DIGESTION. Most of the food substances taken by animals for nourishment require some alteration before they can be ab sorbed into the blood and in this way carried to all parts of the body. The conversion of foodstuffs into diffusible or assimilable substances is known as digestion and is carried out in the ali mentary canal, mainly by the enzymes secreted by the various glands. The food introduced into the mouth begins its long jour ney through the alimentary canal, where it comes into contact with the digestive juices and thus undergoes chemical disintegra tion, the products being finally absorbed. The three chief func tions of the digestive tract are (i) propulsion of food along the tract; (2) secretion of digestive juices by glands which are con nected with the tract by means of ducts or situated in the walls of the tract; (3) absorption of the final products of digestion.
This operation is known as the establish ment of a salivary fistula. The results have been compared with observations on man obtained in cases where a fistula be came established as the result of accidental injury. The salivary glands must be divided into two groups according to their struc ture and the composition of the secretion.
The first group consists of the mucous glands (submaxillary and sublingual glands) which secrete viscid saliva, rich in the gluco-protein mucin. The second group comprise the serous glands (parotid gland), the juice of which contains no mucin and is therefore watery; it con tains, however, some other proteins mainly of the globulin type. In man and certain other animals, both sets of glands secrete the enzyme ptyalin. Before and after the periods of intake of food, the glands are at rest, for the mois ture of the mouth depends chiefly on the continuous secretion of small glands covering the mucous membrane, and not on the secretion of the salivary glands.
Function and Composition of Saliva.—On the administration of food, all the salivary glands begin to secrete, the amount of secretion being proportional to the length of time the food remains in the mouth. It is, however, not only food substances which evoke secretion. This power is also possessed by certain chemical substances which often are not swallowed but ejected from the mouth, as for instance acids, alkalies, salts and various irritants such as pepper, mustard, etc.; secretion is even evoked by some substances whose irritant nature is due to purely mechanical properties, as is the case with fine sand and certain powders. It is obvious that many of these irritants play a con siderable role in our daily menu, though they cannot be regarded as nutritive substances. The main function of saliva is to soften and lubricate, in order to make the food able to pass through the comparatively narrow oesophagus tube to the stomach. In the case of irritants, the purpose of saliva is to dilute them, and to protect the mucous membrane of the mouth by covering it with a layer of viscid mucin. The primary function of the saliva is therefore physical, but in man and those animals whose saliva contains ptyalin, there is the further function of assisting in the chemical decomposition of the higher carbohydrates.
The composition of saliva secreted on administration of the two classes of stimuli (food and irritants) is very different. When food is given, the mucous glands secrete a viscid saliva, rich in mucin, but when irritants are administered, the secretion con tains hardly any mucin. This difference in viscosity can be dem onstrated by observing the length of time taken by different samples of saliva to flow through a capillary tube, and comparing the rates with that of water. For instance, in one experiment, icc. of water took 6 seconds to pass through the viscosimeter, of saliva obtained on introduction into the mouth of 0.5% HCl took 8 seconds, of an emulsion of mustard 9 seconds, of 2.5% NaC1 9 seconds, while icc. of saliva obtained on adminis tration of bread took 95 seconds, of meat 175 seconds, of milk 231 seconds and of dried powdered meat 255 seconds. On deter mining the organic and inorganic constituents of the saliva, it was found that the "alimentary" saliva from the submaxillary gland contained about 0.99% of organic matter, and about 0•4% of inorganic, while that secreted after administration of irritants contained only about 0. 1-0.2 % of organic matter, and about the same percentage of inorganic matter, namely from These peculiar differences in the composition of saliva are ex hibited only by the mucous glands. The parotid saliva varies little, and with both types of substance has approximately the same composition (0.9-1.0% of organic and 0.35-0•48% of inor ganic matter) . The organic substances are proteins and ptyalin, and the inorganic are chiefly potassium chloride, which appears in considerably larger quantities than in the blood, sodium chlo ride, sodium bicarbonate and potassium sulphocyanide.
Mechanism of Salivary Secretion.—The amount of saliva secreted depends on the length of time any particular substance remains in the mouth, and also on the extent to which the sub stance can mechanically or chemically stimulate the mucous membrane of the mouth. Dry substances always evoke a far more copious secretion than liquids. The results of an actual set of observations will serve as an illustration. The following substances were administered for one minute each. Dry bread and the same soaked in water; the resulting secretion measured 3.9cc. and i•4cc. respectively; with dry meat powder and the same soaked in water, the secretions were 4.5cc. and 1.9cc. re spectively; and with dry sand and the same soaked in water, 2.8cc. and 0.4cc. It is obvious that the purely mechanical stimu lation caused by the various substances is enough to bring about secretion. Pure water at body temperature evokes no secretion, but saliva is secreted on administration of both hot and cold water, and in each case the composition is the same as that ob tained on administration of irritants. The concentration of the chemical stimuli is also of considerable importance. For instance, on administering HC1 in concentrations of o. i , 0.2, 0.3, 0.4 and for one minute the total secretion was in one experiment 7.4, 8.i, 9.2 and 9.5cc. respectively.
The movements of mastication do not evoke salivary secretion in the absence of the higher parts of the central nervous system; the well-known effect of smell and sight of food is in this case also absent. The secretory effect of these stimuli is the result of association, and will be discussed in the section on conditioned reflexes. The mechanism of salivary secretion is based on a reflex act. Foodstuffs or irritants, in virtue of their chemical or me chanical nature, stimulate the peripheral nerve endings of the sensory nerves of the mouth and tongue, namely the lingual and the glossopharyngeal nerves. The nervous impulse passes along these nerves to the salivary centre in the medulla, and is there transmitted by the efferent (secretory) nerves to the correspond ing salivary glands. The higher centres are not necessary for the normal reflex salivary secretion. In dogs in which the brain has been destroyed above the medulla, all the characteristics of the salivary secretion are preserved; moreover, the composition and amount of the secretion depend on the nature of the stimulus in the usual way. After injury to the medulla or after section of both sensory nerves of the mouth, secretion cannot be evoked either by the act of eating, or by irritants.
Nerve Connections.—The chief secretory fibres of the two mu cous glands were discovered by Ludwig in 1851. They run in the chorda tympani, which is a branch of the facial nerve. The secretory fibres of the parotid gland pass along the glossopha ryngeal nerve. Electrical stimulation of these nerves evokes an immediate and copious secretion from the corresponding glands, the rate of secretion being proportional to the strength of the stimulation. All the salivary glands also receive a nerve supply from the sympathetic system, via the cervical sympathetic nerve. The saliva obtained from the mucous glands after stimulation of the cerebral nerves of the dog is more copious and less viscid than that obtained after stimulation of the sympathetic nerve.
Stimulation of the cerebral nerves produces a very considerable vasodilation and therefore increases the blood supply to the gland, while stimulation of the sympathetic nerves produces vaso constriction to the point of almost arresting the circulation. The correlation formerly drawn was that the extent of secretion and the composition of the saliva were dependent on changes in the blood supply accompanying the stimulation of the corresponding nerves. But it is now generally accepted that the composition of the secretion depends little if at all on the blood flow. At any rate, the saliva does not become more concentrated if on stimu lating the cerebral nerve the blood flow is reduced to its original level nor does it become more dilute if the blood flow is arti ficially increased. The differences in the composition of the saliva and the amount secreted in the normal animal during ad ministration of various substances is certainly not dependent on changes in blood flow (as proved by direct measurements) ; neither is it dependent on the presence of the sympathetic fibres. After section of all the sympathetic connections, the secretion remains viscid in the case of food, and fluid in the case of irritants.
The part played by the sympathetic nerves in normal secretion is not definitely known. After section of the latter, the secretion hardly changes, while after section of the cerebral nerve it ceases. Artificial stimulation of the sympathetic nerve, however, pro duces a slight flow of saliva, and causes definite histological changes in the gland. Besides the secretory and vasomotor fibres, the sympathetic nerve contains fibres which stimulate some con tractile elements around the secretory cells, and thus help to empty the gland of the viscid juice. The cerebral nerves have no such fibres. The secretory nerve endings of the cerebral salivary nerves are completely paralysed by atropine while the vasodilator nerves are left intact—a further proof that secretion is not due to vasodilation.
Secretion is not filtration of water from the blood through the gland with a certain washing out of stored substances, but is an active process, the energy for which is derived from oxidations within the gland itself. This is most conclusively proved by the fact that during secretion the gland may develop a hydrostatic pressure in its ducts that is much greater than the blood pressure. The exact nature of the secretory process is not known, and none of the physico-chemical processes that are known to take place in the organism supplies an adequate explanation.
In the pharynx, the food passes a region common to the respiratory and digestive system, but the respiratory passages are temporarily closed. The act of deglutition is impossible unless the larynx is free to move. The bolus is now shot rapidly into the region of the medium and lower constrictors of the pharynx, and then into the oesophagus. Liquids and semi-solids quickly pass down the oesophagus to its cardiac end. Here the passage becomes less rapid, the fluid escaping slowly in a narrow stream into the stomach. The average time for a complete act of deglu tition is about 6 seconds for liquids and semi-solids, but dry food substances may take as long as 15 minutes to reach the stomach. The propulsion of liquids is mainly due to the movement of the back of the tongue, but that of solids is due to the contraction of the constrictors of the pharynx and the oesophagal muscles, which slowly push the food towards the stomach.
The passage of food along the oesophagus is assisted by a reflex inhibition of the wall, which is succeeded by a contraction. In every complete act of deglutition there are thus two waves which pass along the oesophagus, one of relaxation and the other of con traction. If however several deglutitions follow one another at short intervals, the wave of contraction has no time to develop, and the succeeding waves of relaxation fuse with one another, thus causing a relaxation of the oesophagus along its whole length. The tube therefore becomes an open passage through which large amounts of liquid can pass into the stomach by mere force of gravity. When swallowing stops, a strong wave of contraction develops. These waves of relaxation and contraction are due to a reflex, and they are not arrested by complete transverse section of the oesophagus, but are stopped by section of its nerves.
There is an important interdependence between respiration and deglutition, for every act of deglutition inhibits a respiratory movement. In the absence of this correlation, food might easily slip through the open respiratory passages into the trachea, which may actually happen in cases of paralysis of the laryngeal mus cles. The arrest of respiration may last as long as 6 seconds. That deglutition is impossible in the absence of a bolus is shown by the fact that a man with an empty mouth can perform only four or five swallowings in rapid succession, after which swallow ing becomes impossible for a time. The first acts of deglutition were possible because of the presence of saliva in the mouth; after rinsing the mouth with a weak solution of atropine even a single deglutition is impossible without taking some liquid.
Except during the period of digestion, the gastric glands are at rest, a little mucus being secreted by the superficial epithelial layer. Within about 5 minutes of the intake of food, the gastric gland begins to secrete. The secretion gradually increases in rate, and considerably outlasts the actual period of eating.
The Reflex Phase.—In order to determine whether it is the act of eating or the entry of food into the stomach that brings about gastric secretion, Pavlov performed the following operation. In a dog in which a gastric fistula had been established, he made a transverse section of the oesophagus in the neck, and sutured the two ends to the skin, so that anything that was swallowed dropped out from the open end of the oesophagus and could be eaten again. The animal had of course to be fed either through the lower end of the oesophagus or through the gastric fistula. Animals operated on in this manner live as long as they would normally, and experience no discomfort whatever. When these animals are fed through the mouth (sham feeding), the gastric glands begin to secrete, exactly in the same manner and after the same latent period as in the normal act of eating. The secretion lasts for hours so long as sham feeding is continued, and after its termination the secretion gradually declines, and finally ceases within 10-20 min utes. The conclusion from these experiments is that the onset and the maintenance of the secretion is a reflex which, like that of the salivary secretion, originates in the mouth. The afferent nerves for this reflex are the same as for the salivary secretion, while the secretory fibres run along the vagus nerve. The centre for gastric secretion lies in the medulla. This reflex secretion does not involve the co-operation of the higher nervous centres, and is readily ob tained in dogs whose entire f ore-brain has been removed. After section of both vagi, the reflex cannot be evoked, just as happens in the case of the salivary glands after section of their respective secretory nerves.
The rate of gastric secretion, the amount of juice secreted, and the composition of the juice (see the section on Nutrition) vary little with different food substances. The juice obtained after administration of fats is deficient in pepsin. The experiments with sham feeding were repeated and confirmed in the case of a man in whom a gastric fistula had to be established on account of stricture of the oesophagus. The amount of juice secreted by an average sized dog may be as much as 200CC. after half an hour of sham feeding, but the secretion may vary considerably.
Part Played by the Higher Centres.—Like the amount of saliva, the amount of gastric juice secreted is largely dependent on appe tite. A hungry animal may give, in the same period of time, 5 times more juice than an animal which recently has been fed. It is not only contact with the mucous membrane of the mouth that evokes the reflex, but also the sight and smell of food, and in fact all those stimuli which the animal associates with food. These effects are entirely dependent on conditioned reflexes (i.e. on the higher centres), which in ordinary life play an extremely impor tant part in regulating the activities of all the systems of animals and man; amongst these activities are those of the alimentary glands, which stand in close relation to the central nervous system. Administration of tasteless food, monotony in food, and gross irregularity in the time of feeding will all affect gastric secretion. If the intake of food is too rapid, the secretion will not have time to develop to its maximum, and the food will remain undigested for a considerable time. It is known that the amount of juice secreted, and therefore the digestive and nutritive properties of the food, depend in the long run not so much on the weight or calorific value of the food as on how we eat it, how it is prepared and served, and how we prepare ourselves and concentrate on its intake. However, if man's nutrition depended entirely on his wisdom, only a few would survive, and the organism has, in the case of gastric secretion, a mechanism which is controlled inde pendently not only of the higher centres, but also of the medullary reflex mechanism.
The Chemical Mechanism.—This mechanism was also dis covered by Pavlov. If certain food substances are introduced through a fistula directly into the stomach, secretion of the gastric juice ensues. This secretion is independent of the nervous system, and can be obtained in a stomach after section of all its nerves. The secretion is best observed in animals in which a portion of the stomach has been separated from the rest and transplanted to the outside (gastric pouch). The pouch may be made so as to preserve its innervation intact, or after section of all the nerves. In the first case, sham feeding will of course produce its usual effect, since this secretion depends on the integrity of the nerves; but in the latter case sham feeding will have no effect. Introduction of certain food substances into the main part of the stomach will, after a latent period of io-15 minutes, evoke secretion from the main stomach as well as from the isolated portion, regardless as to whether the nerves are cut or left intact. It is obvious that, in these experiments, since the food substance is never in contact with the transplanted part of the stomach, the secretion cannot be due to a local chemical or mechanical stimulation.
As regards the nature of the substances producing secretion on entry into the stomach, it is known that unchanged food sub stances, whether carbohydrates, fats or proteins, are unable to produce this secretion. The secretion is however evoked by the presence of the products of the digestion of proteins (peptones, albuminoses) and of fats (fatty acids, soaps). Substances which may be extracted from meat and vegetables on boiling (probably the albumoses) also evoke the secretion if they are introduced directly into the stomach. A most illustrative example is provided by the following experiment. Direct introduction of raw meat into the main part of the stomach, after a latent period of about 5 minutes, brought about a considerable secretion from the iso lated pouch; a similar introduction of an equal quantity of meat which had been boiled for several hours produced no secretion at all, but the water in- which the meat had been boiled caused the same secretion as raw meat. Boiled meat which had been sub jected to gastric digestion in vitro produced a very large secretion. The experiment is practically duplicated with vegetables, but on a smaller scale, except that the peptic digestion of the thoroughly boiled vegetables makes no appreciable difference.
There are however proteins which do not yield any extractive substances which are capable of stimulating gastric secretion (for instance egg-white), though on digesting them with gastric juice they acquire strong stimulating properties. In general, we can say that extractive substances from proteins, the products of the digestion of proteins but not proteins themselves, and the products of the digestion of fats but not .fats themselves bring about gastric secretion when introduced into the stomach, and this secretion is not under the control of the nervous system.
Two Phases.—The whole gastric secretion may thus be divided into two phases, the first reflex phase (through the vagus nerve), and the second or chemical phase. The first phase is by far the most important—it starts the digestion of proteins, and thus leads to the production of those chemical substances which will further stimulate the secretion of gastric juice. But how much more than mere custom there is in the taking of soup before a meal; in this way we administer to the stomach extractive sub stances derived from meat or vegetables, and thus ensure that, even in the absence of appetite, our food will meet with some gastric juice in the stomach.
The mechanism underlying the chemical phase of secretion is not yet clear. It is, however, known that the products of digestion of proteins, etc., need not come into contact with the fundal part of the stomach at all; they must, however, come into contact with the mucous membrane of the pylorus, and this is the way in which they produce their effect. There is much evidence for the view that, under the action of these stimulations, a substance (generally called gastrin [Edkins]) is liberated by the pylorus into the blood; the blood then brings this substance to the fundal glands and stimulates them to secrete the juice. That the stimulus is carried by the blood stream can be regarded as proved, at least in cases of transplantation of parts of the stomach to the thigh and chest of the animal, for extractive substances on introduction to the main stomach evoke secretion in the transplanted part.
Besides the two phases of gastric secretion, there are no other methods of evoking secretion, and in any given case the amount of gastric juice secreted, in a complete act of eating, is equal to the sum of the effects of the nervous phase and the chemical phase. Atropine, which paralyses all secretory nerves, does not affect the second phase of secretion.
The Effect of Fats.—Neutral fats have a peculiar effect on gas tric secretion. On administration of fats, the amount and strength of the gastric juice are diminished. This effect is supposed to be due to a reflex originating in the duodenum. It is certainly not due to clogging of the orifices of the gastric glands, for substances with the same viscosity have no effect. Fats when administered to the mouth quickly enter the duodenum, and there augment the pancreatic secretion and diminish the gastric secretion. Fats become digested by the pancreatic juice, and the products of their digestion are regurgitated into the stomach, where they stimulate the gastric secretion by liberating the gastrin bodies from the pylorus. The effect of fats on the gastric secretion passes through three phases, the reflex, the inhibitory and the chemical.
It is obvious that in the case of complete feeding, the production of the gastric juice, depending on the two phases of secretion and on the inhibitory effect of fats, will be typical for each of the three main food substances. In the case of carbohydrate food, the secretion is very much like that in sham feeding—rapidly rising, then falling off within an hour or so ; the nervous phase pre dominates, the chemical phase being negligible since the carbo hydrates and their products have hardly any stimulating effect on gastric secretion. In the case of proteins, the chemical phase is well pronounced and superimposes itself on the nervous phase, and the secretion is prolonged at its maximum for over two hours. Then as the food leaves the stomach the secretion gradually diminishes. In the case of fats, the nervous phase is cut short'as soon as food enters the duodenum, but the secretion is again favoured by the chemical phase setting in, the net result being a considerable prolongation of the period of gastric secretion. With mixed food, secretion will be the result of a summation of all these individual factors.
Gastric sect etion is not evoked by the mechanical stimulation of the gastric mucous membrane, as was supposed before the true mechanism of gastric secretion was known. Water and alcohol both cause a slight secretion. The products of the digestion of carbohydrates do not seem to have any effect on gastric secretion, but carbohydrates themselves increase the strength of the gastric juice, and if they are present in the food in sufficient amount the concentration of pepsin may be actually doubled. The mechanism of this effect is not known.
When food is taken, it accumulates in the fundus and is sepa rated from the pylorus by a strong contraction (the transverse band or the prepyloric sphyncter). After a few minutes, waves of contraction begin to appear slightly on the fundal side of the transverse band, and travel slowly towards the pylorus. These waves gradually increase in strength so that the pylorus may present a series of constrictions. The semi-digested food is thus brought into close contact with the pylorus mucous membrane. The pylorus, however, remains closed, and the food is therefore squeezed back, and forms a reflux stream towards the fundus. The food thus becomes thoroughly mixed with the gastric juice. The fundus of the stomach is now exercising a steady pressure by the contraction of its muscular walls, so that the digested food is forced to enter the pylorus. At varying intervals, the time de pending on the nature of the food, the pylorus opens, and a little of the digested food enters the duodenum. As digestion proceeds, the fundus increases its pressure on the gastric contents while the pylorus opens at more frequent intervals. The stomach thus gradually empties itself, and the whole organ acquires the shape of a curved tube. At the end of digestion, the pylorus may even open to allow the passage of undigested material.
The contractions of the stomach, and its method of emptying, are very similar in man and the carnivorous animals. The fore going description applies to the events which succeed the taking of a considerable mixed meal. If water alone is taken, the pylorus opens within a very short time, and the fluid reaches the duodenum within a few minutes. The importance of this becomes obvious when it is remembered that practically no absorption of water takes place in the stomach, but only in the intestine.
Pylorus and Duodenum.—The movements of the two portions of the stomach can be observed also on anaesthetised animals, and even on a stomach which has been excised and placed in warm salt solution. They must therefore have their origin in the walls of the stomach itself. The vagus nerve supplies the muscles with fibres, the stimulation of which increases the contractions. The opening of the pylorus is more dependent on the nervous mech anism. If both vagi are cut, the emptying of the stomach becomes difficult on account of the diminution in the strength of the contractions, and also because the opening of the pylorus is not easily brought about. The food thus remains in a semi digested form (since the secretion of the juice is also diminished) for a long time in the stomach; it undergoes putrefaction and the animal may die of autointoxication. The opening of the pylorus does not only depend on the intragastric events but also, as shown by Pavlov, on the condition of the duodenum. The pylorus remains firmly closed so long as the contents of the duodenum remain acid. If alkaline fluid or water is introduced into the stomach, and at the same time some weak acid is injected into the duodenum by means of a duodenal fistula, no fluid passes out of the stomach until the acid is neutralised by the secretion of the pancreatic juice.
When the pylorus is open, not only do the contents of the stomach enter the duodenum, but also the contents of the duo denum regurgitate into the pyloric cavity. Such regurgitation is a normal occurrence, and takes place in the digestion of any food, but is especially conspicuous in the digestion of fats. Fats are not digested in the stomach ; they pass on to the duodenum where they are converted into glycerol and fatty acids which, in the alkaline medium, form soaps. While in the duodenum, fats cause (a) an inhibitory effect on gastric secretion, and (b) a contraction of the pylorus. As soon as the fats are digested, the pyloric sphyncter opens, and large amounts of the products of the di gestion together with bile and pancreatic juice regurgitate into the pylorus, where they increase gastric secretion by chemical stimula tion. We must consider the action of the sphyncter as dependent on the central nervous system and on the "acid control." Can non's experiments have shown that "hunger pangs" are associated with and probably due to the rhythmic contractions of the stomach which occur about meal-times, especially if they are delayed.
The secretion of pancreatic juice has been studied in animals in which a fistula of the pancreatic duct has been established (the operation is similar to that of establishing a salivary fistula) . Like the salivary glands and the glands of the stomach, the pan creatic gland is at rest except during the periods of digestion. The secretion begins soon after administration of food but it lags behind the gastric secretion, the maximum of which precedes the maximum of the pancreatic secretion by about an hour. The rate of pancreatic secretion, after a meal of proteins or carbohydrates, is on the whole very similar to that of the gastric secretion, but in the case of fats it is somewhat different. The similarity in the histological structure of the pancreas and the salivary glands has led physiologists to believe that the mechanism of secretion of these glands is the same, that is to say that the pancreatic secre tion is controlled by a secretory nerve.
The Secretory Innervation of the Pancreas.—The secretory fibres were discovered by Pavlov to run in the vagus nerve. How ever, stimulation of the vagus never produces anything like the normal quantity of the juice, and the whole secretion is rather peculiar. The vagus nerve has to be stimulated for a very long time before the secretion will appear. The vagus produces a strong contraction of the larger ducts of the gland, and thus prevents the juice from leaving the gland. But even independently of this contraction of the ducts, the amount of juice secreted is very small (about zocc. during a period of stimulation of 5-6 hours, as against a normal secretion of over i 5occ. after entry of a pound of meat) .
Furthermore, the composition of the juice so obtained is not like that which is secreted under normal conditions. It is over 10 times more concentrated, both in its protein and enzyme content. When boiled, it coagulates in a lump like egg-white, while the normal juice becomes only slightly flocculent ; it is also less alkaline than the normal juice, and therefore the trypsinogen of the "vagus juice" is apt to undergo spontaneous activation, and is more easily activated by enterokinase than the normal juice (the rate of activation is slower the more alkaline the juice). Nevertheless, the vagus nerve is a true secretory nerve; on stimu lation, it produces very considerable histological changes in the gland, far greater changes than in the case of normal secretion, and the nerves are completely paralysed by atropine. It may be con cluded that, so far as causing the output of solids and enzymes is concerned, the vagus stimulation does the same or more than the taking of food, but as regards the passage of water from the blood into the ducts it is much less effective.
We also owe to Pavlov the discovery that introduction of acid into the duodenum of animals or anaesthetised animals is followed by a profuse pancreatic secretion, which lasts as long as the acid is being absorbed. The similarity between this effect and the secretion of saliva (on administration of acid into the mouth) led Pavlov to believe that the pancreatic secretion is also based on a reflex mechanism, the efferent path from which follows the vagi. He soon found, however, that section of the vagi, or in fact destruction of the entire nervous system, does not prevent the secretion of the pancreatic juice on administration of acid into the small intestine. Administration of acid into the stomach, into the large intestine or anywhere else has no effect whatever.
Gastric Juice.—The discovery of the effect of acids is far more important than could be imagined at first sight. Pure gastric juice contains about 0.5% HC1 but usually, on account of dilution with saliva and food, the acidity of the gastric contents is reduced to about o. 2-0.3 %. The acid enters the duodenum and causes the pancreatic gland to begin to secrete. The first phase of gastric secretion becomes of outstanding importance, for it not only causes a further stimulation of gastric secretion, by giving rise to the products of digestion, but it also indirectly causes the continu ation of digestion, for the acidity of the whole gastric contents leads to the secretion of the pancreatic juice.
Appetite, in that it augments the nervous phase of gastric digestion, is the trigger that sets the whole digestive tract into activity. This fact so much impressed Pavlov that he organized, next to his laboratory, a special department where the gastric juice of dogs was (and still is) obtained by sham feeding in large quantities. This material was sterilized and sold at a low price to the general public at the rate of several thousands of bottles a year. The improvement of digestion and nutrition in cases of dyspepsia, cancer, achlorhydria, loss of appetite and chronic gastritis was immense.
The Chemical Phase of Pancreatic Secretion.—The mechanism of the secretory effect of acid was discovered by Bayliss and Star ling in 1902. They found that, on pounding up some scrapings of the intestinal mucous membrane with dilute acid and filtering, they obtained a filtrate that produced a copious flow of pancreatic juice when it was injected into the blood. This discovery was not only of great value in elucidating the mechanism of pancreatic secretion, but it was also of general importance in physiology, for it was the first time it could be shown that a chemical substance, manufactured under definite conditions by one organ, could be liberated into the blood stream and conveyed to another organ, which it would excite to activity. Since this discovery, a number of other substances of the same nature have become known. Bayliss and Starling described them as chemical messengers, and gave them the name of hormones (q.v.). The hormone of the small intestine was called secretin, or pancreatic secretin, to distinguish it from other members of the same class.
Secretin can be extracted from the small intestine by various solvents, e.g., water, alcohol, salt solutions, etc. It is not an en zyme, and is not destroyed by boiling. That secretin is normally transported by the blood stream is most convincingly shown by experiments with crossed circulation, and perfusion of the isolated pancreatic gland. If two arteries of two dogs are connected in such a manner that the blood of one animal freely mixes with that of the other, and if acid is injected into the duodenum of one of the animals, the pancreatic glands of both dogs begin to secrete. Also, if a pancreas is cut out of the body and perfused with blood under pressure so as to keep it alive, and if a solution of secretin is injected into the blood, the isolated pancreas im mediately responds by secretion of the juice. In this secretory mechanism, we have a very striking example of a correlation be tween the activities of two different parts of the body, effected by chemical means. When the acid chyme enters the intestine, a certain amount of secretin is liberated into the blood stream. The resulting secretion of the alkaline pancreatic juice neutralizes the acid chyme, and the liberation of secretin (and therefore of pancreatic juice) comes to an end. So long as the duodenal con tents are acid, the pylorus remains closed, but as soon as they are neutralised, the pylorus opens to allow another portion of the acid gastric contents to pass. In this way, the pancreatic secre tion is maintained throughout the whole period of digestion.
chemical composition of secretin is not known, and secretin has not yet been obtained in a pure form. The usual extracts of the mucous membrane of the small intestine contain, besides secretin, a large number of impurities, especially a sub stance named histamine, which has a considerable vasodilator effect on the capillaries of all organs. Thus after the injection of crude preparations of secretin, the blood pressure falls, some times very considerably. It has been proved that the induced pancreatic secretion is not caused by the fall of blood pressure itself. The proof rests on the following observations. The vaso dilatory substances can be extracted from almost every organ, but secretin is only present in the small intestine. With certain solvents, it is possible to extract a depressor-free secretin. In slightly alkaline medium, secretin is destroyed while the vaso dilatory substances remain intact. The action of secretin is not paralysed by atropine, showing that secretin acts directly on the pancreatic cells, and not on the nerve-endings of the secretory nerves. The composition of the secretion and the chemical mecha nism of pancreatic secretion are apparently the same in all ani mals ; at least, secretin extracted from the intestine of any animal will cause pancreatic secretion in any other animal. In the foetus, secretin is found in a very early stage of development.
The question now arises as to the correlation between the nervous and the chemical mechanisms of pancreatic secretion. The correlation is not yet clear, but we know of one instance in which the secretion, or rather the composition of the juice, is determined by the cooperation of the vagus nerve—that is in the case of injection of fats. Injection of neutral fats or of soaps into the duodenum evokes a secretion of very concentrated juice that is rich in enzymes. After section of the vagi, or after in jection of atropine, the quantity of the secreted juice is unaltered, but it is now poor in enzymes. In many cases also sham feeding, when the entry of the gastric juice into the duodenum is prevented, will evoke a small secretion of very concentrated juice, some time before the appearance of gastric secretion; this secretion is absent after section of the vagi.
Stimulation of the vagi, superimposed upon the pancreatic se cretion which has been evoked by injection of secretin, does not modify the rate of secretion but greatly enriches the juice in en zymes. It seems that the nervous mechanism is chiefly concerned with the removal from the cells of the pre-stored enzymes, while the chemical mechanism regulates the passage of water and alkali from the blood through the gland into its system of ducts. Histo logical observations support this point of view since, after the considerable secretion of pancreatic juice evoked by chemical means, the pancreas looks only slightly exhausted, while after the small secretion evoked by stimulation of the vagus the gland be comes a picture of maximal exhaustion.
From the point of view of digestion, the only important constit uents of bile are the bile salts (sodium taurocholate and gly cocholate) . The digestive functions of bile are:— (I) Activating the lipase of the pancreatic juice.
(2) Increasing the emulsification of fats by lowering the surface tension.
(3) Dissolving fatty acids and soaps.
(4) Increasing the peristaltic movements of the intestinal tract.
(5) Increasing the bile production on reabsorption of bile salts into the blood.
During the periods of digestion, the flow of bile is increased. This is due to two factors :—(a) the emptying of the gall bladder, and (b) an increased formation of bile.
The muscular wall of the gall bladder is under a nervous control, the vagus conveying motor, and the sympathetic inhibitory fibres. The entry of the products of gastric digestion and of the acid chyme into the duodenum sets the reflex in operation. The actual secretion of bile, however, is independent of the nervous system, and continues even after all the nerve connections of the liver have been severed. It is mainly dependent on the blood supply to the liver and, if other conditions are the same, the bile flow in creases with increase of blood flow. Absorption of food substances, of acid, and especially of fats increases the production of bile. This is ascribed by some to the liberation of the pancreatic secretin.
The bile salts are reabsorbed in the intestine and conveyed via the portal vein back to the liver, which removes them from the blood, thus preventing their entry into the general circulation where they would be intensely poisonous (see JAUNDICE). The bile salts increase the production of bile, and thus a comparatively small amount of bile salts undergoes repeated resecretion during a comparatively short time. The entry of bile into the digestive tract, and therefore the stimulating effect of bile salts upon bile production, is stopped at the end of digestion by the closure of the sphyncter of the common bile duct.
The intestinal juice on standing divides itself into 2 fractions, a sediment which is chiefly composed of the mucus secreted by the goblet cells of the digestive tract and desquamated epithelium, and a liquid part containing enzymes (see section on nutrition ; the enzymes are enterokinase. erepsin, nuclease, amylase, invertase, lactase and lipase maltase; the Brunner's glands of the duodenum secrete an enzyme similar to pepsin). The lower down the tract, the larger is the sedimentation, until the secretion in the large intestine is composed of mucus and is devoid of enzymes.
There are no definite indications of any nervous control of intestinal secretion. Section of the nerves produces a great increase in the flow, but this is usually attributed to the hyperaemia ensuing after section of the nerves, which contain a large amount of vaso constrictor fibres. Some physiologists regard this secretion as due to section of special inhibitory nerves.
Intravenous injections of secretin increase the secretion of intestinal juice, and Starling regarded the mechanism of intestinal secretion as identical with that of pancreatic secretion, namely that in both cases the stimulus is due to the liberation of the same agent, viz. secretin. However, experiments on animals with a transplanted loop of the intestinal tract (kept under normal con ditions) make this view untenable. On feeding such an animal, the secretion of the transplanted part is not increased as it would have been if the hormone mechanism were the operative factor. Pavlov's experiments show that the stimulus for intestinal secre tion is, like that of pyloric secretion, local mechanical stimulation of the mucous membrane.
Some Experiments.—The following experiments may serve to illustrate this point. The secretion of the intestinal juice from the small isolated portion was measured before and after feeding the animal with various food substances. The juice was collected by means of a small tube inserted in the isolated loop. Before feed ing, the spontaneous secretion varied between 2.0 and 2.8cc ; after intake of meat, it was 2.5cc., after bread 3.occ., after milk i.7cc., and after mixed food i.6cc. Only in the case of feeding with fats did the secretion of the isolated portion slightly but definitely increase (from 3.o to 5.occ.).
With these results should be com pared the experiments with local mechanical and chemical stimu lation of the transplanted part.
The spontaneous secretion was o.o–o.5cc. per hour ; when a rub ber tube was introduced into the intestinal loop, the secretion in creased to 4cc.; when glass beads were placed in the intestines, it increased to 8.7cc.; when o.5% HC1 was injected into the intes tine and then removed, the hourly secretion increased to 20CC. The stimulation by either of the above methods of some part of the in testine has no effect on the rest of the tract, showing that the effect is mainly if not entirely local. These local stimuli have hardly any effect on the secretion of the sediment ; they only increase the pro duction of the enzyme-containing liquid part of the juice.
Some observers have found that stimulation of the vagus nerve increases the secretion of the juice after a very long latent period. It is possible, however, that the increased flow is due to a more vigorous contraction of the intestines, for the vagus is the motor nerve of the intestinal muscles.
A very interesting Correlation has been discovered as regards the concentration of enterokinase in the intestinal juice and the pan creatic juice. The transplanted loop of the intestine secretes a juice which becomes progressively poorer in enterokinase, so that a few months after the operation it almost entirely loses the power to activate trypsinogen (see section on Enzymes). If however the mucous membrane is brought for a short time (2-3 minutes) into contact with the pancreatic juice (the juice may be diluted to as much as one in moo), the concentration of enterokinase increases. Alkali and boiled pancreatic juice have no such effect. The concentration of other enzymes of the intestinal juice is not affected by such treatment of the intestine with pancreatic juice.
The Movements of the Small Intestine—It is known that the intestinal tract is in a state of constant movement, the analysis of which presents great difficulties because several types of con traction may occur simultaneously or in rapid succession, either at the same point or at neighbouring positions. Different authors have given different descriptions of these movements, and have used different nomenclatures but in spite of this confusion it may be said that the small intestine exhibits three kinds of contractions. These are as follows :—(a) the rhythmic segmentation (also lcnown as pendular movements or swaying movements) ; (b) the peristaltic contraction (also known as the mysenteric reflex) ; and (c) the tonic contractions.
Rhythmic Contractions.—Direct observations of an exposed part of the intestine show that slight waves of contraction pass over its surface. Records by means of instruments show that both the circular and the longitudinal muscular coats take part in these contractions, which recur at the rate of io-15 a minute. These contractions involve only short stretches of the intestine. They easily can be produced artificially by stimulating the gut either electrically or mechanically. On application of such a stimulus, the part immediately stimulated quickly contracts, the contraction spreading one or two centimetres along the intestine. These rhythmic contractions may originate spontaneously in any part of the intestinal tract, especially at those parts which are subjected to some tension. The propagation of this contraction goes from muscle fibre to muscle fibre at an average rate of about 5cm. per second.
These rhythmic contractions are unaffected by section of all the nerves of the intestine, in fact they are entirely myogenic in origin. They are even independent of the local nervous network of the intestinal wall, for strips removed from the longitudinal coat of the small intestine entirely free from any remains of the nerve plexus continue their rhythmic contraction. (The nervous network of the intestine is made up of Auerbach's plexus and Meissner's plexus.) In order to observe the rhythmical contractions, isolated por tions of the intestine can be removed from an animal after its death ; these portions should be kept at body temperature, sur rounded with a solution containing salts in the same proportion as those in blood (Ringer's fluid), and richly supplied with oxygen. In the normal animal, the rhythmic contractions cause a thorough mixing of the contents of the gut with the secretions of the various glands, but they do not help to pass the food along the intestinal tract, for each contraction squeezes the food in both directions. A column of food may thus remain at the same level in the gut for a considerable time.
Peristaltic Contractions.—The onward progress of the food is caused by true peristaltic contractions which involve contraction of the intestine above the food mass, and relaxation below. This contraction and relaxation travels down the intestinal tract in the form of two waves, and in this way the food is slowly propelled towards the large intestine. The peristaltic contractions involve the co-operation of the local nervous system of the intestine, and they. are absolutely abolished by painting the intestine with drugs which paralyse nerves (e.g., nicotine, cocaine), but still continue after severing the nervous connection between the intestine and the brain and spinal cord. The direct irritating effect of food, or the application of an experimental stimulus, evokes an immediate contraction above and relaxation below (sometimes described as "the law of the intestines"). Anti-peristalsis is not observed in the small intestine.
Tonic Contractions.—The third type of movement, which is known as the tonic contraction, is common to all plain muscles, and is determined by a state of sustained partial contraction of the muscle. Neither during the wave of relaxation observed as the forerunner of the wave of contraction in peristalsis, nor during the periods in between the rhythmic segmentation, is the intestine completely relaxed ; it always maintains a certain tone, which may be greater or less. Thus the two forms of contraction (already described) are superimposed upon the tonically contracted state of muscles. In some cases, the intestinal tone may be intense. It is claimed that colic pains are due to this form of contraction.
Although the mechanism of all these three forms of contraction is entirely peripheral, they can be increased or decreased by im pulses from the central nervous system. The vagus nerve carries nerve fibres to the intestine which stimulate its movements, while the splanchnic nerves diminish or even abolish them. The lowest 2CMS. of the small intestine exhibits a thickening of the circular muscular coat, the ileocolic sphincter (valve), which relaxes in front of a peristaltic wave and contracts if there is any regurgita tion from the large intestine. This sphincter presents a marked contrast to the rest of the small intestine in that its innervation is reversed, the vagus being the inhibitory and the splanchnic the excitatory nerve.
The Movements of the Large Intestine.—The contents of the small intestine are gradually transferred into the large intestine. In carnivora, the digestion and absorption are both nearly com pleted at the ileocolic valve, but in herbivora a large part of the processes of digestion and absorption occur in the large intestine and in the caecum. As regards his large intestine, man takes an intermediate position between these two groups of animals.
The movements of the large intestine can best be observed by means of the X-ray method, after feeding a meal containing some bismuth. The food first fills the proximal part of the large intes tine. The distension brings about a wave of contraction which starts at the end portion of the ascending colon, and slowly travels in a backward direction, passing the food towards the caecum; the ileocolic valve prevents its escape into the small intestine. These contractions are not preceded by a wave of relaxation, and there fore should not be regarded as anti-peristaltic waves. As the whole contents cannot escape into the caecum, certain portions slip back. These movements thus have the same effect as those of the pylorus; they bring the food into closer contact with the walls of the alimentary canal. In this way the intestinal movements favour the absorption of substances that escaped absorption in the small intestine.
The distension of the caecum occasionally excites a true peristal tic wave which travels in a forward direction and drives the semi solid residue of the food towards the distal part of the colon. The intensity of the peristaltic waves and of the backward contraction vary greatly in different kinds of animals, and even in different individuals of the same species. In man they are not well pro nounced, and the caecum and the ascending colon seem to be more or less passive. About 400 grammes of semi-liquid material passes the ileocolic valve daily ; of this, about 25o grammes is water with some nutrient material, which is absorbed in the large intestine; the remaining 15o grammes form the faeces.
The large intestine, like the small, has a nervous system of its own in the form of a network of nerve cells and fibres lying in between the muscular layers. The movements of the large intestine are primarily dependent on this network, but they can be increased under the influence of the pelvic visceral nerve, or diminished by the inferior mesenteric nerves which belong to the sympathetic nervous system. A distinguishing feature of the distal colon is its complete subordination to the spinal centres. It remains inactive until, on account of distension, it is reflexly excited through the pelvic visceral nerve; it is then completely emptied. In man,' the emptying of the rectum is largely assisted by contractions of voluntary muscles of the pelvis and of the abdominal wall.
In herbivore, the large intestine plays an important part in the digestion of cellulose, not because of the secretion of some special enzyme which could effect this digestion, but because of the rich bacterial flora of the large intestine. The splitting of cellulose is due to the action of bacteria, and it results in the formation of simpler carbohydrates, viz., sugars. Thus the cellulose which forms vegetable cell-walls can be utilized by the animal.