Part 15

The immediate causes of the physiological deposition in the formation of bone are so obscure that only more or less probable explanatory theories are advanced, to all of which obvious objections arise. The causes of a pathological precipitation may be regarded as equally hidden. It is apparent, however, that old age usually furnishes the necessary factors. This in part may be due to the feeble nutrition associated with impairment of function in advancing years. In part it may be the result of the numerous opportunities offered in a long life for the occurrence of inflammation, the products of which are frequently infiltrated with calcareous salts. The latter are apparently kept in solution by the action of living cells, for, though presented to all in the fluids of the body, they are precipitated most constantly in dead parts or in the vicinity of those cells whose function is presumably lessened from disease or age. The solvent action of living cells is further demonstrated by the effect of the giant-cells in removing calcium salts from living or dead bone.

The causes of calcification are therefore to be regarded as local, depending upon a destruction or weakening of the cells of a part--conditions which are directly attributable to an interference with nutrition. The deposition of calcium salts thus represents a disorder of nutrition, and may be experimentally produced by agencies which occasion a necrosis of tissues.

Although the immediate causes of the precipitation of the calcium salts must be expressed somewhat vaguely, the places and effects of their accumulation are sufficiently well known, as are the resulting appearances. The presence of these salts in sufficient quantity produces a homogeneous, granular, strongly refractive appearance of the cell or intercellular substance, in addition to a greatly increased resistance to pressure. When muriatic acid is added to the affected part, the salts are dissolved, with the escape of abundant bubbles of gas when a carbonate is present, and with a rapid fading of the glistening appearance, without effervescence, {88} when the salt is a phosphate. After the removal, the cell or intercellular substance is readily recognized, with such modifications in its appearance as may be due to the action of the strong acid. The parts in which this deposition or infiltration has taken place are either relatively normal in appearance or variously altered from disease, and the calcium salts are to be regarded as absorbed from the constituents of the food and deposited, or as taken up and transferred from the bones of the body. That both sources are drawn upon is obvious from the abnormal presence of calcareous material in the soft parts, in connection with increased density of the bones, as well as with a diminution in the density of the latter. The term calcification is more correctly applied to the presence of the salts in normal tissues other than bone, or in the products of disease not simulating bone-cartilage in structure. A pathological ossification is to be considered present when an actual new formation of bone has taken place so limited and so situated as not to suggest a tumor of bone, or when the calcium salts are deposited in a new-formed tissue whose structure stimulates that of bone-cartilage.

Tissues which may become calcified are, in the first instance, the connective tissues, and of these fibrous tissue and cartilage are especially liable. Epithelial, muscle--in particular the unstriped variety--and ganglion-cells may also become calcified. The frequency with which blood-vessels, especially arteries, are affected is such that it is regarded as almost normal in advancing years that calcareous material should be deposited within the vascular walls. A distinction is drawn between an ossification and a calcification of the blood-vessels. The former term should be limited to the osteoid plates so often found as circumscribed thickenings of the aortic intima, and which are obviously new-formed patches of fibrous tissue in which the calcium salts are accumulated. A calcified artery, on the contrary, is one usually of a size varying between that of the common iliac and the temporal arteries, whose wall has become rigid and unyielding, suggestive of a pipe-stem, from the presence of calcareous deposits in the muscular middle coat.

From the frequency with which the osseous plates of the aorta are associated with the fatty and fibrous changes in chronic inflammation of the intima, the so-called atheromatous degeneration of the same, it is customary to speak of the calcified artery at the wrist or temple as an atheromatous artery or as evincing an atheromatous degeneration. The common feature in the aortic changes and in the calcified muscular coat is the element of age. They are frequently, though not necessarily, associated. The one is the result of an inflammatory process productive of a new, fibrous, tissue in which the calcium salts are infiltrated; while the other is due to a deposition of the latter in the normal, pre-existing, muscular elements of the vessel.

Calcification and ossification of blood-vessels are frequent when the latter become dilated, as in aneurisms, whether these occur as circumscribed tumors or as a serpentine elongation and widening of the affected vessel.

Cartilage is also a tissue which presents a double relation to calcareous deposition. On the one hand, there may exist an ossification resulting from the extension of a growth of bone from the perichondrium into the cartilage. The structure of this bone presents all the details found in {89} normal bone--lacunæ, lamellæ, and marrow-spaces. On the other hand, a section of the cartilage, especially the costal cartilages, may contain opaque, gray, or grayish-yellow patches, grating under the knife, which are wholly due to the presence of calcium salts in the hyaline intercellular substance of the cartilage. This calcification of the cartilage, which may also involve the capsules of the cells, is frequently associated with an ossification, although this relation is in no way essential.

Calcification of the placenta, of the fibrous framework of the lungs, of the mucous membrane of the stomach, or of the atrophied glomeruli of the kidney, are well-recognized instances of the infiltration of calcareous material in normal or atrophied tissues. On the contrary, ossification of the fibrous inflammatory products of the pleura, pericardium, and peritoneum are instances of a pathological bone-formation, analogous in its nature to that met with in the intima of the aorta. The fibrinous and fibrino-cellular products of the inflammation of serous surfaces are favorable positions for the deposition of calcium salts, as are thrombi arising from the walls of blood-vessels. The latter are rather instances of the calcification of dead parts, analogous to the members of the group which includes the formation of calculi and concretions, the calcification of the dead foetus in abdominal parturition, of cheesy lymphatic glands, and of cheesy material in the lungs and elsewhere. Finally, there remains the calcification of tumors of the most varied nature, the salts being present either in living or dead parts of the tumor.

Instances of the deposition in the tissues of other than calcareous salts are abundantly met with in gout. In this disease cartilage, ligaments, and tendons, bone-marrow, muscle, the endocardium and aorta, the membranes of the brain and spinal cord, the skin and kidneys, may contain deposits of acicular crystals and amorphous granules. Although these deposits are largely composed of sodium urate, calcium urate may be present with other salts, as sodium chloride and calcareous compounds. According to Ebstein, the earthy salts in gout are deposited in necrotic patches of previously diseased tissue. The local conditions are therefore analogous to those concerned in the formation of chalky concretions.

Concretions and calculi are collections of earthy salts, the former lying within tissues, the latter being present in canals opening externally. Both represent the results of a deposition in and upon organic material, which is often an inflammatory product, at times surrounding a foreign body acting as the exciting cause of the inflammation.

The earthy matter of which the concretion is composed consists mainly of carbonate and phosphate of calcium, while the chemical properties of the calculi often vary in accordance with the nature of the secretion which flows by them. The salivary, pancreatic, intestinal, lachrymal, and prostatic calculi are chiefly formed of calcareous salts. These salts also are an important, if not the chief, constituent of biliary and urinary calculi. In the former pigment, bile acids, and cholesterin may also be present. Urinary calculi are of still more varied composition, containing not only the calcium salts, as the oxalate, phosphate, and carbonate, but also uric acid and the urates of sodium and ammonium, in addition to the ammoniaco-magnesian phosphate.

The infiltration with calcium salts may prove beneficial as well as {90} injurious--beneficial under those circumstances where further changes might prove harmful, as in the softening of cheesy material or the maceration of a dead foetus in the abdominal cavity. The calcification of certain tumors, as the fibro-myoma of the uterus, is equally sanatory, the further growth of the calcified parts being thus checked. The calcification of an aneurismal sac may prove beneficial in strengthening a weakened blood-vessel.

The injurious effects are seen more particularly in case of the calcareous infiltration of the middle coat of arteries. Such vessels become converted into rigid and unyielding tubes at various parts of their course, and the nutrition of peripheral parts becomes correspondingly lessened. Hence, in great measure, the liability of old people to serious inflammatory processes from trivial irritation of peripheral portions of the body, such inflammations often terminating in gangrene.

The calcification and ossification of the cardiac valves and the calcification of attached thrombi, furnish frequent and constant occasion for disturbances in the functions of the heart, resulting in dilatation and hypertrophy, with the sequence of symptoms of chronic valvular endocarditis.

The great clinical importance of the presence of calcium salts in the circulatory apparatus is such that further reference in this place to its results is unnecessary, as its special relations are more important than its general features.

Calculi act as local causes of inflammation, and their presence is likely to be followed by ulceration, abscess, and stenosis, perhaps obliteration, of the smaller canals in which they may lie.

Pigmentation.

The pathological pigmentation of the body results, presumably, from the metamorphosis of the coloring matter of the blood or from the introduction from without of pigments insoluble in the fluids of the body. The former of these methods has recently been studied by Langhans and Cordua, and the present views of this subject are chiefly due to their observations, as well as to the earlier investigations of Virchow and others.

The hæmoglobin contained in red blood-corpuscles is considered to be composed of a coloring matter, hæmatin, combined with an albuminate, globulin. When blood is removed from the body the hæmoglobin is readily separated from the corpuscles by various agents, and is then dissolved in the plasma, which becomes lac-colored. This solubility of the hæmoglobin is of importance in connection with the absorption of extravasated blood. During the time necessary for this process to take place, observable changes are apparent in the color of the affected part when its seat is superficial, especially cutaneous. These changes in color are largely dependent upon the modifications undergone by the hæmoglobin.

It is well known that a yellowish discoloration of the general surface frequently takes place when extensive internal hemorrhages have occurred, constituting a form of jaundice (hæmatogenous) attributed to the presence of the coloring matter of the blood. As yet there has been no satisfactory chemical analysis of this diffused pigment, which if not hæmatin must be regarded as its derivative, although a coexistent increase of the urobilin in the urine has been observed. The association of the stained skin and urine, {91} in the absence of causes favoring an absorption of bile-pigment, leads to the inference that the abnormal discoloration is due to the absorption into the circulating fluids of the body of a pigment dissolved out of the extravasated red blood-corpuscles. This view is confirmed by the microscopic examination of the latter, which discloses the presence of pale, shadowy, round outlines enclosing faintly granular material, which are regarded as decolorized red corpuscles. In the course of a few days glistening crystals and granules of a yellowish-red color make their appearance in the midst of the unabsorbed blood. The crystals are usually oblique rhombic prisms, varying in size from the larger symmetrical shapes to the more minute, apparently granular, forms. Acicular crystals are also to be met with, more yellow than red in color, and are sometimes present in great abundance, although they may be wholly absent. Virchow has applied the term hæmatoidin to these crystals. Owing to the resemblance in the chemical reactions of solutions of hæmatoidin and of the biliary coloring matter, bilirubin, and to the similar crystalline forms of the latter, it has been maintained that the two are identical. Late investigations indicate that solutions of crystals with the appearances of hæmatoidin are not invariably alike in their reaction. A solution of these in chloroform may become decolorized when acted upon by a dilute alkali, or it may not be thus altered. Bilirubin presents the former relation, while chloroform solutions of the coloring matter of the yelk of egg and of the corpus luteum, called lutein or hæmolutein, are not decolorized by an alkali. Although the crystalline forms of hæmatoidin and bilirubin are not to be distinguished, it is not to be conceded that the two substances are identical. As Maly, the latest writer on this subject, states, the term hæmatoidin is merely indicative of a microscopical picture. Although the identity of the coloring matter of the blood and of the bile is not admitted, the intimate relation of the two is not only suggested by the similarity of crystalline form, but by the relation determined between urobilin, bilirubin, and hæmoglobin. Urobilin is the coloring matter extracted from the urine in fever by Jaffé, and it has since been obtained from bilirubin by Maly, who has given it the name of hydrobilirubin. This hydrobilirubin has also been derived from hæmoglobin. According to Maly, this genetic relation between the coloring matter of the blood and bile, shown in the production of hydrobilirubin, is the only chemical evidence of the connection of the two pigments.

Hæmatoidin is to be regarded not only as directly derived from solutions of hæmoglobin, but as originating through the medium of indifferent cells. Langhans claims that this pigment is formed within movable cells which accumulate in great numbers in the vicinity of the blood-clot, and, in virtue of their amoeboid properties, take into themselves the extravasated corpuscles, entire or in fragments. The indifferent cell may become enlarged into a giant-cell, and then contain numbers of whole or disintegrated red corpuscles. In time these colored corpuscles and fragments become smaller, more glistening, and darker-colored, and eventually are transformed into granular or crystalline hæmatoidin. These granules may be set free by the fatty degeneration of the cell, or may be transferred within the cell to distant parts.

{92} The diffusion and absorption of a solution of hæmoglobin, and the formation of crystals of hæmatoidin from the same or through the medium of cells, are supplemented by an apparent inspissation and condensation of the hæmoglobin. The resulting dark-brown pigment may remain at the seat of the hemorrhage indefinitely, and may be accompanied with reddish-brown flakes, which, as shown by Kunkel, are composed of hydrated ferric oxide.

Another feature in the absorption of extravasated blood is to be found on examination of the nearest chain of lymphatic glands. These may be seen swollen, of a dark-red color, and homogeneous surface. In density and color, as well as shape, they suggest the small supplementary spleens so frequently met with. These glands owe their change in appearance to the presence of large numbers of unaltered red blood-corpuscles which have entered the lymphatics traversing the region of hemorrhage. Within the lymph-glands they undergo a metamorphosis similar to that taking place at the part from which they were transferred. In the course of weeks or months there remains in the place of extravasation simply pigment, either as crystals or granules. Such pigment may remain for years imbedded within the tissues, or it may become absorbed, no trace of the original disturbance remaining. Its removal may take place presumably through a local solution of the pigment or the transfer of the granules or crystals by means of wandering cells to the nearest lymphatic glands or to the more remote parts of the body. An eventual elimination may occur through the secretions, especially the urine or bile, or there may result a deposition and permanent retention of the granules.

The investigations of Langhans are especially interesting, as suggesting efficient means for the production of pigment by cells whose function is intimately connected with pigmentation, as the cells of the rete Malpighii, of the choroid, and of certain tumors. The observations of Gussenbauer, however, lead to the conclusion earlier advanced by Virchow, that pigment may be produced by the diffusion into cells, outside the vessels, of a solution of the pigment of the blood in the plasma of the latter. A precipitation of this dissolved pigment into granules is considered as eventually taking place.

The method of origin of pigment thus described applies only to those discolorations which are unquestionably due to the metamorphosis of the coloring matter of the blood. Examples are furnished not only by the extravasation of blood on a large scale, but also by the escape of red blood-corpuscles in small numbers. Such an escape takes place from the pulmonary vessels in chronic obstruction to the admission of blood into the left side of the heart. The resulting brown induration of the lungs owes its color to the metamorphosed blood-pigment which is present as hæmatoidin in the interstitial tissue of the lungs, as well as contained within amoeboid cells in the alveolar and bronchial cavities.

It is probable that a similar transformation of hæmoglobin takes place in the spleen and elsewhere in melanæmia. In this condition the black granules of pigment, although differing in color and form from hæmatoidin, contain iron, and have received the name melanin. These granules are either free in the blood or are contained within the white {93} blood-corpuscles. Their origin in the spleen is directly suggested by their frequent presence, often in considerable numbers, in the large, so-called splenic, corpuscles of the blood in the hepatic capillaries. Eventually, the pigment is found at more remote points in the circulation, and becomes fixed in the interstitial tissue of the various organs of the body.

The black pigment of the cells of melanotic tumors, also called melanin, is not to be directly traced to the hæmoglobin. Virchow early called attention to the absence of iron in such pigment. Ferrated and non-ferrated varieties of melanin are thus to be recognized, the term being used in the same way as hæmatoidin, indicative of a microscopical appearance. A still further complication in the composition of melanin is suggested by Kunkel, who has isolated a ferrated pigment from melanotic tumors. It shows, however, with the spectroscope, no relation to hæmatin, bilirubin, or hydrobilirubin. That its nature is similar to the normal pigment of the skin and choroid is suggested by the customary origin of the melanotic tumors in such pigmented tissues, and by the resemblance in appearance and reactions.

That pigment of the most varied sort may be introduced into the body from without, and may remain indefinitely in the organism, is sufficiently well known from the results of tattooing. What is essential in such cases is, that the pigment shall be finely divided and insoluble in the fluids of the body. The most important of such pigmentations are those taking place through inhalation into the lungs. The reception by this channel of particles of soot is so common that it is most exceptional for the lungs of an adult to be free from the bluish-black discoloration due to this agent. Particles of coal-dust presenting the details of vegetable structure are met with in the lungs of individuals exposed to an atmosphere charged with this material. The worker compelled to inhale the dust of iron eventually accumulates a store of this substance, the quantity of which is essentially dependent upon the length of exposure, the degree of impregnation of the atmosphere, and the insufficient nature of the protectives employed.