Disease and Its Causes by William Thomas Councilman

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There is no sharp line separating health from disease; changes in the
tissues of the same nature, or closely akin to those which are found
in disease, are constantly occurring in a state of health. The
importance of parasites in causing disease has led to the conception
of disease as almost synonymous with parasitism; but it must be
remembered that the presence of parasites living at the expense of the
body is perfectly consistent with a state of health. Degeneration,
decay and parasitism only become disease factors when the conditions
produced by them interfere with the life which is the normal or usual
for the individual concerned.

All the changes which take place in the cells are of great importance
in conditions of both health and disease, for life consists in
cooerdinated cell activity. The activities of the cells can be divided
into those which are nutritive, those which are functional and those
which are formative. In the functional activity the cell gives off
energy, this loss being made good by the receipt of new energy in the
form of nutritive material with which the cell renews itself. In
certain cells an exact balance seems to be maintained, but in those
cells whose activity is periodic function takes place at the expense
of the cell substance, the loss being restored by nutrition during the
period of repose. This is shown particularly well in the case of the
nerve cells (Fig. 13). Both the functional and nutritive activity can
be greatly stimulated, but they must balance; otherwise the condition
is that of disease.

[Illustration: FIG 13.--NERVE CELLS OF AN ENGLISH SPARROW (_a_) Cells
after a day's full activity, (_b_) cells after a night's repose. In
(_a_) the cells and nuclei are shrunken and the smaller clear spaces
in the cells are smaller and less evident than in (_b_). (Hodge)]

The formative activity of cells is also essential to the normal state.
Destruction of cells is constantly taking place in the body, and more
rapidly in certain tissues than in others. Dried and dead cells are
constantly and in great numbers thrown off from the surface of the
skin: such epidermic appendages as the hair and nails grow and are
removed, millions of cells are represented in the beard which is daily
removed. Cells are constantly being destroyed on the intestinal
surface and in the glands. There is an enormous destruction of the
blood cells constantly taking place, certain essential pigments, as
that of the bile, being formed from the haemoglobin which the red blood
corpuscles contain and which becomes available on their destruction.
All such loss of cells must be made good by the formation of new ones
and, as in the case of the nutritive and functional activity, the loss
and renewal must balance. The formative activity of cells is of great
importance, for it is by means of this that wounds heal and diseases
are recovered from. This constant destruction and renewal of the body
is well known, and it is no doubt this which has given rise to the
belief, widely held, that the body renews itself in seven years and
that the changes impressed upon it by vaccination endure for this
period only. The truth is that the destruction and renewal of most
tissues in the body takes place in a much shorter interval, and, as we
shall see, this has nothing to do with the changes concerned in
vaccination. All these activities of the cells vary in different
individuals, in different parts and at different ages.

The lesions or injuries of the body which form so prominent a part of
disease vary in kind, degree and situation, depending upon the
character of the injurious agent, the duration of its action and the
character of the tissue affected. The most obvious injuries are those
produced by violence. By a cut, blood vessels are severed, the
relations of tissues disturbed, and at the gaping edges of the wound
the tissue usually protected by the skin is exposed to the air,
resulting in destruction of the cells contained in a thin layer of the
surface. The discoloration and swelling of the skin following a blow
is due to rupture of vessels and escape of blood and fluid, and
further injury may result from the interruption of the circulation.

By the application of heat the tissue may be charred and the albumen
of the blood and tissue fluids coagulated. Living cells are very
susceptible to the action of heat, a temperature of 130 degrees being
the thermal death point, and even lower temperatures are fatal when
their action is prolonged. The action of the heat may produce definite
coagulation of the fluid within the cells in the same way that the
white of an egg is coagulated. Certain of the albumens of the body
coagulate at a much lower temperature than the white of the egg (as
the myosin, one of the albumens of the muscle which coagulates at 115 deg.
F., egg white coagulating at 158 deg. F.), and in addition to such
coagulation or without it the ferments within the cell and to the
action of which cellular activity is due may be destroyed.

In diseases due to parasites, the parasite produces a change in the
tissue in its immediate vicinity often so great as to result in the
death of the cells. The most general direct cause of lesions is toxic
or poisonous substances, either introduced from without or formed in
the body. In the case of the parasitic diseases the mere presence of
the parasite in the body produces little or no harm, the injury being
caused by poisons which it produces, and which act both locally in the
vicinity of the parasite and at a distance, being absorbed and
entering the blood stream. How certain of the poisonous substances act
is easy to see. Strong caustics act by coagulating the albumen, or by
the withdrawal of water from the cell. Other poisons act by forming
stable chemical compounds with certain of the cell constituents and
thereby preventing the usual chemical processes from taking place.
Death from the inhalation of illuminating gas is due to the carbon
monoxide contained in this, forming a firm chemical union with the
haemoglobin of the red corpuscles so that the function of these as
oxygen carriers is stopped.

In order that most poisons may act, it is essential that they enter
into the cell, and they cannot do this unless they are able to combine
chemically with certain of the cell constituents. To this is due the
selective action of many poisons. Morphine, for example, acts chiefly
on the cells of the brain; strychnine acts on the cells of the spinal
cord which excite motion and thus causes the characteristic muscular
spasm. The poisonous substances produced by bacteria, as in the case
of diphtheria, act on certain of the organs only. Different animal
species owe their immunity to certain poisons to their cells being so
constituted that a poison cannot gain entrance into them; pigeons, for
example, cannot be poisoned by morphia. Individual variations play an
important part also; thus, shellfish are poisonous for certain
individuals and not so for others. Owing to the variability of living
structures a substance may be poisonous at one time and not at
another, as the following example shows. A man, very fond of crab
meat, was once violently poisoned after eating crabs, being at that
time seemingly in his usual state of health, and no illness resulted
in others who had partaken of the same crabs. Two months later a
hearty meal of crabs produced no ill result. There are also
individuals so constituted that so simple a food as the egg is for
them an active poison.

The lesions produced by the action of injurious conditions are usually
so distinctive in situation and character that by the examination of
the body after death the cause of death can be ascertained. The
lesions of diseases may be very obvious to the naked eye, or in other
cases only the most careful microscopic examination can detect even
the presence of alterations. In the case of poisons the capacity of
the cell for adaptation to unusual conditions is of great importance.
It is probable that certain changes take place within the cells, owing
to which the function can be continued in spite of the unusual
conditions which the presence of the poison brings about. It is in
this way that the habitual use of such poisons as morphine, alcohol
and tobacco, to speak only of those best known, is tolerated. The cell
life can become so accustomed to the presence of poisons that the cell
activities may suffer in their absence.

_Repair_ of the injuries which the body receives is effected in a
variety of ways. We do not know how intracellular repair takes place,
but most probably the cells get rid of the injured areas either by
ejecting them, or chemical changes are produced in the altered cell
substance breaking up and recombining the molecules. When single cells
are destroyed, the loss is made good by new formation of cells, the
cell loss stimulating the formative activity of the cells in the
vicinity. The body maintains a cell and tissue equilibrium, and a loss
is in most cases repaired. The blood fluid lost in a haemorrhage is
quickly restored by a withdrawal of the fluid from the tissues into
the blood, but the cells lost are restored by new formation of cells
in the blood-forming organs. The blood cells are all formed in bone
marrow and in the lymph nodes, and not from the cells which circulate
in the blood, and the stimulus to new cell formation which the loss of
blood brings about affects this remote tissue.

In general, repair takes place most easily in tissues of a simple
character, and where there is the least differentiation of cell
structure for the purposes of function. A high degree of function in
which the cell produces material of a complex character necessitates a
complex chemical apparatus to carry this out, and a complicated
mechanism is formed less easily than a simple one. In certain tissues
the cells have become so highly differentiated that all formative
activity is lost. Such is the case in the nerve cells of the brain and
spinal cord, a loss in which tissue is never repaired by the formation
of new cells; and in the muscles the same is true. The least
differentiation is seen in those cells which serve the purpose of
mechanical protection only, as the cells of the skin, and in these the
formative activity is very great. Not only must the usual loss be
supplied, but we are all conscious of slight injuries of the surface
which are quickly repaired.

Repair, other things being equal, takes place more easily in the young
than in the old. New formation of cells goes on with great rapidity in
intra-uterine life, the child, beginning its existence as a single
cell one two hundred and fiftieth of an inch in diameter, attains in
nine months a weight of seven pounds. The only similar rapidity of
cell formation is seen in certain tumors; although the body may add a
greater amount of weight and in a shorter time, by deposit of fat,
this in but slight measure represents a new formation of tissue, but
is merely a storage of food material in cells. The remarkable repair
and even the new formation of entire parts of the body in the tadpole
will not take place in the completely developed frog.

Repair will also take place the more readily the less complicated is
the architectural structure of the part affected. When a series of
tissues variously and closely related to one another enter into the
structure of an organ, there may be new formation of cells; but when
the loss involves more than this, the complicated architectural
structure will not be completely replaced. A brick which has been
knocked out of a building can be easily replaced, but the renewal of
an area of the wall is more difficult. In the kidney, for example, the
destruction of single cells is quickly made good by new cell
formation, but the loss of an area of tissue is never restored. In the
liver, on the other hand, which is of much simpler construction, large
areas of tissue can be newly formed. For the formation of new cells in
a part there must be a sufficient amount of formative material; then
the circulation of the blood becomes more active, more blood being
brought to the part by dilatation of the vessels supplying it.

Repair after a loss can be perfect or imperfect. The tissue lost can
be restored so perfectly that no trace of an injury remains; but when
the loss has been extensive, and in a tissue of complex structure,
complete restoration does not take place and a less perfect tissue is
formed which is called a scar. Examination of the skin in almost
anyone will show some such scars which have resulted from wounds. They
are also found in the internal organs of the body as the result of
injuries which have healed. The scar represents a very imperfect
repair. In the skin, for example, the scar tissue never contains such
complicated apparatus as hair and sweat glands; the white area is
composed of an imperfectly vascularized fibrous tissue which is
covered with a modified epidermis. The scar is less resistant than the
normal tissue, injury takes place more easily in it and heals with
more difficulty.

Loss brought about by the injuries of disease can be compensated for,
even when the healing is imperfect, by increased function of similar
tissue in the body. There always seems to be in the body under the
usual conditions a reserve force, no tissue being worked to its full
capacity. Meltzer has compared the reserve force of the body to the
factor of safety in mechanical construction. A bridge is constructed
to sustain the weight of the usual traffic, but is in addition given
strength to meet unusual and unforeseen demands. The stomach provides
secretion to meet the usual demands of digestion, but can take care of
an unusual amount of food. The work of the heart may be doubled by
severe exertions, and it meets this demand by increased force and
rapidity of contraction; and the same is true of the muscles attached
to the skeleton. The constant exercise of this reserve force breaks
down the adjustment. If the weight of the traffic over the bridge be
constantly all that it can carry, there quickly comes a time when some
slight and unforeseen increase of weight brings disaster. The
conditions in the body are rather better than in the case of the
bridge, because with the increased demand for activity the heart, for
example, becomes larger and stronger, and reserve force rises with the
load to be carried, but the ratio of reserve force is diminished.

This discussion of injury and repair leads to the question of old age.
Old age, as such, should not be discussed in a book on disease, for it
is not a disease; it is just as natural to grow old and to die as it
is to be born. Disease, however, differs in many respects in the old
as compared with the young and renders some discussion of the
condition necessary. Changes are constantly taking place in the body
with the advance of years, and in the embryo with the advance of days.
In every period of life in the child, in the adult, in the middle-aged
and in the old we meet with conditions which were not present at
earlier periods. There is no definite period at which the changes
which we are accustomed to regard as those of old age begin. This is
true of both the external appearances of age and the internal changes.
One individual may be fully as old, as far as is indicated by the
changes of age, at fifty as another at eighty.

With advancing age certain organs of the body atrophy; they become
diminished in size, and the microscopic examination shows absence or
diminished numbers of the cells which are peculiar to them. The most
striking example of this is seen in the sexual glands of females, and,
to a less degree, in those of the male. There is a small mass or
glandular tissue at the root of the neck, the thymus, which gradually
grows from birth and reaches its greatest size at the age of fifteen,
when it begins slowly to atrophy and almost disappears at the age of
forty. This is the gland which in the calf is known as the sweetbread
and is a delicious and valued article of food. The tonsils, which in
the child may be so large as to interfere with breathing and
swallowing, have almost disappeared in the adult; and there are other
such examples.

In age atrophy is a prominent change. It is seen in the loss of the
teeth, in the whitening and loss of the hair, in the thinning of the
skin so that it more easily wrinkles, in the thinning and weakening of
the muscles so that there is not only diminished force of muscular
contraction, but weakening of the muscles of support. The back curves
from the action of gravity, the strength of the support of the muscles
at the back not counteracting the pull of the weight of the abdominal
viscera in front. The bones become more porous and more brittle.

The effect of atrophy is also seen in the diminution of all functions,
and in loss of weight in individual organs. That the brain shares in
the general atrophy is evident both anatomically and in function.
Mental activity is more sluggish, impressions are received with more
difficulty, their accuracy may be impaired by accompanying changes in
the sense organs, and the concepts formed from the impressions may
differ from the usual. The slowness of mental action and the
diminution in the range of mental activity excited by impressions, and
the slowness of expression, may give a false idea of the value of the
judgment expressed. The expression changes, the face becomes more
impassive because the facial muscles no longer reflect the constant
and ever changing impressions which the youthful sense organs convey
to a youthful and active brain. That the young should ape the old,
should seek to acquire the gravity of demeanor, to restrain the quick
impulse, is not of advantage. Loss of weight of the body as a whole is
not so apparent, there being a tendency to fat formation owing to the
non-use of fat or fat-forming material which is taken into the body.
One of the most evident alterations is a general diminution in the
fluid of the tissues, to which is chiefly due the lack of plumpness,
the wrinkles of age. The facial appearance of age is given to an
infant when, in consequence of a long-continued diarrhoea, the tissues
become drained of fluid. Every market-man knows that an old animal is
not so available for food, the tissues are tougher, more fibrous, not
so easily disintegrated by chewing. This is due to a relative increase
in the connective tissue which binds all parts together and is
represented in the white fibres of meat.

Senile atrophy is complex in its causes and modes of production. The
atrophy affects different organs in different degree and shows great
variation in situation, in degree and in progress. Atrophic changes of
the blood vessels are of great importance, for this affects the
circulation on which the nutrition of all tissues depends. While there
is undoubted progressive wear of all tissues, this becomes most
evident in the case of the blood vessels of the body. It is rare that
arteries which can be regarded as in all respects normal are found in
individuals over forty, and these changes progress rapidly with
advancing age. So striking and constant are these vascular changes
that they seem almost in themselves sufficient to explain the senile
changes, and this has been frequently expressed in the remark that age
is determined not by years, but by the condition of the arteries.
Comparative studies show the falsity of this view, for animals which
are but little or not at all subject to arterial disease show senile
changes of much the same character as those found in man.

There is another condition which must be considered in a study of
causes of age. In the ordinary course of life slight injuries are
constantly being received and more or less perfectly repaired. An
infection which may but slightly affect the ordinary well-being of the
individual may produce a considerable damage. Excess or deficiency or
improper food, occasional or continued use of alcohol and other
poisons may lead to very definite lesions. Repair after injury is
rarely perfect, the repaired tissue is more susceptible to injury, and
with advancing age there is constant diminution in the ease and
perfection of repair. The effect of the sum of all these changes
becomes operative: a vicious circle is established in which injury
becomes progressively easier to acquire and repair constantly less
perfect. There is some adjustment, however, in that the range of
activities is diminished, the environment becomes narrower and the
organism adapts its life to that environment which makes the least
demands upon it.

Whether there is, entirely apart from all conditions affecting
nutrition and the effect of injuries which disturb the usual cell
activities, an actual senescence of the cells of the body is
uncertain. In the presence of the many factors which influence the
obvious diminution of cell activity in the old, it is impossible to
say whether the loss of cell activity is intrinsic or extrinsic. The
life of the plant cell seems to be immortal; it does not grow old.
Trees die owing to accidents or because the tree acquires in the
course of its growth a mass of tissue in which there is little or no
life, and which becomes the prey of parasites. The growing tissue of a
tree is comprised in a thin layer below the bark, and the life of this
may seemingly be indefinitely prolonged by placing it in a situation
in which it escapes the action of accidental injuries and decay, as by
grafting on young trees. Where the nature of the dead wood is such
that it is immune from parasites and decay, as in the case of the
Sequoias, life seems to be indefinitely prolonged. The growing
branches of one of these trees, whose age has been estimated with
seeming accuracy at six thousand years, are just as fresh and the tree
produces its flowers and fruit in the same degree as a youthful
brother of one thousand years. Nor does old age supervene in the
unicellular organisms. An amoeba assimilates, grows and multiplies
just as long as the environment is favorable.

Old age in itself is seldom a cause of death. In rare cases in the
very old a condition is found in which no change is present to which
death can be attributed, all organs seem to share alike in the
senescence. Death is usually due to some of the accidents of life, a
slight infection to which the less resistant body succumbs, or to the
rupture of a weakened blood vessel in the brain, or to more advanced
decay in some organ whose function is indispensable. The causes and
conditions of age have been a fertile source for speculation. Many of
the hypotheses have been interesting, that of Metschnikoff, for
example, who finds as a dominating influence in causing senescence the
absorption of toxic substances formed in the large intestine by
certain bacteria. He further finds that the cells of the body which
have phagocytic powers turn their activity against cells and tissues
which have become weakened. There may be absorption of injurious
substances from the intestines which the body in a vigorous condition
is able to destroy or to counteract their influence, and these may be
more operative in the weaker condition of the body in the old.
Phagocytes will remove cells which are dead and often cells which are
superfluous in a part, but there is no evidence that this is ever
other than a conservative process. Since it is impossible to single
out any one condition to which old age is due, the hypothesis of
Metschnikoff should have no more regard given it than the many other
hypotheses which have been presented.

Death of the body as a whole takes place from the cessation of the
action of the central nervous system or of the respiratory system or
of the circulation. There are other organs of the body, such as the
intestine, kidney, liver, whose function is essential for life, but
death does not take place immediately on the cessation of their
function. The functions of the heart, the brain and the lungs are
intimately associated. Oxygen is indispensable for the life of the
tissues, and its supply is dependent upon the integrity of the three
organs mentioned, which have been called the tripos of life.
Respiration is brought about by the stimulation of certain nerve cells
in the brain, the most effective stimulus to these cells being a
diminution of oxygen in the blood supplying them. These cells send out
impulses to the muscles concerned in inspiration, the chest expands,
and air is taken into the lungs. Respiration is then a more
complicated process than is the action of the heart, for its
contraction, which causes the blood to circulate, is not immediately
dependent upon extrinsic influences. Death is usually more immediately
due to failure of respiration than to failure of circulation, for the
heart often continues beating for a time after respiration has ceased.
Thus, in cases of drowning and suffocation, by means of artificial
respiration in which air is passively taken into and expelled from the
lungs, giving oxygen to the blood, the heart may continue to beat and
the circulation continue for hours after all evident signs of life and
all sensation has ceased.

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