REGENERATION OF INTERNAL ORGANS. HYPERTROPHY. ATROPHY
It is a more or less arbitrary distinction to speak of internal in
contrast to external organs, since the latter contain internal parts;
but the distinction is, for our present purposes, a useful one,
especially in regard to the question of regeneration and liability to
injury. In this connection we shall find it particularly instructive to
examine those cases of regeneration of internal organs that cannot be
injured, under natural conditions, without the animal itself being
destroyed. An illustration of this may be given. The liver, or the
kidney, or the brain of a vertebrate can seldom be exposed to accidental
injury without the entire animal being destroyed, although, of course,
diseases of various kinds may injure these organs without destroying the
animal, but cases of the latter kind are not common.
The experiments made by Ponfick (’90) on the regeneration of the liver
in dogs and in rabbits gave the most striking results. Ponfick found
after removal of a fourth, or of a half, or even, in a few successful
operations, of three-fourths of the liver, that, in the course of four
or five weeks, the volume of the remaining part increased, and in the
most extreme case, to three times that of the piece that had been left
in the body. The first changes were found to have begun as early as
thirty hours after the operation, when the liver cells had begun to
divide. The maximum number of dividing cells was found about the seventh
day, and then decreased from the twentieth to the twenty-fifth day, but
cells were found dividing even on the thirtieth day. These dividing
cells appeared everywhere throughout the liver, and were no more
abundant at the cut-edges than elsewhere. There takes place, in
consequence, an increase in the volume of the liver, rather than a
replacement of the part that is removed. The increase takes place in the
cells of the old part, the lobules swelling up to two, three, or even
four times their former size. No new liver lobules seem be formed. The
old tubules of the liver also become larger, owing to an increase in the
number of their cells. Since the change takes place in the old part, and
is due to an increase in size of the lobules, tubes, etc., the process
is spoken of as one of hypertrophy rather than of regeneration.
Kretz found a case in which the entire parenchyma of the liver seemed to
have been destroyed, presumably by a poison from some micro-organism,
and later a regeneration of the tissue had taken place. If this
conclusion is correct, it shows that sometimes an internal organ may
meet with an injury that does not directly destroy the rest of the body,
and the animal may survive.
The regeneration of the salivary gland of the rabbit described by
Ribbert is another example of an internal organ that can seldom be
injured, and yet can be replaced after artificial removal. Weismann
(’93) has recorded an experiment in which half of a lung of triton was
cut off. After fourteen months the lung had not been restored in four
individuals, and in one “it was doubtful whether a growth of the lung
had not taken place, but even in this case it had not recovered its
long, pointed form.”
The regeneration of the eye in triton was first made known by Bonnet.
The right eye was partly cut out, and after two months it had completely
regenerated. Blumenbach, in 1784, removed the anterior part of the bulb
of the eye of “_Lacerta lacustris_.” Six months later a smaller bulb was
present. Phillipeaux (’80) found that if the eye of an aquatic
salamander was not entirely removed, a new eye regenerated; but if the
eye was completely extirpated a new eye did not appear. Colucci, in
1885, described the regeneration of the lens of the eye of triton from
the edge of the optic cup. Wolff, later, independently, discovered the
same fact, and it has been more recently confirmed by E. Müller (’96),
W. Kochs (’97), P. Rothig (’98), and Alfred Fischel (’98). The most
important part of this discovery is that the new lens develops from the
margin of the optic cup, and not from the outer ectoderm, as it does in
the embryo. This result will be more fully discussed in a later chapter.
It is highly probable in this case that the regeneration stands in no
connection whatsoever with the liability of the eye to injury, for of
the large number of salamanders that have been examined, none has been
found with the eye mutilated. The position of the eye is such that it is
well protected from external injury, and the tough cornea covering its
outer surface would also further protect it from accidental injury. When
we recall the high degree of structural complexity of the eye, its
capacity to regenerate, if only a portion of the bulb is left, and its
power to replace the lens if this is removed are certainly very
remarkable facts. We find here, I think, an excellent refutation of the
incorrectness of the general assumption of a connection between
regeneration and liability to injury. Moreover, since there is no
evidence whatsoever to show that the eyes in these animals are ever
subject to diseases caused by bacteria, and much evidence to show that
they are not so injured, we are still further confirmed in our general
conclusion.
It has been known for a long time that even in man the lens of the eye
is sometimes regenerated after its removal. The regeneration has been
supposed to take place from the old capsule of the lens, or possibly
from a piece of the lens left after the operation; but whatever its
origin, the fact of its regeneration in man, and in other mammals also,
is a point of some interest in this connection.
Podwyssozki (’86) found that regeneration may take place in the kidney
of certain mammals,--best in the rat, more slowly in the rabbit. The
restoration of the lost part takes place first by replacement of the
epithelium. The old canals may then push out into the connective tissue
that accumulates in the new part, but there is no new formation of
canals or of glomeruli. According to Podwyssozki the regeneration of the
kidney is less complete than that of any other gland. Peipers has
reinvestigated the subject, and his results agree in the main with those
just given. He finds in addition that new canals may grow out from the
old ones into the new part.
Podwyssozki and Ribbert (’97) have found that the salivary gland has a
remarkable power of regeneration. Ribbert removed a half (or even more
than this) of the salivary gland of the rabbit. In the course of two or
three weeks new material had developed over the cut-surface. In one case
at least five-sixths of the gland had been taken out, and at the end of
three weeks the gland had regenerated to its full size. Microscopic
examination showed that the greater part of the gland was made up of new
lobes, some of which were as large as, others smaller than, the normal
lobes. The new part contained new tubes with terminal acini. These had
arisen from the tubes of the old part. The connective tissue of the new
part also came from that of the old. In this case a true process of
regeneration takes place from the cut-surface; in addition a certain
amount of enlargement, or hypertrophy, also takes place in the old part.
Ribbert believes there is a connection between the process of
hypertrophy and of regeneration of such a kind that the more active the
one, the less active the other.
Regenerative changes are known to occur in other internal organs besides
these glandular ones. Broken bones are united, if brought in contact, by
a process that involves a certain amount of regeneration. Although new
bony tissue may be formed at the region of union, the bones of mammals
and of birds do not seem able to complete themselves, if a part is
removed, except to a limited extent. While the broken bones of the leg
or of the arm have the power of reuniting if held for some time in
place, yet in nature this condition can seldom be fulfilled, and the
animal with a broken leg or wing will most probably be killed.
Nevertheless, since the bones have this power at whatever level they may
be broken (but only if they are kept together artificially), the process
can scarcely have been acquired through the liability of the parts to
injury. We find here another instance of a useful process existing in
animals, but one that could not have been acquired by exposure of the
part to injury. It is probable that this same property is found in all
the bones of the body,--in those that may occasionally be injured, and
in those that are not.
The muscles have also the power of regenerating, although few
experiments have been made except in those forms in which the whole leg
can regenerate, yet there are a few observations that show that even in
mammals, in which the leg or the arm cannot regenerate as a whole, a
certain amount of regeneration of the muscles themselves may take place.
It has been known for a long time that if a nerve is cut a new nerve
grows out from the cut-end, and may extend to the organs supplied by
that nerve. The process takes place more successfully if the peripheral
part is left near the cut-end from which the new nerve grows. Whether
this old part only serves to guide the new part to its proper
destination, or whether it may also contribute something to the new
nerve, as, for instance, cells for the new sheath, is not finally
settled. The general opinion in regard to the origin of the new nerve
fibres is that the central axis or fibril grows from the cut-end. That
this power could have been acquired for each nerve as a result of its
liability to injury is too improbable to discuss seriously.
The central nervous system of the higher vertebrates seems to have very
little power of regeneration, and although in some cases a wounded
surface may be covered over and a small amount of connective tissue be
formed, the development of new ganglion cells does not seem to occur. In
other animals, as the earthworm, planarian, and even in the ascidian, as
shown by Loeb, a new entire brain may develop after the removal of the
old brain, or of that part of the body in which it is contained.
This examination of the power of regeneration of internal organs in the
vertebrates has shown that it is highly improbable that there can be any
connection between their power of regeneration and their liability to
injury. That the internal organs may be occasionally injured by
bacteria, or by poisons made in the body, may be admitted, but that
injuries from this source have been of sufficient frequency to establish
a connection, if such were indeed possible, between their power of
regeneration and their liability to injury from these causes is too
improbable a view to give rise to much doubt. These results taken in
connection with those discussed in the preceding chapter go far toward
disproving the view that the power of regeneration has a connection with
the liability of a part to injury.
_HYPERTROPHY_
The hypertrophy, or unusual enlargement, of organs has long attracted
the attention of physiologists, and the extremely interesting
observations and experiments that have been made in this connection have
an important although an indirect bearing on the problem of
regeneration. Ribbert, as has been pointed out, holds that the processes
of hypertrophy and of regeneration stand in a sort of inverse relation
to each other, but it is doubtful, I think, if any such general relation
exists. Two kinds of hypertrophy are now generally distinguished:
functional hypertrophy, which takes place when a part becomes enlarged
through use; and compensating hypertrophy, which takes place when one
organ being removed another enlarges. The enlargement in the latter case
may, of course, be brought about by the increased use of the parts that
enlarge, but as this is not necessarily the case, the distinction
between the two processes is a useful one. The causes of compensating
hypertrophy are by no means simple, and several possibilities have been
suggested to account for the enlargement. The best ascertained facts in
connection with hypertrophy relate almost entirely to man and to a few
other mammals.[51]
By hypertrophy is meant an increase of the substance of which an organ
is composed. Swelling due to the imbibition of water or of blood-serum
is not, in a technical sense, a process of hypertrophy. Virchow
distinguishes two kinds of hypertrophy: (1) Hypertrophy in a narrower
sense in which the enlargement is due to an increase in the size of the
cells of which an organ is composed. This enlargement of the individual
cells leads of course to an increase in the size of the whole organ. (2)
Hyperplasy due to an increase in the number of cells of which an organ
is composed, which also causes an enlargement of the whole organ if the
cells retain the normal size. The division into functional and
compensating hypertrophy given above is a physiological distinction, and
both of these processes might occur in Virchow’s subdivisions.
Giants may be looked upon as hypertrophied individuals, since all the
organs of the body are larger than the normal. The enlargement is, in
this case, not due to external influences, but to some peculiarity of
the organism itself. Whether the size is due to more cells being
present, as seems probable, or to the cells being larger, or to both,
has not, so far as I know, been determined for man. In a mollusk,
_Crepidula fornicata_, in which large and small adult individuals occur,
it has been shown by Conklin (’98) that the difference is due entirely
to the larger number of cells in the larger individual. In this case
external conditions, in so far as they retard the maximum possible
growth of the individual, are responsible for the differences in size.
The distinction is, in this case, rather between large normal
individuals and dwarfs, than between giants and normal or average
individuals.
The voluntary muscles of the body of man grow larger, and may be said to
hypertrophy, as a result of doing certain kinds of work. The muscles of
the hand and arm grow large through use, and become smaller again if not
used; but the muscles of the fingers of a musician do not hypertrophy,
although the total amount of work done may be very large. It is only
when muscular work is done against great resistance that enlargement of
the muscles takes place. The factors that may bring about the
enlargement will be discussed later.
The kidneys seem to give the most satisfactory evidence of compensating
hypertrophy. Nothnagel[52] states that it has been shown in man, in the
rabbit, and in the dog, that when one kidney has been removed the other
enlarges; and that this takes place both for young animals, in which the
kidneys have not reached their full size, and in adult animals, in which
the remaining kidney becomes larger than normal. In the adult the
enlargement is due to hypertrophy, in Virchow’s sense, in the tubules
and in the epithelium of the canals. In the young animal there is, in
addition, a hyperplastic growth that leads to an increase in the number
of glomeruli, etc.
Experiments have shown that the same amount of urea is excreted by the
animal after the removal of one kidney as before; in fact, this is true
immediately after the operation, before any increase in the size of the
organ has taken place. This means that, under normal conditions, the
kidneys do not perform their maximum of work. It is important to observe
in this connection that the remaining kidney gets more blood than it
would get if the other were present. Nothnagel sums up the changes that
take place in this way: First, the removal of one kidney; second, an
increase in the flow of blood in the remaining kidney; third, an
increase in the functional activity and excretion of this kidney;
fourth, along with the increase in the flow of blood, there is a
necessary increase in the amount of food that is brought to the kidney
in the blood; fifth, this food is taken up in larger amount than before
by the cells, which leads to an increase in the growth of the cells,
which produces hypertrophy. The increase in size, looked at from this
point of view, Nothnagel says, has nothing mysterious about it. The
enlargement seems to be an adaptation; but the enlargement does not take
place because it is an adaptive process, but because it cannot be helped
under the conditions that arise. We shall return again to Nothnagel’s
interpretation, when we come to consider other views.
Experiments of the sort just described are most easily carried out on
the paired organs of the body, such as the salivary glands, the tear
glands, the mammæ of the female, and the testes of the male. In regard
to the latter two organs the evidence, especially in the case of the
testes, is conflicting, but the recent experiments of Ribbert seem to
give definite results. Nothnagel had found that after the removal of one
testis there is no hypertrophy of the other. He pointed out that this
result does not stand in contradiction to his hypothesis in regard to
the kidneys, for the loss of one testis does not lead to a greater
functional activity in the other. Each acts for itself alone. The result
shows further, he adds, that the process of hypertrophy is not an
adaptive one, but a physical or a physiological process. Ribbert on the
contrary thinks that even Nothnagel’s statistics give evidence of
hypertrophy, and Ribbert’s own experiments give unmistakable evidence of
a considerable enlargement of the remaining testis. In his experiments,
young rabbits were used that were born of the same mother and in the
same litter. One of the testes was removed from some of the individuals,
and after some months the remaining testis was taken out and its weight
compared with that of the control animal. In sixteen out of seventeen
experiments there was found to be a noticeable increase in the single
testis as compared with either testis of the control animal. The results
show that in some cases the single testis weighs almost as much as the
two together of the control animal. It is important also to notice that
in this case the enlargement has taken place in an organ that has not
been active, as was the case with the kidney.
Ribbert has also shown that hypertrophy takes place in the mammæ of the
rabbit after the removal of some of them. Five out of the eight mammæ
were removed in three cases, and seven out of the eight in two other
cases from young rabbits about two months old. Ribbert found that if the
operator is not careful to remove completely all the tissue of a mamma
an active regenerative process takes place from the part that remains.
After five and a half months the single remaining mamma of one animal
measured six and one-half by three and four-fifths centimetres, and the
corresponding one in the control animal five and three-fourths by three
and one-half centimetres. The glandular tissue was also found less
developed in the control animal.
In another experiment the rabbit experimented upon bore young when it
was six and a half months old. Soon after the birth of the young and
before the mamma had been used the animal was killed and the single
mamma that had been left was measured. It was much enlarged and
projected more than the normal mammæ. It measured nine by five
centimetres. In a normal control animal[53] the corresponding mamma
measured seven by five centimetres. The number of acini was in the
proportion of sixteen in the animal operated upon to ten in the normal.
The results show a distinct compensating hypertrophy, due to a
hyperplastic increase in the number of elements of the gland.
A further example of compensating hypertrophy has been found after the
removal of the spleen, when the lymphatic glands of other parts of the
body become enlarged. There are also observations which go to show that
after the removal of some of the lymphatic glands others undergo an
enlargement.
Ziegler[54] has given a critical review of the various opinions and
hypotheses that have been advanced to account for the process of
hypertrophy. According to Cohnheim[55] hypertrophy in bones, muscles,
spleen, and glands is due to hyperæmia, _i.e._ increased blood supply.
He thinks that neither mechanical nor chemical stimuli can cause
directly new processes of growth. Recklinghausen[56] thinks that
hypertrophy is not due to any extent to an increase in the food supply.
Samuel[57] explains hypertrophy as due to a removal of, or to a decrease
in, the resistance to growth and also to the influence of the nerves.
Klebs[58] thinks that three factors enter into the problem, (_a_)
inherited peculiarities, (_b_) overfeeding, (_c_) a removal of the
controlling influences. Weigert believes that reparative processes are
due to the removal of influences that prevent growth, and not to a
direct stimulus. He thinks that a stimulus may start a functional act,
but can never start a nutritive or a formative one. Good nourishment,
for instance, may bring a tissue to a maximum development that is
predetermined by innate peculiarities, but “idioplastic forces” are not
thereby increased. Pekelharing[59] thinks that hypertrophy is due to a
disappearance of a resistance to growth, and also to a stimulus causing
proliferation.
We see from these various opinions how little is really known; how
little has been determined as yet by experiment as to the causes that
bring about hypertrophy. Many of the views are more or less plausible in
the absence of direct, experimental evidence, but it remains for the
future to decide as to the correctness of all of them. They are valuable
as suggestions, in so far as they show the different possibilities that
must be taken into account.
Ziegler first advocated the view, in the first edition of his
_Lehrbuch_, that hypertrophy is due to a lessening of the resistance to
growth. He thinks that while hyperæmia and transudation may support the
new growth, they are never the only cause of the formation of new
tissue. While Virchow’s view that any injury to the body or to an organ
excites proliferation finds support in the work of Stricker and Grawitz,
yet the view has been combated by Cohnheim and by Weigert, and is no
longer held by many pathologists. Ziegler points out that as a result of
his own work, and that of his students, traumatic and chemical lesions
are not followed at once by new growth of the tissue, but by
degeneration of the tissue, and by changes in the circulation that lead
to exudations. The new growth begins, at the earliest, eight hours after
the operation, and generally only after twenty-four hours. Also after
mechanical, chemical, or thermal injuries, a long interval elapses
before phenomena of growth begin. The injury itself does not appear to
produce the growth, but brings about those conditions that lead to
cell-multiplication. Ziegler discusses what is meant by the idea of a
lessening of the resistance to growth. He himself does not mean by this
that hypertrophy depends on changes in the physical conditions, because
it is known that living phenomena are the outcome of chemical processes
and it is, therefore, _à priori_ probable that the effect is brought
about by chemical substances in the fluids of the tissues. These
substances affect functional actions, and may even bring about
regenerative changes. This action of chemical substances on the
formative activity of the cell is theoretically possible in either of
two ways; first, chemical substances of definite concentration are set
free, or, second, chemical substances are present in the normal
condition that prevent proliferation, but if their influence should be
counteracted by other substances the conditions become favorable to
growth. It is known in the case of certain unicellular organisms, that
derive their nourishment from the surrounding medium, that their
increase in number may be retarded by the presence of certain chemical
substances. It is also known that certain organisms may themselves
produce chemical substances that prevent their own multiplication. It
is, therefore, at least conceivable that after a part has been injured a
new substance may be produced that acts upon and destroys in the organ
itself the substances there present that have prevented its further
growth. The other interpretation is that in the breaking down of the
tissue of the organ a substance is produced that excites the cells to
proliferation.
Klebs suggested that the accumulation of the leucocytes at the wounded
surface may act as a stimulus to growth, and that the chromatin of their
nuclei might be absorbed by the cells of the tissue, and combining with
the nuclei of these cells bring about the new growth. But Ziegler points
out that we now know that although the leucocytes are dissolved and
absorbed over the wounded surface, no process of absorption, of the sort
postulated by Klebs, takes place. Ziegler thinks that Nothnagel is wrong
in supposing that an increase in the blood supply, bringing with it an
increase in the nourishment, can account for the hypertrophy of the
kidney. On the contrary he believes that the growth is the result of an
increase in the function of the organ due to the increase of the
chemical substance, urea, that is brought to the secreting cells. The
muscles of the body also hypertrophy as a result of their activity and
not as a result of the additional blood supply.
In connection with these problems of hypertrophy it may be pointed out
that, under certain conditions, blood vessels may enlarge and their
walls become thickened. To cite a single example, Nothnagel found that
if the femoral artery of the rabbit is tied, the blood vessels, that
come off immediately above the ligature, and which have already, through
their subdivisions, connections in the muscles with other branches of
the same femoral artery (that come off below the ligature), grow larger
after a time. This he believes to be due, in the first instance, to the
increased speed of the blood in the vessels, and thereby the bringing to
these arteries of an increased food supply. Other writers have given
different interpretations. Ziegler himself believes that several factors
may be capable of bringing about the result. He thinks it improbable
that the increase in the food supply can alone be the cause, and thinks
it much more probable that the increased work that the vessels must
perform while carrying more blood will account for the enlargement.
In connection with this discussion it may not be unprofitable to recall
that in the regeneration of the lower animals we find simpler conditions
in which proliferation of the cells takes place under circumstances
where many of the factors suggested in the above discussion are absent.
In the first place we find that new growth may occur without any
increase in the nourishment that is brought to the organ. Regeneration
takes place in the entire absence of food, except so far as it may be
stored up in the tissues. Even in a planarian that is starving and
decreasing in size, proliferation of new cells will take place if a part
is removed. In many of the lower forms there may be proportionately even
a much greater proliferation than in the regeneration and hypertrophy in
the mammalian organs. It is true that proliferation may be more active
if the tissues are well fed, but this does not show that the presence of
food is a factor in the proliferation except so far as it keeps the
proliferating cells in their best condition for growth. It is possible
in many animals, more especially in some of the lower forms, to force
them to grow rapidly by supplying them with a large amount of food, and
conversely by decreasing the food to delay the growth. While this shows
that the rate of growth is, within certain limits, a function of the
amount of food, there may be also other factors that enter into the
result, and in all cases there is an upper limit beyond which it is not
possible to make the animal grow any larger.
That the presence of certain substances may bring about the enlargement
of a part must be admitted as probable. It has been shown, for instance,
that after the removal of certain lymphatic glands other glands may
become larger. This appears to be due to the greater activity of the
gland, brought about probably by the presence of an increased amount of
some specific substance. In this instance the result can scarcely be due
to a decrease in the physical resistance to growth or to an increase in
the blood flow, except so far as this is brought about by the increased
activity. It is, of course, possible, even if it cannot be positively
shown in the case of the lymphatic glands, that a substance in the blood
causes the hypertrophy in certain organs, while in others, as in the
kidney, an increase in the blood flow may be also a factor in its
hypertrophy.
The view held by several pathologists, that hypertrophy and regeneration
may be caused by the removal of a physical resistance to growth, cannot
be looked upon as a very probable hypothesis. The experiments in
grafting of hydra and lumbriculus show that regeneration may still take
place when the physical resistance has been reëstablished by grafting
two pieces together. These results, which are more fully described in a
later chapter, demonstrate that the growth is due to other influences.
A comparison with the lower animals shows that proliferation takes place
when all but three of the factors considered in connection with
hypertrophy and regeneration in the higher forms have been eliminated.
These are, first, the action of substances that act either directly or
as counteracting some substance already present, as Ziegler suggests;
second, an innate tendency in the organism to complete itself; and,
third, the use of the organ. It is impossible that the second factor
enters into the problem of hypertrophy. In those cases in which
regeneration takes place when a part of an organ is removed, as in the
case of the liver, for example, the result may possibly also involve the
second of the two factors, for the process is much like that of
morphallaxis in the lower animals.
If it be granted that the growth in a hypertrophied organ is brought
about by some substance that increases the function of that organ, can
we suppose the phenomenon of regeneration to be due to similar factors?
In other words, can we reduce both phenomena to the same principle? The
case is complicated by two facts that may be illustrated by concrete
examples. If a piece is cut from the middle of the body of lumbriculus
new cells are produced at both ends of the piece. If we suppose the
proliferation is brought about by the accumulation of certain substances
in the piece, we must still invoke other factors to account for the
differentiation of the proliferated material, since a head forms at one
end and a tail at the other. All the hypothesis can do in itself is to
account for a proliferation, not for the differentiation, and, both in
the case of hypertrophy and in that of regeneration, it is the formation
of new structures that we are chiefly concerned with, rather than the
simple act of growth or of proliferation. If a piece of a hydra is cut
off, the whole piece changes into the typical hydra form. Here there is
no extensive process of proliferation, and the change is in the old
part. It seems highly improbable that the production of substances in
the piece could account for its change of form. These examples will
suffice to show that in the process of regeneration it is very
improbable that the change is brought about by special substances that
may develop or be present in the part. We must suppose that during
regeneration the formation of the typical form is not the result of a
stimulus originating in a chemical substance acting upon the living
material, but due to changes brought about directly in the living part
itself. We must conclude, therefore, that despite the apparently close
connection between the phenomena of hypertrophy of uninjured organs and
of regeneration, they may often involve different factors.
If specific substances can bring about the hypertrophy of an organ, it
is still not clear at present whether they do so by directly causing new
growth, or whether their presence only stimulates the organ to greater
activity and the activity of the organ is the cause of its growth. Since
it must be supposed that in each organ a different specific substance
brings about its activity and the consequent hypertrophy, it seems more
probable that the result is due to the activity itself rather than to a
stimulus from the substance. This view is further supported by the fact
that in the case of the muscles and of the blood vessels the hypertrophy
is directly connected with their use. The greater use brings about a
larger supply of blood, but the blood is only different in amount and
not in its quality. It must be confessed that it is difficult to see how
the use of a part could make its growth increase, for by use the tissues
break down; and we are not familiar with any other processes within the
body that make for the building up of an organ in more than an inverse
ratio to its breaking down. We are, however, familiar with phenomena of
building up due to an increase in the food supply. It might appear from
this to be more in accordance with what we find, to assume that the
hypertrophy is solely due to an increase in the food supply; yet there
are other facts known that show that an organ does not increase in size
simply because it gets more blood, and that this occurs only when the
organs have a greater functional activity. It is a safer conclusion, I
think, at present to assume that both the activity of the organ and the
increase in its supply of food acting together are factors in the
result. On the other hand we are so much in the dark concerning the
functioning and growth of organs that we can do little more, as the
preceding pages show only too clearly, than speculate in the vaguest
sort of way as to what changes take place; but since the processes seem
to be within reach of experimental methods we can hope in the near
future to learn more of how the processes of hypertrophy are brought
about.
_ATROPHY_
It would not be profitable to enter into a general discussion of the
many cases of absorption, or of atrophy of parts of the organism, but a
few examples may be given that have a general bearing on the topics
discussed in this chapter. The more noticeable cases arise through
disuse of an organ, as shown, for example, in the decrease in size of
the muscles of man when they are not used. Since this may take place in
a single group of disused muscles, when no such change occurs in other
muscles of the same individual that are in use, the most obvious
explanation is that the decrease is due directly to disuse. Since the
blood that goes to all the parts is the same, the diminution cannot be
ascribed to any special substance in the blood. The flow of blood into
the disused muscle is less than when the muscle is used, and it might be
supposed that atrophy is directly caused by the lessened nourishment
that the muscle receives. There is also the possibility that the
decrease is brought about by the accumulation of certain substances in
the disused muscle itself, but since, in general, the breaking down of
the muscle is most active when it is used, it seems improbable that the
result can be due directly to this cause, unless indeed it could be
shown that the substances produced by a disused muscle are different
from those in an active muscle.
Lack of food, as is known, may cause organs to decrease, the fat first
disappearing, and then in succession in vertebrates, the blood, the
muscles, the glands, the bones, and the brain. Certain poisons may also
affect definite organs and bring about a decrease in size, as when the
thymus and mammæ decrease from iodine poisoning, and certain extensor
muscles after lead poisoning. Atrophy may also be brought about by
pressure on a part, as when the feet or waist are compressed. In old age
there may be a decrease in some of the organs, as in the bones, the
testes and ovary, and even in the heart.
Degenerative changes appear even in the young stages of some animals, as
when the tail of the tadpole is absorbed and the arms of the pluteus of
the sea-urchin are absorbed by the rest of the embryo.
Especially interesting are the cases of absorption that take place when
organs are transplanted to unusual situations in the body. Zahn
transplanted a fœtal femur to the kidney, where it continued to grow but
was later absorbed. Fischer transplanted the leg of a bird’s embryo to
the comb of a cock, where it continued at first to grow, but after some
months degenerated. The spleen, the kidney, and the testis have been
transplanted, but they degenerate, and, in general, the larger the
transplanted piece the more probable its degeneration. Small pieces of
the skin have been transplanted from one individual to another, and it
has been found that small pieces maintain themselves better than large
pieces. Ribbert’s recent experiments in transplanting small pieces of
different organs have been more successful than earlier experiments in
which larger pieces were used. The first difficulty seems to be in
establishing a blood supply to the new part, in order to nourish it. If
the piece is quite small, it can absorb the substances, necessary to
keep it alive, from the surrounding tissues, until the new blood supply
has developed.
In the lower animals grafting experiments have been more successful,
because the parts can remain alive for a longer time. It is important to
find, however, that even in these cases, a part grafted upon an abnormal
region of the body is usually absorbed. Rand shows that if the tentacles
of hydra become displaced, as sometimes happens when a piece containing
the old tentacles regenerates (Fig, 48, _A-A³_), the misplaced
tentacles are absorbed; and I can confirm this result. In hydra, the
hollow tentacles are in direct communication with the central digestive
tract, and a displaced tentacle seems to be in as good a position as a
normal one, as far as its nourishment is concerned, yet it becomes
absorbed.
Rand also found, in other experiments, that when the anterior end of a
hydra is grafted upon the wall of another hydra, the piece may maintain
itself if it is large; but it is slowly shifted toward the base of the
hydra to which it is grafted, and then the two separate in this region.
If the graft is small, it may be entirely absorbed into the wall of the
animal to which it is attached.
Marshall found that if the head of a hydra is partially split in two,
each half-head completes itself (as Trembley had already shown). The
body then begins slowly to separate into two parts, beginning at the
angle between the two heads, until finally the two parts completely
separate. King (1900) has repeated the experiment in a large number of
cases with the same result. It seemed that the division might be brought
about by the weight of the halves causing the gradual separation of the
body, but King has shown that this is not the case, for, when a double
form remained hanging with its head down, it still divided into two
parts (Fig. 47, _A_). In this case, the weight of the two heads would
cause the parts to come together rather than to separate, if gravity had
any influence of the sort suggested. Marshall and King have also shown
that if the posterior end of a hydra is split in two, the two parts do
not continue to separate, but one of the two, if the pieces have been
split some distance forward, may become constricted from the other, and,
producing new tentacles at its apical end, become a new individual.
I have carried out a series of experiments on planarians of a somewhat
similar nature. If the posterior end is split in two, the separation
extending into the anterior part of the worm (Fig. 44, _C_), each half
completes itself, but the halves do not separate unless they happen to
tear themselves apart. If one of the pieces is cut off, not too near the
region of union with the other half, a new posterior end, replacing that
cut off, regenerates. If, however, the piece is cut off quite near the
region or union of the halves, the piece that is left may be absorbed.
The absorption of misplaced parts in the lower animals cannot be
explained, I think, by any lack of nutrition, especially in the case of
the tentacles of hydra. The result may be due either to the displaced
part not receiving exactly those substances, perhaps food substances,
that it gets in its normal position, or it may be due to some formative
influence. At present we are not in a position to decide between these
alternatives, and, while the former view seems more tangible, and the
latter quite obscure, the latter may nevertheless be found to contain
the true explanation. If the view that I have adopted in regard to the
organization--namely, that it can be thought of as acting through a
system of tensions peculiar to each kind of protoplasm--is correct, it
may be possible to account for the absorption of misplaced parts by some
such principle as this.
_INCOMPLETE REGENERATION_
A somewhat unusual process of regeneration takes place when the
jelly-fish, _Gonionemus vertens_, is cut into pieces. As first shown by
Hargitt, the cut-edges come together and fuse, and the pieces
[Illustration: FIG. 39½.--_A._ Aboral view of _Gonionemus vertens_.
_A¹._ Side view of same. Dotted line in each indicates where jelly-fish
was cut into halves. _B, B._ New individual from a half. As seen from
above and from the side. _C, C¹._ New individuals from a ¼ piece. As
seen from above and from the side. _D._ New individual from a piece less
than ¼. It contained a part of one of the radial canals. A new
proboscis with mouth regenerated in all pieces, but no new canals or
tentacles.]
assume the form of a bell, but the missing parts are not replaced.[60] I
have worked on the same form and obtained substantially the same
results. If the jelly-fish is cut in two, as indicated by the dotted
line in Fig. 39½, _A_ and _A¹_, each half closes in and assumes
the form shown in _B, B_. Each new jelly-fish has only the two original
radial canals that each half had when separated from the other. A faint
line along the region of fusion of the pieces seems to represent a new
radial canal,--it is not represented in the figures,--and each
half-proboscis has completed itself. There are not formed any new
tentacles, except perhaps one, or a few more, where the cut-edges meet.
Thus there is actually very little regeneration, although the typical
jelly-fish form is assumed by the half-piece. If a jelly-fish is cut
into four pieces, each piece containing one of the radial canals, the
pieces also assume the bell-like form, as shown in _C, C¹_. A new
proboscis develops from the proximal end of the old radial canal, and
since this end is often carried to one side during the closing in of
the piece, the new proboscis lies not at the top of the sub-umbrella
space, but, as seen in the figure, quite to one side. Pieces even
smaller than these one-fourth jelly-fish will assume the bell-like form,
especially if they contain a bit of the margin of the old bell and a
part of one of the radial canals, as shown in Fig. 39½, _D_. Although
I have kept these partial medusæ for several weeks, and have fed them
during this time, I have found that the missing organs do not come back.
That these pieces do undergo a certain amount of regeneration is shown
by the formation of a new proboscis, and, in certain cases, a new radial
canal. Even the tentacles may be partially regenerated, as Hargitt has
shown,--especially, as I have found, if the margin of the bell is cut
off very near the base of the line of tentacles. Small knobs appear
along the cut-edge, but the pieces die before regeneration goes very
far. If, however, the margin is cut off in only one quadrant, new
tentacles may be produced along the cut-edge.