canals are probably also present in the matrix, uniting the lacunæ, through which lymph plasma circulates (vid. researches of Flesch, Budge, Solger (88, II), van der Stricht (87), etc.).

To obtain chondrin, a piece of cartilage matrix is placed in a tube containing water. This is hermetically closed and heated to 120° C., after which it is opened and the fluid filtered and treated with alcohol. A precipitate of chondrin is the result. This substance is insoluble in cold water, alcohol, and ether, but soluble in hot water, although, on cooling, it gelatinizes. In contrast to gelatin, chondrin is precipitated by acetic acid. This precipitate does not redissolve in an excess of this acid but disappears in an excess of certain mineral acids.

6. BONE.

(a) Structure of Bone.-Bone nearly always develops from a connective-tissue foundation, even where it occurs in places formerly occupied by cartilage.

The inorganic substance of bone is deposited in or between the fibers of connective tissue, while the cells of the latter are transformed into bone-cells.

As in connective tissue, so also in bone, the ground-substance is fibrous. Between the fibers remain uncalcified cells, bone-cells, each of which rests in a cavity of the matrix-lacuna.

Primarily, bone consists of a single thin lamella, its later complicated structure being produced by the formation of new lamellæ in apposition to the first. During its development the bone becomes vascularized, and the vessels are inclosed in especially formed canals known as vascular or Haversian canals.

The bone-cells have processes that probably anastomose, and that lie in special canals known as bone canaliculi. Whether, in man, all the processes of bone-cells anastomose is still an open question.

The appearance presented by a transverse section of the shaft of a long bone is as follows: In the center is a large marrow cavity, and at the periphery the bone is covered by a dense connectivetissue membrane, the periosteum. In the new-born and in young individuals the periosteum is composed of three layers-an outer layer, consisting mainly of rather coarse, white fibrous-tissue bundles that blend with the surrounding connective tissue; a middle fibro-elastic layer, in which the elastic tissue greatly predominates; and an inner layer, the osteogenetic layer, vascular and rich in cellular elements, containing only a few smaller bundles of white fibrous tissue. In the adult the osteogenetic layer has practically disappeared, leaving only here and there a few of the cells of the layer, while the fibro-elastic layer is correspondingly thicker (Schulz, 96). A large number of Haversian canals containing blood-vessels, seen mostly in transverse section, are found in compact bone-substance.

Lamellæ of bone are plainly visible throughout the ground-substance, and are arranged in the following general systems:

First, there is a set of bone lamellæ running parallel to the external surface of the bone, while another set is similarly arranged around the marrow cavity. These are the so-called fundamental, or outer and inner circumferential lamella (known also as periosteal and marrow lamella). Around the Haversian canals are the concentrically arranged lamellæ, forming systems of Haversian or concentric lamella. Besides the systems already mentioned, there are found interstitial or ground lamella wedged in between the Haversian

Fig. 76.- Longitudinal section Figs. 77 and 78.-Lamellæ seen from the surface; through a lamellar system.

a, Primitive fibrils and fibril-bundles; c, bone-corpuscles with bone-cells; d, bone canaliculi.

or concentric systems of lamellæ. Some authors group the interstitial lamellæ with the systems of fundamental lamellæ.

Lying scattered between the lamellæ are found spaces known as bone corpuscles (Virchow) or lacuna. These are present in all the lamellar systems. It is very probable that all the lacunæ are in more or less direct communication with each other by means of fine canals called canaliculi (1.1 p to 1.8 μ in diameter). It can be demonstrated without difficulty that the lacunæ of a single lamellar system communicate not only with each other, but also with those of

adjacent systems. In the lamellæ adjoining the periosteum and marrow cavity the canaliculi end respectively in the subperiosteal tissue and in the marrow cavity. The canaliculi of the Haversian lamellæ empty into the Haversian canals.

Fig. 79.-Segment of a transversely ground section from the shaft of a long bone, showing all the lamellar systems. Metacarpus of man; X 56. Technic No. 152.

The lamellæ of bone are composed of fine white fibrous-tissue fibrils, embedded in a ground-substance, in which they are arranged in layers, superimposed in such a way that the fibrils in the several layers cross at about a right angle, forming an angle of 45° with

the long axis of the Haversian canal. It is as yet undecided whether the mineral salts (phosphate and carbonate of lime, sodium chlorid, magnesium salts, etc.) are deposited in the ground-substance (v. Ebner) or in the fibrillæ (Kölliker). The lacunæ (13 to 31 μ long, 6 to 15 wide, and 4 to 9 thick) have, in common with the canaliculi, walls which present a greater resistance to the action of strong acids than the rest of the solid bone-substance. In each lacuna there is found a bone-cell, the nucleated body of which practically fills the lacuna, while its processes extend out into the canaliculi.

The Haversian canals contain blood-vessels, either an artery or a vein or both. Between the vessels and the walls of the canals are perivascular spaces bounded by endothelial cells, resting on the adventitious coats of the vessels and the sides of the canals. Into these spaces empty the canaliculi of the Haversian system. Lymphspaces beneath the periosteum and at the periphery of the marrow

cavity communicate directly with the canaliculi of the circumferential systems.

All the lacunæ and canaliculi should be thought of as filled by lymph plasma which circulates throughout, bathing the bone-cells and their processes. The formed elements of the lymph are probably too large to force their way through the very small canaliculi. The plasma current probably flows from the periosteal and marrow regions toward the Haversian canals.

Between the lamellæ are bundles of fibers (some of which are calcified), which can be demonstrated by heating the bone, or in decalcified preparations on staining by certain methods. These are the so-called fibers of Sharpey; in the adult they contain elastic fibers.

In the circumferential lamellæ are found canals, not surrounded by concentric lamellæ, which convey blood-vessels from the periosteum to the Haversian canals. These are called Volkmann's canals.

The structure of bone-marrow will be discussed with the bloodforming organs.

(b) Development of Bone.-Nearly all the bones of the adult body are, in the earlier stages of embryonic life, preformed in embryonic cartilage. As development proceeds, this embryonic cartilage assumes the character of hyaline cartilage, its cells becoming vesicular, and probably disappearing. In the matrix, however, there are formed spaces that are soon occupied by cells and vessels which grow in from a fibrous-tissue membrane (the future periosteum) surrounding the cartilage fundaments of the bones. These cells deposit a bone matrix in the cartilage spaces. Bone developed in this manner is known as endochondral or intracartilaginous bone. In certain bones-namely, those of the vault of the skull and nearly all the bones of the face-there is no preformation in cartilage, these bones being developed from a connective-tissue foundation. They are known as intramembranous bones. As will become evident upon further discussion of the subject, the formation of fibrous-tissue bone (intramembranous) is not confined to bones not preformed in cartilage. In bones preformed in cartilage, fibrous-tissue bone develops from the connective-tissue membrane surrounding the cartilage fundaments, the two types of bone-development going on simultaneously in such bones. Attention may further be drawn to the fact that nearly all endochondral bone is absorbed, so that the greater portion of all adult bone, even that preformed in cartilage, is developed from a foundation of fibrous tissue. The two modes of ossification-endochondral or intracartilaginous and intramembranous—even though appearing simultaneously in the majority of bones, will, for the sake of clearness, be discussed separately.

I. Endochondral Bone-development. The cartilage that forms the fundaments of the bones preformed in cartilage has at first the appearance of embryonic cartilage, consisting largely of cells with a small amount of intercellular matrix. These fundaments are surrounded by a fibrocellular membrane-the perichondrium. Ossification is initiated by certain structural changes in the embryonic cartilage, in one or several circumscribed areas, known as centers of ossification. In the long bones a center of ossification appears in the middle of the future diaphysis. In this region the intercellular matrix increases in amount and the cells in size; thus the embryonic cartilage assumes the character of hyaline cartilage. This is followed by a further increase in the size of the cartilage-cells, at the expense of the thinner partitions of matrix separating neighboring cells, while at the same time lime granules are deposited in the matrix remaining. During this stage the cells appear first vesicular, distending their capsules, then shrunken, only partly filling the enlarged lacunæ. They stain less deeply, and their nuclei show degenerative changes. The center of ossification, in the middle of which these changes are most pronounced, is surrounded by a zone in which these structural changes are not so far advanced and which has the appearance at its periphery of hyaline cartilage.

Simultaneously with these changes in the cartilage, a thin layer