General Physiology: An Outline of the Science of Life

The origin of lactic acid from proteid has been proved by the investigations of Gaglio ('86), which show that the lactic acid of the blood depends only upon the quantity of ingested proteid, not upon that of the carbohydrates. Finally, that carlonic acid also, which all living substance without exception expires throughout its life, is derived from the decomposition of proteid and not from that of non-nitrogenous substances, is at once evident from the fact that in carnivora life can be maintained continually with proteid food alone. This important fact proves in general that from proteid all those substances can be formed that are continually excreted by the organism, as well as all the substances that are necessary to maintain life.

Formerly a sharp distinction was drawn between animal- and plant-cells as regards the kind of chemical transformations that take place in them. It was said that in the plants synthetic processes take place almost exclusively, in the animals analytic processes only ; and this idea has persisted until recent times. But that such a fundamental difference exists was energetically disputed more than twenty years ago by Pfliiger (75, 1). As a matter of fact, as the above consideration has shown, the difference consists only in that the plant-proteid of the chlorophyll-bodies has retained from early times the property of assimilating inorganic material, while animals require for the construction of their living substance organic food-material already prepared. Nevertheless, synthetic and analytic processes take place in both the plant and the animal body. In the plant the decomposition of carbonic acid must precede the synthesis of starch ; in order that the starch may be further elaborated, it must first be decomposed into simple kinds of sugar, and so on. Finally, in the plant also there occurs the whole series of cleavages that are associated with the decomposition of the proteid molecule, with dissimilation, exactly as in the animal body. But syntheses take place in the animal body to a great extent. The further elaboration of the digested proteids, fats, and carbohydrates towards the construction of living substance involves extended synthetic processes, and it has been seen that the majority of the products of retrogressive proteidmetamorphosis are formed synthetically out of the cleavageproducts of the proteids. Hence analytic and synthetic processes go hand in hand in the animalas in the plant-cell, and the old distinction into analytic and synthetic organisms is merely the expression of an earlier stage of our knowledge of the chemical processes in living substance.

Living substance excretes transformation-products in the same proportion in which it receives substances from the outside and transforms them ; the substances given out are as varied as those taken in. But with our slight knowledge of the transformations und with the overwhelming number of substances excreted by the various forms of cells, we can say in a very few cases only by what processes the substances are derived. As regards most of them, it is not known whether they are derived from assimilatory or dissimilatory transformations ; evidently a large quantity of byproducts are formed in both the ascending and the descending portions of the metabolic series, whether by simple cleavage, or by synthesis from the cleavage-products or other substances which are excreted by the organism either for some further use or as useless products. This last point, as to whether the excreted substances are of still further use in the life of the organism, or are removed as useless products, as slag, has caused a distinction to be recognised among the substances given off. Although it is difficult to make this distinction sharp, because of the extraordinary variety of different products, the use of it is advisable

from practical considerations. The substances given off from the cell, among which occur gaseous, liquid, and solid substances in all grades of consistency, are distinguished as secretions when they play a still further useful role in the life of the organism, and as excretions when they are removed to the outside as useless residue. Accordingly, secretions are contrasted with excretions. We will look for a moment somewhat in detail at the two groups of substances and at the mode of their output.

Like the taking-in of food, so also the manner of output of substances varies, according as the latter are gaseous, dissolved or solid. The output of gaseous or dissolved substances evidently takes place under the same conditions and in the same manner as such substances are taken in, for here there is the same process reversed. In many cells, e.g., in many unicellular organisms, it is very probable that the so-called contractile vacuole (Fig. 57), a drop of liquid within the cell which is alternately emptied and filled by rhythmical contractions of the protoplasm of its wall, attends to the expulsion of dissolved substances. It is supposed that the latter, together with the water that during the diastole of the vacuole streams in from all sides out of the protoplasm, accumulate in the vacuole and at its systole are given off to the outside.

It is clear that every cell excretes primarily substances that are derived from its own metabolism. But in the compound cellcommunity, especially of the animal organism, there exist also cells which in addition have undertaken for the whole body the excretion of certain other materials. Thus, the cells in the convoluted uriniferous tubules of the kidney excrete the urea that is prepared by the liver-cells and passed into the blood, by receiving it from the blood and giving it off to the outside. Other cells of the kidney, those of the so-called glomeruli, the microscopic capsules in which the blood-capillaries are twisted into knots, greedily suck up the water from the blood to excrete it as the water of urine into the pelvis of the kidney.

In the mode of output of solid substances two types again are distinguished. They are essentially different according as the excreted substances either occur in the cell itself in a dissolved condition, and become solid only at the moment of excretion, or lie within the living substance as solid masses, which are to be given off as such to the outside. In the former case, which is realised in the excretion of most skeletal substances, such as chondrin, chitin, and lime, the same conditions are present as in the excretion of dissolved sub-

stances in general, except that sooner or later after their exit from the living cell the substances assume a solid form. The solidifying of the excretions at the surface does not prevent the repetition of the process, and thus eventually all substances of the kind become excreted and solidified upon the outside. Thus originate the cell-membranes of tissue-cells, the cellulose coats of plant-cells, the chitinous coats of insects, and the calcareous shells of Foraminifera.

This process and at the same time the mode of growth of these superficial structures can be illustrated by an experiment which IG. 57.— A, Amoeba. A pale contractile vacuole lies in the endoplasm beside the dark nucleus £, Paramcecium. At each pole is a star-shaped contractile vacuole ; the upper is in the act of contracting, while the lower is beginning to fill itself from several small drops of liquid that are flowing together. was suggested by Traube, and was much discussed in his time. If a drop of a thick solution of gelatine be allowed carefully to fall into a solution of tannin, there appears about the drop a so-called precipitation-membrane of gelatine tannate, since at the surfaces of contact of the gelatine and the tannin the two substances undergo a chemical combination. This precipitation-membrane shows the peculiar phenomena of growth both in surface and in thickness, and on account of its similarity to a living cell Traube's drop of gelatine in the tannin solution has been termed an " artificial cell." Since the gelatine solution attracts water to itself, tannin in solution comes constantly through the membrane to the

drop. At the surface of the latter the tannin is united with the gelatine, and thus the continual apposition of new layers leads to the thickening of the membrane. The water, however, presses into the interior of the drop, so that this constantly swells and increases in size. By this process there appear continually in the precipitation-membrane extremely fine holes and cracks ; these, however, become closed by new precipitate at the moment of their appearance. Thus, the artificial cell grows continually and uniformly larger until all the gelatine is in combination. The formation and growth of the membrane, which in the large drop

take place relatively rapidly, proceed very gradually in the small living cell. In botany a fruitless discussion has been going on for a long time over the question whether the cellulose-membrane of the plant-cell is formed by intussusception, i.e., by the deposition of new particles between the old ones, or by apposition, i.e., by the deposition of particles upon the outside.1 This discussion arose in connection with Nageli's unhappy comparison of, or rather distinction between, growth in crystals and growth in organisms. Lately the view has been gradu- FIG. 58.— ceii-waii of a pith-ceil of ally accepted that both modes lead to £E£V<§S±g»>l"$£ the growth of the membrane-the one strasburger.) £o growth in surface, the other to growth

of the cell itself is enlarged, the membrane is extended. In the process, as a rule, no actual cracks appear, as in the artificial cell, but as a result of the extension the spaces between the single particles of the membrane become wider and larger, so that new particles of protoplasm can enter in. But, on the other hand, the stratification of the membrane parallel to the surface, which is visible under high magnifying powers and with increasing thickness becomes constantly more distinct, shows that increase in thickness by apposition is also present (Fig. 58).

If the cells in their metabolism produce substances and excrete them to the outside continually, extensive solid masses are gradually formed, which in multicellular tissues, where the products of the individual cells blend together, form the so-called intercellular substances, such as in cartilage and bone (Figs. 59 and 60). But the substances are not always excreted at once to the outside ; in many cases they are stored up as a solid mass in a vacuole in the cell itself, particle after particle being added to them as in a crystal. Thus, starch-grains in plant-cells, and calcareous needles

and stars in echinoderms and sponges, are formed within the cell itself, and only after they have reached a certain size are they given off to the outside by the customary mode of excretion of solid bodies (Fig. 61). Amoeba shows best the mode of excretion of substances that lie in the interior of the cell as solid masses. It has been seen that FIG. 59. — Cross-section of bone. The compact ground-substance lies between the star-shiped bonecells. In the middle of the section is a cross-section of a bonecanal. (After Hatschek.)

FIG. 60. ^Hyaline cartilage. Between the individual cells a solid, hyaline ground-substance has been excreted. (After Hatschek.) in the ingestion of food by Amoeba the food-ball enclosed in a food-vacuole lies finally within the protoplasm. In this vacuole, which may be termed a digestive vacuole, all digestible substance becomes dissolved, and passes into the protoplasm ; but the indigestible residue, such as shells of algae and of diatoms and the chitinous masses of rotifers, remain in the vacuole, and become excreted in the following manner : By the creeping of the Amoeba the digestive vacuole in the streaming protoplasm comes to lie very near the surface, so that its contents are separated from the medium merely by a thin delicate wall of protoplasm. In such a case the wall breaks very easily by the protoplasm flowing in all

FIG. 61. — Formation of a triradiate calcareous star in an echinoderm cell. (After Semon.) directions away from the thinnest place, and the contents of the vacuole together with the solid mass are emptied to the outside (Fig. 62). This mode of removal of solid constituents from the protoplasm is found exclusively in cells that do not possess a membrane, and hence chiefly in amoeboid cells of all kinds. A transition between the method of output of liquids and that of solids is represented by the secretion of mucus. The mucous

cells, which in the compound organism play so very important a role in protecting the internal surfaces and keeping them smooth and moist by their secretion of mucus, are always cylindrical. The nucleus, surrounded by somewhat more solid protoplasm, lies at the bottom of the cell-body, while the upper end of the cell, which borders the free surface of the membrane, is formed by a FIG. 62. — An Amosbain four successive stages of excretion of the undigested residue of food.

substance, mucigen, that is continually being transformed into mucus. During the quiet activity of the cell a little of the secretion passes constantly to the thin liquid layer that covers the surface of the tissue. But during energetic, sudden secretion the whole mass that forms the upper part of the cell is shoved out (Fig. 63) and blends with the drops cast out of the neighbouring cells into a thick, gummy covering of mucus. The FIG. 63. — Mucous cells. A, Three isolated cells. S, Seven adjacent cells, of which the three at the left are full, the four at the right are empty. (After Schiefferdecker.)

peculiarity of many holothurians, those cucumber-shaped forms of echinoderms, of transforming their thick, solid skins upon stimulation in a short time into a glistening, viscous slirne, is very remarkable and not yet explained. In general, the cell-physiological investigation of the process of secretion promises to afford many very interesting general physiological facts. It is neither necessary .nor possible to examine here in detail the whole series of secretions and excretions which plant and animal cells afford in their metabolism ; our consideration shall therefore, be limited to the most important of these.

Since it is characteristic of secretions to be of use to the organism, it is easy to understand that many secretions remain continually within the organism and are not given off to the outside. Hence two groups of secretions can be distinguished, according as after their formation they are at once given off or are retained continually in the organism, whether in the cell or upon its surface ; in neither case in the cell-community of the compound organism is it always necessary that the secretion be of use to that particular cell that affords it.

Among the secretions that after their production learn the organism there are, in the first place, the ferments, which have to do with digestion and appear in both animals and plants. Thus, in animals the cells of the salivary glands produce ptyalin, which transforms starch into grape-sugar ; the cells of the gastric glands, pepsin, which peptonises proteids, and rennet -ferment or chymosin, which mediates the coagulation of casein ; and the cells of the pancreas ptyalin for the digestion of starch, trypsin for the peptonising of proteids, and steapsin for the splitting of fats. Ferments occur likewise in plants, such as the so-called carnivorous plants, which catch insects, hold them and digest them by the secretion of peptonising ferments. An example of such a plant is Drosera, which grows in the swamps. Whether the very effective ferments that are produced in the milky juice of some plants, such as Carica papaya, and are not cast out upon the surface, are to be regarded really as secretions in the present sense or only as excretions (by-products of metabolism) is thus far not decided, since the significance of these in the life of the plant has not yet been discovered. In unicellular organisms, further, the ferments are of great importance for the nutrition of the cell when these organisms, as is the case with the bacteria, come into contact with organic food and are obliged first to liquefy solid food-stuffs in order to be able to absorb them.

Other secretions, such as the wide-spread mucin, of which mucus consists, are of great importance. Mucin protects the cell itself from external influences that can harm it, such as direct contact with objects; with strong stimulation the mucous cell produces a thick layer of mucus separating the former from the body that touches it ; this is the case with the mucous cells of the trachea when a foreign body comes into the throat. Further, the mucus of the saliva serves to make masticated food smooth, so that the masses of food can glide more easily through the narrow gullet. In this lies the chief importance of the saliva in man; here, on account of its too brief action, the ptyalin, which works only in an alkaline liquid, and hence in the acid gastric juice is made immediately ineffective, can hardly exercise its amylolytic power. Finally, mucus serves for attachment, especially in the lower animals and unicellular organisms. Rhizopoda secrete upon the surface of their protoplasmic bodies a delicate mucous covering with which they stick themselves to the bottom in order to creep about, and with which also they hold fast food-organisms that swim against them, in order to draw the latter into their own bodies and digest them. A similar importance as protective media is possessed by the fats which, such as the sebum, are produced by the sebaceous glands of the skin ; they protect the skin from too great evaporation and render it supple.

Further, as Stahl ('88) has shown by a series of experiments, many secretions act in a different manner solely as protective media in animals and especially plants : such are ill-smelling or ill-tasting adds and ethereal oils. The organisms are protected by them from being devoured. Most of these cases present interesting phenomena of adaptation to definite conditions, which have arisen through natural selection and constitute contrivances advantageous to the organism. The same is true also of other cases in which plants, by means of good-smelling and goodtasting secretions, such as ethereal oils and honey, attract insects whose coming and going are useful, perhaps indispensable, to the plants ; the animals bear awray pollen upon their legs and deposit it upon the female flowers so that the latter are fertilised. Such adaptations, often astonishingly fitting, are especially common among plants, and the physiology of secretion touches here most closely the interesting field of the mutual relations of plants and animals.

Finally, as secretions in the widest sense there may be recognised also substances produced in the cell, such as starch, aleur onegrains, fat-droplets, etc., which are stored in the cell for a time as reservematerial and later are used in metabolism. Among the secretions that after their production r&main in the organism, there belong almost exclusively pigments and substances that form skeletons. The former appear mostly in the form of fine granules, remain continually in the cell-body, and possess a special importance in the colour-changes of the animal, which is not yet entirely explained. The great majority of skeletonforming substances are excreted to the outside. Sometimes they are laid down within the cell itself and later extruded, as are the calcareous needles and plates of the Holothuria ; sometimes they

are secreted at once upon the surface of the cell in the form of membranes, shells, and coatings, such as cell-membranes, the c^te-membrane of plant-cells, the chitinous coats of insects, the silicious cases of diatoms, the delicate latticed skeletons of Radiolaria (Fig. 64), and the calcareous shells of Foraminifera ; FIG. 64.— Silicious skeletons of Radiolaria. (After Haeckel.) A, Dorataspis, B. Thcoconus. and sometimes they are stored in the tissues between the individual cells as the so-called connective substances, such as chondrin in cartilage, glutin in bone, calciiim phosphate in bone, and the great number of supporting or skeletal substances which belong to the albuminoids and in the different groups of animals have compositions very different and as yet little known.

The excretions are much fewer in number than the secretions. Chief among them are the products of retrogressive proteidmetamorphosis which are excreted by all living substance. Among gaseous excretions the most important one, whose production is associated with the life of every cell without exception, is carbonic acid, the end-product of respiration ; it is produced chiefly by the oxidation and the decomposition of proteid, but under certain circumstances by the fermentation of carbohydrates. As has already been seen, in addition to carbonic acid, plants excrete oxygen, which is derived from the splitting-up of the carbonic acid received from their green parts. It has, therefore, been thought that the supposed contrast in the metabolism of plants and of animals, already spoken of, is to be found

in the fact that plants take in carbonic acid and give out oxygen, while animals, vice versa, take in oxygen and give out carbonic acid. But later experiments have shown that, in reality, this contrast does not exist. It is true that animals inspire oxygen, employ it for the combustion of living substance, and expire carbonic acid as the product of such combustion. But plants do the same. In them this fundamental vital phenomenon of respiration is merely concealed by the consumption and the splitting-up of carbonic acid ; the latter, however, has nothing to do with respiration itself, but is preliminary to the construction by the plant of the first organic substance out of inorganic materials. If the metabolism of plants be examined at a time when no starchformation is going on, when no carbonic acid is being split up, but when the life of the plant is being expressed in other ways, as in the night or in darkness, it is found, by gasometric experiments analogous to those above described, that the plant consumes oxygen and expires carbonic acid like the animal. In the plant, therefore, the process of respiration is not to be confounded with the process of assimilation of starch : the latter requires carbonic acid to be taken in and split up and oxygen to be given out, and thus conceals the respiration which is constantly taking place beside it. Respiration, i.e., the taking-in of oxygen and the giving-out of carbonic acid, is a general metabolic phenomenon.

Among liquid excretions water occurs everywhere, and substances dissolved in water. Because of the small quantity of these various excretions, in the present state of micro-chemical reactions it is usually not possible to demonstrate them for the individual cell ; hence they must be studied in the compound cellcommunity. In the plant, water is excreted and evaporated during transpiration through the so-called stomata of the leaves. By the action of special guard-cells the stomata can be closed and opened, and thus the output of water by the plant can be regulated very delicately. In animals there are special glands, the kidneys and sweat-glands, the cells of which excrete the water, together with the products of retrogressive proteid-metamorphosis, out of the body-liquids, and pass them to the outside.

Most of the non-nitrogenous products of proteid-decomposition are oxidised completely to carbonic acid and water, so that the latter leave the body as the almost exclusive end-products. But intermediate products also arise, which, excreted by certain cells, have a different fate within the body. This is true especially of lactic acid, which, among other things, is excreted by the musclecells into the blood and can be found there, but does not leave the body as such in the urine. That sarco-lactic acid or para-lactic acid is derived from the decomposition of proteids, and not from the ingested carbohydrates, is proved by the experiments of

Gaglio ('86), already mentioned. But the sarco-lactic acid is still further transformed in the body, for, as has been seen, the experiments of Minkowski ('86) upon geese in which the liver was extirpated have shown that lactic acid, presumably combined with ammonia, is consumed in the synthesis of uric acid. The nitrogenous products of proteid-decomposition are the wellknown substances which have already been met with frequently, especially urea, uric acid, hippuric acid, creatin, and the nuclein bases, xanthin, hypoxanthin or sarkin, adenin, and guanin. These are excreted chiefly in the urine and represent the compounds in which all the nitrogen taken in in the food leaves the body, apart from an inconsiderable quantity in the sweat and the faeces.