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Originally appearing in Volume V20, Page 924 of the 1911 Encyclopedia Britannica.
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OTHER TISSUE PRODUCTS Mucoid.—In many pathological conditions we have degenerative products of various kinds formed in the tissues. These substances may be formed in the cells and given out as a secretion, or they may be formed by an intercellular transformation. In the mucinoid conditions, usually termed " mucoid " and " colloid " degenerations, we have closely allied substances which, like the normal mucins of the body, belong to the glucoproteids, and have in common similar physical characters. There is neither any absolute difference nor a constancy in their chemical reactions, and there can be brought about a transition of the " colloid " material into the " mucoid," or conversely. By mucoid is understood a soft gelatinous substance containing mucin, or pseudomucin, which is normally secreted by the epithelial cells of both the mucous membranes and glands. In certain pathological conditions an excessive formation and discharge of such material is usually associated with catarrhal changes in the epithelium. The desquamated cells containing this jelly-like substance become disorganized and blend with the secretion. Should this take place into a closed gland space it will give rise to cysts, which may attain a great size, as is seen in the ovarian adenomata. In some of the adenoid cancers of the alimentary tract this mucoid material is formed by the epithelial cells from which it flows out and infiltrates thesurrounding tissues; both the cells and tissues appear to be transformed into this gelatinous substance, forming the so-called " colloid cancer " (fig. 42, Pl. IV.). The connective tissue is supplied normally with a certain amount of these mucinoid substances, no doubt acting as a lubricant. In many pathological conditions this tissue is commonly found to undergo mucoid or myxomatous degeneration, which is regarded as a reversion to a closely similar type—that of foetal connective tissue (fig. 43, Pl. IV). These changes are found in senile wasting, in metaplasia of cartilage, in many tumours, especially mixed growths of the parotid gland and testicle, and in various inflam-, matory granulation ulcers. In the wasting of the thyroid gland in myxoedema, or when the gland is completely removed by operatioh, myxomatous areas are found in the subcutaneous tissue of the skin, nerve-sheaths, &c. Colloid.—T his term is usually applied to a semi-solid substance of homogeneous and gelatinous consistence, which results partly from excretion and partly from degeneration of cellular structures, more particularly of the epithelial type. These cells become swollen by this translucent substance and are thrown off into the space where they become fused together, forming colloid masses. This substance differs from the mucins by being precipitated by tannic acid but not by acetic acid, and being endowed with a higher proportion of sulphur. In the normal thyroid there is formed and stored up in the spaces this colloid material. The enlarged cystic goitres show, in the distended vesicles, an abnormal formation and retention of this substance (fig. 44, P1. V.). Its character is readily changed by the abnormal activities which take place in these glands during some of the acute fevers; the semi-solid consistence may become mucoid or even fluid. Serous degeneration is met with in epithelial cells in inflammatory conditions and following on burns. The vitality of these cells being altered there is imbibition and accumulation of watery fluid in their cytoplasm, causing swelling and vacuolation of the cells. The bursting of several of these altered cells is the method by which the skin vesicles are formed in certain conditions. Glycogen is formed by the action of a ferment on the carbohydrates—the starches being converted into sugars. The sugars are taken up from the circulation and stored in a less soluble form—known as " animal starch "—in the liver and muscle cells; they play an important part in the normal metabolism of the body. The significance of glycogen in large amounts, or of its absence from the tissues in pathological conditions, is not clearly understood. It is said to be increased in saccharine diabetes and to be greatly diminished in starvation and wasting diseases. Fat.—Fatty accumulations in the tissues of the body are found in health and in pathological conditions; these are usually recognized and described as fatty infiltrations and fatty degenerations, but there are intermediate conditions which make it difficult to separate sharply these processes. The fatty accumulations known as infiltrations (figs. 45 and 46, Pl. V.) are undoubtedly the result of excessive ingestion of food material containing more neutral fats than the normal tissues can oxidize, or these, as a result of defective removal owing to enfeebled oxidative capacities on the part of the tissues, become stored up in the tissues. In acute and chronic alcoholism, in phthisis, and in other diseases this fatty condition may be very extreme, and is commonly found in association with other tissue changes, so that probably we should look on these changes as a degeneration. Adiposity or obesity occurs when we have an excessive amount of fat stored in the normal connective-tissue areas of adipose tissue. It may be caused by various conditions, e.g. over-nutrition with lack of muscular energy, beer-drinking, castration, lactation, disturbed metabolism, some forms of insanity, and may follow on some fevers. Fatty degeneration is a retrogressive change associated with the deposit of fatty granules or globules in the cytoplasm, and is caused by disorganized cellular activity (figs. 26 and 27, P1. II.). It is frequently found associated with, or as a sequel to, cloudy swelling in intense or prolonged toxic conditions. Over and above the bacterial intoxications we have a very extreme degree of fatty degeneration, widely distributed throughout the tissues, 922 which is produced by certain organic and inorganic poisons; it is seen especially in phosphorus and chloroform poisoning. The changes are also common in pernicious anaemia, advanced chlorosis, cachexias, and in the later stages of starvation. In diabetes mellitus, in which there is marked derangement in metabolism, extreme fatty changes are occasionally found in the organs, and the blood may be loaded with fat globules. This lipoemic condition may cause embolism, the plugging especially occurring in the lung capillaries. Fatty degeneration is common to all dead or decaying tissues in the body, and may be followed by calcification. Autolysis is a disintegration of dead tissues brought about by the action of their own ferments, while degeneration takes place in the still living cell. The study of autolytic phenomena which closely simulates the changes seen in the degenerating cell has thrown much light on these degenerative processes. These conditions may be purely physiological, e.g. in the mammary gland during lactation or in sebaceous glands, caused by increased functional activity. It may follow a diminished functional activity, as in the atrophying thymus gland and in the muscle cells of the uterus after parturition. Any of the abnormal conditions that bring about general or local defective nutrition is an important factor in producing fatty degeneration. The part played by fats and closely allied compounds in normal and abnormal metabolism need not here be discussed, as the subject is too complex and the views on it are conflicting. It will be sufficient to state briefly what appears to be the result of recent investigation. The neutral fats are composed of fatty acids and glycerin. In the physiological process of intestinal digestion, the precursors of such fats are split up into these two radicles. The free fatty acid radicle then unites with an alkali, and becomes transformed into a soluble soap which is then readily absorbed in this fluid condition by the epithelial cells of the mucous membrane. There it is acted on by ferments (ii aces) and converted into neutral fat, which may remain in the cell as such. By the reverse action on the part of the same ferments in the cell, these neutral fats may be redissolved and pass into the lacteals. Many cells throughout the body contain this ferment. The soluble soaps which are probably conveyed by the blood will be quickly taken up by such cells, synthetized into neutral fats, and stored in a non-diffusible form till required. The fat in this condition is readily recognized by the usual microchemical and staining reactions. As fat is a food element essential to the carrying out of the vital energies of the cell, a certain amount of fatty matter must be present, in a form, however, unrecognizable by our present microchemical and staining methods. Some investigators hold that the soaps may become combined with albumin, and that on becoming incorporated with the cytoplasm they can no longer be distinguished as fat. If from some cause the cell be damaged in such a way as to produce disintegration of the cytoplasm, there will be a breaking down of that combination, so that the fat will be set free from the complex protein molecule in which it was combined as a soap-albumin, and will become demonstrable by the usual methods as small droplets of oil. This splitting up of the fats previously combined with albumin in the cell by the action of natural ferments—lipases—and the setting free of the fats under the influence of toxins represent the normal and the pathological process in the production of so-called fatty degeneration. Calcification.—Calcification and calcareous deposits are extremely common in many pathological conditions. There are few of the connective tissues of the body which may not become affected with deposits of calcareous salts (fig. 47, Pl. V.). This condition is not so frequently seen in the more highly differentiated cells, but may follow necrosis of secreting cells, as is found in the kidney, in corrosive sublimate poisoning and in chronic nephritis. These conditions are quite distinct from the normal process of ossification as is seen in bone. Many theories have been advanced to explain these processes, and recently the subject has received considerable attention. The old idea of the circulating blood being supersaturated with lime salts which in some way had first become liberated from atrophying bones, and then deposited, to form calcified areas in different tissues will have to be given up, as there is no evidence that this " metastatic " calcification ever takes place. In all probability no excess of soluble lime salts in the blood or lymph can ever be deposited in healthy living tissues At the present day both experimental and histological investigations seem to indicate that in the process of calcification there is a combination of the organic substances present in degenerated tissues, or in tissues of low vitality, with the lime salts of the body. From whatever cause the tissues become disorganized and undergo fatty degeneration, the fatty acids may become liberated and combine with the alkalies to form potash and soda soaps. The potash and soda is then gradually replaced by calcium to form an insoluble calcium soap. The interaction between the soaps, the phosphates and the carbonates which are brought by the blood and lymph to the part results in the weaker fatty acids being re-placed by phosphoric and carbonic acid, and thus in the formation of highly insoluble calcium phosphate and carbonate deposits in the disorganized tissues. Pathological Pigmentation.—These pigmentary changes found in abnormal conditions are usually classified under (I) Albuminoid, (2) Haematogenous, (3) Extraneous. r. The normal animal pigments and closely allied pigments are usually found in the skin, hair, eye, supra-renal glands, and in certain nerve cells. These represent the albuminoid series, and are probably elaborated by the cells from albuminous substances through the influence of specific ferments, This pigment is usually intracellular, but may be found lying free in the intercellular substance, and is generally in the form of fine granules of a yellowish-brown or brown-black colour. In the, condition known as albinism there is a congenital deficiency or entire absence of pigment. Trophic and nervous conditions sometimes cause localized deficiency of pigment which produces white areas in the skin. Excessive pigmentation of tissue cells (fig. 48, Pl. V.) is seen in old age, and usually in an accompaniment of certain atrophic processes and functional disorders. Certain degenerative changes in the supra-renal glands may lead to Addison's disease, which is characterized by an excessive pigmentary condition of the skin and mucous membranes. This melanin pigment is found in certain tumour growths, pigmented moles of the skin, and especially in melanatic sarcomata (fig. 49, Pl. V.) and cancer. The action of the sun's rays stimulates the cells of the skin to increase the pigment as a protection to the underlying tissues, e.g. summer bronzing, " freckles," and the skin of the negro. The coloured fats, or lipochromes, are found normally in some of the cells of the internal organs, and under certain pathological conditions. This pigment is of a light yellow colour, and contains a fatty substance that reacts to the fat-staining reagents. Little is known regarding this class of pigment. 2. Haematogenous pigments are derived from the haemoglobin of the red blood corpuscles. These corpuscles may break down in the blood vessels, and their colouring material (haemoglobin) is set free in the serum. But their disintegration is more commonly brought about by " phagocytosis " on the part of the phagocytic cells in the different organs concerned with the function of haemolysis, i.e. the liver, spleen, haemolymph glands and other tissues. The 'haemoglobin may be transformed into haematoidin, a pigment that does not contain iron, or into a pigment which does contain iron, haemosiderin. The haematoidin pigment may vary in colour from yellowish or orange-red to a ruby-red, and forms granular masses, rhombic prisms or acicular crystals. It can be formed independently of cell activity, nor does it require oxygen. These crystals are extremely resistant to absorption, are found in old blood clots, and have been known to persist in old cerebral haemorrhages after many years. Haematoidin in normal metabolism is largely excreted by the liver in the form of bilirubin. Haemosiderin, an iron-containing pigment (probably an hydrated ferrous oxide), is found in more or less loose combination with protein substances in an amorphous form as brownish or black granules. Cellular activity and oxygen appear to be essential for its development; it is found usually in the cells of certain organs, or it may be deposited in the intercellular tissues. Haemosiderin in the normal process of haemolysis is stored up in the cells of certain organs until required by the organism for the formation of fresh haemoglobin. In diseases where haemolysis is extreme, particularly in pernicious anaemia, there are relatively large quantities occasionally as much as ten times the normal amount of haemosiderin deposited in the liver. In hepatogenous pigmentation (icterus or jaundice) we have the iron-free pigment modified and transformed by the action of the liver cells into bile pigment (bilirubin). If the discharge of this pigment from the liver by the normal channels be prevented, as by obstruction of the main bile ducts, the bile will accumulate until it regurgitates or is absorbed into the lymph and blood vessels, and is carried in a soluble state throughout the tissues, thus producing a general staining—an essential characteristic of jaundice. 3. In extraneous pigmentation we have coloured substances either in a solid or fluid state, gaining entrance into the organism and accumulating in certain tissues. The channels of entrance are usually by the respiratory or the alimentary tract, also by the skin. Pneumonokoniosis is due to the inhalation of minute particles of various substances—such as coal, stone, iron, steel, &c. These foreign particles settle on the lining membranes, and, by the activity of certain cells (fig. 5o, Pl. V. and fig. 30, Pl. III.), are carried into the tissues, where they set up chronic irritation of a more or less serious nature according to the nature of the inhaled particles. Certain metallic poisons give rise to pigmentation of the tissues, e.g. in the blue line on the gums around the roots of the teeth due to the formation of lead sulphide, or in chronic lead poisoning, where absorption may have taken place through the digestive tract, or, in the case of workers in lead and lead paints, through the skin. Prolonged ingestion of arsenic may cause pigmentary changes in the skin. If silver nitrate salts be administered for a long period as a medication, the skin that is exposed to light becomes of a bluish-grey colour, which is extremely persistent. These soluble salts combine with the albumins in the body, and are deposited as minute granules of silver albuminate in the connective tissue of the skin papillae, serous membranes, the intima of arteries and the kidney. This condition is known as argyria. Various coloured pigments may be deposited in the tissues through damaged skin surface—note, for example, the well-known practice of " tattooing." Many workers following certain occupations show pigmented scars due to the penetration of carbon and other pigments from superficial wounds caused by gunpowder, explosions, &c. Hyaline.—This term has been applied to several of the trans-parent homogeneous appearances found in pathological conditions. It is now commonly used to indicate the transparent homogeneous structureless swellings which are found affecting the smaller arteries and the capillaries. The delicate connective-tissue fibrillae of the inner coat of the arterioles are usually first and most affected. The fibrils of the outer coat also show the change to a less extent, while the degeneration very rarely spreads to the middle coat. This swelling of the walls may partly or completely occlude the lumen of the vessels. Hyaline degeneration is found in certain acute infective conditions; the toxins specially act on these connective-tissue cell elements. It also seems to be brought about by chronic toxaemias, e.g. in subacute and chronic Bright's disease, lead poisoning and other obscure conditions. The hyaline material, unlike the amyloid, does not give the metachromatic staining reactions with methylene-violet or iodine. The chemical constitution is not certain. The substance is very resistant to the action of chemical reagents, to digestion, and possibly belongs to the glyco-proteids. Amyloid.—The wax-like or amyloid substance has a certain resemblance to the colloid, mucoid and hyaline. It has a firm gelatinous consistence and wax-like lustre, and, microscopically, is found to be homogeneous and structureless, with a trans-lucency like that of ground-glass. Watery solution of iodine imparts to it a deep mahogany-brown colour; iodine and sulphuric acid occasionally, but not always, an azure-blue, methyl-violet, a brilliant rose-pink and methyl-green gives a reaction very much like that of methyl-violet, but not so vivid. The reaction with iodine is seen best by direct light; the reactions with the other substances are visible only by transmitted light. The name "amyloid " was applied to it by Virchow on account of the blue reaction which it gives occasionally with iodine and sulphuric acid, resembling that given with vegetable cellulose. It is now known to have nothing in common with vegetable cellulose, but is regarded as one of the many albuminoid substances existing in the body under pathological conditions. Virchow's conjecture as to the starchy nature of the substance was disproved by Friedrich and Kekule, who confirmed Professor Miller's previous finding as to its albuminous or protein nature. Oddi in 1844 isolated from the amyloid liver a substancecomposition C1sH2sNa2NSO17. Krawkow in 1897 clearly demonstrated it to be a proteid in firm combination with chrondroitin-sulphuric acid. As probably the protein constituent varies in the different organs, one infers that this will account for the varying results got from the analysis of the substance obtained from different organs in such cases. This amyloid substance is slowly and imperfectly digested by pepsin—digestion being more complete with trypsin and by autolytic enzymes. There is no evidence that this material is brought by the circulating blood and infiltrates the tissues. It is believed rather that the condition is due to deleterious toxic substances which act for prolonged periods on the tissue elements and so alter their histon proteins that they combine in situ with other protein substances which are brought by the blood or lymph. Amyloid develops in various organs and tissues and is commonly associated with chronic phthisis, tubercular disease of bone and joints, and syphilis (congenital and acquired). It is known to occur in rheumatism, and has been described in connexion with a few other diseases. A number of interesting experiments, designed to test the relationship between the condition of suppuration and the production of amyloid, have been made of late years. The animal most suitable for experimenting upon is the fowl, but other animals have been found to react. Thus Krawkow and Nowak, employing the frequent subcutaneous injection of the usual organ-isms of suppuration, have induced in the fowl the deposition within the tissues of a homogeneous substance giving the colour reactions of true amyloid. When hardened in spirit, however, the greater part of this experimental amyloid in the fowl vanishes, and the reactions are not forthcoming. They were unable to verify any direct connexion between its production and the organism of tubercle. These observations have been verified in the rabbit, mouse, fowl, guinea-pig and cat by Davidsohn, occasionally in the dog by Lubarsch; and confirmatory observations have also been made by Czerny and Maximoff. Lubarsch succeeded in inducing it merely by the subcutaneous injection of turpentine, which. produces its result, it is said, by exciting an abscess. Nowak, however, found later that he could generate it where the turpentine failed to induce suppuration; he believes that it may arise quite apart from the influence of the organisms of suppuration, that it is not a biological product of the micro-organisms of disease, and also that it has nothing to do with emaciation. It is a retrogressive process producing characteristic changes in the fine connective-tissue fibrils. The change appears to begin in the fibrils which lie between the circular muscle fibres of the middle coat of the smaller arterioles and extends both backwards and forwards along the vessels. It spreads forwards, affecting the supporting fibres out-side the epithelium of the capillaries, and then passes to the connective-tissue fibrils of the veins. The secreting cells never show this change, although they may become atrophied or destroyed by the pressure and the disturbance of nutrition brought about by the swollen condition of the capillary walls. The circulation is little interfered with, although the walls of the vessels are much thickened by the amyloid material (fig. 51, Pl. V.). Amyloid Bodies.—These are peculiar bodies which are found in the prostate, in the central nervous system, in the lung, and in other localities, and which get their name from being very like starch-corpuscles, and from giving certain colour reactions closely resembling those of vegetable cellulose or even starch itself. They are minute structures having a round or oval shape, concentrically striated, and frequently showing a small nucleus-like body or cavity in their centre. Iodine gives usually a dark brown reaction, some-times a deep blue; iodine and sulphuric acid almost always call forth an intense deep blue reaction; and methyl-violet usually a brilliant pink, quite resembling that of true amyloid. They are probably a degeneration-product of cells. Spurious Amyloid.—If a healthy spinal cord be hung up in spirit for a matter of six months or more, a glassy substance develops within it quite like true amyloid. It further resembles true amyloid which Schmiedeberg had previously obtained from cartilage and named " chondroitinic-sulphuric acid " (Chondroitinschwefelsaure). It also occurs in bones and elastic tissue, but is not present in the normal human liver. Oddi does not regard it as the essential constituent of amyloid, chiefly because the colour reactions are forthcoming in the residuum after the substance has been removed, while the substance itself does not give these reactions. Quite likely the amyloid may be a combination of the substance with a proteid. The soda combination of the acid as obtained from the nasal cartilage of pigs had the in giving all its colour reactions. The reaction with methyl-violet, however, differs from that with true amyloid in being evanescent.
End of Article: OTHER TISSUE
OTHMAN (c. 574-656)

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