Chapter II
No Sharp Line Of Demarkation Between Health And Disease.—The Functional Nutritive And Formative Activities Of Cells.—Destruction And Repair Constant Processes In Living Matter.—Injuries To The Body.—The Effect Of Heat.—The Action Of Poisons.—The Lesions Of Disease.—Repair.—The Laws Governing Repair.—Relation Of Repair To Complexity Of Structure And Age.—The Reserve Force Of The Body.— Compensatory Processes In The Body.—Old Age.—The Diminution Of Resistance To The Effect Of The Environment A Prominent Factor In Old Age.—Death.—How Brought About.—Changes In The Body After Death.— The Recognition Of Death.
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 coördinated 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.
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 hæmoglobin 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° F., egg white coagulating at 158° 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 hæmoglobin 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 hæmorrhage 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.
By this general death is meant the death of the organism as a whole, but all parts of the body do not die at the same time. The muscles and nerves may react, the heart may be kept beating, and organs of the body when removed and supplied with blood will continue to function. Certain tissues die early, and the first to succumb to the lack of oxygenated blood are the nerve cells of the brain. If respiration and circulation have ceased for as short a time as twelve minutes, life ceases in certain of these cells and cannot be restored. This is again an example of the greater vulnerability of the more highly differentiated structure in which all other forms of cell activity are subordinated to function. There are, however, pretty well authenticated cases of resuscitation after immersion in water for a longer period than twelve minutes, but these cases have not been carefully timed, and time under such conditions may seem longer than it actually is; and there is, moreover, the possibility of a slight gaseous interchange between the blood and the water in the lungs, as in the case of the fish which uses the water for an oxygen supply as the mammal does the air. There are also examples of apparent death or trances which have lasted longer, and the cases of fakirs who have been buried for prolonged periods and again restored to life. In these conditions, however, all the activities of the body are reduced to the utmost, and respiration and circulation, so feeble as to be imperceptible to ordinary observation, suffice to keep the cells living.
With the cessation of life the body is subject to the unmodified action of its physical environment. There is no further production of heat and the body takes the temperature of the surroundings. The only exceptions are rare cases in which such active chemical changes take place in the dead body that heat is generated by chemical action. At a varying interval after death, usually within twelve hours, there is a general contraction and hardening of the muscles due to chemical changes, probably of the nature of coagulation, in them. This begins in the muscles of the head, extends to the extremities, and usually disappears in twenty-four hours. It is always most intense and most rapid in its onset when death is preceded by active muscular exertion. There have been cases of instantaneous death in battle where the body has remained in the position it held at the moment of death, this being due to the instantaneous onset of muscular rigidity. The blood remains fluid for a time after death and settles in the more dependent parts of the body, producing bluish red mottled discolorations. Later the blood coagulates in the vessels. The body loses moisture by evaporation. Drying of the surface takes place where the epidermis is thin, as over the transparent part of the eye and over areas deprived of epidermis. Decomposition and putrefaction of the body due to bacterial action takes place. The bacteria ever present in the alimentary canal make their way from this into the dead tissue. Certain of these bacteria produce gas which accumulates in the tissues and the body often swells enormously. A greenish discoloration appears, which is due to the union of the products of decomposition with the iron in the blood; this is more prominent over the abdomen and appears in lines along the course of the veins. The rapidity with which decomposition takes place varies, and is dependent upon many factors, such as the surrounding temperature, the nutrition of the body at the time of death, the cause of death. It is usually not difficult to recognize that a body is dead. In certain cases, however, the heart's action may be so feeble that no pulse is felt at the wrist, and the current of the expired air may not move a feather held to the nostril or cloud the surface of a mirror by the precipitation of moisture upon it. This condition, combined with unconsciousness and paralysis of all the voluntary muscles, may very closely simulate death. The only absolute evidence of death is given by such changes as loss of body heat, rigor mortis or stiffening of the muscles, coagulation of the blood and decomposition.