The term Regeneration is applied to the restoration of portions of the body which have been lost by injury or disease. The regeneration of a part is to be carefully distinguished from mere growth or hypertrophy. A tissue may be able under suitable stimulation to reproduce its elements, and increase in size; but for the replacement of a lost part, if at all considerable, there must be, virtually, a renewal of the process of development. In order to such a renewal of development the cells of a part must carry with them a considerable share of the original germinal material by the action of which the animal was formed in the process of development. Such an extension of the determining power occurs very extensively in plants which seem in most of their parts to have the powers of formation of the whole. In the animal kingdom it is much more limited.
The reproduction of lost parts in their entirety occurs readily in some of the lowest forms of animals. In the hydra, if the creature be cut in two, each half will develop into a complete animal, and the process may be repeated indefinitely. This power of reproduction of the whole animal from a part seems confined to those creatures which, like plants, can propagate by spontaneous fission or gemmation. When we come to animals higher in the scale the power of reproduction seems to be limited to the restoration of lost limbs, antennae, etc.
Without going into details, which will be found by reference to Paget's "Lectures on Surgical Pathology," it may be said that there are indications which seem to show that there is some kind of law according to which the reparative power in each perfect species is in inverse proportion to the amount of change which the animal has passed through in its development from the embryonic to the perfect state. It is as if, in the process of development, the formative power as distinguished from mere growth were gradually exhausted, and the process of reproduction, which we have seen to be, as it were, a renewal of that of development, only occurs when this power has been comparatively little expended. It appears, for instance, that in insects the power of reproducing antennae or limbs is limited to those species which have attained the perfect state through a comparatively simple and direct course of development. It is consistent with this view that in the larval state insects show a much greater power of reproduction than when perfect. The larva of one of the higher insects will be able to reproduce its limbs, while the perfect insect is not.
In man, and in the vertebrata in general, the long course of development seems largely to exhaust the reproductive power of the body, and, in the adult state at least, the;>ower of restoration of lost parts is very limited, and the processes concerned are almost as much related to growth of tissue as to development. In the embryonic state it is probable that the power of restoring lost parts is much greater than in the adult. Some children are born with a short arm, at the extremity of which are imperfectly developed fingers; it is probable that in these cases amputation of the arm has occurred in iitero, and an attempt at restoration has followed.
In the human being after birth it may be said that restoration of lost structures is almost confined to the epithelial and connective tissues and to the blood. Along with the connective tissues we have, of course, blood-vessels, which are readily reproduced, and we may also, to a limited extent, include nerve-fibres, which, as we shall see afterwards, are sometimes restored.
The blood is gradually regenerated when in consequence of haemorrhage its bulk is reduced. The fluid portion is rapidly restored, the white corpuscles are also soon replaced, but the red corpuscles somewhat more slowly. (See Ansemia).
The epithelial structures of the body are to a large extent continually undergoing a physiological process of loss and regeneration. The hairs of men and animals fall out at intervals and are restored; the feathers of birds undergo a similar process; the nails and horny layer of the epidermis are continually lost and replaced by new-formation. The plucking out of hairs or feathers, or the removal of nails is followed by their restoration, so long as the papilla? are not destroyed. It is an interesting fact that when the whole distal phalanx of the finger is removed, or even the two terminal phalanges, there may be a partial restoration of the nail in that which has become the terminal phalanx. There is also a case recorded in which a boy, apparently affected with ichthyosis, regularly shed his nails. (See references in Recklinghausen).
On the general surface of the skin and mucous membranes there is normally a continous shedding of the surface epithelium, and a karyomitosis in the deeper layers to replace that which is lost; a kind of physiological regeneration therefore. When, by accident or otherwise, a superficial portion of epithelium is shed before its time, it will be replaced by the requirements of the body. When the whole thickness of the epithelium is destroyed the gap is by degrees filled by the proliferation of the epithelium at the edges of the wound, as we have already seen in the case of the cicatrization of a granulating wound. According to the observations of Klebs the new-formed epithelium acquires a slight power of amoeboid movement, so that it can proceed to the spot which it is to occupy.
The proliferation of the epithelium proceeds by the process of karyomitosis. In the accompanying illustration (Fig. 69), the fibrous transformation of the nucleus and the other changes, as seen in the cornea of the rabbit, some days after a portion of the epithelium had been removed, are shown. In the normal cornea and in the Malpighian layer of the epidermis there are evidences of a similar process by which, we may presume, the physiological regeneration occurs. Gland epithelium also to some extent undergoes a physiological loss and regeneration. The secretion of some glands implies a destruction of cells and their restoration. According to Bizzozero, who examined the various glands in respect to the activity of karyomitosis, the sebaceous glands, the mucous glands of the stomach, Lieberkiihn's glands in the intestine, and the uterine glands, are actively engaged in regenerating their epithelium, and consequently lose it in the process of secretion. In glands which normally present an active new-formation of their epithelium it is not surprising that regeneration occurs when parts are lost, but even in the kidney and liver where there is no such normal proliferation, loss by disease induces a new-formation. Thus in acute nephritis the epithelium is to a large extent shed, and we may find desquamated epithelium lying in the tubules, while young epithelium lines them. In acute yellow atrophy of the liver also, there is great destruction of the hepatic cells, and there is often visible along with that a new-formation of cells as if there were an attempt at restoration. In both of these organs also, a loss of substance induces a new-formation, which may be regarded either as a compensatory hypertrophy or a regeneration.
Fig. 69. - Regeneration of epithelium in cornea of a rabbit, a, Fibrous transformation of nucleus; b, partial separation of the fibres and hour-glass change of nucleus; c, complete division of nucleus; d, complete division of cell. (Eberth).
The lens of the eye, which in its development is an epithelial structure, may be in part or in whole regenerated, after its removal on account of cataract.
Connective tissue, as we have seen, is frequently regenerated, and the new-formed tissue is the means of union, of wounds. Blood-vessels are similarly restored, forming really part of the connective tissue.
Cartilage seems scarcely capable of regeneration, at least in the adult. Fractures of the cartilaginous ribs are united by bone, and wounds of cartilage are replaced by connective tissue or bone. Experiments on young animals show that in them there may be considerable regeneration, and it is probably so also in the human subject.
Nerve-fibres are regenerated after division of nerve-stems. A simple section of a nerve may be followed by immediate union, and the function may be restored in a few days. Even when portions of nerves have been removed (as much as 2 inches) there is a restoration of function, but at a much longer interval. In order to this there is a new-formation of nerve-fibres from the central extremity, and these meet those of the peripheral end. The division of a nerve, unless there be immediate union, implies, as we shall see further on, a remarkable change in the whole peripheral portion from the point of section onwards, and when restoration occurs there is a regeneration of the axis-cylinder apparently by growth* outwards from the central end. The power of regeneration and accommodation of nerves is further shown by the fact that, after transplantation of skin, when the parts are separated from their nervous connections, there is a restoration of sensation.
Muscle is, to a limited extent, liable to regeneration. Wounds of muscles are usually united by connective tissue, although subcutaneous wounds, as proved by experiment, often heal without cicatrix. Weber found also that in the neighbourhood of fractures no cicatrices existed in the muscles, although they had undoubtedly been torn by the ends of the bones. In the healing of wounds in muscles by granulation, it is believed by some that a new-formation of muscle takes place to some extent, the muscle nuclei taking part in the process. There is also a restoration of muscle after atrophy and degeneration. In emaciating fevers there is a great atrophy of the voluntary muscles and a restoration as convalescence advances. Fatty degeneration of muscle is probably followed, as in other cases of fatty degeneration, by absorption of the affected structures, and this again involves a regeneration. In these cases the muscle nuclei are not lost, and they seem to be the agents in regeneration.