gard to some of the glands, this has been satisfactorily demonstrated. It has been found, for example, that the livercells contain the glycogenic matter formed by the liver;' and it has been further shown that when the cellular structures of the pancreas have been destroyed, the secretion is no longer produced.' There can be hardly any doubt with regard to the application of this principle to the glands generally, both secretory and excretory. Indeed, it is well known to pathologists, that when the tubes of the kidney have become denuded of their epithelium, they are no longer capable of separating from the blood the peculiar constituents of the urine.

With regard to the origin of the principles peculiar to the true secretions, it is impossible to entertain any other view than that they are produced in the epithelial structures of the glands; and the old idea that they exist ready-formed in the blood, though adopted by some physiologists of the present day,' cannot be maintained. While the secretions contain inorganic salts transuded in solution from the blood, the organic constituents, such as pepsin, ptyaline, pancreatine, etc., are readily distinguished from all other albuminoid principles by their peculiar physiological properties; although some of them are apparently identical with albumen in their ultimate composition and in most of their chemical reactions.

It may be stated, then, as a general proposition, that the characteristic elements of the true secretions, as contradistinguished from the excretions, are formed de novo by the epithelial structures of the glands, out of material furnished by the blood; and that their formation is by no means confined to what is usually termed the period of functional activity of the glands, or the time when the secretions are poured out, 1 SCHIFF, De la nature des granulations qui remplissent les cellules hépatiques: Amidon animale.-Comptes rendus, Paris, 1859, tome xlviii., p. 880.

2 BERNARD, Mémoire sur le pancréas, Paris, 1856, pp. 17 and 69.

MILNE-EDWARDS, Leçons sur la physiologie, Paris, 1862, tome vii., p. 282.

but takes place more or less constantly when no fluid is discharged.

It is more than probable that the formation of the elements of the secretions takes place with fully as much activity in the intervals of secretion as during the discharge of fluid; and most of the glands connected with the digestive system seem to require certain intervals of repose, and are capable of discharging their secretions for a limited time only.

When a secreting organ is called into functional activity— like the gastric mucous membrane, or the pancreas, upon the introduction of food into the alimentary canal—a marked change takes place. The circulation in the part is then very much increased in activity; thus furnishing the water and the inorganic elements of the secretion. This difference in the vascularity of the glands during their activity is very marked when the organs are exposed in a living animal, and is one of the important facts bearing upon the mechanism of secretion. Beaumont observed this in his experiments on St. Martin, and was the first to show conclusively that the gastric juice is secreted only when food is taken into the stomach, or some stimulation is applied to its mucous membrane.' Bernard, in his experiments on the pancreas, noted the pale appearance of the gland during the intervals of digestion, and its reddened and congested condition when the secretion flowed from the duct; and these observations have been confirmed by all who have experimented upon the glands in living animals.

In later experiments upon the circulation in the salivary glands and its relation to secretion, Bernard has investigated this subject fully, with the most definite and satisfactory results. His observations were made chiefly on the submaxil

1 BEAUMONT, Experiments and Observations on the Gastric Juice, and the Physiology of Digestion, Plattsburg, 1833, p. 103.

* BERNARD, Mémoire sur le pancréas, Paris, 1856, p. 43.

3 BERNARD, Leçons sur les propriétés physiologiques et les altérations patho

lary gland in dogs; and he has shown that during the func tional activity of this organ, if a tube be introduced into the vein, the quantity of blood which may be collected in a given time is four or five times that which is discharged in the intervals of secretion.' It was ascertained, also, that the venous blood coming from the gland contained much less water than the arterial blood; and on comparing the quantity of water lost by the blood in its passage through the gland in a given time with the quantity discharged in the saliva, they were found to exactly correspond.'

The differences in the quantity and the composition of the blood coming from the glands during their repose and their activity have an important bearing upon the mechanism of secretion. As far as the composition is concerned, these differences appear to be mainly dependent upon the modifications in the circulation. When the gland is in repose, the blood coming from it has the usual dark, venous hue and contains the ordinary proportion of carbonic acid; but during secretion, when the quantity of blood passing through the organ is increased, the color is nearly as bright as that of arterial blood, and the proportion of carbonic acid is very small. At this time, also, the blood is frequently discharged from the vein pulsatim to the distance of several inches. The cause of this difference in color is very easily understood. During the intervals of secretion, the blood is sent to the gland for the purposes of nutrition and the manufacture of the elements of the secretion. It then passes

logiques des liquides de l'organisme, Paris, 1859, tome ii., p. 272, et seq.; Du rôle des actions réflexes paralysantes dans le phénomène des sécrétions.—Journal de l'anatomie et de la physiologie, Paris, 1864, tome i., p. 507, et seq.; Leçons sur les propriétés des tissus vivants, Paris, 1866, p. 400, et seq.

1 Unpublished lectures delivered by Bernard at the College of France in the summer of 1861.

• Unpublished lectures, 1861; Journal de l'anatomie et de la physiologie, Paris, 1864, tome i., p. 513; and Leçons sur les propriétés des tissus vivants, Paris, 1866, p. 401.

BERNARD, Liquides de l'organisme, Paris, 1859, tome ii., p. 296.

through the part in moderate quantity and undergoes the usual change from arterial to venous, in which a great part of the oxygen disappears and carbonic acid is formed; but, when secretion commences, the ordinary nutritive changes are not sufficient to deoxidize the increased quantity of blood, and the venous character of the blood coming from the part is very much less marked.'

These facts enable us to form a pretty clear idea of the mechanism of secretion; though the exact nature of the forces which effect the changes of the organic principles of the blood into the characteristic elements of the secretions is not understood. Experiments, however, have shown that in the act of secretion there are two tolerably distinct processes:

1. It may be assumed that at all times the peculiar secreting cells of the glands are forming, more or less actively, the elements of the secretions, which may be washed out of the part or extracted by maceration; but during the intervals of secretion, the quantity of blood received by the glands is relatively small.

2. In obedience to the proper stimulus, when a gland takes on secretion, the quantity of blood which it receives is four or five times greater than it is during repose. At that time, water, with certain of the salts of the blood in solution, passes into the secreting structure, takes up the characteristic elements of the secretion, and fluid is discharged by the duct.

In all the secretions proper, there are intervals, either of complete repose, as is the case with the gastric juice or the pancreatic juice, or periods when the activity of the secretion is very greatly diminished, as in the saliva. These periods of repose seem to be necessary to the proper performance of the function of the secreting glands; forming a marked contrast with the constant action of the organs of excretion. It

1 This subject is more fully discussed in vol. i., Blood, p. 106, under the head of "Color of the Blood."

is well known, for example, that the function of digestion is seriously disturbed when the act is too prolonged, from the habitual ingestion of an excessive quantity of food. With regard to the pancreas this fact has been demonstrated in the most satisfactory manner. The experiments of Bernard and others have shown that this organ is peculiarly susceptible to irritation; and when a tube is fixed in its duct, after a time the flow of the secretion may become constant, leaving no intervals for repose of the gland. When this occurs, the fluid discharged loses the character of the normal secretion and is found to possess none of its peculiar digestive properties.' In one or two instances in which the irritation of the tube introduced into the pancreatic duct did not produce a constant secretion, the fluid, which was discharged intermittently in the normal way, possessed all its physiological properties.

From the considerations already mentioned, it is evident that the secretions, as the rule, are formed by the epithelial structures of the glands. There has been a great deal of speculation with regard to the mechanism of this action of the cells. As we before remarked, this question cannot be considered as settled. It does not seem probable that the cells are ruptured during secretion and discharge their contents into the ducts, for under these circumstances we should expect to find some of their structure in the secreted fluid; whereas, aside from accidental constituents, the secretions are homogeneous, and do not contain any formed anatomical elements. There is no good reason for supposing that this action takes place, and that more or less of the glandular epithelium is destroyed whenever secretion occurs; and, in the present state of our knowledge, we can only assume that the secreting cells induce catalytic transformations in the organic elements of the blood and modify transudation, without pretending to understand the exact nature of this process.

1 See vol. ii., Digestion, p. 337.

BERNARD, Mémoire sur le pancréas, Paris, 1856, p. 46.