of normal undried bone without the separation of marrow or blood is given by Hoppe-Seyler thus:

It

may

be said roughly that two-thirds of the solids present in bone consist of inorganic matter and one-third of organic substances. Zalesky's analyses are as follows:

When a bone is soaked in acid (5 per cent. hydrochloric acid, or a saturated solution of picric acid, &c.), it is but little altered in appearance, but it is soft and flexible and has lost two-thirds of its weight; the inorganic salts have been dissolved out by the acid. The opposite process, the destruction of the organic matter, may be accomplished by heating the bone to a white heat; the organic matter is thus burnt away, and the bone then appears somewhat whiter than normal, and has lost one third of its weight.

The organic constituents of bone consist of

a. Ossein. This is the most abundant of the organic matters in bone. It is identical with collagen (see p. 471). By boiling with water it is converted into gelatin.

b. Elastin. This is present in small quantities only. Some of the perforating fibres and a thin membrane lining the Haversian canals, lacunæ, and canaliculi form the source of this substance in bone.1

c. Proteids and nuclein—from the cells.

d. Fat. This is always present in small quantities, even after the removal of all connective tissue and marrow.

The inorganic constituents of bone are—

a. Calcium phosphate-Ca,(PO). This is the most abundant of the mineral matters present in bone.

b. Calcium carbonate-CaCO3. c. Calcium chloride-CaCl.

d. Calcium fluoride-CaFl.

e. Magnesium phosphate-Mg (PO4)2.

f. Small quantities of sulphates and chlorides.

This membrane lining the Haversian canals was supposed by Brösicke to be composed of keratin; but H. E. Smith (Zeit. Biol. xix. 469) has conclusively shown that this is not

the case.

Numerous analyses of the bones of different animals are given in full in Hoppe-Seyler's Physiol. Chemie' (p. 105). The total amount and relative proportion of the inorganic constituents is, however, very constant in different animals, and the average from the analyses of Heintz, Recklinghausen, and Zalesky (quoted by Hoppe-Seyler) is as follows:

:

(The numbers represent percentages of the total ash)

From his own numbers Zalesky has calculated the probable composition of the mineral constituents of bone.

Calcium in combination with fluorine, chlorine, &c.

Hoppe-Seyler believes that the characteristic inorganic ingredient of bone, dentine, and enamel is one which has the same constitution as the mineral apatite. The formula for apatite is :

Ca,,Fl(PO)

In another variety chlorine takes the place of the fluorine:

Ca,,Cl(PO1)

Very small quantities of these compounds, however, occur in bone; the chief compound is one built on the same plan, in which the radicle CO, takes the place of the Fl, or Cl.:

CaCO3(PO4)

In other words, if such a compound exists, it is a combination of three molecules of calcium phosphate with one of calcium carbonate:

During the deposition of earthy matter in tissues like bone and shell the deposit occurs, not in crystals, but in the form of globules and granules. In 1857 George Rainey showed that certain crystalline substances when deposited in viscous solutions assume globular and cell-like forms. These globular bodies are

1 A large number of other analyses will be found in Gamgee's Physiol. Chem. pp. 278-280, quoted from Frémy, Ann. de Chim. et de Physique (3), xliii. 47-107. The general result is approximately the same as that given above. In contrast with what is found in true bone, the analysis of the calcified cartilage of the ray may be given: ash per cent. 3000; calcium phosphate 277; magnesium phosphate trace; calcium carbonate 43. Fossil bones also analysed by Frémy show a smaller percentage of organic matter than recent bones; they yield gelatin on boiling.

2 Rainey, Quart. Journ. Micros. Science, 1858. See also Ord, On the Influence of Colloids on Crystalline Form, London, 1879.

termed calcosphærites by Harting. Ord has shown also how in urine the presence of albumin and other colloid substances influences the crystalline form of urinary sediments, causing the angles of the crystals to be rounded, the molecules arranging themselves not in straight lines, but with a curvilinear disposition.

DENTINE, ENAMEL, AND OTHER CALCAREOUS AND

SKELETAL STRUCTURES

Dentine consists, like bone, of water (10 per cent.) and solids (90 per cent.). The solids are organic and inorganic. The organic solids are rather less abundant than in bone; they consist of collagen and elastin; the latter is derived from the lining of the dentinal tubules. The inorganic solids are like those in bone. From Aeby's analyses, Hoppe-Seyler calculates that the solid matter of dentine is composed of the following constituents :

Enamel. This is the hardest tissue in the body; in the adult it contains 95-97 per cent. of mineral matter, in the infant 77-84 per cent. Hoppe-Seyler's quantitative analyses give the following mean result:

The inorganic matter thus resembles that in bone and dentine. The organic matter does not yield gelatin; this is interesting in view of the fact that enamel is not of a connective-tissue origin, but is epithelial (epiblastic).

Crusta petrosa, or cement.-This is simply bone both from a histological and chemical point of view.

Scales of fishes.-The scales differ in structure in different groups of fishes: in the Elasmobranchs they are composed of true dentine; the Ganoid scales are covered with a brightly polished plate of enamel; this is very rarely found in the Teleostean fishes, in which the scales are bony; the Dipnoi have horny scales.

Pearls from oysters were analysed and found to consist of calcium carbonate 91-72, animal matter 594, and water 2.23 per cent. They are not soluble in vinegar unless pulverised (Harley).1

Tortoise-shell.-The shield of the tortoise is firmly fixed to the skeleton: it consists of a layer of epidermis or tortoise-shell composed of horny matter or keratin and a layer of bone beneath.

1 Proc. Roy. Soc. xliii. 461.

The exo-skeleton of the armadillo is composed of bony plates.

Egg-shells (see Eggs). Shells of invertebrates (see p. 454).

Otoliths.-These concretions, formed in various parts of the auditory organs of all animals, consist chiefly of calcium carbonate in a crystalline form; the

FIG. 77.-Crystals of Calcium Carbonate from an otolith, consisting of small thick columnar crystals, combinations of rhombohedra, and hexagonal prisms.

crystals are imbedded in mucus.'

Phleboliths.- Phleboliths or venous calculi have a tendency to form in veins in which, from dilatation of the coats, the circulation is abnormally slow, as in the veins of the prostate and bladder, and in varicose veins anywhere. They commence, no doubt, as deposits of fibrin, and to this the less soluble salts of the blood adhere, chiefly phosphate of calcium, and in less quantity the sulphates of calcium and potassium. Calcareous deposits in atheromatous arteries have a similar composition.

Brain-sand. The gritty particles found in the pineal body and in the choroid plexuses are composed of earthy matter (phosphate and carbonate of lime, with a little phosphate of magnesia and ammonia) mixed with organic matter. This substance is not a product of disease, but is present at all ages, and even in the foetus.

FIG. 78.-Corpora amylacea from human brain.

Its amount increases with age."

The corpora amylacea found in the follicles of the pineal gland and pituitary body are coloured brown with iodine, and blue with iodine and sulphuric acid. They are non-nitrogenous, but as they do not yield sugar on treatment with boiling dilute sulphuric acid they are probably not carbohydrate in nature. A colloid substance like that in the thyroid vesicles is sometimes found in the alveoli of the anterior lobe of the pituitary body.

THE FAT OF BONE MARROW

C. Eylert described in ox-bone marrow a new fatty acid melting at 72-5° C., of the formula C2H2O2, which he called medullic acid. As nothing further was discovered as to the properties and salts of this acid, P. Mohr reinvestigated the matter. The fatty acids were separated in the usual way, and the hypothetical acid was found to be nothing but stearic acid; the acids in the marrow fat being present in the following proportions: palmitic acid, 22; stearic acid, 10; and oleic acid, 63 per cent.

1 Dahnhardt, Endolymphe und Perilymphe,' Arbeiten d. Kieler physiol. Instit. p. 186. Barruel, 1838, quoted by Dahnhardt.

2 Quain's Anat. ii. 327.

3 Hoppe-Seyler, Physiol. Chem. p. 689.

4 Wittstein's Vierteljahrschrift f. prakt. Pharm. ix. 330.

5 Zeit. Physiol. Chem. xiv. (1890) 390.

CHAPTER XXIII

THE CONNECTIVE TISSUES IN DISEASE

INTRODUCTORY

THE diseases in which the connective tissues are involved are numerous, but our knowledge of pathological chemistry in this direction is limited.

In actual post-mortem experience chemical methods are comparatively seldom resorted to, as a naked eye or microscopical examination of the organs gives the observer, as a rule, sufficiently complete information of the morbid condition present.

Many of the morbid conditions affecting connective tissue differ from the normal condition in degree rather than in kind. Thus there may be excess of white fibres, producing what is known as fibroid degeneration, cirrhosis, or sclerosis; or excess of fat may occur as in general obesity; in this condition widespread fatty degeneration of heart fibres, kidney, liver, &c. may occur in association with increase in the amount of adipose tissue. In another class of cases hypertrophy may be not general, but localised, forming what is known as a tumour ; thus there are bony tumours (exostoses), cartilaginous tumours (enchrondromata), fatty tumours (lipomata), tumours composed of jellylike connective tissue, as in certain forms of nasal polypi, and so forth. Tumours of this kind are composed of tissue, showing practically no difference from that normally present in the body, and when removed show little or no tendency to recur. There are other new growths of connective-tissue origin which are malignant; these constitute the numerous class of the sarcomata. A sarcoma, speaking roughly, is composed of embryonic connective tissue in which the cellular elements are especially numerous and active; and malignancy runs parallel to the activity and rate of growth of these cells. One especially malignant form of sarcoma is that known as melanotic sarcoma. The pigment melanin separated from the tumour has been the subject of several chemical investigations, a brief résumé of which will be given.

Another disease which will demand special notice is that known as myxedema; and in connection with bone diseases we shall have to

K K