
2. Digestion in the Mouth.—The first of the digestive secretions which food comes into contact with is the saliva. This is the mixed secretion from the various glands, salivary and other, the ducts of which open in the mouth. The saliva, which is for the most part produced by the three large salivary glands, the parotid, the sub-maxillary and the sub-lingual, is a colourless or a slightly turbid viscous fluid with a faintly alkaline reaction and of low specific gravity. It contains a very small proportion of solids, which vary somewhat in amount and character in the secretions of the different glands. Mucin and traces of other proteins are present. Small amounts of potassium sulphocyanide may nearly always be detected. The functions of the saliva are twofold. First, it has a mechanical action moistening the mouth and the food and thus aiding mastication and swallowing by securing the formation of a proper bolus of food; it also assists by binding the particles together, an action of special importance when the food is dry. Second, in man and in some of the lower animals the enzyme ptyalin exerts an action in digestion on part of the carbohydrates of the diet. The starches or polysaccharides are broken down, first of all to the simple dextrins and then to the still more simple disaccharide, maltose. The further breakdown of the maltose is carried out in the intestine by the action of a ferment maltase which does not exist at all or only in the merest traces in the buccal secretion. The action of ptyalin on starches is thus very similar to that of acids, except that it stops at the formation of maltose. Ptyalin acts best at a temperature of about 40° C. and in a neutral or faintly alkaline medium, its action being inhibited by the presence of even very dilute solutions of the mineral acids. If the acid be in sufficient amount the enzyme is destroyed. For this reason the action ceases in the stomach whenever the bolus is completely permeated by the gastric juice. As it takes time for the gastric juice thoroughly to permeate the food mass, which remains for a considerable period in the fundus of the stomach unmixed with the secretion, salivary digestion goes on for about half an hour after food is taken.
3. Gastric Digestion.—The passage of food from the mouth to the stomach will be dealt with later. The stomach has two digestive functions: (1) It acts as a store chamber permitting a full meal to be taken; (2) It acts as a digestive organ of importance in preparing the food for further attack in the intestinal canal. But the stomach cannot be regarded as an essential organ, since it has been removed in dogs and in man without apparent interference with nutrition and health.
Gastric digestion is brought about by the action of the gastric juice, a clear watery, colourless and strongly acid fluid with a specific gravity of about 1003. The amount of solids present is extremely small, about 0·3%. They consist of protein, nucleic acid, lecithin and inorganic salts, in addition to the more important constituents, the enzymes and hydrochloric acid.
The amount of hydrochloric acid present in the juice varies with the period of digestion. In man the maximum acid concentration is about 0·2%. The acid exists in the stomach in two forms as free hydrochloric acid and as combined hydrochloric acid. The amount of each depends on various factors: (1) the secretion itself; (2) the nature of the food; and (3) the rapidity with which the stomach empties itself, &c. For instance, after a protein-free meal the hydrochloric acid is for the most part free, whereas, when protein is present, it combines with it and, unless secreted in very large amount, most of the acid is in a fixed condition.
The hydrochloric acid is formed by the activities of certain gland cells in the middle region of the stomach, and the fact that it does not exist as such in the blood proves that it is formed within these cells. Further, it has been found that the gastric mucous membranes of starving dogs contain 0·74% of sodium and potassium chloride, much more than is present in any other organ or in the blood plasma. That the chlorine comes from the sodium chloride in the food has been shown by the fact that, when the tissues are deprived of this salt, and sodium bromide is given, hydrobromic acid may appear in the gastric secretion.
​ The hydrochloric acid is essential for the action of the gastric enzyme, pepsin, in splitting up the protein of the food. In addition to this, the acid has a slight action in splitting polysaccharides and disaccharides. Lastly, it acts as a bactericidal agent, preventing bacterial decomposition from taking place, and it may thus prevent certain noxious bacteria, taken in in the food, from gaining access to the intestinal tract, where there is a chance of their flourishing in the rich alkaline medium. It is owing to the presence of hydrochloric acid that gastric juice can be kept for prolonged periods without undergoing putrefaction.
The quantity of juice secreted varies with the nature of the food consumed. Thus in one experiment, after the use of a test meal consisting of 25 grammes bread and 250 c.c. tea, there was a flow of 106 c.c., whereas in another case with an ordinary meal there was an output of practically 600 c.c. gastric juice.
Pawlow has shown that not only does the amount of juice secreted vary with the nature of the food ingested but that the digestive activity of the secretion also varies in the same way. He gives the following table:—
Thus each separate food gives rise to a definite hourly secretion of the juice and to a characteristic alteration in its properties. The meat diet brings about a very rapid flow, the maximum output taking place within the first two hours; with bread the maximum output is even earlier. With milk somewhat later. When the juice is examined as regards its digestive activity, it is found that with meat the most active juice is secreted within the first hour, with bread in the second and third hours, and with milk in the sixth hour.
According to the nature of the food, the stomach seems to be stimulated to form a secretion which will best serve its purpose and give the minimum of waste. It thus works economically.
The principal ferment found in the gastric juice is pepsin, a ferment which acts only in the presence of a mineral acid. The action proceeds best at a temperature of about 37° C. in an acid medium of 0·2% to 0·3%. Pepsin is elaborated in the so-called chief cells of the gastric glands as an inert precursor—propepsin. It is only when it comes into contact with the acid of the juice that it is activated and rendered capable of attacking the protein of the food.
As already mentioned, the main function of the gastric juice is to deal with the protein moiety of the food and to prepare it for further digestion in the intestine.
The first result of the action of this secretion on protein matter is to render it soluble-a meta protein or acid albumin (syntonin), being formed. This body may be regarded mainly as the product of the action of the hydrochloric acid independently of the pepsin.
The following steps of decomposition are the result of the action of pepsin. From the meta protein primary and secondary proteoses, the so-called proto-, hetero- and deutero-albumoscs are formed, and nom these peptones are finally produced. The result of this process of digestion or hydrolysis induced by the pepsin is that complex protein substances of high molecular weight are converted into simpler bodies of comparatively low molecular weight. Formerly it was believed that the action of the pepsin on protein could not carry the decomposition further than the peptones, but recently it has been shown that still further splitting can be brought about, and that the simple amino acids of which the protein molecule is built up can be produced. This latter process, however, takes a very long time even under favourable circumstances, and it probably never occurs under normal conditions. The contents of the stomach-products of protein digestion-are passed on into the duodenum, chiefly as proteoses and peptones.
In addition to the principal ferment of the gastric juice some workers hold that another enzyme is present. This is the ferment rennet, rennin, or chymosin, the sole action of which, so far as is known at present, is to bring about the curdling of milk, the curd formed being dealt with in the ordinary way by the pepsin. Clotting of milk under the action of rennin occurs at a suitable temperature with great rapidity. This process is said to take place in two stages: (1) the rennin converts the caseinogen of the milkinto para casein, and (2) this paracasein unites with the lime salts present in the milk and forms the curd or precipitate. That lime salts are absolutely essential for this process of clotting has been shown by the fact that, if they are removed by precipitation as by oxalates, no clotting will take place even after the addition of a large amount of active rennin. Immediate clotting takes place, however, when the necessary lime salts are restored. Many observers now hold that this rennet action is not the property of a specific ferment but simply another phase of the action of pepsin. For this view, which has been put forward by well known workers, there is much to be said and certainly the power of curdling milk is not confined to the stomach, but has been found in various tissue extracts, and, indeed, wherever proteolytic enzymes are found.
The speed with which the stomach is emptied depends to a great extent on the nature of the food. Plain water leaves the stomach almost at once, salt and sugar solutions at a somewhat slower rate. Milk under the action of rennin curdles. The whey rapidly leaves the stomach, whereas the casein and fat are retained for further treatment. On a mixed diet, emptying of the stomach in man proceeds very slowly, requiring about four hours. Cannon, by feeding with food impregnated with bismuth and using X-rays, showed that carbohydrates leave most rapidly, then mixtures of carbohydrates and proteins, then proteins, then fats, and finally mixtures of fats. and proteins. The diet which remains longest in the stomach is a mixture of fats and proteins-rich food, as it is popularly called. Here two factors enter to prevent rapid emptying: (1) the presence of much fat, and (2) the acid secretion engendered by the abundant protein.
There is no doubt that fats present in fine emulsion can be decomposed in the stomach. The action proceeds in a medium which is slightly acid or neutral, being entirely prevented by the presence of strong acids and alkalis. Many workers believe this gastrolipase to be of pancreatic or intestinal origin, and suppose that it gains entrance to the stomach by a reflux flow through the pylorus. Evidence is accumulating to show that this view is correct.
By means of pepsin and gastrolipase proteins and fats are dealt with. No specific enzyme for carbohydrates has been found in the stomach in man. Certainly a small amount of polysaccharide decomposition takes place, but this is dependent (1) on the ptyalin which comes from the mouth, and (2) on a certain amount of hydrolysis due to the action of the free hydrochloric acid.
4. Digestion in the Intestine.—The passage of food from the stomach to the intestine will be considered later. The food so far digested in the stomach is known as chyme, and it is passed on to undergo intestinal digestion under the influence of (1) the enzymes of the pancreas, and (2) of other enzymes present in the different secretions of the intestine. Digestion in the intestine may accordingly be described under these two heads.
(a) Pancreatic Digestion.—The pancreatic juice is the secretion from the pancreas and is discharged into the duodenum. The secretion obtained from a fistula of the pancreatic duct varies in character according to whether the opening into the duct has been made recently or some time before the examination. It is a clear, usually thin fluid with a specific gravity of about 1008, and with an alkaline reaction. It contains a certain amount of protein and ash. The most important inorganic constituent is sodium carbonate, which gives the alkaline reaction (alkalinity is, as NaOH＝0·47%). This alkaline salt, along with that contained in the intestinal juice, plays an important part in neutralizing the acid chyme. "
In the pancreatic secretion there are at least three important enzymes, each with a definite action: (a) trypsin, the proteolytic enzyme which brings about the further breakdown of the food proteins; (b) a diastase which deals with the carbohydrates, and (c) a lipase which acts on the fats.
(a) Trypsin.—This ferment, in the form in which it is secreted—trypsinogen—is inert. Before it can exert its hydrolytic action it must be activated. This activation is brought about by another enzyme which is found in the intestinal tract—enterokinase. The conversion is brought about as soon as the trypsinogen comes into contact with the enterokinase, the merest trace of which suffices to activate a large amount of trypsinogen.
Trypsin acts on the protein just as pepsin does, by bringing about hydrolytic changes. It differs from the latter in acting best in an alkaline or neutral medium. Its effect is much more energetic than that of pepsin, so that the protein molecule is more completely decomposed. Whilst it generally finishes the decomposition which the pepsin has begun, it can break down the original protein quite as easily if not more easily than does pepsin, and it carries the splitting as far as the comparatively simple crystalline bodies, the amino acids, or groups of these, the polypeptides, bodies intermediate between the complex peptones and the simple amino acids of which the protein is built up.
The character and properties of the products formed in such digestion depend on the nature of the protein acted upon. As will be seen from the following table these proteins vary fairly widely in the proportion of amino acids which they contain.
Whether any of the polypeptides found in digestion are further broken down in the course of normal pancreatic digestion is a moot point, but E. Fischer and E. Abderhalden have shown that many of the synthetic polypeptides prepared by them can be broken into their constituents by the action of trypsin. The previous peptic digestion seems to play some part in the extent to which tryptic digestion is carried out, as one of these observers has demonstrated that protein digested first with pepsin and then with trypsin gives a smaller yield of polypeptide and a larger yield of monamino acids than when digestion has been carried out with trypsin alone.
b. Diastase.—This ferment is found in the pancreatic juice apparently secreted in an active form, although some observers hold that it also is secreted in a zymogen form. It is practically identical in its action with the ptyalin of the saliva, converting starch into maltose. It deals with all the starchy food which has escaped conversion into the simple sugars by the ptyalin.
c. Lipase.—Most of this ferment, if not all, is apparently secreted in the form of a zymogen. There is evidence that the bile is the activating agent here, just as the enterokinase acts in the case of trypsin. Lipase can act in any medium acid. neutral, and alkaline, and both on emulsified and non-emulsified fats. It converts the fats by a process of hydrolysis into fatty acids and glycerin. Kastle and Loevenhart found that not only can this enzyme break up fats into their components, but that it also has the power to act in the reverse direction, and in this way bring about the union of fatty acids and glycerin so as to form fats, a process which occurs in the intestinal epithelial cells after absorption.
In addition to these three enzymes the pancreatic juice may contain traces of others, for example, a rennet-like ferment which curdles milk. This again, as in the case of the stomach rennet, is held by some to be only another phase of proteolytic action. Maltase is also said to be present in small amount, as is also lactase under certain conditions. In pancreatic, as in gastric digestion, the nature of the food is said to play a part in controlling the amount and the composition of the secretion with respect to its ferments. The action, if it does exist, is not very well defined.
b. Intestinal Digestion.—By this is meant the other digestive processes which go on in the intestine under the action of the secretion of Lieberkühn’s follicles—the succus entericus. This is a yellowish, often opalescent, strongly alkaline fluid. The alkalinity is due to the presence of sodium carbonate. It contains a small amount of protein, shed epithelial cells, &c. The secretion of some 170 c.c in 24 hours has been observed in a short loop of human intestine by H. S. Hamburger and E. Hekma, but it is almost impossible to get a measure of the actual amount of secretion from the whole gut. Most of the ferments are present in very small amount in the intestinal juice. They seem to be actually within the epithelial lining of the intestine, for extracts made from the intestinal mucous membrane are richer in ferments than the secretion.
Apparently the intestinal secretion contains no trace of a ferment acting on native protein, but a ferment—erepsin—is present in fair amount in the intestinal mucous membrane and in small amount in the secretion, which acts in an alkaline medium on proteoses, peptones, and on casein, converting them into crystalline products of the nature of amino acids.
Another ferment, arginase, has been isolated from the intestinal mucous membrane by A. Kossel and H. D. Dakin, which splits the diamino acid arginin into urea and ornithin. A lipase has also been detected which is very similar to pancreatic lipase; it, however, attacks only emulsified fats.
Several carbohydrate hydrolysing enzymes have been described in the small intestine. Invertin, the ferment which splits cane-sugar, is present in small amount in the secretion, more abundantly in the extract of mucous membrane. In all probability it deals with the saccharose after or in process of absorption. Maltase is also present in large amount, and here again in greater amount in the extract than in the secretion. The presence of lactase has been much discussed, and it seems probable that suckling animals do possess this enzyme. Some workers have stated that an intestinal diastase is to be found, but, if so, it is present in very small amount.
In the large intestine a small amount of erepsin has been discovered at the upper end. Any digestion which does take place is probably either bacterial in origin, or due to ferments which have originated in the lower end of the small intestine, and which have been carried down.
5. Bile.—This fluid, in all probability, has little direct action in ordinary digestion, although it contains substances which act indirectly. The bile salts act as solvents for fats and fatty acids, and as activators of pancreatic lipase. The salts also serve to keep cholestrin in solution. Bile is to be looked upon rather as the excretion, the result of the hepatic metabolism, than as a digestive juice. Various workers have shown that when the bile is prevented from entering the intestine owing to a fistula having been made, the animal or patient may continue to enjoy good health, thus proving that this fluid is not essential to any of the digestive processes which normally take place.
Bile as secreted has an orange-brown colour, but the colour varies according to the pigment present. It is more or less viscous (not so viscous as bile taken from the gall bladder) and has a specific gravity of about 1010. It has a slightly alkaline reaction, a bitter taste and a characteristic smell. The daily output is, for a normal individual, over 500 c.c On analysis it is found to have over 2% of solids, of which more than half are organic. It contains in addition to a nucleo-albumin, derived mainly from the bile passages and gall bladder, bile acids, bile pigments, cholesterin, lecithin, fats, &c. The most abundant solids are the salts of the bile acids, of which in man the most important is sodium glycocholate, sodium taurocholate being present in very small amount. The bile acids are formed in the liver cells, and when the duct is ligatured they tend to accumulate in the blood.
The pigments amount to only about 0·2%. In human bile the chief pigment is bilirubin, whilst in herbivora biliverdin is more abundant. They are derived from the haemoglobin of the blood, but the pigments are iron-free. They may be regarded as purely excretory products arising from the breakdown of the haemoglobin of effete blood corpuscles.
Cholesterin is a monatomic alcohol, and is probably a waste product. It occurs in the bile only in small amount, and there is some evidence that it is not secreted by the liver cells but is added to the bile from the bile passages. Fats and lecithin are both derived from the liver cells. Of the inorganic constituents phosphate of calcium is the most abundant.
The secretion of bile is practically continuous, but it seems to enter the duodenum intermittently. The taking of food increases the flow of bile, the amount of the increase depending to a certain extent on the nature of the food. A protein meal has been found to have the greatest effect and a carbohydrate one the least. The entry of the acid chyme into the duodenum is the stimulus which brings about the ejection of the bile. Pressure on the liver also seems to cause a flow (see section II.).
In connexion with bile secretion attention may be drawn here to a peculiar enterohepatic circulation which is stated to exist. The bile salts are partly absorbed from the intestine, to be carried again by the portal blood to the liver and to be again eliminated. By this circulation the entrance of various alkaloidal and ptomaine poisons into the general circulation may be prevented.
Faeces.—The bulk of the waste matter arising from the foods along with the secretions from the alimentary canal form the faeces. On an absorbable diet the faeces are almost purely intestinal in origin. As a channel of excretion of nitrogenous metabolic waste products they are not very important, although the work of C. Voit indicates that they do play a certain part. The nature of the excreted nitrogenous substances has not been fully examined. Of the inorganic constituents iron is probably for the most part excreted into the large intestine. It is, however, very difficult to come to any definite Conclusion as to what is unabsorbed material and what excreted.
II. The Mode of Formation of the Digestive Secretions
1. Salivary Glands.—The secretion from the various glands is generally evoked by nervous impulses, through the secretory ​ nerves. K. Ludwig found that the stimulation of the chorda tympani produced a copious flow of watery saliva from the submaxillary gland, and a general dilatation of the blood-vessels supplying the gland. The same is the case in the sublingual gland. In addition to the chorda tympani fibres also pass to the gland through the cervical sympathetic, and when these are stimulated the saliva excreted is viscous and turbid, and contains much solid matter, while the blood-vessels are contracted. The conclusion formerly drawn was that the flow of saliva was dependent on the increased blood supply. But it has been definitely proved that true secretory fibres exist. If atropine be administered before stimulation of the chorda tympani, the dilatation of the vessels takes place, but no flow of saliva. Further, if the circulation be cut off from the gland the stimulation of the chorda tympani may cause a temporary flow of saliva.
The parotid gland is supplied by the auriculo-temporal nerve which receives its secreting fibres from the glossopharyngeal. Stimulation of these fibres brings about an abundant watery secretion poor in solids. Stimulation of the sympathetic fibres system is not followed by any salivary flow, yet it has an effect on the gland, for, if after the sympathetic has been stimulated a secretion be evoked by stimulation of the glossopharyngeal nerve, the saliva secreted is very rich in organic solids.
2. Gastric Glands.—The control of the gastric secretion seems to be under two entirely different mechanisms. Pawlow has clearly shown that the stomach is supplied with secretory nerves which reach that organ through the vagus. The stimuli which bring these nerves into action are the sight, the odour or the taste of food. That the course of the stimulus is through the vagus is shown by the fact that an abundant flow of juice may be caused so long as the vagi are intact, but this flow does not take place when these nerves are cut. Between the stimulation and the secretion there is a lengthy latent time amounting to several minutes. The other stimulus of the secretion is apparently a chemical one. Pawlow states that mechanical stimulation of the mucous membrane fails to bring about a flow of juice, but Beaumont in his classical observation on the stomach of St Martin found that the insertion of a tube did cause a flow. There may be certain substances either present in the food or developed in the course of digestion, which directly stimulate the secretion originally started by a nervous reflex. E. Starling has drawn attention to this chemical mode of stimulating different organs. To the substances known and unknown which evoke the action, he gives the name of hormones, and such “hormone” action he does not limit merely to the secretory organs but extends to all cases where one organ is stimulated by chemical products formed in the same or another organ. Attention has already been drawn to the influence of different food-stuffs on the amount and nature of the gastric secretion.
3. Pancreatic Secretion.—The stimuli which evoke this secretion are again two in number. Many have failed to demonstrate that the secretion of the pancreas is under nervous control, but Pawlow and his school have shown that stimulation of the vagus evokes a secretion of pancreatic juice. This flow, as in the case of the stomach, has a latent period of several minutes. Most modern workers hold that the most effective stimulus to the pancreatic flow is the chemical one—a hormone discovered by W. Bayliss and E. Starling, who found that extracts of the duodenal mucous membrane made with dilute hydrochloric acid when injected into the blood caused a flow of pancreatic juice. The active substance present in this extract is known as “secretin,” and is supposed to be formed under natural conditions by the action of the acid chyme on a prosecretin. This secretin is not of the ordinary zymin nature, as it is not destroyed by boiling and is soluble in alcohol. The secretin when formed must be absorbed into the blood and then carried round the circulation to the pancreas before it can act.
4. Intestinal Juice.—The mode of action of the stimuli which evoke this secretion has not yet been fully investigated. As has been stated, it is quite possible that very little ferment is secreted, and that ferment action mainly takes place within the cells after the various substances have been absorbed. How far the flow is controlled by nervous action, and how far by hormone action, is not known.
III. Motor Mechanism of the Alimentary Canal
Mastication:—This is a purely voluntary act, and consists of a great variety of movements produced by the various muscles in Connexion with the lower jaw. By the act of chewing the food is thoroughly broken up and intimately mixed with the saliva.
Deglutition.—The food after thorough mastication is collected on the surface of the tongue, principally by the action (voluntary) of the buccinator muscles, and by the contraction of the tongue muscles it is passed backwards. As soon as the food by the action of the tongue enters the pillars of the fauces the action becomes involuntary and reflex. The soft palate is raised to prevent the food entering the nasal cavity, and the larynx is shut off by closure of the glottis, and approximation of the arytenoid cartilages to one another and to the back of the epiglottis. The food is now passed on into the oesophagus proper by the constrictors of the pharynx. In the oesophagus the downward movement varies with the nature of the food swallowed. If it be fluid it reaches the lower end of the oesophagus in about three seconds and lies at the lower end of the gullet for two or three seconds before entering the stomach. When the consistency is firmer the progress downwards is much slower. Either by the force exerted by the wave of contraction passing down the gullet or by some inhibition of the sphincter, the cardiac orifice opens and permits the food to enter the stomach.
Stomach Movements.—For our knowledge of these we are indebted principally to the work of Cannon, who studied them by feeding an animal with food containing bismuth and then following the movements of the shadow of the food on a screen by means of the X-rays. Soon after food is taken it is found that a contraction begins somewhere about the middle of the stomach and slowly passes towards the pylorus. This is followed by others, in man at regular intervals of about twenty seconds, so that the pyloric part of the organ is soon in active peristalsis. The fundus of the stomach is not actively concerned in these movements; it simply acts as a reservoir. At certain periods, but not with each peristaltic wave, the pyloric sphincter relaxes and allows a portion of the fluid acid chyme to escape into the duodenum. It only opens when stimulated by fluid material; if solid food be forced against it it remains tightly closed. Grützner, by experiments with feeding with different coloured foods, has shown that the food at the fundus may remain undisturbed for quite prolonged periods. In this connexion it must be remembered, of course, that the food is not lying loose in a sack larger than the contents. The cavity of the stomach is only the size of the amount of food present; in other words, the food exactly fills the cavity. The motor nerve fibres to the stomach run in the vagi, which also contain fibres inhibitory to the cardiac sphincter. The splanchnic nerves mainly contain inhibitory fibres. The automatic movements are probably in connexion with the intrinsic plexus of Auerbach, since they continue after section of the extrinsic nerves.
Intestinal Movements.—The intestines owe their peculiar movements to the arrangement of their muscular coats, which are disposed in two layers, an inner circular, and an outer longitudinal. The movements are of two kinds, the so-called swaying myogenic contraction and the peristaltic waves. The former are rapid and have very little to do with the downward movement of the contents. Probably their action is to mix the contents, since Cannon has shown that these contents, in the lower animals at least, get divided into segments. From time to time the separated segments are caught in the course of a peristaltic wave and carried downward a short distance. Then again in their new situation the rhythmic contractions break up the contents anew.
The peristaltic movements are much more powerful. Under normal conditions they begin at the pylorus and passing downwards carry the intestinal contents onwards. The normal movement progresses slowly, although under abnormal conditions ​ peristaltic waves may become extremely violent and rapid, and may indeed run over the whole length of the intestine within a minute. The muscular coat in front of the contracting zone is relaxed, as is that behind the wave. The waves are probably due mainly to the circular fibres, the longitudinal pulling the gut up over the contents as they are forced onwards. The downward movement seems to be due to some definite arrangement within the intestinal wall, since it has been shown that, when a segment of bowel has been cut out and then the continuity of the canal made good by fixing the section so that the lower end of the excised portion is fixed to the upper divided end of the real gut, upward peristalsis takes place in this segment. An anti-peristalsis has been described in which the movements are all towards the stomach. Under certain conditions the introduction of foreign substances, as hairs, &c., may evoke such anti-peristaltic waves.
The rhythmical movements are held by some to be purely myogenic in origin, as they still continue after section of all the nerves and when the intrinsic ganglia in the intestinal wall have been thrown out of action by the application of nicotine. But recent work by R. Magnus would tend to show that they are controlled by Auerbach’s plexus. Peristaltic waves, on the other hand, according to W. Bayliss and E. Starling, although they continue and indeed may become more energetic after section of the extrinsic nerves, are prevented by the application of nicotine and cocaine; in other words, it is presumed that peristalsis is a complicated reflex action through the intrinsic ganglia. The intestines are therefore not dependent for their movement on their connexion with the central nervous system, although of course their activity is more or less regulated by such a connexion.
As regards the movements of the large intestine, they resemble those of the small, although they are much less frequent. The forward movement is slow, thus permitting of the solidification of the contents by the removal of the Water. In the first part of the large intestine anti-peristaltic movements are frequent, the regular peristaltic downward movements only becoming prominent when the descending colon is reached to carry contents to the rectum. The anti-peristalsis serves a useful purpose in giving time for the absorption of the fluid in the formation of faeces. The rate at which the contents travel along the intestine varies greatly. Under average conditions the food residue reaches the ileo-caecal valve between the small and large intestine at about four to four and a half hours after a meal, while it takes nine hours to reach the splenic flexure of the colon.
Defaecation.—Food residues, cellular debris and substances derived from the various secretions of the gastro-intestinal tract are forced downwards by peristalsis, and eventually reach the rectum and accumulate there as the faeces. The pressure of the solid and semi-solid mass gives rise to a definite sensation and a desire to empty the rectum. The faeces are retained within the canal partly by the horizontal direction of the rectum before it opens into the anal canal, and partly by the action of two sphincter muscles. At the act of defaecation the strong internal sphincter is first of all relaxed, but unless the rectal stimulus is very strong, the external can be kept contracted, as it is to a certain extent, under the control of the will. The act of defaecation normally is partly voluntary and partly involuntary. The voluntary part consists in the contraction of the abdominal muscles, the closure of the glottis, and the relaxation of the external sphincter and of the levator ani muscle, thus allowing the horizontal part of the rectum to become more vertical; the involuntary in the energetic contractions of the muscular walls of the colon and rectum which sweep the contents of the whole colon downwards. There is a centre in the lumbar enlargement of the spinal cord which presides over the sphincter muscles and probably over the whole involuntary mechanism of defaecation.
Vomiting.—Sometimes the gastric contents are ejected through the cardiac opening of the stomach instead of through the pylorus. The act is a reflex one, probably originally protective in nature, irritation of the gastric mucous membrane being the most frequent cause. The act is generally preceded by a feeling of nausea and a copious salivation, succeeded by a series of powerful expiratory efforts with the glottis closed. The diaphragm is held firmly contracted, then a convulsive contraction of the abdominal muscles with a simultaneous opening of the cardiac orifice of the stomach brings about the sudden ejection of the contents. The wall of the stomach may also contract and press upon the contents. During the act the glottis is firmly closed, and at the same time, if the act be not too violent, the gastric contents are prevented from entering the nasal cavity by the contraction of the soft palate.
IV. Absorption
Mouth.—No absorption of food-stuffs takes place here.
Stomach.—Absorption from the stomach occurs only to a small extent. Water passes rapidly through the stomach and is practically unabsorbed. Salts are apparently absorbed in a limited amount from their watery solution, the extent of absorption depending to some extent on the concentration of the solution. Sugar is also absorbed to a small extent from its solutions, the greater the concentration the greater being the amount of sugar taken up. Alcohol is readily absorbed from the stomach. A small amount of the products of protein digestion may be absorbed/ There is no evidence that fats are absorbed under any conditions in the stomach.
Intestine.—The greatest absorption of the foods takes place in the intestine, especially in the small intestine. It has been shown that over 85% of the protein has disappeared before the lower end of the small intestine is reached. How does the absorption take place? There are two channels for the removal of the material from the intestine: (1) the blood capillaries spread in the villi, and (2) the lacteals also present in the villi. The foods may reach the blood direct or through the various lymph channels into the thoracic duct and finally into the blood. The lacteals of the villi are channels for the absorption of the fatty parts of the food. The products of the digestion of the proteins and carbohydrates reach the body directly through the capillaries via the portal system.
Can absorption be explained by the ordinary laws of diffusion and osmosis, or are there certain selective activities of the living epithelial lining? The work of R. Heidenhain, E. Weymouth Reid, and others shows clearly that whatever part the physical laws play in this exchange, there are other activities also at work. For instance, an animal’s own serum can be readily absorbed from its intestine, as can also salt and other solutions of higher concentration than that of the blood. Such absorption cannot be explained by ordinary physical laws. In all such cases of absorption the epithelial lining of the gut must be intact and uninjured. O. Cohnheim and others have shown that when the epithelial lining is damaged or destroyed, the intestinal wall behaves like any other animal membrane, and the physical laws governing osmotic pressure come into play. Whether the nervous system plays any part in this absorption is not yet determined.
The form in which the various products resulting from digestion are absorbed must next be considered.
Carbohydrates.—These reach the body, as already mentioned, by way of the blood, and in the form of monosaccharides or simple sugars. F. Rohmann found that the absorption of the disaccharides is dependent on the invert ferment action, and not upon their osmotic characters. E. Weinland too has shown that if lactose be put into a lactase-free intestine, no absorption takes place, the lactose gradually disappearing under bacterial action, whereas when the ferment lactase is present glucose and galactose the products of its splitting are absorbed as readily as cane-sugar and maltose. E. Voit has also demonstrated the fact that the body deals with its carbohydrate supply in the form of mono-saccharides. He injected solutions of various sugars, mono- and di-saccharides, and found that the simple sugars were retained, whereas the double sugars were excreted in the urine. The only di-saccharide which can be dealt with in the body is maltose, as there is a maltase present in the blood which splits it. Carbohydrates which are not absorbed from the intestine are disposed of by bacterial action, giving rise to various fatty acids, carbon dioxide, &c.
Fats.—Fats are absorbed from the intestine in the form of fatty acids and glycerin; i.e. in the form in which they exist after the action of the lipase. That a resynthesis takes place in the epithelium is shown by the fact that fatty acids are of equal value with fat as a source of energy, and that as fat absorption goes on fat droplets are seen to grow in the protoplasm away from the free margin of the cells. As already mentioned, the fat is removed by the lacteals from the cells to the thoracic duct, and then to the general circulation. A small amount of the fat may pass into the body via the blood, but this is practically all retained by the liver. The amount of fat absorbed depends a good deal on the nature of the fat, especially with reference to its melting-point, fats of low melting-point being most readily taken up.
Protein.—The older workers held that the protein was absorbed in ​ the form of proteose and peptone. In support of this it was stated that both proteoses and peptones could be detected in the blood stream. The result of the most recent work tends to show that the material is absorbed in the form of the amino acids either simple or in complex groups, the polypeptides, and that if proteoses or peptones be absorbed they are attacked by the intra-cellular enzyme erepsin, which breaks them down into the simpler products as soon as they are within the intestinal mucous membrane. Certain proteins appear to be absorbed unchanged; for instance, blood serum disappears from the intestine without apparently any change through zymin attack. This fact is made use of in practical medicine, as, when administration of food by the mouth is impossible, patients are frequently kept alive by the giving of nutrient enemata. That the food thus given is absorbed is shown by the increase of nitrogen excretion in the urine.
In the large intestine very little absorption of nutrient matter takes place under normal conditions, mainly of course because most of the absorbable material is removed whilst the food is in the small intestine. That protein matter can be absorbed is shown by the above statement regarding nutrient enemata. The principal substance absorbed here is water; and thus the excreta become firm and formed.
V. Metabolism
In all living matter there is a constant cycle of chemical changes going on, a constant breaking down (catabolism), and a correspondingly constant building up (anabolism). Unless the former is covered by the latter wasting and finally death must supervene. These two changes together make up the metabolism, and the study of this involves a study of the fate of the food absorbed both when it is used immediately and after it has been stored in the tissues of the body. Protein matter is undoubtedly the main constituent of protoplasm, but in what form it exists there is absolutely unknown. One thing is certain, that for the maintenance of life a constant supply of protein matter is necessary. In fact it might be said that this is the essential food and keeps the body alive, fats and carbohydrates being merely subsidiary. In the mammalian organism with which we are specially concerned a supply of these latter substances is also necessary to yield the energy required. The amounts of these various food stuffs which should be present in a suitable diet are dealt with under Dietetics (q.v.). Here we are only concerned with the part played by the different materials in the various chemical changes which are the basis of vital activity.
Not many years ago physiologists were very much in the position of unskilled labourers who saw loads of heterogeneous material being “dumped” for building purposes, but who did not know for what particular purpose each individual substance was used. Thanks, however, to the brilliant work of E. Fischer we are no longer in this position. Gradually our knowledge is being broadened by actual facts obtained by direct experiment, or by inference from previous experiments. But it is still far from complete. It is only possible to outline what is at present known about the part played by the different food constituents in metabolism.
Proteins.—Since these alone contain the nitrogen necessary for the building up and repair of the tissues they are essential and will be dealt with first. In considering the digestion of proteins it was shown that in all probability all protein food was reduced in the intestine to comparatively simple crystalline bodies. O. Loewi has shown that an animal can be maintained in health without loss of weight by feeding it on a diet consisting of amino acids obtained by prolonged pancreatic digestion in place of proteins. In addition to these acids abundant carbohydrates and fats were given. It has since been shown that the presence of carbohydrate a certain amount of is absolutely essential before utilization of the amino acids can take place. Further. it has been demonstrated that only a mere fraction of the total amino acids resulting from pancreatic digestion is sufficient as the source of nitrogen supply for the animal organism. Not only so, but, in spite of the attempt to insist on the polypeptides as being the valuable nuclei for the rebuilding up of protein in the body, it has been shown that mixtures of amino acids from which the polypeptides have been removed can serve as the nitrogen supply.
What then does the body gain by breaking down food material to such simple bodies, if it is immediately to be resynthesized? This complete breakdown appears to be to facilitate rebuilding. The protein in the protoplasm of each animal is characteristic and to build up these different proteins the material must be separated into its nuclei. An experiment carried out by E. Abderhalden shows this very clearly. A protein gliadin absolutely different in constitution from the proteins of blood plasma was fed to an animal from which much of its blood had been removed, so that an active reformation had to take place. The question to be solved was whether by feeding with a protein so absolutely different in constitution the nature of the freshly forming serum protein could be radically changed. But the newly-formed serum was found to be exactly the same in constitution as the old. The tissues had selected simply those nuclei of the gliadin which were required and had rejected the others.
In addition to this breakdown of protein in the intestine, another factor of importance comes into play. After absorption from the lumen of the gut the amino acids are not wholly conveyed as such by the portal blood to the liver. That the portal blood contains a greater amount of ammonia than the systemic blood has long been known, and Jacoby and Lang have shown that many tissues, and among them the intestinal tissues, are able to split off from the amino acids their amino group NH$_2$. Thus it would seem probable that any excess of the amino acids formed does not reach the liver as such but denitrified as members of the fatty acid series. The ammonia split off is also conveyed to the liver and is excreted for the most part as urea, within the first few hours after a protein meal. Thus, in all probability very early after absorption and before the products of digestion enter into combination or any synthesis occurs, all excess of the absorbed nitrogen is disposed of. The rest of the products circulate in the blood, yielding to the cells the materials of which they are in need. On the other hand some investigators still, hold that resynthesis into a neutral protein like serum albumin takes place in the intestinal wall immediately after absorption of the digest products. That the leucocytes play an important part in carrying the products of protein digestion to the tissues is indicated by the enormous increase in their number which occurs during the digestion and absorption of protein foods. How they act, whether simply as carriers of the products of protein digestion combined or uncombined, and how they give the material to the tissues is unknown.
Carbohydrates are generally assumed simply to serve the purpose of yielding energy in their combustion to CO$_2$ and H$_2$O, and to act as protein sparers, i.e. they save the ingestion of large amounts of costly protein material as a source of energy. There may, however, be other activities in which the ingested sugars play a part, for instance, in the utilization of the nitrogen of proteins. It has already been indicated that the nitrogen in the products of pancreatic digestion can be used only when a sufficient amount of carbohydrates is given at the same time. Only carbohydrates seem to be able to do this, for it has been found that when isodynamic amounts of fat are given the utilization does not take place.
When taken into the body in excess of the immediate requirements the sugar is not utilized all at once, but any excess is stored in the form of glycogen both in the liver and the muscles. This glycogen is an insoluble polysaccharide, and is only utilized according to the requirements of the body, especially during muscular exertion. Carbohydrates, when taken in in excess, are also stored in the tissues in the form of fat. This was demonstrated by the feeding experiments of Lawes and Gilbert at Rothamstead. They took two young pigs of a litter, killed and analysed one, then fed the other for a definite time upon food of known composition, determining the amount of protein absorbed by analysing the urine and the faeces. They then killed the pig and by analysis ascertained the amount of fat put on. They found that this was far in excess of the amount of the protein of the food which had been absorbed and was also in excess of what could have been formed from the small amount of fat in the food. The fat must therefore have been formed from the carbohydrates of the food. The consumption of larger amounts of sugar than can be used or stored as glycogen results in its passing straight through the body and being excreted in the urine. This condition is known as alimentary glycosuria. The power of using and storing sugar varies greatly in different individuals and in the same individual at different times.
Fats.—The fats simply serve as stores of energy. After ingestion, if in small amount, they are, like carbohydrates, oxidized to the same final products CO$_2$, and H$_2$O. If in larger amount they are stored as fat, to serve as a reserve in case of need, in the body tissues. Like the carbohydrates they serve as the sources of part of the energy dissipated as heat, but they are not so efficient as sparers of protein material, evidently in part at least because they are less easily digested and absorbed.
Factors which influence Normal Metabolism.
1. Fasting.—During fasting the body draws upon its own reserve of stored material for the requirements in the production of energy, and the rate of breakdown varies with the energy requirements. An individual who is kept warm in bed therefore stands fasting longer than one who is compelled to take exercise in a cold place. The breakdown of tissue during the early days of a fast is much greater than later, for as the fast progresses the body becomes more economical in its utilization of tissue. During a fast the tissues do not all waste at an equal rate; those which are not essential are utilized at a much greater rate than those which are essential to the maintenance of the organism. For instance, it has been shown that during a fast the skeletal muscles may lose over 40% of their weight, whereas an essential organ like the heart loses only some 3%.
The essential tissues obtain their nourishment from the less essential probably by ferment action, a process which has been ​ termed autolysis. The autolytic products of the stored material in the tissues are practically identical with those which arise during the ordinary gastro-intestinal digestion.
2. Muscular Work.—The muscular tissue plays the most important part in general metabolism. Not only is muscle the most abundant tissue present, but it is constantly active and is the great energy-liberating machine of the body. Formerly it was believed on the authority of Liebig that muscular work was done at the expense of the protein material, but it has been conclusively shown that the real source of energy in moderate work is the non-protein material, carbohydrates and fats; of these the former plays the greater part in a man on ordinary diet. If, however, the supply of non-nitrogenous material be insufficient, then the energy has to be supplied by the protein and the output of nitrogen is thus increased. Variations in the amount of creatinin and uric acid (both products of muscle metabolism) excreted have been described. In hard work it is sometimes found that there may be no immediate rise in the nitrogen output on the day of the work, but that an increase is manifest on the second or third day after. While the excretion of nitrogen shows no increase proportionate to the work done, the output of carbon dioxide produced by the combustion of the carbohydrates and of the fats is increased proportionately to the work done.
3. Internal Secretions.—Evidence is accumulating to show that the activities of the various tissues of the body are presided over and controlled not merely by the action of the nervous system but also by chemical substances, the result of the activity of certain organs. To these chemical substances, as already stated, the name of hormones has been given.
The hormone which has been most thoroughly investigated is adrenalin, a perfectly definite chemical compound consisting of a secondary alcohol linked to a benzene ring. It is a product of the central or medullary part of the suprarenal bodies. The medullary part of these organs is developed from the sympathetic part of the nervous system, and adrenalin acts as a stimulant to the terminations of the sympathetic nerves which spring from the thoracoabdominal region. These nerves control the small arteries, and the main action of adrenalin is to cause a powerful contraction of these vessels, and as a result a great rise in the arterial blood pressure. For this purpose it is now largely used in medicine. The constant supply of adrenalin in small quantities seems to play an important part in keeping up the tone of the blood vessels, and when, as a result of disease of the suprarenals, the supply is cut off a serious train of symptoms supervenes.
Allied to adrenalin is a hormone derived from the pituitary body. This also causes a constriction of the small arteries except those of the kidney, which it dilates. An increased flow of urine is produced.
In the thyroid gland a substance, iodothyrin, is constantly being produced, and this appears to exercise a stimulating action on the rate of chemical exchange in the various tissues. Under its administration the waste of both proteins and fats is increased. When the thyroid is removed or destroyed by disease a condition of decreased chemical change and mental sluggishness results, accompanied often by nervous tremors.
A difficulty in explaining these symptoms is caused by the fact that in the thyroid are imbedded four small parathyroids, and it is possible that these produce a special hormone. It has been suggested that this exercises a particular influence upon the nervous system, but further evidence is wanting.
The well-known effects of removal of the ovaries or testes on the development and character of an animal is due to the absence of the special hormone or hormones of these structures. These hormones appear to be produced, in the case of the testes at least, not in the true genital cells, but in the intermediate cells, since it has been found that ligature of the duct, which leads to destruction of the genital cells, does not abolish the development of the sexual characters of the animal.
There is growing evidence that from the ovaries different hormones may be produced in varying amounts which play an important part in regulating the phenomena of sexual life.
The thymus gland is a structure lying in the front of the neck, which is best developed at the time of birth, grows very slowly after birth, and atrophies when the age of puberty is reached. In castrated male animals it continues to grow and persists throughout life. There is some evidence that it may exercise some effect upon the growth of the testes, probably by hormone action.
Pancreas.—Within recent years it has been shown that the internal secretion of this organ plays a very important part in the metabolism of sugar. When the organ is completely extirpated the animal becomes diabetic, i.e. sugar appears in the urine and the animal emaciates. How the internal secretion effects the combustion of the sugar is not yet known. Some workers hold that the action of the pancreatic internal secretion is to control the sugar formation in the various sugar-forming organs, of which the liver is the chief, others that it dominates the utilization of sugar as a source of energy by the muscles.
These are some of the best-known examples of the way in which the products of the activity of one organ modify the functions of other organs. In all probability many more examples of hormone action will be discovered, and it will be found that it plays probably even a more important part than the nervous system in the coordination of function in the animal.
Other factors, besides these already dealt with, play a part in modifying the various metabolic processes, as age, temperature, climate, &c. Very little, however, is definitely known about these various factors.
Water and inorganic salts are quite as essential for the well-being of the body as the energy-yielding proteins, carbohydrates and fats. They, however, probably undergo little or no change in the body; they are excreted pretty much in the same form in which they are ingested. Although they are not subjected to any very great change yet they are of immense importance. No animal tissue can carry on its work in the absence of the various salts. Many experiments have been carried out in which animals have been fed on food as free from salts as possible, and, although the food was much in excess of the energy requirements, yet all these animals died, whereas other animals to which similar food with salts was given throve well. The most important acids are hydrochloric and phosphoric, and the most important bases sodium of potassium. Calcium and magnesium are also of importance, especially where bone formation is taking place. Another element of really vital importance is iron, which is required for the formation of haemoglobin.
VI. Excretion
While we know comparatively little of the intermediate stages in the breakdown of the food constituents, and more particularly of the protein moiety, our knowledge of the final products of the metabolic changes excreted is fairly full. The urine is the main channel of excretion for the nitrogenous waste products. CO$_2$, arising for the most part from the metabolism of carbohydrates and fats, is excreted mainly through the lungs. Water is excreted by the lungs, the kidneys and the skin.
So far no entirely satisfactory explanation has been given of how a fluid like urine, having an acid reaction and containing about one hundred times as much urea and generally more than twice as much sodium chloride as the blood, is formed in the kidneys. The urine is a yellowish fluid which varies greatly in its depth of colour, from pale amber to a deep brown. It has a specific gravity of about 1020, varying with the percentage of solids in solution, and it usually has an acid reaction. It is a fluid of complex character, containing, as already mentioned, practically all the waste nitrogen of the body. Among the principal organic substances present are urea, ammonia, purins (uric acid and the so-called purin bases, xanthin, &c.), creatinin, conjugated sulphates, various aromatic bodies and many other substances in small amount, together with the water and inorganic salts.
The following table from Folin gives a good idea of the average composition of the urine as regards the nitrogen-containing constituents, and its variation according to the nature of the diet when this is free of creatin creatinin and the precursors of the purins:—
Urea, which forms the chief nitrogenous constituent, amounting on an ordinary diet to about 30 grms. per diem, is for the most part formed in the liver, from ammonia obtained either directly from the blood after absorption from the intestine, or resulting from the denitrification of the amino acids. It may also arise in part from the diamino acids and from uric acid.
Ammonia is present in the form of ammonium salts, and forms about 4% of the total urinary nitrogen. It may exceed this amount under certain conditions, for the most part pathological. The ammonia is utilized by the body to neutralize acids which arise during the various metabolic processes.
Purins (uric acid, xanthin, hypoxanthin, &c.) are all members of a series which have as their common nucleus a body which E. Fischer called purin. The most important member of this series is uric acid. It forms about 2% of the total urinary nitrogen. Recent work has shown that it has two quite definite sources of origin: (1) from ingested food containing the precursors, and (2) from the tissue metabolism. The first is known as the exogenous source, and the second as the endogenous. This acid is chemically known as trioxy-purin, and may be regarded as the union of two urea molecules with a three-carbon chain fatty acid. All the uric acid formed in the body is not excreted as such, part being, as already mentioned, converted into urea. The amount which is converted into urea varies ​with the species of animal. In man, Burian and Schur state that one half of the total amount is so converted. Some workers, like Wiener, hold that uric acid may be synthesized in the body, but while this is undoubtedly so in the case of the bird, in the mammal it has not been definitely established. The other chief purin bodies present in urine are xanthin and hypoxanthin, purins less oxidized than uric acid; the first is a dioxypurin, and the second is a monoxypurin. The main source of total purin supply would seem to be muscle metabolism. The mother substances from which all are derived in the body are the nucleins. These complex bodies are apparently first broken down by enzyme action to aminopurins. These in their turn have their amino groups split off, and then, according to the degree of oxidation, the different purin bodies are formed.
Creatinin.—The physiological significance of this substance is as yet unknown. The daily excretion varies little with the character of the diet, provided, of course, that the diet be creatin creatinin free. It appears to be proportional to the muscular development and muscular activity of the individual. Hence it would seem to be derived from the creatin of muscle, a substance which is very readily changed into creatinin outside the body. In the body the conversion of creatin into creatinin seems to be strictly limited and hence when creatin is taken in flesh in the food it tends to appear as such in the urine. It would seem that it is either in great part decomposed in the body into what we do not at present know or that, as suggested by Folin, it may be used as a specialized food. Whatever its source, after urea and ammonia it is one of the most important nitrogenous substances excreted, the daily excretion being about 1·5 grms.
The sulphur excreted in the urine comes chiefly from the sulphur of the protein molecule. It is excreted in various forms. (1) As the ordinary preformed sulphates, that is, sulphur in the form of sulphuric acid combined with the ordinary bases. (2) As ethereal sulphates, that is, in combination with various aromatic substances like phenol, indol, &c. (3) In the form of so-called neutral sulphur in such substances as cystin, which are intermediate products in the complete oxidation of sulphur.
Phosphorus appears linked to the alkalis and alkaline earths as phosphoric acid. A very small part of the phosphoric acid may be eliminated in organic combination such as the glycero-phosphates, &c.
Sodium (mostly as sodium chloride), potassium, calcium and magnesium are the common bases present in the urine. The lungs are the important channel of excretion for the waste product of carbon metabolism CO$_2$ (see Respiratory System); and also a very important channel for the excretion of water. As regards the skin, the sweat carries off a large amount of the water, but it is difficult to determine the total amount. It has been estimated that about 500 c.c. is excreted per diem under normal conditions. Sweat contains salts, chiefly sodium chloride, and organic waste products. Of the organic solids excreted from this source urea forms the most important under normal conditions. Under pathological conditions, especially when there is interference with free renal action, the amount of nitrogenous waste excreted may become quite important. There is also a small amount of CO$_2$ excreted by this channel. (D. N. P.; E. P. C.)