COLUMBIA LIBRARIES OFFSITE HX64099369 QM551 .P61 1897 Textbook- RECAP msm IB i ! SB | HsHBbSIH r<: ■HI fc; 1 H II 1 1 ' ■' , : ' ' III* h| a ffia ■ .. ■ ! ; i§i§ili 1 1 HBI #£?&'] I i! HR^fll 1 ■ ■V-'-, :■;-; | B ; i '•■"< \ j ■ ft rt5iV •p£/ /^7 Columbia - Voluntary-muscle fibres 62 74. Diagram of arrangement of contractile substance 64 75. Muscle-fibres, showing Cohnheim's fields 65 76. Voluntary muscle in transverse section 65 77. Branched fibres of voluntary muscle 65 78. Heart-muscle, showing branched fibres 66 79. Heart-muscle fibres in section 67 80. Injected voluntary muscle 67 81. Developing voluntary muscle 68 82. Nerve-cell from cerebral cortex 70 83. Nerve-cell isolated from spinal cord 71 84. Nerve-cell of first type 72 85. Nerve-cell of second type 72 86. Basket-work around Purkinje's cell 72 87. Nerve-cell from sympathetic [Retzius) 73 88. Medullated nerve-fibres ... 74 89. Ultimate fibrillar of axis-cylinder 74 90. Medullated nerve-fibres treated with osmic acid . 75 91. Silvered nerve-fibres 75 92. Non-medullated nerve-fibres 76 93. Section of nerve-trunk 77 94. Section of single funiculus of nerve 78 95. Supporting tissues of nerve-centres 79 96. Longitudinal section of spinal ganglion 80 97. Section of portion of spinal ganglion 80 98. Ganglion nerve-cell, showing spiral fibre {Schiefferdecker) 81 LIST OF ILLUSTRATIONS. xv FIG. PAGE 99. Termination of sensory nerve fibres 83 100. Termination of sensory nerve fibres within the epidermis 84 101. Special nerve-endings within the epidermis (Ranvier) 84 102. Tactile corpuscles — simple and compound 85 103. Tactile corpuscle of Meissner 1 Schiefferdecker) 85 104. Simple spherical end-bulb (Krause) 86 105. Genital corpuscle (Krause) . . 86 106. Simple cylindrical end-bulbs (Schiefferdecker) 86 107. Corpuscle of Vater, or Pacinian body (Ranvier) 87 108. Herbst's corpuscle 87 109. Nerves of involuntary muscle 89 no. Nerves of voluntary muscle 90 in. Motor end-plate of voluntary muscle 90 112. Golgi's corpuscle, or tendon-spindle (Ciaccio) 91 113. Nerve-fibres accompanying a small artery 92 114. Nerves ending in glands 93 115. Section of human artery 94 116. Endothelium of artery of frog 94 117. Cell-spaces of intima of human aorta 95 118. Fenestrated membrane of intima of human aorta 95 119. Muscle-cells from human artery 96 120. Section of aorta of child 96 121. Small arteries and capillary 97 122. Section of human vein 98 123. Capillary blood-vessels 99 124. Section of human heart, showing endocardium 100 125. Section of human heart, including valve 101 126. Section of human heart, including pericardium 102 127. Developing capillary blood-vessels 103 128. Section of developing heart 104 129. Human colorless blood-cells 105 130. Human blood-cells 107 131. Red blood-cells of man and of amphiuma 109 132. Human blood-cells, showing effects of reagents 109 133. Human blood, showing blood-platelets, fibrin, etc no 134. Haemin crystals from human blood ...- in 135. Lymph-spaces within fibrous tissue in profile 115 136. Lymph-spaces in surface view 116 137. Lymph-capillary 116 138. Lymphatics of silvered diaphragm 116 139. Perivascular lymphatic enclosing an artery 117 140. Section of human thoracic duct 117 141. Elements of adenoid tissue 118 142. Diffuse adenoid tissue 119 143. Simple lymph-follicle 119 144. Section of lymph-gland 120 145. Section of lymphatic gland, including cortex . . 120 146. Section of lymphatic gland, including medulla 121 147. Section of lymphatic gland, showing details of structure 121 148. Section of spleen 123 149. Section of spleen, showing trabeculse and reticulum 123 150. Section of large trabecula of spleen 123 151. Section of human spleen cutting a Malpighian corpuscle 124 152. Portion of channel within splenic pulp 125 153. Diagram of relations of splenic vessels to pulp-tissue 126 xvj LIST OF ILLUSTRATIONS. FIG. PAGE 154. Section of human thymus body 127 155. Portion of periphery of follicle of thymus body 127 156. Portion of same follicle, showing Hassall's corpuscles 127 157. Peritoneal endothelium 129 158. Section of peritoneum 130 159. Section of synovial membrane 131 160. Section of ten-day rabbit embryo 133 161. Diagram of typical mucous membrane 136 162. Cells of basement-membrane 137 163. Diagram illustrating form of glands 137 164. Tubular glands 138 165. Section of racemose gland 139 166. Section of human parotid gland 139 167. Serous acini of parotid gland 140 168. Mucous acini of sublingual gland . 140 169. Section of lingual glands 141 170. Serous and mucous acini of glands 141 171. Developing salivary gland 142 172. Section of human oral mucous membrane 144 173. Longitudinal section of molar tooth 146 174. Section of dried tooth, including enamel and dentine 146 175. Interglobular spaces of dentine 147 176. Section of enamel 147 177. Section of dried tooth, including cementum and dentine 148 178. Section of young tooth and pulp 149 179. Section of jaw of rabbit embryo with early dental ridge 149 180. Model of embryonal jaw {Rose) 150 181. Section of jaw of rabbit embryo — dental ridge 150 182. Section of jaw of rabbit embryo— enamel organ 150 183. Section of jaw of cat embryo — dental papilla 151 184. Section of jaw of cat embryo with four developing teeth 151 185. Section of enamel organ of cat embryo 152 186. Section of developing tooth of cat embryo 153 187. Section of human tongue, showing conical papillae 154 188. Section of human tongue with fungiform papilla 154 189. Section of circumvallate papilla from child's tongue 155 190. Section of taste-bud from circumvallate papilla 155 191. Salivary corpuscles from human saliva 156 192. Section of tonsil of dog 157 193. Section of tonsil of child 157 194. Section of tonsil of child, showing structural details 158 195. Section of human oesophagus 161 196. Section of human stomach 163 197. Peptic gland from stomach of dog 163 198. Transverse sections of gastric glands of dog 164 199. Portion of peptic gland of dog 164 200. Pyloric glands from human stomach 165 201. Section of pyloric region of human stomach 165 202. Section through pylorus of child's stomach 165 203. Section of injected stomach of cat 166 204. Nervous plexuses of human stomach ( Slohr) 167 205. Longitudinal section of human small intestine 168 206. Tubular glands of large intestine of dog 169 207. Transverse section of follicles of large intestine 169 208. Longitudinal section of villus of dog's intestine 170 LIST OF ILLUSTRATIONS. xvii FIG. PAGE 209. Transverse section of villus of dog's intestine , 170 210. Longitudinal section of large intestine of child 171 211. Section of duodenum of cat 171 212. Section of human large intestine 172 213. Peyer's patch from small intestine of cat 172 214. Section of small intestine of child 173 215. Section of injected small intestine of cat 174 216. Section of liver of hog 176 217. Section of human liver 177 218. Diagram of structure of liver 177 219. Section of injected human liver 178 220. Hepatic cells from human liver 178 221. Section of uninjected human liver 178 222. Section of centre of lobule of human liver 179 223. Section of liver of frog 179 224. Section of rabbit's liver, showing bile-capillaries 180 225. Section of dog's liver, showing interlobular vessels 180 226. Transverse section of large bile-duct 181 227. Section of human parotid gland 183 228. Acini of human parotid gland 183 229. Section of human sublingual gland 184 230. Section of human pancreas 185 231. Human pancreas, showing area of immature cells 186 232. Section of developing gut of rabbit embryo 187 233. Sagittal section of nine-day rabbit embryo 188 234. Longitudinal section of human kidney (Henle) 191 235. Section of human kidney, showing general arrangement 192 236. Section of partially-injected human kidney 193 237. Diagram of the kidney 194 238. Uriniferous tubules of human kidney 196 239. Section of kidney of amphiuma 197 240. Constituents of medulla of human kidney 197 241. Section of medulla of human kidney 198 242. Section across papilla of human kidney 199 243. Section of injected kidney of dog 200 244. Transverse section of human ureter 201 245. Section of human bladder . 202 246. Developing kidney of rabbit embryo 204 247. Developing kidney of rabbit embryo 205 248. Developing kidney of cow embryo 205 249. Diagram illustrating structure of testicle 207 250. Section of human testicle 208 251. Section of human seminiferous tubule 209 252. Spermatogenesis in testicle of dog 209 253. Spermatogenesis in testicle of musk-rat 210 254. Spermatogenesis in testicle of musk-rat 210 255. Spermatogenesis in testicle of musk-rat 211 256. Human testicle, showing interstitial cells 211 257. Section of tubule of human epididymis 212 258. Section through epididymis of child 213 259. Human spermatozoa 215 260. Human spermatozoa, highly magnified 215 261. Section of penis of child 217 262. Erectile tissue of human penis 217 263. Section of human prostate gland 220 xviii LIST OF ILLUSTRATIONS. FIG. PAGE 264. Human prostate gland, showing muscle 221 265. Section of ovary of cat 224 266. Human ovary with Graafian follicle 225 267. Section of cortex of cat's ovary 226 268. Ovum from ovary of cat 227 269. Section of medulla of human ovary 228 270. Section of corpus luteum of rabbit 229 271. Portion of tubules of parovarium 230 272. Transverse section of human oviduct 231 273. Section of human uterus 232 274. Section of uterine cervix of child 233 275. Active human mammary gland 238 276. Acini of active human mammary gland 239 277. Atrophic human mammary gland 240 278. Human milk and colostrum-corpuscles 242 279. Wolffian bodies and sexual glands of rabbit embryo 242 280. Indifferent sexual gland of rabbit embryo 243 281. Section of developing ovary of kitten .... 244 282. Diagram illustrating development of sexual organs 245 283. Longitudinal section of larynx of child 247 284. Longitudinal section of epiglottis of child 248 285. Section of trachea and oesophagus of child 249 286. Section of human bronchus 251 287. Diagram of air-passages of lung 251 288. Section of human lung 252 289. Section of silvered lung of kitten 253 290. Section of injected and inflated lung of cat 254 291. Section of human pleura 256 292. Section of thyroid body of child 257 293. Acini of human thyroid body 258 294. Developing pulmonary tube of rabbit embryo 259 295. Developing lungs of rabbit embryo 259 296. Developing thyroid body of rabbit embryo 260 297. Developing lateral thyroid area of rabbit embryo 260 298. Section of human skin 261 299. Epidermis of human skin 262 300. Section of epidermis of human skin 262 301. Section of negro's skin 264 302. Section of child's finger, including nail 266 303. Section of human scalp 267 304. Human hair 268 305. Hair-follicle from human scalp 269 306. Transverse sections of hair-follicles 270 307. Section of hair-follicle near its mouth 270 308. Section of hair-follicle, highly magnified 271 309. Section of sebaceous gland from human scalp 273 310. Section of human sweat-gland 275 311. Developing skin from human fcetus 277 312. Developing skin from foetal kitten 279 313. Developing hair from foetal kitten 279 314. Section of skin of fcetal kitten 279 315. Degenerating hair-follicle from human scalp 280 316. Section of skin of human fcetus 281 317. Brain-membranes of child 282 318. Section of human spinal cord from cervical region 285 LIST OF ILLUSTRATIONS. X1X FIG PAGE 319. Diagram of fibre-tracts of spinal cord 286 320. White matter of spinal cord 287 321. Section of human spinal cord from thoracic region 288 322. Section of human spinal cord from lumbar region 289 323. Central canal and commissures of spinal cord of calf 289 324. Anterior horn of gray matter of spinal cord of man 290 325. Anterior horn of gray matter of spinal cord of calf 291 326. Diagram of cells and fibres of spinal cord {Lenhossek) 292 327. Neuroglia cells of embryonal spinal cord {Lenhossek) 294 328. Section of injected human spinal cord 295 329. Diagram of decussations of medulla | Testut\ 296 330. Diagram of decussating tracts of medulla ( Teshit- Duval) 297 331. Diagram of medulla through olivary bodies [Testut- Duval) 297 332. Diagram of sensory decussation of medulla ( Testut-Duval ) 298 ^zz- Diagram of medulla through olivary bodies {Testut-Duval) 298 334. Section of medulla of child 299 335. Section through human pons ( Testut- Stilling) 302 336. Section through human cerebral peduncle {Krause) 303 ^2,7- Section of human cerebellum 305 338. Diagram of nerve-cells of cerebellum 306 339. Section of human cerebellum 307 340. Section of cerebellar cortex of dog (Retzius) 309 341. Section of human cerebral cortex 312 342. Section of silvered human cerebral cortex 313 343. Nerve-fibres of human cerebral cortex 314 344. Section across cornu Ammonis (Henle) 316 345. Diagram of constituents of cornu Ammonis {K. Schaffer) 317 346. Section across optic thalamus {Schwalbe-Meynert) 320 347. Section across corpora quadrigemina ( Quain- Meynert) 322 348. Section of human olfactory bulb {Henle) 324 349. Section of olfactory bulb of rabbit {Retzius) 325 350. Diagram of cerebral association fibres \Schaefer- Meynert) 326 351. Section of human pituitary body 328 352. Section of pineal sense-organ of lizard embryo 329 353. Section of human pineal body 330 354. Corpora amylacea from human brain 330 355. Section of human suprarenal body 331 356. Section of rabbit embryo, showing open neural tube 332 357. Section of rabbit embryo, showing closed neural tube 333 358. Primary wall of neural tube {His) 333 359. Germ-cells and neuroblasts (His) t>2>Z 360. Germ-cells and spongioblasts {His) 334 361. Spongioblasts from neural tube iHisi 334 362. Section of human cornea 2io7 363. Fibrous tissue of cornea of ox 338 364. Corneal corpuscles of calf t,^> 365. Corneal spaces of calf 339 366. Corneal spaces of calf 339 367. Plexus of corneal nerves 340 368. Section of walls of human eyeball 341 369. Section of human choroid 342 370. Human choroid from surface 343 371. Section of human ciliary processes 344 372. Section through ciliary region of human eye 345 373. Section of iris and lens of human eye 347 XX LIST OF ILLUSTRATIONS. FIG. PAGE 374. Injected iris from eye of dog 348 375. Irido-corneal angle of human eye 350 376. Diagram of retinal elements (Kallius after Ramon y Cajal) 352 2,77- Section of human retina 353 378. Human retina at macula lutea {Max Schultze) 357 379. Human retina at ora serrata 358 380. Transverse section of human optic nerve 359 381. Section of part of human optic nerve 359 382. Longitudinal section of human optic entrance 360 383. Portions of human crystalline lens 362 384. Fibres of human crystalline lens 362 385. Section through anterior segment of human eye 363 386. Section of human eyelid 368 387. Section of human lachrymal gland 371 388. Primary optic vesicle of rabbit embryo ^73 389. Developing lens and optic cup of rabbit embryo ^73 390. Choroidal fissure in developing eye of rabbit embryo 2>73 391. Developing eye of rabbit embryo 375 392. Section through developing eye of rabbit embryo 376 393. Section of human external auditory canal (Riidinger) 378 394. Human tympanic membrane and malleolus {Riidinger) 379 395. Section of human Eustachian tube ( Testut) 382 396. Section of membranous labyrinth of cat 384 397. Section of utricle of rabbit, showing otoliths 385 398. Section of semicircular canal of cat 386 399. Membranous semicircular canal of cat 387 400. Longitudinal section of cochlea of guinea-pig 388 401. Section of cochlea of cat 390 402. Section of Corti's organ of guinea-pig 392 403. Diagrammatic view of Corti's organ ( Teslut) 393 404. Section through auditory pit of rabbit embryo 398 405. Section through otic vesicle of rabbit embryo 398 406. Section through developing ear of rabbit embryo 399 407. Section through developing cochlea of rabbit embryo 400 408. Section of human respiratory nasal mucous membrane 402 409. Section of olfactory mucous membrane of child 403 NORMAL HISTOLOGY. CHAPTER I. THE CELL AND THE TISSUES. Histology, literally, the science of tissues, represents that part of general morphology which treats of the structural elements of organisms, by the various arrangement of which the textures and organs of the body are formed. The term is, evidently, equally applicable to the structural components of plants as well as to those of animals; "histology," however, is usually accepted as relating especially to animal tissues, "vegetal histology" expressing the extension of the study to the tissues of plants. At first sight apparently complex and numerous, the structures composing the animal economy are really made up of but few elementary tissues ; these latter may be divided into four funda- mental groups: Epithelial tissues; Connective tissues; Muscular tissues; Nervous tissues. Each of these tissues may be further resolved into the compo- nent morphological constituents, the cells and the intercellular substances. All animal cells are the descendants of the embryonal elements derived from the division of the primary parent cell — the ovum; the intercellular substances, on the other hand, are formed through the more or less direct agency of the cells. The animal cell may exist in either the embryonal, matured, or metamorphosed condition. The embryonal cell, as represented by the early generations of the direct offspring of the ovum, or by the lymphoid or colorless blood-cells of the adult, is a FlG t small irregularly round or oval mass of finely granular gelatinous substance — the protoplasm or cell-contents Colorless blood'ce" exhibitins amoeboid mOTement- — in some part of which a smaller and often indistinct spherical body — the nucleus — lies embedded. In the embryonal condition, 12 NORMAL HISTOLOGY. Fig. 2. when the cell is without a limiting membrane and composed al- most entirely of active living substance, the outlines are frequently changing, these variations in shape being known as amoeboid movements, from their similarity to the changes observed in the outline of an active amoeba, one of the simplest forms of animal life. As the embryonal cell advances in its life-history, the surrounding conditions to which it is subjected induce, with few exceptions, further specialization. Among the earliest of such effects is the condensation of the peripheral zone of the cell, whereby the reten- tion of a definite form is greatly favored; such peripheral condensa- tion may progress to the production of a distinct limiting membrane — the cell- wall. This structure is very frequently wanting; when present, however, it is usually so thin that its optical expression is a single delicate line. The cell-wall is to be regarded as a product of the specialization of a portion of the protoplasm, rather than as an essential part of the cell. The adult cell consists of the protoplasm, or cell-contents, possibly limited by a cell-wall, en- closing a nucleus, which latter, in turn, often con- tains one or more minute spherical bodies, the nu- cleoli. The more or less definite and characteristic forms which the elements of the various tissues possess on reaching their full development, depend largely upon the changes effected by growth and dif- ferentiation in the proto- plasm during the younger condition of the cells. The protoplasm of which the greater part of cells is composed, using the term in its broadest application and as sy- nonymous with cell-contents, usually appears as a finely granular semi-fluid or gelatinous substance, in which darker and coarser granules or other particles of extraneous matters are often embedded. The structure of protoplasm is now recognized as far more com- plicated than was formerly supposed, comprising a highly elastic and extensible portion — the spongioplasm — and an interstitial, Typical cell, — ovum of cat : a, protoplasm ; i, nucleus ; c, nuclear membrane ; d, nucleolus ; e, true cell-wall, closely applied to the surrounding secondary envelope, the zona pellucida. THE CELL AND THE TISSUES. 13 seemingly less active substance — the hyaloplasm. The active contractility which has been generally credited to the spongioplasm has been recently questioned (Schaefer), since the characteristic amoeboid movements of living cells are by some attributed to the changes taking place within the hyaloplasm. The arrangement of these constituents of the protoplasm is vari- able. When they exist closely and uniformly intermingled, the customary finely granular appearance of the cell-contents is produced; not infrequently, however, the spongioplasm is disposed as a more or less well-defined reticulum. In living cells this reticulation is transient, and, to a certain degree, acci- dental, since it often depends upon an unequal distribution of the hyaloplasm induced by the presence of vacuoles or of particles of foreign substance, as se- cretion within glandular epithelium. Chemically, protoplasm consists of various albuminous substances in com- bination with a special nitrogenous pro- teid, plastin, together with water and SaltS. It is probable that in the albu- Structure of the cell : a, spongio- id . 1 it- r plasm, arranged as reticulum, hyalo- minous substances alone the property of v, ',. ° Jr. ,, . „ * \ ,, r 1 J plasm lies within the latter; b, cell- COntraCtilitV resides; the plastin, On the wall; <:, chromatin filaments, between other hand, offers great resistance to Whiles nuclear matrix : *, nuclear e> membrane; e, nucleo us. those reagents, as acids, gastric juices, or trypsin, which dissolve the albuminates. The amount of plastin present within the fibrils forming the intercellular reticulum is not constant, but subject to considerable variation. In addition to the hyaloplasm, the meshes of the spongioplasm frequently contain particles of foreign substances ; the latter may be fatty matters, pigment granules, particles of secretion elaborated within the cell itself, or extraneous material. The nucleus is limited by a distinct wall, the nuclear membrane, and is traversed by a variably elaborate framework of nuclear fibrils, between which lies an interfibrillar, probably semi-fluid, sub- stance, the nuclear matrix. In recognition of the marked affinity for certain dyes possessed by these threads, the substance composing the fibrils is often termed chromatin, while the but slightly staining nuclear matrix is designated achromatin. The nuclear fibrils, how- ever, contain an additional constituent, linin, which is achromatic and holds in place the deeply dyed particles of chromatin. Suspended within the nuclear net work, lying often in close rela- tion with the fibrils, one or more minute spherical bodies may be seen ; these are the nucleoli, regarding whose true significance, at 14 NORMAL HISTOLOGY. present, little is definitely established. The nucleolus is highly refracting, and, when subjected to appropriate stains, takes on a color differing from both nucleus and protoplasm, suggesting, at least, a distinct chemical condition. This body lies closely approxi- mated to, but separated from, the nuclear fibrils, being an indepen- dent member of the cell; this fact is especially evident in such ele- ments as ganglionic nerve-cells, or ova, where the nucleolus appears with exceptional distinctness. Its disappearance during the division of the nucleus, and its subsequent reappearance within the newly- formed nuclei, lend weight to the supposition that the nucleolus plays but a subordinate role in the life-history of the cell ; its true value, however, has yet to be determined. In addition to the parts of the cell generally recognized, recent investigators have described the occasional presence of an irregularly spherical body, lying within the protoplasm in the vicinity of the Fig. 4. Fig. 5. 7,' A, cell from pancreas of salamander: n, nucleus ; J>, paranucleus. B, sexual cell of leech : n, nucleus ; /, paranucleus ; c, centro- some. (After Platner.) Segmenting ova of asraris megalocepliala : n, nucleus ; a, centrosome, surrounded by attraction-sphere ; p, po- lar body. (After Boveri.) nucleus, to which the name accessory nucleus, or paranucleus (yNcbenkern of the Germans), has been applied. According to Plat- ner, the paranucleus is an extrusion of the nucleus, and is subject to great variation in size and appearance; the nature and function of this body are at present still obscure, and need further investigation. Likewise, the presence of a very small, round, highly-refracting body — the centrosome, or pole-corpuscle — has been established within the nucleus of sexual and other cells. The centrosome is itself surrounded by an area named the attraction-sphere. While these bodies have been shown to exist during the condition of rest, it is especially in connection with the changes incident to the division of the nucleus that they become most conspicuous, since their di- vision and subsequent migration inaugurates the complex cycle of nuclear changes.. THE CELL AND THE TISSUES. 15 THE VITAL MANIFESTATIONS OF THE CELL. The characteristics which distinguish the structural units of living organisms from those of the inorganic world, may be conveniently grouped as — Vegetative, Metabolism, Growth, Reproduction; Ani- mal, Irritability, Motion. Metabolism is that process by which the cell selects and assimi- lates, from the surrounding food-materials, those substances adapted to the particular needs for its nutrition and function, so changing and incorporating into its own substance the materials so acquired that they become an integral part of the cell. By a still further exercise of this process the assimilated materials are converted into new substances, which may be retained within the cell, or, as is frequently the case, given up as the various secretions of the body. Growth, the natural sequence of assimilation, may affect the cell equally in all parts, thereby producing a uniformly enlarged ele- ment; such normal or typical increase is, as a rule, hindered by the impression of neighboring elements, such limitations resulting in many local alterations of form, as conspicuously seen in epithelial tissues. It is, however, the principle of unequal growth that exerts the greatest influence in producing specializations of form, as exam- ples of which the cells of muscle, the crystalline lens, or connective tissue are familiar. Reproduction, the culminating phenomenon of the life-history of the cell, occurs by two modes : a. By direct division — without karyokinesis. b. By indirect division — with karyokinesis. Direct division, by which a cell rich in protoplasm, as the white blood-corpuscle, constricts, cuts off, and sets free a portion of itself, while undoubtedly taking place in the Fig. 6. multiplication of the /?g£1 flifcl__^ r^fllL simplest organisms, l^lj^^g) X^pj^^x^ v^W^ ~"® Or OI tUe least Gil- Direct cell-division of colorless blood-corpuscle. ferentiated elements of higher types, is no longer regarded, as formerly, as the most important and usual mode of cell reproduction ; the observations of the last decade have shown that its occurrence must be accepted rather as exceptional than as customary. Indirect division, preceded by the complicated cycle of nuclear changes collectively termed karyokinesis, is now recognized as being the usual mode of the reproduction of cells of all kinds, in pathological as well as in normal conditions. The recognition and elucidation of these important phenomena have been largely due to i6 NORMAL HISTOLOGY. the brilliant investigations of Hemming, Strasburger, v. Beneden, Schleicher, Rabl, and others have added much to the accurate knowledge of the lifediistory of the cell. When the cell undergoes a complete and typical mitotic division, the following changes occur : (i) The centrosome increases in size, passes into the protoplasm, and, later, divides into two ; the nucleus enlarges, while the chro- matin greatly increases, the fibrils becoming con- torted to form a dense convolution, whose twisted threads run generally transverse to the long axis of the nucleus and parallel to the plane of the future cleavage; these fibrils constitute the (2) Close skein, or spirem. The chromatin fibrils further thicken, be- Fig. 8. coming less convoluted, and forming irregularly- arranged loops, known as the (3) Loose skein. The question whether these skeins are composed of the contortions of one long fibre, or whether they con- tain several shorter ones, has, as yet, not been defi- nitely determined ; observa- tions made on the cells of lower forms, however, ren- der it not improbable that a single thread constitutes the entire convolution. The fibrils of the loose skein now separate at their peripheral turns, so that a number — about twenty- four (Flemming, Rabl) — of distinct loops are formed; the closed ends of these are directed towards a common centre, around which, but removed some little distance, they become arranged. The enclosed clear space is the polar field. During the formation of the skeins the nuclear membrane disappears, its former position being marked for some time longer by a clear zone or halo surround- ing the nucleus and defining the boundary of the latter from the cell-contents. Coincidently with the formation of the loose skein, delicate striae make their appearance within the nucleus, so disposed Close skein, — diagram of nuclear fibrils : A, seen from the side ; B, from the polar field, P; C, from anti-pole, GP. (After Rabl- Schiefferdecker .) Loose skein : nuclear spin- dle has appeared in polar field, P. (After Rabl-Schief- ferdecker.) THE CELL AXD THE TISSUES. 1 7 that together they present a double cone, whose apices are directed towards the poles of the future new nuclei, as determined by the new centrosomes, surrounded by the attraction spheres, now known as the "polar striation ,•" these acromatin figures constitute the nu- clear spindle. The chromatin fibrils grow thicker and, at the same time, shorter, and arrange themselves so that the closed ends of the loops encircle the polar field, giving rise, when seen from its surface, to the wreath; seen from the side, however, the loops or V's appear as radiating fibrils, and constitute the (4) Mother-star, or aster: the apparent differences, therefore, between the wreath and the aster depend upon the point of view, and not upon variations in the arrangement of the fibres. Another very important change is now observed. (5) Each of the loops undergoes longitudinal cleavage, split- ting up into double the number of segments: these are now entirely rearranged, the first step being (6) A rapid separation into two groups, passing towards the poles of the future new nuclei, as indicated by the foci of the nuclear spindle. Around these points as centres, a deli- fig. 9. cate radial marking — the polar striation — ap- p pears. The halves of the longitudinally-cleft ^- ?~j— -. ^ fibrils are so disposed that one of each pair of //*"") _.„_ C/V\ sister-segments passes along the guiding lines of f / ( / f\ \\ the achromatin spindle to each of the groups, thus insuring an accurate and equal division of the original chromatin between the new nuclei. The chromatic segments, becoming further aggregated about the equator of the nuclear spindle in their migration, form a compressed mass, known as the (7) Equatorial plate. * As the newly-grouped fibrils pass outward towards their respective poles, the free ends of the receding segments become united by delicate threads of achromatin — the connecting filaments — which stretch between the corresponding limbs of the separating seg- q p ments. With the completion of migration the Rearrangement and cardinal features of the division of the nucleus "afr0m°the ^fdT"^' have been established, since the subsequent from the polar field, /\- stages are but repetitions, in inverse order, of the Rabi^L&rdecter* changes already instituted. Following the stage of the equatorial plate, the fibrils group themselves about the poles of the spindle and form * The term '' equatorial plate" has been employed by some authors to indicate the later phases of the aster stage. i8 NORMAL HISTOLOGY. (8) The daughter-stars, or diaster, each of these corresponding to a new nucleus. About this time the cell-protoplasm, which until now has been almost passive, begins to exhibit a constriction of its body, which impression now steadily progresses until the protoplasm of the cell completely separates into the portions destined to become the bodies of the cells, enveloping the new nuclei. The karyokinetic cycle is completed by each (9) Daughter-wreath or star in turn assuming (10) The stage of the daughter-skeins, at first loose and afterwards close; on obtaining nuclear membranes and the nucleoli reappearing, the new nuclei finally pass into the stage of rest. Fig. 10. B D Diagram illustrating the migration and redisposition of the segments of chromatin, guided by the achro- matic lines : A , mother-star ; B and C, stage of equatorial plate ; D, daughter-stars. (After Rabl.) In recapitulation, the above changes may be tabulated as follows: Resting Mother-Nucleus : the inauguration of division is marked by migration and division of centrosome, increase of chromatin, resulting in the formation of 1. The Mother- Skein (Spirem): a. Close skein, — Disappearance of nucleoli. Disappearance of nuclear membrane. b. Loose skein, — Separation of skein into segments. Appearance of polar field. Rearrangement of segments around polar field to form 2. The Mother-Wreath, or Aster: Appearance of nuclear spindle. Longitudinal cleavage of chromatin segments. 3. Migration of Segments (Meta kinesis): Segments pass towards the poles of the new nuclei. Equatorial plate produced by massing of migrating seg- ments. THE CELL AND THE TISSUES. Separation of segments into polar groups. Appearance of connecting filaments. 4. Daughter- Wreaths, or Asters : Beginning division of cell-protoplasm. 5. Daughter-Skeins : a. Loose skein. b. Close skein. Completion of new nuclei. Acquisition of nuclear membranes. Reappearance of nucleoli. Completed separation of cell-protoplasm. Resting Daughter-Nuclei. 19 Fig. 11. A' Cells from the epidermis of very young larva of newt : A , resting nucleus ; B, close skein ; C, loose skein ; D and E, mother-stars, seen from the polar field and appearing as the wreath stage ; F, mother- star from the side ; G, migration of segments ; H, daughter-stars ; / and J, segments grouped about new polar fields (in J the protoplasm exhibits constriction) ; K, daughter-skeins, — division of nucleus complete with slight constriction of cell-body; L, completed division of nucleus and protoplasm. As closely connected with the division of the ovum, and probably, also, with that of many other cells, the behavior of the minute intra- nuclear bodies — the centrosomata (Boveri), or pole-corpuscles (v. Beneden), and their surrounding attraction-spheres — has attracted the attention of recent investigators. The centrosome 20 NORMAL HISTOLOGY. during the resting stage is single, but its multiplication early takes place in the dividing nucleus and anticipates the establishment of the poles of the new nuclei; the apices of the nuclear spindles coincide with the attraction-spheres, which are, probably, potent factors in determining the exact position of the spindles and, consequently, the plane of division. Fission of the nucleus is ordinarily followed by cleavage of the protoplasm, the resulting new cells being entirely distinct elements. A deviation from this usual procedure is; however, some- times encountered where the division of the nucleus has not been followed by cleavage Fig. 13. Fig. 12. Segmenting ova of ascaris megalocephala : A , cell Large marrow-cell : the nu- contains nucleus, two centrosomes (c), surrounded by cleus has undergone repealed attraction-spheres, and adherent polar body (p)\ B, division without cleavage of the beginning polar striation around the centrosomes and protoplasm, attraction-spheres ; C, cell viewed from polar field, the striation proceeding from the centrosome ; D, cell seen from the side, apices of nuclear spindle correspond with centrosomes. (Afier Boveri.) of the cell-protoplasm, the latter remaining undivided even after the repeated division of the nuclei. Examples of such ' ' endogenous' ' formation are seen in the multinucleated giant marrow-cells. These complicated phenomena can be satisfactorily observed only in suitable preparations and with adequate optical appliances; the dividing-cells of the surface epithelium of very young larval newts (ten to twenty millimetres long) supply admirable views of all stages of karyokinesis. In order to obtain permanent preparations, how- ever, these transient changes must be ' ' fixed' ' by powerful reagents, insuring the instantaneous death of the tissue (see Appendix); otherwise the cycle, which occupies only from two to three hours, and often even less time, will have been completed, and all trace of the figures lost. The command of at least five hundred diameters, with unexceptionable definition, is likewise essential for the careful study of these changes. While most favorably seen in fixed and stained preparations, the karyokinetic figures may be observed in living cells, thus proving that they in* no wise depend upon reagents for their existence. THE CELL AND THE TISSUES. 21 The foregoing vital manifestations, being chiefly concerned in the mere existence and perpetuation of the cell, are appropriately termed vegetative ; irritability and motion, on the contrary, are the ex- pressions of a higher and more individual existence, and hence are called animal. It is to be remarked that the term "animal," as here employed, must not be regarded as indicating distinctions be- tween plants and animals; for this purpose such manifestations are inadequate, since the elements of certain plants (Mimoseae, Dionaea) possess irritability, and the protoplasm of others (Myxomycetes, Volvocineae) exhibits motion in a marked degree. Irritability is that property of living matter by virtue of which external influences are responded to by changes within the cell; these changes may, in turn, induce secondary phenomena. Instances of such impressions are frequent among the lower forms, where surface elements, or, as among the still simpler unicellular protozoa, the pe- ripheral zone of the protoplasm common to the entire animal, exhibit susceptibility to external stimuli. Among the higher animals irri- tability is manifested by nerve-cells, which, through their processes, influence other tissues. Concerning the exact nature of the intimate changes taking place within the cell, the sum of which we call nervous phenomena, little is known; it is probable, however, that the al- buminous constituents of the protoplasm are the particular seat of these obscure molecular changes. Motion, more or less pronounced, is a characteristic of all ani- mal cells — and, likewise, of very many vegetal ones — during some portion of their existence. The development and specialization of the adult cell usually result in limitation of the activity of the protoplasm, by reason both of its decrease and of its intimate relations with the surrounding tissues; the cells exhibiting motion in the adult condition are those which retain, to a certain degree at least, their embryonic type: such are the lymphoid and connective-tissue cells. Motion may be exhibited by elements devoid of, as well as by those provided with, special appendages. The lowest degree of this vital manifestation is encountered in the streaming of the protoplasm within cells, as in plants, enclosed within limiting membranes which do not permit such motion to affect the exterior of the cells. Con- spicuous examples of the more marked effects of protoplasmic streaming are familiar in the changes readily observed in amoebae or in the colorless blood-cells of higher types. In these latter elements, however, the motion is manifested rather in change of form than by marked variation in position. The highest expression of motion is displayed by those cells whose protoplasm has undergone specialization, resulting either in the pro- duction of a peculiar tissue, as that of the voluntary muscle fibre, or 22 NORMAL HISTOLOGY. of external appendages, as the cilia of many unicellular organisms or of the epithelial elements of the higher animals. Since every cell is derived from a pre-existing cell, it follows that all the cells of the organism are the descendants of the parent ele- ment— the ovum. The ripe mammalian egg, while small in com- parison with many other ova, is among the largest histological elements, measuring about .2 millimetre in diameter, and, further, possessing all parts of the typical cell. Before the ovum is capable of uniting with the male sexual element to carry out the changes attendant upon fecundation, it passes through a cycle of preparatory stages collectively known as maturation. These changes consist in the repeated very unequal division of the ovum, resulting in the expulsion of minute portions of its proto- plasm, the polar bodies ; of these latter, usually two are extruded. Maturation and fecun lation in ova of uscaris meg.ilocephala : /, n, nucleus of ovum before matura- tion ; s, entering spermatozoon ; //, nucleus (h) has passed to periphery of cell preparatory to di- viding; j, spermatozoon now within the ovum ; ///, nucleus dividing into first polar body I/) ; m, male pronucleus resulting from spermatozoon ; lV,p,p', first and second polar bodies, the last still in process of formation ; m, male pronucleus ; V, p, p', polar bodies ; f and m, respectively female and male pronuclei, in contact but not yet fused ; c, centrosomes, indicating poles of nuclear spindle ; VI, pronuclei now fused ; striation proceeds from centrosomes preparatory to division of ovum. (After O. Hertwig.) The nucleus which appears within the ovum after the formation of the polar bodies is the female pronucleus. Upon the completion of these phenomena, maturation has taken place and the ovum is prepared for the reception of the male sexual element. Under THE CELL AND THE TISSUES. 23 favorable conditions the spermatozoa reach the ovum, when a single element penetrates the envelopes of the egg and is received within the protoplasm of the female cell. The entrance of the spermatozoon causes a new disturbance within the ovum, resulting in the formation of the male pronucleus. Subsequently the latter joins with the female pronucleus, the fusion of the two pronuclei being followed by a temporary disappearance of all nucleus within the ovum. Shortly afterwards the new nucleus of segmentation appears, so called from the fact that within this body cleavage of the ovum is first established. The process of segmentation following the fertilization of the ovum is essentially one of indirect cell-division, in which the stages, although modified in certain details, are essentially the same as those already described. The mammalian ovum undergoes a total segmentation; although the resulting segments are, strictly regarded, not quite equal in size, yet, as a matter of simplicity, they may be regarded as such, and the division characterized as total equal segmentation. The repeated cleavage of the segmentation-spheres into which the ovum is divided soon produces a mass of innumerable cells con- stituting the blastoderm ; the latter, by continued division and further differentiation, subsequently gives place to a cell-area, in which at first two layers, an outer and an inner, and later a third middle stratum, of cells appear. These more or less imperfectly defined tracts constitute the important primary blastodermic layers, the ectoderm, mesoderm, and entoderm, from which are derived all the tissues of the body. The reader must be referred to the various text-books of embryology for a detailed account of the complicated and often obscure processes of maturation, fertilization, segmentation, and blastulation, of which only the most salient points have been indicated above. THE TISSUES. Every tissue is composed of two parts, — the cellular elements and the intercellular substance. Upon the first of these depends the vitality of the tissue, while its physical properties are determined by the character of the second. The physical condition of the inter- cellular substances includes a wide latitude, varying from that of a fluid, as blood or lymph, through all degrees of density, until, by the additional impregnation of calcareous matters, the well-known hardness of bone or dentine is attained. The proportion between the cellular elements and the intercellular substance of mesodermic tissues varies with age and development, the intercellular substance in the early stages being scanty and very 24 NORMAL HISTOLOGY. yielding, while with adolescence they may become tough and re- sistant. Accompanying the growth of the tissue, an increase of the intercellular substance usually takes place through the direct or indirect participation of the cells, these latter, in consequence, suf- fering marked reduction in number and size. The younger the mesodermic tissue, the richer is it in cells and the poorer in intercellu- lar substances; conversely, the older the tissue, the more prominent the intercellular substance and less conspicuous the cellular elements. A marked example of this law is presented by tendon, where, in the embryonic condition, the cells constitute the greater bulk of the tissue, while in the adult the intercellular fibrous tissue so overwhelms the cellular elements that reagents are frequently necessary to satis- factorily demonstrate their existence. While increase of the intercellular substance usually accompanies the growth of the mesodermic tissues, those derived from the ecto- and entoderm present a marked contrast. In these latter tissues the intercellular constituent is represented by the very scanty cement substance, increase in which occurs only as necessitated by the growth of the surrounding cells, the proportion between the two elements being practically constant throughout life. Instances of this constant relation are seen in the varieties and modifications of the epithelial tissues. The primary blastodermic layers — ectoderm, mesoderm, and entoderm — early exhibit histological differences which suffice to distinguish the one from the other, and especially to indicate, at least in a general manner, the tendency of the outer and inner layers to Fig. 15. Blastodermic layers of rabbit embryo: a, ectoderm ; b, entoderm ; c, entodermal cells destined to form notochord ; m, mesoderm. form epithelial structures in contrast to the less compact and more reticular formations of the mesoderm. The epithelia of the genito- urinary tract, however, are marked exceptions in their origin, being derived, as well as the connective and muscular tissues, from the mesoderm, in this respect constituting conspicuous specializations. THE CELL AND THE TISSUES. 2$ Derivatives of the Primary Blastodermic Layers. From the ectoderm are derived — The epithelium of the outer surface of the body, including that of the conjunctiva and anterior surface of the cornea, the external auditory canal, together with the epithelial append- ages of the skin, as hair, nails, sebaceous and sweat glands (including the involuntary muscle of the latter). The epithelium of the nasal tract, with its glands, as well as of the cavities communicating therewith. The epithelium of the mouth and of the salivary and other glands opening into the oral cavity. The enamel of the teeth. The tissues of the nervous system. The retina; the crystalline lens. The epithelium of the membranous labyrinth. The epithelium of the pituitary and pineal bodies. From the mesoderm are derived — The connective tissues, including areolar tissue, tendon, cartilage, bone, dentine of the teeth. The muscular tissues, with the exception of the muscle of the sweat-glands. The tissues of the vascular and lymphatic systems, including their endothelium and circulating cells. The sexual glands and their excretory passages, as far as the termination of the ejaculatory ducts and vagina. The kidney and ureter (but not the bladder). From the entoderm are derived — The epithelium of the digestive tract, with that of all glandular appendages except those portions derived from ectodermic origin at the beginning (oral cavity) and termination of the tube. The epithelium of the respiratory tract. The epithelium of the urinary bladder and urethra. The epithelium of the thyroid and thymus bodies, the atrophic primary epithelium of the latter being represented by Hassall's corpuscles. 26 NORMAL HISTOLOGY. CHAPTER II. THE EPITHELIAL TISSUES. The free surface of the skin and of the various mucous membranes is covered by epithelium, which affords protection to the more delicate parts lying beneath. In this tissue the intercellular con- stituent is reduced to a minimum, being represented alone by the scanty cement-substance between the cells; the latter, in consequence of this relation, form practically an unbroken sheet. The epithelia are best grouped under two chief heads — squamous and columnar. The designation as tessellated or pavement is not distinctive, since either variety may present a mosaic when viewed from the free surface. These tissues may be classified in several divisions as below indicated. VARIETIES OF EPITHELIUM. / Squamous. II. Columnar. a. Simple — consisting of a single layer — a. Simple. b. Stratified — consisting of several layers — b. Stratified. Ill Modified, a. Ciliated; b. Goblet; c. Pigmented. / V. Sped a It zed. a. Glandular epithelium; b. Neuro-epithelium. The epithelium contains no blood-vessels, the nutrition of the tissue being maintained by the absorption of the nutritive juices conveyed by means of the intercellular clefts within the cement- substance. The nervous supply of epithelium is likewise ordinarily very scanty, the existence of nerve-fibrils within the epithelium in many localities being doubtful; in certain regions possessed of high sensibility, as the corneal or tactile surfaces, the termination of nerve- fibres among the epithelial elements may be regarded as definitely established. The epithelial cells usually rest upon a basement- membrane, or membrana propria, a modification of the subjacent connective tissue of which it is part. The principal distributions of the various forms of epithelium follow. THE EPITHELIAL TISSUES. 27 Simple squamous epithelium occurs in but few places: Partially lining the tympanic cavity, including the mastoid cells ; parts of the membranous labyrinth ; the infun- dibula and alveoli of the lungs ; the posterior surface of the anterior capsule of the crystalline lens ; parts of ducts of glands ; the capsule of the Malpighian body and the descending limb of Henle's loop in the kidney; choroid plexuses and parts of brain-ventricles. Stratified squamous epithelium occurs widely distributed, cover- ing— The skin and its extensions, as the external auditory canal, conjunctival sac, and cornea; the mouth, lower part of pharynx, and oesophagus ; the epiglottis and upper part of larynx, together with the false and true vocal cords ; the pelvis of kidney, ureter, bladder, beginning and end of male and entire female urethra; the vagina. Simple columnar epithelium occurs: a. Non-ciliated, in — The digestive tract, from the oesophageal opening of stomach to anus, as well as in the larger ducts of the glands com- municating with this tube ; ducts of mammary glands ; seminal vesicles and ejaculatory ducts ; membranous and penile portions of urethra. b. Ciliated, in — Oviduct, uterus, and part of canal of cervix ; greater part of brain-ventricles and canal of spinal cord. Stratified columnar epithelium occurs : a. Non-ciliated, in — Terminal part of the vas deferens ; olfactory part of nasal fossae. b. Ciliated, in — The Eustachian tube and parts of tympanic cavity ; lachry- mal passages ; respiratory part of nasal fossae, with com- municating sinuses ; ventricle of larynx, trachea, and branchiae ; epididymis and first part of vas deferens. Squamous Epithelium. When occurring as a simple layer, the flattened, polyhedral, nucleated plates form a regular mosaic ; such epithelium is found but seldom in the human body, the lining of the air-sacs of the lung, the posterior surface of the anterior capsule of the crystalline lens, the membranous labyrinth, and a few other localities being its principal seats. 28 NORMAL HISTOLOGY. Fig. 16. A far more usual arrangement is as several layers, constituting the stratified squamous variety. The isolated cells of such epi- thelium differ greatly in form, size, and appearance according to the layer from which they are taken. The cells com- posing the deepest stratum are not scaly, but irregularly columnar, resting, with slightly expanded bases, upon the sub- jacent membrana propria. The irregular borders of these cells join with neighboring elements in such a manner that minute intercellular clefts are formed ; these are occupied by the yielding cement-sub- stance, and allow the passage of the nutrient juices, as well as of the migratory leucocytes, or wandering cells. The nuclei of the columnar elements are oval, and often situated nearer the outer ends of the cells. Passing from the basement-membrane towards the free surface, the form of the cells undergoes a radical change. The pronounced columnar type belongs to the deepest layer alone ; the cells next FlG- l8- become irregularly polyhedral, Fig. 17. Squamous epithelium from frog's skin, viewed from the free surface. Stratified squamous epithelium in section, from the cornea : the deepest cells are columnar ; the superficial are scaly plates. Isolated cells of stratified squamous epithelium : a, surface-cell ; b and c, cells from middle layers ; d, from deepest stratum. then gradually expand in the direction parallel to the free surface, and become, finally, converted into the large thin scales so characteristic of the outer layers of stratified squamous epithelium. The cells constituting the middle strata are irregularly polyhedral, and not infrequently seem to be mutually connected by means of delicate processes, which bridge the intervening intercellular clefts and establish a direct continuity between the neighboring cells ; when such elements are isolated, the delicate threads are broken and the disassociated cells appear as if beset with minute spines : these con- THE EPITHELIAL TISSUES. 29 Fig. 19. Prickle - cells from middle strata of the epidermis. stitute the prickle-cells. During the journey to the free surface the character of the protoplasm also alters, the cells losing in vitality and becoming keratose or horny to a greater or less degree. The extent to which these changes occur depends upon the external conditions affecting the tissue : on mucous surfaces kept con- tinually moist by secretions the cells retain their plasticity and nuclei ; where, on the contrary, they are exposed to the desiccating influences of the atmosphere, they lose their nuclei and become dry and horny, as conspicuously seen in the superficial cells of the epidermis. Fatty granules and small oil-drops, sometimes, also, adherent masses of bacteria, are common in the superficial cells. As the young growing cells of the deeper layers increase in size and numbers, they push those of the super- imposed strata towards the free surface, where the older superficial cells become loosened and gradually set free, constituting the physio- logical desquamation continually taking place. In certain localities, as in the urinary bladder, the columnar cells of the deep layer rapidly assume the scaly character of the superficial strata ; such epithelium possesses relatively few layers, and, from the facility with which the type of the cells changes, is often described as "transitional." It is to be remembered that such epithelium constitutes not a distinct variety, but only a modification of the stratified scaly group. Columnar Epithelium. The columnar epithelium, when occur- ring as a single layer of cells, constitutes the simple columnar variety, which, however, enjoys a much wider distribution than the corresponding squamous group. The taller or shorted columnar cells rest upon the membrana propria with their bases, and join their neighbors with more or less accuracy. The free or outer ends of the cells in some localities, as, conspicu- ously, in the intestine, are char- acterized by the presence of a narrow marginal zone, or basal border : this exhibits a vertical striation, which, on the addition of a reagent, as water, often breaks up into a series of rods, resembling very robust cilia. When the single layer of these epithelial cells is replaced by several, as in the stratified columnar Fig. 21. Fig. 20 Simple columnar epi- the ium from intestine : the free ends of the cells present a peculiar striated border -zone. Highly magnified. Stratified columnarepi- thelium from vas defer- ens : the deepest layer consists of small cells, between which the co- lumnar cells extend. 3Q NORMAL HISTOLOGY. Fig. 22. Fig. 23. variety, the outermost cells alone are distinctly columnar ; these are usually modified at their outer ends, becoming pointed, forked, or club-shaped, in order to fit between the irregularly polyhedral and pyriform elements of the deeper strata. The nucleus is situated about the middle of the columnar surface cells, and somewhat eccentrically nearer the basement-membrane in the deeper cells. The protoplasm of columnar epithelium often contains particles of mucous secretion, indicating the beginning of those changes which result in the produc- tion of the goblet-cells. Modified Epithelium. The free surfaces of the epithelium in particular localities, as noted in detail in the foregoing summary, are armed with minute hair-like processes, or cilia ; these, by their constant active vibration, create a current, which serves to free the mucous membranes from accumulation of mucus and of- fending foreign or irritating sub- stances. Cilia are specializations of the protoplasm, with which they are probably directly and intimately connected ; widely dis- tributed and attached to the various forms of epithelium in the lower animals, in man and the higher mammals cilia are limited to columnar cells. The exact number of individual cilia attached to the free surface of a single cell varies, but there are, probably, between one and two dozen such appendages usually present. Their length likewise differs with locality, those lining the human epididymis being about ten times longer than those of the trachea. When analyzed, by careful observation of favorable cells in not too rapid vibration, the motion will be seen to consist of two parts — a rapid primary move- ment, directed to correspond with the general current, and a slower secondary return to the original position, the free end of the cilium describing a course resembling that of a whip-lash. The vibrations, whose rate has been estimated at about ten per second, do not occur simultaneously in all the cells, but exhibit a progression, one cell after the other taking part in the motions, whereby a series of distinct waves of ciliary motion is produced ; in addition, a certain periodicity or rhythm often characterizes the vibrations. When favorable conditions obtain, including a sufficient supply of moisture, oxygen, and heat, ciliary motion may be maintained for Ciliated epithelium from trachea : g; a cell filled with mucus about to be discharged. Isolated elements of ciliated columnar epi- thelium from trachea : o, m, i, cells from sur- face, middle, and deep- est strata. Fig. 24. THE EPITHELIAL TISSUES. ■, I many hours, and even for days ; the cells of cold-blooded animals in general continue to vibrate longer than those of mammals. The rapidity of the ciliary motion is readily influenced by tem- perature and reagents. While the application of gentle heat stimu- lates, the motion is temporarily arrested by a reduction to 50 C, and permanently impaired by an elevation above 500 C. Increased motion is at first produced by the addition of weak alkalies or acids, followed, however, by a permanent suspension after the prolonged action of these reagents. Cold, chloroform, etc., on the contrary, effect a prompt reduction and, finally, stoppage of the vibrations. On surfaces clothed with columnar epithelium, certain cells are distinguished by unusually clear protoplasm and exceptional size; these are the goblet- cells, whose peculiar elliptical or chalice form results from the accumulation of mucoid substance elaborated within their protoplasm. When the dis- tention becomes too great, the cell bursts in the direction of least resistance, evidently towards the free surface, and the secretion is poured out on the surface of the mucous membrane. Goblet-cells occur on all surfaces covered by columnar epithelium, but with especial profusion in the large intestine. These elements may be regarded as corresponding to the unicellular glands of the lower animals ; in the large mucous glands, as the mucous acini of the submaxillary and sublingual, the majority of the secreting elements are in a condition similar to that of the goblet-cells. The protoplasm of epithelial cells often becomes invaded by par- ticles of foreign substances ; thus, granules of fatty and proteid matters are very commonly encountered, while the presence of granules of eleidin in certain cells of the epidermis characterizes the stratum granulosum. When these invading particles are colored, as when composed of melanin, the pro- toplasm of the affected cell acquires a brown or black tint, and is then known as pigmented epithelium ; such cells are constant in the deeper layers of the epidermis, especially of certain races, and in the outer layer of the retina. Specialized Epithelium. Reference has been made to the goblet-cells as being, tempo- rarily at least, sufficiently specialized to represent unicellular glands ; when the elements become permanently modified to engage in the elaboration of secretion they are recognized as glandular epithelium. Goblet - cells from large intestine con- taining mucous secre- tion. Fig. 25. Pigmented epithelium from outer layer of ret- ina : the nuclei («) still uninvaded. 32 NORMAL HISTOLOGY. The cells lining the ultimate divisions of glands are the modified extensions of the epithelial investment of the adjacent mucous membrane, of which they are the direct outgrowths. Glandular epithelium varies in form from columnar (pancreas) to spherical (parotid) and polyhedral (liver). The protoplasm of such cells is generally more or less filled with particles of secretion, upon whose quantity and arrangement the apparent condition of the protoplasm largely depends. Sometimes the latter is almost entirely displaced by fatty matters, as in the sebaceous glands or in the active mammary acini, or, again, is so encroached upon by particles of secretion that a reticulation of the protoplasm is very conspicuous. The elements lining parts of certain glands exhibit more or less stria- tion, on account of which peculiarity such cells are known as rod-epi- thelium ; examples of this are seen in the ducts of the salivary glands, and in the irregular and, to a less evident degree, the convoluted portions of the uriniferous tubules of the kidney. The epithelial coverings of those areas towards which the terminations of the nerves of special sense are particularly directed undergo high Glandular epithelium : small acinus from a serous racemose gland. Rod-epithelium : a, 6, c, isolated epithelial cells from uriniferous tubules of rat (after Heidenhain) ; d, rod-epithelium from submax- illary duct of dog. (After Schieffer decker.) specialization, resulting in the production of perceptive elements, to which, as a group, the name neuro-epithelium has been applied. The rod- and cone-cells of the retina, the hair-cells of Corti's organ and other parts of the membranous labyrinth, the olfactory cells of the nasal fossae, and the taste-cells of the taste-buds, are all familiar examples of such specialized epithelium. In these elements two parts are present — an inner, containing the nucleus, and corresponding to the usual proto- plasm of the cells, and an outer, peripherally- directed segment, which is highly specialized, and not infrequently terminates in' stiff, rigid, hair-like processes. The outer segment re- ceives the stimuli from external impressions, while the inner, centrally-directed, segment stands in close anatomical relation with the nerve-fibres. Isolated neuro-epithe- lium from no6e : o, olfac- tory cells ; s, sustentacular elements. THE EPITHELIAL TISSUES. 33 -x '■^fe r'-v i ■P s§ • 'ihz* Sfe* ". . /~ P •',; ;.,. '"V"- M- \. '•'<%'' t ■ . 'M ENDOTHELIUM. Although endothelium is intimately related to the connective tissues, being but modifications of the cells of this group, it is con- venient to describe this tissue in the present place. Endothelium forms a covering of the free surface of those spaces not directly communicating with the external atmosphere, including, therefore, the lining of the various serous cavities, as the pleura, pericardium, and peritoneum (disregarding the communication established through the oviduct), of the synovial surfaces of joints, of the heart and blood-vessels, as weil as of the numerous lymphatic spaces FlG- 29- and vessels. These cells occur normally as a single layer of thin, irregularly poly- hedral plates of variable size and of great delicacy ; they possess an oval, sometimes kidney-shaped, nucleus; they never overlap, and usually unite with neighboring cells by serrated and tortuous lines of cement-substance. The endothelial plates covering the serous membranes are, in general, polyhedral, re- sembling in outline the simple scaly epithelium; those lining the blood-vessels are elon- gated, irregular spindles, while those found in the lymphatic vessels are often still more unsym- metrical, being limited by very tortuous boundaries. For the satisfactory study of endothelium resource to silver staining (see Appendix) must be had, by which method the inter- cellular cement-substance is colored deeply brown or black, appear- ing as dark, frequently-interrupted boundary-lines. In such prepara- tions the points of union common to several cells are often marked by small, deeply-stained areas — the stigmata, or pseudo-stomata. These figures are regarded by some as minute openings filled by silver-stained albuminous substances ; according to Klein, however, many of these stigmata are the protruding stained processes of con- nective-tissue cells. In addition to these areas of questionable import are true distinct openings, the stomata, which establish direct com- munication with the adjacent lymphatic channels ; the diaphragm, 3 mm m Endothelium from peritoneal surface of diaphragm, stained with silver : n, nucleus of endothelial plate ; s, one of the intercellular clefts or stigmata. 34 NORMAL HISTOLOGY. Fig. xo. and especially the septum separating the peritoneal sac from the abdominal lymph-cavity of the frog, exhibit well these pores. The larger stomata are lined by several small granular guard- cells, whose expansion and contraction largely influence the size of the openings. The development of epithelium is intimately associated with the exten- sions of the great ecto- and entodermic tracts, since, with the exception of the epithe- lium of the greater part of the genito-urinary organs, the epithelia are the direct descendants of the outer and inner embryonic layers. The cells lining the passages con- nected with the sexual glands, as well as the urinary tract as far as the bladder, are derived from those of the Wolffian body and duct, and hence have, with these latter, a common mesoblastic origin. The simple arrangement of the cells in the earlier stages gradually gives place to the more com- plex disposition of the mature tissue. The development of endothelium forms part of the history of the changes taking place within the extensive mesodermic areas ; from the specialized sheet, or mesothelium, bounding the primary body-cavity of the young embryo, the endothelium of the pleural, pericardial, and peritoneal cavities directly descends, while the lining cells of the vascular and lymphatic channels trace their origin to the differentiation of certain of the mesodermic elements. Endothelium from the septum cisternal of frog, stained with silver : a, one of the true stomata, lined with guard-cells; 6, intercellular cleft ; «, nucleus. THE CONNECTIVE TISSUES. 35 CHAPTER III. THE CONNECTIVE TISSUES. The important group of connective substances — the most widely- distributed of all tissues — is the direct product of the great meso- blastic tract, axial as well as peripheral ; the several members of this extended family are formed by the differentiation and specialization of the intercellular substance, wrought through the more or less direct agency of the mesoblastic cells. The variation in the physical characteristics of these substances is due to the condition of the intercellular constituents of the tissues. Taken during the period of embryonal growth, they are represented by a semi-gelatinous, soft, plastic mass ; a little later, the still soft, but already definitely formed, growing connective tissue exists, which is soon replaced by the yielding, though strong, adult areolar tissue. Grouped as masses in which the white fibrous tissue predominates, the marked tough- ness of tendon is reached ; or where large quantities of yellow elastic tissue are present, great extensibility is secured. A further conden- sation of the intercellular substance produces the resistance of the matrix of hyaline cartilage, with the intermediate gradations pre- sented by the fibrous and elastic varieties ; the ground-substance becoming additionally impregnated with calcareous salts, the well- known hardness of bone or dentine is attained. In all these varia- tions in the density of the intercellular substance the cells have undergone but little change — the connective-tissue corpuscle, the tendon-cell, the cartilage-cell, and the bone-corpuscle being morpho- logically identical. The principal forms in which connective tissue occurs are, — 1 . Mucous tissue, as in the jelly of Wharton of the umbilical cord. 2. Growing, immature tissue, as in very young animals or in old embryos. 3. Areolar tissue, as in the subcutaneous and intermuscular tissues. 4. Dense mixed fibrous a?id elastic tissue, as in the sclera, fasciae, etc. 5. Dense white fibrous tissue, as in tendon, cornea. 6. Dense elastic tissue, as in the ligamenta subflava. 7. Cartilage — fibrous, elastic, and hyaline varieties. 8. Bone. 9. Dentine. 10. The reticulum of adenoid tissue. 36 NORMAL HISTOLOGY. 11. The supporting connective tissue of the nervous system. 1 2. The supporting and uniting framework of the various organs. 13. Adipose tissue. The cellular elements of the connective tissues are usually de- scribed as of two kinds — the proper and the migratory or Fig Connective-tissue cell from young subcu- taneous tissue : 2v, wing-like expansion seen in profile. Fig. 32. "fixed" or connective-tissue cells 'wandering" cells. The former, in their typical and unrestrained con- dition, are flattened stellate pro- toplasmic plates, each with a nu- cleus occupying the thicker part of the body of the cell, from which branched processes extend; in some instances the protoplasm extends in several planes as thin, plate-like wings. The nuclei are limited by distinct membranes, and frequently contain well-marked nucleoli. While possessing in its early condition the plate-like form in a greater or less degree, the ordinary connective-tissue cell, owing to its participation in the formation of the intercellular tissue, suffers greatly during the later stages of its history; the expanded cell-body soon gives place to smaller outlines, while the protoplasm diminishes until the once large element is reduced to the inconspicuous spindle-cells of adult areolar tissue, in which only a thin envelope of protoplasm sur- rounds the nucleus. The connective- tissue cells, when rich in protoplasm and under favorable conditions, are capable of exhibiting amoeboid move- ments, the variations being, however, limited to alterations of form brought about by the extension or retraction of the protoplasmic processes. Associated with the flattened, plate- like elements of connective tissue, in many places are found the highly- vacuolated plasma-cells of Waldeyer. These are of uncertain form, often irregular, extended, or spindle, and consist of soft protoplasm, which, owing to the numerous vacuoles contained, presents an appear- ance in marked distinction to that of the ordinary branched cell. The plasma-cells probably bear a somewhat constant relation to young tissues in which the formation of new blood-vessels is still progressing. Embryonal connective tissue : the inter cellular substance is only slightly differen tiated. Subcutaneous areolar tissue : c, c, some of the connective-tissue corpuscles ; ui, migratory cells ; v, plasma-cell ; e, elastic fibres. THE CONNECTIVE TISSUES. 37 In addition, occasional peculiar granule-cells must be recognized. These elements, entirely distinct constituents of connective tissues, often appear spherical in form, and are distinguished by the con- spicuous granularity of their protoplasm, the granules possessing a strong affinity for eosin and many aniline stains. The granule-cells occur in especial pro- fusion in the vicinity Fig. 33- of blood-vessels, and seem to be intimately connected with the formation of adipose tissue. In contrast to these larger connective-tis- sue elements, irregu- larly round or ovoid smaller cells are often present, which, from their ability to change their position as well as form, are termed the wandering cells. These consist of small, nucleated masses of active protoplasm, characteristic of the lymph or colorless blood-cells with which they are identical, usually being really leucocytes which have passed out of the vessels into the surrounding tissues, through which they wander as transient guests. The protoplasm of the fixed cells sometimes exhibits accumula- tions of dark particles, the elements then appearing as the large, irregularly branched pigment-cells, Fig. 34. which form con- spicuous ob- jects in the con- nective tissues of many of the lower animals ; in man, such cells occur prin- cipally within the choroid and iris, and in certain parts of the pia mater. The pigment-cells vary in shape and size ; usually stellate and of mod- erate extent in the higher vertebrates, they assume the most elabo- rate and grotesque forms and reach enormous dimensions within the tissues of the lower animals. Fig. 35. Special connective-tissue elements : p, vacuolated plasma-cells ; g, granule- cells. Pigmented connective-tissue cor- puscles from the choroid. Pigment-cell from newt's skin. -g NORMAL HISTOLOGY. The immediate vicinity of the blood-vessels is a favorite locality for pigment-cells, their arborescent processes often forming a net- work completely enclosing the vessel. The supporting stroma of various organs of many of the lower animals frequently contains such cells, the liver constantly presenting con- spicuous groups of deeply-pig- mented elements. Pigment- cells are capable of spontaneous movement, the changes in- cluding not only alterations or retractions affecting the pro- cesses— phenomena directly influenced by the action of the light — but likewise decided alterations in position and location of the cells. The granules of the dark-brown pigment are usually regarded as composed of melanin derived from the coloring-matters of the blood; recent investigations, however, render it probable that, while appar- ently the same, the dark pigment found within the various tissues is by no means always identical in composition. The isolated particles when examined with high amplification are but slightly colored, the charac- teristic tint appearing only when the pigment-granules are massed. Whether the colored particles are taken up by the cells as pre-existing pigment-granules, or whether they are produced within the proto- plasm of the cell, is still undecided ; the evidence, however, seems to favor the conclusion that the particles possess an extra-cellular origin. The arrangement of the connective-tissue cells varies with the age and density of the tissue. Where the cells retain the stellate type, a pro- toplasmic net-work extending through- Fig. 39. Plate -like connective- tissue cells found in ten don. Cell-spaces of dense con- nective tissue in which the cells lie : silvered ground- substance ; from the cornea. Connective - tissue (corneal) corpus- cles : these cells occupy the spaces within the ground-substance. out the tissue is formed by the union of the processes ; examples of such disposition are seen in young mucoid tissues, the cornea, and other connective substances rich in cells. Parallel rows of closely- THE CONNECTIVE TISSUES. 39 placed quadrate elements are seen in tendon, while sheets of flattened endothelioid plates characterize basement-membranes and envelop the bundles of fibrous tissue. In the denser structures the cells occupy spaces within the ground-substance ; these spaces usually communicate directly with one another by means of minute channels, or canaliculi, and form a complicated system of "juice-canals" through the entire tissue. Within these tissue-spaces, or lacun" trip rvni deeply staining areas. J c a> J I cal hyaline variety is usually understood, that form first claims attention. Hyaline cartilage, so named from the transparent, apparently homogeneous character of the intercellular matrix, enjoys a very THE CONNECTIVE TISSUES. 45 Fig. 50. wide distribution, occurring as the articular cartilage of bones, costal cartilages, the larger cartilages of the larynx, trachea, or bronchi, nose, Eustachian tube, etc. ; in the embryo the entire skeleton, with the exception of the vault of the cranium, the bones of the face, and the greater part of the lower jaw, is mapped out by primary hyaline cartilage. The homogeneity of the hyaline matrix is only apparent, since, as long ago pointed out by Leidy, the intercellular substance may be resolved into bundles of fibrous connective tissue, which, however, are so closely united and intimately blended by the cementing ground- substance that the presence of the fibres is, ordinarily, not evident. After prolonged boiling, cartilage matrix yields chondrin. Embedded within the hyaline matrix lie the cartilage-cells ; these are irregularly oval or angular nucleated protoplasmic bodies, which, during life, almost fill the spaces, or lacunae, which they occupy. In adult tissue usually two or more cells share the same compartment, the original occupant of the space having undergone division, so that two, four, or even more daughter-cells form a single group. The matrix immediately sur- rounding the lacuna is specialized as a layer of different density, thereby as- suming the appearance of a distinct limit- ing membrane, described as the capsule. A further differentiation of the ground- substance is seen in the greater intensity with which the more recently formed matrix enveloping the cells stains; such re- sulting figures constitute the cell-areas. It is to be remembered that the cartilage- cells are but connective-tissue cells, and that the lacunas correspond to the lymph- or cell-spaces found in other dense connective tissues. Since it is usual to find these cell-spaces in communication through minute channels, or canaliculi, their absence and the apparent isolation of the lacunae in cartilage are to be regarded as deviations from the typical arrangement ; among some lower forms, however, such a communication exists, the minute canaliculi passing between the neighboring lacunae. The free surface of the cartilage is covered by an envelope of dense connective tissue, the perichondrium ; this consists of an external Hyaline cartilage with perichon- drium (/») attached : y, zone of youngest cartilage-cells; tit, hyaline matrix enclosing the lacunae contain- ing the cartilage-cells ; /, space from which the cell has been lost. .5 NORMAL HISTOLOGY. or fibrous layer of dense fibro-elastic tissue and an inner, much looser stratum, between the fibres of which are numerous connective- tissue cells. This inner portion is intimately concerned in the pro- duction of new cartilage, and is known as the chondrogenetic layer. The cells of the latter arrange themselves in rows parallel to the surface, and gradually assume the characteristics of the cartilage corpuscles, being at first spindle-shaped, but gradually assuming the more spherical form. The new cells soon become surrounded by the recently-formed matrix, which, at first small in amount, soon in- creases so that the groups of cartilage-cells become separated by more extensive tracts of intercellular substance ; as the nests of cells formed by the division of the original single occupant of the lacuna recede from the perichondrial surface they lose their primary parallel disposition and become irregularly arranged and further separated. Sometimes in those portions most removed from the perichondrium the ground-substance appears granular ; this feature is intensified when a deposition of calcareous matter takes place, which not infre- quently happens in old subjects. Elastic cartilage is distinguished by the presence of elastic fibres within the intercellular substance. The typical hyaline matrix is confined to areas of limited extent immedi- ately surrounding the cell-nests, while the in- tervening matrix is penetrated by net- works of elastic fibres extending in all directions. The cells within the lacunae, in the midst of the hy- aline areas, resemble closely the usual ele- ments of hyaline car- tilage. Elastic cartilage has a much less general distribution than the hyaline variety, occur- ring principally in the cartilages of the ex- ternal ear, part of the Eustachian tube, epi- glottis, arytenoid cartilages, cartilages of Wrisberg and of Santorini. This tissue presents an opaque, yellowish tinge in contrast to the Fig Fig. Elastic cartilage from the epi- glottis : c, cartilage-cells sur- rounded by a very limited area of hyaline matrix (K) ; the remaining part of the intercellular substance is penetrated by net-works of elastic fibres (e), cross-sections of which appear as minute points. Fibro-cartilage from the knee-joint : c, cartilage- cells surrounded by very limited areas of hyaline matrix (h) ; the space be- tween these areas is occu- pied by the fibrous tissue. THE CONNECTIVE TISSUES. *j opalescent, bluish tint of the hyaline variety. It is covered by a perichondrium of the usual description. Fibro-cartilage, as implied by its name, is largely composed of interlacing bundles of fibrous connective tissue, embedded in which the round or oval cartilage-cells lie, singly or in groups, immediately surrounded by a narrow zone of hyaline matrix. The number of the cells and the proportion of fibrous tissue present differ in various specimens. Fibro-cartilage is found in comparatively few localities : around the margin of articular surfaces and within certain joints, the sym- physes and the intervertebral disks, constitute its chief distribution. The tissue is closely akin to tendon, presenting a white, tough, re- sistant but pliable tissue. A proper perichondrium is wanting. The development of cartilage proceeds directly from the ele- ments of the mesoderm. The primary close aggregation of the embryonal cells, which early indicates the position of the future cartilage, subsequently gives way to a looser disposition of the cells, resulting from the appearance of the young matrix. After the formation of the perichondrium, the cartilage grows by the addition of new layers beneath the membrane. Fig. 53. BONE. Bone is a dense form of connective tissue impregnated with lime salts. Composed of the same histological elements as other compact connective tissues, bone differs from these in having a deposit of calcareous matter within the interfascicular cement-substance, to which peculiarity the well-known hardness of the tissue is due. The microscopical appearance of bone varies with the character of the prepara- tion, especially as to whether the earthy matter has been removed before sectioning, or whether thin plates of dried bone are examined ; it is in sections of dried bone that the classical pictures of this tissue are seen. Dependent upon the arrangement of the matrix, two varieties of bone are recog- nized— spongy and compact. Although the spongy bone is, as we shall see, the fundamental form, yet the compact variety alone presents all the structural peculiarities of the tissue. A transverse section of the compact osseous tissue constituting the shaft of one of the long bones presents a number Transverse section of dried bone : h, one of the Haversian canals, about which the lamellae are con- centrically disposed, constituting the Haversian systems ; g, the ground or interstitial lamella;. Fig 4g NORMAL HISTOLOGY. of round or oval openings — the Haversian canals — each sur- rounded by a broad band or zone composed of concentrically- disposed lamellae ; the canal and the surrounding lamellae form an Haversian system. Seen in longitudinal sections, the Haversian canals appear as extended channels, some closely corresponding in their course with the general axis of the bone, while others run obliquely and es- tablish free communication between the adjacent canals. The concentric bone lamellae in such sections appear as parallel bands bordering the large channels. The Haversian canals communicate with the central marrow-cavity, of which they are really continuations ; variable in width and length, each canal contains an extension of the bone-marrow, comprising a delicate connective-tissue reticulum, rich in cells, blood-vessels, and lymphatics. The areas between the Haversian systems are filled out by osseous lamellae, disposed without regard to the concentric systems ; these are the interstitial or ground lamellae, and represent the older parts of the bone, being the remains of the primary spongy net-work of periosteal bone. The concentric lamellae constituting the Haversian systems are secondarily deposited within the enlarged spaces of the bony reticu- lum. In addition to the lamellae already mentioned, superficial os- seous strata encircle the bone on Fig. 55. both its outer and inner (medul- lary) free surfaces ; these are the outer and inner circum- ferential or fundamental la- mellae. Between the bundles of the ground - matrix spindle - shaped spaces — the lacunae — are seen, from which minute channels — the canaliculi — radiate in all direc- tions ; these dark, stellate figures with their minute lateral canals form a system of intercommunicating lymph-spaces within the bone ; the canaliculi belonging to the same space or to the adjoining lacunae of the same Haversian system anastomose with one another, but not with the canals of different systems. Longitudinal section of dried bone : h, Haversian canals opened lengthwise and bordered by the longitudinally-cut lamellae. The lacuna? and canaliculi of dried bone under high amplification. A bone-cell lying within the lacuna of the osseous matrix : decalcified and stained. THE CONNECTIVE TISSUES. 40 In dried bone the spaces are filled with air, the lacunas and cana- liculi consequently appearing dark and sharply defined when viewed by transmitted light. The lacunae, sometimes improperly called "bone-cells," in dried preparations are empty, or, at most, contain the remains of the soft, protoplasmic bodies, the true bone-cells, which during life partially fill the spaces ; these, like the cells of other dense connective tissues, lie within the lymph-spaces of the ground- matrix. In sections of young, well-stained, decalci- fied fresh bone, after the usual manipulations, the bone-corpuscles are seen as nucleated, stellate, protoplasmic bodies, whose processes extend into the canaliculi ; in adult and old bones, however, the cells become reduced in size and very inconspicuous. The lacunae being lenticular, they present different figures according to the direction in which they are sectioned : cut transversely, they appear as short, narrow ovals ; opened longitudinally, but not parallel to the lamellae, they are seen as long, narrow, elliptical figures ; while when cut longitudinally, and at the same time parallel to the lamellae, they present a broad, oval surface, sometimes almost circular ; the canaliculi, extending in all planes, appear much the same in all sections. The periosteum, an envelope of vascular connective tissue, closely invests the outer surface of all bones except the articular facets. This important structure is composed of Fig. 57. two portions — an outer, j\ dense, protective, fibrous layer, and an inner, much looser stratum, rich in cells and blood-vessels, which, from its intimate relations to the formation of bone, is known as the osteogenetic layer. This latter contains within its meshes numerous round or spindle cells, many of which later be- come bone-forming ele- ments— the osteoblasts. If a decalcified bone be sectioned parallel to the superficial lamellae, especially if these be of a spongy bone, or if the outer lamellae be forcibly torn off, a number of transverse or perpendicular fibres of 4 Fragments torn from the surface of a decalcified bone : A, surface ; B, oblique view ; s, Sharpey's perforating fibres ; /, the lacunae. c0 NORMAL HISTOLOGY. more or less delicacy will be exposed ; these are the perforating fibres of Sharpey, and represent periosteal fibres which have failed to undergo calcification ; of these Kblliker recognizes two kinds — those entirely soft and uncalcified, the most numerous and, at the same time, the smallest ; and those partly calcified and of larger size, which, in fact, are bundles of fibrous tissue. Sharpey' s fibres are most numerous in the superficial lamellae of spongy bones, although found in the interstitial lamellae of other bones, pinning together the lamellae which they transfix. The perforating fibres, being derived from the periosteum, never occur in the lamellae of the Haversian systems, since the latter, it will be found, are not directly produced by the periosteum, but as secondary deposits. Additional elements of the bone-matrix are the elastic fibres, which are found in the outer fundamental lamellae, as well as occasion- ally in the deeper interstitial lamellae; these elastic fibres are generally associated with the uncalcified Sharpey' s fibres ; not infrequently the elastic fibres are contained within the uncalcified bundles of fibrous tissue composing the large perforating fibres. Marrow of Bone. The cavities within bones, as well as the elaborate intercommunicating nutrient channels extending through- out the osseous tissue, are filled with the highly vascular marrow, which genetically is an extension of the osteogenetic layer of the periosteum, since the primary marrow is a direct ingrowth and ex- tension of this latter tissue. The marrow of all bones in very young animals is red in color ; after a certain time, however, that con- tained within the shafts of the tubular and the spaces of some other bones assumes a lighter tint, finally becoming of a straw color, owing to the ^^ accumulation of fat within '.V;, the marrow-cells. Depend- Y :' ' .'■"■■% ing upon this difference, two •'•;] varieties — the red marrow and the yellow marrow — ;..v;-. are recognized: it is to be "'^-' remembered that the red Elements of the bone-marrow: g-, multinucleated marrOW is genetically the gwnt-cell, or myeloplax ; ,„, marrow-cells ; „, granule- 0jder ^ represents the primary condition. The elements of the red marrow comprise a delicate connective- tissue reticulum supporting a rich vascular distribution, composed of arterioles breaking up into numerous capillaries, which, in turn, give place to venous radicles of large size and extremely thin walls. The THE CONNECTIVE TISSUES. 51 meshes of the tissue contain great numbers of soft, plastic connective- tissue elements, the marrow-cells ; many of these, in actively- growing bone, become the osteoblasts. In yellow marrow the majority of the marrow-cells have undergone transformation into fat-cells. Additional huge, irregular, multinucleated, protoplasmic masses are occasionally encountered; these are the giant-cells, or myeloplaxes (Robin), and are of interest as being elements es- pecially concerned in the absorption of osseous tissue, being iden- tical with the osteoclasts (Kolliker). These cells, with their nuclei, offer an example of what formerly was described as the endogenous mode of cell-formation. Dentine is analogous to bone, although differing in details of arrangement, since it is derived from embryonal connective tissue. The matrix becomes calcified, and contains, embedded within the ground-substance, numerous long, parallel, partly-branched tubes, the dentinal tubules. These correspond with the lacunae of bone, enclosing in some places delicate processes, the dentinal fibres. A more extended account of the structure and development of den- tine will be found in connection with the structure of the teeth. Development of Bone. With the exception of the bones of the vault of the cranium, of the face, and of part of the lower jaw, the skeleton is mapped out, in its fcetal condition, by solid cartilages which correspond in form more or less closely with the future bones. The Fig. 59. primary embryonal cartilage is of the hyaline variety, being extremely rich in cells, many of which are engaged in division; the cell-groups are separated by a relatively small amount of inter- cellular substance, and the outer surface of these solid cartilages is closely in- vested by an important membrane, the primary periosteum. When bone is formed at the Centres Primary embryonal cartilage repre- . . . . senting one of the carpal bones: /, Of OSSlficatlOn Within the Cartilage, It IS perichondrium, or primary periosteum; termed endochondral bone ; when n< nutrient canals extending from the formed directly from and beneath the periosteum, periosteal bone. While quite complicated in its sequence of changes, it must be remembered that endochondral development results in the formation of structures which are largely temporary, and which finally, for the most part, suffer absorption. The permanent bones of the skeleton are, chiefly, the products of 52 NORMAL HISTOLOGY. the periosteum ; where bone is developed directly from the periosteum, and without being mapped out by primary cartilage, the process is spoken of as intermembranous bone-formation, although differ- ing in no important respect from that producing the periosteal bone. Endochondral Bone. found changes within the Fig. 60. mm® , 0&k> Developing bone — centre of ossifica- tion in a carpal bone : z, area of enlarged cartilage- lacuna and calcified matrix ; c, young cartilage-cells. The first indications of the future pro- solid cartilage correspond in position to the so-called centres of ossification, and consist in an increase in the size of the embryonal cartilage-cells, as well as in the amount of intercellular sub- stance separating the cell-nests, followed by a characteristic rearrangement of the enlarged cells into vertical rows or columns ; in the matrix between and around these columnar groups a cal- careous deposit subsequently takes place. These enlarged cartilage-cells, surrounded by the calcified matrix, are the primary areolae of Sharpey. Simultaneously with the changes noted the osteogenetic tissue of the periosteum has increased and sent processes from a number of points into the solid cartilage towards the centre of ossification ; the progress of the periosteal ingrowth is accompanied by the absorption of the cartilage until the focus of central calcification is reached, when the greatly enlarged cartilage-lacuna? are opened up and the spaces brought into direct communication with the primary marrow- cavities. The fate of the cartilage-corpuscles has been the sub- ject of discussion ; it may be assumed as established that these cells undergo degeneration and play no part in the formation of the new bone. This periosteal ingrowth constitutes the vascularization of the cartilage. The process of breaking down the cartilage-cells and opening up the large lacunas goes rapidly forward, resulting in the extension of the primary marrow-cavity; the primary marrow, filling this latter space, is, as already pointed out, the direct deriva- tive of the inner layer of the periosteum. The primary marrow-cavity, or medullary space, soon becoming of considerable size, is bordered by the zone of calcifying cartilage ; this area includes the columns of flattened cells and enlarged lacunas, which pass into the broken and partly-absorbed larger lacunas, the secondary areolae, opening into the primary marrow-cavity. While the horizontal matrix septa between the transversely ex- panded lacunae disappear, the vertical partitions lying between the THE CONNECTIVE TISSUES. 53 columns of the cells suffer much less reduction, and, as a result, remain and project into the marrow-cavity as irregular trabeculae of calcified cartilage. The marrow-cells rapidly multiply and arrange themselves as a layer upon the surface of the cartilage- FlG- 6l- trabeculae ; now called osteoblasts, they busy themselves in enveloping these with a covering of true osseous tissue. Si- multaneously with the deposition of the bone the calcified cartilage within the trabeculae undergoes absorption, so that the amount of cartilage en- cased by the new bone gradually diminishes and finally disappears, the entire net-work of anas- tomosing trabeculae being now composed of true os seous tissue. This newly- formed net-work consti ■^Yyc"^ V( - Vi-S^. SHIP© ( «»n *^** ) seous tissue. This newly- h.' V shafts of the long bones, ^^^^^i'li-'^ft^SX^^s *&% ■ u... . „n.„„ t!> ' ' ^k'*i? X )ti . -^^1,kSJ-^ -* <»# 3i shafts of the long bones, is but temporary, after- wards entirely disappear- ing, except at the ends of the bones, where it per- Developing bone— from the end of a long bone : a, area sistS as the Cancellous of re^anfnS cartilage-cells ; ,,area of enlarged lacuna ;c, zone of calcined matrix ; m, primary marrow-spaces contain- tlSSUe of the extremities. ing the osteogenetic tissue ; b, trabecular of new bone cover- It will be noticed that 'ng the remains (r) of the calcified cartilage-matrix. in the changes above described the cartilage is not directly converted into bone, ossification being a process of substitution, the new bone replacing the primary cartilage. Starting near the middle of the long bones, the process of calci- fication and absorption of the cartilage and the formation of the primary spongy bone proceed towards the extremities, the original cartilage gradually disappearing, the loss being made up by incre- ments of new cartilage deposited on the surface beneath the peri- chondrium. 54 NORMAL HISTOLOGY. Periosteal Bone. Simultaneously with the formation of the central spongy endochondral bone the cells of the osteogenetic layer of the periosteum are actively engaged in likewise producing osseous tissue, the trabeculae of which unite to form the peripheral net-work of periosteal bone, this in many Fig. 63. Developing bone — trabecula of endochondral bone: a, the new bone; 6, bone-cells; c, still unabsorbed remains of calcified cartilage-matrix. Developing bone — the surface of portion of bone-trabecula, exhibiting the conversion of the osteoblasts into the bone-corpuscles : b, lacuna with young bone-cell ; o, osteoblasts arranged on the surface of the newly-formed osseous matrix (m) ; at / an osteoblast just being isolated. places forming an outer envelope closely embracing the central endo- chondral bone. The details of the process by which the osteoblasts are converted into the bone-cells are the same in both the intracartilaginous and the periosteal formation. The bone-matrix, deposited through the agency of the cells, gradually accumulates around the osteoblast, until this lies completely surrounded by the young matrix, when, after its isolation from the marrow-cavity, it becomes the bone-corpuscle. At first the canaliculi are wanting, as are, also, calcareous matters ; these later appear. The conversion of the original spongy into compact bone depends upon the development of additional lamellae within the meshes of the primary osseous net-work. As an initial step, a local absorption takes place, resulting in the enlargement of the pri- mary medullary spaces contained between the trabecular of the periosteal net-work ; these osseous bands are thus reduced to thin bony partitions between large oval cavities, the Haversian spaces. A new growth of bone subsequently takes place within these spaces, THE CONNECTIVE TISSUES. 55 the osteoblasts depositing new bone upon the walls of these cylin- drical cavities, layer upon layer, until only a small central channel — the Haversian canal — remains as the representative of the large Haversian space. The outer boundary of the Haversian system, therefore, corresponds to the limits of the Haversian space, while the remains of the primary bone-trabeculae constitute the older interstitial lamellae of the adult tissue. Osseous tissue, wherever developed, is formed through the agency of the osteoblasts, the deriva- tives and descendants of the special- ized mesoblastic cells of the embryo ; whether in endochondral or periosteal formation, the bone-producing elements Fig. 64. Fig. 65. Developing bone— both periosteal and endochondral: Developing bone— longitudinal section f, outer fibrous, o, inner osteogenetic layer of perios- of embryonal phalanx : e, the primary teum ; /, trabecular of periosteal bone covered by the cartilage of the extremities of the bone ; osteoblasts; e, endochondral bone; ;«, primary marrow- a, zone of enlarged and vertically-dis- cavities. posed cartilage-lacunar ; c, zone of calcifi- cation ; t, trabecular of calcified carti'age covered with new bone ; m, marrow- cavity ; b, periosteal bone formed directly beneath the overlying periosteum,/. arrange themselves over the surfaces of the cartilage-trabeculae or the periosteal fibres respectively, and soon are surrounded by osseous c5 NORMAL HISTOLOGY. matrix ; this gradually thickens and encloses the osteoblasts, which now lie within minute bays or recesses, the entrances to which become gradually contracted, until the opposed FlG- 66- edges join and the cells lie within lacunae completely surrounded by the bone-matrix : the osteoblasts have now become the bone- cells. The matrix is deposited as lamellae, especially marked in the bone formed in the later stages of fcetal life ; between these are included the lacunae. The matrix is at first soft and possessed of a distinct fibrillated structure in which the subsequent deposit Developing bone^portion of of lime salts— principally the phosphate and trabecula undergoing absorp- carbonate takes place. bt^t.w^ix^nT: When, on the contrary, bone or carti- nucleated osteoclast lying within lage is absorbed, it is through the agency JaceuanbaSOrpti0n"pit' 0r Howship's of the giant-cells, the osteoclasts, or chon- droclasts (Klein); these large multinucleated elements usually lie upon the surface of the bone-trabeculae within larger or smaller pits which have been excavated by them ; these are Howship's lacunae. In recapitulation, the following summary of the phases of de- velopment during the growth of a tubular long bone may be noted : i. Solid embryonal cartilage. 2. Enlargement and rearrangement of cartilage-cells and lacunae and calcification of matrix at centre of ossification. 3. Penetration of periosteal tissue to the focus of calcification ; vascularization of the cartilage. 4. Formation of medullary spaces by the breaking down of lacunae surrounded by the zone of calcifying cartilage. 5. Covering of the surface of calcified cartilage trabeculae by the layer of osteoblasts and the production of an enveloping sheath of true bone. 6. Resulting central net-work of endochondral bone, with gradual absorption of encased cartilage trabeculae. 7. Absorption of central spongy bone in shaft and formation of central marrow-cavity. 8. Formation, meanwhile, of peripheral periosteal 7iet-work of spongy bone. 9. Conversion into compact bone by partial absorption of tra- beculae to form Haversian spaces ; secondary deposit of concentric lamellae within these spaces forming Haversian systems of compact bone. THE CONNECTIVE TISSUES. cy 10. Absorption of inner lamellce of compact bone as the shaft increases in diameter by the deposition beneath the periosteum ; production of enlarged medullary cavity. ii. Continued absorption of endochondral central bone until the latter is found alone in the epiphyses, where it continues to be pro- duced at the expense of the intermediate cartilage during the entire future growth of the bone. 58 NORMAL HISTOLOGY. CHAPTER IV. THE MUSCULAR TISSUES. Contractility is possessed, to a certain degree, in common by- all cells rich in active protoplasm ; the distinguishing characteristic of muscular tissue, however, is that this property is so conspicuously developed in highly specialized structures, and that the contractions take place along definite lines in limited directions alone. Con- tractile tissue or muscle occurs in two principal forms: (i) as the non-striated, smooth, or vegetative muscle, usually beyond the control of the will, and hence called involuntary , and (2) as the striated, striped, or animal muscle, which, being influenced by volition, is known as voluntary . The sharp differences separating the two groups of muscle in man and the higher animals cannot be regarded as fundamental, since in the embryonal condition of these higher forms temporarily, and in the adult form of the lower types permanently, the striped and non- striated varieties of muscle depend upon the degree of specialization rather than upon inherent differences. It is a suggestive fact that long before the cells forming the embryonal heart show indications of differentiation into muscle-tissue the contractions of the organ have commenced. The association of the striped fibres with response to the will and, on the contrary, of the plain tissue with involuntary action must be, likewise, only provisionally accepted, since in some animals the development of marked striae never takes place in the voluntary fibres. Standing between and connecting the extremes of these groups is the cardiac muscle of the higher vertebrates, in which the fibres are striated, although beyond the control of the will. NON-STRIATED OR INVOLUNTARY MUSCLE. Non-striated, smooth, or involuntary muscle, while never occurring in large individual masses, enjoys a wide distribution ; its principal localities are — 1. The Digestive Tract: the muscularis mucosae from oesophagus to anus and the delicate bundles of mucosa and villi ; muscular tunic from the lower half of oesophagus to anus. 2. The Accessory Digestive Glands: in the large excretory ducts of liver, pancreas, and some salivary glands ; also in the gall-bladder. 3. The Urinary Tract : in the capsule and the pelvis of kidney, ureter, bladder, and urethra. THE MUSCULAR TISSUES. 59 4. The Male Generative Organs: in epididymis, vas deferens, vesiculae seminales, prostate body, Cowper's glands, cavernous and spongy bodies of penis. 5. 77/.? Female Generative Organs: in oviducts, uterus, and vagina ; in the erectile tissue of external genitals ; in broad and round ligaments, and in erectile tissue of nipple. 6. The Respiratory Tract: in the posterior part of trachea; encircling bands in bronchial tubes, and bundles within pleura. 7. The Vascular System : in the coats of arteries, veins, and larger lymphatics. 8. The Lymphatic Glands : in the capsule and the trabecule of spleen ; sometimes in the trabecular of lymphatic glands. 9. The Eye : in iris and ciliary body, and in eyelids. 10. The Integument : as the arrectores pili connected with the hair-follicles ; in sweat and some sebaceous glands ; in skin covering the scrotum and parts of the external genitals. Involuntary muscle is composed of delicate spindle, often rib- bon-like, fibre-cells ; these vary greatly in size, measuring 75-225 ,u* long and 4-8 fi wide. The cells found in arteries are short Fig. 67. Isolated involuntary-muscle cells from intestine Involuntary-muscle cells from mesentery of of man. newt: «, nuclei; f, axial fibre; m, transverse markings on surface of cell ; B, muscle-cell with forked extremity. and flat, being but 25-45 f1 l°ng and 9-12 /-* wide; the largest ele- ments are found in the gravid uterus, where they reach a length * 1 ^ (micron) =the 1000th part of a millimetre. 6o NORMAL HISTOLOGY. Fig. 69. of over 500 [i and a breadth of 20 p.. Occasional cells with bi- furcated ends are encountered, especially among the lower verte- brates. The spindle muscle-cell is invested with a very delicate, homo- geneous, hyaline sheath, closely resembling elastic tissue, and corresponding to the sarcolemma of the striated fibre ; within this envelope lies the soft, semi-fluid, contractile protoplasm, embedded in which, near the centre of the cell, lies a characteristic, narrow, rod-shaped nucleus. Delicate longitudinal fibrillae sometimes can be made out extending the entire length of the cell ; these are re- garded by many histologists as representing the actively contractile parts of the cell, the surrounding protoplasm being largely passive. Transverse markings are also often seen ; these correspond in posi- tion to local variations in the diameter of the cell, and are probably due to corrugations in the enveloping mem- brane. The individual spindle-cells are closely fitted together and united by an albu- minous cement-substance ; they are dis- posed in groups or bundles, which, on cross-section, are made up of rounded polygonal areas of varying size, the larger possessing round nuclei, while the smaller have none. Since these areas are the sections of nucleated spindle- cells, the large nucleated fields corre- spond to sections passing through the nucleus of the cell, while the small ones are sections of the cell fall- ing near the pointed ends. The bundles of muscle-cells are arranged to form layers or sheets, as in the digestive tract, or net-works, as in the eye, pleura, etc. FlG- 7o. Examined in longitudinal sec- tion, or in considerable masses, it is difficult to distinguish the individual component fibre- cells, the involuntary muscle in such cases closely resembling Involuntary muscle in longitudinal section : the fibrOUS Connective tlSSUe ; how- muscle-cells are often cut obliquely, and hence appear .1 the numerous more or Involuntary muscle in transverse section : portions of three bundles are represented, separated by areolar tissue (a) : the nucleated areas are sections of the muscle-cells through their nuclei ; the smaller figures repre- sent sections of the cells cut nearer the ends. shorter than when isolated. ever, less regularly disposed rod- shaped nuclei, and the absence of the delicate wavy fibres, together with the impression of greater density, usually suffice to establish the identity of the muscle. THE MUSCULAR TISSUES. 61 The connective tissue uniting the larger bundles of muscle-cells supports the blood-vessels and nerves. The larger blood-vessels break up into capillary net-works, which pass between the muscle- cells. The nerves, derived principally from the sympathetic system, likewise penetrate the intercellular spaces and terminate between the cells in the manner more fully described in the chapter devoted to nerve-endings. Lymphatics occur, as in parts of the digestive tract, closely associated with the muscular tissue. STRIATED OR VOLUNTARY MUSCLE. Striated or voluntary muscle, in addition to the extensive system attached to the skeleton, supplies the special muscles connected with many organs, including the tongue, pharynx, middle ear, larynx, upper half of the oesophagus, diaphragm, generative organs, etc. This form of muscle is composed of long, irregularly cylindrical fibres, each of which represents the high specialization resulting from the development of the single original embryonal cell ; the fibre is, therefore, the structural unit of the striated muscular tissue, and corresponds to the spindle fibre-cell of the involuntary variety. The fibre of striped muscle comprises {a) the sarcolemma, {b) the muscle- nuclei, and (c) the muscle-substance. Each fibre is closely invested by a clear, homogeneous, elastic sheath — the sarcolemma — which, ordinarily, so tightly adheres to the enclosed muscle-substance that the two are optically blended together; in favorable positions, Fig. 71. as where breaks in the sarcous substance occur, or after the action of water, the sarcolemma is separated from the muscle-substance, and is then seen in profile as a delicate line spanning the break in the continuity of the fibre. The sar- colemma forms a closed sac completely envel- oping the contractile substance of the fibre. Immediately beneath the sarcolemma, lying within minute depressions on the surface of the muscle-substance, are the muscle-nuclei. These are oval or fusiform, usually placed parallel to the long axis of the fibre, and sur- rounded, especially at their ends, by a small amount of granular protoplasm. These accumu- lations represent the meagre remains of the indifferent protoplasm which has not undergone conversion into the highly specialized muscle-substance of the fibre. In mammalian muscle the nuclei lie always upon the surface of the sarcous substance of the fibre and immediately beneath the sarco- Voluntary-muscle fibres, somewhat broken after treatmeat with water, showing the sarcolemma (s) in several places. 62 NORMAL HISTOLOGY. lemma; in the majority of other vertebrates, however, the nuclei are distributed irregularly throughout all parts of the contractile substance. These differences are well shown in the accompanying figures. The muscle -fibres present alternate light and dark transverse markings, or striae, to which the tissue owes its characteristic appear- ance. The highly specialized contents of the sarcolemma are composed of two substances pos- sessing different refractive prop- erties, that forming the dark bands being doubly refracting, or anisotropic, while that of Fig. 72. i Fibres of voluntary muscle in section : A , human fibres, with nuclei upon the surface and beneath the sarcolemma ; B, fibres from frog, with nuclei embedded within the muscle-substance. Voluntary muscle, portions of two fibres show- ing the characteristic transverse markings ; the lighter band is divided by the row of minute beads constituting the intermediate disk : a, termination of muscular substance and attachment of adjoin- ing fibrous tissue ; n, nuclei of muscle-fibres. the light striae is singly refracting, or isotropic. When fresh or well-preserved mammalian muscle is examined under high am- plification it is seen that the dark striae, or transverse disks, are not unbroken homogeneous bands, but that each is composed of a number of minute prismatic elements placed side by side and sep- arated from one another by a thin layer of a substance corresponding to and continuous with that forming the light zone. This latter, in addition, is divided transversely by a delicate interrupted line or row of dark dots — the intermediate disk, or membrane of Kranse. That part of the light zone between the dim intermediate and trans- verse disks constitutes the lateral disk. The explanation of these appearances has caused many and pro- longed discussions, and even at present, notwithstanding the careful study bestowed upon the subject, the exact structure of voluntary muscle must be regarded as still unsettled. Heretofore two promi- nent and opposed views have prevailed : the one regards the fibre as composed of parallel longitudinal rows of minute prisms forming fibrillae (as rows of bricks placed end to end); the other considers the fibre as built up by the apposition of their disks, whose diameter corresponds to that of the entire fibre (as cheese-boxes piled one THE MUSCULAR TISSUES. 63 upon the other). After treatment with alcohol, the fibres of striped muscle readily split up lengthwise into delicate bundles, which, with care, may be subdivided to such an extent that the resulting threads embrace in their width only a single row of alternating light and dark elements. These ultimate fibrillae were formerly considered by Kolliker as the normal elements of the fibre ; the dark prisms of these fibrillae correspond to the sarcous elements, which were regarded by Bowman as the component units of muscular tissue. The transverse cleavage of the fibre following the action of diluted mineral acids, on the other hand, has been upheld as representing the natural division. According to Krause, the fibre is divided through the light bands by a number of transverse partitions con- tinuous with the sarcolemma ; these assumed septa appear as delicate broken lines — the membranes of Krause — and are identical with the intermediate disks already mentioned. Adopting this view, the fibre is composed of numerous thin zones or contractile disks, each of which embraces the dark dim band in its centre and half of the light stripe at either end. Each contractile disk is further sub- divided by vertical partitions extending between the neighboring membranes of Krause, thus forming in every disk a row of com- partments or muscle-caskets. The portion of the dim band con- tained within each muscle-casket has been regarded as itself being composed of a series of thin prisms of contractile substance — the muscle-rods. After renewed critical study of the subject, Rollett has presented a view regarding the structure of voluntary muscle which not only offers the most plausible solution of this difficult problem, but is, likewise, in harmony with the history of the development of the tissue. According to this theory, the muscular tissue is composed of the highly specialized, darker, anisotropic contractile substance, and the relatively passive, lighter, semi-fluid, isotropic sarcoplasm. The contractile substance is arranged as delicate spindles, the appo- sition of whose thicker parts produces the dim transverse disk seen under medium amplification ; at either end the spindle is prolonged as an extremely thin thread, which terminates in a minute sphere or bead ; the apposition of these beads in the transverse row gives rise to the appearance of the interrupted line constituting the inter- mediate disk, or Krause' s membrane. The darker anisotropic sub- stance forms, therefore, numbers of continuous contractile fibrillae, which extend in parallel bundles the entire length of the fibre ; all the remaining interfibrillar space within the sarcolemma is filled with the lighter sarcoplasm, which appears faintly granular in preserved tissue, but is, probably, almost fluid during life. On comparing this description with the usual appearances presented by striated muscle, 64 NORMAL HISTOLOGY. Fig. 74. it will be seen that the lateral apposition of the thicker parts of the contractile fibrillce produces the dark band, or transverse disk, while the row of minute spherical masses appears as the interrupted dark line bisecting the light zone, or intermediate disk. The threads bridging between these beads and the chief mass of the fibrillae are too delicate to be appreciated under ordinary powers, and that portion of the fibre corresponding to the lateral disk consequently appears as if made up of the lighter sarcoplasm alone. In certain forms of invertebrate muscle a more complicated arrangement exists, since on either side of the intermediate disk a row of dark granules crosses the light lateral disk, forming a dim secondary disk ; these gran- ules are connected with the intermediate and transverse disks by delicate bridges of con- tractile substance, along which they occur as local thickenings. The dim transverse disk sometimes contains a central lighter band, the median disk of Hensen, which is due, probably, to diminished thickness of the con- tractile fibrils. The contractile fibrillae, however, are not uniformly distributed throughout the fibre, but are aggregated into bundles — the muscle- columns — each of which is enveloped in a thicker layer of the sarcoplasm than the partitions separating the individual fibrillae. In transverse section each muscle-fibre presents a number of small, polygonal, dark areas, enclosed by lighter lines, which areas, under high amplification, exhibit minute punctations. These areas are sections of the muscle-columns and correspond to Cohnheim's fields, the dots being sections of the individual constituent fibrillae ; the lighter intervening and surrounding substance is the sarcoplasm, thicker layers of which surround and separate the larger groups into which the muscle-columns are further collected. The individual muscle-fibres, which usually are not circular in cross-section, but rather irregularly polygonal with rounded angles, are held together by a small amount of areolar tissue, the endo- mysium. They are grouped into primary bundles, which latter are enveloped and separated from other primary bundles by the thicker bands of connective tissue constituting the perimysium. The primary bundles are united to form larger secondary groups or fasciculi, upon the width and arrangement of which the coarseness A, diagram of arrangement of the contractile substance according to the view of Rol- lett : the granular figures rep- resent the contractile elements, the intervening light areas the sarcoplasm ; B, small muscle- fibre of man ; the correspond- ing parts in the two figures are indicated : t, i, I, respectively the "transverse, intermediate, and lateral disks ; n, muscle- nuclei. THE MUSCULAR TISSUES. fa or the fineness, macroscopically appreciable, of the muscle largely depends. The entire muscle is invested in a fibrous sheath, the epimysium, derived from the denser layers of the interfascicular connective tissue. When contraction takes place, the entire muscle becomes shorter and, at the same time, broader ; the striae also participate in the changes, becoming narrower. Fig. 75. These phenomena, however, affect only a A B limited part of the fibre at one time, consecu- tive portions being influenced in regular se- quence, so that the changes pass along the fibre as a contraction wave ; after the passage of the wave the muscle resumes its previous condition. In short muscles the individual fibres quite frequently extend the entire length ; in long ones, on the contrary, the fibres are shorter than the muscle, being generally some 30-45 mm. long; sometimes, however, the fibres reach a length of 120 mm. by 10—50 mm. in width (Felix ). The fibres, as a whole, are gen- erally somewhat spindle-shaped, being slightly larger in the middle ; the ends of the fibres are more or less pointed, although blunted or club-shaped, and, more rarely, Muscle-fibres in transverse section, highly magnified : A, portion of human muscle : the small, irregular areas are the fields of Cohnheim (c) ; B, semi-diagrammatic view show- ing the groups of muscle col- umns composing Cohnheim's fields ; n, nucleus ; m, groups of muscle-columns. Fig. 76. branched, extremities are not un- common. Branched and anas- tomosing fibres frequently occur (Gage), especially in the tongue Fig. 77. Voluntary muscle in transverse section : the irregular polyhedral areas (_/") are the individual muscle-fibres in section, held together by the en- domysium (t>) ; the primary bundles of the fibres are enclosed by the denser perimysium (/). Branched voluntary-muscle fibres from the tongue. and ocular muscles. When the individual fibres do not extend the length of the entire muscle, the sarcous substance terminates in 5 56 NORMAL HISTOLOGY. pointed or rounded extremities, while the sarcolemma is united with the endomysium of the surrounding fibres. The muscle-substance is never directly continuous with adjacent tissues, but is always enclosed within the sac of the sarcolemma ; the union between the fibres and other structures is effected by the blending of the endo- mysium of the muscle-fibres with the connective tissue of the attach- ments, whether these be tendon, periosteum, perichondrium, or subcutaneous tissue ; the sarcolemma closely invests the sarcous contents, being simply received into the connective tissue without becoming directly continuous. CARDIAC MUSCLE. The muscular tissue of the heart, as well as of the cardiac ends of the large veins, forms an intermediate group of contractile tissue, standing in its development between the simple spindle non-striated cell on the one hand and the highly differentiated striped fibre on the other. Among the lower vertebrates (fishes, amphibians) the cardiac muscle is composed of nucleated spindle-cells possessing distinct transverse striations and often branched ends ; in man and the higher vertebrates these spindle- cells give place to short, striated, cylindrical fibres, provided with lateral processes. By the apposition of these richly-branched cells a close, narrow-meshed net-work is formed, the Heart - muscle, showing ;uncture between the individual elements being- several joined branched Jm ° fibres: around the poles of indicated by transverse lines of cement-sub- the nuclei are aggregations stlllCP of pigment-granules. ' I he peculiarities ol heart-muscle are — i. The absence of the sarcolemma, the transversely striated and more faintly longitudinally marked muscular tissue being naked. 2. The situation of muscle-nuclei within the sarcous substance, usually near the centre of the cell. 3. The characteristic arrangement of the contractile fibrillae, since these are so placed that the peripheral fibrillae are grouped into flat, ribbon-like muscle-columns, somewhat radially disposed about the circumference of the fibre ; the remaining central portion is occupied by prismatic bundles of fibrillae, together with the nuclei and the associated protoplasm (Ranvier, Kolliker). The small masses of pro- toplasm which surround the muscle-nuclei usually contain minute fat-drops and pigment-granules. The amount of pigment normally present varies with age, increasing from the tenth year (Maass). Heart-muscle fibres in sec tion : the peripheral zone is composed of radially-ar- ranged groups (/) of muscle- columns ; a zone (c) of less differentiated sarcoplasm surrounds the nucleus. Fig. THE MUSCULAR TISSUES. 67 Sometimes, in preserved tissue, the position of the nucleus is occu- pied by a clear vacuole. Ranvier has called attention to certain differences in the muscles of the rabbit, describing two varieties — the red or especially dark, (semitendinosus, soleus) and the white or pale (adductor magnus). The red muscles are char- acterized by slow response to electrical stimulus, less regular transverse striation, greater dis- tinctness of longitudinal markings, and great number of round nuclei. The blood-vessels of striated muscle are very numerous. The larger vessels, together with the nerve-trunks and, less frequently, the lymphatics, are contained within the perimy- sium, where they give off numerous smaller branches ; these, in turn, extend between the primitive bundles and break up into extremely thin capillaries, which form a characteristic rectangular-meshed net-work around the indi- vidual muscle-fibres. The longer sides of the meshes correspond with the axis of the fibre. At various points along the course of these vessels peculiar dilatations, or ampullae, occur, the object of which is, probably, the relief of sud- den temporary interference with the circulation during muscular contractions. The relation be- tween the capillary blood-vessels and the muscu- lar fibres of the heart is very intimate ; in many places the vessels lie embedded within or even en- tirely surrounded by the muscular tissue (Meigs). Lymphatic vessels occur in striated muscle in small numbers, but are entirely wanting in many small muscles ; when distinct lymphatic vessels do occur, they are confined to the larger and looser masses of the perimysium (Kolliker). The nerves supplying the striated muscle include the principal trunks which run within the perimysium, where they subdivide into smaller groups of medullated fibres, in order to reach the individual muscle-fibres ; these latter receive their nervous supply at certain points only, the nerves passing to the muscle to end in the special end-plates in the manner described more fully in connection with the peripheral nerve-endings. The development of all varieties of muscular tissue is closely related to the mesoderm, of which they are the direct descendants. The plain or non- striated muscle is formed by the differentiation, Injected voluntary mus- cle : the capillaries form rectangular-meshed net- works enclosing the indi- vidual fibres. 68 NORMAL HISTOLOGY. within certain areas, of the irregular mesodermic elements into the elongated fusiform fibre-cells. In suitable preparations all gradations between the ordinary embryonal connective-tissue cells and the muscular elements may be observed, emphasizing the common ancestry of the two forms of tissue. Voluntary muscle, representing a higher specialization, is de- rived from definite areas constituting the inner layer of the muscle- plates, which are referable to the early stages of the primary segmenta- tion into somites. The cells of the muscle-plate soon elongate, with pro- liferation of the nuclei, to become the primitive muscle-fibres. These at first consist of greatly extended ele- ments, possessed of numerous nuclei and composed of granular indifferent protoplasm. After a time the fibre exhibits a differentiation into longi- tudinal striae, which, later, are supple- mented by the transverse markings characteristic of voluntary muscle. The sarcolemma appears about the time the longitudinal markings are seen. The striations are limited, at first, to one side of the fibre, then extend over the entire periphery, but still for some time do not reach the centre of the fibre, an inner zone of undiffer- entiated sarcoplasm occupying the middle. Later, this area also becomes converted into striated tissue, while the once numerous nuclei are reduced to the few collected beneath the sarcolemma. Cardiac muscle, likewise, develops from the mesoderm immediately surrounding the primary heart-tubes, the contractions of the cells being displayed even before the histo- logical differentiation becomes apparent. In its development it represents an intermediate stage, since the original spindle-cells be- come converted into protoplasmic fibres containing a central area which always remains less differentiated and nearer its primary con- dition of indifferent sarcoplasm than the peripheral portions of the fibre. The fibres of Purkinje, found in the hearts of certain rumi- nants, represent muscular fibres in which the sarcoplasm remains in part still undifferentiated. Developing voluntary muscle: A, young muscle cells; a, very young spindle-cell ; i, older element, exhibiting indications of future striation on one side ; the remaining part of the cell is composed of the undifferentiated sarco- plasm ; B, embryonal muscle-fibres pos- sessing many nuclei and traces of strise ; C, developing muscle-fibres in section ; in the larger fibres a differentiated peripheral zone of striae (d) is seen in section ; an area of still indifferent sar- coplasm occupies the centre of the fibre and surrounds the nucleus («). THE NERVOUS TISSUES. 69 CHAPTER V. THE NERVOUS TISSUES. The nervous system is composed of three principal parts — the tissues originating nervous impulse, the nerve -cells ; the structures serving to transmit such impulses, the nerve-fibres ; and the tissues uniting and supporting the nervous elements, the neuroglia and connective-tissue framework. The nerve-cells are the primary elements, being older in the development of the individual as well as in the evolution of the nervous system. In certain inverte- brates both generation and transmission of the impulse are performed by the same cell, the peripherally situated protoplasm serving to convey and expend the force originating within the more centrally lying parts of the cell. Such simplicity, however, is unusual, the nerve-cell soon becoming specialized and separated from the pe- ripheral area with which it is connected. NERVE-CELLS. Nerve- or ganglion-cells of man and other vertebrates differ greatly in form and size, since they may be either spherical (Gasserian, spinal, or other ganglia), ellipsoidal (spinal cord), pyriform (cere- bellum), pyramidal (cerebrum), or stellate (spinal cord), and vary from 10 to 100 /jl in size ; the huge cells of the spinal cord are among the largest elements of the body. In general the cells of motor areas are largest, those found in the convolutions bordering the central fissure and in the anterior cornua of the spinal cord being of conspicuous size. The ganglion-cells are composed of granular or striated proto- plasm, containing a large round or oval vesicular nucleus within which lies a prominent nucleolus ; after certain stains the protoplasm, nucleus, and nucleolus present distinct tints. Many nerve-cells are deeply colored, owing to the presence of considerable quantities of pigment-granules around the nucleus ; a certain amount of pigment within the protoplasm is almost constant. The protoplasm of every nerve-cell is prolonged into at least one and usually several processes, dependent upon the number of which it is customary to speak of nerve-cells as unipolar', bipolar, or multipolar. Since an apolar nerve-cell is, evidently, functionally useless, it is doubtful whether such cells ever normally exist ; apolar cells are frequently seen in preparations, but the absence of the 7° NORMAL HISTOLOGY. Fig. 82. processes is only apparent, being due either to mutilation or to the process lying without the plane of the section ; where processes are really wanting, an immature or pathological condition must be suspected. The processes of nerve-cells are of two principal kinds — the protoplasmic (dendrits) and the axis-cylinder {neurits) pro- cesses. When a cell possesses but one, this is always an axis- cylinder process. The proto- plasmic processes or dendrits rapidly undergo division, splitting up and sub- dividing until the resulting branches form rich net-works or arborizations of slender threads, which frequently interlace, but probably never actually join, with similar fibrils of adjacent cells. Nerve-cells, in one sense, are but nucleated local accumula- tions of the interfibrillar pro- toplasm, which latter may be termed neuroplasm (K61- liker) ; the large striated multipolar ganglion-cells may be regarded as switch -boards for the redistribution of the numerous ultimate fibrillae continued into the axis-cylin- ders. The fibrillae pass off in Nerve-cell from the cerebral cortex, exhibiting the divergent paths alone the striationsof the protoplasm and the conspicuous char- 1 C U^ 11 acter of the nucleus and the nucleolus: /, pigment- Several processes OI the Cell, granules : a, axis cylinder process ; b, I, apical and tQ form new combinations and lateral protoplasmic processes. , , . relations. The peculiarities formerly supposed to constitute the distinguish- ing characteristics of the axis-cylinder processes are no longer suf- ficient in the light of recent advances in our knowledge regarding the structure of the nervous system. The investigations of Golgi and others have shown that, in addition to greater delicacy and a straighter course, the axis-cylinder processes present variations which separate ganglion-cells into two groups — cells of the first and cells of the second type. Nerve-cells of the first type include elements, as those of the motor areas, possessing the characteristic axis-cylinder processes THE NERVOUS TISSUES. nX directly continuous with the axis-cylinder of the 7ierve-fibre. While these processes, when compared with the richly-divided protoplasmic, may be regarded as unbranched, the existence of delicate lateral off- shoots, or collateral fibrils, has been established ; these delicate branches pass backward towards the gray matter, within which they end. Nerve-cell from the spinal cord, isolated by maceration and teasing ; the numerous branched pro- toplasmic processes are somewhat displaced and distorted, owing to manipulation : a, axis-cylinder process. Nerve-cells of the second type are distinguished by the be- havior of the axis-cylinder process ; this, instead of passing into the white matter to become the centre of a nerve-fibre, never leaves the gray matter in which the ganglion-cell lies, but, after a longer or shorter course, rapidly tindergoes division and subdivision in the production of a terminal arborization of delicate fibrillar ; these ramifications are limited entirely to the gray matter, their exact manner of ending and their relations to other cells varying in dif- ferent parts. The free division of the axis-cylinder process does not curtail the branching of the protoplasmic extensions, which are often very conspicuous, notwithstanding the numerous bifurcations of the former. In some instances the axis-cylinder processes of cells of this type split up into fibrils which enclose the bodies of other nerve-cells within basket-like net-works ; a notable ex- ample of this arrangement exists in the cerebellum around the cells of Purkinje. 72 NORMAL HISTOLOGY. Fig The axis-cylinder processes usually are directed towards the nearest mass of white matter, since the axis-cylinder of the nerve- fibre becomes continuous with that of the cell. Exceptional arrangements are sometimes encountered, as where one process of a bipolar cell becomes wound about the remaining straighter fibre, con- stituting a spiral process ; such cells are comparatively frequent in the sym- pathetic ganglia of the frog. Ganglion-cells lie within peri-cellu- lar lymph-spaces, which appear with greater or less Fig. 85. distinctness ac- p.lji){$'f/1 cording to the condition of the Fig. 86. Nerve-cell of first type — from cere- bral cortex: p',p, protoplasmic pro- cesses directed respectively towards the free surface and laterally ; a, axis-cylin- der or nerve-process giving off collateral branches, c, c. Golgi staining. Nerve-cell of second type — from cerebellum : /, branched protoplasmic processes ; c, cell- body ; a, axis-cylinder process breaking up into arborization («), but entirely confined to gray matter. Golgi staining. Basket-work, formed by the extensions of the branched axis -cylinder process of a nerve-cell, surrounding the body of one of the ganglion-cells of Purkinje : p, base of branched process of I'ur- kinje's cell ; n, fibrils con- stituting basket-work. protoplasm of the enclosed cell ; when this is contracted and shrunken the space is, obviously, more conspicuous than when almost entirely filled by the cell. These lymph-spaces are limited by a delicate, elastic, hyaline membrane, and lined with nucleated endothelial plates ; on the exit of the axis-cylinder a delicate prolongation of this sheath accompanies the fibre as the neuri- lemma. NERVE-FIBRES. Depending upon the character of the investing coats, nerve-fibres appear as two kinds — the medullated, or white, and the non- medullated, or gray. These do not, however, constitute two sharply defined and distinct classes, but depend upon variations in the condition of fibres, which often represent both varieties at dif- THE NERVOUS TISSUES. 73 Fig. 87. ferent portions of their course. Every medullated nerve-fibre loses its white substance of Schwann and becomes non-medullated before reaching its ultimate distribution. The majority of nerve-fibres constituting the great cerebro-spinal tract may be classed as med- ullated, although numbers of gray fibres likewise occur here ; the non-medullated fibres are especially numerous in the sympathetic system, where they predominate, as well as in certain of the cranial nerves, as the olfactory. While the character of the fibre, as to whether it is motor or sensory, bears no relation to its size, the length of the fibre seems to directly influence its diameter, since fibres having long courses possess greater width than those extending for much shorter distances. A typical medullated nerve-fibre consists of the following parts : 1. The axis -cylinder, surrounded, possibly, by its sheath, or axilemma (Kiihne). 2. The medullary substance, or white matter of Schwann. 3. The neurilemma, or sheath of Schwann, with the nerve-corpuscles. Perfectly fresh, uninjured, medullated nerve -fibres, when examined by transmitted light, appear as homogeneous, hyaline cylinders, with dark contours and no appreciable structure ; seen by reflected light, the fatty character of the medullary substance is indicated by the glisten- ing appearance of the fibres, and their dull white color when viewed in masses. Shortly after death the fibres exhibit characteristic double contours, enclosing an apparently structureless centre ; later, the fibres become mottled by irregular spherical masses, derived from the dis- torted medullary substance. The axis-cylinder appears, in fresh nerves or in those fixed with osmic acid and teased, as an inconspicuous, clear, delicate rod extending along the central part of the fibre, or, perhaps, projecting beyond the outer sheaths at the broken end. The longitudinal striations occasionally seen, under high amplification, in carefully fixed preparations, are indi- cations of the ultimate fibrillae of which the axis-cylinder is com- posed ; these fibrillae are cemented together by a finely granular, interstitial substance, or neuroplasm (Kolliker). According to Kiihne, the axis-cylinder is enveloped by a special, delicate, elastic Nerve-cell from a sym- pathetic ganglion of frog, showing the tortuous course and terminal net-work of the spiral fibre : n, neuri- lemma continued as a deli- cate sheath. ( After Ket- zius.) -4 NORMAL HISTOLOGY. sheath — the axilemma (Kiihne) ; other authorities regard this appearance as an artihcial production. Since every axis-cylinder is connected with the corresponding process of a nerve-cell, axis-cylinders may be regarded as direct conciliations of the ganglion-cells, their component fibrillar Fig. 88. forming uninterrupted paths which con- nect the periphery with the presiding nerve-centres. On approaching its ter- mination, the axis-cylinder splits into smaller bundles of component fibrillae ; these groups subsequently divide, until, finally, the naked ner- Fig. 8q. vous threads, singly or in small groups, reach their ultimate destination. The nerve-nbrilla? not in- frequently exhibit nu- merous minute fusiform enlargements or vari- cosities along their course, giving to the fibrils a characteristic beaded appearance, es- pecially after gold-stain- ing. The medullary sub- stance, or white matter of Schwann, surrounds the axis-cylinder, and forms the most con- spicuous investment of the fibre. The existence of a narrow lym- phatic cleft described as lying between the medullary substance and the axilemma is still uncertain. The medullary substance consists of two parts : one of these occurs as a delicate reticulated frame- work, composed of a resistant material probably resembling neuro- keratin (Kiihne and Ewald) ; the other fills the interstices of the reticulum and appears as a semi-fluid, highly refracting, fatty sub- stance— the myelin — which affords protection to the enclosed axis- cylinder. Other authorities regard the reticulated framework as the effect of reagents, citing the variability in the appearances of the net-work as opposed to its presence as a normal constituent of the coat. At regular intervals along the medullated nerve-fibres well-marked annular constrictions occur ; these are the nodes of Ranvier, and mark the interruption of the white substance of Schwann at certain points. Medullated nerve-fibres : A , teased in salt solution, x, shortly after death ; y, a node of Ranvier ; z, post-mortem distortions of med- ullary substance. B, an isolated stained fibre; a, axis-cylinder ; r, node of Ranvier; tn, medullary substance ; n, neurilemma, beneath which a nerve-corpuscle is seen in the lower segment. Gold-stained axis- cylinder (a), showing component fibrillar ; i, varicose nerve- fibrilla; near their termination. THE NERVOUS TISSUES. 75 Fig. 90. Owing to the absence of the middle coat in these positions, the outer sheath, or neurilemma, is brought into contact with the continuous axis-cylinder. The portions of the fibre included be- tween two constrictions — the internodes, or internodal segments — vary in length with the size of the fibre, being longer (about 1 mm.) in large and much shorter in thin fibres. Each internode pos- sesses a single nerve-cor- puscle, usually about its middle, and probably elon- gates during the growth of the nerve. The neurilemma is not broken by the nodes into segments, but forms a continuous sheath. When a medullated nerve - fibre branches, the bifurcation cor- responds in position to a node of Ranvier. After treatment with silver nitrate the positions of the nodes of Ranvier are rendered conspicuous by the appear- ance of minute dark-brown crosses ; the transverse arm is formed by the stained, internodal albuminous sub- stances, forming an annular disk, sometimes called the constricting band (Ranvier), while a stained portion of the axis-cylinder con- tributes the less distinctly marked vertical lines of the cross. Closely-placed transverse markings, known as Frommann's lines, as well as bi-conical swellings, occasionally are noted along the axis- cylinder after treatment with silver ; their significance, however, is still undetermined. The medullary substance is very prone to post-mortem change, the coagulated or partly disintegrated myelin producing various grotesque distortions in the contour of the nerve-fibre. After treat- ment with osmic acid and other reagents, the white substance of Schwann displays oblique markings which are, apparently, clefts or incisions involving the middle coat ; relying upon these appearances, many regard the medullary substance as made up of elongated pieces, the Schmidt-Lantermann segments, several of which are in- cluded within each internode. Medullated nerve- fibres after treatment with osmic acid, from frog: A , fibre displays the incisions of the me- dulla, or Schinidt-Lan- termann segments; B. the medullary substance exhibits a reticulated appearance. Silvered nerve-fibres : A, small bundle of medullated fibres displaying the silver crosses atseveral nodes ; B, node of Ranvier under high power: the horizontal limb of the cross is produced by the stained intersegmental cement-substance ; the ver- tical limb is formed by the colored axis-cylinder; C, silvered axis-cylinder show- ing a bi-conical enlarge- ment and the transverse markings or lines of From- mann. Fig -5 NORMAL HISTOLOGY. The neurilemma, sheath of Schwann, or primitive sheath, the outer covering of the nerve-fibre, is a delicate, homogeneous, elastic membrane, closely investing the medullary substance, and resembling the sarcolemma. On its inner surface, placed at regular intervals corresponding to the position of the nodes of Ranvier, are the nerve-corpuscles, meagre accumulations of protoplasm sur- rounding the oval nuclei. The medullated fibres of the white matter of the brain and spinal cord, as well as those composing the optic and acoustic nerves, are noteworthy as being without a neurilemma, the surrounding neuroglia in these positions assuming the support and covering of the fibres. The non-medullated, pale, or Remak's fibres, as indicated by the first name, are devoid of medullary substance, consisting of the axis-cylinder and the more or less modified neuri- lemma ; such fibres, when aggregated, appear as grayish, semi-transparent bands. While every medullated nerve-fibre, before reaching its pe- ripheral distribution, loses the white substance of Schwann and becomes sooner or later a non- medullated fibre, the nerves constituting the sympathetic system especially represent this group, and evince the distinctive tendency to give off branches, which unite to form the char- acteristic plexuses. The presence of both va- rieties of fibres, however, in nerve-trunks is quite usual ; a conspicuous example of this asso- ciation is found in the vagus of the dog, where large bundles of both kinds are included within a common sheath. The fibrillae constituting the axis-cylinders of non-medullated fibres are especially distinct, this feature being probably due to the generous amount of neuroplasm separating the fibrillae ; not infrequently local accumulations of this interfibrillar substance occur, producing the conspicuous varicosities seen along the course of the fibres. The nerve-nuclei are far more numerous than in medullated fibres ; they are, however, irregularly distributed, lying upon the surface of the fibre and beneath the outer delicate sheath. This enveloping sheath — the attenuated representative of the neurilemma — is often difficult or impossible to distinguish, being very thin and closely adherent to the fibre. The smallest nerve-fibrils are probably without this coat, the fibrillae continuing as naked bundles, with the exception of the imperfect covering afforded by the numerous overlying nerve-nuclei. Non-medullated nerve-fibres are prone to form rich plexuses, the Non-medullated nerve- fibres from the sympa- thetic system : the nucle- ated fibres join to form a plexus. THE NERVOUS TISSUES. 77 junction of several fibres being frequently marked by characteristic triangular areas, in which a number of the nerve-nuclei are often collected. Fig THE NERVE-TRUNKS. The nerve-fibres already described are associated in bundles — the funiculi — which, in turn, may be grouped to constitute the large macroscopic nerve-trunks. The funiculi differ greatly in diameter, a number of varying size being usually included within the nervous cord ; in very small nerves, however, a single funiculus may suffice to form the entire trunk. While both kinds of fibres are grouped in bundles, the nerves composed principally of medullated fibres present the more typical arrangement. On transverse section of such trunks the individual nerve-fibres appear as small, round, nucleated cells, whose somewhat eccentrically placed nuclei are the axis-cylinders in section, while the contours of the cell-like areas are formed by the sections of the neurilemma ; the shrunken granular or concentrically marked masses within the apparent cell-walls are the remains of the medullary substance. These sec- tions of the fibres are held in place by a delicate connective tissue — the endoneurium — extending among and surrounding the individual fibres. When the nerve- bundle, or funiculus, is small, the nerve-fibres are uniformly dis- tributed, and it is spoken of as simple ; when large, however, the fibres are usually divided into irregular groups by stronger fibrous trabecular, thus forming a compound funiculus. The individual nerve-fibres vary greatly in diameter (from 2 to 20 ,«), even adjoining fibres often exhibiting marked differences. In general, the cerebro- spinal nerves possess the largest fibres, the sympathetic much the smallest (2 to 4 fi), while the components of many of the cranial nerves occupy an intermediate position. Each funiculus is invested by a robust connective-tissue sheath — the perineurium — between the fibrous lamellae of which are seen Section of portion of a nerve-trunk including three bundles, or funiculi, surrounded by the perineurium (/) ; the funiculi, together with the bloodvessels and adipose tissue, are united by the more general epineurium (e) ; the sections of the individual nerve-fibres are held in place by the endoneurium ; /, fat-cells, near which are the sections of blood-vessels. 78 NORMAL HISTOLOGY. the nuclei of the endothelioid plates lying within the interlamellar lymphatic spaces. The endoneurium is directly continuous with the perineurium, of which it is the intrafunicular extension. Where a nerve-trunk comprises several funiculi, these are held together and enveloped by a loose general connective tissue — the epineurium — which supports the blood- Fig. 94. vessels and lymphatics, and often contains masses of adipose tissue ; the external layer of the epineurium is usually somewhat condensed. When the funiculus divides, the new bundles receive a prolongation of the peri- neurium, the investment becoming thinner with each successive division. On nearing their final destination, the funiculi break up into small groups or single fibres, which are covered by an attenuated extension of the formerly robust perineurium ; this invest- ment constitutes the sheath of Henle, and consists of a delicate fibrous envelope lined with endothelioid plates ; in some cases these latter alone represent the entire sheath. The larger blood-vessels enclosed within the epineurium give off branches, which surround the funiculi and break up into capillaries passing within the endoneurium among the fibres. The lymphatics are represented by irregular clefts within the endoneurium, which are connected with the interlamellar spaces of the perineurium ; from these the lymph is taken up and carried off by the more definite lymphatic channels running within the epineu- rium. The nerves of the larger trunks — the nervi nervorum — are dis- tributed within the epineurium, and are said to terminate, in many cases, in special bodies which resemble in general type the spherical end-bulbs of Krause. A single funiculus more highly magnified ; the apparent small nucleated cells are sections of the nerve-fibres and their axis-cylin- ders : a, axis-cylinder ; iv, med- ullary substance ; n, neurilemma ; e, endoneurium ; p, perineurium ; b, connective-tissue cells of same. THE SUPPORTING TISSUES OF THE NERVE-CENTRES. The essential constituents of the nervous system, the cells and fibres, when associated in large masses, as in the cerebro-spinal tract, are held in place and supported by two varieties of sustentacular tissue. On examining suitably prepared sections of these organs, the cells and fibres appear everywhere to be embedded within a finely reticulated ground-substance, whose composition is especially complex in the gray matter. The basis of this reticulum is the THE NERVOUS TISSUES. yg neuroglia, a peculiar form of ectodermic tissue, with, therefore, close relations to the neurogenetic tract. Neuroglia consists of extremely branched elements, or glia-cells, whose numerous pro- cesses break up into brush-like bundles of Fig. 95- delicate fibrils, which A pass in all directions among the nervous ele- ments, filling more or less completely all inter- stices. The body of the glia-cells is frequently stellate, possessing a nu- cleus and staining in- tensely with certain dyes. The demonstration of these neuroglia elements Supporting tissues of nerve-centres : A , extensions of the peripheral connective tissue of the pia mater ; B, neuroglia- cells, one of which is seen in profile (s). Golgi staining. is very striking in Golgi silver preparations, where they appear as dark, spider-like figures which send out delicate fibrils in all directions. In the gray matter the ground-reticulum is composed of the minutely ramifying ter- minal threads of the processes of the nerve-cells, the axis-cylinders of the nerve-fibres, together with the extensions of the neuroglia elements. The groundwork surrounding the nerve-fibres within the white matter serves the purpose of covering as well as of support, and replaces the neurilemma. In addition to the dense reticulum formed by the neuroglia, con- stituting the special sustentacular tissue of the nervous system, pro- longations from the enveloping pia mater likewise penetrate within the nervous masses and contribute connective-tissue trabeculae, which form a supporting framework throughout the organs. These connective-tissue ingrowths constitute the septa, which in many places, as conspicuously in the spinal cord, separate the nervous matter into distinct tracts and areas. The finer ramifications of these partitions fade away in delicate extensions which mingle with the fibrils of the neuroglia-cells. It is evident, therefore, that the sup- porting tissue of the nervous system can no longer be regarded simply as a form of connective tissue, since, in addition to the un- doubted connective tissue present, the larger part is contributed by the peculiar ectodermic structure, the neuroglia. THE STRUCTURE OF GANGLIA. Along the course of certain nervous cords, such as those consti- tuting the sensory roots of the spinal nerves, the trunks of many of 8o NORMAL HISTOLOGY. the cranial nerves, and especially of the sympathetic system, groups of nerve-cells occur associated with the nerve-fibres in the form of ganglia ; these may be large and conspicuous masses, as the Gasserian Fig. 96. Spinal ganglion, in longitudinal section, from cat : the groups of nerve-cells lie embedded among the bundles of the nerve-fibres. ganglion of the trifacial nerve, or their size may be microscopic, as many of the interstitial ganglia connected with the distribution of the sympathetic fibres. The outer covering of the ganglion consists of a fibrous envelope, a condensation of the adjacent epineurium in many cases, from which prolongations extend among Fig. 97- the nervous elements, where they break up into delicate bundles of connective tissue, which serve for the union and the support of the cells and the fibres. Some of the nerve-fibres pass through the ganglion on their way to more distant points with- out joining any of the nerve- cells, while many others end in or take origin from these elements. The presence or absence of the medullary coat depends upon the char- acter of the component fibres of the nerve-trunk ; before joining a nerve-cell, however, the medullary substance disappears, while the neuri- lemma of the fibre continues and becomes the nucleated capsule Section of spinal ganglion more highly magnified : g, the nerve-cells, cut in various planes, surrounded by the nucleated sheath (c) ; a, the medullated nerve- fibres, on which several nodes of Ranvier are seen ; b, cells of the supporting connective tissue. THE NERVOUS TISSUES. Fig. enclosing the individual nerve-cells. These latter possess, in general, a spherical form, and are usually provided with one or two, seldom more, processes ; in the bipolar cells the processes frequently pass from opposite poles to become continuous with the afferent and efferent fibres. In the ganglia of some of the lower vertebrates bipolar cells occur in which one process becomes invested by the turns of the other or spiral fibre. Unipolar cells exist in which the single process divides into T-branches extending almost at right angles ; such cells occur also in man. The development of all nerve-fibres and nerve-cells must be referred to the elements derived from the invaginated ectoderm forming the neural tube. Without entering upon an exhaustive account of the process, many details of which are still uncertain, it may be accepted that the primary neural ectoderm differentiates into two varieties of cells — the neuroblasts and spongioblasts. The nerve- fibres are formed as outgrowths from the primi- tive nerve-cells or neuroblasts. This may take place either in one direction alone, from the centre towards the periphery (centrifugally), as in the formation of the efferent fibres of the motor-nerve roots of the spinal cord ; or, as in the production of the afferent (sensory) nerves, the neuroblasts may be somewhat removed from the central nervous mass, occupying the position of the spinal ganglia, and send out fibre-pro- cesses in two directions, one set growing into the nerve-centre {centripetally), while a second group of fibres extends towards the periphery {centrifugally). In all cases the nerve-fibres are formed as outgrowths from the primary nerve-cells ; in later stages the cells concerned in extending the nervous path may disappear after the establishment of the tract. The spongioblasts, on the other hand, are especially concerned in the production of the neuro- glia-cells, these ultimately becoming transformed into the close reticu- lar formation supporting the nervous elements. The nerve-fibres are at first pale and possess neither medullary substance nor neurilemma. The acquisition of the white substance of Schwann occurs much later, the exact mode of its production, however, being by no means certain ; whether the medullary sub- stance owes its formation to the influence of the axis-cylinder, or its origin must be referred to the more or less direct agency of the ele- 6 Ganglion nerve-cell with spiral fibre from the sym- pathetic of frog : Sp F, the spiral fibre surrounding the straight process (Cf) and dividing at a node of Ran- vier ( Th) ; s, neurilemma. (After Sckieffer decker.) g2 NORMAL HISTOLOGY. ments represented by the nerve-nuclei, future investigation must determine. If traced to the axis-cylinder, the sheath must be classed as ectodermic tissue ; as mesodermic, on the other hand, if referred to the nerve-corpuscles. The period at which the medullary coat appears in the various groups of nerves is variable, but constant for given tracts ; account has been taken of this fact with great advantage in the laborious investigations of tracing the path of many nerve- tracts composed of medullated fibres. The neurilemma may be regarded as certainly derived from the differentiation of surrounding mesodermic cells, as likewise the more general connective-tissue envelopes constituting the endoneurium, the perineurium, and the epineurium of the nerve-bundles. THE PERIPHERAL NERVE-ENDINGS. 83 CHAPTER VI. THE PERIPHERAL NERVE-ENDINGS. Terminations of Sensory Nerves. A medullated nerve, in passing to its ultimate distribution, first loses the medullary sub- stance, or white matter of Schwann, which ends abruptly at some bifurcation of the nerve corresponding in position to a node of Ran- vier. The fibre continues for a variable distance non-medullated, being covered with the neuri- lemma and the nerve-cor- FlG- 99- puscles ; these coats become reduced gradually until the neurilemma disappears, the nerve-nuclei then alone re- maining as an imperfect in- vestment of the axis-cylinder. The nuclei soon occur less frequently, until finally they disappear and the bundles of nerve-hbrillae, by this time greatly reduced owing to re- peated division, continue as naked axis-cylinders ; these unite to form a widely-meshed ground-plexus, possessing characteristic triangular, nu- cleated nodal points where the bundles of fibrillae meet. The axis-cylinders sooner or later break up into their component primitive fibrillae, which frequently interlace to form rich net-works, or terminal plexuses, within the connective tis- sue of the organ supplied ; these net-works quite often are situ- ated immediately beneath the epithelium ; in immediate proximity with the basement membrane fine fibrillae emerge from the plexus, enter the epithelium, and terminate in pointed or club-shaped free endings between the epithelial cells. The nerves of common sen- sation frequently end in this manner, including, probably, many nerves of the skin, cornea, and mucous membranes. Many sensory nerves, however, terminate in special endings of Termination of sensory nerve fibres ; portion of the plexuses occupying the anterior layers of the cornea ; gold preparation : n, n, nodal points of the coarser ground-plexus; b, small bundle of nerve-fibrils which breaks up into the terminal arbor (t) of ultimate fibrillae; v, fibrils showing varicosities. 84 NORMAL HISTOLOGY. Fig. ioo. varying complexity : of such specialized structures over a dozen (onus have been described; since a number of these occur only among the lower vertebrates, the more important types alone will be here considered. The special sensory nerve endings may be grouped as — i. Tactile Cells. 2. Tactile Corpuscles. 3. End-Bulbs. The tactile cells are found within the deeper layers of the epi- dermis or the adjacent stratum of the corium, and may be either simple or compound ; the former are oval nucleated elements, 5-12 p. in size, and resemble ganglion-cells. The centrally-directed portion of the cells is embraced by a peculiar crescentic expansion — the tactile meniscus— with which the nerve-fibre is probably connected. Where two or more such cells are associated to receive the nerve-fibre, a compound tactile cell results ; the corpuscles of Grandry and of Merkel, found respectively in the epidermis of birds and of mammals, are examples of such structures. The medullated nerve-fibre, on meeting the cells, loses its neurilemma and Henle's sheath, these coverings becoming fused with the connective- tissue capsule of the corpuscle ; the axis-cylinder passes between the cells, to become lost within an intercellular flattened tactile disk ; the medullary substance terminates at the point where the axis-cylinder Termination of sen- sory nerve-fibres within the epidermis ; gold prep- aration : e, deeper layers of epidermis ; c, subja- cent connective tissue ; «, nerve-fibrillae pene- trating among the epi- thelial cells. Fig. ioi. ■-; enters the disk. The dark stellate figures sometimes seen in gold prep- arations of the epidermis, lying between the epithelial cells, and known as the cells of Langerhans, do not rep- resent nerve-endings, as for- merly claimed, but are prob- ably migrated wandering cells. The more elaborately ar- ranged compound tactile cells and the simpler tactile cor- puscles, such as the spherical end-bulbs of the conjunctiva, are closely related, their differences being but slight ; the various Special nerve-endings within the epidermis ; gold preparation : N, nerve-fibre entering the epithelium and dividing into the fibrils which are connected with the tactile disks (;«) ; upon these latter rest the tactile cells, c. (After Ranvier.) Fig. 102. Tactile corpuscles from the bill of duck : A , simple, B, compound, corpuscle ; t, tactile cells; d, tactile disks; n, medullated nerve- fibres entering the nucleated capsules (s) into which the neurilemma continues. Fig. 103. THE PERIPHERAL NERVE-ENDINGS. gC tactile corpuscles present increasing degrees of complexity of struct- ure, the most highly specialized ending of this class being the tactile corpuscle of Meissner, found in the skin of the palmar surfaces of the fingers and of the toes. The corpuscles of Meissner are oval elliptical bodies, 45-140 /* long and 35-55 1* wide, situated usually at the apices of the papillae of the corium ; they possess nu- merous transversely-placed nuclei, which, with the edges of the indis- tinctly defined tactile cells, produce the characteristic transverse or some- what spiral markings. Each cor- puscle is supplied with one or two, sometimes three or four, medullated nerve-fibres, which are invested with Henle's sheaths; the fibres may undergo numerous windings before entering the corpuscle, the sheath of Henle, together with the neurilemma, becoming continuous with the fibrous envelope of the corpuscle. The nerve- fibres retain their medullary substance for a short distance, but later lose this sheath and break up into a number of non-medullated fibres ; these latter subdivide into fibrillae, which pursue a spiral course throughout the corpuscle, being connected here and there with terminal disks. The com- pressed tactile cells themselves are usually indis- tinctly defined, the transversely-placed nuclei and the outlines of the cells producing the transverse markings. A large number of the nuclei seen, however, belong to the superficial layers con- tributed by the connective-tissue coverings. As to the exact course and mode of termination of the nerve- fibrillae within these tactile corpuscles, much uncertainty still exists. The spherical end-bulbs of the conjunctiva and of other mucous membranes, as well as the genital and the articular nerve-corpuscles, must be included in this class of nerve-endings ; these bodies are all formed on the same general plan, the differences in their structure being limited to the details of arrangement. The End-Bulbs. The third group of special nerve-terminations embraces the nerve-endings of a cylindrical type in contrast to the ,) [y^$k\ Bl N Tactile corpuscle of Meissner from the skin of human toe : N, the nerve entering the complicated group of tactile cells com- posing the corpuscle ; Bl, blood-vessel accompany- ing the nerve-fibre. (After Sch ieffe rdecke r. ) 86 NORMAL HISTOLOGY. spheroidal form of those already considered. Just as in the preceding group, so here the simpler endings lead from the tactile cells to the more highly specialized structures ; the cylindrical end-bulbs of the conjunctiva of the calf are the simplest members Fig. 104. Qf this group, while the corpuscles of Vater, or the Pacinian bodies, are its most highly special- ized representatives. The nerve-endings of this class are composed of three parts — the cap- Fig. 105. sule, the inner bulb, and the nerve-fibre. Upon the arrangement and development of these the differences distin- guishing the individual endings chiefly depend. In the simpler forms of end-bulbs, as those found in the conjunctiva and the oral mucous membrane of certain mammals, the body is borne upon a stalk, which contains the medullated nerve-fibre and, possibly, a minute blood- vessel enveloped in connective tissue. The sheath of Henle invest- ing the nerve is prolonged into Fig. 106. the nucleated capsule. The latter b encloses a conspicuous cylindrical mass of granular or faintly striated a pale substance — the inner bulb — within which the free axis-cylinder Simple spherical end- bulb from the human con- junctival mucous mem- brane : «, the medullated nerve-fibre which disap- pears within the capsule. (After Krause.) Genital corpuscle from the human clitoris ; this ending represents a group of partly fused simple spherical end- bulbs : n, nerve-fibres entering the capsule. (After Krause.) lies, terminating often in a slightly marked knob-like expansion. The medullary substance ends where the nerve-fibre enters the inner bulb. Further complexity in the struct- ure of the end-bulbs is largely due to elaboration of the capsule ; this latter becomes laminated and very thick, while the inner bulb likewise exhibits new details of structure. Since the intermediate forms in the series of end-bulbs do not occur in man, the highly specialized corpuscles of Vater, or the Pacinian bodies, may at Simple cylindrical end-bulbs from the scleral conjunctiva of calf : n, nerve-fibre passing into the inner bulb (b) ; A*, neurilemma which, with perineurial sheath ( C), continues as the capsule, C. (After Schieffer decker.) THE PERIPHERAL NERVE-ENDINGS. §7 once be considered. These structures, widely distributed in man and mammals, are elliptical, semi-transparent bodies, some 2-3 mm. long and half as broad, which occur along the nerves supplying the skin, especially of the hands and feet, the external genitalia, the joints of the extremities, the periosteum of certain bones, the peri- toneum, and many other localities. Of the three component parts of the typical end-bulb, the capsule has undergone the greatest development in the corpuscles of Vater, being composed of 25-50 concentric connective-tissue lamellae, each of which possesses an outer transverse and an inner longitudinal layer of fibres, and is lined by a single layer of endothelial Fig. 107. cells ; the nuclei of these plates are seen in profile throughout the capsule. The individual lamellae Fig. 108. Corpuscle of Vater, or Pacinian body, from the mesentery of cat : N, nerve-fibre enclosed within the perineurial sheath, with which the lamellae of the capsule (Kfis) are connected ; K, nuclei of the endothelial plates of same ; Jk, inner bulb enclosing the axis-cylinder {ax), which at Thp di- vides into the terminal branches. (After Ranvier.) Herbst's corpuscle from the bill of duck : m, medullated nerve-fibre passing into the interior of the capsule, where the axis-cylinder lies within the granular inner bulb («) surrounded by a row of nuclei ; the spindle nuclei appear between the outer and less closely placed lamellae of the capsule. are separated by a clear serous fluid, which is largest in amount be- tween the peripheral layers, since the lamellae immediately surround- ing the inner bulb are thinner and more closely placed. The lamellae of the capsule are often united along a longitudinal area — the intra- capsular ligament — which corresponds to the course by which the nerve-fibre gains entrance to the inner bulb ; occasional trabecular 88 NORMAL HISTOLOGY. also pass between the adjacent lamellae. After silver stainings the corpuscles of Vater appear to be completely invested with a mosaic of endothelial plates ; these markings are due to the cells which line the inner surface of the outer lamellae. The core of the corpuscle is occupied by a light granular or faintly striated cylindrical mass — the inner bulb — composed, seemingly, of an almost homogeneous tissue, closely resembling protoplasm, in which nuclei and indistinct fibrils sometimes are seen. Within and corresponding to the axis of the inner bulb lies the free axis- cylinder, ending frequently in a slightly expanded terminal knob ; the medullary substance surrounds the axis-cylinder as far as the inner bulb, where it disappears. The small artery usually accompany- ing the nerve-fibre within the stalk of the corpuscle gives off fine branches to be distributed to the outer layers of the capsule. The corpuscles of Herbst, found in birds, closely resemble the Vaterian corpuscles of mammals, possessing, however, a less devel- oped capsule and an inner bulb beset with a single or double row of nuclei. From the foregoing sketch it will be seen that, taking the tactile cells as a ground-form, the special nerve-endings are developed along two lines : one type is represented by the spherical tactile cor- puscle, composed of winding nerve-fibres bearing tactile disks placed between tactile cells and enveloped within a capsule ; the other by the cylindrical end-bulb, in which the central nerve- fibre lies within a cylindrical inner bulb, enveloped by a capsule developed to a greater or less degree. As the highest representative of the first group stand the complex tactile bodies of Meissner ; of the second group, the corpuscles of Vater. The following table indicates the relations of some of the principal forms of special sensory nerve-endings : Simple Tactile Cells. ( Ground- Form. ) Epidermis of man and mammals. Compound Tactile Cells. Grandry 's Corpuscles : Epidermis of birds. Merkel 's Corpuscles : Epidermis of mammals. Tactile Corpuscles. (Spherical.') Spherical End- Bulbs : Conjunctiva and mucous membranes of man. 89 THE PERIPHERAL NERVE-ENDINGS. Ley 'dig 's Corpuscles : Skin of amphibians and reptiles. Genital Corpuscles : Clitoris, penis, etc., of man, etc. Articular Corpuscles : Phalangeal joints of man, etc. Tactile End- Bulbs : Skin of bill, lip, etc., of birds. Meissner s Corpuscles : Cutis of hands, toes, etc., of man. End-Bulbs. ( Cylindrical. ) Cylindrical End-Bulbs : Conjunctiva and mucous membranes of mammals. End- Capsules : Buccal glands of hedgehog ; tongue of elephant. Herbsf s Corpuscles : Skin and mucous membranes of birds. Key-Retzius Corpuscles : Skin of bill of birds. Vaters Corpuscles : Cutis and many other situations in man and mammals. NERVE-ENDINGS IN MUSCLE AND OTHER ORGANS. Non-Striated Muscle. The sympathetic nerves supplying this tissue are composed of bundles of non-medullated nucleated fibres, and are enveloped by a thin perineurium ; these fibres are associated as small bundles and unite to form the ground-plexus, in the nodal points of which ganglion-cells usually occur. From this net-work Fig. 109. Nerves of involuntary muscle from the plexus of Auerbach of intestine of dog ; gold preparation : g, nodal points of plexus containing ganglion-cells ; «, bundles of non-medullated nerve-fibres ; from these the small branches (/) extend which give off the fibres directly supplying the muscular tissue. small branches are given off, which join to make up the intermediate plexus ; fine bundles of intramuscular fibrillae further extend directly to the contractile tissue. The fibrillae pass between the 9o NORMAL HISTOLOGY. Fig. iio. Nerves of voluntary muscle of rabbit ; gold preparation : n, small bundle of medullated motor nerve-fibres, from which fibres pass to the individual muscle-fibres (m) and bear the motor end-plates ; s, some of the sensory nerve-fibres sup- plying the muscle. primary bundles of. the muscle-cells, and probably terminate in finely pointed or slightly thickened free ends ; the direct connection be- tween the nerve-fibrillae and the nuclei of the muscle-cells is, at best, extremely doubtful. Striated Muscle is supplied with both motor and sensory nerves ; the latter are distributed as a loose net-work, the fibrillae of which appar- ently terminate between the individual muscle- fibres. The medullated nerve- fibres composing the motor supply of a vol- untary muscle unite to form an intramuscular plexus, from which small bundles of nerve-fibres spring, and subsequently divide in such manner that a single medullated axis-cylinder passes to each muscle-fibre. At the point where the nerve pierces the sarcolemma the medullary substance abruptly ends, while the neurilemma, blended with the sarcolemma, joins the peri- neurial (Henle's) sheath in forming the telolemma, or the sheath investing the end-organ. The axis-cylinder, now beneath the muscle-sheath, continues upon the surface of the sarcous sub- stance, and, later, breaks up into a number of somewhat tortuous ultimate fibrillae, which irregularly unite and end in thickened bulbous extremities. The terminations of the nerve are embedded in a flattened nucleated mass — the sole-plate — composed of soft faintly granular protoplasm, which resembles sarcoplasm and is closely applied to the surface of the muscular together with the embedded nerve-fibrillae, in Motor end-plate of voluntary muscle from rabbit: n, medullated nerve-fibre passing to muscle (w1, on the surface of which the axis-cylinder ends in the dark arborescent figure ; the latter lies em- bedded within the nucleated sole-plate (s) composed of granular protoplasm. substance ; this mass, constitutes the motor disk, or end-plate. Each muscle-fibre possesses usually but a single end-plate ; in exceptional cases, however, there may be two or more ; likewise, THE PERIPHERAL NERVE-ENDINGS. 91 several nerve-fibres instead of a single one may supply the end-plate. The nerve-endings in the voluntary muscle of amphibians and bony fishes differ from the foregoing in the absence of the granular protoplasmic disk, and in the more diffuse disposi- tion of the terminal nerve- fibres. The axis-cylinders, in these cases, branch into fibrillae which extend for some distance parallel to the axis of the muscle- fibre and end in slight bulbous expansions ; gran- ular pyriform nuclei also occur along the course of these fibrillae. The muscle-spindles described by Kuhne, and considered by some (Kerschner) as special sensory nerve endings, appear to be transient developmental structures connected with the cleav- age of the muscle-fibres (Kolliker). Tendon. In addition to the sensory end- plates of tendon, studied by Kolliker, Rollett, Sachs, Golgi, and others, which consist of an intri- cate net-work of pale non - medullated fibres, Golgi has described pe- culiar nerve-endings in tendon to be found in the immediate vicinity of the union with the muscle. Fs mm #§■■ m Et Ev Golgi's corpuscle or tendon-spindle from the human tendo Achillis; gold preparation : N, nerve-fibres surrounded by the perineurial sheath (Fs) spreading out into the reticular ramifications (Ev) of the axis-cylinder; A, the tendon- bundles, one of which is separated at b ; Mf, the muscle- fibres; R, node of Ranvier. (After Ciaccio.) Q2 NORMAL HISTOLOGY. These tendon-spindles appear as sharply-defined, greatly-elon- gated, elliptical masses (in the rabbit .25-75 mm- l°ng ar>d .02-.01 mm. broad), one end of which extends upon the tendon, while the muscular pole is usually, although not always, continuous with the adjoining muscle-fibres. The tendon-spindle is composed of a distinct connective-tissue capsule, which, embracing two or more of the primary bundles of the tendon, becomes united with the sheath of the latter ; the inner surface of the spindle is covered with endo- thelial plates. Medullated nerve-fibres to the number of two, three, or four join the organ near its widest part, sometimes, however, at one end ; after repeated division as medullated fibres, the nerves spread out on the surface of the tendon as pale non-medullated fibres, whose axis-cylinders unite to form a richly but irregularly meshed arborescent figure ; the ultimate fibrillar, in addition to the net-work, present numerous knobbed free ends. Blood-Vessels. The blood-vessels are accompanied by nerve- fibres derived from the sympathetic system ; in addition to the pale fibres, a few medullated ones usually take part in the production of the irregular net-work surrounding Fig. 113. the larger vessels. From this plexus fine branches are given off, which ultimately end between the muscu- lar bundles of the media and within the fibro-elastic tissue of the adven- titia. The capillaries are accom- Nerve-fibres accompanying a small artery panied ancJ partly SUITOUnded by (v), from the mesentery of rabbit ; gold prep- J aration. delicate non-medullated nerve- fibres. The muscular tunics of the large lymphatic trunks are supplied with nerves in a manner similar to the blood-vessels ; the delicate, thin-walled lymphatics are probably without nerves. Glands. A detailed account of the nervous supply of the larger glands will be given in connection with the consideration of the several organs ; it may be mentioned here, in general, that the more important glands are provided, in addition to the medullated nerves often found passing through the substance of the gland in their course to the contiguous skin or mucous membrane, with nervous bundles in which non-medullated fibres predominate, but in which some medullated ones also occur. These bundles form an interlobular plexus, rich in ganglion-cells, which accompanies the larger excretory ducts and blood-vessels, and gives off a few branches to be distributed to the muscular coats of these tubes. Thin bundles of pale fibres bear the smaller ducts company as far as the primary groups of acini, and there break up into minute bundles of free axis-cylinders passing THE PERIPHERAL NERVE-ENDINGS. 93 Fig. 114. between the acini. The nerve-fibrillae may be traced readily to the membrana propria of the acini, around which a net-work is spun ; regarding their ultimate distribution and relation to the secreting cells much uncertainty still exists, notwithstanding many elaborate investigations and positive statements. The exact mode in which the nerves terminate within the acini is still doubtful ; it is probable, however, that the fibrillae end between, or in apposition with, the ends of the secreting cells directed towards the basement-membrane ; proof of direct con- nection between the nerve-fibrillae and the se- creting cells, as often described, is wanting. Likewise the mode of termination of the med- ullated fibres, which, as already stated, con- tribute to form the interlobular net- work, is uncertain ; in some glands, as in the pancreas of the cat and the buccal glands of the hedge- hog, they terminate in special nerve-endings resembling the corpuscles of Vater. The perceptive apparatus connected with the termination of the nerves of special sense include the highly specialized epithelial struct- ures made up of the neuro-epithelium ; the rod- and cone-cells of the retina, the hair-cells of the internal ear, the olfactory cells of the nasal fossae, and the gus- tatory cells of the taste-buds are important examples of such tissue. In these structures the specialized epithelium forms the apparatus for the reception of the external stimuli, while the nerve-fibres provide for the further transmission of the impressions so appreciated. The relation between the receptive cells and the conducting nerve-fibres must be, evidently, very intimate ; a direct anatomical continuity between the two, however, must be regarded as extremely doubtful in the light of recent research. Nerves ending in glands, from the parotid of dog ; gold preparation : s, group of secreting cells of single acinus; n, nerve-fibre lying outside the membrana pro- pria and giving off twigs which enclose the acinus within a net-work of ter- minal nerve-fibrillae. 94 NORMAL HISTOLOGY. CHAPTER VII. THE CIRCULATORY SYSTEM. The circulatory apparatus comprises the channels for the con- veyance of the blood-stream, the vessels, and the dilated and special- ized portion of the vascular tube, constituting the heart, for the pro- pulsion of the current. In development and structure the several parts of the vascular system possess much in common, although variations in the details of the walls of the blood-channels suffice to distinguish the different portions. THE BLOOD-VESSELS. The blood-vessels occur in three forms, as arteries, veins, and capillaries, the latter constituting an expanded system of thin- walled tubules, intimately related to the organs, and especially de- signed to facilitate the interchanges be- Fig. 115. tween the nutritive current which they carry and the tissues through which they pass. The arteries possess three coats — the inner, or intima, the middle, or media, and the external, or adventitia. Since these coats vary in relative thickness and Fig. 116. JSP mm Section of human artery of medium size: 7, the intima, consisting of the endothelium (gi^fft**T2p* MM :-> Section of aorta of child: /, M, and A , respectively intima, media, and adventitia. The thick stratum of sub-endothelial tissue and the layer of longitudinally disposed bundles of muscle (b) are peculiarities of the inner coat. THE CIRCULATORY SYSTEM. 97 posed muscular tissue within the adventitia of other vessels (su- perior mesenteric, splenic, renal, and iliac arteries). In passing from medium-sized ar- teries towards smaller vessels, the coats become reduced in thickness, the media being earliest affected. The intima of the smallest ar- terioles consists of an endothelial layer alone, the middle coat in- cludes but a single layer of muscle- cells, while the external tunic is re- duced to a few longitudinal bundles. The vessels intermediate between small arteries and true capillaries no longer possess a complete layer of muscle-cells, the media being represented in such arterioles by scattered groups of circularly placed spindle-cells, forming an imperfect muscular sheet, which partially en- circles the vessel. The nuclei of these circular muscle-cells are trans- versely placed, while those of the endothelial plates are usually longi- tudinal or parallel with the axis of the vessel A, small human artery, in which the coats are reduced each to a single layer of cells ; the media here consists of only one layer of muscle-cells (w), which are seen in optical section : i, intima ; a, adventitia ; e, nuclei of the endothelial plates. B, an arteriole just before becoming a capillary ; the vessel still possesses muscle-cells {>»), but these are now arranged as irregular groups. C, true capillary vessel, consisting of only an endothelial coat, the other tunics having disappeared ; the nuclei are those of the endothelial plates. THE VEINS. The veins possess the same tunics as the arteries, but, in general, are characterized by thinner walls and a preponderance of connective over the muscular and elastic tissues. There is, further, less regu- larity and constancy in the structure of the coats. The inner layer of the intima consists of a single layer of endo- thelial cells, rather broader and more polyhedral in form than those lining the arteries, the spindle shape being best marked in the smaller veins. The subendothelial tissue contains numerous con- nective-tissue corpuscles, and, in the larger veins, is arranged in distinct lamellae. An inner elastic membrane is generally present, in some cases taking the form of a fenestrated layer. The media consists of circular bundles of muscle-cells, associated with lamellae of fibro-elastic tissue in the larger veins. This coat is best developed in the veins of the inferior extremities, less so in those of the upper limbs. The muscle-tissue of the veins is sub- ject to many variations, both in amount and in arrangement, that 7 Qg NORMAL HISTOLOGY. of the media is very scant or altogether wanting in a number of veins, including the thoracic part of the vena cava, the internal and external jugular veins, the veins of the pia and dura, of the retina, of bone, and of the corpora cavernosa. Certain veins possess longi- tudinal muscular bundles in the inner part of the media ; such are the mesenteric, umbilical, iliac, and femoral. The adventitia, often the thickest coat of the vein, consists ol stout net-works composed of bands of fibro-elastic tissue ; in some veins additional bundles of plain muscle occur within this tunic. Among the venous trunks possessing well- Fig. 122. marked, longitudinally arranged muscu- lar tissue in the external coat are the abdominal cava, azygos, hepatic, portal, splenic, axillary, superior mesenteric, renal, spermatic, and external iliac veins. The veins of the gravid uterus contain muscular tissue in all the coats, the prin- cipal bundles running longitudinally. The valves with which many veins are provided consist of crescentic folds of the inner tunic of the vessel, strengthened by additional fibro-elastic tissue ; in some instances the muscular bundles extend for a short distance into the valve. The base or the attached margin of the valve is often its thinnest part, the free edges being somewhat thickened. The striated car- diac muscular tissue is continued for a short distance in the walls of those parts of the venae cavae and of the pulmonary veins immediately adjoining the heart ; the explanation of this fact is found in the derivation of these portions of the vessels from the tissues of the primitive heart- tube. THE CAPILLARIES. The capillaries establish the only communication, with few excep- tions, between the arteries and the veins, and, further, provide the intimate anatomical relation between the nutritive current and the tissues of the body necessary for the maintenance of the integrity and functional activity of the various organs. As exceptions to the usual intervention of the capillaries between the arterial and venous radicles, the direct communication between these vessels existing in the erectile tissue of the genital organs, in the spleen, and in some parts of the peripheral circulation, as in the tips of the fingers and toes and of the nose, may be mentioned. Section of human vein of medium size: /, M, and A, respectively intima, media, and adventitia. THE CIRCULATORY SYSTEM. 99 Fig. 123. Capillary blood-vessels from mesentery of young dog: n, the capillaries, with the nuclei of the endothelial plates, lying within the connective tissue (g). The capillaries form rich net-works in almost all tissues and organs, the principal localities where these vessels are wanting being epi- thelium, the hairs, the nails, teeth, cartilage, the cornea, the crys- talline lens, and certain parts of the nervous system. The capillary net-works vary in the size both of the meshes and of the constituent vessels. The average diameter of the capillaries is 7-10 ,'j. ; the smallest are found in the brain, retina, and muscle ; the largest in bone-marrow, dentinal pulp, and the liver. The closest meshes are found in the air-vesicles of the lungs, the choroid, the liver, and other glands ; the widest in the serous membranes, tendon, etc. Young tissues are more richly supplied than old ones. The capillaries consist of a single layer of endothelial cells, united by intercellular cement-substance ; they are, consequently, protoplasmic tubes of high vitality, admirably designed to facilitate the interchanges constituting nutrition. After staining with silver the endothelial plates are seen as extended spindle-cells, united by irregular lines of darkened cement-substance ; at the points where the vessels branch, irregular triangular cells are not infrequently seen. In such preparations, likewise, along the lines of union or at the juncture of several plates, irregular darkened areas — the stigmata — may be observed ; these are probably minute spaces occupied by stained albuminous sub- stances ; these areas are supposed to aid the diapedesis or trans- migration of the blood-cells. Some capillaries are invested by an imperfect adventitious coat, formed by a net-work of surrounding branched connective-tissue cells, and resembling the reticulum present in lymphoid tissue. The intimate relation existing between the endothelium of the vessels and the surrounding connective-tissue corpuscles is well exhibited in young growing tissues, as the omentum. The peculiarities distinguishing the capillaries from the small " capillary" arteries or veins consist not so much in the size of the vessels — for the capillaries may have absolutely the greater calibre — as in the character of their walls. The true capillary possesses no muscle-cells, these first appearing in irregular groups beyond the limits of the capillary vessel ; in those cases where, as in certain veins, muscular tissue is wanting, the character of the adventitia of the vein will aid in determining the character of the vessel. Small blood-vessels — the vasa vasorum — provide for the nutri- IOO NORMAL HISTOLOGY. tion of the walls of the medium- and large-sized arteries and veins. These vessels arise some distance from the area which they tupply, frequently coming from a different branch or, as in the case of the veins, from a neighboring arterial stem. The nerves of blood-vessels are mainly derived from the sym- pathetic system, and hence are principally of the non-medullated kind ; a tew medullated fibres, however, are usually present. The nerves accompanying the blood-vessel give off branches, which form surrounding plexuses ; from these minute bundles pass, whose com- ponent fibrillar are distributed to the media and the adventitia. The capillaries are accompanied by correspondingly delicate fibres. Lymphatic clefts and vessels are found in the external coat of the larger vessels. In many places, as in the nerve-centres, including the organs of special sense, in the peritoneum, etc., the lymphatic clefts of the adventitia unite to form a large ensheathing circular sinus — the perivascular lymph-space — which separates a portion of the adventitia from the remainder of the vessel ; as a result of this arrangement, the blood-vessel seemingly lies within the lymph-space. Perivascular lymphatics may be readily observed in the peritoneum of the frog. THE HEART. The heart-walls consist of three layers — the endocardium, the muscular layer, and the pericardium. The endocardium forms the serous lining of all parts of the organ, becoming continuous with the inner tunic of the blood-vessels at the several cardiac orifices. The inner free sur- face of the heart is covered with a single layer of polyhedral nucleated endothelial cells. These latter rest upon the substance proper of the endocardium, a stratum composed of fibrous connective tissue mingled with a felt- work of elastic fibres ; the elastic net-works are especially well developed in the auricles, in certain parts of which the broad fibres join to form fenestrated membranes. The outer connective-tissue layer of the endocardium is continuous with the perimysium of the muscular tissue. The heart-valves are formed by duplica- tures of the endocardium strengthened by bands of fibrous tissue enclosing numerous The endocardial layer of the auricular side of the Fig. 124. Secti n of human heart show- ing endocardium : a, endothe- lium ; b, subendothelial con- nective-tissue stroma in outer layer (c), containing net-work of elastic fibres (e) ; d, trans- versely-cut bundles; f, mus- cular tissue. elastic fibres. THE CIRCULATORY SYSTEM. IOI auriculo-ventricular valves is thicker than that of the ventricular surface. The roots or attached portions of these valves possess thickenings — the annuli fibrosi — composed of supplementary- masses of fibro-elastic tissue. The auricular muscle is continued into the valves for about one-third of their width, following closely the general contours of the fold. Within the larger chordae tendineas the papillary muscles extend for some distance, in addition to which isolated muscle-bundles are also sometimes present. The semilunar valves possess a thin elastic layer on the arterial surface, aug- mented by a thick stratum of connective tissue, the bundles ex- tending parallel with the margin of the valve; increased strength is secured by a nbro-elastic nodule, or corpus Arantii, which occupies the middle of each leaflet. Beneath the ventric- ular endocardium, in many animals (deer, sheep, calf, pig, horse, goat, dog, certain birds, etc.), but not in man, peculiar bands — the fibres of Purkinje — occur; these are muscular fibres whose transverse striations are limited to the pe- ripheral zone, while their centre is occupied by a large continuous mass of nucleated pro- Section of the heart, including a leaflet of the semilunar valve of the pulmonary artery of child : a, a, cardiac, b, b, arterial, surface ; c, recess behind the valve (/), constituting part of a sinus of Valsalva; d, free border of valve ; e, thickening near edge of valve corresponding to a corpus Arantii ; g , endothe- lium, h, intima, i, media, k, adventitia, of the pulmonary artery ; the adventitia is continuous with the principal fibrous layer of the endocardium ; m, cardiac muscle ; n, areolar tissue. toplasm. The fibres of Purkinje represent an embryonal condition of the muscular tissue, since the peripheral part of the fibre alone has undergone differen- tiation, while the central portion has remained indifferent protoplasm. Among some lower vertebrates, as fishes, a similar condition of the muscle-fibres is constant. 102 NORMAL HISTOLOGY. The muscular tissue of the heart possesses the peculiarities already described in Chapter IV. : it is composed of short, branched, nucleated fibre-cells, devoid of a sarcolemma, which unite to form an intricate net-work. The naked muscle-fibres are enveloped within a perimysium and are grouped into primary and secondary bundles, which are associated to form lamellae disposed in a very irregular and complex manner. The muscular tissue of the auricles is arranged in general as an outer transverse and an inner longitudinal layer, many small ad- ditional bundles deviating from the principal disposition to pursue independent courses in various directions. The muscle-bundles of the ventricles have a very intricate arrangement, the majority extending in an irregular oblique or spiral direction, some, in fact, describing a figure- of-eight in their course. The pericardium, which invests the exterior of the heart, and by reflection forms the pericardial sac, resembles the endocardium in possessing a single layer of endothelial plates covering its free surface, and a stratum of fibro-elastic con- nective tissue beneath. The parietal pericardium is distinctly thicker than the visceral, all the constituent layers being better developed. The subpericardial tissue covering the heart is continuous with the intermuscular connective tissue of the outer muscular layer ; in this posi- tion numerous fat-cells lie between the bundles of the fibrous and the muscular tissue. The blood-vessels supplying the muscle of the heart are derived as branches of The principal trunks are situated in the larger interlamellar masses of connective tissue, within which they divide into numerous twigs giving origin to the capillaries ; the latter penetrate the primary muscle-bundles, among and parallel to which they run. The relation between the individual muscle-fibres and the capillaries is more intimate than usually supposed, since, as shown by Meigs, the blood-vessels deeply impress the fibres, and in many places are surrounded completely by the muscular tissue. The extraordinary demands made upon the nutrition of the heart- tissue as the result of its remarkable functional activity explain the Section of human heart, including pericardium: a, endothelium of pericardial surface ; b, subendo- thelial fibrous tissue ; c, net-works of elastic fibres ; d, subpericardial areolar tissue containing fat-cells embedded between pericardium and muscle (e) ; v, blood-vessel. the coronary arteries. THE CIRCULATORY SYSTEM. IO3 necessity for such close arrangement. The deeper fibrous layers of the pericardium and of the endocardium receive numerous capil- laries, a few being also found within the chordae tendineae and the valves. The lymphatics of the heart are very numerous. They form a comprehensive system, embracing the lymph-spaces occupying the clefts between the muscle-fibres and the rich net-works of more definite channels extending within the pericardium and endo- cardium, including the valves. These two sets of lymph-radicles communicate but sparingly and pursue largely independent courses. Lymphatic vessels also accompany the branches of the coronary arteries. The rich nervous supply of the heart is derived from the coro- nary plexuses, and includes numerous medullated fibres coming from the pneumogastric, as well as the non-medullated sympathetic fibres proceeding from the cervical ganglia. Numerous microscopic gan- glia are found along the course of the larger nerve-trunks accom- panying the branches of the coronary arteries, especially in the longitudinal interventricular and in the auriculo-ventricular furrows. Many additional small groups of ganglion-cells occur within the muscular tissue associated with the fibres supplying the intimate structure. The nerves and the blood-vessels are covered by the visceral pericardium. The development of all parts of the circulatory apparatus takes place within the mesoderm ; while possessing a common origin, the blood-vessels and the heart, however, develop in- dependently, and, for a time, are distinct and dis- FlG- I27- connected. The earliest blood-vessels appear near the periphery of the vascu- lar area, outside the limits of the proper body of the embryo ; later and second- arily they extend centrally and unite with the primitive heart and those parts of the large trunks which have been formed coincidently within the embryo. The mesodermic elements within certain tracts near the periphery of the vascular area undergo proliferation, which results in the pro- duction of deeply staining densely nucleated areas known as the blood-islands of Pander ; these are the direct progenitors of the Developing capillary blood-vessels within the omentum of young rabbit : a, a, elongated protoplasmic processes connecting the walls of the newly-formed capillary (c) with the angioblastic connective-tissue corpuscles (b). lo< NORMAL HISTOLOGY. earliest blood-vessels and the first blood-cells. The blood-channels appear within the nucleated ' ' islands' ' as spaces which follow the partial breaking down of the inner portions of the areas. The peripheral zone of the nucleated cell-mass becomes the endothelium of the future blood-vessel, while, probably, certain of the enclosed mesodermic elements persist as the primary blood- cells. After a time the mesoderm surrounding the newly-formed endothelial tube differentiates into the muscular and other tissue of the remaining coats. The endothelium is, therefore, genetically the oldest part of the vessel, although its characteristic appearance, as seen in silvered adult tissue, is not visible until further differentiation has taken place. The blood-channels are further extended by the fusion of elongated mesoblastic cells with those of the walls of the primary vessels, the lumina of the latter gradually entering the solid processes, which are thus converted into tubes. After the development of the earliest vessels in the manner indicated, the formation of all new vessels subsequently, in pathological processes as well as in normal ones, is associated closely with the connective-tissue cells, since solid protoplasmic processes of the united cells become later the walls of the young vessel. The development of the heart resembles that of the extra- embryonic vessels in so far that the part first formed— the primary endothelial tube — originates by the differentiation of the mesodermic cells and the hollowing- out of the tissue Fig. 128. , . 1 , T • 1 , lying enclosed. In its very early stage the mammalian heart exists as two distinct and widely-separated tubes, which later unite to form a single sac. Outside the primary endothelial heart the mesoderm differ- ~nT entiates into the muscular tissue 01 the Section ofa pan of the develop- cardiac wall, but for some time the endo- ine heart of a rabbit embryo of ... , , , , eleven days: e, the endothelial thehal and muscular layers continue as tube, within which lie several of independent tubes, the inner endothelial the primary nucleated red blood- <• ■ • i , cells (6); m, the slightly differ- lming appearing as a shrunken cast repro- entiated mesoblastic cells, which ducing the contours of the larger muscular later become the muscular tissue. ^r-., • i < organ. I he two tunics are connected by numerous bridging bands, which increase in number and size with the progress of the development of the organ ; these primary tra- becular are represented in the adult organ by the columnae carneae and musculi pectinati. The pericardium originates as the special- ized layer of mesoderm — the mesothelium — forming the immediate boundary of the general primary body-cavity, of which the peri- cardial sac is only a constricted portion. THE CIRCULATORY SYSTEM. THE BLOOD. I05 While, when physiologically considered, the blood is regarded, with Bernard, best as an internal medium of exchange, histologically it may be classed as a mesodermic tissue possessing a fluid inter- cellular substance, the liquor sanguinis ; in the latter float the cellular elements — the blood-corpuscles. The morphological constituents of the blood are of two kinds, the colorless or white corpuscles and the colored or red cells ; to these must be added a third variety, the blood-platelets or blood-plaques, which are probably constant and independent ele- ments. THE COLORLESS CELLS OF THE BLOOD. The colorless blood-cells, or leucocytes, are not peculiar to the blood, since they originate in lymphoid tissues and are carried by the lymphatic trunks into the blood-current, in which fluid they usually are observed. These cells represent a widely-distributed element, whose names Fig. 129. are as various as are the localities in which it is encountered. The "lymph-corpuscle," "lymphoid cell," "adenoid cell," "white blood -cell," "leucocyte," " leucoblast, " "wandering cell," etc., are but different names for the same morphological element. The colorless blood-cell consists of a minute Colori«sbiood-ceiisofman, highly magnified : r, cor- nucleated mass of active protoplasm, when at puscie in condition of rest, rest, presenting a round or spherical form and af a sPherical mass of Prot°- . ... . plasm ; the other cells are measuring about 10 ;j. in diameter. In its actively moving and exhibit usual condition, however, the outline of the a hyaline aPParent'y stru«- . . . ureless substance in the most corpuscle is undergoing continual variation, advanced pans of the cells, these changes being known as amoeboid on account of their similarity to those exhibited by the amoeba. Under moderate amplification the protoplasm of the leucocyte appears faintly granular and includes a single nucleus, rarely multiple, which is ordinarily somewhat obscured by the overlying cell-contents. Additional coarse granules are of frequent occurrence, especially within the protoplasm of particular cells ; these latter Ehrlich clas- sifies, according to the affinity of their granules for certain stains, into a-cells (acidophile, eosinophile), fi-cells (amphophile, indulinophile), y-cells (mast-cells), §-cells (basophile), and e-ce//s (neutrophile). The exact nature and significance of such cells, however, are still uncertain. Under high amplification the protoplasm of the white blood-cell often displays an imperfect reticulation as a transient I06 NORMAL HISTOLOGY. structure, as well as nuclear fibrils. Pole-corpuscles and at- traction-spheres have been described by Flemming as constant constituents of the white blood-corpuscle. Division of these elements in many instances undoubtedly is accompanied by the regular cycle of karyokinesis ; very commonly, however, it is equally certain, the colorless corpuscles are reproduced by direct, amitotic division. Examination of actively moving cells under high amplifi- cation emphasizes a distinction in the character of the protoplasm, that part of the cell constituting its most advanced portion seem- ing more homogeneous than the remainder of the body of the cell. The colorless cells of human blood are larger than the red corpuscles, but are much fewer in number, the ratio between the two kinds of elements being, under normal conditions, about three hundred and fifty red cells to one white corpuscle. The actual number of white cells present, however, depends upon various cir- cumstances, since during digestion the number of colorless elements is increased, while fasting greatly reduces the proportion of the leucocytes ; in general these cells are more numerous in venous than in arterial blood. The colorless blood-cells must be regarded as playing a double rdle : in addition to maintaining an ever-available store of reserve active protoplasm with which to meet and to repair the destructive processes taking place normally as well as in disease, they are actively engaged in the absorption of solid and fatty matters, being capable of taking up and carrying away injurious debris. Certain of these cells — the phagocytes of Metschnikoff — seem especially aggressive in their attacks against offending foreign substances, within a limited degree including possibly the waging of a successful warfare on obnoxious microbes. THE COLORED CELLS OF THE BLOOD. The adult mammalian red blood-cell represents a condition of retrogression, since in its development it has suffered the loss of its nucleus and a profound metamorphosis of its protoplasm, changes of such importance that some authorities dispute the propriety of regarding the mammalian red blood-corpuscles as true cells. The presence or absence of the nucleus within the colored corpuscle, together with its general form, furnishes a basis for a division of all vertebrate bloods into — A. Those having nucleated, oval red corpuscles : including fishes (except cyclostomata, which have round, discoidal cells, as the lamprey), amphibians, reptiles, and birds. B. Those having non-nucleated, round, discoidal red cor- THE CIRCULATORY SYSTEM IO7 puscles : including man and other mammals, except the camel family, which have oval, non-nucleated red blood-cells. Since an oval corpuscle on being subjected to certain reagents may present a circular outline, the presence or absence of a nucleus offers the most reliable means of differential diagnosis between mammalian and other bloods. The human colored blood-cell is a small round disk, measuring about 8 /J. in diameter, and exhibiting individually a faint greenish- yellow tinge. The well-known color of the blood appears only when great numbers of FlG- I3°- these corpuscles are massed ; the term " red" conventionally applied to these elements is, strictly regarded, incorrect and less appro- priate than "colored." The two surfaces of the blood-disk are not perfectly flat, the centre of the corpuscle being slightly biconcave, while its edges are rounded, biconvex, and Human biood-ceiis: w,coior- somewhat thickened : in consequence of this less corpuscle, surrounded by ,. . .. . . ,, r .. , r 1 red cells ; those at r exhibit a peculiar blSCUlt form, all planes Of the partially-formed rouleau. corpuscle are not seen accurately focused at one time, the centre usually appearing either darker or lighter than the marginal parts of the cell, depending upon the focal adjustment. The structure of the colored blood-corpuscles is still a subject of discussion. According to the generally accepted view, the cor- puscles consist of two parts : (a) the transparent, colorless, apparently homogeneous, and plastic stroma, extensible and pliable to a high degree, and (b) the coloring matter, or haemoglobin, which is held within, and uniformly distributed throughout, the former. This conception of the corpuscle assumes the presence of a uniform though highly flexible stroma-mass of definite form, colored by the imbibition of the soluble haemoglobin. On the other hand, the behavior of these elements when treated with water, upon the addition of which the corpuscles swell, lose the discoidal form, and become globular, as well as the suggestive appearances following the staining with aniline of such bleached corpuscles, the outlines of the cells then showing as distinct rosy rings, offers strong arguments, in the opinion of not a few, for the belief that the red corpuscles are minute sacs, consisting of a limiting membrane and the colored fluid contents. The nuclei of the red cells, when present, lie embedded within the colored stroma ; in perfectly fresh or circulating corpuscles they are made out with great difficulty, since they possess a refractive index almost identical with that of the other parts of the cell. After reagents, or after the expiration of some minutes, the nuclei become IQ8 NORMAL HISTOLOGY. very evident, and correspond in appearance and structure with those of other cells, one or more nucleoli often being visible. In fresh blood the red corpuscles within a few minutes arrange themselves in rows or piles by the apposition of their broader sur- faces, thus forming figures which, from their resemblance to rolls of coin, are termed rouleaux. The cause of this phenomenon is still uncertain, although it is not improbable that it is to be attributed to the presence, in the fresh corpuscles, of a film of a nature repelling the liquor sanguinis and favoring the adhesion of the disks ; the rouleaux are only temporary, the corpuscles later spontaneously separating and remaining apart. It is of interest to note that only discoidal corpuscles of mammalian bloods (including, however, the discoidal cells of the lamprey) run together to form these figures, the projecting nuclei and the slight biconvexity of the oval nucleated cells affording surfaces evidently unfavorable for adhesion. The average diameter of the red corpuscles in the various races of mankind is identical, being between 7 and 8 [i, or about 1 -3200th of an inch. The size of the animal bears no relation to that of its red blood- cells, as shown by the following measurements of some mammalian bloods, based on the observations of Gulliver : Millimetre. Millimetre. Millimetre. Elephant . . . .0092 Guinea-pig . . .0071 Pig 0060 Sloth 0086 Dog 0071 Horse 0059 Whale 0080 Rabbit 0070 Cat 0058 Man 0079 Bear 0070 Sheep 0048 Beaver 0076 Mouse 0067 Goat 0040 Monkey . . . .0074 Ox 0048 Muskdeer . . .0024 The largest corpuscles are those of the amphibians, the red cells of the frog measuring .0016 mm. in breadth by .022 mm. in length, those of the triton, .019 by .029, and those of the proteus, .035 by .058. The maximum size is reached in the huge red cells of the amphiuma, which are no less than .046 mm. wide by .075 mm. long, and are readily distinguishable by the unaided eye. The number of colored cells normally present in one cubic millimetre of human blood, as determined by the haemacytometer, is about five millions ; these figures are modified by sex, the male subject usually having more corpuscles than the female. The number of red corpuscles varies in different animals : the carnivora possess a greater number of cells in a given quantity of blood than do the herbivora ; in birds the proportion is still larger ; while in the sluggish amphibians the number of the huge red cells is reduced to thousands. Effect of Reagents applied to Human Blood. No elements THE CIRCULATORY SYSTEM. IO9 Fig. 131. Red blood cells of man and of am- phiuma, magnified lo the same extent to show the size of the human cor- puscles in comparison with that of the largest known blood-cell. are more sensitive to changes in environment or to the effects of reagents than are the cells of the blood. An appreciation of the alterations referable to external causes is important as guarding against unwarranted conclusions as to the existence of pathological conditions, since not infrequently ap- pearances which lead the tyro to infer disease may be ascribed to influences acting on the corpuscles outside the body. If fresh blood be exposed to a current of air, subjected to undue pressure or to other disturbing influences, alterations of the corpuscles at once take place. One of the most common distortions affects the exterior of the red corpuscles, and results in the formation of a number of minute projections, or spines, pro- ducing a condition known as crenation. Saline Solutions. The application of a weak saline solution or of urine is attended with similar effect ; if the strength of the reagent be gradually increased, a corresponding progressive degree in the distortion is observed, until, finally, upon the addition of a concentrated brine, a shrivelled, shapeless mass replaces the former discoidal red corpuscle. The reaction is less marked upon the colorless cells, weak salines pro- ducing no perceptible change, while a slight shrinkage is noticeable after the stronger solutions. Water. Upon the application of water the colored cells swell up, lose the discoidal form, and become spherical, and at the same time part with their coloring matter, the haemoglobin ; the latter, being dissolved, leaves the bleached and colorless stroma to form the "ghost." That the red corpuscles are not destroyed by the water, as sometimes stated, may be demonstrated by the addition of a suitable aniline dye, when the presence of the bleached corpuscles is made evident by the colored rings which mark their outlines. The action of water upon the living color- less blood-cells is somewhat different. These corpuscles cease their amoeboid movements, retract their Fig. 132. Reactions of human blood- cells with various reagents: A , effect of treatment with water upon the white (w) and the colored cell (r) ; B, red cells after the addition of saline solutions, crenation following the application of weak solu- tions, great shrinking and dis- tortion (s) succeeding the action of the concentrated reagent ; C, action of dilute acetic acid on the colorless cell (w) and on the red cor- puscle (r) ; D, red blood-cell after the addition of one-per- cent, solution of tannic acid. no NORMAL HISTOLOGY. processes, become round, and swell up into larger spheres ; mean- while, the protoplasm resolves itself into a number of sharply-cut granules, which, owing to their suspension within a fluid of less density than the blood-plasma, exhibit the active dancing or oscil- latory movements which constitute the " Brownian motion," a phenomenon entirely physical in nature. The nuclei of the colorless cells after treatment with water appear as clear or slightly granular areas among the vibrating particles. After a time the distention of the corpuscle becomes too great, and rupture takes place, followed by the escape of the particles of disintegrated protoplasm. Acids. Upon the addition of weak acetic acid the red cells become rapidly decolorized, at the same time losing the discoidal form and approaching the spherical. The protoplasm of the color- less corpuscles clears up entirely, the nuclei coming very con- spicuously into view. Upon subsequent treatment of acid prepara- tions with aniline, the nuclei of the white cells appear deeply stained, while the red cells are outlined by faintly-colored rings. Tannic acid, when applied to the red corpuscles in weak (one- half to one per cent.) solutions, produces a peculiar effect: the coloring matter of the corpuscle is coagulated as it escapes from the cell and becomes conspicuous as a minute accumulation adhering to one edge of the corpuscle. Where strong solutions of tannic acid are employed, the haemoglobin is coagulated within the corpuscle before it has had an opportunity to escape, producing appearances which have been mistaken for nuclei and other details of cell-structure. The Blood-Platelets. If human blood be drawn directly into a drop of osmic acid solution (one per cent. ) or of a three-fourths per cent, solution of sodium chloride, Fig. 133. covered at once, and examined with a high A b power, numbers of small, colorless, circular ^ r~\ C\ disks will be seen on careful observation ; Mfog^-s \j\jU these are the blood-platelets of Bizzozero, Cyp 'W-. rmX7 sometimes called the third corpuscular ele- %&g 2l^yPv~~~"~ ments °f tne blood- They are very unstable, ^T^ prone to disintegration, and are variable in a, human red blood-ceils and size, possessing an average diameter of about blood-platelets (/); ^minute Qne.third Qf that of the red cdls . they fatty (?) particles, which occur _ ' m m J isolated or in masses; b, fibrin occur singly, but show a marked disposition filaments, among which lie par- together in groups preparatory to tially disintegrated blood-plate- ° . . , , lets. breaking up into the minute particles long known as the granules of Max Schultze. Unless great precaution is taken to insure the immediate action of the preserving fluids, the blood-platelets will not be seen in their normal form. THE CIRCULATORY SYSTEM. TII These bodies may be recognized in the circulating blood, as ob- served by Osier and others, and are constant, although numerically variable, elements of mammalian bloods. The peculiar elongated elliptical "blood-spindles" found in the blood of other vertebrates are probably to be regarded as the homologues of the blood-plaques of mammals. While the presence of the blood-platelets as distinct, constant, and normal constituents of the human blood is now gener- ally recognized, authorities are far from accord as to their significance. The evidence at present seems to point to a close relation between these bodies and the process of coagulation, in view of their probable active role in the production of the factors in the formation of fibrin. Fibrin filaments are to be observed in a drop of blood mounted in the usual manner for microscopical examination and allowed to stand for some time in a moist chamber ; they appear as very delicate straight interlacing threads which occupy the interspaces between the corpuscles and frequently radiate from a common centre, con- taining a group of partially broken-down blood-platelets. Additional minute particles are to be seen in human blood, regarding the nature, source, and significance of which much has been surmised and but little definitely established. These include the small colored disks, the microcytes or the haematoblasts of Hayem, according to whose authority they constitute an important source of the red corpuscles ; by others they are regarded as sep- arated portions of the ordinary red cells. Other minute, colorless, often highly refracting, granules are encountered floating in the liquor sanguinis; such are the elementary particles of Zimmer- mann and the granules of Max Schultze. These particles differ in nature as well as in source ; some probably are derived from the disintegration of the white corpuscles and of the blood-platelets, others from that of the FlG- endothelial plates of the vascular channels, while many represent fatty granules absorbed during digestion or taken up, possibly, in the course of pathological processes. Blood-Crystals. The coloring matter of the Ha:min cr>'sta's, ,ro,m dried ° human blood. blood— the haemoglobin — readily crystallizes in man and most mammals as elongated, rhombic prisms ; the haemo- globin crystals of the squirrel and of the guinea-pig, however, are respectively hexagonal plates and rhombic tetrahedra. These blood- crystals, of a deeper or lighter red color according to their size, often form in preparations of blood which have been sealed and allowed to stand after the addition of a few drops of water ; the blood of the rat is especially favorable for their production. If dried blood be treated and thoroughly mixed with glacial acetic acid (the addition I 12 NORMAL HISTOLOGY. of a few granules of common salt being advantageous in the case of old clots), on slightly heating until bubbles appear, numbers of dark-brown irregular rhombic prisms form. These are the haemin crystals of Teichmann, which are positive indications of the presence of blood, but have no value in the determination of its source. They vary greatly in size and considerably in form, the peculiar unequally-notched ends presented by the larger crystals being quite characteristic. DEVELOPMENT OF THE BLOOD-CORPUSCLES. The origin of the colorless blood-cells must be referred to the lymphoid tissues, since these elements are identical with those occurring within the lymph with which they are poured into the blood-current. The colorless corpuscles appear later than the red cells, the first ones probably entering the circulation as migratory mesodermic elements. The lymphatic or ade?wid tissues, however, undoubtedly constitute the principal sources of the colorless blood- corpuscles, which are produced by the division of the numberless masses of active protoplasm contained within the various aggrega- tions of lymphoid tissue throughout the body. The multiplication of existing colorless cells which takes place normally, but which is especially active under the stimulus of patho- logical conditions, accounts for the origin of a certain number of white corpuscles ; the division of the cellular elements of connective tissue is regarded by some as an additional source of these blood- cells. The efferent lymph-streams passing from the lymphatic tissue, as well as the blood contained in the splenic vein, are richer in color- less cells than are the corresponding afferent currents, showing that the augmentation is due to the new elements contributed by the lymphoid tissues through which the currents pass. The origin of the colored blood-cells is usually considered as taking place during two epochs — before and after birth. It must be remembered, however, that such division is conventional and largely arbitrary, since the period at which the primary embryonic processes of such formation cease and are replaced by those maintained throughout life is uncertain and variable ; in man and mammals born in a condition of advanced development the production of blood-corpuscles within the marrow is instituted before the termina- tion of intra-uterine life. Before Birth. The first blood-cells originate outside the body of the embryo, within the angioblastic cells of the mesodermic tract of the vascular area. Certain cells of this layer increase in size and undergo proliferation of their nuclei, forming multinucleated areas known as the blood-islands of Pander. These subsequently THE CIRCULATORY SYSTEM. 113 unite into an irregular net-work, the nodal points of which are dis- tinguished by an active production of new nuclei. Some of these acquire protoplasm and later become the endothelium of the blood- vessel, while others, more centrally situated, are converted into the primary blood-corpuscles, the intervening tissue undergoing liquefaction to constitute the blood-plasma. These earliest blood- cells, although destined to become the red corpuscles, are at first colorless masses of active protoplasm, provided with nuclei and exhibiting amoeboid movements. After a time the protoplasm gradually acquires the characteristic tinge and assumes a discoidal form, the elements then constituting the nucleated red blood-disks of the embryo. The earliest red cells unquestionably increase by the division of the primary corpuscles, the reproduction being attended by the changes of karyokinesis. This multiplication of the early red corpuscles probably ceases in man long before the end of gestation, the embryonal colored corpuscles meanwhile becoming smaller and losing their nuclei, so that at birth all the nucleated red cells have disappeared. The exact details of the metamorphosis from the embryonal to the adult form are still uncertain. There is no evidence at present to establish the descent of the red corpuscles from the colorless cells, the two being distinct elements having independent origins. The liver must probably be reckoned among the situations in which the formation of blood-cells takes place during embryonal life ; in this same category is included the spleen by some authorities, indeed, Bizzozero regards it as a post-natal source. After Birth. Of the many suggested sources for the post-natal production of the red blood-cells, of which great numbers must be formed constantly to replace those continually undergoing destruction, the red marrow of bones is undoubtedly the most important. Among the more common elements of the red marrow, cells usu- ally are to be observed which strongly resemble the embryonal red blood-corpuscles, being distinguished from the ordinary marrow- •cells by their haemoglobin-colored protoplasm, smaller size, and unstable nuclei. These cells, often called the erythroblasts, are undoubtedly transitional forms of red blood-corpuscles, the nuclei disappearing and the protoplasm assuming the usual appearance of such elements. As to the source of the erythroblasts, however, whether they are transformed colorless marrow-cells or distinct elements, the descend- ants of the red corpuscles of the embryo, much uncertainty still exists. There are strong reasons for regarding the latter supposition the true indication of their nature and origin, the production of the red corpuscles both before and after birth being thus closely related. Direct transformation of the colorless cells, production within the 11a NORMAL HISTOLOGY. spleen, and growth from the blood-platelets, or haematoblasts of Hay em, have been advanced from time to time as additional sources of origin of the red blood-corpuscles. Without entering upon a detailed critical consideration of the evidence supporting these views, it may be stated that, at present at least, they all lack the conclusive proof of unimpeachable direct observation. Concerning the rela- tions of the ' ' haematoblasts' ' much confusion exists in consequence of the application of the term to different objects by various writers. The exceptionally small red corpuscles, or " microcytes," together with those of unusually large diameter, may be regarded as ex- pressing the extremes of variation in size to which all morphological elements are subject. The formative processes within the red bone- marrow may be regarded, in the light of our present knowledge, as the most important source, if, indeed, not the sole authentic one, of the new red blood-corpuscles produced throughout life. Mention may be made in this place of the problematic organs the so-called arterial glands, which include the coccygeal and carotid glands. The first of these, the glandula coccygea, or Luschka's gland, occurs near the tip, in front of the apex, of the coccyx, associated with the middle sacral artery, which contributes the blood-vessels largely forming its pea-sized mass. The carotid gland lies at the bifurcation of the common carotid artery, frequently between the resulting branches, and appears as a somewhat flattened ovoid nodule. These peculiar bodies are identical in structure, both consisting of dense arterial net-works surrounded by irregular groups of granular polyhedral cells, whose presence suggested the once supposed glandular nature of the organs. The entire plexiform mass is invested by connective tissue, from which fibrous septa pene- trate between the vascular structures. Numerous non-medullated nerve-fibres are also present. The true nature and function of these rudimentary organs are en- tirely unknown, and probably will remain so until the embryology of these bodies is better understood. THE LYMPHATIC SYSTEM. 115 CHAPTER VIII. THE LYMPHATIC SYSTEM. The lymphatic system consists of two parts — the lymph-channels and their contents the lymph, and the lymphatic tissue. The former may be represented by irregular interfascicular clefts between the bundles of fibrous tissue or by vessels with well-defined walls, while the latter may exist as diffuse adenoid tissue, the simple lym- phatic nodule, or the complicated compound lymph-gland. THE LYMPH-CHANNELS. The lymphatic spaces, the radicles of the more distinct vessels, are almost universally present, since they exist in almost every locality where connective tissue abounds, forming intercommuni- cating systems of greater or less perfection throughout the Fig- j35- various organs. The relation between the connective tissue and the lymph-radicles is very intimate, and it may be assumed that all interfascicular clefts are directly or indirectly con- nected with the lymphatics. In loose areolar tissues, as the sub- cutaneous, the lymph-Spaces Lymph-spaces between bundles of fibrous tissue ... , . A \ t • 1 seen in profile, from the human cornea :£,<£, bundles are lll-ClenneCl CleltS, irregular 0f fibrous tissue ; s, lymph-spaces containing flattened in form and size, which are connective-tissue ceils. bounded by the neighboring bundles of fibrous tissue and lined by an imperfect layer of endo- thelioid connective-tissue cells. In the denser forms of fibrous tissue, as the central tendon of the diaphragm, cornea, etc., the lymph-spaces are more limited and form well-defined intercommuni- cating systems of canals, or "juice-channels ;" of such the corneal spaces and the bone-lacunae are familiar examples. These spaces are filled incompletely by the connective-tissue cor- puscles, which usually are applied to one wall of the cavity to form a partial lining. The number of cells occupying a single space varies : sometimes several lie side by side (kitten's cornea) united by lines of cement-substance ; in such cases, after silvering, the cells present the appearance of endothelial plates. The large serous u6 NORMAL HISTOLOGY. cavities, as the peritoneal or pleural sacs, are, in principle, greatly-dilated lymph-spaces, lined by FiG modified connective-tissue cells, the en- dothelial plates, which by mutual press- ure become polygonal in outline ; in- but Lymph-spaces of cornea, surface view : a, the spaces within the ground-substance (c) con- nected by the minute canals (6), or canaliculi. Lymph - capillary from silver-stained mesentery of frog: a number of lymph- corpuscles occupy the deli- cate endothelial tube which constitutes the vessel. stead of a few cells sufficing for the formation of a lining membrane, as in the case of the minute Fig. 138. lymph-space, innumerable ele- ments are required to clothe the large serous cavity. The lymphatic spaces within the connective tissue join to form definite channels at the margins of the fibrous tissue, the lymph being carried by the lymphatic vessels from the organs to the adjacent masses of adenoid tissue, the lym- phatic glands. The lymph- vessels immediately succeed- ing the spaces may be regarded as the lymphatic capil- laries, being protoplasmic tubes of great delicacy, com- posed of a single layer of en- dothelial plates. The contours of the lym- phatic vessels are not uniform, but present numerous dilatations and constrictions, which indicate the positions of the imperfect valves : Lymphatics of silvered diaphragm of rabbit : s,s, lymph-spaces lying within the deeply-stained ground- substance ; /, /, lymphatic vessels lined with endo- thelium and possessing valves (v) and corresponding dilatations. THE LYMPHATIC SYSTEM. 117 Fig. 139. Perivascular lymphatic (b) enclosing a small ar- tery (a), from the silvered mesentery of frog : c, branching lymphatic cap- illary. these latter consist of a fold of endothelium, strengthened often by a minute quantity of elastic tissue. The relation of the lymph-spaces to the capillary blood-vessels on the one hand and to the lymphatic vessels on the other is very inti- mate ; in certain localities, as in the omentum, indirect communication between the blood-vessels and lymphatics is established by means of the spaces of the groundwork of the dense connec- tive tissue (Klein). Many nerve-trunks are en- closed by perineurial lymphatic channels, into which the lymph-spaces of the surrounding tissue open. The blood-vessels of the central nervous system, especially of the retina, likewise are surrounded by distinct perivascular lymph- sheaths, formed by the enlargement and con- fluence of the clefts within the adventitia of the vessels. In some membranous structures, notably the amphibian mesentery, the vessels lie encased within distinct endothelial tubes. Lymphatic vessels of large size have walls of considerable thickness, resembling those of the veins. In such vessels three coats are recog- nizable— the inner, or endothelial, the middle, or muscular, and the outer, or connective tissue. The thoracic duct possesses a well-developed intima, composed of a considerable layer of subendothelial connective tissue con- taining a net-work of longitudinally dis- posed elastic fibres. The muscular tissue of the media is supplemented by bundles of involuntary muscle extending length- wise within the outer coat, which in the vessel under consideration is particularly robust. The lymph contained within the lym- phatic vessels, like the blood, consists of two parts — the clear, straw-colored plasma, or liquor lymphae, and the cellular elements, the lymph-cor- puscles. The cells of the lymph are small nucleated masses of active proto- plasm, when at rest presenting a spherical form and measuring about .01 mm. in diameter ; in their usual condition of activity, however, their outlines Fig. 140. ^SPHs 395 X Transverse section of human tho- racic duct : i, >«, and o, respectively the inner, middle, and outer tunics ; .r. endothelial lining, beneath which lies the fibrous stratum containing net-work of longitudinal elastic fibres (y); z, longitudinally disposed bun- d'es of muscular tissue within adven- titia ; v, capillary blood-vessels. n8 NORMAL HISTOLOGY. are continually undergoing the changes effected by amoeboid move- ment. These elements, in short, possess all the peculiarities of the colorless blood-corpuscles with which, in fact, they are identical. In addition to the lymph-corpuscles, numerous fatty granules are usually present within the plasma ; in the lymphatic vessels of the intestinal tract the absorption of fatty matters is made conspicuous by the presence of the chyle, an emulsion occupying the so-called lacteals, or chyle-vessels ; these latter are not distinct tubes, but only those portions of the lymphatic net-work which convey the milky-looking chyle during certain stages of digestion. The sources of the lymph-corpuscles are those already con- sidered in connection with the colorless cells of the blood, the lym- phoid or adenoid tissues of the body being unquestionably the most important and prolific seats for the production of these elements. The presence of a few cells within the lymph-radicles, between their commencement and the first masses of adenoid tissue occurring on their course, is due to the entrance within the vessels of migratory cells from the surrounding connective tissue ; only after the lymph- stream has passed through considerable masses of lymphoid tissue do the corpuscles appear with profusion. THE LYMPHATIC TISSUES. Lymphatic, lymphoid, or adenoid tissue usually occurs as circumscribed masses known as lymphatic nodules or "glands;" in certain localities, however, as in parts of the mucous membranes of the larynx, the pharynx, the stomach, the intestines, etc., ill-defined masses of diffuse lymphatic tissue occur. These are recognized as aggregations of small round cells, fading away among the surround- ing structures. Lymphatic tissue, wherever found, is com- posed structurally of two elements — the deli- cate connective-tissue reticulum, on the surface of the fibres of which plate-like, often stellate, connective-tissue corpuscles are applied, and the small round cells contained within the reticulum. These elements — the lymphoid or adenoid cells — become the lymph-cor- puscles and the colorless blood-cells on their escape from the denser reticulum into the lymph-current and their subsequent entrance into the blood. The variations in the compactness with which the cells are lodged Elements of adenoid tissue from partially brushed sec- tion of lymphatic gland of child : a, fibres of reticulum ; b, lymphoid cells ; c, ex- panded connective - tissue plate. THE LYMPHATIC SYSTEM. Iig within the net-work constitute the denser or looser forms of adenoid tissue found in the lymphatic nodules ; ordinarily the cells are so closely placed that the reticulum is greatly masked, satisfactory views of the latter being obtained only in sections of great thinness or after the cells have been removed by brushing or by violent agitation. The reticulum of lymphoid tissue consists of intertwining and anastomosing bundles of connective tissue ; along the fibrous trabecular, especially at the nodal points, Fig. 142- Fig. 143. flattened plate-like or stellate connective-tis- sue cells are applied after the manner of an imperfect endothelial investment. In parts of many adenoid struct- ures the delicate re- ticulum seems to be formed by the union of the protoplasmic pro- cesses of the branching connective-tissue cells themselves ; this ar- rangement, however, is usually only seem- ing, the cells really being applied to the surface of the fibres and not constituting an integral part of the reticulum. It is probable that in the splenic pulp and in a few other localities the processes of the stellate cells do unite to form protoplasmic net-works. Diffuse adenoid tissue represents the least specialized form of the lymphoid structures ; the mucosas of the digestive and of the respiratory tracts afford good illustrations of the presence of such tissue. Simple lymphatic nodules, or solitary follicles, stand next in differentiation ; these are found in almost all mucous membranes (those of the bladder and of the sexual organs excepted), while they occur in great numbers in the respiratory and digestive tracts, the solitary glands of the latter being important examples of these structures. The simple nodules consist of oval masses of adenoid tissue, limited by a delicate connective-tissue wall or capsule, com- posed of fibrous lamellae. The adenoid tissue of such simple follicles presents no considerable variations in its arrangement, that occupy- ing the more central portions of the nodule, however, being fre- Diffuse lymphoid tissue occu- pying deeper layers of mucosa of human stomach : the lym- phoid cells infiltrate the fibrous tissue between the glands with- out being definitely limited. Simple lymph -follicle from conjunctiva of dog : a, lym- phoid tissue, limited by the fibrous capsule (b) ; c, sur- rounding connective tissue. 120 NORMAL HISTOLOGY. quently somewhat less closely packed than the tissue at the periphery. The afferent lymph-vessels conveying the lymph to the simple follicles break up at the periphery of the nodule into branches, which distribute the lymph to the adenoid tissue ; corresponding efferent vessels carry off the fluid returned from the lymphoid tissue and unite to form larger lymphatic trunks. Compound lymphatic follicles, the lymphatic glands of gross anatomy, are formed by the aggregation and partial fusion of a Fig. 144. •>ci Section of lymph-gland from child, showing general arrangement of lymphoid tissue and lymph- sinuses: a, capsule from which trabecular (b, b) extend ; c, masses of dense adenoid tissue composing the cortical follicles ; d, the same, of the medullary cords ; e, lymph-sinuses. Fig. 145. number of simple nodules. These structures enjoy a wide distri- bution, and are represented by the numerous chains of deep and superficial lymph-glands, of which the axillary and inguinal glands are familiar instances. The periphery of these lymph-glands is occupied by a firm capsule composed of fibrous connective tissue, inter- mingled with which, in the largest glands, bundles of involuntary muscle are sometimes present. At the position of entrance and exit of the larger blood-vessels and the efferent lymphatic trunks, usually opposite the most convex surface of the organ, the capsule dips deeply into the interior of the gland and forms the hilum. The space included within the capsule is subdivided into a peripheral zone, the cortex, and a centrally situated part, the medulla, which at the hilum reaches Section of lymphatic gland of child, including portion of cortex at periphery : c, capsule ; s, loose tissue of the lymph- sinus ; /, denser lymph-tissue of the cortical follicle. THE LYMPHATIC SYSTEM. 121 the exterior. The details of arrangement distinguishing these portions of the gland depend primarily upon the distribution of the trabeculae which continue the tissue of the capsule into all parts of the Organ. The trabeculae, composed of stout bundles of fibrous tissue, ex- tend from the inner surface of the capsule towards the hilum and divide the cortex into a number of imperfect spherical compartments which enclose masses of adenoid tissue, the cortical follicles, which correspond to simple lymph-follicles. The continuations of the tra- beculae towards the centre of the gland unite at much more frequent intervals and form throughout the medulla a series of incomplete par- titions which separate imperfect compartments occupied by elongated masses of adenoid tissue, the med- ullary cords. These latter and FlG- J47- the cortical follicles constitute one continuous mass of dense lymphoid ■ I ■ .;*, Section of lymphatic gland of child, in- cluding portion of medulla : t, part of tra- becula, on either side of which narrow lymph-sinuses are seen, bounded by denser structure of medullary cords (/). d Portion of human lymph-gland, showing de- tails of structure : a, lymph-sinus ; b, adenoid tissue ; c, trabecular ; d, coarser reticulum of lymph-sinus : e, expanded connective-tissue plate applied to fibres ; /, lymphoid cells. tissue, which follows the contours of the spaces occupied, but does not completely fill the compartments formed by the fibrous trabeculae. The spaces included between the fibrous trabeculae and the masses of dense adenoid tissue are occupied by a very loose reticulum and sparingly distributed lymphoid cells ; these channels are the lymph- sinuses, into which the lymph brought by the peripherally-situ- ated afferent vessels is poured and through which it finds its sluggish course, thus securing the opportunity of taking up numerous new cells in its journey through the organ. The lymph-sinuses form a freely intercommunicating system of canals throughout the gland, beginning at the periphery, where they receive the afferent lymph- vessels, and ending in the hilum, where the lymph is collected and carried off by the efferent trunks. 122 NORMAL HISTOLOGY. The trabeculae all along their course give off numerous ramifi- cations ; each of these breaks up into still finer bands, until the final divisions of the fibrous tissue terminate in the delicate reticulum con- stituting the supporting framework in whose meshes the lymphoid cells are held. In the areas of denser tissue the cells are so closely- placed that the supporting reticulum is almost completely masked. The surfaces of the fibrous bundles and partitions, especially those directed towards the lymph-sinuses, support numerous plate- like connective-tissue cells, in places these elements constituting almost an endothelial covering. The blood-vessels supplying the lymphatic glands are arranged as two groups : the one set gains entrance at the periphery and is distributed principally to the capsule and larger trabeculae ; the other group enters at the hilum, the majority of the arterial branches pass- ing directly into the lymphoid tissue, while a few follow the course of the larger septa ; these, following the latter course, give off numerous twigs to the surrounding adenoid tissue, the terminal branches con- tinuing to the capsule, where they finally are distributed. The cap- illaries derived from the breaking up of the arterial twigs entering at the hilum especially ramify through the denser adenoid tissue, avoid- ing the loosely reticulated lymph-sinuses. The distribution of the nerves passing to the compound lymphatic glands is uncertain, the supply including bundles of both the medullated and the pale fibres. In addition to the numerous well-developed compound lymphatic follicles, many of which, as the mesenteric and the bronchial glands, reach conspicuous dimensions, certain organs present special modifi- cations of adenoid tissue ; such are the spleen and the fully-developed thymus body, which therefore may be included with propriety in the account of the lymphatic structures. THE SPLEEN. The spleen may be regarded as a specialized compound lymphatic gland, modified by the arrangement of its blood-supply. The organ is invested by a firm capsule, composed of a dense felt-work of bundles of fibrous tissue, with which are mixed numerous elastic fibres. The outer surface of the capsule, with the exception of a limited area, is covered by the serous coat of the peritoneum, the union between the two being very intimate. On the inner surface the capsule is continuous with numerous prolongations, the trabeculae. These penetrate deeply into the interior from all sides, and by the free union of their processes form a spongy connective-tissue framework throughout the organ, enclosing an elaborate system of intercommunicating spaces occupied by the lymphoid tissue. THE LYMPHATIC SYSTEM. 123 In certain animals (dog, cat, hog) the capsule contains bundles of involuntary muscle ; these are only exceptionally present in man. Fig. 148. Section of spleen of dog, showing general structure : a, capsule, from which trabecular extend ; sec- tions of these latter are seen in several places, as at d ; b, tissue of splenic pulp ; c, c, Malpighian corpuscles ; e , sections of blood-vessels. Likewise, bundles of muscular tissue are constituents of the trabecular in many mammals, including man to a limited degree ; the muscle- cells are distin- Fig Fig. 150. guishable from the surrounding connective tissue by their rod- shaped nuclei. The stoutest tra- becular are found at the hilum, which corre- sponds to the position at which the larger blood- vessels enter and leave the organ. The lymphoid tissue filling the intertrabecular spaces exists in two forms — as the loose adenoid tissue which, together with the Section of human spleen, showing trabecular (it) and fibrous reticulum (6) continued into the surrounding splenic pulp ; c, lymphoid cells Transverse section of large trabecula of human spleen : a, fibrous tissue, containing a few groups of plane muscle-cells (i) ; c, extension of trabecula into fibrous reticulum ; d, lymph- corpuscles. 124 NORMAL HISTOLOGY. Fig. 151. ■&:&' *fc^ intimately related vascular channels, forms the splenic pulp, and as the cylindrical or spherical masses of dense adenoid tissue ensheath- ing the arteries, constituting the Malpighian corpuscles. The largest trabecular support the branches of the splenic artery ; on entering at the hilum, these twigs receive a strong fibrous invest- ment, or adventitious sheath, which accom- panies the vessel and becomes gradually reduced as the arte- ries diminish in size ; finally, this sheath blends with the con- nective-tissue frame- work of the paren- chyma. Many of the smaller branches of the splenic ar- tery are deflected from the trabec- ular and enter the surrounding tissue, where they become ensheathed at irregu- lar intervals by cy- lindrical or spherical masses of dense adenoid tissue and constitute the Malpighian corpuscles. The artery usually pierces the mass somewhat eccentrically, sometimes, however, passing near the centre. Numerous small twigs are distributed to the tissue composing the corpuscles ; after forming a net-work they eventually open into the channels of the pulp ; the main artery of the Malpighian corpuscle has a similar destination. The form of these ensheathing masses of adenoid tissue varies in different animals ; in some (guinea-pigs) the arteries are accompanied throughout their entire course by a layer of lymph-cells, while in others (man, cat) the investment is limited to irregularly spherical masses ; between these extremes numerous intermediate forms exist. The peripheral zone of the Malpighian corpuscle is usually denser than the central part, an arrangement favoring the sharp demarca- tion of the body from the surrounding looser parenchyma ; in man the corpuscles are less clearly defined than in many lower animals. The splenic pulp, which makes up the larger part of the bulk of the organ, consists of a loose net-work of slender bands and imperfect septa, composed of delicate fibres and broad plate-like connective- 1 Section of human spleen cutting transverse. y a Malpighian cor- puscle : a, section of the somewhat eccentrically situated artery ; b, capillaries distributed to the tissue of the corpuscle ; /, the sur- rounding lymphoid tissue of the splenic pulp. THE LYMPHATIC SYSTEM. 125 Fig. 152. Portion of channel within splenic pulp from human spleen : a, endothelioid connective-tis- sue plates of the imperfect wall of the space ; b, red blood-corpuscles ; c, lymphoid cells ; d, larger amoeboid elements, containing pigment- granules ; e, large multinucleated cell. tissue cells. The processes of the latter unite with one another to form imperfect partitions ; in young animals multinucleated plates are frequently encountered. Ad- hering to the delicate reticulum, partially occluding the channels throughout the pulp, are numerous lymphoid cells or leucocytes, which are largely the offspring of the ele- ments forming the adenoid tissue. The spaces of the splenic pulp are additionally occupied by num- berless colored blood-cells, brought by the arteries which open directly into the channels within the pulp ; the dark-red appearance of the organ is thus explained. As a re- sult of the breaking down of numer- ous worn-out red blood-cells, — in which process of destruction the leucocytes may take an active part, — pigment - granules, both free and within the lymph-cells, are con- stantly encountered. The splenic pulp, in addition to giving origin to numerous leucocytes, in common with other lymphoid tissues, is regarded by some histologists as the birthplace, as well as the " grave- yard," of a certain number of colored blood-cells; the evidence, however, upon which such views rest is far from conclusive. The blood-vessels of the spleen form an important part of the organ. After entering at the hilum, the splenic artery gives off tra- becular branches which rapidly diminish in size by repeated division. As already described, many of the smaller arteries leave the septa and become ensheathed by the Malpighian corpuscles, to which they contribute with capillary net-works. A certain number of the arteries extend the entire length of the trabeculae, and hence never become encased within the masses of adenoid tissue ; both these latter and those bearing the corpuscles eventually open into the spaces of the pulp, pouring their streams of blood into the parenchyma. The pulp-spaces communicate, on the other hand, with a wide-meshed net-work of venous channels ; the latter unite to form a number of large veins, which pass out at the hilum in company with the principal arteries. All the blood conveyed by the smaller arteries finally reaches the spaces of the splenic pulp, whether directly or indirectly after having first passed through the tissue composing the Malpighian corpuscle ; 126 NORMAL HISTOLOGY. Fig the blood then slowly traverses the partially obstructed channels within the pulp and is collected by the venous spaces and passed on to the larger veins, by which it escapes from the organ. The retarded current within the splenic pulp is favorable to the removal and destruction of the worn-out red cells and to the acquisition of additional leucocytes. Within the pulp, while passing from the arteries to the veins, the blood is probably not confined to channels provided with defi- nite walls, but comes into direct relation with the lymphoid tissue. The lymphatics of the spleen are limited to the connective-tissue framework of the organ, in which they form a superficial plexus in the deeper layers of the capsule, and a deeper plexus within the trabecular. The lymphatic clefts within the adventitia of the arteries communicate with the deeper lymphatics of the trabeculae ; regarding the definite relations of the deeper lymphatics our knowledge is incomplete. The nerves of the spleen are composed mostly of non-medullated fibres, although a few of the medullated variety are present ; they are distributed to the walls of the blood- vessels ; also ganglion-cells have been ob- served along the nerve-trunks. Diagram of the relations of splenic vessels to the tissue of the pulp : a, v, small arterial and venous branches of splenic vessels within trabecula {t, t) ; one twig of artery is diverted and becomes ensheathed by tissue of the Mal- pighian corpuscle, M ; the remain- ing part of the artery follows the trabecula and passes directly into the spaces of the pulp — in either case the arterial branches termi- nate in the spaces (/, /) within the pulp surrounded by the lym- phoid tissue (/, /) ; the venous radicles take up the blood and carry it from the spaces of the pulp into the larger venous trunks. THE THYMUS BODY. The thymus body is included among the lymphatic tissues on ac- count of the histological characteristics of the fully-developed organ ; in its early stages, however, the bulk of the organ is epithelial in nature, being derived from the endodermic cells and closely resem- bling many glands in its earliest growth. The rapid invasion of mesodermic tissues, at a later period, so changes the character of the organ that tissues of a lymphoid type predominate, while the original epithelial structures are reduced to mere rudimentary remains. The entire organ usually consists of two lateral lobes, more or less intimately united, composed of numbers of lobules, held together by the interlobular areolar tissue and enveloped within the general fibrous capsule of the organ. The irregularly ovoid lobules, 5-10 mm. in diameter, are further divided by connective-tissue septa into compartments, each of which includes several smaller secondary THE LYMPHATIC SYSTEM. 127 lobules ; these, in turn, are made up of groups of the primary alveoli or follicles. The latter closely resemble lymph-follicles in structure, being limited by a fibrous envelope giv- Fig. 154. ing off slender tra- becular, which are soon lost in the deli- cate reticulum of connective tissue pervading all parts of the follicles. The meshes of the re- ticulum are occupied by numerous lym- phoid cells, among which many capillary blood - vessels run. The adenoid tissue of the peripheral zone, or cortex, of the follicles is more Section of human thymus body, showing general arrangement of follicles : a, fibrous tissue enveloping lymphoid tissue and sending septa (<»') between the follicles (b) ; d, interfollicular tissue, contain- ing blood-vessels (c). Fig closely packed with cells than that occupying the centre, or medulla, in consequence of which variation the medulla appears lighter than the denser cortex. Scattered throughout the follicles ■ C jtfr, ■■■:r% JVC—- - --J,;iK^*'~ Portion of the same follicle, showing corpuscles of Hassall (a), which represent the original epithelial constituents of the organ. -fe#£-y Portion of the periphery of one of the folli- cles of the foregoing section, more highly magnified : a, fibrous tissue ; b, lymphoid tissue, containing numerous capillaries (c). round or oval bodies are seen, which vary greatly in number and size (20-175 /./), usually stain but faintly, and present an irregularly concen- I28 NORMAL HISTOLOGY. trie striation, with occasional nuclei ; these bodies are the corpuscles of Hassall, or the concentric corpuscles. They represent the re- mains of the epithelial structures which, as already stated, in the early stages of the thymus constitute the principal tissue of the organ. The larger blood-vessels of the thymus run within the inter- lobular connective tissue, giving off branches which penetrate the follicles and break up into a rich capillary net-work supplying the adenoid tissue of cortex and medulla. As may be inferred from the character of the organ, the lym- phatics occur in large numbers. The radicles coming directly from the follicles are received by the interlobular vessels, which, in turn, communicate with the superficial net-work occupying the surface of the organ. Bundles of nerve-fibres accompany the ramifications of the arteries and veins, to the coats of which they seem principally to be distributed. The thymus body reaches its highest development about the second year, after which time it gradually diminishes, undergoing retrogressive changes and absorption, until, by the eighteenth to the twenty-first year, the characteristic tissues have disappeared or have been replaced by fibrous connective tissue and fat. THE SEROUS MEMBRANES. The serous membranes are intimately related to the lymphatic system, since the cavities which they enclose form parts of the gen- eral lymph -tract of the body; when considered in their widest sig- nificance they include the lining of all cavities clothed with endothe- lial cells and cut off from atmosphere. Regarded in a more limited and critical sense, such cavities may be separated into certain groups, following which the connective-tissue linings may be divided into : a. The serous membranes proper, as the peritoneum, the pleura, and the pericardium. b. The synovial membranes, including the synovial capsules of the joints, the synovial sheaths of tendon, and the synovial bursae placed between opposed movable surfaces to reduce friction. c. The endothelial lining of the vascular system, comprising that of the heart, of the blood-vessels, and of the lymphatics. d. The lining of various spaces developed within the connective tissues ; such spaces are usually small and provided with very rudi- mentary linings ; they may be, however, of considerable size, as in the case of the perilymphatic spaces of the internal ear. The serous membranes proper, represented by the peritoneum, the pleura, the pericardium, and the tunica vaginalis, are all derived as constrictions from the originally single pleuro-peritoneal cavity THE LYMPHATIC SYSTEM. 129 first formed. In the closed sacs constituted by the serous mem- branes a parietal and a visceral layer are always distinguishable ; the connection of these with the subjacent structures is slight or intimate according to the character and amount of the subserous tissue. Every organ which projects beyond the wall of the serous pouch into its cavity must be enveloped by the serous membrane to a greater or less degree. When the organ remains closely attached to the wall of the body-cavity, as does the kidney, it obtains only a partial serous investment ; where, on the other hand, the organ leaves the parietes and encroaches upon the cavity, the serous invest- ment becomes almost complete, as in the case of the small intestines. In all cases the viscera lie outside the serous sac, the membrane which constitutes the lining of the space being pushed before the encroaching organ to form a serous covering more or less complete. The serous cavity of greatest extent — that of the peritoneum — in the female presents an exceptional arrangement in possessing outlets at the orifices of the oviducts ; in this connection, however, it must be remembered that the oviduct is the persistent Mullerian duct, which is only one of a number of tubes formed during early foetal life by evagination of the primary serous membrane, thus establishing communication with surfaces exterior to the serous cavity. While such tubes in the higher animals are only transient, in the lower types they may remain as permanent structures. The serous membranes are sufficiently thin and transparent to permit the color of the underlying parts to be seen readily through them ; moderate strength, extensi- bility, and elasticity are among their physical properties. These membranes consist of the endothelium covering their free surface and resting upon the connective-tissue stroma, which constitutes the chief substance of the membrane ; external to this layer a variable amount of subserous tissue usually is pres- ent. The endothelium comprises a single layer of the large, thin, irregularly - polyhedral connective - tissue plates already described and figured in Chapter II. In addition to the minute deeply-stained intercellular areas, or pseudo-stomata, true openings, or stomata, also exist in the sev- eral serous membranes. These orifices are especially well seen in silver preparations from the posterior wall of the frog's peritoneal 9 Fig Peritoneal endothelium of dog, silver-stained ; several pseudo- stomata are seen as dark areas among the cells. !,0 NORMAL HISTOLOGY. cavity (Fig. 30) ; but they may be demonstrated also in the tissues of man and of the higher animals : the central tendon of the dia- phragm, on which they were first discovered in the peritoneum by von Recklinghausen, offers a favorable place for their study. In addition to the stomata occurring in the peritoneum covering the diaphragm, similar apertures have been observed in the omentum, the pleura, and the pericardium. The stomata, either directly Fir 1 ^8 • or through minute canals, lead into the sub- jacent lymphatic vessels and are surrounded by cuboidal or spherical guard-cells. The stroma of the serous membranes con- sists of interlacing bundles of white fibrous tissue, mingled with elastic fibres, which are especially numerous in the more superficial Peritoneum in section from partS) where they frequently form a reticular dog: /, peritoneum proper. y consisting of endothelium of layer. I he interstices between the fibrous free surface and subendotheiiai bundles are occupied by the ground-sub- fibrous stroma containing net- . , r . work of elastic fibres; s, sub- stance ; the latter alter a time in some cases, peritoneal vascular connective as m tne omentum, Suffers local absorption, interfascicular orifices then partially taking its place. The serous membrane, which in its earlier condition forms a continuous sheet, may become riddled with apertures, and is said to be fenestrated. Where the ground-substance and stroma are well developed and of considerable thickness, particularly in the vicinity of folds, adipose and sometimes lymphoid tissue occur in addition to the blood-vessels and lymphatics. The ground-substance in places where dense is penetrated by an intercommunicating system of lymph-spaces opening into the lymphatic vessels of the serous membrane. Branched connective-tissue cells are also frequently seen with processes extending between the endothelial plates of the free surface ; such processes when stained with silver probably form the pseudo-stomata already mentioned ; other protoplasmic exten- sions of the cells may come into relation with the walls of the blood- vessels or of the larger lymphatics. The subserous layer, where well developed, is composed of loosely-arranged bundles of fibro-elastic tissue, between which blood- vessels and lymphatics, with migratory leucocytes, are situated. The blood-vessels of serous membranes contribute wide-meshed net-works both to the layer of proper stroma and to the subserous tissue ; in positions where tracts of adipose or of lymphoid tissue exist, the capillaries form net-works enclosing the fat-sacs or the lymphoid masses. The lymphatics of serous membranes are very numerous, and are represented by the definite lymphatic vessels and the lymph-spaces THE LYMPHATIC SYSTEM. 131 within the ground-substance ; by means of the stomata and the minute passages leading from them the lymphatics communicate with the serous cavities, while, on the other hand, they join with the wide, irregular lymph-channels within the subserous tissue. The nerves supplying these membranes are limited, those which are present being largely derived from the sympathetic system, com- posed of pale, non-medullated fibres destined chiefly for the blood- vessels. The few fibres passing into the substance of the membrane form a loose reticulum throughout its deeper layers, from which finer fibrillar extend beneath the surface. The synovial membranes, which constitute a second group of serous membranes, include the lining of the clefts developed within the connective tissue (mesoderm) surrounding opposed movable surfaces, embracing the capsules enclosing the articulating surfaces of the various joints, the synovial sheaths in which the tendons glide, and the bursal sacs interposed between surfaces ; these varieties of synovial membranes are known respectively as the articular, the vaginal, and the vesicular. Synovial membranes differ from the serous in the character of their secretion ; that of the former — the synovia — is a glairy, viscid fluid, resembling the white of egg, well adapted for the lubrication of the opposed parts, and contains fat particles, lymphoid cells, and degenerated endothelial plates. Fig. 159. Section of synovial membrane at edge of articular surface : s, s, tissue of synovial membrane bearing villous projections (z/, v) ; x, position at which tissues of membrane become continuous with those of periphery of cartilage ;_/, group of fat-cells ;/, fibrous tissue constituting peripheral zone of cartilage (c). The secretion moistening serous membranes is thinner, watery, and less suited to the reduction of friction. The articular synovial membranes surround the joints, tightly embracing the bones and enclosing them within their sacs, but do not extend over the articulating surfaces, which are composed of j„ NORMAL HISTOLOGY. naked cartilage, over whose surfaces of contact not even the imper- fect endothelial covering is continued ; tendons or other structures traversing the joint-cavity receive an investment of the synovial membrane. The marginal zone, embracing the attachment of the membrane to the cartilage, is marked by the gradual alteration of the tissues of the synovial membrane to assume the characters first of fibro-cartilage, and finally of the typical articular cartilage of which the membrane then seems a part. The synovial sacs, originating as clefts within the mesoderm surrounding the extremities of the young bones, exhibit a structure corresponding to slightly condensed connective tissue. The mem- brane is composed chiefly of closely-felted bundles of fibrous tissue, mingled with elastic fibres, containing the usual connective-tissue elements ; the free surface of the membrane possesses an imperfect covering of connective-tissue cells, which, when closely placed, as in the younger tissue, present the characters of an endothelium ; when less densely arranged, they retain their processes and appear as branched elements, resembling those of other dense fibrous tissues ; in the vaginal membranes the cells are often elongated to correspond with the axis of the sheath. Cleft folds of the synovial membrane project into the serous cavity as the Haversian fringes ; they are free processes of the membrane containing vascular loops and, in the larger ones, fat ; the smaller secondary fringes, or villi, often present as finger-like processes attached to the edges of the larger folds, contain no blood-vessels, but consist principally of small, irregularly-round cells, separated by a scanty intercellular substance. In some cases these villi enclose a denser core, which consists of fibrous bundles ; occasionally the entire villus is formed of fibro-cartilage, the superficial round cells being wanting. Blood-vessels are quite numerous within the synovial mem- branes, as well as in the subjacent tissues, nearly all parts of the joints being generously supplied. Many of the Haversian fringes contain vascular tufts, while the termination of the blood-vessels around the margin of the cartilages is marked by vascular loops possessing greatly dilated terminal arches. The nerves of the synovial membranes, by no means numerous, form a loose plexus beneath the free surface ; in connection with the joints, peculiar special nerve-endings, the articular end-bulbs of Krause, have been found attached to the nerve-fibres; Pacinian corpuscles have likewise been observed in relation with the synovial membranes. The serous surfaces lining the blood-vessels and the lymphatic THE LYMPHATIC SYSTEM. 133 channels and spaces have been considered in connection with their respective systems. The development of the lymphatic system in all its parts involves the mesoderm alone. Very early in the life-history of the embryo, shortly after the appearance of the three blastodermic layers, the mesoderm undergoes cleavage into two leaves, the separation affecting the mesodermic layer on either side as far as the lateral margin of the uncleft axial band. The resulting sheets of meso- dermic tissue become the parietal layer i' (somatoplenric) and vis- ceral layer {splanchnopleuric) ; the former clings to the ectoderm to become the future wall of the body-cavity, while the latter adheres to the entoderm to form the wall of the digestive tube. The space included between these leaves is the primitive body- cavity, or ccelom, and the mesodermic tissue forming its imme- diate wall becomes dif- ferentiated into a special Fig. 160. lining — the mesothe- lium — whose elements are the ancestors of the later endothelium. The fully-formed se- rous membranes, represented by the peri- toneum, the pleura, the pericardium, and the tunica vaginalis, are all derived as constric- tions from the common pleuro - peritoneal sac, or body - cavity, first formed, the subdivision of which into the above- mentioned special serous compartments occurs secondarily and at a much later period. Bearing in mind the origin of the primary lining of the serous membranes, the claims of endothelium to near kinship with con- nective tissue must be admitted ; likewise, the reasons for regarding endothelium as distinct in nature from epithelium will be appreciated. Inasmuch as the epithelium of the genito-urinary tract is derived indirectly from the mesoderm, it is related genetically to the endo- thelium of the abdominal serous membrane. In the course of the differentiation and growth of the fibrous con- nective tissue, clefts appear within the ground-substance between the bundles of young tissue, which become the lymph-spaces of the Transverse section of" ten-day rabbit embryo, showing the cleavage of the mesoderm and the formation of the primary body-cavity : E, ectoderm ; M, M, the letters occupy the body-cavity and have the parietal (/) and visceral (v) layers of the cleft mesoderm respectively above and below them ; the immediate lining of the cavity constitutes the mesothelium ; En, entoderm ; A'', neural canal ; c, notochord ; s, s, cavities within the somites — really parts of the body-cavity; a, one of the paired primitive aortas. j ^. NORMAL HISTOLOGY. maturer stages. The formation of the lymphatic vessels takes place in a manner very similar to that by which the blood-channels are produced. The protoplasmic net-works established by the united processes of the connective-tissue corpuscles are at first solid ; sub- sequently they acquire a lumen and become converted into a series of protoplasmic tubes, the nuclei of whose endothelial plates are de- rived from the proliferated nucleus of the original elements. The earliest lymph-corpuscles are, probably, migrated mesoblastic cells which have entered the young vessels. The additional coats of the larger lymphatic trunks are derived from the condensation and differentiation of the surrounding young connective tissue. The development of the lymphoid tissue occurs at a rela- tively late period. The position of the future lymph-gland is indi- cated by a cleft or fissure which appears within the mesoderm and completely isolates the gland-area on all sides except that destined to become the future hilum, where the tissue devoted to the produc- tion of the gland and the surrounding mesoderm are continuous. The development of the lymphoid tissue is marked by increased numbers and greater compactness of the mesodermic elements ; the supporting reticulum, the capsule, and other details of the adenoid tissue appear later. The development of the spleen begins about the commence- ment of the third month, some time after the pancreas has become defined ; a condensation of the mesodermic cells, lymphoid in character, within the primitive omentum, or the mesogastrium, in the near vicinity of the pancreas, is the earliest indication of the future organ. The lymphoid aggregation first established is sup- plemented by the elements lying beneath the peritoneum, which differentiate into elongated spindle-cells especially devoted to the formation of the trabeculae and connective-tissue framework. Numerous blood-vessels soon grow into the splenic tissue, the sub- sequent accumulations of lymphoid cells within the tissue around some branches of the arteries giving rise to the Malpighian cor- puscles. The history of the development of the thymus body demon- strates an origin markedly at variance with the character of the fully- formed organ, since, notwithstanding the pronounced lymphatic type of the tissue constituting almost the entire body when most complete; its structure in the earliest stages corresponds entirely to embryonal epithelium which is derived as the direct outgrowth of the ento- derm. The first trace of the thymus body appears as a cylindrical bud of entodermic tissue springing on either side from the third pharyngeal pouch, or inner visceral furrow. The epithelial nature of the early thymus is for some time very evident, the original cell- THE LYMPHATIC SYSTEM. 135 mass appearing also similar to the earliest stage of a glandular area ; repeated division rapidly converts the at first simple cylindrical aggre- gation into a complex figure, in which an elongated main part bears numerous lateral branches. At a later period the surrounding meso- derm becomes richer in cells and more compact and grows into the original epithelial structure, the result of which invasion is the final complete atrophy and disappearance of the epithelial constituents, with the exception of the inconspicuous but constant corpuscles of Hassall, which alone bear witness to the primary epithelial nature of the orean. 136 NORMAL HISTOLOGY. CHAPTER IX. MUCOUS MEMBRANES AND GLANDS. Fig. 161. All passages and cavities directly or indirectly communicating with the exterior of the body and the atmosphere are lined by mucous membranes. These structures consist of two parts : the connective-tissue stroma, or tunica propria, and the epithelial covering ; the outer surface of the connective-tissue layer is quite usually special- ized to form an extremely delicate basement-membrane, or mem- brana propria, which thus separates the epithelium from the under- lying tissue and forms a third constituent of the mucous membrane. The basement-membrane is often scarcely demonstrable as a distinct layer, while in certain organs, as many glands or the hair-follicles, it is highly developed. The epithelium of mucous surfaces varies both in character and in arrange- ment, as already described in Chapter II. The proper substance or stroma of the mucous membrane consists of a felt-work of bands of fibrous connective tissue together with net-works of elastic fibres ; these latter may be so plentiful that an especial elastic layer is formed, as in parts of the respiratory tract. Numerous con- nective-tissue cells lie between or upon the fibrous bundles, the flattened plate- like cells forming in many places par- tial linings for the interfascicular lymph- spaces found throughout this layer. Not infrequently the surface of the connective-tissue stroma is beset with numerous elevations or papillae, over which the epithelium extends. Such irregularities, when slight, may be present without impressing the free surface of the mucous membrane, since the epithelial layer completely fills the depres- sions between the elevations : when very pronounced, the papillae or folds of the connective tissue produce such conspicuous sculpt- urings of the surface as the papillae of the tongue or the rugae of the vagina. Diagram of a typical mucous mem- brane : e, epithelium of free surface con- tinuing into the glandular depression to become the secreting cells ; h, base- ment-membrane separating epithelium and connective-tissue stroma ; s, s, fibro-elastic tissue of tunica propria ; v, blood vessels forming net-works beneath epithelium and around gland. MUCOUS MEMBRANES AND GLANDS. 137 Fig. 162. Mucous membranes may be invaded to a greater or less degree by lymphoid cells, as in many localities in the digestive tract ; sometimes, as in the villi of the small intestine, the tissue assumes still more closely the lymphoid type, a delicate connective-tissue reticulum supporting the lymphoid cells. The membrana propria, or basement-membrane, usually appears as a delicate homogeneous line beneath the epithelium. It must be regarded as a modification of the connective tissue, and when well developed, after suitable staining with silver, appears as a more or less complete covering of flattened, endothelioid cell-plates. The deeper layers of the mucous mem- brane fade away into the surrounding areolar tissue or into the adjacent submucosa ; sometimes, how- ever, the mucosa is limited by a delicate zone of involuntary muscle, the muscularis mucosae, consisting often of two distinct, although delicate, layers of muscle-cells. Mucous membranes are usually provided with glands, which in their simplest type are depressed portions of the general mucous surface, lined with modified epithelium — the secreting cells. A single cell may constitute an entire gland, instances of such arrangement being found in the unicellular glands of the lower forms ; the familiar goblet-cells are, in fact, such structures ; it is, however, the more developed forms of secreting apparatus which the term "gland" usually represents. Glands are of two chief varieties, tubular and saccular, each of these occurring as simple and compound. Simple tubular Plate-like endothe- lioid connective tissue cells constituting base- ment-membrane. Diagram illustrating the forms of glands : A , simple tubular ; B, compound tubular ; C, modified (coiled) tubular ; D, simple saccular ; K, compound saccular, or racemose. glands are frequent, the peptic glands and the mucous follicles of the intestines being well-known examples. Compound tubular glands vary in complexity, from a simple bifurcation of the fundus, j,g NORMAL HISTOLOGY. as in many pyloric or uterine glands, to the intricate arrangement of the tubules of the kidney or the testicle. Simple saccular glands do not occur in the higher animals, but are conspicuous in the lower types, as in the integument of am- phibians. Compound saccular, or racemose, glands, on the other hand, are represented in man and mammals by such important organs as the pancreas and the salivary glands. In the least complex type of gland, the simple tubular, the two fundamental parts of all glands are distinguishable in their primi- tive form : these are the deeper actively secreting portion, the fundus, and the superficial division, or duct, through which the products of the secreting cells escape. Dilatation of the fundus of the primitive type produces the simple saccular gland ; division of the fundus and of part of the duct originates the compound tubular variety ; repeated cleavage and subdivision of the duct, with accompanying expansion of the associated terminal tracts, lead to the production of the com- pound saccular, or racemose, type. The tubular glands may exist as perfectly straight cylindrical depressions ; more usually, however, the tubes are somewhat wavy or tortuous : when the torsion of the fundus Fig. 164. reaches its highest expression, such modi- fications as the coiled sweat-glands result. Glandular epithelium is the direct de- rivative of the cells covering the adjacent mucous membrane, so modified and special- ized as to adapt it to the requirements of the several parts of the gland. In simple tubular follicles the cells of the adjacent free surface pass into those lining the neck of the gland with little change ; cells of the increased size and spherical form become more pronounced towards the fundus, where the elements assume the characters of se- creting epithelium. The cells lining the upper part of the duct of such glands not infrequently exhibit a distinctly imbricated arrangement ; this is well seen in the peptic glands. The greater complexity of the racemose glands resulting from the system of freely branching excretory tubes renders the recognition of several parts desirable. These are, towards the ducts, proceeding from the ter- minal compartments, the alveoli or acini, the intercalated or intermediate tubules, the intralobular tubes, the interlobular Tubular glands : A, simple tubu- lar crypt from human small intes- tine ; B, compound tubular gland from pyloric end of human stomach. MUCOUS MEMBRANES AND GLANDS. 139 ducts, and the excretory ducts, which latter usually unite to form a single common duct of large size. At the open end of the acinus the lining cells of the latter become flattened or cuboidal, and, together with the basement-membrane, are directly continuous with the similar structures forming the walls of the narrow intermediate tubule ; the latter succeeds the acinus as the continuation of the narrow intercellular clefts of several adjacent acini, and, after a longer or shorter course as a delicate narrow- lumened canal, passes into the intralobular tube. The distinctive characters of the latter are its larger lumen and the columnar epithe- lium, many cells of which exhibit a distinct vertical striation through- out the peripheral zone next the basement-membrane. The branch- ing intralobular tubes, on emerging from the lobular tissue, join to form the interlobular duct which occupies the connective tissue lying between and holding together the divisions of the glandular sub- Fig. 165. Fig. 166. Section of racemose gland showing relation of glandular tissue to origin of duct : x, acini lined with secreting cells which are directly continuous with those of the intermediate tubule (2) ; y, interlobular connective tissue. Section of the human parotid gland showing the interlobular tissue : s, s, se- creting cells of surrounding acini ; d, inter- lobular duct ; v, blood-vessels within the fibrous tissue ; g, group of ganglion-cells. stance. The interlobular ducts are clothed with simple columnar cells, which form a passive lining to the canal for the conveyance of the secretions of the more active parts of the gland. Towards the free surface of the mucous membrane the interlobular ducts unite to form the chief, often single, excretory duct of large lumen, whose walls for a variable distance from the point of discharge are covered with epithelium similar to that covering the adjoining mucous surface ; this is soon replaced, however, by the columnar cells which then continue into the smaller tubes. In the large ducts the subepithelial tissue is strengthened by net-works of elastic fibres. The saccules or alveoli are limited by a basement-membrane 140 NORMAL HISTOLOGY. upon which rests a single layer of irregularly spherical or polygonal secreting cells ; these latter do not entirely fill the acinus, but leave an intra-cellular cleft, in which the system of tubes for the conveyance of the secretions commences. Glands are often divided into serous and mucous, a differentia- tion depending upon the peculiarities of the cells lining the acini as well as upon the character of their secretion. The cells of the serous glands are distinguished by being distinctly granular, generally spherical in form, readily and deeply stained with carmine, and by having conspicuous nuclei situated near the centre of the cells ; the elements of the mucous glands, on the contrary, are distended, Fig. i Fig. 167. Serous acini of human pa- rotid gland ; the deeply-stain- ing granular cells are sur- rounded by the basement- membrane. Mucous acini of human lingual gland: the secreting cells (a), being loaded with the slightly-staining secretion, appear clear and transparent ; c, c, crescentic masses of granular cells — the demi-lunes of Heiden- hain ; b, interacinous connective tissue. very clear and transparent, slightly stained with carmine, and have the nuclei displaced to the outer edge of the cells, not infrequently immediately beneath the basement-membrane. In the embryonal pre-functionating condition these two kinds of glands are identical, both as to mode of origin and histological characteristics ; the varia- tions and the conspicuous differences subsequently appearing depend on differences of physiological function and character of secretions, and not on structural differences in the original cells. Fluids elaborated by the serous glands are thin and watery, appear- ing within the protoplasm of the secreting cells as minute dark gran- ules ; the general appearance of the cells depends upon the number of these granules stored up within their protoplasm. When a serous gland is in a condition of rest, the cells are loaded with granules, and consequently they appear larger, darker, and more granular ; after active secretion the cells are exhausted and contain fewer granules, appearing, therefore, smaller, clearer, and less granular. MUCOUS MEMBRANES AND GLANDS. 141 The mucous glands secrete a clear, viscid, homogeneous sub- stance, or mucine, having little affinity for carmine, but staining deeply with haematoxylin. During rest the cells of such glands become loaded and distended with the mucoid secretion, while the nuclei are crowded to the periphery of the cells ; under these condi- tions the cells lining the acini appear clear with well-defined outlines, and, on the sides next the basement-mem- brane, present a thin zone containing the displaced nuclei and granular protoplasm. After prolonged secretion the exhausted cells contain relatively little mucoid sub- stance ; hence the threads of the protoplasm are no longer widely separated, but are more closely placed ; in consequence of these changes the cells assume appearances resembling those of the elements of the serous glands, being smaller, darker, and more granular than the cells of the quies- cent mucous gland. In the acini of mucous glands small crescentic groups of granular, deeply-staining cells are often seen lying between the clearer elements and the basement-membrane ; these are the crescents of Gia- nuzzi, or the demi-lunes of Heidenhain, the significance of which has caused extended discussion. These crescents represent, most Lingual glands from tongue of cat : a, b, the serous and the mucous acini containing respec- tively the granular and the clear cells. Fig. 170. B r a ',%&8&!&r r A and B, serous and mucous acini in different stages of functional activity: r, condition of rest, the cells being gorged with secretion ; a, condition of exhaustion after great activity : following the discharge of the secretion the elements of the protoplasm become more closely placed, producing an appearance of increased granularity. probably, groups of quiescent or exhausted cells which have been displaced and crowded to the periphery of the acinus by the dis- tended more centrally situated active cells. The view regarding the crescents as composed of young cells destined to replace those de- stroyed by active secretion is opposed by the absence of partially disintegrated cells as well as by that of all manifestations of cell division. The vascular supply of glands is always rich. The larger blood- vessels, conveyed by the submucosa, send off branches into the 142 NORMAL HISTOLOGY. Fig mucosa to break up into capillaries which enclose the tubules and acini in close net-works, lying outside but in intimate relation with the basement-membrane, an arrangement favoring the passage of substances from the blood into the protoplasm of the secreting cells, which are thus placed between the blood-current on the one hand and the lumen of the gland on the other. Numerous lymphatic spaces are contained within the connective tissue surrounding the acini and the tubules, some of the clefts being immediately beneath the membrana propria and in close relation with the gland. The nerve-supply of glandular structures is often very rich. The nerve-trunks accompany the larger blood-vessels in the submucous tissue and give off numerous small bundles which follow the smaller arteries in their distribution to the mucosa, where they form delicate plexuses about the acini and the tubules immediately outside the basement-membrane. The exact mode of the final termination of the nerves and their relation to the individual secreting cells are still matters for investigation ; whether the fibres pierce the basement- membrane to terminate among the glandular epi- thelium, while probable, must be regarded as still unproved. The development of glands proceeds from the epithelial tissue of the young mucous mem- brane, the penetrating cylinder of epithelium rep- resenting ectodermic or entodermic tissue, except in those cases where the glands are formed in connection with the parts of the genito-urinary tract derived entirely from the mesoderm. The first trace of the glands consists of a cylindrical ingrowth of the epithelium into the subjacent mesodermic tissue, both the tubular and the saccular glands alike starting as simple epithelial processes. Where, however, the struct- ure is destined to become a gland of the racemose type, the branching cords of epithelial elements early indicate the nature of the future gland as distinguished from one of the compound tubular variety ; since, in this case, the terminations of the epithelial masses soon become markedly ex- panded and club-shaped, from which dilatations the ultimate divisions or primary alveoli of the racemose glands are extended secondarily. The epithelial cords, at first solid, later acquire a lumen which extends as far as the terminal compartments of the gland. Sometimes, as conspicuously instanced by the liver. Developing salivary gland from fifteen-day rabbit embryo. The ectodermic ingrowth has divided into secondary branches which termi- nate in slightly expanded club - shaped ends : e, epithelium of oral sur- face ; in, young connec- tive tissue of future tunica propria into which the epithelium grows. MUCOUS MEMBRANES AND GLANDS. j^? the primary arrangement of the gland is modified by subsequent changes to such a degree that the original plan of its structure is recognized with difficulty. The sexual glands are so highly special- ized that in their development they deviate materially from the mode of the formation of the typical secretory organs. Ordinarily the elaborating glandular cells are ectodermic and entodermic in origin, while the basement-membranes and supporting tissues are meso- dermic. 144 NORMAL HISTOLOGY. CHAPTER X. THE DIGESTIVE TRACT. Fig. 172. THE MOUTH. The mucous membrane of the oral cavity consists of the epi- thelial covering and the connective-tissue stroma or tunica propria ; the deeper layers of the latter fade insensibly into the subjacent tissues which unite the mucous membrane with the surrounding deeper parts. The epithelium lining the entire oral cavity is of the stratified squamous variety, continuous with the epidermis on the one hand and with the covering of the pharynx on the other. The tunica propria is composed of interlacing bundles of fibrous connective tissue containing elastic net- works, and possesses numerous simple papillae which encroach on the epithelial layer, but do not appear on the free surface of the mucous membrane. The latter is broken in many places by the openings of the ducts of the numerous glands which occupy the submucosa and deeper parts of the mucosa. In the transition of the skin on the lips, where the skin passes into the mucous membrane, the epithelium is greatly thickened, while the connective- tissue layer decreases in thickness ; the subepithelial papillae here become very prominent. The hair-follicles disappear, but the sebaceous glands still are present, especially near the angles of the mouth and in the upper lip. The mucous membrane covering the cheeks adheres tightly to the bucci- nator muscle, and possesses small papillae ; that covering the gums is dense, and contains numerous well-marked papillae beneath the epithelium, the submucous tissue being closely united with the peri- osteum. The portion covering the hard palate is thin and firmly united to the periosteum, while that investing the soft palate, the uvula, and the fauces is much thicker, less dense, possesses numerous mucous glands, and, in many places, is so densely crowded with lym- phoid cells that the entire mucous membrane assumes the appearance of adenoid tissue. Section of oral mucous membrane of child ; the surface of the fibrous tunica propria is broken by minute papillae, which contain the endings of the blood- vessels and the nerves. The papillae are covered by the stratified squamous epithelium. THE DIGESTIVE TRACT. j^ The oral mucous membrane is thickly beset with small mucous racemose glands in nearly all parts. These are especially well marked on the lips, the cheeks, the under surface of the tongue, and the soft palate, constituting, respectively, the labial, the buccal, the lingual, and the palatine glands ; on the gums and the hard palate such structures are absent or present in very limited numbers. The acini are situated within the deeper layers of the mucosa, while the •ducts pierce the superficial layers to open on the free surface. The squamous epithelium of the latter is continued within the duct usually as far as its first division. Small lateral isolated groups of acini, ■constituting accessory mucous glands, sometimes open into the long narrow excretory duct of the main glandular mass during its journey to the free surface. The larger blood-vessels supplying the oral mucous membrane lie within the submucous tissue and give off branches which extend through the deeper layers of the mucosa to the superficial portions of the connective-tissue stratum ; on reaching the outer boundary •of the latter the arteries break up into rich subepithelial capillary net-works, or, where papillae are present, enter the minute elevations to supply their apices with terminal capillary loops. The capillaries likewise enclose the acini of the oral glands. The lymphatics begin in the irregular net-work of interfascicular spaces between the connective-tissue bundles of the tunica propria ; these spaces unite to form definite lymphatics in the deepest layers of the mucosa, which in turn are taken up by the larger lymph- vessels of the submucous tissues. Nerve-fibres, largely of the medullated variety, accompany the blood-vessels, and form a subepithelial plexus ; special terminations — the end-bulbs — are found in the apices of some of the papilla?, while additional numerous tactile corpuscles occur on the lips. THE TEETH. In principle, and among many of the lower animals in fact as well, the teeth may be regarded as hardened papillae of the oral mucous membrane. The teeth are firmly retained within their appropriate sockets by the close attachment afforded by the alveolar periosteum which holds together the alveolus and the root of the tooth. The perios- teum lining the alveolus is composed of dense fibrous tissue, whose fibres have a general transverse disposition : elastic tissue is almost wanting, nerves and blood-vessels being, however, numerous. At its neck the tooth is especially embraced by the thickened perios- teum, which then becomes continuous with the periosteum covering the alveolar process of the jaw and with the gum. 146 NORMAL HISTOLOGY. The tooth comprises the dentine, the enamel, and the cemen- tum. The dentine, or ivory, principally contributes the bulk and the characteristic form of the tooth, completely enclosing- a central pulp- cavity, except where the narrow nutrient canal, admitting the blood- vessels and nerves to the pulp, pierces the apex of the fang. The dentine is composed of a matrix or ground-substance, which, as that of bone, must be regarded as modified connective tissue, formed of bundles of FlG- l73- fibrous tissue intimately united and subsequently impregnated with calca- reous salts. Piercing the ground- substance and appear- ing under low amplifica- Longitudinal section of molar tooth of kitten : a, pulp-cavity, continued by canals (_/") to apices of roots ; d, dentine ; e, en- amel ; c, cementum ; /, alveolar periosteum ; n, neck of tooth ; b, osseous tissue of jaw. Section of dried human tooth showing portions of enamel and dentine : a, ground-substance of dentine ; b, branching dentinal tu- bules ; c, terminal zone of tubules within the enamel (d). tion as a radial striation, the dentinal tubules extend the entire thickness of the dentine as minute channels ; they are seen espe- cially well in sections of the dried tooth in which the canals are filled with air. Starting from the pulp-surface with a diameter of 20-26 fi, the dentinal tubules pass in a slightly wavy and spiral course through the dentine, to terminate in irregular clefts, the interglobular spaces, situated at the juncture of the dentine with the enamel or the cementum. THE DIGESTIVE TRACT. I4y The tubules give off numerous secondary canals along their course, by which means the adjacent tubules communicate ; on approaching the enamel or the cement the tubules undergo repeated division, the resulting smaller secondary channels corresponding in their general direction with the larger canals. The marked parallel curves described by the dentinal tubules pro- duce optical effects which are appreciated as a coarse striation con- centric with the outline of the pulp-cavity ; these appearances, known as Schrager's lines, may be seen in sections with the unaided eye. That part of the dentinal matrix immediately surrounding the tubules is especially dense and resistant, and constitutes the so-called den- tinal sheaths which may be isolated by acids. Within the tubules lie the delicate dentinal fibres, which are the modified processes of the connective-tissue cells forming the peripheral layer of pulp- cells. When cut across the tubules appear circular or slightly oval, and contain a minute dot, the dentinal fibre in transverse section. Want of uniformity in the calcification of the outer zone of dentine gives rise to the incremental lines of Salter. The interglobular spaces are irregular stellate intercommuni- cating clefts situated at the margin of the dentine, into which open on the one hand a number of dentinal tubules and on the other hand the Fig. 175. Fig. 176. Interglobular spaces of dentine from dried human tooth : i, i, spaces into which certain dentinal tubules {d) open. Section of enamel from dried human tooth : a, b, longitudinal and trans- verse views of enamel rods. spaces or the lacunae of the cementum. Each space contains a pro- toplasmic body, the connective-tissue cell, the processes of which unite with the dentinal fibres. The enamel covers the exposed parts of the softer underlying dentine, and is composed of irregular 4-6-sided columns, the enamel prisms, closely placed and generally vertical to the surface of the dentine. After suitable isolation the enamel prisms appear slightly varicose in outline, the minute concavities producing the irregular dark bands often seen traversing the prisms. The prisms are held together by a delicate layer of cement-substance and grouped into Fig j^g NORMAL HISTOLOGY. bundles which cross one another, producing the alternate dark and light radial bands seen in the enamel. The additional dark lines extending more or less parallel to the free surface of the tooth — the stripes of Retzius — are probably due to inequalities in growth and density. At birth, and for a variable time thereafter, the outer sur- face of the enamel is covered by a delicate but resistant cuticle, the membrane of Nasmyth, composed of keratose epithelial plates, the remains of the enamel organ. This cuticle is soon worn away after the teeth are actively used. Next the dentine numerous clefts exist for a short distance between the enamel prisms ; they com- municate with the interglobular spaces and thus indirectly with the dentinal tubules. The cementum, or crusta petrosa, invests the fang of the tooth and closely resembles in structure ordinary bone ; the lamellae extend parallel to the dentine, as do likewise the long axes of the bone lacunas. Where the cementum reaches a considerable thickness, as at the apex of the root of the tooth, Ha- versian canals may exist, although usually these are wanting ; the outer layers of the cement contain fewer and smaller lacunas. The lacunae communicate with the dentinal tubules, while the protoplasmic processes of their contained bone-cells may come in contact with the filaments of the odonto- blasts lying within the dentinal tubules. The pulp consists of a matrix of soft embryonal connective tissue, in which nu- merous stellate and spindle cells form pro- toplasmic net-works by their anastomosing processes. At the periphery the connective- tissue elements are arranged as layers of elongated cylindrical cells perpendicular to the inner surface of the dentine, in contact with which they lie ; these cells are the odontoblasts, being the representatives of the cells which were actively engaged in producing the dentinal matrix. The protoplasm of many of these cells is prolonged peripherally as delicate threads into the dentinal tubules, the processes becoming modified to form the stiff elastic dentinal fibres ; centrally, the odontoblasts frequently are connected with the stellate connective-tissue cells. The pulp is richly supplied with blood-vessels and nerves. The arteries run in the long axis of the tooth, breaking up into capillary net-works which are closest in the periphery. The nerves accom- Section of human tooth at the junction of the dentine and the cementum : D, dentine with its tubules, which communicate with interglobular spaces (B) and with lacunae of cementum (C). Fig. 178. THE DIGESTIVE TRACT. j.g pany the larger blood-vessels as medullated fibres ; these give off filaments which pass to the layers of odontoblasts, among which they extend as pale fibres. The ulti- mate distribution of these latter is still unsettled ; the assertion that fine fibrillar accompany the dentinal fibres into the tubules lacks confirmation. Distinct lymphatic vessels have not been demonstrated within the pulp, although the clefts within the matrix between the connective-tissue fibres represent the lymph-spaces and are in close relation with the adjacent lym- phatic channels. DEVELOPMENT OF THE TEETH. The teeth of man and the higher animals are really exaggerated papillae, the peripheral parts of which have become specialized and have under- gone calcification. The ectoderm con- tributes the enamel, while the dentine, cementum, and pulp are derived from the mesoderm. A linear thickening of the primitive oral epithelium marks the earliest indication of the formation of the teeth ; in man this band appears before the end of the sixth week (Rose), and is adherent to the under surface of the epithelial layer. Following the ex- pansion of this ectodermic thickening a con- tinuous lateral projection, the dental ridge, grows obliquely into the mesodermic tissue. The dental ridge continues to grow back- ward towards the mandibular articulation, forming an unbroken arch of ectodermic tissue connected with the under side of the oral epithelium. The line of this attach- ment is later marked on the oral surface by a longitudinal furrow, the dental groove, which has been long known, and which was formerly regarded as the initial step in the dental development. While the dental ridge constitutes a shelf-like common epithelial invagination, the position and further development of the individual teeth are marked by local thickenings along the under surface of Section of young tooth of child, show- ing peripheral portion of pulp and ad- joining dentine : b, pulp-cells, some of which send processes (a) within dentinal tubules ; c, stroma of delicate connective tissue; d, blood-vessels. Fig. 179. Section of jaw of rabbit embryo, showing thickening of ectodermic epithelium (ec) from which dental ridge (e) begins its growth into mesoderm (m). j r0 NORMAL HISTOLOGY. the ridge. These secondary aggregations are the first indications of the enamel organs of the temporary teeth. After the establish- FlG. 1 80. Fig. 181. Model of jaw of human embryo of 40 mm. : r, r, arch of increased epithelium constituting dental ridge; /, local thick- enings corresponding to positions of future enamel sacs. (After RSse.) Section of jaw of rabbit embryo, showing dental ridge cut across : ec, oral ectoderm ; e, epithelial outgrowth corre- sponding to future enamel organ ; m, mesodermic tissue. Fig. 182. ment of these structures the ectodermic tissue composing the dental ridge atrophies and eventually disappears in the intervals between the individual teeth. The enamel sacs of the permanent teeth are formed at a later date from the remains of the dental ridge, those for the three permanent molars being derived from a special extension of the dental ridge which grows independently of ectodermic attachments. The primitive enamel organ which grows from the dental ridge at first con- sists of a solid cylindrical process of epi- thelial tissue ; soon, however, the ex- tremity becomes club-shaped and slightly tortuous, and later distinctly expanded and flask-shaped. Coincident with these changes the surrounding mesoderm be- gins to exhibit proliferation and conden- sation of its elements, this differentiation marking the earliest stage in the forma- tion of the important mesodermic dental papilla, which very soon becomes a conical mass of closely-aggregated meso- dermic elements. Along with the growth of the latter the now expanded end of the ectodermic plug becomes indented Section of jaw of rabbit embryo, showing later stage of enamel organ, which now exhibits differentiation into outer (b) and inner (e) cells : m, mesodermic tissue which at a has undergone already some condensa- tion ; ec, oral ectoderm. THE DIGESTIVE TRACT. 151 or invaginated to form an epithelial cap, which embraces the meso- dermic dental papilla, and, from its future important function, is known as the enamel organ. The impression of the dental papilla upon the overlying enamel organ is probably not to be attributed to mechanical obstruction op- posed to the advancing ecto- dermic tissue, but has its cause in more deeply lying laws of ex- pansion along lines of unequal growth. As the invagination of the enamel organ progresses, more and more of the dental papilla becomes covered, until about two-thirds of the meso- dermic cone are embraced within the sides of the ectodermic cap. The enamel organ itself under- goes a differentiation into three distinct layers : the outer layer, directly continuous for a long time with the ectodermic cells of the oral cavity, is composed of one or two layers of low columnar or polyhedral cells ; at the point where they are reflected to form the inner, invaginated part of the original epithelial sac, the cells become elongated and Fig. 184. Section of jaw of cat embryo ; the dental papilla is seen as a projecting conical mass (/) of con- densed mesoderm, whose summit is enveloped by the invaginated enamel organ (e) ; ec, oral epi- thelium, still attached by the atrophic isthmus (a) with the enamel organ, whose outer (6), middle (c), and inner (d) layers are differentiated; e', beginning of enamel organ for permanent tooth. Section of jaw of cat embryo with four developing teeth slightly farther advanced than in the pre- ceding stage: ec, oral epithelium; a, dental groove; e, enamel organ; /, /, dental papillae; m, mesodermic tissue ; b, b, bone. distinctly columnar, constituting the inner layer of the enamel organ containing the beautiful enamel cells. The outer and inner layers jr2 NORMAL HISTOLOGY. of the enamel organ are separated at first by the narrow zone of epithelial elements of the middle layer ; the cells of the latter soon undergo characteristic changes, owing to an accumulation of fluid, resulting in the complete transformation of the cells, which become pressed together and reduced to thin plates, the tissue appearing as if composed of irregularly anastomosing connective-tissue fibres rather than of epithelial elements. The enamel organ retains for a considerable time its connection with the epithelium of the oral cavity, a thin atrophic cord of cells indicating the position of the former robust stalk. At the side FlGJ 5- 0f this attachment a lateral cylin- drical projection early marks the beginning of the development of the second enamel organ for the permanent tooth. The columnar cells of the inner layer alone are concerned in the production of the enamel. This process consists essentially of a ,) y gradual deposition on the inner ' side of the enamel cells — that is, next the new dentine — of homo- geneous prisms arranged verti- cally to the surface of the inner layer of the enamel organ. The layer of enamel increases by the addition of increments deposited from within out, the latest-formed enamel always lying immediately internal to the inner layer of the enamel organ. During the later stages the inner and outer layers are approximated at the expense of the intervening middle layer, which finally becomes reduced to an attenuated stratum, the other coats of the enamel sac coming almost in actual contact. During the changes described in the enamel organ the central dental papilla is actively engaged in producing the dentine. The top and sides of the papilla are covered by a layer of elongated, columnar or pyriform connective-tissue cells, the odontoblasts, which are the immediate agents in causing the deposition of the dentinal matrix, the formative process being similar to that producing bone. The dentine is first formed at the apex of the papilla, and appears as a thin lamina of homogeneous matrix into which the delicate processes of the odontoblasts extend, becoming the dentinal Section of developing tooth from cat embryo : m, mesodermic tissue condensed in dental pa- pilla (/), at whose summit osteoblasts (d) are forming young dentine (c) ; inner layer (a) of enamel organ is engaged in producing layer of young enamel (5) ; e, middle, k, outer layer of enamel organ. Fig. 186. THE DIGESTIVE TRACT. ,r, fibres ; the canals left within the matrix to maintain the nutrition of the tissue constitute the dentinal tubules, the homologues of the lacunae and canaliculi of bone. With the continued growth the sides of the papilla as well as the apex be- come covered by the layer of newly- formed dentine ; the central part of the dental papilla remains, after all the dentine has been formed, as the pulp-tissue, into which the blood- vessels and nerves grow at a later period. At first both dentine and enamel are soft, the impregnation with lime salts occurring subsequently ; the layer of the soft, most recently formed matrix is readily distin- guished in stained sections from the older calcified tissue. The cemen- tum, wanting during foetal life, is produced by the alveolar periosteum. ■~ ''.'-2. Section of developing tooth from cat em- bryo, portion of preceding figure more highly magnified : nt, mesodermic elements consti- tuting pulp-tissue ; /.layer of odontoblasts en- gaged in producing dentine (/;) ; a and 6, cells of middle layer, c and d, cells of inner layer of enamel organ ; e, zone of young enamel. THE TONGUE. The bulk of the tongue is com- posed of variously-disposed bundles of striated fibres of the lingualis, together with those of the accessory muscles, over the unattached surfaces of which the oral mucous membrane is reflected. The muscular tissue of the organ is arranged in bundles extending in three planes : (i) vertically and slightly radially (genio-hyoglossus, vertical fibres of lingualis and hyoglossus) ; (2) transversely (trans- verse fibres of lingualis) ; (3) longitudinally (lingualis superior and inferior, and styloglossus). A vertical median partition, the septum lingualse, divides the muscular tissue into two halves ; the inter- fascicular spaces are filled by delicate connective tissue and fat, in which lie embedded numerous small lingual glands. Many of the muscle-fibres find insertion in the deeper layer of the mucosa, into which their sarcolemma fades. Branched striped muscle-fibres are of common occurrence in the tongue. The mucous membrane forms the most conspicuous part of the organ. That covering the sides and inferior surfaces of the tongue is thin, containing small papillae and numerous mucous glands : on reaching the superior surface the mucous membrane greatly increases in thickness, and presents additional conspicuous irregularities, the 154 NORMAL HISTOLOGY. the filiform or conical, papillae. The papillae are of three kinds the fungiform, and the circum vallate. The conical papillae are widely distributed, occurring on all parts of the upper surface of the tongue. They consist of a conical or cylindrical elevation of the connective tissue of the mucosa, .5-2.5 mm. in height, covered with a thick layer of epithelium, the cells of which, as the most exposed part of the papillae, are partially removed by abrasion, the remaining epi- thelium presenting a ragged sur- face. The fungiform papillae are likewise found on all parts of the tongue, but they are fewer in number, lower, and broader than the conical, appearing as isolated but distinct red points. The connective-tissue stalks of these papillae are composed of a dense felt-work of fibrous tissue, and bear secondary papillae on their upper surface, the epithelium completely enveloping the entire connective-tissue core. The circumvallate papillae, usually eight to ten in number, are placed in two rows forming a /\ at the posterior part of the dorsum of the tongue. Each consists of a large flattened fungiform papilla surrounded by a deep furrow and secondary encircling ridge or all — an arrangement which has suggested the name. The upper Section of human tongue showing conical papillae: a, connective tissue of mucosa, which forms core of papillae; b, b, partially abraded epithelium; ^.masses of epithelial cells filling interpapillary recesses. Fig. 188. ^ |fe,'/'l:l ^ SU mS- surface of the mucosa is beset with minute secondary elevations, which, however, are not apparent on the free surface, being hidden by the thick stratum of covering epithelium. Lying altogether within the epithelium lining the sides of the deep circular furrow, the taste -buds appear as inconspicuous oval bodies ■:>p^f^:_:::^g^r Section of tongue of child, showing a fungiform papilla; the connective-tissue stroma is covered by the epithelium. THE DIGESTIVE TRACT. lcc occupying almost the entire thickness of the epithelium. Additional taste-buds are found in the folds in the vicinity of the circumvallate papillae, as likewise on some fungiform papillae. At the sides of the Fig. 189. ' ''/::}t ,-2 Fig Section of circumvallate papilla from tongue of child : a, main central elevation, surrounded by the annular ridge (b) and the intervening deep furrow; c, taste-buds within the epithelium; d, ducts of neighboring glands (g;^) ; e, blood-vessels. tongue, just in front of the anterior pillars of the fauces, are groups of parallel folds containing a number of taste-buds ; these folds con- stitute the papillae foliatae, which are highly developed in some of the lower animals, as in the rabbit. The taste -buds are oval, flask-shaped bodies, embedded within the epithelium, occu- pying usually the entire thickness of the latter, with their long axes placed in general vertically to the free surface of the epithelium. Each taste-bud consists of an enveloping layer of greatly-elongated epithelial cells, the cortical or tegmental cells, which form a complete covering, except over a small area correspond- ing to the superficial pole of the bud ; at this point a minute canal, the taste-pore, connects the interior of the bud with the surface of the mucous membrane. Within the epithelial capsule lies a group of highly-specialized elements, the gustatory cells. These neuro-epithelial elements appear as spindle, rod-like, or forked cells, each being possessed of an oval nucleus situated about the centre of the elon- gated body. The peripheral or outer ends of these cells are usually prolonged with fine pointed extremities, some of which terminate in stiff hair-like processes projecting within the taste-pore almost as Taste-bud from circumval- late papi la of child. The oval structure is limited to the epithelium (e) lining the furrow, encroaching slightly upon the adjacent connec- tive tissue (_/■) ; o, taste-pore through whicli the taste-cells communicate with the mucous surface. jc6 NORMAL HISTOLOGY. far as the free surface. The inner or central ends of the gustatory- cells are prolonged as slender, sometimes forked, processes ; the minute swellings or varicosities which these extensions often exhibit are supposed to indicate the direct connection of the neuro-epithelial cells with the fibres of the nerve of the special sense of taste. It must be remembered, however, that no such continuity has been or is likely to be demonstrated. The submucous and interfascicular tissue of the tongue contains numerous glands, both of the mucous and of the serous type. The mucous glands resemble those of other parts of the oral cavity, being small racemose clusters of acini more or less filled with clear mucoid secretion. They are situated in the deeper layers of the submucous tissue, as well as between the bundles of the muscle-fibres, principally in the posterior part of the tongue, although a group of small mucous glands (Nuhn's) is found near the tip. The ducts of those at the root of the tongue are some- times lined by ciliated epithelium. The serous glands are limited to the immediate neighborhood of the circumvallate and of the foliate papillae. The acini appear darkly granular and pour out a thin watery secretion well adapted to aid in producing gustatory impressions. The mucous membrane covering the root of the tongue contains also much adenoid tissue, which occurs either as diffuse masses or as circumscribed irregularly spherical lymph-follicles, 1-5 mm. in diameter. The position of these follicles is fre- quently indicated by slight elevations of the mucosa, in the centre of which a minute pit leads into the interior of the lymphatic crypt. The epithelium lining such recesses is completely in- filtrated with lymphoid cells, while the surround- ing- diffuse adenoid tissue contains several minute Salivary corpuscles ° from human saliva: x, spherical masses of denser structure. group of corpuscles near Among the formed elements observed in the epithelial cells; y, cor- ° puscie which has burst, saliva the so-called salivary corpuscles are allowing granules to es- conspicuous. These are spherical bodies, some- cape ; z, salivary cor- r 111 1 puscie highly magnified, what larger than the leucocytes, and possess a showing granules and cJistinct nucleus and minute granules within the cell-contents ; under high amplification these gran- ules exhibit the agitation characteristic of the molecular or Brown- ian motion. The salivary corpuscles are derived from the adenoid tissue of the mouth, and are really escaped lymphoid cells, which, in consequence' of the action of the saliva, become swollen by the imbibition of a fluid less dense than the tissue-juices ; they thereupon exhibit a reaction similar to that seen when the colorless blood-cell is treated with water. THE DIGESTIVE TRACT. 157 The blood-supply of the tongue is very rich, the vessels forming a superficial net-work in the mucosa, from which minute twigs as- cend within the papillae to terminate at the summit in close capillary plexuses. The acini of the various glands are surrounded by capillaries, as are also the lymph-follicles through the adenoid tissue of which many minute vessels extend. The capillary net-works supplying the mus- cular tissue follow the general arrangement and direction of the mus- cular fibres, surrounding the latter by the characteristic rectangular- meshed net-works. The lymphatics of the tongue are numerous ; they are arranged as a superficial plexus within the submucous tissue, which re- ceives the lymphatics from the bases of the papillae ; the FlG- l93- latter vessels, in turn, take up the smaller trunks having their ^ IMMSPBfip: "" Fig. if II Section of tonsil of dog : a, epithelium of mucous membrane passing into central recess (6), where it becomes infiltrated with lymphoid cells ie) : c , lymph-nodules embedded within diffuse adenoid tissue ; d, neighboring mucous glands. Section of tonsil of child ; the epithelium of adja- cent surface passes into the deep pits which extend into the adenoid tissue. origin in the numerous interfascicular lymph-spaces within the cen- tral papillary connective tissue. The lymph-follicles at the root of the tongue are well provided with lymphatics, which surround the follicles and give off radicles to the adenoid tissue. i58 NORMAL HISTOLOGY. The nerves supplying the mucous membrane — the glossopharyn- geal and the lingual branch of the trifacial — end either beneath the epithelium in the usual manner, or in close relation with the organs of special sense — the taste-buds. Numerous microscopic ganglia also occur along their course, especially in connection with the fibres of the glosso-pharyngeal nerve. THE TONSILS. The tonsils represent compound lymphatic glands, while con- siderable variation exists as to form and size, each organ consisting of an aggregation of from ten to eighteen lymph-follicles, closely resembling those found at the root of the tongue embedded within the sur- rounding diffuse adenoid tissue. The entire mass is separated from the adjacent structures on the attached borders by a fibrous capsule, and is §1 covered with a reflection of the oral epithelium on the mucous surface, in- cluding the deep central pit on which the lymph-follicles abut. The epi- thelium covering the folds and de- pressions of these surfaces is com- Fig. 194. aSgUa Section of child's tonsil, showing the details of the epithelium and part of the lymphoid tissue from preceding figure under higher amplification. Numerous mucous glands occupy the immediate vicinity of the tonsils, into the crypts of which the glands pour their secretion to mingle with the shed epithelium and lymphoid cells occupying the recesses. Great numbers of the escaped lymphoid cells pass into the oral cavity to become salivary corpuscles, of which the tonsils are a most important source. Blood-vessels and lymphatics occur in large numbers within the adenoid tissue ; venous and lymphatic plexuses surround the organ receiving the radicles issuing from the interior. Lymph- channels encircle the individual follicles, and afterwards communicate with the larger peripheral vessels. Regarding the ultimate distribution of the nerves little is defi- nitely known ; fibres have been traced into the subepithelial plexus. THE DIGESTIVE TRACT. THE PHARYNX. 159 The pharynx consists essentially of a fibrous tunic, within which lies the mucous membrane with the submucous tissue, while without are arranged the fibres of the constrictor and other muscles ; three coats, the mucous, the fibrous, and the muscular, are recognized, therefore, as forming its walls. The histological differences distin- guishing the upper, or respiratory, from the lower, or digestive, portion of the sac depend largely upon variations within the mucosa, especially as to the character of the epithelium. The upper, respiratory division of the pharynx is clothed with stratified ciliated columnar epithelium containing numerous goblet- cells, while the part situated below the level of the soft palate is cov- ered with stratified squamous cells similar to those lining the oral cavity. The tunica propria, or stroma of the mucosa, is formed of a felt-work of fibrous bundles, together with a variable, in certain parts large, quantity of elastic tissue. The subepithelial surface of the mucosa, where covered by the squamous cells, is beset with numerous small papillae ; these, however, are wanting beneath the ciliated epithelium. Small mucous pharyngeal glands occur in many places ; they are especially numerous in the deepest layers of the mucosa in the immediate vicinity of the orifices of the Eustachian tubes, occurring less frequently towards the lower part of the pharynx. The mucous membrane contains a considerable quantity of adenoid tissue ar- ranged as numerous lymph-follicles in the upper part of the cavity ; these follicles closely resemble those found at the root of the tongue, existing isolated or in groups. A conspicuous aggregation of such structures lies on the posterior wall of the pharynx between the openings of the Eustachian tubes, constituting the pharyngeal tonsil, appropriately so named in view of the similarity of its struct- ure to that of the palatine organs of like name. Some of the mucous glands here also open into the central crypt. The submucous tissue unites the mucous membrane with the fibrous coat, whose dense felt-work of fibro-elastic bundles forms a structure frequently termed the pharyngeal aponeurosis. Its pos- terior part is greatly thickened and forms the raphe to which the constrictor muscles are attached. The muscular coat is formed of the striped fibres constituting the constrictor and other muscles, with whose general arrangement the disposition of the muscular tissue agrees. External to the muscular coat an irregular investment of areolar tissue attaches the pharynx to the surrounding structures. The larger blood-vessels, lymphatics, and nerve-trunks take j6o NORMAL HISTOLOGY. their course within the submucous tissue, and send off branches to supply the mucosa in a similar manner as in the mouth. The lym- phatics are exceptionally numerous in the vicinity of the lymph- follicles, around which they form net-works continuous with those of the nasal cavity, the oesophagus, and the larynx. The nerves supplying the pharynx, derived from the cranial and sympathetic trunks taking part in the formation of the pharyngeal plexus, contain both medullated and non-medullated fibres, associ- ated with minute ganglia. Small twigs are given off from the larger branches to terminate in the subepithelial tissue and among the acini •of the mucous glands and the lymphatic follicles. The walls of the digestive tract, from the oesophagus to the anus, are composed of four tunics — the mucous, the submucous, the muscular, and the fibrous or serous. The muscular coat, usually thickest and most rigid, is the most essential structure in maintaining the form of the tube. The mucosa is distinguished by the highly-specialized secreting apparatus which it contains, as well as by the variations and the modifications of its surface ; the difference between the several divisions of the digestive tract is dependent largely upon the changes in the character of this tunic. The submucosa loosely connects the mucous coat with the mus- cular, and affords space for the larger blood-vessels, the lymphatics, and the nerves, as well as for some few glandular structures and lymphoid masses. The fibrous coat gives additional strength to the walls of the digestive tube, and presents a smooth external serous surface in those parts of the tract which receive a reflection from the peritoneum. THE CESOPHAGUS. The walls of the oesophagus comprise four coats — the mucous, the submucous, the muscular, and the fibrous. The mucous membrane is a continuation of that of the pharynx, and corresponds closely with the latter in structure. The stratified squamous epithelium rests upon the connective- tissue matrix, the tunica propria, the inner surface of which bears numerous small papillae completely hidden by the thick overlying epithelium. The deeper layers of the mucosa are separated from the submucous coat by longitudinal bundles of involuntary muscle, the muscularis mucosae ; these muscular bundles, absent in the upper part of the oesophagus, first appear as irregular and inter- rupted groups, which become more numerous until, from the middle of the tube on, they form a continuous longitudinally-disposed layer. The submucous coat is composed of loosely-united connective tissue, serving for the conveyance and support of the larger blood- THE DIGESTIVE TRACT. 161 vessels, lymphatics, and nerves. Within the submucosa are placed likewise the acini of the mucous glands ; these are rather more numerous on the anterior surface, their ducts piercing the mucosa and opening on the free surface of the mucous membrane, being lined throughout the greater part of their length by columnar epi- thelium. In the lower portion of the oesophagus, particularly about Fig. 195. Section of human oesophagus: a, squamous epithelium of surface resting upon fibrous tissue of mucosa, the deeper part of which is occupied by muscularis mucosae (6); c, submucous coat, con- taining glands (h) ; d, e, respectively circular and longitudinal muscular tunics ; e', e', bundles of striped muscle-fibres. the cardiac orifice, the mucous glands are very plentiful and lie within the mucosa. The muscular tunic consists of two layers, an inner circular and an outer longitudinal, whose component bundles are held together by the connective-tissue septa which pass between the fas- ciculi in all directions. The character of the muscular tissue varies in the several portions of the tube. That contained within the wall of the upper third of the oesophagus is entirely of the striated variety, while the muscular tissue of the lower third is exclusively j62 normal histology. non-striped or involuntary in character ; in the middle third both kinds exist, the striated fibres gradually disappearing as the non-striped fibres increase. The latter extend highest in the circular coat and somewhat farther in the anterior than on the posterior wall. The last traces of voluntary muscle appear as short, isolated striped fibres among the surrounding fasciculi of non-striated tissue. The fibrous coat envelops the muscular tunic externally, strength- ening the tube and affording attachment to the surrounding areolar tissue connecting the oesophagus with neighboring organs. Con- siderable elastic tissue is found in this coat, the elastic fibres forming net-works intimately connected with the bundles of involuntary muscle. The larger blood-vessels penetrate the outer coats and ramify within the submucous tissue, from which branches pass to supply the muscular and mucous tunics, the capillaries within the latter ending as net-works within the inner part of the tunica propria. The lymphatics of the deeper layers of the mucosa terminate in the larger vessels of the submucosa. Numerous nerve-fibrillae pass from the submucous tunic into the mucosa to end beneath the epithelium. THE STOMACH. The stomach must be regarded as a dilated and specialized portion of the general digestive tube, its walls consisting of the four coats common to the other parts of the tract — namely, the mucous, the submucous, the muscular, and the serous or fibrous tunic. The mucous membrane is covered by a simple columnar epithelium, the squamous cells of the oesophagus abruptly ter- minating at the cardiac orifice to be replaced by the columnar ele- ments of the gastric epithelium, many of which are goblet-cells. The free inner surface of the stomach presents, in addition to the conspicuous folds or rugae, minute inequalities and pits, which mark the openings of the gastric glands ; the mouths of the latter show as minute depressions, between which the intervening por- tions of the mucosa extend as apparent elevations. The gastric glands are of two kinds— the peptic glands, situ- ated in the middle and cardiac thirds, and the pyloric glands, found in the pyloric third of the stomach. Both varieties are limited to the mucosa, extending in length the entire thickness of this coat. The peptic glands are slightly wavy, simple tubular depressions, in which a duct, a neck, and a fundus are recognized. In excep- tional cases the fundus is divided, while in nearly all it is tortuous or spiral, its extremity being often sharply bent at right angles to the general axis of the tube. The columnar epithelial cells of the ad- THE DIGESTIVE TRACT. 163 jacent gastric mucous membrane pass into the ducts of the glands with little change, becoming imbricated, and, towards the neck, shorter and more spherical in outline. At the neck, the narrowest part of the tube, the cells Fig- i97- are more cuboidal, and assume a columnar or v a {'*. pyramidal form as they approach the fundus. 1| The chief or central cells bound the lumen § . .) § Fig. 196. ^N.\V ftfttaa ,/- , -- v Section of human stomach, showing general arrangement of its coats : a, mucosa containing the tubular peptic glands ; e, muscularis mucosae separating the layer of glands from the underlying submucous coat (5) ; h, blood-vessels ; c, c' , respectively the circular and longi- tudinal muscular layers ; d, the fibrous tunic covered with the peri- toneum. Peptic gland from stomach of dog : a, wide mouth and duct which re- ceive tha terminal divisions of the gland ; b, c, neck and fundus of the tubes ; e, central or chief, d, parietal or acid, cells. of the gland and form the bulk of the glandular epithelium. Each cell contains a spherical nucleus embedded within the granular pro- toplasm, whose exact condition depends upon the state of functional activity. In addition to the chief or central cells, a second variety, the parietal or acid cells, exists in the peptic glands. As indicated by their name, the parietal cells are situated in the periphery of the gland immediately beneath the basement-membrane, usually separated from the lumen by the intervening central cells. Minute lateral 164 NORMAL HISTOLOGY. intercellular clefts or canals in many places afford direct commu- nication between the parietal cells and the lumen of the tube. The parietal cells are irregularly distributed from the fundus to the Transverse sections of peptic glands from stomach of dog : A, plane of section passes through ducts near free surface ; a, lumen of glands ; b, surrounding fibrous stroma of mucosa ; B, plane of section passes through fundi near terminations of tubules ; the sections of the latter are arranged in groups separated by connective tissue. neck of the gland ; but they are especially numerous in the vicinity of the neck. These cells are larger than those lining the lumen, polygonal or triangular in outline, and possessed of a pale, faintly granular protoplasm surrounding a round or oval nucleus. In preparations of human stomach, the parietal cells are not infrequently the most con- spicuous and best defined, since the central cells are prone to disintegrate. On approaching the pyloric ring, the simple tubular peptic glands are gradually replaced by the compound glands, until, near the intestinal opening, these alone are present. The pyloric glands are characterized by their relatively long, wide ducts into which the several divisions of the body open ; the tubular com- partments are wavy and tortuous, and frequently end in slightly expanded extremities. The duct is lined by tall columnar epithelium, the cells be- coming lower and broader as they approach the neck and towards the fundus. The cells contain finely granular protoplasm, and do not secrete mucus, but a thin albuminous fluid. Parietal or acid cells do ?wt occur in the pyloric glands, being confined to the true peptic glands. The gastric glands, while very uniformly dis- tributed through all parts of the stomach, are arranged in groups, the individual tubules of which are separated by very delicate partitions of the connective a Portion of gland of dog magnified : a, central or next the peptic highly a, the chief cells lumen (c) ; b, b, the parietal or acid cells connected with the lumen of the tube by short lateral branches which extend to the cells. THE DIGESTIVE TRACT.. I65 tissue, thicker layers of fibrous tissue enveloping the entire group. Numbers of lymph- cells are intermingled with the fibrous tissue of the mucosa ; in the vicinity of the pylorus considerable patches of diffuse adenoid tissue lie around and among the ends of the gastric follicles and constitute the Fig. 200. lenticular glands. The muscularis mucosae oc- cupies the deepest layer of the Fig. 201. .'/ KW-~ i\ Section of pyloric glands from human stomach : a, mouth of gland leading into long, wide duct (b), into which open the terminal divisions; c, connective tissue of the mucosa. Section of pyloric region of human stomach, showing irregular mass of adenoid tissue lying between the gastric tubules (g, g) constituting a lenticular gland ; s, submucous tissue. tunica propria, and is composed of an inner circular and an outer longitudinal layer of non-striped muscle ; the tissue of the muscu- Fig. 202. Longitudinal section of child's stomach passing through pyloric orifice : S, I ', the gastric and the in- testinal surface ; /, pyloric glands, which gradually extend into the submucosa to become Brunner's glands (b) ; a, simple follicles of the intestinal mucosa ; .s, submucosa ; t, the greatly thickened layer of circular muscle constituting the pyloric ring ; /, longitudinal muscular tunic. laris mucosae extends within the interglandular septa, often as far as the free surface of the mucous membrane, beneath which the muscle- cells disappear. The submucosa is a coat of considerable thickness, composed of a felt-work of fibro-elastic bundles of varying size, but so loosely interwoven that the mucosa may be shifted readily within con- 1 66 NORMAL HISTOLOGY. siderable latitude upon the underlying muscular tunic. The large prominent folds, or rugae, of the stomach involve both the mucous and the submucous coat, the latter forming the connective-tissue frame-work of the elevation over which the mucosa with its glands is reflected. Within the mesh-work of connective-tissue bundles are supported the larger blood-vessels, lymphatics, and nerves. The muscular tunic comprises two principal sheets of involun- tary muscle, disposed as an inner circular and an outer longitudinal layer ; towards the cardiac end of the stomach irregular bundles of oblique fibres constitute an imperfect third layer. The pyloric orifice is guarded by a fold of mucous membrane supported by the submucosa and strengthened by a conspicuous local annular thickening of the inner circular layer of muscle ; the outer longi- tudinal muscular layer and the serous coat pass over into the intes- tinal wall without partici- Fig. 203. pating in the formation of this gastro-duodenal valve. The serous coat is composed of bundles of fibrous connective tissue, together with rich net- Works of elastic fibres, while the peritoneal sur- face is covered with a single layer of the charac- teristic endothelial plates. The narrow areas included between the folds of the peritoneum along their lines of reflection are, of course, devoid of the serous covering ; at these points the vessels and the nerves pass to and from the stomach. The larger arteries, after penetrating the outer coats, divide within the submucosa into smaller branches, one set of which pierces the muscularis mucosae to be distributed to the mucous membrane, while the other enters the muscular and serous tunics. The vessels supplying the mucosa form a rich subepithelial capillary net- work, as well as mesh-works surrounding the gastric glands, the cap- illaries lying immediately beneath the basement in close proximity to the glandular epithelium. The branches distributed to the outer Section of injected stomach of cat : a, rugae consisting of the mucosa and a core of submucous tissue (6) ; c, d, the circular and longitudinal layers of muscle ; all the dark lines represent the blood-vessels filled with the carmine- gelatin mass ; the larger trunks break up in the submucosa, sending twigs into the mucous and muscular tunics. THE DIGESTIVE TRACT. 167 layers form long-meshed capillary net-works, from which the muscle- bundles and fibrous tissue derive their supply. The larger lymphatic trunks accompany the blood-vessels and form a coarse plexus within the submucous tissue ; a much closer net- work of. smaller lymphatics occupies the deeper part of the mucosa, from which radicles ascend between the glands to end beneath the epithelium in slightly dilated blind extremities. Peripherally -situated lymph-vessels drain the masses of adenoid tissue. In addition to the lymphatics of the mucosa, the larger vessels of the submucosa take up those from the muscular coat. The nerves of the stomach, after piercing the serous coat, take up a position between the circular and longitudinal muscular layers, in which situation they form a rich plexus, consisting of both medul- Fig. 204. y M Surface views of nervous plexuses of stomach of young child. A , Auerbach's plexus : g, groups of ganglion-cells ; r, underlying muscular tissue. B, Meissner's plexus : g, groups of ganglion-cells ; b, blood-vessel. (After St'okr.) lated and pale fibres ; at the nodal points of this net-work numerous microscopic ganglia are situated, the whole forming the intramuscular ganglionic plexus of Auerbach. From this plexus fibres are distributed to the serous coat and to the longitudinal layer of muscle, as well as to the outer part of the circular layer. The intramuscular net-work is continued by numerous small bundles of fibres, which, after piercing the inner layer of cir- cular muscle, and giving off lateral twigs to the inner part of the same, enter the submucosa to form there a second ganglionic plexus similar to the one lying between the muscular layers : this is the plexus of Meissner. The submucous plexus sends off numerous fibres into the mucosa, which are distributed beneath the epithelium 1 68 NORMAL HISTOLOGY. and to the gastric glands ; the exact mode of termination of these nerve-fibrilla: within the mucosa, however, is still undetermined. THE INTESTINES. The four coats of the stomach are continued, with little modifica- tion, into the mucous, the submucous, the muscular, and the serous tunics of the intestinal wall ; the variations characterizing the several divisions of this tube are dependent largely upon modi- fications and specializations of the mucous membrane. The free inner surface of the small intestine is studded over with small cylindrical elevations — the villi — projecting into the intestinal lumen and bathed in the juices of the canal. In addition to the villi, which are found through the whole extent of the small intestine, the mucous membrane is thrown into transverse or oblique per- manent folds — the val- vulae conniventes — which extend partially around the tube, and are most marked in the duo- denum and the jejunum ; these folds increase the area of the mucous sur- face, and are beset with villi the same as the sur- rounding parts of- the mucosa. These projections, the villi and the valvulae conniventes, are peculiar to the small intestine and serve to distinguish it from the large. The mucosa is covered by a single layer of columnar epithelium resting upon the basement-membrane. The prismatic cells contain finely granular protoplasm and oval nuclei, the latter being usually situated within the inner half of the cell. The outer free ends of the cells are invested by a peculiar cuticular zone, or basilar border, a well-defined continuous band exhibiting, in suitably preserved specimens, a fine vertical striation. The significance of these mark- ings is still uncertain, especially in view of the fact that, after the action of such reagents as water, the border breaks up into rods resembling very coarse cilia ; the striation is regarded by others as the expression of fine parallel canals. Longitudinal section of human small intestine, showing general relation of the folds constituting the valvulje conni- ventes to the mucosa and submucous coat; the latter con- tributes the fibrous core over which the mucosa with its villi and glands extends. Fig. 206. THE DIGESTIVE TRACT. j5q Goblet- cells are numerous, many epithelial elements having be- come distended with mucoid secretion : in carmine preparations the cells appear as clear, oval breaks in the contour of the epithelium. While occur- ring throughout the entire digestive tube, the goblet-cells are especially numerous in the large intestine, where not infrequently the majority of the epithelial elements are in this condition. During certain stages of digestion the protoplasm of the epithelium may contain oil-drops taken up from the intestinal contents. Migratory leuco- cytes are also found in the intercellular clefts. The epithelium rests upon a mem- brana propria — the endothelium of Debove — composed of flattened connective-tissue plates. The villi consist entirely of the tissues of the mucosa, the epithelium extending over the projecting portions of the tunica propria to form a complete investment of the finger-like processes. The centre of each villus is occupied by the absorbent chyle-vessel, or lacteal, a slightly club- shaped lymphatic radicle, which ends blindly near the apex of the villus and whose walls are composed of a single layer of endothelium. The tissue surrounding the lacteal and forming the bulk of the projection approaches in character quite closely adenoid tissue, con- sisting of a fibrous reticulum holding many lymphoid cells within its meshes. The central lacteal lies enclosed within a capil- lary net-work, extending through the greater part of the villus and connecting the afferent arteriole and efferent veins. Imme- diately surrounding the lacteal, and in inti- mate relation with it, numerous delicate vertical bundles of non-striped muscle, derived from the underlying muscularis mucosae, ascend towards the tip of the villus. The components of the villus are held together by the common adenoid tissue, in whose interstices lie many lymphoid cells and, during certain stages of digestion, numberless fatty granules. At Simple tubular glands of large intestine of dog: the epithelial elements lining the follicles have become very largely converted into goblet-cells. Fig. 207. Transverse section of follicles of large intestine of dog : the individual tubules are separated by the fibrous stroma of the mucosa. 170 NORMAL HISTOLOGY. Fig. 208. such times the contents of the lacteals appear milky, in consequence of the emulsion formed by the ab- sorbed oil ; during the intervals of digestive inactivity the lacteal con- tains the clear, straw-colored fluid usually found within lymphatic ves- sels. The villi disappear abruptly at the ileo-cascal valve and are not present in the large intestine. Among the structures of the in- testinal wall usually included as "glands" two distinct groups must Fig. 209. Longitudinal section of villus from intestine of dog, highly magnified : a, columnar epithelium containing goblet- cells (b) and migratory leucocytes (/z) ; c, basement membrane ; d, plate-like connective-tissue elements of core; e, e, blood-vessels ; f, absorbent radicle or lacteal. Transverse section of villus from intestine of dog : a, a, blood-vessels ; b, lacteal. be recognized — the true and the false glands, the latter being simple or compound lymph-follicles. These structures therefore fall under the appropriate headings : Intestinal True-Glands. Glands of Licbcrkuhn. Glands of Brunner. Intestinal Lymph-Follicles. Solitary glands. Agminated glands. The follicles, crypts, or glands of Lieberkuhn are very nu- merous, forming an almost continuous layer of simple tubular de- pressions throughout the intestines, large as well as small. They occupy nearly the whole depth of the mucosa, their wavy extremities approaching the muscularis mucosae. The columnar epithelium of the free surface passes directly into the tubules to become the spherical secreting cells, many of which undergo mucoid distention and THE DIGESTIVE TRACT. 171 Lieberkiihn' s glands He between the Fig. 210. Longitudinal section of large intestine of child : a, a, simple tubular glands ; b, submucous tissue ; c and d, circular and longitudinal layers of muscle. FlG. 211. conversion into goblet-cells, bases of the villi, but are found upon the valvulae conniventes, since the latter depend on the elevation of the submucosa for their formation, the mucosa being reflected over the pro- p^ jecting underlying tunic. In the lower part of the large in- testine the glands of Lieber- kiihn increase in size, becom- ing longer and possessing wider mouths, their orifices appearing as minute pits. The duodenum, especially in its upper part, possesses an additional layer of true secreting structures in the glands of Brunner. These are the direct continuations and higher specializations of the pyloric glands of the stomach. In passing from the stomach into the intes- tine these tubules undergo repeated division, and, at the same time, sink deeper and deeper into the mu- cosa, finally reaching below the limits of this layer to take up a position within the siibmucosa of the duo- denum, beneath the over- lying layer of the follicles of Lieberkiihn within the mucosa. Brunner's glands, or the duodenal glands, appear as groups of short, wide, tubular acini, dis- posed about long, slender ducts which pass from the . Section of duodenum of cat : a, mucosa containing the Submucous tiSSUe through villi {/) and the follicles of Lieberkiihn (/), and pierced by the mUCOSa tO OOen OI1 the tne c'ucts (f>) °f tne glands of Brunner (/;) within the sub- t mucosa (c) ; b, muscularis mucosae ; d, d' , circular and lon- lnteStllial Surface between gitudinal layers of muscle ; e, fibrous tunic. ^ c d 172 NORMAL HISTOLOGY. Fig. 212. the orifices of the follicles in the depressions between the bases of the surrounding villi. The glands, owing to the rapid branching of their tubules, more closely approach the racemose type than the compound tubular to which they really belong, as shown in their direct deriva- tion from the com- pound tubular pyloric crypts. The secretion of these duodenal glands is serous and not mucous, the cells being filled with dark granules. The solitary glands are isolated lymph - follicles scat- tered through the entire intestine ; they are, however, most abundant in the lower part of the ileum and in the first portions of the large intestine. They are situated primarily within the mucosa, al- though they frequently lie also within the submucous coat ; when well Fig. 213. Section of human large intestine, containing solitary gland : a, mucosa ; b, submucosa ; c, c' , circular and longitudinal layers of muscle ; d, serous coat. <;V, "- - ' "- ■&'- - -&'■■■ ■ "3p- Si V./B /t :;) /:'■'• &■ Section of small intestine of cat, showing a Peyer's patch (d, d) cut crosswise : a, b, c, respectively mucous, submucous, and muscular coats. developed, they encroach upon the mucosa to such an extent that their inner pole slightly projects upon the free surface of the intestine. The lymphoid tissue is somewhat denser in the periphery of the fol- licle, beneath its limiting capsule, than towards the centre ; but the THE DIGESTIVE TRACT. 173 lymphoid cells are everywhere so closely packed that the support- ing reticulum of connective tissue is masked. In the upper part of the duodenum numerous ill-defined masses of adenoid tissue occupy the mucosa between the follicles and represent the lenticular glands of the stomach. The agminated glands, or Peyer's patches, are large, oval groups of closely aggregated lymph-follicles, held and blended to- gether by diffuse adenoid tissue. These patches vary in size and number, and are usually limited to the lower two-thirds of the small intestine, reaching their highest development in the ileum, where they may attain a length of 9-1 1 cm. ; between twenty and thirty patches generally are present, while they are relatively better devel- oped in young than in old subjects. The agminated glands appear first within the mucosa, but later encroach largely upon the submucous tissue. The lymph-follicles of which these patches are composed become somewhat pyramidal, owing to pressure, and lose much of their individuality, the demarca- tion into separate follicles being best preserved along the outer Fig. 214. s^SSS 1 ^r 1 , fibro-muscular coat ; c, surrounding areolar tissue. comprise an outer fibrous adventitia and an inner mucous membrane. The latter, in addition to the columnar epithelium, consists of the tunica propria, containing many elastic fibres and some delicate bundles of involuntary muscle, irregu- larly disposed as circular and longitudi- nal bundles. Small mucous glands also occur within the mucosa of the larger canals and of the hepatic duct. The inter- lobular bile-ducts may be distinguished from blood-vessels of the same size by their lining of columnar epithelium. The blood-vessels of the liver, as already described, are of primary impor- tance in determining the arrangement of the hepatic tissue. The blood brought by the interlobular branches of the portal vein passes into the lobule at the periphery by the numerous twigs ; these, on entering the lobule, form a closely anastomosing intra- lobular capillary net-work, which converges to a central intra- lobular vein. The central vessel is vertically placed with regard to the general plane of the capillary net-work, and empties into the ad- jacent sublobular veins, which are branches of the hepatic vein, lying within planes generally at right angles to those of the portal vessels. The hepatic artery has directly nothing to do with the elabora- tion of the especial products of the organ, its particular province being to supply the blood for the nutrition of Glisson's capsule and of the interlobular structures, including the blood-vessels and the bile-ducts. Minute arterial twigs are distributed to the walls of these tubes, where they end in delicate capillary net-works, which, in turn, at the periphery of the lobule, pour their contents into the intralobular net-work of the portal vein. The lymphatics of the liver constitute a superficial and a deep system. The superficial lymphatics accompany the branches of the arteries supplying the capsule, and form a close-meshed sub- serous net-work within the capsule. The interlobular blood-vessels are accompanied by numerous lym- phatics, whose ramifications and anastomoses constitute the deeper plexus. The presence of lymphatics within the parenchyma of the liver is still a matter of dispute. According to Disse, the lym- phatic channels exist throughout the lobule as perivascular canals, surrounding the capillaries and separating them from direct contact with the secreting cells. j 32 NORMAL HISTOLOGY. The main nerve-trunks of the liver enter at the transverse fissure in company with the blood-vessels and the lymphatics. The fibres consist largely of the non-medullated, together with a smaller number of the medullated variety. These nerves run within the interlobular connective tissue in company with the hepatic artery. They may be traced with certainty to the periphery of the lobule ; regarding the exact mode of their ultimate distribution, however, nothing is definitely known. Minute ganglia occur along the interlobular trunks. The gall-bladder, or bile-sac, possesses walls composed essen- tially of the same tissues as those of the larger bile-ducts, these consist- ing of a mucous membrane supplemented by oblique bands of invol- untary muscle and an outer fibrous coat. The mucosa is thrown into minute folds or rugae, which unite and interlace to form a net- work of ridges and give to the surface of the mucous membrane a reticulated appearance. The blood-vessels, the lymphatics, and the nerves form net-works within the mucosa, which usually terminate in the superficial or inner layers of the tunica propria. THE ACCESSORY DIGESTIVE GLANDS. These include the salivary glands — the parotid, the submaxillary, and the sublingual — and the pancreas. While in their quiescent, immature condition all are similar, after full functional development is attained the variation in the character of their secretions leads to the recognition of two groups— the serous and the mucous sali- vary glands. Those of the serous type, regarded as the true sali- vary glands, are represented in man and mammals by the parotid gland and the pancreas. The mucous glands are best represented in man and many animals by the sublingual, although the presence of serous acini places this organ, strictly considered, within the cate- gory of the mixed glands. The muco-serous or mixed glands are exemplified by the sub- maxillary of man and many mammals (as apes, guinea-pig, etc.); in other animals (as dog or cat) this gland is entirely mucous, while in certain others (as the rabbit) it is a true serous gland. THE SALIVARY GLANDS. The parotid is a compound saccular or racemose gland, en- veloped in a general fibrous capsule from which stout connective- tissue septa penetrate the organ, dividing the gland into lobes. These latter are subdivided by fibrous partitions into numerous lob- ules, each of which, in turn, is composed of groups of the ultimate saccules or acini. THE DIGESTIVE TRACT. j 3, The large excretory duct of the parotid gland, or Stenson's duct, contained within the interlobular connective tissue, is composed of a fibro-elastic tunica Fig. 227. V .*tm$m.-h. >.*, & dm Wfyje&w*1* propria, lined by a simple low columnar epithe- lium, and strengthened externally by fibrous tissue. Passing into the smaller ducts, the salivary tubes, the cylindrical epithelium becomes slightly taller, and exhibits a distinct vertical radial striation in its outer zone. On entering the intralobular divisions of the ducts, or interme- diate tubes, the columnar epithelium is replaced by low flattened cells, which finally pass into the dilated terminal compartments, be- coming directly continuous with the secreting cells lining the acini. The acini are limited by the basement-membrane, the prolonga- tion of that of the smaller ducts, and almost completely filled by the irregularly polyhedral glandular epithelium, the narrow intercellular cleft which remains representing the commence- ment of the lumen of the system of ducts. The appearance of the cells of the acini varies with the stages of secretion ; when quies- cent and filled with the serous secretion, the cells appear larger, clearer, and less granular, while after functional activity and in the ex- hausted condition they are smaller, darker, and more granular, the granules of the protoplasm lying closely packed, and not, as when the gland is at rest, sepa- rated by the intervening particles of stored-up secretion. The sublingual gland possesses the general arrangement already considered in connection with the parotid gland, its peculiarity being the absence of the intermediate division of the duct, the intralobular or " mucous" tubes passing at once into the acini. The cells lining the saccules are encountered in all stages of secre- tion. During rest the majority are clear, being filled with homo- geneous viscid mucus. After the discharge of this secretion, fol- S<-ction of human parotid gland, exhibiting general ar- rangement of lobules (a) ; b, interlobular connective tissue containing large ducts (c) and blood-vessels (v) ; d, intra- lobular ducts. Fig. 228. Section of human parotid gland, including several acini : d, cut intralobular duct. 1 84 NORMAL HISTOLOGY. lowing prolonged activity, the cells appear smaller, dark and granular, and closely resemble the elements of the serous glands, since the mucoid substance separating the particles of the cell pro- toplasm has been removed, thereby allowing the displaced proto- plasmic granules once more to approach closely. Not all the cells in the resting acini are in the same secretory condition, since quite usually certain cells have failed to participate in the activity of their neighbors, and, in Fig. 229. consequence, appear as crescentic groups of granular cells lying immediately next the basement-membrane at the periphery of the acinus, where they have been crowded by the larger mucus-filled elements. These cres- centic groups constitute the demilunes of Heidenhain or the crescents of Gia- nuzzi, and are aggregations of cells which section of human sublingual jiave not participated in secretion. The ex- gland : among the clear cells lining the mucous acini are cretory tube ol the sublingual gland, or the nests (g, g) of granular eie- duct of Bartholin, consists principally of a ments which constitute the _ . . . . :..,.,. demilunes of Heidenhain. fibro-elastic tunica propria, within which is a single layer of low columnar cells, while out- side extends a supplementary layer of fibrous tissue. The submaxillary gland is a mixed gland, certain lobules being composed of acini of the serous type, while neighboring divisions contain those of the mucous variety. ,The excretory channel, or the duct of Wharton, resembles that of the parotid gland, dividing into the smaller tubes lined by striated '" rod" epithelium, passing thence into the intermediate tubules, with low cuboidal cells, which lead into the serous acini filled with dark granular cells on the one hand, or into those filled with mucous cells and granular crescents on the other. The vascular supply of the salivary glands is very rich ; while the arrangement of the blood-vessels in the several glands presents unimportant differences, their distribution is according to the same general plan. The larger arteries accompany the excretory ducts of the glands within the interlobular fibrous septa, where they give off branches which pass between the lobules and later penetrate the tissue of the lobules to end in rich capillary net-works enclosing the acini. The capillaries lie immediately outside the basement-membrane in prox- imity to the secreting cells. The veins follow the general course taken by the arteries. The lymphatics are represented by indefinite interfascicular clefts between the acini, which are taken up by definite lymph-vessels THE DIGESTIVE TRACT. I85 situated within the interlobular connective tissue, the larger trunks accompanying the main blood-vessels. The nerves distributed to the salivary glands constitute a rich supply, composed of both medullated and pale fibres. From the larger trunks of the interlobular net-works, along the course of which minute ganglia occur, smaller branches enter the lobules and extend between the acini. Regarding the ultimate distribution of the many fibres passing to the glandular tissue little is definitely known, not- withstanding the laborious investigations undertaken with a view to solve this difficult problem. The nerve-fibres may be traced to the basement-membrane of the acini, around which net-works are formed ; as to the further fate of the fibrillae, however, little can be regarded as proved. While an intimate relation between the nerves and the secreting cells may be assumed as undoubtedly existing, no direct continuity between these structures has been established, not- withstanding the already-published assertions and elaborate descrip- tions of such connections. Fig. 230. THE PANCREAS. The pancreas is, as aptly described by its German name, " Bauch- speicheldruse," the abdominal salivary gland, belonging to the serous type, and closely corresponding in structure and in the nature of its secre- tion to the parotid gland. The connective-tissue framework of the organ divides the glandular tissue into lobes, which are subdivided by septa into the lobules, these, in turn, being com- posed of groups of acini. The laminated fibrous connective tissue constituting the walls of the pancreatic duct is clothed by a single layer of columnar epithelium. The branches of the main duct divide at once into the long intermediate tubules, the intralobular ducts, or salivary tubes, being wanting ; it follows that the vertical striation of the epithelium lining these tubes, so conspicuous in sections of the parotid gland, is absent in the pancreas. The cylindrical cells of the larger ducts gradually pass into the lower cuboidal and flattened plates lining the intermediate tubules. The acini of the pancreas are more tubular than those of the parotid gland, while the secreting cells suggest more strongly the cylin- drical or pyramidal type than those of the salivary gland ; these cells are further characterized by the presence of a zone, next the Section of human pancreas, in- cluding several acini and two ducts : the cells present a central granular and a peripheral clear zone. NORMAL HISTOLOGY. Fig. 231. lumen of the acinus, containing numbers of highly refracting par- ticles, while the peripheral outer half of the cells contains the nucleus and is comparatively free from the granules. The relations, how- ever, between the clear and granular zone of the pancreatic cells are not constant, but vary with the condition of functional activity. During the earliest stages of digestion, when the cells are filled with secretion, the clear zone occupies almost the entire cell, the granules being confined to a narrow belt immediately around the lumen ; towards the close of a period of functional activity, on the contrary, the granules occupy the greater part of the cell, while the clear zone is reduced to a narrow peripheral area ; during fasting the clear and the granular zone about equally divide the cells. On examining sections of pancreas under low amplification, certain round or oval areas appear lighter and less dense than the ordinary tissue of the organ. These peculiar areas, or bodies of Langerhans, under high magnification prove to be composed of groups of small, imperfectly-developed acini, among and about which ramify rich capil- lary net-works, whose frequently tortuous course and lobulated ar- rangement recall somewhat the glomeruli of the kidney. These areas probably represent groups ot imperfectly-developed acini ; they are well seen in the pancreas of man and most mammals. The blood-vessels of the pan- creas are distributed very similarly to those of the salivary glands. The larger arterial branches run within the interlobular connective tissue, sending off vessels which pass between the lobules and supply the glandular parenchyma with twigs. These latter enter the lobules and form net-works which en- close the individual acini within the capillary reticulum. The capil- laries lie beneath the basement-membrane in close relation with the glandular epithelium. The veins accompany the arterial trunks within the connective tissue. The lymphatic vessels also accompany the arteries, lying be- tween the lobules and receiving as tributaries the lymph-radicles originating within the lobule between the acini. The larger nerve - trunks are confined to the connective tissue between the divisions of the gland, in which situation many accompanying microscopic ganglia also are found. The ultimate termination of the nerve-fibres, Section of human pancreas, exhibiting one of the areas (a) of immature gland-cells ; i, the usual acini THE DIGESTIVE TRACT. I87 as in the case of the salivary glands, is still undetermined ; the fibrillar are traceable to the basement-membrane of the acini, but their further accurate disposition remains undecided. The development of the digestive tract and its appendages in- volves all three blastodermic layers, the mesoderm and the ento- derm, however, being the ones participating to the greatest extent. The epithelium of the mucous membrane, together with that of the glandular structures connected therewith, is the direct derivative of the entoderm, with the exception of that lining the oral cavity ante- rior to the fauces and the salivary and oral glands, the epithelium of which parts originates from the ectodermic invagination. For a short distance within the anus, likewise, the ectoderm contributes the cells lining the gut. As already pointed out, the enamel and the dentine are also products respectively of the ectoderm and of the mesoderm. The formation of the gut-tract consists essentially of a process of folding off and closing together of the ventral body- Fig. 232. plates, which are composed of the entoderm united with the visceral layer of the meso- derm. The tube thus formed begins in the cephalic region of the embryo as a blind, somewhat dilated pouch, the primitive pharynx, which for a short time is separated from the primary oral recess, or stomodaeum, by a parti- tion, the pharyngeal plate, consisting of the opposed ectoderm and entoderm ; after the rupture of this plate the gut-tract communicates directly with the exterior through the oral cavity. A somewhat similar process takes place at the lower part of the primitive digestive tube, whereby the anus becomes established. For a con- siderable time the gut communicates with the cavity of the umbilical vesicle through its duct. The several divisions of the primary diges- tive tube, its wall consisting of epithelial lining and supplementary mesodermic tissue, undergo differentiation and acquire distinctive characters, which, however, depend largely upon the differentiation of the embryonal epithelial layer. The division of the tube into particular regions begins with the stomach, which as early as the fourth week in the human embryo is distinguishable as a spindle-shaped enlargement. With the sub- sequent rapid increase in the size of the organ, the tissues constituting Transverse section of nine-day rabbit embryo, show- ing formation of primitive gut (g) by approximation of ventral plates composed of visceral layers of mesoderm and entoderm (e) ; m, m, body-cavity bounded by parietal and visceral sheets of mesoderm ; n, neural canal. 1 88 NORMAL HISTOLOGY. Fig its walls also become augmented by many new elements, the meso- dermic cells differentiating into a narrow looser zone next the ento- derm, which later becomes the submu- cosa, and a broader, more compact stratum, representing the future mus- cular tunic. The entodermic cells, at first arranged as a single layer, soon undergo local proliferation, the resulting groups of cells disposing themselves as minute cylindrical masses, which are the earliest traces of the peptic glands. These increase in length and later en- croach upon the underlying mesoderm. In the young gland six to eight tubular divisions communicate with a single duct, but as development advances the ducts divide, with a corresponding dimi- nution in the number of terminal com- partments connected with each. The pyloric glands appear about the same time as do the peptic, or at about the tenth week of foetal life, the cells ac- quiring their characteristic form and appearance during the later stages. At first and during a considerable period the cells lining the peptic glands are all of the same variety ; later certain elements become distinguished by the accumulation of coarse granules within their protoplasm ; these constitute the acid or parietal cells, usually appearing towards the close of the fourth month of foetal life. The intestinal divisions of the primitive gut also depend for their distinctive characters on the differentiation of the entodermic epithelium and of the adjoining mesoderm, which together constitute the mucosa. The villi, distinguishable by the tenth week, are at first relatively short and thick and less numerous than later, when additional projections are developed. It is of interest to note that in the early stages villi appear in both the large and the small intes- tine, these structures subsequently atrophying and disappearing in the large gut while they increase in size and importance in the re- maining parts of the tube. Coincidently with the formation of the villi the entodermic epithelium sends outgrowths into the mesoderm between the villous projections ; these, at first solid, cylinders repre- sent the early stages of the simple tubular glands ; with the gen- Sagittal section of nine-day rabbit embryo : B, B', neural canal and brain vesicles; m, ectodermic invagination which contributes the lining of anterior part of future oral cavity ; /, primitive pharynx, the blind upper end of the primitive gut (g) lined with entoderm, in this stage separated from ectoderm by septum ; U, umbilical duct connect- ing gut with umbilical vesicle ; h, h', arterial and venous segments of young heart ; delicate endothelial tube seen lying within primitive muscular walls. THE DIGESTIVE TRACT. j go eral increase in the thickness of the young mucosa these structures lengthen and obtain their lumen. The lower ends of the glands throughout the period of their growth are the seats of active cell proliferation and the points at which the division of their fundi com- mences in the production of the compound tubules. The endothe- lium covering the serous surfaces of the intestinal tract is the direct descendant of the differentiated mesoderm, the mesothelium, lining the body-cavity. The development of the accessory glands of the digestive tube, including the liver, the pancreas, and the salivary glands, follows the same general plan. The epithelial covering of the primitive mucous membrane sends cylindrical masses of entodermic or ectodermic elements, as the case may be, into the surrounding mesoderm ; the originally single cord of cells very soon undergoes division, a richly-branched system of epithelial tubes early represent- ing the future gland. The liver originates as a ventral outgrowth of the intestinal epithelium into the septum transversum ; very soon this branches, the two hepatic diverticula following so closely upon the stage of the single outgrowth that the latter is sometimes overlooked. The walls of the distal ends of the diverticula soon become greatly thickened, which areas of entodermic epithelium represent the earliest traces of the hepatic tissue. Regarding the details of the further stages in the growth of the more complicated livers opinions do not agree ; it is probable, however, that the hepatic cords of the mammalian organ are attributable to the same general plan of development as are other tubular glands, the com- plicated arrangement of the secreting tissue resulting from incomplete separation and subsequent fusion of the cell-cords. The invasion of the epithelial areas by the blood-vessels breaks up the entodermic tissue into the cell-nests which occupy the intercapillary spaces. Two forms of liver- cells are present during the greater part of fcetal life, large polyhedral elements, and small round cells, the latter disappearing shortly after birth ; the relation between the two varieties is not clearly established, but the small cells are probably younger stages of the larger. Multinucleated cells of considerable size also occur within the blood-vessels of the embryonal liver; these are regarded as connected with the production of red blood-corpuscles before birth. The lining of the bile-vessels and of the interlobular bile-ducts, together with the hepatic cells, is a derivative from the entoderm, while the connective tissue and blood-vessels, as well as the tissues of the walls of the bile-vessels other than the epithelial lining, are contributions from the mesoderm. The pancreas appears shortly after the liver as a dorsal diver- ticulum, which extends from the gut into the primitive omentum, jqO NORMAL HISTOLOGY. or mesogastrium, sending out hollow buds and lateral branches. The organ first lies parallel to the sagittal axis of the body, afterwards changing its position so as to lie transversely, the former anterior ex- tremity passing to the left. In many mammals ventral diverticula appear in addition to the dorsal outgrowth : to what extent these are formed in man, and to which portions of the organ they contribute, is still uncertain. The presence of more than one pancreatic duct in cer- tain animals is explained by the persistence of the embryonal condition. The tubular acini of the organ are developed in a manner similar to that in which those of the other salivary glands are formed : the cylinders of entodermic cells send off branches, which, in turn, give rise to secondary buds, the lumen of the original diverticulum ex- tending into the terminal compartments of the gland. The ingrowth of the surrounding mesoderm establishes the division into lobules and supplies the interlobular connective tissue. THE URINARY ORGANS. I9I CHAPTER XL THE URINARY ORGANS. THE KIDNEY, The kidney is a highly-developed compound tubular gland, com- posed of pyramidal lobules which correspond in number with the renal papillae and Malpighian pyramids : in the adult, however, their distinctness is lost, since they become blended to- gether. On laying open the fresh organ by a longitudinal section, two regions are ap- preciable, the cortex and the medulla. The cortex is readily distin- guished as the periph- eral granular zone em- bracing the outer third, while the medulla ap- pears radially striated and occupies the re- maining two-thirds of the gland. The inner surface of the medulla, next the pelvis, presents a num- ber of eminences, or papillae, at whose apices open the large terminal uriniferous tubules or excretory ducts. Each renal papilla is the cul- minating point of a sys- tem of dividing and sub- dividing tubules, which collectively form a pyramidal mass, the base of which corresponds to the surface of the organ, while its apex is the papilla. These pyramidal tracts constitute the lobules of which the kidney is com- Longitudinal section of human kidney, exhibiting genera! relations of macroscopic details: A. renal artery; U, ureter ; C, one of the calices into which a papilla projects; 1, cortex containing labyrinth (/) and medullary rays (/«) ; 2, medulla; M, Malpighian pyramids, some obliquely cut at 3 ; b, bound- ary layer ; B, columns of Bertini ; 4, masses of adipose tissue ; 5, branches of renal artery. (After Henle.) 192 NORMAL HISTOLOGY. posed. In the adult human organ all traces of such divisions have usually disappeared ; during fcetal life, however, the lobules are dis- tinctly seen, a condition which is permanently retained in many of the lower animals. The medulla is occupied by 8-18 striated conical Malpighian pyramids, the apices of which correspond to the papillae, while their bases occupy the line of juncture between the cortex and the medulla. Each pyramid exhibits Fig. 235. alternating light and dark striae, these markings being respectively the uriniferous tubules and the blood-vessels. The masses of the organ ex- tending between the sides of the Malpighian pyra- mids as far as the pelvis constitute the columns of Bertini, and are trav- ersed by the large blood- vessels. At certain points along their bases the striae of the Malpighian pyramids are continued into the cortex as slender, tapering bun- dles of parallel tubules, which form the medul- lary rays, or pyramids of Ferrein. By the penetration of these bun- dles the cortex is sub- divided into the med- ullary rays and the labyrinth, the latter ap- propriately so named on Section of human kidney, including cortex and portion of medulla, showing general arrangement of tissues. Cortex (C) is imperfectly subdivided by bundles of parallel tubules constituting the medullary rays (m) ; between these lies the labyrinth (/) containing the Malpighian bodies (x) ; in places {x') the glomerulus has fallen out, leaving the empty capsule ; b and v, sections of blood-vessels. account of the great tortuosity of the component uriniferous tubules. The dark-red points irregularly studded over the labyrinth indicate the position of the Malpighian bodies. In sections parallel to the free surface the medullary rays appear as groups of tubules sur- rounded by the labyrinth on all sides. The blood-vessels of the labyrinth are enveloped in connective tissue, which latter represents the interlobular tissue of other glands and the boundaries of the primary lobules. The secreting THE URINARY ORGANS. 193 parenchyma of the organ is held in place by the interstitial con- nective tissue ; this is present between the tubules in most parts of the kidney in very small quantities, — the immediate vicinity of the Malpighian bodies and the papillary region of the medulla being exceptions, since considerable amounts of the interstitial tissue are present in these localities. The connective tissue of the kidney be- comes condensed at the periphery of the organ, where it forms a fibrous investment, over which, in addition, the special capsule extends. The Malpighian bodies are situated exclusively within the cortex, and are limited to the labyrinth. They consist of two parts— a spherical mass of convo- luted capillary blood-ves- Fig. 236. sels, the glomerulus, or the Malpighian tuft, and the surrounding expanded extremity of the uriniferous tubule, the capsule of Bowman. The glomer- ulus is supplied by an afferent artery, which divides into several branches ; each of these breaks up into numerous capillaries, which are united by delicate con- nective tissue into groups or lobules. The blood escapes from the convo- luted capillaries of the glomerulus by the effer- ent vessel, which passes out by the side of the en- tering artery. The glomerulus, as usually seen in sections, seems to lie within the capsule, the blood-vessels having apparently pierced the latter to gain entrance. The vessels, however, really are outside the cavity •of the capsule, since one surface of this structure has been pushed in before the advancing tuft during its development. The masses of convoluted capillaries are closely invested by the reflected portion of the capsule, which likewise dips in between the vascular lobules of the glomerulus. The invaginated portion becomes continuous 13 Section of human kidney partia ly injected : a, interlobu- lar artery giving off afferent twig (6) ; c, efferent vessel passing into intertubular capillaries {d) ; e, convoluted capillaries of glomeru'us ; /, ouier layer of Bowman's cap- sule, the nuclei of whose cells sh nv at g ; h, uriniferous tubule in transverse section, i, ii oblique section. 194 NORMAL HISTOLOGY. Fig. 2.37. Pelvis Diagram of the kidney, showing the course of the uriniferous tubules and of the blood vessels ; for convenience the medulla is represented as greatly shortened. The various divisions of the tubule — Bowman's capsule, neck, proximal convoluted, spiral, descending and ascending limbs and loop of Henle'sloop, irregular, distal convoluted, arched collecting, straight collecting, and excretory duct — are indicated by their initial letters : a, e, and c, respectively the afferent, efferent, and capillary blood-vessels ; s, stellate vein ; v r, vasae rectae. THE URINARY ORGANS. 195 with the outer layer of the capsule at the stalk of the glomerulus, at which point the vessels and the capsule are intimately united. Each uriniferous tubule begins within the labyrinth as the dilated capsule of Bowman. A greatly constricted neck, situated at the pole of the Malpighian body opposite the position of the vascular stalk, leads into the first or proximal convoluted tubule, which is characterized by its considerable size and tortuous course. Leaving the labyrinth, to which it has thus far been confined, the tubule enters the medullary ray and passes towards the medulla as the slightly wavy spiral portion ; on reaching the medulla a marked diminution in the size of the tubule takes place, the reduced tube passing into the medulla as far as the papillary zone as the descend- ing limb of Henle's loop, the narrowest part of the entire urinifer- ous tubule. The spiral tubule is practically the beginning of the descending limb of Henle's loop, and takes the place of this arm in the medullary ray, into the constitution of which, strictly regarded, it does not enter. Just before reaching the loop itself the tubule becomes slightly larger, obtaining a diameter which is retained throughout the loop and the ascending limb ; on again reaching the cortex, the ascend- ing limb enters the medullary ray as its second constituent until it once more enters the labyrinth, to become, for a short distance, the conspicuous irregular tubule. The succeeding second or distal convoluted portion resembles very closely the proximal part of like name, possessing a similar size and tortuous course. The uri- niferous tubule finally leaves the labyrinth as the arched collecting tubule, to enter, for the third time, the medullary ray as the straight collecting tube. In consequence of the frequent union of canals of smaller size, the collecting tubes rapidly increase in diameter as they traverse the medulla, until, in the papillary layer, the narrow tubules have become the large excretory ducts, or tubes of Bellini, whose orifices on the free surface of the papillae are recognizable by the unaided eye. A certain number of tubules probably do not form loops of Henle, but pass directly to become the collecting canals (Rose). From the foregoing it will be seen that the Labyrinth contains : Malpighian bodies — glomeruli and cap- sules ; Constricted necks of tubules ; Proximal convoluted tubules ; Irregular tubules ; Distal convoluted tubules ; Arched collecting: tubules. 196 NORMAL HISTOLOGY. Medullary ray contains Medulla contains : ( Spiral tubules ; < Ascending limbs of Henle 's loops ; I Straight collecting tubules. Descending limbs of Henle1 's loops ; The loops ; Ascending limbs of the loops ; Collecting tubules of all sizes. While the labyrinth is characterized by the irregular and tortuous course of its tubules, the medullary ray and the medulla are dis- tinguished by the longitudinal, generally parallel arrangement of their components. The wall of all parts of the tubule consists of the basement-mem- brane and the lining epithelium ; the variations in the character of the latter are so numerous that it is desirable to consider each portion of the tubule in detail. 1. The capsule, the expanded and invaginated blind termination of the uriniferous tubule, is lined with a single layer of large, flattened epithelium, resembling endothelial plates. This covers, likewise, Fig. 23S. Portions of the various divisions of the uriniferous tubules drawn from sections of human kidney : A, Malpighian body; x, squamous epithelium lining the capsule and reflected over the glomerulus ; y, z, afferent and efferent vesse s of the tuft ; e, nuclei of capillaries ; n, constricted neck marking passage of capsule into convoluted tubule; B, proximal convoluted tubule; C, irregular tubule; D and F. spiral tubules ; E, ascending limb of Henle's loop ; G, straight collecting tubule. the portion reflected over the glomerulus. In ordinary preparations the presence of the cells is indicated by the delicate spindle nuclei seen in profile ; the numerous nuclei seen within the tissues of the THE URINARY ORGANS. jg^ glomerulus include those of the walls of the blood-vessels and of the interstitial tissue, as well as those of the capsular epithelium. 2. At the neck the flattened epithelium abruptly becomes cuboidal and rapidly assumes the character of the lining of the convoluted tubule. The existence of ciliated epithelium at the neck or within the capsule in the mammalian kidney has been asserted, but not satis- factorily established ; in many of the lower animals, however, as in the amphibians, the presence of cilia is readily demonstrated, as is like- wise the existence of tubules opening directly into the peritoneal cavity. Such trumpet-shaped orifices — the nephrostomata — represent a partial persistence of the primitive type of excretory organ, in which the tubules pass directly from the body-cavity to the outer surface. 3. The proximal convoluted tubule is clothed with low co- lumnar or cuboidal cells, whose granularity and transparency vary with the stage of secretion, as do likewise the thickness of the epi- thelium and the size of the lumen of the canal. The outer zone of Section of kidney of amphiuma : the peritoneal surface (b, i) exhibits one of the nephrostomata (0), lined with ciliated cells; d, glomerulus sur- rounded by capsule ; u, uriniferous tubules ; v, capillaries filled with red blood-cells. Fig. 240. A CEDE Portions of the constituents of the medulla from the human kidney : A , B, collecting tubules ; C, D, descending and ascending limbs of Henle's loop ; E, blood-vessel. the epithelium, next the basement-membrane, presents more or less clearly the vertical striation distinguishing rod-epithelium. The demarcation of the individual cells is not sharply marked, their boundaries being indistinctly defined. 4. The epithelium of the spiral tubule closely resembles that of the preceding portion, consisting of similar low columnar elements possessing granular protoplasm but less marked striations. 198 NORMAL HISTOLOGY. Fig. 241. 5. The conspicuous diminution in diameter which marks the pas- sage of the spiral tubule into the descending limb of Henle's loop is accompanied by a change in the character of the lining epithelium. The low columnar cells are replaced by flattened, transparent plates, whose nuclei, thicker than the bodies of the cells, encroach upon the lumen of the tubule as minute spindle-shaped projections ; since the latter are situated often on opposite sides of the tube, its lumen in section appears as a wavy channel. 6. Shortly before reaching the loop, at a point within the de- scending limb corresponding with the increased diameter of the tubule, the epithelium becomes polyhedral, possessing flattened nuclei and faint striations ; the lumen is distinct in this region, although narrow. This character is retained by the epithelium throughout the loop and the ascending limb as far as the succeed- ing portion of the tube. 7. The irregular tubule is distinguished by its small and uncertain lumen and its distinctly striated epi- thelium ; the thickness of the latter and, conse- quently, the size of the canal vary with the con- ditions of secretion. 8. The lining of the dis- tal convoluted tubule resembles that of the proxi- mal, the epithelium being granular, indistinctly sepa- rated into individual cells, and presenting a striated outer zone ; the lumen of the canal depends largely upon the thickness of the lining cells, which changes with the func- tional activity of the secretory elements. 9. The succeeding segment, the arched collecting tubule, con- tains low cuboidal, transparent cells, which, with slight alteration, become the epithelium of the straight collecting tubule. 10. Passing into the medulla, the cells of the collecting tubules become markedly columnar, which form they retain with increasing distinctness throughout the remainder of their course. The large Section of medulla of human kidney : 7v, large collect- ing tubules ; x and_y, descending and ascending limbs of Henle's loops ; z, loops of Henle ; v, blood-vessels. THE URINARY ORGANS. I99 excretory ducts, or tubes of Bellini, in the papillary region present a beautiful example of simple columnar epithelium in the tall, transparent, and clearly-defined cells with which they are lined. These cells, the largest epi- thelial elements within the Fig. 242. kidney, are defined from one another with great dis- tinctness, and possess oval nuclei situated somewhat nearer their outer bound- aries. The blood-vessels with- in the kidney are very plen- tiful. The renal artery, entering at the hilum, passes through the sinus within the submucous tissue which occupies the space between the wall of the pelvis and the neighboring paren- chyma ; during its course through the sinus several small twigs are given off for the nutrition of the struc- tures in the immediate vicinity. Before entering the glandular tissue the renal artery breaks up into a number of large branches, which traverse the parenchyma through oblique channels within the inter- pyramidal tracts, or columns of Bertini, to gain a position at the juncture of the cortex and medulla corresponding to the bases of the Malpighian pyramids. At this point they bend sharply to form a series of horizontal arches, from which two sets of vessels spring— the ascending interlobular cortical arteries and the arteriae rectae of the medulla. The straight cortical branches, passing towards the free surface of the organ, give off short, curved lateral twigs to supply the affer- ent vessels of the glomeruli. These branches divide into groups or lobules of convoluted capillaries ; the latter, in turn, join to form the slightly smaller efferent vessels, which carry off the still arterial blood from the Malpighian bodies. The efferent vessels soon break up into capillary net-works which surround the tubules of the labyrinth and the medullary ray. These net-works are taken up by the interlobular veins which accompany the arteries, and pass to the pelvis, where they aid in forming the large renal veins. The vessels collecting the blood from the peripheral zone of the cortex Transverse section of papillary region of medulla of hu- man kidney, more highly magnified : C, large collecting tubules ; x and y, descending and ascending limbs of Henle's loops ; v, blood-vessels. 200 NORMAL HISTOLOGY. converge to certain points, where they form the venae stellatae ; these veins afterwards pass into the labyrinth and follow the inter- lobular vessels. The arteries supply- ing the medulla enter as straight vessels, the arteriae rectae, which undergo repeated divis- ion to form rich inter- lobular net-works reach- ing as far as the papillae, where the orifices of the excretory ducts are sur- rounded by capillaries. The blood within the medulla is collected by the venae rectae, which accompany the corre- sponding arteries and empty into the large veins situated at the juncture of the cortex and the medulla. The large venous trunks pass obliquely through Section of injected kidney of dog, showing general disposi- tion of blood-vessels : a and b, large arterial and venous branches situated at junction of cortex (C) and medulla ( M), which break up into ascending interlobular twigs (c) and de- scending straight vessels (I, I') ; e,f, afferent and efferent ves- sels of glomeruli (g) ; h, intertubular capillary net-works; i, peripheral venous trunks, which collect the blood from sub- capsular net-works (k). the medulla, along with the arteries, to reach the pelvis, where they join with their fellows to form the renal veins. The lymphatics of the kidney are arranged as two sets of vessels ; a superficial sys- tem ramifies within the deeper layers of the capsule, while a system of deeper channels passes in company with the blood-vessels into the interior of the organ to communicate with the numerous lym- phatic clefts and spaces which exist within the intertubular connective tissue. Regarding the ultimate distribution of the nerves of the kidney, little is known with certainty beyond the fact that they enter the parenchyma in company with the blood-vessels, around which they form net-works of non-medullated fibres; the nerve-fibres have been traced between the tubules, where they form meshes immediately outside the membrana propria. The ultimate distribution of the fibrillar and their relations to the secreting cells are still uncertain. THE URINARY ORGANS. 20 1 THE RENAL SINUS AND THE URETER. The greater part of the renal sinus is occupied by the dilated, pouch-like expansion of the upper extremity of the excretory duct of the kidney, the ureter, embracing the pelvis and its subdivisions, the calices, and the infundibula. These cavities, together with the protruding portions of the renal papillae, are invested by a membra- nous structure consisting of three coats, the mucous, the muscu- lar, and the fibrous. The mucous coat is covered with stratified squamous epithelium, which comprises relatively few layers of cells, and is frequently termed " transitional," in view of the rapid change Fig. 244. Transverse section of human ureter: a, irregular lumen, lined by mucous membrane, which con- sists of epithelium (&), tunica propria (c),and submucous tissue (d); e,f, longitudinal and circular bundles of muscular tunic ; gt additional longitudinal muscular bundles ; h, fibrous tissue ; i, blood- vessels. from the columnar elements of the deep layer to the squamous ones of the superficial stratum. The tunica propria, or stroma of the mucous membrane, consists of a felt-work of fibro-elastic bundles, contains a few small racemose glands, and passes insensibly into the inconspicuous submucous tissue. The muscular coat is arranged as an inner longitudinal and an outer circular layer composed of bundles of involuntary muscle cells. On the papillae the circular bundles are especially well developed, enclosing the renal tissue somewhat as a sphincter. The outer fibrous coat consists of irregularly-placed bundles of connective tissue, which connect the organ with the surrounding structures. The walls of the ureter 202 NORMAL HISTOLOGY. proper contain the same layers that are found in the pelvic portion of the tube ; the muscular tunic, however, is somewhat better de- veloped, and in the lower part of the ureter is augmented by an addi- tional imperfect external longitudinal layer, although the latter is represented in places by only a few scattered bundles of non-striped muscle. THE URINARY BLADDER. The bladder is composed of the same coats that are found in the ureter, the mucous, the muscular, and the fibrous, together with the serous surface in those parts of the organ which possess a peritoneal covering. The epithelium of the bladder corresponds to that lining the ureter and Fig. 245. the renal pelvis, being of the stratified squamous ' ' transi- tional" type. The mucous membrane at the base of the bladder contains small race- mose glands ; minute lymph- follicles are also found within the mucosa. The involun- r^3 tary muscle is arranged in three general layers, an in- ner and an outer longitu- :,■•.'' dinal enclosing a middle '-' V circular stratum; the bun- dles composing these tunics are, however, so irregularly disposed that the layers are very imperfectly defined. At the base of the organ the inner longitudinal muscular bundles increase in size, while those of the augmented circular layer constitute the internal vesical sphincter. The blood-vessels of the ureter and the bladder sup- ply the muscular and mucous coats with rich capillary net- works, the one situated within the mucosa of the bladder being especially rich. The lymphatics have much the same distribution as have the blood-vessels, net- works being found within the deeper layers of the mucosa, as well as more sparingly within the muscular tissue. The nerves supplying Section of human bladder: a, squamous epithelium covering the folds of the tunica propria ; b, submucous tissue; c, d, irregularly-disposed circular and longi- tudinal bundles of non-striped muscle ; e, fibrous tis- sue of serous coat. THE URINARY ORGANS. 20% the ureter and the bladder are largely composed of sympathetic fila- ments comprising both medullated and non-medullated fibres. The fibres pass into the mucosa as far as the epithelium ; but whether they penetrate between the epithelial cells is still undetermined. Numbers of microscopic ganglia are situated along the course of the nerves of the bladder, this organ affording in smaller animals a favorable situation for studying ganglion-cells and nerve-fibres, as well as involuntary muscle cells. THE URETHRA. The urethra, both male and female, consists of a mucous coat, strengthened by a variable muscular tunic and by fibrous tissue. The female urethra is lined throughout by a stratified squa- mous epithelium, which rests upon a basement-membrane cover- ing the numerous small papillae with which the surface of the tunica propria is beset. These papillae are especially plentiful and well developed near the termination of the canal, in the vicinity of the meatus. The tunica propria, or stroma of the mucosa, is composed of interwoven bundles of fibrous and elastic fibres, the superficial layers of which, particularly in the vicinity of the internal orifice, are infiltrated with lymphoid cells. Small acinous glands are sparingly present. The muscular tunic is well developed and arranged as an inner longitudinal and an outer circular layer of non- striped .muscle. The intermuscular connective-tissue lamellae contain many elastic fibres. The male urethra is lined with epithelium, the character of which varies in the different portions of the canal. In the prostatic part the epithelium resembles that lining the bladder, being of the transi- tional variety ; this passes gradually into the stratified columnar type of the investment of the membranous part, which in turn gives place to a single layer of simple columnar cells in the penile portion. The fossa navicularis is lined with stratified squamous epithelium continuous with that covering the glans. The tunica propria bears numerous papillae, which are particularly well devel- oped within the navicular fossa. The small racemose glands of Littre are found through the entire urethra. Inner longitudinal and outer circular bundles of non-striped muscle surround the pros- tatic portion, extending over the membranous part to be lost on the spongy. In addition, the fibres of the compressor urethrae muscle contribute a distinct muscular investment for the membranous por- tion, which fades away at either border over the penile and prostatic segments. The anterior part of the penile division is destitute of muscular tissue. Outside of the muscular layer a variable fibrous tunic gives additional firmness and strength to the canal. The walls 204 NORMAL HISTOLOGY. of the urethra are liberally supplied with blood-vessels, which form rich capillary net-works beneath the epithelium. The larger lym- phatics lie in the submucosa, where they receive the radicles accom- panying the blood-vessels within the mucosa. The nerves which bear the blood-vessels company find their endings within the super- ficial sub-epithelial layer of the mucosa. The Development of the Urinary Organs. In tracing the history of the formation of these structures the genesis of three distinct divisions must be considered — the development of the kidney and ureter, that of the bladder, and that of the urethra. The permanent kidney is preceded in the embryo by an important although transient excretory organ, the Wolffian body ; the prod- ucts of this organ are carried off and emptied into the primitive intes- tinal canal by its excretory tube, the Wolffian duct. All parts of the Wolffian body and the duct consist of mesodermic tissue alone, these structures arising essentially as outgrowths from the primitive peritoneal lining into the surrounding mesoderm. The mesothelial evaginations so originating constitute the primary tubules of the Wolffian body, from which numerous secondary canals are derived ; the subsequent development of blood-vessels in intimate relation with the tubules produces the primitive Mal- pighian corpuscles of the foetal organ. The first step in the development of the kidney consists in a dorsal outgrowth from the Wolffian duct near its cloacal end ; this diver- ticulum grows forward and parallel with the Wolffian duct until its extremity reaches a position behind and somewhat above the caudal end of the Wolffian body. The primary kidney- tube now expands at its upper end, the dilated portion subsequently undergoing peripheral cleavage into a number of tubular compart- ments. Coincidently with the growth and dif- ferentiation of the epithelial evagination from the Wolffian duct, the mesodermic tissue into which the expanded extremity of the diverticu- lum makes its way becomes greatly condensed. The fundamental structures in the development of the kidney and the ureter are now distinctly defined. The narrow, elongated portion of the outgrowth from the Wolffian duct becomes the epithelial lining of the ureter, while the ex- panded terminal part forms that of the pelvis and of the urinifer- ous tubules. The connective and vascular tissues are derived from Fig. 246. Sagittal section of eleven- day rabbit embryo, show- ing earliest stage of de- velopment of kidney as outgrowth (k) fromWolffian duct (7v) into surrounding mesoderm (;«). THE URINARY ORGANS. 20 = the surrounding mesoderm, the epithelium of the kidney and of its duct alone being the immediate product of the evagination. The formation of the collecting tubes and the uriniferous tubules fol- lows the division and subdivision of the compartments into which the primitive pelvis and calices separate, the entire elaborate' system of tubules resulting from the extension and branching of the primary canals. The surrounding mesodermic tissue early differentiates a limiting zone or primitive capsule, which defines the form of the developing kidney and opposes the growth of the tubules in a straight direction, thereby inducing the marked tortuosity accompanying the subsequent increase in the length of the uriniferous canals. The in- Fig. 248. vagination of the termination of the tubule and the simultaneous devel- Fig. 247. Sagittal section of fifteen-day rabbit em- bryo : the developing kidney presents an oval mass of condensed mesoderm (?>i) into which the tubular compartments (t) of the divided primitive renal pelvis (k) extend. Sagittal section of 30 mm. cow embryo: K, developing kidney, containing Malpighian bodies (AT) and tubules; u, part of renal pelvis ; IV, atrophic Wolffian body ; m, glo- merulus of primary Malpighian body; t, de- generating tubules of the organ. opment of groups of capillary blood-vessels in intimate relation with them give origin to the characteristic Malpighian bodies. The epithelium of all parts of the uriniferous tubules, of the renal pelvis, and of the ureter is derived directly from the outgrowth from the Wolffian duct ; the interstitial connective tissue, the blood-vessels, and other structures are contributed by the surround- ing condensed mesoderm. Since, as has been already stated, the entire Wolffian body, including its duct, is a product of the meso- derm, the epithelial evagination and its derivatives must be referred likewise to the middle blastodermic layer, all parts of the urinary 205 NORMAL HISTOLOGY. tract as far as, bid not including, the bladder being, therefore, of mesodcrmic origin. The development of the urinary bladder is connected with the history of the allantois. The latter grows out of the hind gut as a diverticulum which reaches conspicuous dimensions, in many embryos appearing as a large, flask-shaped sac ; in man, however, the allan- tois is never free, but grows as a stalk in close relations with the other structures passing through the umbilical opening. The portion of the allantoic canal lying within the embryo becomes differentiated into three divisions : the much larger middle segment greatly dilates and eventually constitutes the bladder; the outer division, extending from the bladder to the umbilicus, forms the atrophic urachus, while the narrow inner portion establishes communication between the bladder and the common uro-intestinal passage — the cloaca — and becomes the urethra proper. The primitive ureter, which at first opens in company with the Wolffian duct into the uro- genital sinus, changes the position of its exit until the tube finally assumes its permanent relations and opens into the bladder. The epithelium lining the allantois is a direct extension of the entoderm of the primary gut ; the allantoic derivatives, including the bladder and the urethra, therefore, are clothed with entodermic cells; the muscular and connective tissues of their walls, however, are con- tributions from the mesoderm. The short female urethra, extending from the bladder to the upper part of the vestibule, the representative of the uro-genital sinus, corresponds with the primary vesical canal, and is the ure- thra proper. In the male subject this passage is supplemented and greatly lengthened by the approximation and closure of the folds by which the sinus is converted into the narrow canal extending to the end of the penis. The male urethra, therefore, consists of two morphologically distinct divisions : the urethra proper, which in- cludes that portion of the adult canal lying between the neck of the bladder and the uterus masculinus or sinus pocularis, this division being the strict homologue of the female urethra ; and the remain- ing part of the canal, or supplementary urethra, which represents the closed and extended uro-genital sinus. THE MALE REPRODUCTIVE ORGANS. 207 CHAPTER XII. THE MALE REPRODUCTIVE ORGANS. THE TESTICLE. The testicle is a highly-developed compound tubular gland. The parenchyma of the organ is enclosed within a fibrous capsule of especial thickness and strength, the tunica albuginea, which becomes greatly thickened on the posterior aspect of the testicle to form a dense connective-tissue mass, the mediastinum, or the Fig. 249. corpus Highmori. From the mediastinum stout fibrous septa radiate to the pe- riphery, thus dividing the organ into a number of irregular pyram- idal compartments or lobules, in which the seminiferous tubules are contained. The tunica albu- ginea consists of a dense fibrous felt- work of bundles of nbro-elastic tissue ; the looser, inner layers sup- port numerous blood-vessels, con- stituting the tunica vasculosa. The outer surface of the albuginea, through the greater part of its extent, is covered by the visceral layer of the tunica vaginalis, which supplies a serous investment to much of the testicle, as well as to a portion of the epididymis. The testicle lies behind and out- side the serous sac, the latter be- coming invaginated by the testicle during its descent into the scrotum ; that part of the posterior bor- der of the testicle included between the reflected folds of the tunica vaginalis is devoid of serous covering, and affords a position for the entrance and escape of the blood-vessels, the ducts, the lymphatics, and the nerves. Diagram illustrating the course and the rela- tions of the various constituents of the testicle and the epididymis: a, tunica albuginea; m, the mediastinum ; t, convoluted, s, straignt, por- tions of seminiferous tubules ; r, rete testis ; e, vasa efferentia ; c, coni vasculosi ; te, tube of epididymis ; vd, vas deferens ; va, vas aberrans ; /, paradidymis. 208 NORMAL HISTOLOGY. The seminiferous tubules may be conveniently divided into three portions: (i) the tortuous convoluted tubules, whose wind- ings contribute the bulk of the lobule, (2) the straight tubes, situated in the apices of the pyramidal lobules, and (3) the tubules within the mediastinum, which by their union form the rete testis. The seminiferous tubules terminate in the mediastinum, from which situation the seminal canals are continued by intermediate ves- sels connecting testicle and epididymis ; these intermediate tubules are the vasa efferentia and the coni vasculosi. The former arise from the rete testis, while the latter are the progressively tortu- ous continuations of the vasa efferentia terminating in a mass, the Fig. 250. p;'' Section of human testicle, including portion of tunica albuginea, ex- hibiting general arrangement and structure of tubules : a, tunica albu- ginea ; b, seminiferous tubules cut in various directions ; c, basement- membrane ; d, secreting cells ; e, groups of interstitial cells ;/, intertubular connective tissue. globus major, which represents the sum of the tortuous coni vas- culosi. These last-named canals unite to form the main tube of the epididymis, which is sufficiently convoluted to include its entire length of twenty feet within the inconsiderable bulk of the epididymis. The seminiferous tubules, 130-140 <>■ in diameter, possess walls which are composed of several layers of flattened endothelioid con- nective-tissue plates, applied to which a thin basement-membrane THE MALE REPRODUCTIVE ORGANS. the lining of epithelial cells. within the tubule depends Fig. 251. 209 The pre- upon the & .7 Transverse section of seminiferous tubule from human testicle : a, membrana propria ; b, zone of parietal cells ; c, mother-cells undergoing division ; d, daughter-cells, or spermatoblasts ; e, partially-developed spermatozoa ; /, surrounding intertubular connective tissue. exists ; inside the latter lies cise character of the cells condition of functional activity of the organ ; the notable differences distin- guishing the elements with- in the resting gland from those found in the active organ depend largely upon the infrequency within the former, and the almost uni- versal presence within the latter, of cells actively en- gaged in karyomitotic divis- ion. The different tubules, however, exhibit great vari- ation in the exact stage of these changes, adjacent canals, and, in fact, parts of the same one, often present- ing the extremes of the cycle side by side. Next the basement- membrane of the seminiferous tubule lies a layer of low cuboidal nucleated parietal cells ; this peripheral zone contains cells of two kinds: (1) the sustentacular cells, or Sertoli's columns, which take no part in the formation of the generative elements, and (2) the spermatogenic cells, which pro- duce elements intimately related to the development of the seminal filaments. Inside the outer, peripheral layer, in functionally active organs, an irregular second zone contains many elements with large transparent nuclei and chromatin figures, indicating the progress of cell- division ; these are the mother-cells, the derivatives of the spermatogenic cells of the outer zone, and, in turn, the parents of a numerous progeny of smaller daugh- ter-cells. The nuclei of the latter con- stitute the spermatoblasts, since it is from them that the spermatozoa are directly derived. The inner .zone of the tubule is frequently occupied by fan-shaped groups of 14 Section of testicle of dog, including part of seminiferous tubule : a, zone of parietal cells containing sustentacular elements (_/") ; b, mother - cells ; c, daughter-cells ; d, free nuclei of sper- matoblasts and developing sperma- tozoa. 2IO NORMAL HISTOLOGY. developing spermatozoa, embedded within a finely granular, semi- gelatinous substance. Spermatogenesis varies among the different classes of vertebrate animals ; the account here given refers to man and the higher mammals. The originally round spermatoblasts soon exhibit a tendency to elongate and to become pyriform ; several such cells, with partially- formed spermatic filaments, are often crowded together by the pressure of the surrounding elements, and, in consequence, come to lie in close relation and in apparent union with the centrally projecting protoplasm of the sustentacular cells. Such appearances, probably Fig. 253. Fig. 254. II 1 Section of testicle of musk-rat, ex- hibiting early stage of spermatogenesis : a, membrana propria ; b, zone of pari- etal cells ; c, mother-cells ; d, sperma- toblasts developing into spermatozoa. Section of testicle of musk-rat, showing later stage of spermatogenesis : a, mem- brana propria ; b, zone of parietal cells ; c, mother-cells ; d, fan-shaped masses of ele- ments concerned in producing spermato- zoa (e). entirely the result of mechanical forces, were formerly regarded as indicating an important role on the part of the sustentacular cells in the production of the spermatozoa, an assumption no longer warranted by recent investigations. Coincidently with the changes in the general form of the spermatoblasts, the nuclei undergo mod- ifications of great consequence in the development of the future spermatic elements. The views concerning the genetic relation of the parts of the origi- nal cell to those of the resulting spermatozoon are still at variance. According to Henle, La Valette St. George, and many others, the nucleus of the daughter-cell gives rise to the head, while from the protoplasm are differentiated the middle-piece and the tail. On the other hand, Kblliker has always held, as recently have Biondi and Niessing, that the nucleus undergoes a complicated metamorphosis, producing not only the head, but also the entire spermatozoon, the protoplasm becoming part of the granular debris in which the groups of developing spermatozoa lie embedded. THE MALE REPRODUCTIVE ORGANS. 211 Critical study of many specimens convinces the author that the view attributing to the nucleus the formation of the entire sper- matozoon is correct. Without attempting a detailed account of the complicated cycle, these changes may be briefly stated to con- sist in the increase and accumulation of the nuclear chromatin in a manner resulting in the differentiation of the nucleus into two zones, — an outer, which stains deeply and is rich in chromatin, and an inner, which appears clear and is devoid of chromatin. Coinci- dently with these changes the nucleus escapes from the proto- plasm of the daughter-cell to take up its position, in company with other free nuclei, within the granular re- mains of the extruded cell-proto- plasm. Subsequently the chromatin becomes especially condensed and ac- cumulated at the inner border of the darker outer half of the nucleus ; from this zone of chromatin a deli- Fig. 256. Fig. 255. Section of testicle of musk-rat, dis- playing still later stage of spermato- genesis : spermatozoa are now well advanced and form radially-arranged masses (<^) ; other letters as in pre- ceding figures. Section of human testicle, including parts of three tubules it) and intervening connective tissue ; within the latter lies a group of inter- stitial cells (/). cate projection or spine grows into, and, later, through, the inner clear half of the nucleus ; this outgrowth is the first indication of the future tail of the spermatic element. As the result of the local- ization of the chromatin within the central part of the nucleus, the latter now exhibits three zones : an outer clear cap at the fore- pole, a narrow middle zone filled with chromatin, from which the developing tail-fibre extends, and an inner clear area which reaches as far as the hind-pole and is pierced by the tail. In these three nuclear zones the divisions of the future mature spermatozoon are indicated : the outer clear cap becomes the homogeneous head, the middle chromatin band produces the tail and the middle-piece, 212 NORMAL HISTOLOGY. and the inner clear zone forms the delicate hyaline envelope invest- ing the middle-piece and the tail. Embedded within the loosely laminated intertubular connective tissue, groups of polyhedral nucleated cells occur in greater or less profusion ; these interstitial cells are present within the testicle of man and of mammals generally. But within the interstitial tissue of the boar's testicle they are found in remarkable abundance. The elements, evidently epithelial in nature, are arranged in groups or cylinders in the interstices between the seminiferous tubules, and represent the remains of the epithelial structures of the fcetal Wolffian body. With the termination of the convoluted division of the seminifer- ous tubules the secreting tissue of the gland ends, since the con- tinuation of the seminal canals, effected by the straight tubes and those forming the rete testis, represents the beginning of the elabo- rate system of excretory ducts extending from the testicle to the urethra. On arriving at the straight canals the seminiferous tubules be- come reduced in size (20-30 p.), as well as in number, the thick epithelial lining of the convoluted division being replaced by a single layer of low colum- Fig. 257. nar cells. The short narrow tubuli recti occupy the apices of the pyramidal lobules, and enter the medias- tinum, where they open into the irregular canals of the rete testis. The latter vary in size from mere clefts to channels approaching in diam- eter that of the convo- luted tubules ; they are lined by a single layer of flattened epithe- lial plates. Beginning at the up- per end of the rete tes- tis, the further course of the seminal canal is effected by the ten to fifteen vasa efferentia, which, by their pro- gressively increasing convolutions, form as many conical lobules, the coni vasculosi, the aggregate of which makes the globus major Section of tubule of human epididymis : a, membrana pro- pria ; b, columnar cells crowned with zone of long cilia (c) ; d, layer of non-striped muscle ; e, intertubular areolar tissue ; s, masses of spermatozoa occupying lumen of tube. THE MALE REPRODUCTIVE ORGANS. 213 Fig. 258. of the epididymis. The vasa efferentia and coni vasculosi possess a stratified columnar epithelium, the inner cells bearing long cilia ; this epithelium rests on a robust basement-membrane, out- side of which lies a fibrous coat strengthened in many places by a circular layer of involuntary muscle. The greatly convoluted tube of the epididymis has a similar wall, composed of stratified cili- ated columnar epithelium, a well-marked membrana propria, augmented by fibrous tissue, and a ring of pale muscle ; this mus- cular layer gradually thickens on approaching the vas deferens, in whose wall it becomes a tunic of considerable thickness. The structure of the spermatic duct, or vas deferens, closely re-, peats the arrangement of the tube of the epididymis. A stratified non-ciliated columnar epithe- lium, separated from the tunica propria by a well-defined basement- membrane, covers the mucosa; outside of the latter lies a sub- mucous layer of laminated con- nective tissue, which is embraced by the muscular tunic, consisting of an inner circular and an outer longitudinal layer. The ampulla possesses the same coats as the vas deferens, although in the former the several layers are somewhat thinner. The sem- inal vesicle, likewise, consists of a mucous coat, lined by stratified columnar epithelium, a submucous and a muscular tunic. Small, often branched, tubular glands occur within the mucous membrane of the ampulla and the seminal vesicle. The ejaculatory duct, formed by the union of the vas deferens and the duct of the seminal vesicle, contains a single layer of columnar epithelium, supported by the fibrous tunica propria ; a thin submucosa, together with a slightly developed inner circular and an outer longitudinal stratum of muscle, completes the wall of the duct. Connected with the epididymis are certain atrophic appendages Section through lower part of epididymis of child, showing general structure : a, fibro- serous envelope ; />, sections of convoluted tube of epididymis ; c, vas deferens ; d, intertubular tissue ; e, blood-vessels. 21a NORMAL HISTOLOGY. which represent the remains of foetal organs. Such structures are the paradidymis and the stalked and sessile hydatids. The paradidymis, or the organ of Giraldes, consists of irregular tubules lying among the convolutions of the epididymis, which are the atrophic remains of the tubes of the Wolffian body. They are lined with low columnar or cuboidal epithelial cells, often ciliated, and are surrounded by an envelope of vascular connective tissue. The tubules of the paradidymis are usually closed, and frequently contain small quantities of albuminous fluid. The pedunculated or stalked hydatid, common to both sexes, probably represents a part of the atrophied duct of the pronephros, the anterior segment of the Wolffian body. The sessile or un- stalked hydatid, on the contrary, is limited to the male subject, and is the slightly expanded proximal end of the rudimentary Mul- lerian duct. These sacs are lined generally by cuboidal cells, and often contain a clear fluid. The blood-vessels of the testicle, branches of the spermatic artery, are distributed to the mediastinum and to the loose inner layer — the tunica vasculosa — of the albuginea, including its pro- longations, the septa. From the vessels coursing within these robust fibrous structures smaller twigs enter the connective tissue and pass between the individual tubules, around which they form rich inter- tubular capillary net-works. The corresponding veins accom- pany the arteries. The lymphatics form a superficial capsular net-work, consisting of vessels situated within the tunica albuginea, and a deeper inter- tubular plexus, the radicles of which closely surround the semi- niferous canals. The superficial and the deep lymphatics anastomose to form within the mediastinum larger vessels, which, uniting with those of the epididymis, constitute one of the elements of the spermatic cord. Regarding the distribution of the nerves little is definitely known further than the penetration of bundles of mixed fibres between the seminiferous tubules, around which they form plexuses ; the ultimate termination of the end-fibres is unknown. THE SEMEN. The semen as ejected consists of the secretion of the testicle diluted with that of the seminal vesicles and of the prostate gland, together with the fluid derived from Cowper's glands and the mucous membranes traversed. The secretion proper of the male sexual gland consists almost entirely of spermatozoa ; these latter show no movement when in the concentrated fluid of the testicle or epididy- mis : only after the dilution normally effected by the admixture of THE MALE REPRODUCTIVE ORGANS. 215 Fig. 260. the secretions already mentioned is it that the characteristic active vibratile movements are observed. The spermatozoa are minute highly-specialized elements, each of which bears at one end a long cilium of exceeding delicacy : while differing greatly as to details of form and of size among vertebrated animals, the mammalian sperma- tozoa possess in common three more or less dis- tinctly defined parts, — the head, the middle-piece, and the tail. The human spermatic filament possesses an entire length of 50-60 fi, of which the head con- tributes 3-5 (i, the middle-piece 4-6 /Jt, while the remaining 43-49 i& belong to the tail. The head varies in form accord- ing to the side examined ; when seen on its broadest surface it is egg-shaped, the broader end of the head being directed anteriorly, and the smaller end being con- nected with the middle-piece. Seen in profile, the head is con- . . spermatoblast adhering cavo-convex, and terminates in a to middle-piece. Human spermatozoa as usually seen : a, from the broader surface ; b, from the side ; c, ele- ment with remains of Human spermatozoa highly magnified : h, »i, t, respectively head, middle-piece, and tail ; f, elements seen from the broader surface ; /, from the side. blunt rounded anterior extremity. The greatly diminished middle-piece is connected with the posterior pole of the head, and on the other hand fades away into the long delicate caudal filament. After the action of certain reagents the middle-piece splits up into a number of fibrillar of great tenuity (Bal- lowitz) ; in spermatozoa not entirely matured spiral fibrils are some- times observed in this part of the element. The centre of the sper- matic filament is occupied by the delicate axial fibre, which connects the head with the middle-piece and extends through the middle-piece and the tail. This fibril forms the articulation between the head and the middle-piece, and continues to the extreme end of the tail, the terminal segment being composed of the naked axial fibre alone. Within the middle-piece the axial fibre is ensheathed by a delicate envelope. The characteristic vibrations of the spermatic filaments may con- tinue for a long time after ejaculation : when suitably prepared, and under favorable conditions, these cells retain their vitality for many hours and even days. Human spermatozoa, mounted under cover- glasses and protected from evaporation, have been observed by the author to exhibit distinct vibratile motion after the lapse of over nine days. After death these elements may continue to vibrate for forty- 2I5 NORMAL HISTOLOGY. eight hours, or longer, within the fluids of the seminal tract. Cells capable of such tenacious vitality even under the less favorable con- ditions outside the body, exhibit still greater endurance when aided by the favorable conditions for prolonged life afforded by the normal female generative tract ; in these organs the spermatozoa no doubt often retain their powers of fecundation for weeks. These elements successfully resist the destructive action of ordi- nary reagents, as well as putrefactive changes ; this capability is owing, probably, to the union of the albuminous with the calcareous matters, which latter the spermatozoa contain in large quantity. The seminal fluid as ejaculated contains several constituents recog- nizable by microscopical examination. In addition to the sperma- tozoa there are usually seen spherical or cylindrical masses consisting of a clear, hyaline, glassy substance derived from the seminal vesicles ; numerous small, pale, delicate granules of an albuminous nature ; a few round or oval nucleated cells, whose finely granular protoplasm often contains fat-granules ; cylindrical epithelial cells, and the char- acteristic prostatic concretions or amyloid bodies, which are yel- lowish in color, spherical or triangular in form, and concentrically striated. These concretions appear to be composed of an albuminous substance in combination with a second which corresponds to lecithin (Fiirbringer, Posner). On standing for twenty-four hours the semen separates into an upper clear fluid and a thicker, opaque lower stratum ; the former contains few morphological elements, while in the lower layer these are very abundant. Subsequently, after prolonged standing, two varieties of crystals are frequently encountered, those composed of ammonio-magnesium phosphate and the so-called spermatic crystals. According to Fiirbringer, the latter are formed probably by the action of the semen on the prostatic secretion : since these crystals are found almost constantly, after death, in the fluid of the prostate, and not within the contents of the seminal vesicles, they are more appropriately termed prostatic crystals. They occur usually as prisms or pyramids, colorless, or of a slight amber tint, and break readily on slight pressure. THE PENIS. The penis consists of three somewhat flattened cylindrical masses of erectile tissue, the corpora cavernosa and the corpus spongi- osum, capped by the conical glans, all of which are held together by connective tissue and enveloped by the skin and subcutaneous tissue. The two cavernous bodies are enclosed within a stout fibrous envelope, the tunica albuginea, which reaches a thickness of about THE MALE REPRODUCTIVE ORGANS. 217 i mm., and is composed of closely interwoven longitudinal bundles of white fibrous tissue, intermingled with well-developed elastic fibres. Within this common in- vestment each body is surrounded by an indi- vidual sheath of circu- larly-disposed bundles, which, in the mid-line, takes part in forming the pectinate septum ; in other places the sheaths contribute the trabecular belonging to the enclosed erectile tissue. The trabeculae spring from all parts of the in- vesting fibrous tunics, including the septum, and pass inward, join- ing with their fellows on all sides to form a frame- work, the basis of the cavernous tissue, which occupies the entire cav- ernous body. While the trabeculae are stouter and larger near the periphery than in the centre, the included spaces, on the contrary, are larger near the middle and smaller at the circumference of the cavernous bodies ; to- wards the anterior end of the penis the spaces become gen- erally larger. In addition to the white fibrous tissue com- posing their principal part, the trabeculae contain elastic fibres and unstriped muscles, to- gether with the blood-vessels which the larger bands sup- port. The interspaces of this spongy structure are cavern- ous venous channels, which form an intercommunicating system of canals throughout the cav- ernous body. These spaces, lined with endothelium, and communi- cating on the one hand with the arteries and on the other with Section of penis of child near end : a, corpora cavernosa ; b, fibrous envelope of same ; c, imperfect septum ; d, corpus spongiosum ; e, urethra ; f, sebaceous glands ; g, epithelium of skin ; i, that lining the sac of prepuce ; k, section of latter; k, blood-vessels. Fig. 262. Section of erectile tissue of human penis : v, blood- spaces lined with endothelium ; t, fibrous trabeculae containing bundles of non-striped muscle (m) cut in various directions ; b, blood-vessels. 2i8 NORMAL HISTOLOGY. the veins, during erection become enormously distended, with a cor- responding reduction in the thickness of the intervening trabeculae. The corpus spongiosum in its structure resembles closely the cavernous bodies, being limited by a fibrous tunic from which spring the trabeculae of the cavernous tissue enclosing the venous spaces. The fibrous envelope is less developed than in the case of the cavernous bodies, while the proportion of elastic fibres is greater, peculiarities resulting in less unyielding rigidity in this part of the penis during erection. The fibrous trabeculae of the spongy body are thinner but more uniform in diameter, and the enclosed spaces possess greater similarity in size, although somewhat smaller than the corresponding channels of the corpora cavernosa ; their long axis generally coincides with that of the penis. The erectile tissue of the corpus spongiosum is continued into the glans, the spaces, how- ever, becoming somewhat reduced and provided with finer trabeculae. Immediately around the urethra a zone of condensed fibrous tissue intermingled with a quantity of unstriped muscle occurs, in addition to which a small amount of muscular tissue frequently exists within the fibrous tunic of the spongy body, as well as within the larger trabeculae. The smaller divisions of the arteries of the cavernous bodies, branches of the internal pudic, are supported by the larger bands of fibrous tissue ; from these situations the arteries pass into the capil- lary vessels, which, as a rule, communicate with the blood-spaces of the erectile tissue ; these spaces, in turn, are drained by the venous radicles, which empty into veins escaping at the roots of the penis or into the dorsal vein. Not all the capillaries, however, open into the cavernous spaces, since those destined for the nutrition of the tissues at once terminate in the veins, thus establishing a direct cir- culation, which forms the chief course of the blood during the passive condition of the penis. As a compensative provision for the great expansion of the trabeculae during erection, the arterioles are often so long that they present marked tortuosity, sometimes protruding as twists and loops into the undistended cavernous spaces ; in recog- nition of this peculiarity these vessels have been named the helicine arteries. In addition to the usual channel of the blood into the spaces by means of the capillary vessels, a direct communication exists between the arterioles and the larger spaces at the circumference of the cavern- ous bodies (Langer). The arrangement of the vascular supply of the corpus spongiosium and of the glans is identical with that above described, all the blood, however, being conveyed into the spaces through the capillaries. The masses of erectile tissue, enclosed within their respective THE MALE REPRODUCTIVE ORGANS. 2IQ sheaths, are enveloped in the general areolar tissue supporting the larger blood-vessels, nerves, and lymphatics, the whole being covered in by the investing integument. The skin of the penis is attached over its body by loose subcutaneous tissue, allowing of free move- ment and great distention ; it is distinguished by its dark color, thin- ness, freedom from fat, and, throughout the greater part of its ex- tent, absence of hairs. At the margin of the prepuce the skin as- sumes the character of a true mucous membrane, becoming delicate, rosy, and moist ; the base of the glans is generously supplied with modified sebaceous follicles, the glands of Tyson, sometimes called glandulae odoriferse, on account of their peculiar secretion ; par- tially inspissated accumulations of the latter, together with abraded epithelial scales, constitute the smegma. Upon the glans the in- tegument is very intimately and immovably united to the fibrous tunic of the spongy tissue, and contains large papillae in which rich vascular loops and special nerve-endings are situated; the skin in this situation is free from glands. The lymphatics of the penis consist of a superficial and a deep set : the former extends beneath the integument as a subcutaneous net-work, whose principal vessels accompany the larger blood-vessels in their course and terminate in the superficial inguinal glands, while the latter passes from the cavernous and spongy bodies, along with the deep veins, to the deep lymphatic glands within the pelvis. The lymphatics begin in the interfascicular clefts within the larger trabecular and the dense fibrous laminae which constitute the sheaths of the erectile masses ; delicate radicles continue the lymph-channels from the clefts to the larger lymphatic vessels. The nerves of the penis include trunks derived both from the cerebro-spinal and from the sympathetic system, those from the latter being contributed by the hypogastric plexus ; the sympathetic fibres are distributed entirely to the erectile tissue of the cavernous and spongy bodies. The sensory and motor nerves are ob- tained from the dorsal and superficial perineal branches of the pudic nerve, and terminate within the skin and the mucous membrane. Special nerve-endings, represented by numerous examples of the simple and compound genital corpuscles, as well as by the cor- puscles of Vater, are found in the integument of the glans and of other parts of the penis : the structure of these peculiar bodies has been considered in Chapter VI. THE PROSTATE GLAND. The prostate body is a compound tubular gland. The outer surface of the organ is invested by a stout fibrous covering, the continuation of the contiguous fascia, beneath which lies an 220 NORMAL HISTOLOGY. Fig. 263. inner envelope of involuntary muscle. From the latter muscu- lar septa penetrate in all directions between the acini of glandular tissue ; immediately surrounding the urethra a thick muscular layer also exists. The prostatic acini may be regarded as highly developed ure- thral glands, which they closely resemble, opening by a dozen or more ducts on the free sur- face of the urethra. Of these ducts two of especial size empty on either side of the urethral crest, and, repeatedly subdividing, communicate with the numerous closely - packed acini constituting the cen- tral lobe. The other di- visions of the gland are simpler in structure, since they contain tubular al- veoli, much less closely placed, which open into a slightly wavy duct. The epithelium lining the alveoli is short colum- nar in character, and fre- quently possesses more than a single row of cells, smaller spherical or pyri- form elements filling up the interstices between the outer ends oi the somewhat tapering cells next the lumen. The nuclei of the epithelial elements are situated eccentrically, lying nearer the ends of the cells directed towards the basement-mem- brane. These cells in elderly subjects not infrequently contain pigment. In addition to the fibrous and elastic connective tissue among the acini of the gland, bundles of involuntary muscle pass in all di- rections between the alveoli, and in many places constitute almost the entire tissue separating the adjacent acini. While present in all parts of the gland, the quantity of muscle varies in different parts of the organ ; it is poorest in the central lobe, where the acini are best developed, and richest in the upper part of the posterior post-ure- thral division and in the extreme fore part of the organ. In the low- est part of the posterior segment the involuntary muscle is supple- Section of human prostate, exhibiting general disposition of acini : a, fibrous envelope ; b, groups of tubular acini ; c, sections of prostatic ducts ; e, interacinous fibro-mus- cular tissue. THE MALE REPRODUCTIVE ORGANS. 221 merited by connective tissue in forming the interalveolar partitions. The layer of involuntary muscle surrounding the urethra is continu- ous behind with the vesical sphincter, and in front with the muscular envelope of the membranous portion of the canal. On either side of the urethral crest, which occupies the posterior surface of the prostatic portion, a depression marks the position of the prostatic sinus, into which open the orifices of the twelve to twenty prostatic ducts. These recesses are lined with a continuation of the stratified squamous epithelium which covers the adjacent urethral mucous membrane ; these cells, however, are soon replaced Fig. 264. ■?;■;. '■^toJ^^PI ^t^tiSs&(>£ J Section of human prostat: more highly magnified : a, some of the tubular acini lined with columnar cells ; L, muscular tissue of the intertubular septa. tvithin the ducts by others of the columnar type. As has already been pointed out, the sinus pocularis, or uterus masculinus, occupying the anterior part of the urethral crest, is to be regarded as homologous with the cavity of the vagina and the uterus, the layer of involuntary muscle belonging to the especial wall of the divertic- ulum corresponding to the uterine muscular tissue, while the small tubular glands present within the mucous membrane lining the sinus are the homologues of those of the uterus. The prostate itself, which is developed as a thickening of the urinary tract, cannot be regarded in any sense as homologous with the uterus, notwithstand- ing the apparently close relations with the sinus pocularis, since these relations are secondary and attained in the course of its subsequent growth. The blood-vessels of the prostate gland, branches of the adjacent vesical, hemorrhoidal, and pudic arteries, pass into the interior of the organ within the larger connective-tissue septa, where they break into 222 NORMAL HISTOLOGY. smaller twigs, which follow the ducts into the lobules, the capillary vessels then forming net-works about the individual alveoli. The veins on emerging from the deeper parts of the gland form a rich plexus within the fibrous envelope about the base and sides of the organ. The lymphatics originate within the connective-tissue septa as interfascicular clefts ; these unite with definite channels, which, in turn, form the larger lymphatic trunks accompanying the veins in their course to the neighboring deep lymph-glands. The nerves, derived principally from the hypogastric plexus, are composed of both medullated and non-medullated fibres, and pass along the stouter connective-tissue trabecular towards the glandular compartments ; their ultimate mode of termination is still uncertain. Corpuscles of Vater have also been observed along the course of the more superficial nerve-trunks. The secretion of the prostate gland — the prostatic fluid — is a thin, opalescent, slightly acid liquid, usually containing epithelial cells and granules. The dilution of the secretion of the testicle seems to be an important use of this fluid ; and when so mixed, on standing for some time the thin rhombic prostatic or Charcot's crystals make their appearance. Within the ducts or acini of the prostate gland additional small, irregularly round, laminated bodies, the prostatic concretions, often occur ; these are constant in advanced age, but they are found often also in young subjects ; these accumulations seem to be albumino- calcareous in nature and present a concentric lamination. THE GLANDS OF COWPER. Cowper's glands are two small racemose structures, whose rounded, somewhat flattened masses, 10-13 mm. in diameter, lie be- neath the anterior part of the membranous urethra. Each gland is composed of several small lobes, which pour out their secretion through the long excretory duct into the posterior part of the bulbous portion of the urethra, where a minute orifice marks the termination of the tube. The lobules composing the gland are held together, as well as enveloped, by a common investment of fibrous connective tissue containing some involuntary muscle. The acini are occupied by clear low cylindrical cells, resembling in character and in secretion those of a mucous gland. The epithe- lium lining the small ducts, into which the acini directly open, consists of elements cuboidal in form ; these cells are gradually replaced by taller columnar ones as the urethra is approached. In addition to the epithelium and delicate connective tissue, the walls of the ducts are strengthened by bundles of unstriped muscle. THE MALE REPRODUCTIVE ORGANS. 22\ Cowper's glands secrete a clear, viscid fluid, regarding the use of which little is known with certainty. The blood-vessels supplying Cowper's glands, derived usually as branches of the artery of the bulb, pass between the lobules, in company with the ducts, supported by the intervening connective tissue ; the capillaries form net-works around the individual acini. Lymph-spaces occur within the fibrous envelope and within the larger masses of connective tissue penetrating the organ. The nerves are branches from the pudic nerve : regarding their termination little is definitely known. 224 NORMAL HISTOLOGY. CHAPTER XIII. THE FEMALE REPRODUCTIVE ORGANS. THE OVARY. The ovary is attached to the posterior surface of the broad liga- ment along its shorter straight border, the sides and convex edge of its flattened oval mass being invested by the serous covering contin- uous with the peritoneum of the adjacent surfaces. The serous membrane reflected over the organ is modified both in appearance and in structure, since the usual shining smoothness of its surface is replaced by dulness, and the flat endothelial plates are supplanted Fig. 265. I lai Section of ovary of cat : C, cortex containing peripheral zone of Graafian follicles (g) in various stages of development ; c, well-advanced follicle ex- hibiting ovum (o), discus proligerus (d), and membrana granulosa (in) ; c', c", other large follicles, from which ova are absent ; h, peripheral section of large follicle which membrana granulosa seemingly fills ; s, ovarian stroma; /.corpus luteum ; M, medulla containing many vascular channels (b). by the low columnar cells which constitute the germinal epithelium. The transition of the latter into the usual peritoneal covering is indi- cated by a distinct demarcation around the attachment of the ovary. The ovary is divided into two parts, the cortex and the medulla, the boundaries of which are somewhat conventional and by no means sharply defined. The cortex includes the peripheral zone, contain- ing the Graafian follicles and the ova, and occupies approximately the outer third of the organ, while the medulla embraces the re- THE FEMALE REPRODUCTIVE ORGANS. 22$ maining central portions of the ovary, in which the blood-vessels are conspicuous constituents. The bulk of the organ consists principally of the stroma, together with the contained blood-vessels and the Graafian follicles. The ovarian stroma is a peculiar form of connective tissue dis- tinguished by the great number of its spindle-cells, which, while dis- tributed through all parts of the organ, are especially closely packed in the cortex, particularly near the periphery. The cortical stroma, arranged in variously-directed bundles, is greatly condensed immediately beneath the germinal epithelium, the zone of condensed tissue appear- ing as a distinct peripheral layer, FlG- 266- the so-called tunica albuginea ; the latter, however, does not rep- resent an independent structure, as does the sheath bearing the same name in the testicle, but only a peripheral band of the stroma of especial density. The most important constit- uents of the cortex are the Graafian follicles, which are exclusively limited to this part of the ovary, where they occur in all stages of development. The youngest and least matured Graafian follicles are plentifully scattered through the outer part of the cortex, where in many ani- mals, as the cat and the rabbit, they form almost a complete zone. The most immature fol- licle consists of the ovum sur- rounded by a single layer of flat- tened cells, the progenitors of the membrana granulosa, outside of which lie the cells of the general stroma, without the intervention of a special limiting membrane. Among the immature follicles are others in various stages of more advanced development, in which the ovum is embraced by two or more rows of polygonal cells ; around such ova the stroma is con- centrically disposed, a condition foreshadowing the membrana gran- ulosa and the theca of later stages. The cells which surround the ovum by their division give rise to the numerous elements lining the follicle; they were originally derived from the germinal epithelium 15 Section of human ovary, including cortex : a, germinal epithelium of free surface ; b, tunica albuginea; c, peripheral stroma containing im- mature Graafian follicles (d) ; e, well-advanced follicle from whose wall membrana granulosa has partially separated ; f, cavity of liquor folliculi ; g, ovum surrounded by cell-mass con- stituting discus proligerus. 226 NORMAL HISTOLOGY. 'V ^/- k % % d. as cylindrical masses which penetrate the stroma and undergo prolif- eration. With the increase in size which accompanies their devel- opment the Graafian Fig. 267. follicles pass towards the inner limits of the cortex bordering on the me- dulla, where they un- dergo further enlarge- ment ; after a time their diameter includes al- most the entire cortex, and extends from the medulla to the surface of the ovary. Subse- quently the position of the follicle becomes evi- dent as a distinct pro- jection on the free surface, marking the point at which the final rupture of the sac and the escape of the ovum take place. Such dis- charge usually coincides with the phenomena at- tending menstruation. The mature Graaf- ian follicles appear as clear vesicles, 4-8 mm. in diameter, and, on section, exhibit a char- acteristic arrangement. The follicle is defined from the surrounding tissue by a condensed layer of stroma, which forms a sheath, the theca folliculi ; this envelope is composed of two layers, an outer tunica fibrosa, containing fibrous connective tissue and coarser blood-vessels, and an inner tunica propria, rich in cells, small blood-vessels, and capillaries. Within the theca follows the mem- brana granulosa, consisting of many layers of small polyhedral epithelial cells, the descendants of the single row of original cells contained within the young follicle ; at one point the membrana granulosa presents a thickening, which is continued as a zone of cells immediately surrounding the ovum ; this constitutes the discus proligerus, which remains in contact with the ovum after its escape. The cells of the discus which lie next the ovum are placed vertically ':•>•- ."- •"•.■;• .-■•,'-■ '•.•;v::.^V<".*V,';/ <—■-«..».--_ ^- •„.-—.'» > <*. - ► <■ ^ Section of cortex of cat's ovary, exhibiting large Graafian folli- cle : a, peripheral zone of condensed stroma ; b, groups of im- mature follicles; c, theca of follicle; d, membrana granulosa; e, discus proligerus ; /, zona pellucida ; g, vitellus ; h, germinal vesicle ; ;', germinal spot ; k, cavity of liquor folliculi. THE FEMALE REPRODUCTIVE ORGANS. 227 Fig. 26S. to its surface, forming a radial zone, the corona radiata. The interior of the follicle is occupied by an albuminous fluid, the liquor folliculi, derived probably as an exudate from the blood- vessels of the theca, as well as from the breaking down of some of the central cells of the follicle. Within the discus proligerus lies the ovum, a spherical body about .2 mm. in diameter, enclosed within a distinct membrane, the zona pellucida, which presents a delicate radial striation. These mark- ings are regarded by many as due to the presence of fine canals, which may facilitate the access of fluids and possibly, also, of the spermatozoa to the contained cell. The zona pellucida is a protecting membrane, derived from the cells of the surrounding discus proligerus, and does not, strictly considered, constitute a part of the ovum proper, since it lies outside of the true cell- wall, the vitelline membrane. The protoplasm of the ovum, or vitellus, occupies almost the entire area within the zona pellu- cida, and is limited by the delicate and inconspicuous vitelline mem- brane, which closely approxi- mates the inner surface of the zona pellucida. The protoplasm of the ovum is modified by the presence of numberless particles of fatty matter which lie embedded within the albuminous protoplasm proper. The germinal vesicle, corresponding to the nucleus of the ovum, is situated eccentrically, limited by a distinct membrane, and contains the germinal spot or nucleolus. Of the parts of the ovum, the germinal vesicle is the most important, since in it, as in the nucleus of cells in general, are inaugurated the important changes attendant upon the phenomena of cell division. The threads of chromatin form a loose, irregular net-work throughout the germinal vesicle, the interspaces of which are filled with a substance representing the nuclear juice. While each Graafian follicle contains, as a rule, but a single ovum, exceptions are observed occasionally where two, and even three, ova are found within the same vesicle. The formation of new follicles continues for only a short time after birth ; ovisacs are then most numerous, the entire number contained within the two ovaries of the child being estimated at over Ovum from ovary of cat : d, innermost cells of discus proligerus, between which processes from zona pellucida (z) extend ; 111, vitelline membrane ; z>, vitellus ; g, germinal vesicle ; s, germinal spot. 228 NORMAL HISTOLOGY. Fig. 269. seventy thousand. In view of the unquestionably large number of follicles in very young ovaries, and the relatively small proportion of ova which reach maturity, the degeneration of many follicles, after attaining a certain development, seems certain ; the atrophic remains of such degenerating Graafian vesicles, continually encoun- tered, point conclusively to the fate of a large contingent. The medulla contrasts with the cortex by its looser structure and the number and the size of its vascular canals. The stroma of this portion of the ovary more nearly resembles ordinary connective tissue, the peculiar spindle-cells occur- ring much less abundantly, while the fibrous tissue forms an important con- stituent of the supporting matrix. A considerable amount of involuntary muscle is mixed throughout the fibrous bundles separating and surrounding the numerous blood-vessels. The latter are largely venous, the large sinus- like veins being very conspicuous objects in the medulla. In addition to the elements already described, groups of polygonal inter- stitial cells occur between the bun- dles of stroma-tissue, especially in the medulla, but also within the cortex. These cells are epithelial in character, and represent the remains of the cylindrical cell-masses which grow from the 'Wolffian body into the tissue of the primitive ovary. In some animals the interstitial cells are much more numerous than in the human ovary ; in the rabbit these cells constitute an important part of the stroma of the organ. On the escape of the ovum, the ruptured and partly-collapsed follicle becomes filled with the blood poured out from the torn vessels of the walls of the vesicle ; subsequent changes lead to the conver- sion of the follicle into a corpus luteum. The production of these characteristic bodies depends principally upon the proliferation of the walls of the follicle, in some cases the interstitial cells being in- volved ; the process results in the "plication of the remains of the envelope, as well as in the gradual formation of a mass of polyhedral cells, between which the capillaries derived from the vessels of the follicle extend ; the enclosed area corresponds to the remains of the cavity of the follicle, and is for a time occupied with the yellowish mass composed of the degenerating blood-clot and the membrana granulosa ; these tissues are replaced by a shrunken fibrous area, which is later invaded by the proliferating peripheral cells. When Section of medulla of human ovary : v, vascular canals surrounded by the stroma-cells and the connective tissue; iu, group of interstitial cells derived from Wolffian tubules. THE FEMALE REPRODUCTIVE ORGANS. 229 Fig. 270. 'viif Portion of well-developed corpus luteum from ovary of rabbit : a, polyhedral cells separated by vascular connective tissue ; 6, blood-vessel. best developed, the corpus luteum is sharply defined from the sur- rounding stroma, and in appearance recalls somewhat the liver, the polygonal cells being surrounded by capillary blood-vessels. Subse- quent changes lead to retrogression and disappearance of the cells, the entire mass becoming fibrous and cicatricial in character, but remain- ing visible for many months as an obscure, shrunken, irregularly- plicated body in the midst of the cortical tissues. While the forma- tion of a corpus luteum follows the discharge of every mature ovum, when such escape is followed by pregnancy the yellow body be- comes exceptionally large and well developed, presenting a large round mass, 2-3 cm. in diameter, which retains its distinctive character much more tenaciously than the corpus of ordinary menstruation. These differences led to the distinction of the corpus luteum of pregnancy as the true yellow body as contrasted with the ordinary or false ; the former large symmetri- cally-developed body has been regarded as positive proof of preg- nancy, a conclusion, however, which the repeated observation of identical bodies in the ovaries of virgins by no means upholds : the evidence afforded by such corpora lutea should be regarded as cor- roborative rather than as positive. The blood-vessels of the ovary enter at the hilus along the attached border. They directly penetrate to the medulla, smaller twigs passing to supply the cortex and the Graafian vesicles. Each of these sacs is surrounded by a net-work of vessels, especially con- spicuous in the larger follicles. The venous vessels within the medulla are of large size, the channels resembling sinuses in their tortuous course and thin walls. The lymphatics are numerous within the medulla, while their terminal radicles have been traced within the cortex to the cleft- like spaces within the fibrous tunic of the walls of the larger follicles. The nerves of the ovary include medullated and pale fibres, repre- senting both the cerebro-spinal and the sympathetic system. After passing into the interior of the organ, fine twigs enter the cortex, where they have been traced into the envelope of the larger Graafian follicles. 230 NORMAL HISTOLOGY. THE PAROVARIUM. The parovarium, the epobphoron, or the organ of Rosen- muller, consists of a group of tubular structures lying transversely within the broad ligament, between the ovary and the oviduct ; the short vertical tubules lie irregularly parallel or converge somewhat at their ovarian ends, while their opposite extremities are connected with a longitudinal head-tube of larger diameter, which extends downward often for some distance within the broad ligament. The tubules are lined by low columnar epithelial cells, the represen- tatives of the elements clothing the embryonic canals. The parova- rium represents the partially-obliterated re- Fig. 271. mains of parts of the Wolffian body; the transverse canals correspond to the tubules of the body, while the head-tube is identical with the upper part of the Wolffian duct ; when this latter canal persists throughout the greater part of its original extent it constitutes ' * W'/lfiffi Gartner's duct, the homologue of the vas W w * A deferens. Other foetal remains are sometimes Portion of tubules of par- encountered as rudimentary tubules em- ovarium: it), canals lirnd J with cuboidai epithelium bedded within the broad ligament nearer the embedded within surround- ^^ ^^ ^ parovarium . these struCtUreS ing connective tissue (s). L constitute the paroophoron, and represent the atrophic transverse tubules of the lower portion of the Wolffian body, being homologous with the paradidymis in the male. The closed tubules of the paroophoron are lined by low columnar epi- thelium, and are often occluded by the partially-shed cells. The stalked hydatid of Morgagni frequently forms a conspicuous appendage to the ovary. This pedunculated vesicle represents the remains of the duct of the pronephros, and is common to both sexes ; low columnar or cuboidai epithelium forms the lining of its dilated sac and stalk as far as pervious. THE OVIDUCT. The oviduct, or Fallopian tube, consists of three coats, — an inner mucous, a middle muscular, and an outer serous. The mucous membrane of the oviduct is thrown into longitu- dinal folds, which correspond in their amplitude to the general variation in the size of the tube, being low towards the small uterine end and increasing in height and in complexity on approaching the expanded fimbriated extremity of the canal. On transverse section through the smaller portions of the tube, the longitudinal folds give to the lumen a generally stellate outline, the complexity of the figure 231 addition mucous THE FEMALE REPRODUCTIVE ORGANS. increasing as the sections approach the fimbria, owing to the of numerous secondary plications which there exist. The membrane of the . . r Fig. 272. oviduct consists of a nbro-elastic tunica propria and a single layer of columnar ciliated epithelial cells, whose ciliary wave sweeps from the fimbria towards the uterine end of the tube. All parts of the canal are lined with ciliated cells, in- cluding the inner sur- face of its expanded ovarian end ; at the free edge of the lat- ter the ciliated co- lumnar cells of the tubal surface are re- placed by the flat endothelial plates of the peritoneum which invests the outer aspect of the tube. The outer layers of the tubal mucous membrane contain scattered longitudinal bundles of involuntary muscle, which represent a poorly-developed muscularis mucosae ; outside these a thin layer of fibrous connective tissue answers to a submucosa, and contains the larger blood-vessels and the lymphatics. Glands are absent within the mucous membrane of the oviduct. The muscular tunic consists of a principal inner circular layer of non-striped muscle and a slightly developed outer layer consist- ing of an incomplete zone of longitudinal bundles. The serous coat consists of the nbro-elastic stroma and the endo- thelial plates of the general peritoneum. The blood-vessels of the oviduct are branches from the ovarian and uterine arteries and the corresponding veins ; the arteries pos- sess a tortuous course and extend along the bases of the folds of the mucosa ; from these vessels smaller twigs arise, which break up into the capillary net-works destined for the various coats. The larger lymphatics accompany the blood-vessels and commu- nicate with the lymph-spaces within the deeper layers of the mucosa. The nerves, derived from the ovarian and uterine plexuses, con- Section of human oviduct near fimbria ; a, lumen of tube en- croached upon by complicated folds ; b, layer of ciliated columnar epithelium , c, fibrous tissue supporting plications ; d, circular layer of muscle ; e, longitudinal bundles of muscle-cells \f, external fibrous tissue. 232 NORMAL HISTOLOGY. sist of both medullated and pale fibres ; the principal trunks run in company with the blood-vessels as far as the mucous membrane ; their ultimate distribution and mode of termination are still un- certain. THE UTERUS. The uterus being the fused morphological continuations of the oviducts, similarity approaching identity in the structure of the two segments of the original tube is to be expected ; this resemblance, in Fig Section of human uterus, including mucosa (a) and adjacent muscular tissue (i) ; c, epithelium of free surface and tubular uterine glands (d) ; f, deepest layer of mucosa, containing fundi of glands ; h, strands of non-striped muscle penetrating within the mucosa. fact, exists. The uterus is composed of a mucous, a muscular, and a serous coat, modified to meet the demands of special functions. The mucosa, 1-2 mm. in thickness, consists of a tunica propria formed of delicate bundles of fibrous tissue, intermingled with some elastic fibres and many leucocytes, and the epithelium. The latter is a single layer of ciliated columnar cells, whose ciliary current is directed towards the cervix. The tunica propria contains numer- ous slightly wavy tubular uterine glands, limited by a delicate basement-membrane and lined by an extension of the ciliated colum- nar epithelium of the adjacent mucous surface. Since a submucosa is wanting in the uterine wall, the blind and often forked extremities of the glands abut directly upon the muscular tissue. The mucosa of the uterine cervix differs materially from that of the body of the organ, being thicker and firmer, and within the lower third beset with minute papillae covered with stratified squa- mous epithelium. In the upper half or two-thirds of the cervix THE FEMALE REPRODUCTIVE ORGANS. 2%\ the epithelium is ciliated columnar, similar to that of the body of the organ. In addition to the scattered tubular follicles, the representa- tives of the usual uterine glands, numerous short mucous crypts, with expanded blind extremities, lie embedded within the mucosa ; these pour out the thick glairy mucous secretion which is character- istic of the glands of the cervix. Not infrequently retention of the secretion takes place in some of these mucous follicles, the glands then undergoing transformation into greatly-distended cysts, the ovula Nabothi; these appear as translucent yellowish vesicles em- bedded within the mucosa and readily seen by the unaided eye. In Fig. 274. Section of uterus through lower segment of cervix from child : a, vaginal surface covered with squamous epithelium ; b, c, d, e, variously-disposed bundles of non-striped muscle ; _/", g, blood-ves- sels : h, fibrous tunica propria covered by columnar epithelium (1) ; k, folds of mucosa projecting within lumen of cana! (C). the absence of glands the mucous membrane of the lowest part of the cervix still further resembles that of the adjacent vaginal surface. The exterior of the projecting portion of the cervix is covered with an extension of the vaginal mucous membrane. With the recurrence of each menstrual period the uterine mucous membrane under- goes changes destined to prepare this surface as a favorable place for the reception and retention of the ovum during gestation in the event of impregnation. Greatly-increased vascularity, softening and thickening of the mucous membrane, with increase in the length of the glands and in the number of the leucocytes, are among the changes then taking place. Should impregnation occur, these altera- 2?a NORMAL HISTOLOGY. tions become more pronounced and result in the formation of the decidua. When incidental merely to the phenomena of menstrua- tion, the flow of blood following the rupture of the over-distended capillaries is accompanied by a degeneration of the inner portions of the uterine mucous membrane, including the glands, which are cast off as far as the deepest layers next the muscular tissue ; from this external zone of remaining unimpaired tissue the regeneration of the mucous membrane proceeds. The muscular coat of the uterus consists of bundles of involun- tary muscle separated by bands of connective tissue and surrounding numerous vascular, especially venous, channels. While more or less irregularly arranged, the muscular tissue is disposed in three general strata, an inner, a middle, and an outer layer. The inner layer, upon which directly rests the mucosa, is often regarded as belonging to the mucous membrane, being in fact the hypertrophied muscu- laris mucosae ; it is composed principally of irregular longitudinal or oblique bundles, and contributes about 1.5 mm. of the entire muscular tunic. The middle layer is the most robust, forming the greater part of the muscular wall, consisting chiefly of bundles having a general circular disposition. This layer is also distinguished by the numerous large venous channels enclosed between its bundles ; hence the name, stratum vasculare. The outer layer of muscle, about . 1 mm. in thickness, is made up partly of circular and partly of longitudinal bundles, the latter predominating and being closely related to the overlying serous coat. Many bundles of this outer layer pass obliquely across the fundus and into the broad ligament; some of these enter the round ligaments and accompany the areolar tissue and the blood-vessels composing these structures towards the groin, while others extend along the oviducts ; strong muscular bands also run from the uterus into the ovarian ligaments. The muscu- lature of the cervix is characterized by greater regularity in its arrangement, a distinct inner longitudinal, a middle circular, and an outer longitudinal layer being present. During pregnancy the muscular tissue of the uterus becomes enormously increased, the augmentation depending not only upon the excessive size of the already existing individual muscle-cells, but also upon the appear- ance of additional new muscle-cells. The serous coat of the uterus is composed of the usual constitu- ents of the peritoneum, the fibro-elastic stroma being covered by the outer sheet of endothelium. The blood-vessels supplying the uterus are very numerous. The arteries, branches from the ovarian and the uterine, pass beneath the serous coat into the muscular tunic, where many twigs are given off for distribution to the tissue of this layer ; the capillary vessels pass THE FEMALE REPRODUCTIVE ORGANS. 2^ between and into the muscle-bundles supported by the intervening connective tissue ; the terminal branches reach the mucosa, where they break up into capillaries, which form net-works around the uterine glands and beneath the free surface. In addition to the trunks accompanying the principal arteries, the veins contribute numerous channels to the middle muscular coat, in which they form a plexiform system of thin-walled sinus-like blood-spaces within the intermuscular connective tissue. The lymphatics are represented within the uterine mucosa by a wide-meshed net-work of canals within the deeper layers of the tunic, as well as by blind, slightly club-shaped branches and the interfas- cicular lymph-spaces. Within the muscular tunic lymphatic channels occur among the muscle-bundles, particularly of the middle layer ; these unite with the larger lymphatics lying within the subserous tissue. The nerves supplying the uterus are derived from the inferior hypogastric and the ovarian plexus, together with branches from the lower'sacral nerves ; they consist, therefore, of both medullated and non-medullated fibres : minute ganglia have been observed in con- nection with the latter. The larger trunks send many twigs to the muscular tissue ; the final termination of the branches passing into the mucosa is still undetermined. THE VAGINA. The walls of the vagina consist of a mucous membrane, a muscular coat, and a fibrous adventitia. The mucous membrane is covered with a thick stratified squamous epithelium, which rests upon a tunica propria rich in elastic fibres and leucocytes and beset with numerous papillae ; the latter, when small, do not impress the free surface, the epithelium presenting an uninterrupted plane. Larger elevations, however, occur as the prominent folds constituting the rugae, which include within their structure not only the tissues of the mucosa but also bundles of involuntary muscle and numerous large veins, these latter bestowing upon the parts somewhat the character of cavernous tissue. Leucocytes are plentifully scattered within the mucosa of the entire vaginal tract, but in certain places, particularly in the anterior wall near the orifice of the vagina, these cells are very nu- merous, and give the mucosa the appearance of adenoid tissue ; solitary lymph-follicles also exist. True glands are not found in the vaginal mucous membrane ; the watery acid secretion bathing its surface seems to be the product of the general mucosa. The hymen consists of a crescentic or circular duplicature of the mucous mem- brane strengthened by an intervening layer of fibrous tissue. 2^5 NORMAL HISTOLOGY. The deepest part of the mucosa is continuous with the loosely- woven, highly-vascular submucous tissue , outside the latter follows the muscular tunic, composed of an inner circular and an outer longitudinal stratum of involuntary muscle. These layers are not sharply defined, but are blended with one another by numerous oblique bundles. The outer adventitious coat consists of a dense fibrous tunic, rich in elastic tissue, which contributes greatly to the strength of the vaginal walls : this fibrous coat is best developed in the anterior wall of the canal, where it closely unites the vagina to the bladder, and encloses within its firm, compact mass the urethra. The blood-vessels of the vagina are very numerous ; the larger twigs break up within the submucous tissue into smaller vessels, which pass to supply the muscular coat and the mucous membrane. Those entering the latter terminate in capillary loops lying beneath the epithelium and within the papillae. The veins correspond with the larger arteries, but, in addition, form dense plexiform net- works beneath the serous coat. Around the entrance of the vagina the number and size of the venous channels give the submucous coat the character of cavernous tissue. The lymphatics form net-works within the mucosa and muscularis, which unite with the larger lymph-channels within the adventitia. The nerves supplying the vagina, derived from the hypogastric plexus and from the sacral and pudic nerves, consist of both pale and medullated fibres. Numerous microscopic ganglia occur in con- nection with the sympathetic fibres. Special end-bulbs, or the genital corpuscles of Krause, exist within the vaginal mucosa. THE GENITALIA. The labia majora consist of the folded integument enclosing an abundance of adipose tissue, together with blood-vessels, nerves, glands, and bundles of involuntary muscle ; their outer surface corresponds to the usual integument of the vicinity, while internally they assume partly the character of the adjacent mucous membrane. The median surfaces of the labia contain little fat, but, on the other hand, many bundles of elastic and unstriped muscular tissue. Sebaceous follicles and sweat-glands are numerous, but they are more plentiful on the outer than on the inner surface of the labia. Owing to the unusual quantity of pigment contained within the deeper layers of the epithelium, the labial integument is especially dark. The labia minora, or nymphae, include between their folds of mucous membrane vascular areolar tissue ; their external surfaces resemble somewhat in appearance the adjoining integument of the external labia, with which they are continuous. Vascular THE FEMALE REPRODUCTIVE ORGANS. 237 papillae and well-developed sebaceous follicles are common to both surfaces of the nymphae, but sweat-glands, hairs, and fat are wanting. The interior of the nymphae contains venous spaces in abundance, which, in connection with the unstriped muscle also present, produce a layer resembling erectile tissue. The blood- vessels of the labia majora are similar to those supplying the integu- ment ; in the nymphae the mucous surfaces are beset with vascular papillae, which contain the terminal capillary loops. The lymphatics consist of the interfibrillar lymph-clefts and the more definite channels which are present as small lymphatic vessels accompanying the larger blood-vessels from the areolar tissue. The nerves of the nymphae, derived from branches supplying the lower part of the vagina, include both medullated and pale fibres : numerous special end-bulbs, the genital corpuscles of Krause, represent the particular terminations. The clitoris largely repeats the structure of the corresponding male organ, subject, however, to the modifications incident to the feebler development of the parts. The glans possesses small and large papillae, which contain simple and compound arterial tufts, while some of the smaller elevations are occupied by the peculiar nervous end-bulbs or the genital corpuscles. Sebaceous follicles also surround the glans and are present in the outer layer of the prepuce ; on the glans itself they are almost wanting. The erectile tissue constituting the diminutive corpora cavernosa and the glans consists of the same elements as the corresponding structures of the penis. The mucous membrane lining the vestibule closely resembles that covering the inner surface of the nymphae, and is prolonged inward into the vagina and the urethra. A thick layer of stratified squa- mous epithelium rests upon a tunica propria containing bundles of elastic tissue, and many mucous follicles, the latter being espe- cially abundant in the vicinity of the urethral orifice. The submucous tissue around the vestibule and base of the nymphae is so generously supplied with intercommunicating venous channels that in many places the part assumes the characters of erectile tissue. The glands of Bartholin are two round or oval yellowish bodies, about 1 cm. in diameter, lying on either side of the lower part of the vagina. These structures are the homologues of Cowper's glands in the male ; they are racemose glands, composed of small groups of acini lined with clear mucous cells. Each gland is connected with the inner surface of the nymphae by a long slender duct lined with low cuboidal epithelium. The character of the secretion of these glands is muco-serous. The female urethra differs from the canal in the male in being 238 NORMAL HISTOLOGY. short, very dilatable, and of large size. Its walls consist of a mucosa, composed of fibrous tissue intermingled with many elastic fibres and containing large numbers of leucocytes, and an epithelium of the stratified squamous variety, continuous with the transitional epi- thelium of the bladder on the one hand and with the epithelium of the vestibule on the other. The mucous membrane of the urethra presents longitudinal folds, especially on the posterior wall, and con- tains many tubular mucous glands ; several of these, near the urethral orifice, are of large size. Near the vestibular end of the canal the mucosa contains so many leucocytes that the membrane resembles diffuse adenoid tissue. Outside the submucosa follows involuntary muscle, disposed as an inner thin longitudinal and an outer thick circular layer. Fig. 275. THE MAMMARY GLANDS. The mammary glands are usually described in connection with the female reproductive organs, although these structures are only modi- fied and specialized sebaceous integumentary glands ; strictly re- garded, the mammae, therefore, belong to the consideration of the skin. Each mamma consists of from fifteen to twenty distinct tubo- racemose glands or lobes, which are held together by connective tissue and united into a single hemispherical mass by adipose tissue, which fills all irregularities and interspaces between the divisions of the organ. Each lobe, supplied by its own excretory duct, is sub- divided by penetrating fibrous septa into lobules, which, in turn, are composed of groups of individual acini. The histological details of the secreting portions of the organ vary with the stages of its functional ac- tivity : the following de- scription applies to the active glands as seen during lactation. The acini, usually tu- bular or saccular in form, are grouped together to constitute the lobules ; limited by a distinct membrana propria, they are lined by a single layer of short columnar or polyhedral epithe- lial cells, whose protoplasm differs in appearance with the condition of secretion. At rest, these cells are uniformly granular ; as secre- Section of human mammary gland during lactation : a, a, sections of the large tubular acini which constitute almost the entire lobule; b, interlobular connective-tissue septa. THE FEMALE REPRODUCTIVE ORGANS. 23Q tion advances, their granular protoplasm becomes broken up and displaced by the accumulation of oil-globules within the cell ; these minute oil-drops exist at first as minute separate particles, which gradually increase in size, until finally they become confluent and form a single large globule, which occupies the greater part of the entire cell ; the nucleus in consequence is displaced towards the periphery, next the basement-membrane, where it lies embedded within the thin belt of protoplasm occupying the outer zone of the cell. During secretion the acini possess a comparatively wide lumen, since the epithelial layer forms but a narrow lining to the irregular spherical or tubular spaces. The cells within a single acinus often contain very unequal amounts of oil ; some of the elements are so loaded that the entire cell is occupied by the oil-drop, while, on the other hand, the neigh- boring cells may contain so little oil that the presence of the fatty particles is masked by the general protoplasm. Between the extremes all gra- dations may be found. Upon reaching a certain tension, the contained oil-globules, es- caping in the direction of least resistance, are discharged into the cavity of the acinus, where they, together with the gran- ular debris of old epithelial cells, are collected within an albuminous fluid and consti- tute the lactiferous secre- tion. The assumed destruction of the epithelial cells following the discharge of the oil-globules is improbable, since the cell then simply enters upon a period of rest and repair, during which its powers of secretion are recuperated. In the earliest stage of the activity of the mammary gland, when the flow of milk is first established, the acini, in many cases, still retain their primitive condition of solidity ; while the cells at the periphery remain as the secreting elements, those occupying the centre of the acinus undergo fatty degeneration, some become disintegrated, while others are cast off as masses which constitute the colostrum-corpuscles found in the milk during the first few days. The secretion accumulated within the comparatively large alveoli is carried off by the terminal branches of the ducts, whose walls consist of a basement-membrane and a single layer of low colum- Section of human mammary gland, including sev- eral acini (a) engaged in sluggish secretion of milk; £, epithelial elements containing oil-droplets ; c, inter- acinous connective tissue. 240 NORMAL HISTOLOGY. nar or flattened epithelium. The large excretory canals, the galactophorous ducts, each of which collects the secretion from an entire lobe, pass as distinct tubes to the nipple ; they possess walls of considerable thickness, composed of fibrous and elastic connective tissue, together with some unstriped muscle derived from the nipple. The lining epithelial cells are columnar to within a few millimetres of the external openings of ducts, where the epithelium becomes stratified and continuous with the epidermis. The fifteen to twenty excretory ducts, after a longer or shorter course, converge towards the areola, within whose area they undergo considerable dilatation to form the ampullae, which serve during lactation as temporary reservoirs for the milk. The nipple consists, in addition to the external covering of pig- mented and greatly wrinkled skin which is perforated at the tip by the openings of the excretory milk-ducts, of a central mass composed of the lactiferous canals and the blood-vessels embedded within the fibro-elastic tissue. A considerable amount of unstriped mus- cle exists, disposed as encircling and radiating fibres ; upon the contraction of this muscle, which responds to mechanical stimulus, the erectility of the nipple principally depends. The cutaneous papillae are supplied with numerous nerve-terminations, which insure a high degree of sensitiveness. The subcutaneous tissue of the nipple proper contains Fig. 277. no fat; around its base and over the areola elevations mark the orifices of the scat- tered groups of little racemose structures which constitute the glands of Mont- gomery. The in- tegument of the areola surrounding the base of the nipple usually possesses con- siderable pigment, the amount greatly in- creasing during preg- Section of human mammary gland undergoing retrogressive changes after lactation : a, sections of ducts ; b, atrophic acini ; c, fat-cells ; d, interlobular connective tissue. nancy ; large sweat- glands and numerous well-developed sebaceous follicles are also present within this area. The relative proportion of the glandular structure to the inter- vening connective tissue varies with the condition of functional activity THE FEMALE REPRODUCTIVE ORGANS. 2A1 of the organ. During lactation the secreting tissue predominates, and the septa are reduced to mere partitions ; before pregnancy has taken place the connective tissue and fat form the bulk of the organ, the glandular structures then being represented by the system of ducts and excretory tubes, since the acini are present only as small solid rudimentary cylindrical cell-masses. After lactation the secreting parts of the organ atrophy and beGome much less con- spicuous, some of the acini almost entirely disappearing, while con- nective tissue and fat constitute the greater part of the mamma. The termination of the period of sexual activity is followed by the permanent atrophy of the gland-tissue, which finally is almost complete, the entire mamma being then composed of connective tissue and fat, with scarcely a trace of the former conspicuous se- creting structures. The rudimentary breasts of children of both sexes, and of the adult male, contain principally connective tissue, in which excretory ducts, attached to small groups of immature acini, lie embedded. Under exceptional circumstances the male mammary gland may secrete true milk. The principal blood-vessels supplying the mammary glands run mostly in the superficial tissues somewhat radially towards the areola ; from these vessels on the anterior surface of the organ branches penetrate into the glandular mass and pass between the lobules, giving off twigs which break up into capillaries enclosing the alveoli. The cutaneous papillae are supplied with capillary tufts where not occupied by nervous structures. The vascular supply of the nipple, while generous, does not include cavernous tissue, the erectility of this part being due largely to the muscle. The lymphatics include the radicles enclosed within the fibrous septa of the gland, as well as a net-work of subcutaneous lymph- canals within the more superficial portions of the organ. The lymphatic vessels are closely related to the surrounding chain of lymphatic glands, as well as to those within the axilla. The nerves are distributed more richly to the superficial, cutaneous parts of the organ than to its secreting tissue. They are principally medullated fibres, those supplying the papillae of the nipple and the areola in many cases ending in special tactile corpuscles ; the nerves entering the base of the nipple often bear corpuscles of Vater. The deeper parts of the glands receive principally the pale fibres destined for the control of the blood-vessels, not, however, to the exclusion of medullated fibres ; ganglion-cells have also been ob- served in connection with the latter. Milk is composed microscopically of a clear fluid, the milk- plasma, in which numbers of small oil-globules, 2-5 ,a in diam- eter, together with the granular de*bris of disintegrated cells, are 16 242 NORMAL HISTOLOGY. oo oo; OO n°Oo Qov£9°y°o Human milk : A , usual appearance ; B, shortly after delivery ; a, large colos- trum-corpuscle ; b, small amceboid cells containing oil ; c, colostrum-corpuscles with few oil-droplets. suspended. These globules do not coalesce, owing to the probable presence of a delicate envelope of casein. The addition of acetic acid or of caustic potash destroys the envelope and liberates the oil-droplets, which then run together, forming ir- regular masses. Human milk is usu- ally alkaline. The milk secreted during the first few days after delivery contains large fatty granular - looking bodies known as colostrum - corpuscles ; these bodies probably represent the re- mains of a portion of the epithelial cells which at one time occupied the centre of the then solid acini, but which underwent fatty degeneration and partial destruction on the establishment of lactation. The development of the reproductive organs comprises the genesis of two distinct parts, the sexual glands and their excre- tory ducts. In order to understand the formation of the reproductive organs it is necessary to recall the condition of the foetal excretory structures prior to the appearance of the sexual glands, since the Wolffian body and its duct play important roles in the subsequent development of the generative tract. The Wolffian body consists essentially of a long tube, the Wolffian duct, which extends parallel with the ver- tebral axis throughout the lower part of the body-cavity, and of the transverse Wolffian Fig. 27q. tubules, which join the duct generally at right angles, so that the two parts of the Wolffian body are frequently compared to the back and the teeth of a comb. The tubules are tor- tuous, and bear close relations with tufts of convoluted capillary blood-vessels, much the same as the uriniferous tubules do in the Mal- pighian bodies of the kidney. Some time after the establishment of the Wolffian body and its duct, a second canal, the Miillerian duct, makes its appearance ; Section of rabbit embryo of ten and a half days, showing the Wolffian bodies and the early indifferent sexual glands; w, t, and >n, respectively duct, tubules, and Malpighian corpuscle of Wolffian body ; /, mesothelial surface of primary peritoneal cavity ; gt indifferent sexual glands. THE FEMALE REPRODUCTIVE ORGANS. 2AX this tube lies parallel and in close proximity with the Wolffian duct, its cephalic end opening into the body-cavity, while its lower extremity terminates at first within the cloaca and later within the uro-genital sinus. It is necessary further to distinguish three groups of the Wolffian tubules, since the fate of these portions of the fcetal organ varies ; these divisions are the anterior group, constituting the pro- nephros, the middle or sexual segment, and the posterior rudi- mentary tubules, which give rise to atrophic structures. The development of the sexual glands includes a primary indifferent and a later specialized stage. During the period when the Wolffian body Fig. 280. has attained its greatest growth there ap- '^^i^^^^^fesgssas^ pears on the ventro-mesial surface of the 'j. organ a localized thickening of the meso- s>c,'JP^W§3^<^^^^ thelial elements. This proliferation pro- duces an eminence, the earliest trace of the sexual gland. This for some time is in- Section of peripheral zone of in- different, since its appearance is identical diff«"« sexual gland ftommbb.t rr _ _ embryo: e, mesotheual cells con- ill the tWO Sexes. The indifferent Sex- stituting the later germinal epithe- ual glands soon exhibit two kinds of fum; '•f'm!a eI*mems ^rived a from proliferation of mesoihehum ; elements, the loosely-packed proliferated o, large primordial sexual ceils. small mesothelial elements and the sparingly-distributed much larger primordial sexual cells. In the male, the further changes within the sexual gland include extended proliferation of the early mesothelial elements and their grouping as epithelioid cylindrical masses, the sexual cords ; within the latter lie the large primordial sexual cells, their number, however, in the developing testicle being distinctly smaller than in the corre- sponding female organ. The sexual cords become the seminiferous tubules, remaining solid cylinders throughout fcetal life. The par- ticular fate of the large sexual cells is still uncertain. The surround- ing mesodermic tissue grows into the mesothelial mass and contributes the intertubular connective tissue as well as the denser portions of the framework represented by the tunica albuginea and the trabecular. The system of canals forming the connection between the testicle and the epididymis, including the vasa efferentia and the coni vasculosi, are derived from the tubules of the Wolffian body ; by the ingrowth of these canals into the embryonal testicle the isolated sexual gland is provided with excretory passages. Other remains of the lower tubules of the Wolffian body constitute the para- didymis. The main tube of the epididymis and the vas deferens are the direct representatives of the Wolffian duct. The Miillerian duct in the male is atrophic, since its extreme anterior and posterior parts alone persist ; these remain as the non- 244 NORMAL HISTOLOGY. stalked or sessile hydatid, in close relation with the epididymis, and as the short diverticulum opening into the prostatic portion of the urethra, the uterus masculinus or sinus pocularis, which is therefore the homologue of the uterus. In the female the indifferent sexual gland early exhibits a grouping of the mesothelial elements into cylindrical masses, the sexual co^ds, which in the ovary, however, retain a closer connection with the ger- minal mesothelium than do those of the testicle. Many groups of epithelial elements are disposed vertically to the free surface of the organ, and constitute the primary egg-tubes. In the ovary, as in the testicle, the sexual cords contain the large sexual cells, the latter being much more plentiful in the female than in the male gland. The ovarian stroma originates later as a secondary ingrowth of the surrounding mesoderm between the groups of sexual cells. The genetic relations between the embryonal ele- ments, particularly the large cells, and the ova and the follicular cells of the fully- formed ovary, are still indefi- nite. It may be assumed as established, however, that both these constituents of the later organ are derived from the cells constituting the sex- ual cords, and, therefore, in- directly from the ovarian mesothelium or primitive germinal epithelium. Whether the large sexual cells are the direct ancestors of the ova alone or contribute to the production of the follicular elements as well is uncertain, but it seems probable that the later ova are the immediate descendants especially of the large sexual cells. The passages providing for the escape of the product of the ovaries, the ova, are derived from the Mullerian ducts, their anterior seg- ments remaining distinct tubes, the oviducts, while their middle and posterior divisions become fused and form respectively the uterus and the vagina. The Wolffian body and its duct in the female are represented by rudimentary structures, the parovarium and the paroophoron. The horizontal head-tube of the former is the persistent anterior segment of the Wolffian duct, while the shorter vertical branches are the remains of the Wolffian tubules. The Section of ovary from very young kitten : a, ovarian mesothelium or germinal epithelium, containing large sexual cell (c) ; b, cylindrical epithelial masses consti- tuting egg-tubes ; d, developing stroma. THE FEMALE REPRODUCTIVE ORGANS. 245 presence of a number of the rudimentary canals which constitute the lower atrophic segment of the Wolffian body produces the obscure c Diagrams illustrating development of sexual organs. In all figures //', M, B, and G represent respectively Wolffian duct, Miillerian duct, bladder, and gut. A , indifferent type containing funda- mental parts: s, sexual gland; t, t' , I", Wolffian tubules constituting anterior (pronephros), middle (sexual), and posterior (rudimentary; groups; those of sexual division retain their communication with Wolffian duct. B, male type: T, testicle; e, e' , tubes of globus major derived from middle Wolffian tubules ; z>, tube of epididymis, the persistent Wolffian duct ; s, seminal vesicle ; /, para- didymis; ti ', unstalked hydatid; u' , uterus masculinus, the persistent parts of the Miillerian duct (.'/); A, stalked hydatid; g, Cowper's glands; ;«, penis; K, kidney. C, female type: O, ovary; /', parovarium; /', paroophoron; IV, Gartner's duct when present ; /, fimbria; 0, oviduct; u, uterus; v, vagina ; A, stalked hydatid ; A', kidney. (Modified after Wiedersheim.) paroophoron, the homologue of the paradidymis. The greater part of the Wolffian duct atrophies in the female ; when it persists as a pervious canal it becomes the duct of Gartner. Male. Testicle. Tubules composing glo- bus major. Paradidymis. Tube of epididymis and vas deferens. Stalked hydatid. Sessile hydatid represent- ing fimbria. Uterus masculinus. Usually undeveloped. Bladder and first part of urethra. Remaining parts of ure- thra. Cowper's glands. Penis. Scrotum. Indifferent Type. Sexual gland. Wolffian tubules. Wolffian duct. Duct of pronephros. Miillerian duct. Lower segment of allan- tois. Uro-genital sinus. Genital eminence. Genital ridges. Female. Ovary. Short tubules of parova- rium. Paroophoron. Head-tube of parovarium. Gartner's duct when persistent. Stalked hydatid. Oviduct. Uterus. Vagina. Bladder and urethra. Vestibule. Bartholin's glands. Clitoris. Labia majora. 246 NORMAL HISTOLOGY. CHAPTER XIV. THE RESPIRATORY ORGANS. The respiratory tract consists of two parts, — the system of air- passages, including the nasal fossae, pharynx, larynx, trachea, and bronchial tubes, and special organs, the lungs, devoted to the per- formance of the respiratory function. THE LARYNX. The larynx consists of the cartilaginous framework formed by the thyroid, the cricoid, the arytenoid, and the other smaller car- tilages of Wrisberg and of Santorini, united by the ligamentous membranes and the bands of fibrous tissue, and lined within by mucous membranes ; on the outside the cartilages are covered by fibrous and muscular structures. The mucous membrane of the larynx possesses the same con- stituents as does that of the pharynx, — namely, an epithelium, a tunica propria, and a submucosa. The epithelium covering both surfaces of the epiglottis and the cavity of the larynx as far as the false vocal cords is stratified squamous in character ; at the lower edge of the false vocal mem- branes the epithelium becomes stratified ciliated columnar, which type is retained throughout the ventricle of the larynx. Over the true vocal cords the epithelium once more becomes stratified squamous, beyond which point the stratified ciliated columnar character is again resumed and retained throughout the trachea and the bronchi. Numerous taste-buds, identical in structure with those of the tongue, lie embedded on the posterior surface of the epiglottis. The tunica propria of the larynx is composed of fibrous connec- tive tissue, with which is mingled an especially rich net- work of elastic fibres ; in the true vocal cords, almost the entire membrane con- sists of longitudinal bundles of elastic tissue ; these cords, therefore, are folds of the mucosa, composed principally of elastic fibres, with some fibrous tissue, covered by stratified squamous epithelium and re-enforced externally by the fasciculi of the thyro-arytenoideus mus- cle. In addition, large numbers of leucocytes lie scattered through- out the mucosa ; in the posterior surface of the epiglottis, the false cords, and the ventricle of the larynx the leucocytes are so numerous THE RESPIRATORY ORGANS. 247 that the mucosa assumes the character of diffuse adenoid tissue. The superficial part of the tunica propria is beset with papillae, best developed in those regions which are covered with squamous epi- Fig. 283. 7;V': Longitudinal section of larynx of child, exhibiting vocal cords and ventricle : a, surface above false cord (£) covered with squamous epithelium ; c, true cord covered with squamous epithelium ; V, ven- tricle lined with ciliated columnar epithelium ; d, ducts of mucous glands (g) cut in various direc- tions; m, fibres of thyro-arytenoideus muscle. thelium. The deeper layer of the mucous membrane is of loose structure, and passes into the still looser tissue of the submucosa, which serves to attach the mucous membrane with the surrounding firmer structures. In places the submucous tissue contains mucous follicles, .2-1 mm. in length, lined with columnar cells, many of which are distended with mucous secretion, even to the condition of 2.g NORMAL HISTOLOGY. goblet-cells. The minute groups of glands in the epiglottis lie em- bedded within the pits and openings in its plate of cartilage. The true vocal cords are destitute of FlG- 284' mucous glands. The cartilaginous frame- work of the larynx consists prin- cipally of hyaline cartilage ; to this variety belong the thyroid, the cricoid, and the greater part of the arytenoid cartilages. The epiglottis, the apex and the processus vocales of the aryt- enoid cartilages, together with the cartilages of Wrisberg and of Santorini, are formed of the yellow elastic variety. The little nodules embedded within the lateral thyro-hyoid ligaments, the cartilagines triticeae, are some- times composed of fibrous, at other times of yellow elastic cartilage. On the outer side fibrous connec- tive tissue connects the peri- chondrium with the surrounding structures, the attachment of the muscles being effected by tendinous tissue directly continuous with the investment of the cartilage. The blood-vessels supplying the interior of the larynx terminate within the mucosa in capillary net-works beneath the epithelium ; in those parts where papillae exist these are provided with vascular loops. The lymphatics exist as a superficial net-work of small vessels within the mucosa, and a deeper set, composed of much larger channels, within the submucous tissue ; these latter vessels are of exceptional size on the anterior surface of the epiglottis. The lym- phoid character of the mucosa in certain localities has already been noted ; local aggregations of such cells in the form of lymph- follicles are encountered in man sometimes, and constantly in some of the lower animals (dog,' cat). The nerves distributed to the laryngeal mucous membrane are composed principally of medullated fibres, although pale fibres are present. Longitudinal section of epiglottis of child : a, laryngeal surface ; b, glossal surface ; c, plate of elastic cartilage ; d, acini jf mucous glands. THE RESPIRATORY ORGANS. 249 Fig. 285. immm~ •«!&■ M a* Q?0 IP Wmr THE TRACHEA. The trachea in its general structure resembles the lower part of the larynx : it consists of a fibrous tube, lined by the mucous mem- brane, and strengthened and kept open by a series of incomplete cartilaginous rings. The mucous membrane of the trachea is lined by stratified ciliated columnar epithelium, among whose elements lie num- bers of goblet-cells. The current established by the ciliated epithe- H^: Hum tends to expel mucus or other ' ',:"":"HSb£i. substances. The tunica propria is conspic- uous on account of the large amount of elastic tissue which it contains ; owing to the disposi- tion of the elastic fibres, two zones are recognizable, an inner loosely- thrown-together fibrous layer, containing some elastic tissue, vas- cular loops, and nerve-fibres, to- gether with numerous lymphoid cells, and an outer layer, next the submucosa, made up largely of close net-works of longitudinal elastic fibres. The elastic fibres are particularly robust and abun- dant along the posterior membra- nous wall of the trachea, between the ends of the cartilages. The submucosa is loosely ar- ranged, and connects the mucosa with the fibrous sheath, as well as supports the glands and larger blood-vessels, lymphatics, and nerve-trunks. The tracheal glands are represented by numerous small groups of racemose structures which occupy the submucous layer and communicate with the mucous surface by means of the long excretory ducts. The latter are lined with low columnar epithelium, while the acini contain cuboidal cells. The fibrous coat lies external to the submucosa and forms a complete investment in which the cartilaginous rings are embedded. These latter are C-shaped masses of hyaline cartilage, embracing almost three-fourths of the tracheal tube. The remaining cleft is bridged by the continuation of the fibrous tunic supplemented by I* Section embracing trachea and oesophagus of child : a, b, tracheal and oesophageal surfaces; c, tracheal epithelium ; (/.stroma of mucosa ; e, submucosa ; /, mucous glands ; /;, part of ring cartilage ; g, its perichondrium ; i, fibrous tissue ; k, fibro-muscular tissue of oesophagus ; /, oesophageal epithelium. 2cq NORMAL HISTOLOGY. a layer of transversely-disposed bundles of non-striped muscle. These latter extend for some little distance along the inner side of the cartilages, to whose perichondrium they are attached. The muscle not only exists between the ends of the cartilaginous plates, but also passes across in the intervals between these, thus constituting a con- tinuous layer, which serves to narrow the tube. In addition to the transverse bundles, a few longitudinal muscular bands are present. The outer surface of the fibrous tunic is connected with the surrounding structures by loose areolar tissue. The larger blood-vessels pass to the submucosa, from which smaller twigs are given off to supply the mucous membrane and, partially, the fibrous and cartilaginous structures. The vessels termi- nate within the mucosa in a net-work beneath the epithelium ; the acini of the mucous glands within the submucous layer are surrounded by capillaries. The lymphatics of the trachea are numerous within the mucous and submucous coats, where they constitute plexiform arrangements of large, irregular, thin-walled channels. Lymphatic tissue in the form of solitary follicles also occurs. The nerves contain both medullated and non-medullated fibres. The larger trunks pass within the submucosa and send smaller fibres into the mucosa, where they course as minute naked fibrillae ; the exact mode of their ending is unknown. THE BRONCHI. The larger bronchial tubes repeat almost exactly the structure of the trachea, with such modifications as result from the slighter general development of the several coats incidental to the gradual reduction in the size of the tubes. On reaching the small bronchi the epithelium is reduced to a single layer of ciliated columnar cells. The thickness of the mucosa at first is not greatly diminished, since the loss sustained in the thinning of the elastic tissue of the tunica propria is compensated by the appearance of an additional layer of non-striped muscle situated at the outer border of the mucosa, next the submucosa ; this layer, which corresponds to a muscularis mucosae, forms a com- plete investment, especially conspicuous when the cartilaginous plates diminish. The ring-cartilages of the bronchi become reduced in size, then broken up, and finally replaced by irregular short plates ; these, becoming smaller and infrequent, embrace gradually less of the circumference of the tube, until in the bronchial twigs of the diameter of about one millimetre they altogether disappear. By repeated division the bronchial tubes become greatly reduced in size, the reduction being accompanied by the changes already THE RESPIRATORY ORGANS. 251 Section of portion of bronchus of child : a, epithelium ; b, basement-membrane ; c, stroma of mucosa ; d, layer of in- voluntary muscle ; e, submucosa ; /, acini of mucous glands ; h, blood-vessels ; i, obliquely cut duct of mucous glands. noted ; when the diameter of the twig no longer exceeds one milli- metre the tube is termed a terminal bronchus ; Fig. 286. these divisions open into the somewhat larger al- veolar passages, the walls of which are beset with air-sacs, and from which extend blind ir- regular or pyramidal spaces, the infundi- bula ; each infundibu- lum is surrounded on all sides by the air-sacs, which communicate freely with the former cavity, but not directly with each other. Greater exactness suggests ad- ditional subdivisions of the alveolar duct into vestibule, atrium, and infundibular passage (Miller). The walls of the terminal bronchial tubes consist at first of a single layer of ciliated columnar epithelium, outside of which the mucosa contains longitudinal elastic fibres and thin, irregular, annular bun- dles of non-striped muscle. The mucous glands and the cartilaginous plates are want- ing in the terminal tubes. Within the latter the ciliated cells disappear, a simple columnar epithelium existing for some distance, which, in turn, is replaced by cuboidal cells on approach- ing the alveolar ducts. The walls of the alveolar ducts suffer still further reduction, the fibrous coat becoming greatly thinned, while the mucosa is reduced to a delicate tunica propria of fibro-elastic tissue, in which bundles of non-striped muscle remain. The epithelium of the alveolar passage, at first low cuboidal in character, rapidly assumes a flat polygonal type ; towards the infundibula large flat plates appear among the smaller polygonal cells, and become more numerous as these terminal divisions of the air-passages are neared. Diagram of terminal compartments of air- passage: T.B., terminal bronchus; A.D., alveo- lar ducts ; Inf., infundi- bula, into which open air-sacs. The general character of the epithe- lial lining is indicated. 252 NORMAL HISTOLOGY. Within the infundibulum the epithelial lining consists principally of the large flat endothelioid plates, or respiratory epithelium, be- tween which elements diminutive groups of the smaller polygonal cells appear. In the air-sacs, presently to be described, the large plate-like elements of the respiratory epithelium chiefly constitute the lining. THE LUNGS. The lungs, with their system of air-tubes, correspond in plan of structure and in development to racemose glands, the excretory ducts being represented by the bronchial tubes, and the glandular tissue by the pulmonary parenchyma. The latter is built up of groups of air-sacs enclosed by connective tissue to form lobules, which are associated in larger groups ; these latter in turn are united into the lobes. All these divisions are connected by alveolar tissue, the external surface being additionally covered by the pleura. By the division of the terminal bronchial tube into the alveolar ducts, and the subsequent origin from these of the infundibula and the air-sacs, the part of the pulmonary parenchyma in communica- tion with a single terminal bronchiole forms a pyramidal mass, whose apex corresponds to the terminal bronchus, and whose base, when reaching the free surface, appears as one of the polygo- nal areas marking the exterior of the lung. These larger polygonal fields, made up of many smaller areas which correspond to the compressed infundi- buli, are often defined with great distinct- ness by the pigment accumulated within the connective tissue separating the adja- cent lobules. The air-sacs, air- cells, or alveoli of the lung represent the acini of racemose glands, the similarity being especially marked in the uninflated organ, which still retains its glandular character. Opening into the common passages of the alveolar ducts and the infundibula, the air- Section of human lung : a, infundibula cut in various directions ; b, air-sacs separated by interacinous partitions (c) ; d, masses of interlobular tissue containing accumulations of pigmented par- ticles (e). THE RESPIRATORY ORGANS. 253 sacs are placed closely side by side, and by mutual pressure become polyhedral. Around the opening or base of the air-sac, where it communicates with the infundibulum, the elastic tissue of the latter is arranged as a ring, from which elastic fibres pass in all directions over the air-sac to form its framework. The wall of the air-sac comprises the epithelium, the con- nective-tissue framework, and the capillary net-work. The epithelial lining is represented chiefly by a single layer of large plates, closely resembling endothelium in silvered prepara- tions, among which small polyhedral Fig. 289. cells lie scattered as JjjjjS^&i^t* isolated elements or in groups of two or three. Originally, in the embryonal condition of the tis- sue, only the smaller polyhedral cells are present in the air- sacs and the infun- dibulum, the large plate-like elements first appearing after the tissue has been expanded following inflation of the organ. The small cells, therefore, are to be regarded as genetically identical with the larger, the only difference being that the smaller have never undergone the expansion to which their neighbors have been sub- jected ; during forced expiration the larger cells become diminished in size. Between the cells, frequently at the juncture of the angles of several, minute openings or stomata exist ; they usually connect with microscopic passages leading into the lymphatic channels. By means of these channels particles of inhaled foreign matters, often deeply pigmented, are carried from the air-sacs into the lym- phatics, and become lodged within the interlobular connective tis- sue. Additional particles are carried into the tissues by means of the wandering lymphoid cells which occur within the epithelium of the air-sacs and air-passages. The framework of the air-sac is composed almost entirely of the elastic fibres springing from the annular bundle surrounding the mouth of the sac. These fibres unite to form a net-work which Section of silvered lung of kitten, including portions of infun- dibulum and air-sac : a, small polyhedral epithelial cells covering wall of infundibulum ; b, fibro-elastic framework ; c, large flattened epithelial plates lining air-sac, among which lie small groups of the small cells (d). 254 NORMAL HISTOLOGY. completely surrounds the alveolus and constitutes the septum be- tween the adjoining air-sacs, at the same time supporting the capillary- vessels and the investing epithelium. In addition to the elastic fibres, a very small quantity of fibrous tissue, with a few connective-tissue cells, aids in the construction of the air-sac. The capillary net-work within the walls of the air-sacs is re- markable for the closeness of its meshes, being one of the densest vascular net-works within the body. The larger arterial stems take their course, in company with Fig. 290. the veins, bronchioles, nerves, and lymphatics, within the thicker tracts of interlobular connec- tive tissue ; the smaller twigs extend among the groups of in- fundibula, embracing the openings into the air-sacs with more or less complete rings, from which pass the capillaries enveloping the air- sacs with net-works on all sides. Between the adjoining alveoli lies only a single layer of capillary vessels, which, however, are not confined to a single plane, but encroach alternately upon the adjacent air-sacs as projecting arches or loops. While the interalveolar septa are reduced to a minimum, the two layers of respiratory epithelium lining the adjoining air-sacs, the scanty connective-tissue framework and the capillary net- work constituting their entire bulk, the alveoli belonging to differ- ent, although neighboring, infundibula are separated by distinct connective-tissue partitions ; these increase in thickness as the included divisions of pulmonary substance become larger, and reach their greatest development in the fibrous envelopes ensheathing and separating the lobes. Owing to the accumulation of the pigmented particles conveyed by the lymphatics in the manner already described, the interinfun- dibular and often also the interlobular connective tissue present dark patches, the degree of discoloration varying from a few scattered irregular points to an intense almost uniformly black area. The presence of pigment within the connective tissue emphasizes the outlines and boundaries of the lobules with diagrammatic sharpness. The blood-vessels of the lungs enter at the hilus along with the large divisions of the bronchus ; the smaller branches of the pulmo- Section of injected and inflated lung of cat : a, air-sacs enclosed in dense capillary net-works (i) ; c, larger interlobular branches of pulmonary artery. THE RESPIRATORY ORGANS. 2KZ nary artery follow the air-tubes to their ultimate distribution, the arterioles extending along the respiratory bronchial tubes and alveolar ducts as far as the infundibular septa. They there end in capil- lary net-works which surround the air-sacs in the manner above described. In their course along the respiratory bronchial tubes and the alveolar ducts the pulmonary arterioles give off twigs which form net-works around the air-sacs besetting those passages. The blood of the alveolar net- works is carried away by the radicles of the pulmonary veins, which begin at the margins of the air-sacs. In addition to the system of vessels derived from the pulmonary artery destined for the respiratory function, a second group, for the nutrition of the pulmonary tissues, is distributed by the bronchial arteries. These vessels run in company with the bron- chial tubes and the other blood-vessels within the interlobular con- nective tissue and give off twigs which break up into the capillaries immediately supplying the walls of the air-passages and associated structures. Additional capillaries supply the interlobular areolar tissue and the pleural tissues on the surface of the lungs. The numerous lymphatics of the lung are arranged as two sets, those originating within the connective-tissue septa and those arising in connection with the bronchial mucous membranes. Of the former two groups are recognized, one of which includes the channels beginning within the interlobular fibrous tissue and forming the lymphatics which accompany the branches of the pul- monary blood-vessels ; the other, the superficial set, arises by the radicles connected with the subpleural lymph-spaces, which communicate with the serous cavity of the pleura by means of the minute passages leading from the intercellular orifices of the pleural surface into the subjacent lymph-clefts. The bronchial lymphatics originate within the subepithelial lymph-spaces which communicate with the mucous surfaces of the air-tubes and the alveoli through the stomata; from the subepithelial plexus larger lymph-channels unite with others to form definite lym- phatic canals ; these accompany the blood-vessels to the root of the lung, where the superficial and deep lymphatics meet and are taken up by a few trunks of large size which pass from the lung to the bronchial lymph-glands. Masses of lymphoid tissue of varying extent are associated with the walls of the alveolar ducts and the bronchial tubes, as well as the subpleural and peribronchial areolar tissue. The nerves of the lung include contributions from both the cerebro- spinal and the sympathetic system. The nerve-trunks, made up of medullated and pale fibres, enter the organ at its root and follow the air-tubes and the blood-vessels. Small groups of ganglion-cells 2r(5 NORMAL HISTOLOGY. occur along their course. On reaching the smaller and the terminal ramifications of the bronchial tubes the nerves become broken into fine non-medullated fibrillae, which pass to the muscular tissue of the tubule as well as to the mucous membrane. The exact mode of final termination of the nerve-filaments within the pulmonary tissue is still undetermined. THE PLEURA. The pleura resembles in structure other serous membranes, the general characters of which have been already considered in Chapter VIII. It consists of an endothelial covering, a connective- tissue matrix, and subpleural tissue. The lining of the pleural cavity is not of equal thickness in all parts, Fig. 291. the visceral or pulmonary pleura being thin- nest as well as most firmly attached, while the parietal or costal pleura is thickest, and, owing to the well-developed subpleural tissue J'L- ..:;'■■ ■-'./,.'.. '^.' /"-if*. j i-xistinm in this region, less rigidly adherent. '*%. ^ The endothelium of the parietal portion Section of human pleura cover- possesses ceus more expanded and thinner ing surface of lung: a, endothe- l _ . r Hum; b, fibro-eiastic stroma ; ;«, than those covering the surface of the lung; cut bundle of muscie-ceiis; p, the eiements m this latter position vary in peripheral layer of pulmonary ... . , . ,, - tissue. their size with the changes in the bulk of the pulmonary mass. Between the endo- thelial plates minute stomata exist, which through the minute cana- liculi indirectly communicate with the lymphatic spaces within the subjacent tissue. The stroma of the pleura consists of fine bundles of fibrous connective tissue intermingled with elastic fibres ; within the fibrous lamellae the intercommunicating lymph -channels form a plexus of considerable richness, which communicates on the one hand with the pleural cavity through the stomata and intervening canaliculi, and on the other with the neighboring lymphatics within the subpleural tissue. The latter where developed as a layer of some thickness, as beneath the parietal pleurae, is composed of loosely-disposed areolar tissue, containing many elastic fibres. Upon the lung the subpleural layer is intimately united with the pulmonary tissue, and forms a strong superficial fibrous envelope, in which bundles of non-striped muscle are also present. Within the stroma of the visceral pleura the blood-vessels form a wide-meshed capillary reticulum over the surface of the lung ; superficial vessels communicate with deeper branches surrounding the interalveolar septa. The nerves of the pleura occur as infrequent stems, composed THE RESPIRATORY ORGANS. 257 principally of medullated fibres ; fibrillae are traceable into the sub- pleural tissue, but their exact mode of ending is uncertain. THE THYROID BODY. In view of its topographical relations, as well as a matter of con- venience, it is usual to consider this organ in connection with the respiratory tract, although such association is only incidental and without foundation or morphological significance, unless its descent in common with the respiratory organs as an outgrowth from the pharyngeal entoderm be regarded in such light. The thyroid body is a compound tubular gland whose excre- tory canal, the thyro-glossal duct, in the early stages of the organ, connects the tubules with the mucous surface, where its opening corresponds to the foramen caecum, situated on the dorsum about an inch from the base of the tongue. After a short existence, long before the gland attains its full development, the thyro-glossal duct Fig. 292. Section of thyroid body of child: a, acini distended with colloid secretion, cut in various directions ; b, interlobular connective tissue. undergoes atrophy and more or less complete obliteration ; the acini, consequently, become isolated closed cavities, while the organ is often classed as a ductless gland. The fully-developed adult thyroid gland consists of numerous tubular acini, 40-110 /* in diameter, united by intertubular areolar tissue into lobules ; these, in turn, are joined into lobes by still larger masses of connective tissue, which form on the outside of the organ a general external fibrous envelope. The acini are completely closed, and lined with a single layer of cuboidal or low columnar epithelium, whose component cells rest upon a distinct basement-membrane. The enclosed cavities differ 17 Section of thyroid body, exhibiting de- tail of the acini, which are cut in various directions : c, colloid material distending the larger acini ; /", interacinous connective tissue ; v, blood-vessels. 25g NORMAL HISTOLOGY. according to the size and the distention of the acini ; they usually con- tain a viscid yellowish mass, the colloid substance, produced through the active agency of the cells lining the Fig. 293. acini. In addition to the characteris- tic colloid secretion, detached epithe- lium, leucocytes, migrated plasma- cells, and in very many cases colored blood-corpuscles, are included within the contents of the alveoli. The pres- ence of red blood-cells in various stages of disintegration has suggested the destruction of effete blood-cells as a possible function, in part at least, of this questionable organ. The inter- alveolar tissue contains elements closely resembling plasma-cells. The blood-vessels of the thyroid gland are exceptionally numerous, the arteries being remarkable for their large size and very free anastomoses. From the larger branches, which run within the interlobular tissue, small twigs pass between the alveoli and break up into capillaries surrounding the acini with a close-meshed net-work situated immediately beneath their epithelium. The venous radicles are also numerous, and form the conspicuous superficial plexuses. The plentiful lymphatics occupy the deeper connective-tissue septa between the lobules as well as the fibrous envelopes surrounding the lobes. The deeper lymphatics begin as spaces lying between the bundles of fibrous tissue close to the acini, and frequently contain characteristic colloid substance. Large superficial trunks, provided with valves, carry off the accumulations from the smaller canals. The few nerves which supply the thyroid gland are derived almost entirely from the sympathetic system. The fibres, therefore, are prin- cipally of the pale, non-medullated variety, and seem to be distributed especially to the walls of the blood-vessels ; a few medullated fibres are usually present, but the exact mode of their termination is uncertain. The development of the respiratory organs begins as a ven- tral evagination of the entodermic lining of the primitive pharynx. The caudal extremity of this complex cavity abruptly narrows into the oesophageal division of the primary gut tract. The earliest in- dication of the formation of the respiratory apparatus consists in the extension of the ventro-dorsal diameter of the primitive oesophagus at its pharyngeal end, in which plane it now appears as an irregularly- compressed ellipse. The pulmonary evagination extends caudally for some distance, THE RESPIRATORY ORGANS. 259 Fig. when its expanded extremity divides into two lateral diverticula ■ of these, the right, which is the larger and longer, subdivides into three branches, while the left bears but two. These pouches correspond to the future lobes, and thus early establish the asymmetrical division of the future lungs. The pharyngeal end of the pulmonary tube becomes the larynx, while the remaining portions form the system of air-passages, including the tra- chea and the bronchial tree. In the further development of the bronchial ramifications the same general plan of division is repeated. The already-existing tube divides dichotomously, but the limbs of the forks grow unequally, since the ventral bud becomes the continuation of the stem, while the other becomes a lateral branch. After the entire system of air-passages is established the expanded ends of the terminal buds produce the ultimate divisions of the pul- monary structure. While the entodermal diverticulum thus takes part in the formation of the entire pulmonary tract, its contribution is limited to the epithelial lining of the alveoli and the air-tubes, while the remaining constituents of the respiratory organs are derived from the mesoderm. The mesodermic tissue Part of sagittal section of eleven-day rabbit em- bryo, showing pulmonary evagination : P, primitive pharynx ; r, o, respiratory and oesophageal tubes ; b, body-cavity ; m, mesoder- mic tissue. Portion of section of thirteen-day rabbit embryo, including developing lungs ; mesodermic pulmo- nary masses, L, V ', are covered with primary pleural endothelium and penetrated by bifurcations of primary bronchi (/, t) ; v, blood-vessels ; o, oesophageal tube. surrounds the entodermic diverticula, constituting for a time a con- spicuous mass, into which the epithelial tubes grow. Subsequently the mesodermic area becomes so completely invaded by the rapidly- 26o NORMAL HISTOLOGY. developing system of primary air-tubes and alveoli that its relative quantity is greatly reduced, since it eventually is limited to the connective-tissue framework of the organ. The appearance of the blood-vessels occurs at a later period. The derivation of the greater part of the digestive and of the respiratory tract is identical, — namely, the epithelial structures from the entoderm and the re- maining tissues from the mesoderm. The development of the thyroid body includes the history of two structures which originate independently, but which after a short time in man and other mammals become blended to constitute a single organ : in many animals, however, the mesial and lateral thy- roid areas produce organs which permanently remain distinct. The middle thyroid area, from which originates the true thyroid body, appears as a ventral outgrowth from the entodermic lining of the primitive pharynx at a position corresponding approxi- mately with the second visceral arch. The mesial outgrowth rapidly elongates, and after a time usually loses its attachment with the Portion of sagittal section of twelve-day rabbit em- bryo, exhibiting mesial thy- roid area as epithelial out- growth (r) still connected with pharyngeal entoderm (e) ; nt, surrounding meso- derm. Fig. 297. -.V .'. :,-■■ m" pharyngeal epithelium. The entodermic mass gradually leaves the primitive pharynx and as- sumes a close relation with the paired lateral thyroid areas, with which it eventually fuses. The lateral developmental areas of the thyroid body appear as ventral outgrowths from the entodermic lining of the fourth inner visceral furrow on either side. The epithelial evaginations become elongated cylindrical masses, which undergo active proliferation and extend their bulk as branching cords ; where these are at first solid they subsequently obtain a lumen, and for a time present the character of tubular glands. The later changes include the approximation and final fusion of the two lateral and the single mesial areas to form the thyroid body of the mammalian type. The disappear- ance of excretory ducts and the ingrowth of the surrounding mesoderm result in the division of the organ into lobules and the isolation of the imperfectly-developed acini. Disten- tion of the latter by accumulations of colloid material follows the activity of the secreting cells within the ductless alveoli. eg Portion of section of four- teen-day rabbit embryo, in- cluding lateral thyroid area (/) which is still attached to fourth inner pharyngeal furrow (p) ; m, surrounding mesoderm. THE SKIN AND ITS APPENDAGES. 26l CHAPTER XV. THE SKIN AND ITS APPENDAGES. THE SKIN. The skin consists of two parts : the superficial epithelial layer — the epidermis or the cuticle, derived from the ectoderm — and the deeper connective-tissue layer — the corium or the cutis vera, de- rived from the mesoderm. Blended with the corium and separated from it by no sharp demarcation, the subcutaneous tissue exists Fig. 298. Section of human skin: «, stratum corneum ; b, stratum lucidum ; c, stratum granulosum ; d, stratum Malpighii ; e, /, papillary and reticular layers of corium ; g, stratum of adipose tissue ; h, i, spiral and straight portions of duct of sweat- gland ; k, coiled portion of sweat-gland ; I, vascular loops occupying papillae of corium. usually as a stratum of considerable thickness, which forms a loose attachment between the skin and the adjacent structures. The in- tegument varies in thickness from .3 to 3.75 mm., being thicker on the back of the head, the neck, and the trunk than on their 262 NORMAL HISTOLOGY. anterior aspects, and thicker on the outer side of the limbs than on their mesial surfaces. The epidermis, or the cuticle, is a highly developed stratified squamous epithelium ; while forming a protecting layer to the underlying sensitive corium over the entire surface of the body, the FlG- 3°°- epidermis varies in different regions, in some places, as on the eyelids and brow, not exceeding . i mm. in thickness, while in others, as on the soles of the feet and the palms of the hands, it reaches almost i mm. The epidermis is accurately adapted to the opposed surface of the corium, which is beset with papillae, so that when the two layers are separated :•?■■'*■'.' >i'Tv.o,v.;.\.-..:V,i."' ■>, ..'•.•J.; '.■.'■■■'.'■'.■'..'.■ Epidermis of human skin separated from corium, viewed from beneath : a, thickened areas filling de- pressions between papillae ; b, pits receiving papillas of corium ; c, ducts of sweat-glands. Section of human skin from hand, in- cluding superficial layer of corium and epidermis: a, b, c, d, respectively the stratum corneum, lucidum, granulosum, and Malpighii; e, layer of columnar cells next the corium ; /, fibro-elastic tissue consti- tuting papillary layer of corium. the under surface of the epidermis presents impressions or pits corresponding to the elevations of the rorium which they receive. The cells composing the epidermis are arranged in many irregular layers, the number of which depends upon the cuticular development in any particular region ; where well represented the layers are grouped into two sharply-defined zones, the inner, darker, softer stratum Malpighii and the outer, clearer, denser stratum corneum ; where highly developed the epidermis presents two additional zones, distinguished by the peculiar character of the pro- toplasm of their cells ; these layers are the stratum granulosum and the stratum lucidum. The stratum Malpighii, or rete mucosum, contains the most THE SKIN AND ITS APPENDAGES. 26\ recently formed and most actively growing elements, the deepest of which, next the corium, are perpendicularly placed and possess a distinct columnar character. The irregular and often slightly expanded bases of the deepest cells rest upon the thin basement- membrane, while their outer ends are surrounded by the more poly- hedral elements. Next the layer of columnar cells the elements become broader and polyhedral in form and possess the delicate protoplasmic spines characteristic of prickle-cells. The elements of the succeeding horny layer stand in marked contrast to those of the soft underlying Malpighian stratum, owing to the production of keratin within the protoplasm and the desicca- tion of the cells. These influences are seen in the superficial layers, in the disappearance of the nucleus, and in the reduction of the once large polyhedral cells into the thin compressed horny plates of the outer layer. At the inner border of the horny layer lies a thin band of cells, conspicuous on account of the marked granular appearance of their protoplasm ; these constitute the stratum granulosum, and con- tain granules of eleidin, a peculiar substance, staining intensely in certain dyes, and bearing a close relation to the keratin of the more superficial layers. At the outer border of the granular stratum the horny elements begin ; those lying next the stratum granulosum, however, are in- completely transformed into horny substance, and appear as an ill- defined narrow zone, the stratum lucidum, which contrasts strongly with the darker granular layer. Superficial to the clear zone lie the characteristic cells of the stratum corneum ; these epithelial ele- ments are enlarged and without nuclei, the outermost cells being compressed flattened horny scales, which after desiccation un- dergo desquamation and mechanical abrasion. Over those parts of the cutaneous surface where the epidermis is well developed and destitute of hairs, the stratum corneum differs somewhat from its usual condition in being composed chiefly of large distended bladder-like cells, which probably represent the superficial epitrichial layer of the embryonal skin. Where the epidermis is thin the stratum granulosum is very imperfect, while the stratum lucidum is wanting; under these conditions the superficial cells rapidly dry and become thin horny plates. Pigment-granules are widely distributed throughout the epider- mis, but it is especially within the deeper layers of the stratum Mal- pighii that the larger accumulations are found to which the dusky hue of the skin of many races is due. The pigment-granules do not origi- nate within the epithelial elements, but are conveyed to the epidermis Fig 2g4 NORMAL HISTOLOGY. through the agency of the migratory cells, the cutis vera. The dark tint of the skin of the negro and of other colored races depends almost entirely upon the pigment within the epidermis, since in the adult integument the subepithelial tissue contains comparatively few pigmented cells. While micro- scopical examination shows the pres- ence of pigment some weeks before birth, the dark color is usually not evident until a day or two after- wards, owing to the opaque layer of moist superficial scales which masks the underlying colored cells. The corium, derma, or true skin consists of a felt-work of bun- dles of white fibrous connective tis- sue, with which elastic fibres and non-striped muscle are mingled in varying amounts. The corium is densest in its outer part, where be- neath the epidermis it is beset with papillae, which greatly extend the sensory surface and form the prin- cipal organ of tactile sensibility. The deeper parts of the corium are much looser in structure, since the bundles are coarser and more loosely disposed, fading away into the subcutaneous tissue. These differences have led to the recognition within the corium of an outer, denser stratum papillare and an inner, looser stratum reticulare ; no sharp demarcation exists between the two, the papillary layer blending with the reticular, while the latter in turn passes gradually into the tissues of the subcutaneous stratum. The papillae vary in size, number, and disposition in different regions, being best developed and most numerous on the palmar surface of the hands and the fingers and on the corresponding parts of the feet, where they attain a height of .25 mm.; on the other hand, the papillae may be very slightly developed or even absent. These elevations consist of closely-arranged bundles of fibro-elastic tissue, and support the vascular loops together with the rich ter- minal nerve-supply ; in certain localities the latter includes the highly- specialized tactile corpuscles of Meissner, the corpuscles of Vater, and the various end-bulbs which already have been described in Chapter VI. The simplest type of the papillae is the rounded or blunted conical elevation, but very often such projection becomes Section of negro's skin, including epidermis (a) and papillary layer of corium (6) ; the deepest layers of epidermis (c) contain the pigment. THE SKIN AND ITS APPENDAGES. 26<; cleft and converted into one of the compound variety. The papillae of the hand and the foot are distributed in characteristi- cally-arranged rows, which form elaborate, and for each individual constant and distinctive, ridges on the integumentary surface. These ridges have been found to retain their definite arrangement, or "patterns," from early life to old age unchanged. This constancy in the details of the surface markings has been taken advantage of in securing records by means of impressions for the purposes of identification. Non-striped muscular tissue occurs within the corium in con- nection with the hair-follicles, as the arrectores pilorum, and in the subcutaneous tissue, attached to the under surface of the corium, in particular localities, as in the scrotum, the perineum, the penis, and in and around the nipple. The subcutaneous stratum consists of a reticular framework of loosely-disposed fibro-elastic bundles continued from those of the deeper layers of the corium without sensible interruption ; the inter- fascicular spaces are largely occupied by adipose tissue, which in many places forms a compact layer, the panniculus adiposus. The cellular elements of the subcutaneous tissue are the usual cells of connective tissue, including fusiform and plate-like elements, leucocytes, and fat-cells : while the latter are quite constant con- stituents of the deeper layers of the skin, within the integument of the eyelids, the penis, and the labia minora fat does not occur. THE APPENDAGES OF THE SKIN. These include the nails and the hairs, together with the cutane- ous glands, all of which are directly derived from the ectodermic epithelium of the epidermis. THE NAILS. Each nail consists of a large exposed body, which ends ante- riorly in the projecting free edge, and extends posteriorly as the root some considerable distance beneath the overhanging upper margin of the groove, or nail-fold, receiving the root ; at the sides the borders of the nail are covered by the nail- walls. The nail, which represents an enormously developed stratum lucidum, rests upon a highly vascular and sensitive nail-bed, the posterior portion of which, covered by the root of the nail, is the matrix. The nail- root is usually lighter in color and somewhat opaque, owing to the thickness of the stratum Malpighii ; on the thumb it extends beyond the nail-fold as a pale projecting convex area, the lunula. While attached throughout the extent of the nail-bed. the growth of the nail takes place«from the matrix alone, each newly-formed 266 NORMAL HISTOLOGY. increment pushing before it the older already existing parts at the rate of about one millimetre per week. The nail-bed comprises the corium and that portion of the epidermis corresponding to the stratum Malpighii. The corium consists of the usual bundles of fibro-elastic tissue, which are arranged somewhat parallel to the long axis of the finger, the longitudinal bun- dles being supplemented by vertical ones extending from the perios- teum of the phalanx to the superficial layers. The minute elevations Fig. 302. Transverse section of child's finger, including the nail: a, connective tissue of corium ; b, longi- tudinally corrugated nail-bed ; c, corneous tissue constituting body of nail ; d, its thin edge covered by tissue of nail-wall (_/") ; e, point where stratum Malpighii becomes continuous with nail-bed. which occupy the surface of the corium in transverse section are not true papillae, except posteriorly over the matrix, but longitudinal ridges. They are lowest behind and gradually increase in height towards the front of the nail, terminating abruptly at the point where the latter parts from its bed. The epithelial portion of the nail- bed is principally composed of cells belonging to the stratum Mal- pighii, whose numerous layers fill up the inequalities between the papillae and the ridges of the corium below, and are sharply defined from the substance of the nail above. The transformation of the deeper cells into the horny plates of the nail takes place only over the matrix, where the constantly-recurring division of the epithe- lial elements furnishes material for the growth of the nail. The nail-fold and the nail-wall have the same general structure as the skin. The substance of the nail itself consists of intimately united lamellae of horny epithelial cells, which possess a nucleus and closely resemble the elements of the stratum lucidum ; the older and most superficial layers are made up of compressed horny dry scales, while those composing the last formed and hence deepest layer are softer and more regularly polyhedral, resembling the cells of the stratum Malpighii. THE SKIN AND ITS APPENDAGES. 267 THE HAIR. The hairs, together with their homologues, feathers and scales of the lower animals, are derived entirely from the epidermis, and are therefore of ectodermic origin. These slender flexible horny threads are distributed, with few exceptions, over the entire surface, but differ greatly as to both size and frequency in various regions ; individual and race peculiarities also greatly influence the character of the hair. In general, in straight-haired races the hairs are thicker and coarser and more cylindrical than in crisp-haired races ; Fig. 303 Section of human scalp, showing hair-follicles and sebaceous glands : a, epi- dermis ; b, corium ; c, hair embraced within its hair-follicle ; d, fibrous sheath of follicle ; e, glassy membrane ; /, outer root-sheath ; g, inner root-sheath ; h, expanded terminal bulb of hair ; i, hair-papilla ; k, mouth of follicle from which hair-shaft (/) projects ; m, adipose tissue ; n, blood- vessel ; o, sebaceous glands ; /, arrector pili muscle ; s, portions of sweat-gland. in the negro the hairs are flattened cylinders, small and oval in sec- tion ; dark hair is usually coarser than that of light color. Every hair presents two principal divisions, the part which projects beyond the surface, as the shaft, and the portion embedded 268 NORMAL HISTOLOGY. Fig. 304. within the integument, the root ; at its lower extremity the root ter- minates in a bulbous expansion, the hair-bulb, which at its lowest point is indented to receive the connective-tissue papilla. The hair- bulb lies embraced within a pocket of modified integument, the hair-follicle, to which the corium and the epidermis contribute respectively the fibrous and the epithelial root-sheaths. The hair consists entirely of epithelial cells disposed as three dis- tinctly defined strata, the cuticle, the cortical substance, and the medulla, or pith. The hair cuticle is composed of a single layer of thin, horny, imbricated scales, which envelop the entire sur- face of the hair, both on the root and on the shaft ; in these situations it forms a layer respectively 6-8 ,u and 2-4 p. in thickness. Owing to the imbricated arrangement of the cells, as tiles upon a roof, only their free projecting borders are visible, which produce in surface views the characteristic oblique transverse markings so distinctive of hair; in pro- file the edges of the cells appear as deli- cate serrations. The cortical substance constitutes by far the greater part of the hair, when the medulla is wanting sometimes forming its entire bulk. This portion of the hair- shaft is composed of greatly elongated horny epithelial cells, which possess attenuated nuclei and are so intimately united that the boundaries of the individ- ual elements under ordinary circumstances are not distinguishable. On the root the cells are broader, less horny, and assume more and more the character of the ele- ments of the stratum mucosum as the prox- imal end of the hair-bulb is approached ; immediately around the papilla the- cells of the cortical substance become con- tinuous with the extension of the stratum mucosum, the outer root- sheath. The medulla, or pith, occupies the central tract of the hair-shaft, and extends in favorable examples from near the hair-bulb almost to the extremity of the hair. Many hairs possess no pith, this part being usually wanting in the fine hairs of the general body-surface and the colored hairs of the head, as well as in the hairs of chil- dren under four or five years of age. In the thick short and in the robust long hairs, likewise in most white scalp-hairs, the medulla is present, and constitutes sometimes one-third of the diameter of the hair. A, human hair; the upper half of the figure represents the super- ficial homy cells (h) constituting the cuticle, the lower half, the fibrous structure of the cortical substance and the medulla ; B, isolated ele- ments of the hair ; a, cuticular scales ; 5, thin fibre-cells of cortical substance. THE SKIN AND ITS APPENDAGES. 269 Fig. 305. The medulla is composed of rows of irregular cuboidal or spherical cells, 15-20 ij. in diameter, filled with dark granules, which really are minute air-vesicles ; by reflected light the pith appears silvery-white, while by transmitted light it is dark and opaque. The air gains access to the medulla in consequence of the partial drying out of the soft protoplasm of the cells. In many animals the medulla- cells form a conspicuous and relatively large portion of the hair, and present characteristic details sufficiently dis- tinctive to determine the kind of animal from which the specimen was obtained. The color of the hair depends upon the presence of pigment-granules, diffuse pig- ment, and air. The granular pigment occurs as colored particles varying from light brown to black ; in dark hair the pigment lies within the elements of the cortical substance, as well as often between the cells, the cortex in addition sometimes containing diffuse soluble coloring-matter in combination with the proto- plasm of the cells. Diffuse pigment is en- tirely wanting in white hair, is sparingly present in light blond hair, and exists in abundance in dark blond, red, and dark hair. The hair-follicles are tubular or flask-shaped depressions within the integument (2-7 mm. in length) which tightly embrace the hair-shafts ; those of the finer hairs lie entirely within the corium, while those of the large hairs frequently extend deeply into the subcutaneous stratum. The hair-follicle serves the double purpose of supplying the tissue from which the hair is formed and of affording the necessary attachment and support to the hair after its development. The relation of the hair-follicle to the general integu- ment is best appreciated by remembering that the follicle develops by an ingrowth of the epidermis into the subjacent connective tis- sue ; the hair subsequently appears as the result of the metamorphosis and the differentiation of the cells occupying the most dependent part of the epidermal plug. While in the follicles of the finer hairs the epithelium forms almost the entire structure, in those of the large hairs the surrounding connective tissue takes part to the extent of supplying a strong protective sheath, the fibrous coat. Hair-follicle from human scalp : a, hair ; b, inner root-sheath ; c, outer root- sheath ; d, glassy mem- brane ; e, fibrous sheath ; _/, hair-bulb ; h, hair-pa- pilla. 270 NORMAL HISTOLOGY. Below the openings of the sebaceous glands the hair-follicle consists of the fibrous coat and the stratum mucosum of the epi- dermis only : at its upper extremity the stratum corneum additionally takes part in the formation of the follicle. The fibrous coat of the follicle consists of three layers : the outer, composed of longitudinally- placed bundles of connective tissue, rich in cells, and representing a condensation of the tissue of the corium ; the middle, represented by a layer of circular connective-tissue bundles continuous with the papillary layer of the cutis ; and the inner, a clear, homogeneous, narrow but conspicuous zone, the glassy or hyaline membrane. The latter separates the epithelium from the surrounding fibrous tissue, and corresponds to a highly-developed basement-mem- brane. These layers of the fibrous sheath are not continued to an equal extent over the hair-follicle ; the outer longitudinal layer com- pletely invests the follicle, becomes continuous with the corium, and materially aids in maintaining the form of the follicle. The circular Fig. 307. Fig. 306. Transverse sections of hair-follicles from human scalp : a, hair; £, cuticle of hair ; c, d, inner and outer root- sheath ; e, glassy membrane ;_/", fibrous sheath ; g, surrounding connective tissue of corium ; /;, fat-cells. Transverse section of hair-follicle from human scalp ; plane of section passes through mouth of follicle : a, one of the hairs; b, horny tissue of superficial layers of epidermis ; c, cells of stratum Malpighii ; d, sur- rounding connective tissue. layer extends from the base of the hair-follicle to the orifices of the sebaceous glands, while the glassy membrane, as such, ceases at the mouth of the follicle. Next inside the glassy membrane follow the epithelial layers occu- pying the entire space between the hair and the sides of its follicle. The epithelial tissue is disposed in two well-marked strata, the thicker, many-layered zone next the glassy membrane, which con- stitutes the outer root-sheath, and the much thinner concentric layer composing the inner root-sheath. The former is the direct prolongation of the stratum mucosum of the general integu- THE SKIN AND ITS APPENDAGES. 271 ment, while the latter is derived from a part of the same cells that form the hair itself, and is therefore closely related to the hair. The outer root-sheath being the direct continuation of the stratum mucosum of the adjacent skin, its structure corresponds with that layer of the epidermis ; when well developed, as in the follicles of the larger hairs, this sheath measures 40-60 ft in thick- ness, or more than twice the breadth of the inner root-sheath. In the upper part of the follicle, where the glassy membrane and the circular fibrous layer are wanting, the outer sheath rests directly in contact with the longitudinal layer. The inner cells of the root- Fig. 308. Transverse section of hair-follicle from human scalp, more highly magnified : a, substance of hair, condensed at periphery (5) ; c, cuticular layer, composed of cuticles of hair and of inner root-sheath ; d, e, respectively layer of Huxley and of Henle ; f, outer root-sheath ; g, glassy membrane; h, i, circular and longitudinal bundles of fibrous sheath. sheath are columnar and placed vertically upon the glassy mem- brane, while the cells of the succeeding layers, some five to ten deep, present the polygonal outlines and the intercellular connect- ing threads seen in the corresponding parts of the ordinary epider- mis. The space between the outer root-sheath and the hair is occu- pied by three narrow zones, which collectively form the inner root-sheath, a clear transparent rigid membrane closely embracing the lower two-thirds of the hair-follicle and terminating in the vicinity of the opening of the sebaceous gland. The outer or Henle's layer appears as a light band composed of somewhat elongated 272 NORMAL HISTOLOGY. polyhedral cells, whose protoplasm is very faintly granular and whose nuclei are wanting. Next follows Huxley's layer, consisting of a single or double row of shorter and broader polyhedral cells, which ordinarily display small nuclei ; at the lower part of the follicle these cells contain numerous granules, probably of eleidin. Of the 15-35 ii. representing the entire thickness of the inner root-sheath, Henle's layer contributes about one-third, the remaining two-thirds being made up by the layer of Huxley. The outer surface of Huxley's layer is covered with the clear delicate cuticle of the root-sheath, a single layer of thin transparent plates lying against the cuticle of the hair in such close relation that the two cuticular layers appear as one. The cells of this envelope are imbricated in a manner similar to those of the hair-cuticle, but the free edges of the plates are di- rected in the opposite direction from those of the hair, the serrations of the cuticle of the root-sheath fitting into the impressions on the surface of the hair. The extremity or base of the hair-follicle presents a deep invagina- tion for the reception of the process of dermal connective tissue con- stituting the hair-papilla. The latter is a large, simple, club-shaped elevation, .1—3 mm. in length, which usually contains numerous branched pigment-cells and loops of blood-vessels. The presence of nerves within the papillae, on the contrary, is very doubtful. The most interesting as well as important part of the hair-follicle is immediately around the hair-papillae, since to the differentia- tion of the soft granular polyhedral cells occupying this position the hair, together with the inner root-sheath, owes its formation. These elements are the direct derivatives of the stratum mucosum, and represent the centre of greatest activity ; the elements di- rectly over the papilla supply the material from which the hair proper is developed, while the cells at the lower part of its sides become transformed into the layers of the inner root-sheath. For some dis- tance immediately above the summit of the papilla, polyhedral nu- cleated granular, and often pigmented, cells compose a matrix from wrhich the constituents of the cortical and medullary portions of the hair are directly derived. The muscles of the hairs, the arrectores pilorum, exist as minute flattened plexiform bundles of non-striped muscle, which extend from the most superficial parts of the corium to the hair- follicles ; the muscular band is attached to the fibrous coat of the follicle, below the sebaceous glands, on the side towards which the hair is directed. When the muscle contracts the obliquely-placed follicle becomes perpendicular and the shaft erect, in consequence of which the integument attached about the hair is drawn up, producing the well-known condition of cutis anserina, or "goose-flesh." THE SKIN AND ITS APPENDAGES. 273 Muscular slips frequently encircle the lower part of the follicle, while additional bands sometimes are given off to find attachment in the fibrous sheath of the sweat-glands. Fig. 309. ct-4 THE SEBACEOUS GLANDS. These structures occur so closely connected with the hair- follicles, into which they usually open, that the sebaceous glands may be looked for wherever hairs exist ; in addition, the glands may be present when hair-follicles are absent, as on the external genitalia (labia minora, glans and prepuce of the penis), the eyelids (Mei- bomian glands), and the red edge of the lips. The smallest se- baceous glands are connected with the head-hairs, while the largest are found on the mons Veneris, the labia majora, and the scrotum. The size of these structures is not proportionate to that of the associated hairs, since frequently the fine lanugo hairs possess large glands, a relation also seen in the particularly well developed sebaceous sacs connected with the fine hairs on the nose and the face. The group of acini is usually placed on the side towards which the hairs slope, and occupies the interval be- tween the hair-follicle and the arrector pili muscle, the contractions of the latter aiding in the expulsion of the secretion of the gland. The sebaceous glands are sometimes simple but usually small compound saccular structures possessing short ducts which open into the hair-follicles near their upper extremities. The periphery of the acini, five to twenty in number, is lined by a pe- ripheral layer of cuboidal epithelium, while the greater part of the sacs is filled with cells in various stages of fatty metamor- phosis. The secretion of these glands, the sebum, when fresh at the body-temperature, is a semi-fluid substance consisting of oil-droplets and the debris of broken-down cells ; on exposure to the atmosphere it becomes of the consistence of tallow. Section of portion of seba- ceous gland from human scalp, including part of acinus : a, membrana propria ; b, periph- eral layer of cuboidal cells ; c, elements in which fatty meta- morphosis is beginning ; d, cells filled with fatty particles and exhibiting marked intra-cellular net-works ; e, nuclei 'of cells. THE SWEAT-GLANDS. The sweat or sudoriparous glands are modified simple tubular glands which extend from the free surface of the integument, where 18 274 NORMAL HISTOLOGY. they open by the trumpet-shaped orifices of their wavy ducts to the deepest part of the reticular layer of the corium, or still farther into the subcutaneous stratum, in which position the gland-tube ends as a greatly convoluted spherical mass. The sweat-glands enjoy a very wide distribution, being present in greater or less abundance over the entire body-surface, with the exception of the deeper parts of the external auditory canal and the tympanic membrane. The largest sweat-glands occur in the axilla, at the root of the penis, on the labia majora, and around the anus. While the average diameter of the gland-masses is .3-4 mm., the axillary glands measure 2-7 mm. at their widest part. Each sweat-gland presents two divisions, the greatly convoluted gland-coil and the much straighter, slightly wavy excretory duct ; the former, which repre- sents the secreting portion of the gland, is much wider, both in its general diameter and lumen, than the part constituting the duct. The gland-tube is limited by a membrana propria continuous with that of the skin, outside of which a delicate connective-tissue en- velope gives additional strength ; within the basement-membrane cuboidal or low columnar epithelial cells form the lining of all parts of the gland. In the secreting division of the tube the low columnar cells are disposed as a single stratum, while those lining the duct are arranged as a double layer of small and low polygonal elements ; the cells of the duct are covered next the lumen of the tube with a delicate cuticle. The duct from the secretory portion of the gland to the epidermis maintains an almost constant diameter (20-25 l1) > on entering the epidermis, however, it enlarges to almost double, and on reaching the stratum corium expands into the trumpet-shaped orifice which marks its termination. Within the epidermis the duct loses its distinct walls, the final turns of its spiral, corkscrew-like course being bounded by the horny plates of the epidermis. In ex- ceptional cases the sweat-glands open into the upper part of the hair-follicles, but, as a rule, they reach the free surface by entering the epidermis in the depressions between the papillae of the corium. The terminal secretory segment of the gland-tube, usually single, although sometimes branched, is convoluted to form the char- acteristic coils, which can be seen often with the unaided eye as reddish-yellow spherical masses. The columnar secreting cells (10-20 fi in height) present a single layer of elements whose pro- toplasm is very finely granular and sometimes contains fatty gran- ules, as well as yellow or brown particles ; these latter are espe- cially evident in the ceruminous glands of the external ear, the axillary and the mammary areolar glands. The nuclei of the secreting cells THE SKIN AND ITS APPENDAGES. 2jr are eccentrically placed, while the border of the cells next the lumen presents a thickened edge sometimes described as a cuticle. Immediately outside the epithelial cells, between these and the basement-membrane, lies a thin Fig. 310. layer of involuntary muscle ; this tissue occurs only in the se- cretory division of the tube, and is best developed in the larger glands, where the muscle - cells form a complete layer. The in- dividual convolutions of the tube constituting the coil are held together by delicate connective tissue, which additionally furnishes a fibrous envelope for the entire mass. The average diameter of the secreting portion of the gland is about 65 fi, of which about 30 [i are contributed by the epithelial lining, and about half as much by the fibrous and muscular tunics ; the remaining 20 ft represent the usual lumen. The secretion of the sweat- glands varies with the locality and the character of the glands ; in general the secretion of these structures occurs in two forms, — as the colorless, slightly turbid fluid, devoid of morphological constituents, which is elaborated by the smaller glands and is the sweat proper, and as the thicker oily substances supplied by the large axillary, the circumanal, and the ceruminous glands. The products of these structures consist mostly of water, but contain, in addition, about 1.2 per cent, of solids, in- cluding fat, fat-acids, albuminous matters, urea, and salts in various proportions and combinations. The ceruminous glands of the ear and the glands of Moll of the eyelid must be regarded as modified sudoriparous glands, since they closely correspond to the sweat-tubes in structure. The total number of sweat-glands of the human body has been esti- mated to be about two millions (Krause) ; they are most numerous on the palms of the hands, in which situation 373 occur within a single square centimetre, and are almost as frequent on the soles of the feet ; the glands are most sparingly distributed over the back and the but- tocks, where less than sixty are contained within one square centimetre. Section of coiled part of sweat-gland from human skin : a, a, secreting portion of tubule, cut in various directions ; b, b, parts representing beginning of duct ; c, intertubular conneciive tissue ; d, layer of involuntary muscle inside the basement-membrane; e, cuticular border. 276 NORMAL HISTOLOGY. BLOOD-VESSELS, LYMPHATICS, AND NERVES OF THE SKIN. The blood-vessels supplying the skin are arranged as three sets, which occupy different levels, and are destined especially for the structures lying within the respective layers. The larger arterial vessels run between the superficial fasciae and the integument, generally parallel to the latter, while perpendicular branches are given off which pass towards the free surface and early in their course provide twigs for the supply of the deep-lying fat-clusters, among which the arterioles break up into the capillary net-works. At a somewhat higher level branches are given off to the sweat-glands, superficially to which a net-work is formed by the terminal branches of the ascending arteries, and constitutes a rich subepithelial reticulum distributed to the outermost stratum of the corium. Where well developed, the papillae receive vascular tufts and loops from the subepithelial net-work, the disposition of the loops corre- sponding with the simple or compound character of the papillae. Numerous twigs also provide for the nutrition of the hair-follicles, around which the longitudinal arterioles are connected by the trans- versely-disposed capillary net-works encircling the follicles ; loops are given off to supply the hair-papillae, as well as small branches to the sebaceous glands and the hair-muscles. The veins follow the gen- eral arrangement of the arterial branches. The follicles of the conspicuous tactile hairs of the lower animals are surrounded by the large venous spaces which occupy the cavernous tissue situated between the longitudinal and the circular coat of the fibrous sheath. The numerous lymphatics of the skin are arranged in two gen- eral sets, those extending within the corium and forming the superficial reticulum, and those situated within the subcutaneous tissue and following the larger blood-vessels. The superficial lymphatics begin as the interfascicular clefts of the corium, some of which are contained within the papillae ; these irregular spaces, with their imperfect lining of connective-tissue plates, communicate with the more definite lymph-vessels, which anastomose to form the plexus extending throughout the corium slightly beneath the plane of the closer-meshed reticulum of blood-capillaries. Special net-works of lymph-capillaries surround the hair-follicles and the glands. The deeper set of lymphatics lie within the subcutaneous tissue and con- stitute a loose reticulum of larger vessels, which freely communicate with the closer superficial lymphatic net-works as well as with those sur- rounding the adjacent hair-follicles and the glands. Each of the larger blood-vessels is usually accompanied by two lymphatic trunks of considerable size, which, by means of numerous transverse branches, freely communicate and enclose the blood-vessels within their meshes. THE SKIN AND ITS APPENDAGES. 277 The nerves supplying the skin vary greatly in different regions, the palmar surface of the fingers and the corresponding parts of the toes receiving the richest supply. The larger stems lie within the sub- cutaneous tissue, from which, in addition to twigs distributed directly to the sweat-glands and the involuntary muscle, numerous branches accompany the blood-vessels into the corium to end in various ways. Upon reaching the superficial portions of the corium, after having given off many lateral branches, the ascending twigs break up into bundles, which form a rich subpapillary plexus, con- taining both medullated and pale fibres, and extending beneath the epidermis and the bases of the papillae. The non-medullated fibres are probably destined for the involuntary muscle of the cutis, the glands, and the blood-vessels ; the medullated fibres, on the other hand, are connected with several forms of special nerve- endings. From the superficial plexus within the corium small twigs ascend to the epidermis, some fibres ending immediately beneath the epithelium, while others pass for different distances between the epithelial elements to terminate either as free endings or in connection with the tactile cells. The branches from the subpap- illary plexus which ascend into the papillae are connected with the large tactile corpuscles of Meissner which occupy the non-vas- cular papillae. Within the subcutaneous layer, in many regions, numerous corpuscles of Vater are present. The hair-follicles receive a considerable part of the nerves of the corium, the medul- lated fibres forming loose net-works around the follicles, which they accompany as far as the sebaceous glands, where they divide into the naked fibrillae which are traceable with certainty as far as the glassy membrane and probably end within the external root-sheath. THE DEVELOPMENT OF THE SKIN AND ITS APPENDAGES. The development of the skin in- cludes the participation of the ecto- derm and the mesoderm, which con- tribute respectively the epidermis and the corium. The history of the epi- dermis is closely identified with that of the ectoderm. In the earliest stage the latter consists of a single layer of low cuboidal cells ; later an addi- tional superficial stratum, the epi- trichium, becomes differentiated, the two layers of the ectoderm probably already indicating the corneous and Malpighian strata of the future epid Fig Section of developing skin from human foetus of three and a half months : a, layer of cuboidal cells rep- resenting stratum Malpighii ; b, polyhe- dral elements forming superficial layers ; c, outermost flattened plates, probably the remains of the epitrichial layer ; d, mesodermic tissue forming corium. ermis, although the precise 278 NORMAL HISTOLOGY. relation between the horny layer and the embryonal cells is still un- settled. It is probable that where a well-developed stratum corneum exists the parts of this external to the stratum lucidum represent the metamorphosed epitrichium ; where, however, a true cornified layer is wanting and the superficial cells belong to a highly-developed stratum lucidum, as in the nails, the epitrichium is not represented, since in this case the entire epidermis is derived from the deeper layer of ectodermic tissue (Bowen, Minot). With the general growth the layers of the epidermis increase in number and the innermost cells assume the characteristic columnar character which continues distinctive of the active Malpighian layer. The corium is formed of mesodermic tissue which becomes condensed beneath the epithelial layer and subsequently is beset with numerous papillary elevations ; the development of vascular structures within the young corium takes place along with the dif- ferentiation of a distinct subepidermal zone within the mesoderm. Before the fourth month of foetal life the corium and the subcu- taneous zones have become defined, and a little later fat-cells appear within the last-named layer. The development of the nails depends upon the specialization of the stratum lucidum within certain areas connected with the ter- minal phalanges. The earliest indication of the nail-formation appears about the third month in the human embryo, and consists of a thick- ening of the primitive epidermis over the end of the digit ; the nail-area becomes defined by a furrow and takes up a permanent position on the dorsal aspect of the finger, when an ingrowth of the stratum Malpighii takes place to establish the root of the nail. About the fourth month the upper cells of the Malpighian layer exhibit granules, which play an important part in the cornifi- cation of the epithelial elements in the formation of the nail ; these granules are very similar to, if indeed not identical with, eleidin in their nature. The cells of the stratum lucidum subsequently un- dergo great increase and constitute the body of the nail. Until about the fifth month the young nail is covered superficially by the epi- trichium, here called the eponychium ; the latter then disappears, and finally is represented only by the small epithelial band, the perionyx, which persists across the root of the nail. The final steps in the nail- formation are associated with a process of desquamation of the stratum lucidum, whereby the distal end of the nail is separated from its bed and the existence of a free edge is established. By the addition of young cells at its posterior margin the nail grows in length, while by the increments to its under surface derived from the stratum mucosum at the lunula it increases in thickness ; the thickest part of the nail is, therefore, not at its THE SKIN AND ITS APPENDAGES. 279 root, but at the anterior border of the lunula ; from this point for- ward the nail remains of constant thickness, since it derives no aug- mentation in its passage over the nail-bed. The regeneration of Fig. 312. Section of skin of fetal kitten, showing earliest stage of development of hair : a, epidermis ex- hibiting thickening and elevation of surface ; b, mesodermic tissue, showing indications of con- densation. Fig. 313. Section of skin of foetal kitten, showing ecto- dermic tissue (a) starting to grow into mesoderm (b) as solid epithelial process. the nail after disease or injury depends upon the integrity of the deeper layers of the epithelium. The development of the hair in the foetus proceeds entirely from the ectoderm. The first indication of the process, about the end of the third month, ap- FlG. 314- '^V^W1*' ' "** " pears as a localized prolif- eration of the ectodermic cells, resulting in a slight transient elevation of the sur- face, and, at the same time, in a feeble encroachment on the subjacent raesoder m. This ectodermal projection soon becomes an epithelial cylinder, whose expanded club-shaped extremity pene- trates deeply into the primi- tive corium to form the epi- thelial constituents of the future hair-follicle. The dif- ferentiation of the surrounding connective tissue produces the fibrous root-sheath, while a projection opposite the base of the primitive epithelial fol- licle contributes the tissue of the hair-papilla. The region immediately over the papilla is the seat of greatest activity and differentiation : the central cells, con- taining probably many eleidin granules, become converted into the hair and its inner root-sheath, while the peripheral cells of the Section of skin of foetal kitten, exhibiting hairs in various stages of development : a, superficial layer of epidermis : b, stratum Malpighii from which rudimen- tary hair-follicles extend into connective tissue (c) of primitive corium ; d, e, /, hairs in different stages of their development ; g, sebaceous glands growing from young hair-follicle. 280 NORMAL HISTOLOGY. Fig. 315. cylindrical epithelial mass assume the character of the external root- sheath. Subsequent differentiation in the central mass of formative cells produces the individual layers of the inner root-sheath and of the hair. The young hair, or lanugo, at first lies com- pletely embedded within the epidermis, its exit being opposed by the cells occupy- ing the neck of the follicle ; these cells soften and undergo fatty degeneration, when the young hair forces its way against the superficial epithelial layers. The epidermal scales at first are raised, but afterwards they are broken through by the pointed ex- tremity of the growing hair-shaft. The eruption of the hairs on the head and the eyebrow occurs about the close of the fifth month of foetal life, and is completed about the sixth month on the extremities. The fcetal hairs, forming the downy covering, or the lanugo, never possess a medulla, and are short-lived, ceasing to grow towards the end of gestation ; shortly after, or even before, birth these embryonal hairs are largely shed and replaced by more per- manent successors ; on the face and a few other places, however, the lanugo remains. The general renewal of the hairs after birth corresponds to the periodical change of coat so common among the lower animals ; such renewal is very unusual in man, the replace- ment of the effete hairs continually taking place. As soon as the growth of a hair is arrested the pressure induced by the surrounding soft elastic structures is no longer resisted, and in consequence the hair is separated and lifted from its papilla ; such hairs possess knob-like extremities, which are lodged in corresponding expan- sions of the outer root-sheath. Beneath the terminal knob the cells of this outer root-sheath grow out as a new mass towards the base of the follicle ; from these young cells in due time the new hair is formed, the details of the process corresponding with those of the development of the primary Section of hair-follicle from human scalp, exhibiting changes accompanying growth of new hair : a, old hair, terminating in expanded degenerating end (a') ; l>, inner root-sheath ending in atrophic area at b' ; c, outer root- sheath ; e, glassy membrane ; f, lateral projection marking attach- ment of arrector pili muscle (g); k, mass of new cells derived from root-sheath of old follicle from which formation of new hair will proceed. THE SKIN AND ITS APPENDAGES. 28l hairs. Coincidently with the growth of the secondary shaft the old dead hair becomes shifted towards the surface, loosened, and finally entirely displaced. The development of the sebaceous glands starts as an out- growth from the external root-sheath pf the hair-follicle, from which knob-like projections extend laterally ; these are at first solid flask-shaped processes, the central cells of which become filled with fat-particles. This fatty metamorphosis affects all the cells occupy- ing the axis of the developing gland as far as the root-sheath ; after a time the latter structure is penetrated and the degenerated fatty cell-mass discharged into the hair-follicle as the first sebaceous secretion. From the original tubular projection secondary com- partments are produced by a repetition of the processes of budding and subsequent hollowing out until the entire complement of saccules has been formed. After the disintegration of the central cells, the peripheral elements undergo similar change. The development of the sweat-glands follows closely that of the hairs and the sebaceous follicles ; as in these, so here, the first stage consists in the ingrowth, during the fifth month, of a solid epithelial club-shaped process from the stratum mucosum into the primitive corium. About the seventh month a lumen appears within the tubular mass, an exit, however, for some time being FlG- 3l6- still wanting ; subsequently the obstructing epidermal layers are broken through. Somewhat before the appearance of the lu- men the extremity of the cylin- der undergoes increased growth, resulting in the thickening and convolution of the tube which represents the future coiled division of the gland ; the full expression of the characteristic convoluted arrangement, how- ever, is not attained until shortly before birth. The muscular tissue of the secretory tubes, situated between the basement- membrane and the lining epithe- lium, is present before the close of the ninth month ; its origin is as remarkable as its position, since the muscle-cells are derived from the elements of the adjacent ectoderm. The basement-mem- brane and the fibrous sheath are contributions from the mesoderm. ', blood- vessels. THE CENTRAL NERVOUS SYSTEM. 313 Fig. 342. idal elements, which become more widely separated and ol greater size on approaching the deeper parts of the zone ; in this situation their basal diameter may reach 40-50 p. The pyramidal cells, in addition to the general outlines of their bodies, are distinguished by the arrange- ment of their processes ; the pro- toplasmic ramifications are disposed as the principal apical processes, which extend towards the periphery as far as the sub-pial zone (Retzius) and by repeated division form a rich arborization within the outer layers of the cortex, and as lateral basal processes, which pass obliquely from the base and break up into rich net- works of delicate terminal protoplas- mic threads ; in addition, numerous smaller lateral processes are given off from the sides of the cell. Not- withstanding the profusion of the fibrils resulting from the subdivision of the protoplasmic processes of these cells, it is highly probable that the fibrils terminate without uniting with one another. From the blunt, central end of the cell the axis-cyl- inder process extends into the white matter, where it becomes continuous with a nerve-fibre. These axis-cyl- inder prolongations give off recurrent collateral processes, which bend towards the periphery. The pyrami- dal body of the cell contains a large round or oval nucleus, with a dis- tinct nucleolus, embedded within a finely granular protoplasm, masses of brownish pigment almost always occupying the base of the cell. The larger pyramidal cells are surrounded by pericellular lymph- spaces, which probably communicate with the extensions of the subarachnoidean space continued with the prolongations of the pia accompanying the blood-vessels within the cerebral tissue. 4. The fourth layer embraces a closely-packed zone (.3-. 4 mm.) composed of small, irregular, oval or angular nerve-cells, 7- Section of cerebral cortex (motor area) of child stained by Golgi's silver method : A, layer of neuroglia-cells ; B, layer of small pyramidal ganglion-cells ; C, layer of large pyramidal cells ; D, layer of ir- regular smaller cells. 3M NORMAL HISTOLOGY. 14 ix in diameter ; among the smaller elements a few larger pyramidal cells are often encountered, as well as radiating bundles of med- ullated nerve-fibres. The cells of this layer resemble those of the second, since their axis-cylinder processes are confined to the gray matter, the elements be- cells of the Fig. 343. ing, therefore, second type. 5. The fifth layer indicates the proximity of the white matter by the large areas occu- pied by bundles of radiating nerve-fibres directly contin- uous with the medullary tracts ; within the interspaces between the nerve-bundles lie the small and medium - sized cells, spindle to pyramidal in form, which characterize this layer. While these cells are arranged generally parallel with the fibre- bundles, sometimes, especially at the bottom of the fissures, they are placed at right angles thereto, in the latter case as- suming a pronounced spindle type. The nerve-fibres enter- ing the gray cortex are ar- ranged in bundles, from which arise net - works variously situated and arranged. The radial bundles proceed as such through about half the entire thickness of the cortex ; beyond this level they rapidly separate into the component fibres which take their way between the ganglion - cells. The fibres given off during the course of the bundles form net- works at all depths occupying the interfascicular portions of the layers traversed ; within the deepest part of the fourth layer, how- ever, the nervous fibrillse are especially numerous, and constitute a conspicuous reticulum in preparations stained by Weigert's Section of human cerebral cortex stained by Weigert's method, exhibiting groups of nerve-fibres; part of white matter and inner layers of gray sub- stance shown : F, white matter from which radiating bundles of nerve-fibres («) extend into gray matter ; C, D, and E, third, fourth, and fifth zones of gray matter : cells are faintly stained. THE CENTRAL NERVOUS SYSTEM. 315 method. In the deeper parts of the broad third layer a similar well-marked net-work occurs, the interlacing fibres of which sur- round the nerve-cells of the layer. Beyond this plane nervous reticulations occupy the third and second layers and extend into the outer zone. A limited number of the nerve-fibres terminate within the outer layer as axis-cylinders which run parallel with the free surface, as do also the terminal ramifications of the axis-cylinder processes of some of the ganglion-cells. The recent investigations of Golgi and others have shown that many fibres end without demonstrable direct anatomical continuity with the nerve-cells, although a close relation between the cells and the fibres undoubtedly exists. While the arrangement just described may be regarded as typical for the greater part of the cortex, a few localities are distinguished by modifications which materially affect the histological details. These changes depend upon either an arrested development of the cortex, as in the septum lucidum, or an increased complexity of the cortical arrangement, as in the hippocampal convolution. Less conspicuous variations, affecting one or more layers, are frequently encountered ; thus, the paracentral convolution contains the largest pyramidal cells, the "giant pyramids" (Betz), the entire third layer participating in the increase of size. The occipital cortex is especially differentiated by subdivisions of the third and fourth layers into eight layers (Meynert), while the gyrus cinguli has the third layer separated into an outer group of small and an inner zone of larger cells, the intervening space appearing radially striated on account of the apical processes which cross it ; within the parietal lobes an additional stratum of small pyramidal cells exists between the third and fourth cortical layers. The involuted cortex of the hippocampal region, including the cornu Ammonis, or hippocampus major, and the fascia dentata, presents considerable complexity. On observing a section of this region with low amplification, it will be seen that the cornu Ammo- nis consists of a central gray zone bounded both internally and externally by a stratum of white substance ; the gray zone corresponds to the cortex of other parts, and is continuous with the thickened gray mass constituting the fascia dentata above, and with the cortex of the hippocampal convolution below. The medullary substance of the latter becomes greatly reduced in its passage over the cornu Ammonis, the attenuated stratum of fibres being known as the alveus which is prolonged into the thicker fimbria. The white layer enclosing the gray zone on the mesial surface is a conspicuous thickening of the peripheral zone of the hippocampal convolution. ^x5 normal histology. The several structures composing the cornu Ammonis, examined from the ventricle towards the outer surface, are — i. The alveus, an attenuated layer of medullated nerve-fibres, homologous with the medullary substance of the typical convolu- Section across cornu Ammonis, fascia dentata, and fimbria : Gh, hippocampal convolution ; Fd, fascia dentata, separated from preceding by hippocampal fissure ; Fi, fimbria, composed of transversely cut longitudinal nerve-fibres ; i, 2, medulla of hippocampal convolution con- tinued over cornu Ammonis ( C), as alveus, into fimbria ; 3, layer of large pyramidal cells ; 4, stratum radiatum ; 5, stratum lacunosum ; 6, stratum moleculare ; 7, lamina medullaris involuta ; m, termination of this lamina in longitudinal fibres ; n, nucleus fascia; dentatae ; g, stratum granulosum ; r, reticulated neuroglia-layer covered by thin sheet of nerve-fibres. (After Henle.) tion. The fibres, while pursuing a course generally parallel to the ventricular surface, run somewhat obliquely ; on approaching the fimbria the layer increases in thickness and the nerve-fibres assume a disposition less oblique, until, within the fimbria, their direction almost coincides with the long axis of the cornu Ammonis. THE CENTRAL NERVOUS SYSTEM. 317 2. The stratum oriens, representing the fifth layer of the cortex, and containing among the bundles of nerve-fibres numbers of spindle- form cells, whose processes extend parallel with the free surface. 3. The stratum cellularum pyramidalium, which corresponds to the deeper portions of the third Cerebral layer, and is conspicuous on account of the large pyramidal ganglion-cells. The latter, moderate in size (30-40 //), are arranged in several closely-packed rows, and send their axis-cylinder processes into the adjoining medullary substance of the alveus, while their long apical proto- plasmic processes pass towards the periphery and give to the outer part of the third layer a vertical striation, which has received recognition as 4. The stratum radiatum. This layer consists almost entirely of the long, tapering processes of the pyramidal elements, Fig. 345. Diagram of the constituents of the cornu Ammonis, Golgi staining : H, hippocampal convolution ; C, cornu Ammonis ; F, fascia dentata ; i, fusiform, 2, 3, small and irregular, 4, 5, pyramidal, and 6, small, cells of respective layers ; 7, 8, nerve-cells of fascia dentata ; al, collaterals of pyramidal cells ; course of axis-cylinder processes shown by fine lines. (After Karl Schaffer.) which often show a disposition to divide into numerous branches before reaching the border of the zone. 5. The stratum lacunosum, composed principally of axis-cyl- inders, which extend parallel to the fibre-layer of the alveus, to- gether with the collateral processes from the neighboring nerve-cells. 6. The stratum moleculare, which contains sparingly distributed fusiform or pyramidal ganglionic elements, whose protoplas- ojg normal histology. mic processes extend vertically into the outer part of the zone of pyramidal cells, as well as laterally within the molecular layer ; their axis-cylinder processes, on the contrary, are directed towards the peripheral nerve-fibres, among which they end. 7. The lamina medullaris ifivoluta, constituting the outermost layer of the convolution, lying next the fascia dentata, from which it is separated by the intervening hippocampal fissure and its pial fold. This layer corresponds to the greatly thickened outer zone of the usual cortex, and is largely made up of tangential nerve-fibres which proceed from the gyrus hippocampi, together with numerous terminal fibrillar derived from the processes of ganglion-cells situated in neighboring strata. The fascia dentata must be regarded as the projecting thickened and specialized free edge of the cortical gray matter, lodged within the hippocampal fissure, which it almost fills. The divisions recognizable in this structure, from within outward, are — 1. The nucleus fasciae dentatae, which comprises an oval area containing nerve-fibres continued from the alveus and numerous ganglion-cells. The latter include three varieties of irregularly- disposed elements, the pyramidal cells proper, the representatives of the similar conspicuous constituents of the cornu Ammonis, the polymorphous cells, possessing very numerous processes, and the fusiform cells. 2. The stratum granulosum, distinguished as a conspicuous band of brilliantly staining small pyriform nervous elements, whose protoplasmic processes extend towards the periphery, while the axis-cylinder fibrils in general pass centrally. 3. The stratum moleculare, consisting of a broad reticulated zone of neuroglia, which contains numerous capillary blood-vessels, a few scattered cells, and the extensions of the processes of the nerve- cells ; it almost completely encloses the stratum granulosum, and is itself covered by 4. The stratum marginale, an extremely thin sheet of medul- lated nerve-fibres representing the outer medullary layer of the cornu Ammonis, of which it is the direct, although attenuated, con- tinuation. The fimbria receives the fibres constituting the alveus, and is com- posed entirely of bundles of medullated nerve-fibres, together with the intervening connective-tissue septa ; the thick fibre-bundles extend longitudinally, and are continued into the tracts of the posterior pillar of the fornix. The septum lucidum represents a rudimentary cortex due to the arrest of development following the isolation of this part of the wall of the cerebral vesicle by the growth of the corpus callosum. THE CENTRAL NERVOUS SYSTEM. <>IQ Since the so-called fifth ventricle is really a cut-off portion of the great longitudinal fissure, those surfaces directed towards the cleft correspond to the free surface of the hemispheres ; the rudimentary layer of gray matter, therefore, forms the immediate lateral boun- daries of this space, and is homologous with the cortex of other regions, while the thin white stratum next the lateral ventricles represents the medulla. The mesially-placed gray cortex of the septum lucidum con- tains a thin superficial stratum of medullated nerve-fibres next the interseptal cleft ; following this lies a layer of gray matter con- taining many small pyramidal cells (16-18,".), the apical processes of which are directed towards the surface homologous with the pe- riphery of the hemispheres ; the deeper zone of the gray matter exhibits spindle-cells. The white substance of the hemisphere is represented by the thin stratum of medullated fibres interposed between the gray layer and the ependyma of the lateral ventricle. The blood-vessels supplying the cerebral cortex, after a short course within the pia almost parallel to the free surface, enter the nervous tissue vertically ; the larger arteries pierce the gray matter and enter the medulla, while those of smaller size break up within the gray cortex into capillary net-works. The law, appli- cable to all parts of the nervous system, that regions rich in large nerve-cells are pientifidly supplied with blood-vessels, is illustrated by the distribution of the capillaries within the cortex, where a rich capillary net-work exists within the layer of large pyramidal cells, while the outer cortical zones, on the contrary, possess only a meagre capillary supply : the net-works within the deepest layers of the cortex are intermediate in the closeness of their meshes. The blood- vessels are surrounded by perivascular lymph-spaces, the pial tissue accompanying the vessels as a delicate sheath attached to the adventitia and enclosing a prolongation of the subarachnoidean space. The corpus striatum consists of the special masses of gray matter, the nucleus caudatus and the nucleus lenticularis, and their associated tracts of nerve-fibres. The ventricular surface of the nucleus caudatus is covered by a well-developed layer of ependyma, beneath which lies the zone of gray substance, containing nerve-cells of two kinds : large multipolar cells (25-30 fi), and much more numerous smaller ganglionic elements, whose size is about half that of the former. The outer surface of the caudate nucleus, directed towards the internal capsule, is broken up by numerous bundles of fibres, which penetrate deeply into the gray mass and produce the characteristic white striae exhibited on section. 320 NORMAL HISTOLOGY. The outer division, or the putamen, of the nucleus lenticu- laris closely resembles, both in color and in structure, the caudate nucleus, with which, indeed, it anteriorly becomes continuous. The paler color of the inner segments, the globus pallidus, depends Section across anterior end of thalamus, striatum, and insula : th, anterior end of thalamus ; st.t. stria terminalis ; n.c, nucleus caudatus ; »./., outer segment of nucleus lenticularis ; /.;«,, t in.' , ex ternal and internal medullary lamina receiving fibres (.r) from caudate nucleus ; a'., internal capsule c.e , external capsule; cl, claustrum ; co, cortex of island of. Reil ; co.a., anterior commissure; g: central gray matter of third ventricle, a, its commissure; c.f., section of anterior pillar of fornix b, c, d, e, elements of subthalamic region ; e' , stratum zonale of thalamus ; o, portion of optic tract. (After Schuuilde-Meynert.) not only upon the presence of greater numbers of medullated fibres, but also upon the lighter tint of the yellowish pigment contained within the multipolar nerve-cells. The nerve-cells contained within the claustrum are principally fusiform elements whose long axes correspond in direction with the neighboring free surface. The optic thalamus is composed chiefly of gray matter, through which extend various tracts of nerve-fibres. The surfaces directed towards the ventricles are sharply defined, the upper or dorsal aspect being covered by a layer of medullated nerve-fibres, the stratum zonale, about .8 mm. in thickness, which fade away on the mesial surface ; the outer and ventral borders of the thalamus, on the contrary, are invaded by fibres from the respectively adjacent internal capsule and the subthalamic region. The gray matter of the thalamus is divided by tracts of fibres into a shorter median segment, the inner nucleus, and a longer THE CENTRAL NERVOUS SYSTEM. 321 external division, the outer nucleus, the fore-segment of the thala- mus containing the anterior or upper nucleus. The gray sub- stance composing these segments is traversed in many places by bundles of medullated nerve-fibres ; in the outer nucleus the nar- row fibre-bundles and the zones of gray substance alternate, fusi- form ganglion-cells (20-30 -,n 339 hollowed out within the cement-substance, which consists of the large lacunae or corneal spaces between the lamellae and the small canaliculi extending from the former as fine branching tubes. The corneal corpuscles are usually applied to one wall of the spaces, which they by no means completely fill, while their Fig- 365- processes extend within the branching canaliculi. In addition to the corneal cor- " . ; puscles, wandering cells, together with the tissue- juices, occupy the spaces and canaliculi. ' ; r^, ..... if The posterior limiting \. c& ■ ■■_". membrane, membrane of Descemet, or poste- rior elastic lamina, ap- Curneal spaces from calf: silver preparation. pears as a clear homoge- neous band at the inner boundary of the cornea, sharply defined from the deepest layers of the substantia propria and clothed on its inner surface by endothelium. The membrane differs from the cor- responding anterior lamella in its less intimate attachment with the yG-^st — .. , ^- - \\ Corneal spaces from calf; exhibited spaces in positive picture after interstitial silver injection. fibrous stratum and in possessing the greatest thickness (10-12 //) at the periphery. After prolonged maceration or treatment with suit- able reagents the resistant lamina is separable into a number of thin 340 NORMAL HISTOLOGY. homogeneous layers, which sometimes exhibit a delicate longi- tudinal striation. The posterior corneal endothelium, or endothelium of Des- cemet's membrane, consists of a single layer of regular poly- hedral plates, whose oval nuclei project slightly beyond the bodies of the cells. Blood-vessels are absent in the cornea, except within a narrow zone, about i mm. in width, at the limbus or margin ; in the fcetus, however, the vessels extend well towards the centre and form the precorneal capillary net-work. The lymphatics of the cornea are represented by the system of intercommunicating spaces and canaliculi ; these clefts open into lymphatic radicles at the periphery, which, in turn, communi- cate with the larger anterior lymphatic vessels. Perineurial lymph- channels enclose the larger nerve-trunks, which they accompany for a variable distance into the corneal tissue ; these lymphatic channels communicate directly with the corneal spaces at frequent intervals. The nerves of the cornea are very numerous, and are distributed largely within the anterior layers. They enter at the corneal limbus as some sixty radially-disposed twigs, each of which includes from Fig. 367. Subbasilar plexus of corneal nerves from rabbit ; gold preparation. three to twelve fibres; the latter almost at once, within .5 mm. of the limbus, become non-medullated. Within the substantia propria the nerve-fibres form a coarse ground-plexus at a level corresponding to about the middle third of the corneal tissue ; from this net-work twigs are sparingly given off to supply the deepest layers, while others pass towards the THE EYE AND ITS APPENDAGES. 341 anterior lamellae, in which they form net-works. Immediately beneath the anterior elastic membrane the smaller fibres form the dense subbasilar plexus, while under the epithelium the finest fibrillae constitute the subepithelial plexus, from which delicate naked axis-cylinders ascend and enter the epithelium, to end between the cells as the intra-epithelial plexus. THE SCLERA. The sclera is composed of the same elements as is the substantia propria of the cornea, but they are less regularly disposed and lack the remarkable transparency of the latter. The ground-substance is made up of interlacing bundles of gelatin-yielding fibrous tissue mingled with elastic fibres ; the fibrous bundles are arranged as two principal sets, those extending longi- tudinally or meridionally and those running transversely or equatorially. The interfascicular interspaces are occupied by the stellate connective-tissue plates, which correspond closely to the corneal corpuscles ; in addition, a few small wandering cells are usually present. The sclerotic and cho- roid coats are united by a layer of loose connective tissue, the lamina suprachoroidea, the extensive interfascicular clefts of which form part of the sub- scleral lymph-space. The suprachoroidal tissue consists of many imperfect la- mellae composed of a fibro- elastic groundwork support- ing irregular groups of flattened endothelioid connective-tissue plates ; the broad trabecular join one another at various angles, and include the imperfectly sep- arated compartments of the gen- eral lymph-space. The larger p partitions convey the numerous vascular and nervous trunks in their course to and from the choroid. The deeply-pigmented tissue of the innermost layer of the sclera, next the subscleral space, constitutes the lamina fusca, and is covered with the endothe- 81 Section of human eyeball taken midway be- tween equator and posterior pole : S, sclera ; p, lamina fusca and lamina suprachoroidea ; P, peri- scleral tissue ; C, choroid ; R, retina with its layers indicated by figures. -,2 • NORMAL HISTOLOGY. lial lining of the lymph-cavity. The outer surface of the sclera throughout a large part of its extent takes part in bounding the episcleral space, where it is likewise covered with endothelium. The blood-vessels distributed to the tissue of the sclerotic coat are meagre, although the tunic is pierced by numerous trunks related with the supply of the underlying parts ; such small vessels as are present break up into capillaries passing among the bundles of fibrous tissue. The lymphatics are represented by the intercommunicating cell- spaces which connect with the larger lymph-cavities. The nerves terminating within the sclera constitute fine twigs given off from the larger trunks passing between the sclerotic and choroid coats ; they break up into fibrillar which end as naked axis- cylinders between the bundles as an interfascicular plexus. THE CHOROID. The choroid consists of a connective-tissue stroma supporting numerous blood-vessels. Dependent largely upon the size and arrangement of the blood-vessels, certain layers are distinguished, these being, from without inward : i. The layer of choroidal stroma containing large blood-vessels. 2. The layer of dense capillary net-works — the choriocapillaris. 3. The homogeneous glassy lamina, or vitreous membrane. The stroma-layer, with its large blood-vessels, constitutes the greater part of the choroid. Within a supporting tissue made up Fig. 369. Section of human choroid : a, retinal pigment adhering to vitreous mem- brane (i) ; c, capillary 'ayer, or choriocapillaris ; d, e, large blood-vessels of stroma-layer (f) ; g, lamina suprachoroidea ; h, tissue of sclera. of closely united connective-tissue lamellae, elastic fibres, and branched pigmented cells, the freely branching arterial and venous trunks take their course, appearing as lighter-colored channels within the darker surrounding matrix. The blood-vessels and the stroma THE EYE AND ITS APPENDAGES. 343 are so intimately united that they constitute a layer of considerable consistence. The largest vessels occupy the most superficial part of the stratum, those next in size the middle, while the smallest approach the capillary zone. The most conspicuous of the large superficial blood-channels are the four venae vorticosae, with their whorls of tributaries. These veins occupy positions around the equator at points about equidistant, towards which the smaller vessels converge from all directions, returning the blood not only from the choroid but also from the ciliary body and the iris. The veins of the choroid are often surrounded by perivascular lymph-sheaths. Many of the larger arteries, in addition to the well-marked circu- larly-disposed muscle with which they are provided, are accompanied by external longitudinal bundles of involuntary muscle. The innermost part of the stroma-layer, next the choriocapil- laris, forms a narrow stratum (10 //. in width) which is devoid, or nearly so, of pigment, and constitutes the boundary zone. In the eyes of many animals (horse, cow, sheep) this layer possesses wavy bundles of connective tissue, to whose peculiar arrangement fPmr Human choroid seen from its inner surface, exhibiting surface view of cap- illary net-work, or choriocapillaris \c, c) ; b, b, large blood-vessels of stroma- layer beneath ; a, a, intervening stroma-tissue. is due the metallic reflex sometimes seen from such eyes ; this shining structure is known as the tapetum fibrosum, as distinguished from the iridescent tapetum cellulosum of the carnivora which is dependent upon the presence of several layers of plate-like cells containing innumerable small crystals. The capillary layer, or choriocapillaris, consists of a narrow 344 NORMAL HISTOLOGY. zone, about 10 //. in width, at the inner part of the choroid, composed of a structureless, apparently homogeneous, matrix, in which lie embedded the close capillary net-works derived from the terminal branches of the short ciliary arteries. The vitreous lamina, or glassy membrane, forms the most internal layer of the choroid and supports the retinal pigment. The membrane presents a delicate homogeneous stratum (2 y. in thick- ness), ordinarily without appreciable structure, and is very intimately associated with the adjoining layer of the choroid ; to its inner sur- face patches of retinal pigment frequently adhere on removal of the retina. The nerves of the choroid, non-medullated fibres distributed to the blood-vessels, are derived from the plexus formed within the suprachoroidal tissue by branches given off from the long and short ciliary nerves in their transit through the subscleral space. THE CILIARY BODY. This structure includes that portion of the uveal tract situated be- tween the termination of the choriocapillaris, opposite the ora serrata behind and the ciliary or outer margin of the iris in front. Within this important territory three areas may be distinguished : 1, the ciliary ring; 2, the cili- Fig. 371. ary processes ; 3, the ciliary muscle. The ciliary ring, or orbicu- lus ciliaris, is a circular tract about 4 mm. in breadth, situated immediately in front of the ora serrata and extending to the posterior ends of the ciliary pro- cesses. This zone differs from the choroid in the absence of the choriocapillaris and in the presence of muscular tissue prolonged from the mass of the ciliary muscle ; the character of the stroma also changes, its bulk being here made up of fibrous connective bundles instead of elastic lamellae. The ciliary processes consist of an annular series of some seventy prominent radial vascular folds which project from the inner surface of the ciliary body and arise from the confluence of several of the low ridges on the ciliary ring ; after attaining a height of about 1 mm., they abruptly end at the base of the iris, sinking Section of human ciliary processes ; /, in- terstitial connective-tissue siroma, covered by retinal layers (JZ) ; i, o, inner clear and outer pigmented layers of cells ; _/", fibrous tissue of processes. THE EYE AND ITS APPENDAGES. -,ac to the level of the underlying ciliary muscle. The stroma of the processes is a continuation of the connective tissue of the orbicular zone, this layer being the true prolongation of the choroid, since the muscular tissue must be regarded as an intercalation between the sclerotic and choroid coats. The vitreous lamina is continued as a delicate homogenous membrane, 3 to 4 fi in thickness, over the inner surface of the ciliary processes. Inside this layer the internal face of this entire region, including the ciliary ring and the ciliary body, as well as the iris, is covered by the deeply-pigmented rudimentary layers of the pars ciliaris retinae, consisting of an inner small row of tall columnar elements and an outer sheet of low pig- mented epithelium. Since these layers represent the rudimentary folded anterior laminae of the ectodermic optic vesicle, the ciliary processes and the iris consist of two genetically distinct parts, the Fig. 372. ^fe^. Section through ciliary region cf human eye : A , cornea; a, i, c, its epithelium, substantia propria, and endothelium ; C, scleral conjunctiva, terminating at d\ i?, sclera,- e, sclero-corneal juncture ; D, iris ; E, ciliary body covered by pigment-layer, /; k, fibrous stroma of ciliary processes ; f, bands of pectinate ligament ; g, spaces of Fontana ; s, canal of Schlemm ; v, venous channels ; tn n, o, meridional, radial, and circular (Miiller's) fibres of ciliary muscle; r, subscleral space bridged by fibrous bands. mesodermal connective-tissue stroma, containing blood-vessels and muscle-fibres, and the inner deeply-pigmented ectodermal stratum. ..5 NORMAL HISTOLOGY. The ciliary muscle presents a conspicuous thickening for about i mm. , which extends from the orbicular zone to the base of the iris and bears on its inner surface the connective-tissue stroma of the ciliary processes and the orbicular ring. In meridional sections its mass appears as a triangular area, the cross-section of a three-sided annular band of muscle entirely encircling the eyeball. The triangle thus formed closely approximates a right angle whose sides are unequal ; the shorter anterior side extends from the sclero- corneal juncture towards the ciliary processes, and the longer inner border is prolonged to meet the outer side or hypothenuse at an acute angle at the anterior border of the choroid. The mass of the ciliary muscle consists of interlacing bundles of involuntary muscle, the interspaces between which are filled by connective tissue. The muscular fasciculi are arranged as three sets, the meridional, the radial, and the circular. The meridional fibres lie generally parallel to the sclera, and form a compact layer attached in front at the sclero-corneal junction, near the anterior margin of Schlemm's canal, and behind at the fore margin of the choroid, where, in common with many of the radial fibres, it finds insertion ; in recognition of this attachment, the meridional and radial fibres were named the tensor choroideae. The radial bundles spread out fan-like from their anterior attach- ment, the most external fibres running nearly parallel to the meridio- nal bundles, with which they become continuous, while the anterior pass off at a considerable angle. The circular fibres, the ring-mus- cle of Muller, constitute a distinct group of equatorially-disposed bundles, which occupy the internal angle of the ciliary muscle and extend at right angles to the preceding bundles. The blood-vessels of the ciliary body are especially concerned in supplying the ciliary muscle, to which minute arterial twigs pass from the imperfect vascular circle lying behind the arterial circle of the iris. The numerous nerves of the ciliary muscle are derivatives of the ciliary trunks, which on entering the muscle form a plexus within its substance ; from this plexus fibres pass internally to the iris, outwardly to the cornea, while others are distributed to the ciliary muscle itself. Small ganglion- cells also occur, singly or in small groups. THE IRIS. The iris constitutes the anterior segment of the uveal tract, and consists of a principal stroma-layer covered in front by a reflection of the corneal endothelium and behind by the continuation of the deeply-pigmented rudimentary retinal layers — the pars iridica THE EYE AND ITS APPENDAGES. 347 5. Pigment-layer, of OPTIC VESICLE. retincB. The various components of the iris and their morphological relations may be grouped as follows : 1 . A nterior en doth eliu m . 2. Anterior boundary layer, ~) Continuation of the tissues of the 3. Vascular stroma- layer, > uveal tract proper, constituting 4. Posterior boundary layer, J the stroma-zone. ' a. Anterior layer of pig- N mented spindle - cells representing outer layer b. Posterior layer of pig- mented polygonal cells representing inner layer The anterior endothelium consists of a single layer of thin nu- cleated polygonal plates, the direct prolongation of the corneal endothelium. The protoplasm of the cells is finely granular, but always free from pigment. The anterior boundary layer is formed by modification of the foremost stratum of the iris-stroma ; the connective tissue consti- Fig. 373- Section through part of iris and lens, from human eye : /, iris ; a, anterior endothelium ; 6, anterior boundary layer ; c, vascular stroma ; d, posterior boundary layer; e, pigment-layer continued as far as g on pupillary margin (P) ; f, cut circular muscle-bundles of sphincter; L, surface of crystalline lens; h, anterior lens capsule, %vith anterior epithelium beneath; i, tissue of lens. tuting this layer resembles the reticular tissue of lymphatic struct- ures, comprising several layers of net-works within the interspaces of which lie lymphoid cells in greater or less profusion. The vascular stroma constitutes the chief mass of the iris, and, in addition to its numerous blood-vessels, contains involuntary ,4g NORMAL HISTOLOGY. muscle and nerves. The stroma consists of loose spongy re- ticular connective tissue greatly strengthened by the radially- disposed blood-vessels and nerves, around which the delicate stroma forms ensheathing masses of considerable density. The clefts situated between these adventitious sheaths and the included vessels and nerves form a system of lymphatic channels through- out the iris which communicate with the anterior chamber through the lymph-spaces at the irido-corneal angle. The arteries of the iris spring from the anterior part of the cir- culus arteriosus iridis major, Fig. 374. situated at the ciliary border, and pass towards the centre of the iris as radially-disposed, freely-anasto- mosing twigs ; about 1 mm. from the inner edge of the iris these vessels unite to form a second delicate vascular ring, the circulus arteriosus iridis minor, which marks the division of the iris into its pupillary and ciliary zones, which are respectively 1 mm. and 3-4 mm. in breadth. From this circle the arterioles continue their course towards the pupillary bor- der, and end in the capillary net- work distributed to the sphincter muscle. Capillary reticula exist also within the anterior and pos- terior layers of the stroma. All the capillaries are tributary to the radiating veins which pass to the ciliary border, where they join those of the ciliary processes and finally empty into the radicles forming the venae vorticosae. Bundles of involuntary muscle occupy the pupillary border and the posterior zone of the stroma-layer ; these are arranged as two sets, — the annular bundles encircling the pupillary margin of the iris and constituting the sphincter of the pupil, a muscular zone about 1 mm. in width, and the few scattered radially-disposed bundles extending from the pupil towards the ciliary margin and forming an incomplete, by no means continuous, layer, the dilator pupillae. The posterior boundary layer, or vitreous lamella, appears as a glassy structureless membrane, about 2 (i in thickness, which stretches over the posterior surface of the stroma and supports the pigment-layer : in the nature of its substance this structure closely approaches elastic tissue. The pigment-layer, or pars iridica retinae, is usually so densely Injected iris from eye of dog: P, pupillary margin, around which capillary net-work is formed by vessels proceeding from lesser ar- terial circle. THE EYE AND ITS APPENDAGES. oaq packed with deeply-colored particles that its real constitution is masked. This stratum is composed of two layers, an anterior and a posterior. The anterior or outer layer is formed of radially- arranged spindle-cells which pass without interruption from the ciliary border of the iris to the pupillary margin ; at the ciliary border the cells change their form and arrangement, becoming polyhedral and circularly disposed and continuous with the low pigmented elements constituting the corresponding layer of the ciliary processes. The posterior layer presents a thicker zone (30-35 m) of pig- mented cells, in which the colored particles are so densely packed that the cell-boundaries and the nuclei are completely masked, the entire layer appearing as one continuous mass of pigment. The pigment-layer covers the entire pupillary margin, and often ends as a somewhat thickened free edge slightly in advance of the plane of the iris ; at this border, which represents the free anterior lip of the embryonic secondary optic cup, both strata of the pigment-layer become continuous. The posterior surface of the pigment-layer is covered by a very delicate cuticular membrane, the membrana limitans iridis, which is continued from the similar structure extending over the cili- ary processes ; it appears first at the ora serrata as a new formation, since a true membrana limitans interna, in the sense of a distinct cuticle, does not exist over the retina proper. The marked variation in the color of the iris is largely dependent on the amount and position of its pigment. In blue eyes the stroma of the iris is entirely free from pigment, the latter being confined to the posterior pigment-layer, from which position it is seen through the superimposed iridal strata. With the darker color of the iris its strom a- cells also acquire pigment ; in light gray eyes this is small in amount, in brown eyes greater, while in the darkest eyes the colored particles are very numerous and sometimes appear as almost continuous pigmented areas ; in albino eyes, on the other hand, even the retinal portion of the iris is devoid of pigment. The nerves of the iris, derived from the intra-muscular ciliary plexus, enter the more superficial part of the stroma-layer as med- ullated fibres. Within the iris the nerve-fibres soon lose their med- ullary sheath and form one or two irregular net-works, the most constant of which is a circular plexus in the vicinity of the sphinc- ter muscle ; from this net-work pale fibres are distributed to the substance of the latter muscle. The principal plexus lies anterior to the plane of the chief vascular net-work, the posterior zone of the iris being poorly supplied with nerves. The irido-corneal angle, marking the junction of the cornea, the 35Q NORMAL HISTOLOGY. sclera, the iris, and the ciliary muscle, constitutes one of the most important regions in the eye, not only with regard to its anatomical details, but also in view of its practical clinical significance. As already described, the substantia propria of the cornea passes directly into the ground-substance of the sclera ; in consequence of the rearrangement of the tissue-elements of the two structures taking place soonest in the superficial planes of the cornea, the line of transformation becomes oblique, thereby producing an apparent overlapping of the sclera in front, and a corresponding extension of the cornea behind. The posterior elastic membrane, on reaching the corneal mar- gin, splits up into a number of stiff homogeneous fibres, many of which become attached to the base of the iris and constitute the liga- mentum pectinatum iridis. By the union of the processes from the iris and Descemet's membrane with the elastic fibres derived from the anterior attachment of the ciliary muscle and a few bands from the sclera, a reticulum of thin trabeculae is formed, which occupies the angle between the cornea and the iris. This spongy tissue constitutes an annular mass enclosing a system of intercom- municating cavities, the spaces of Fontana. These clefts, lined Fig. 375. Section through irido-corneal angle of human eye, highly magnified : a, substantia propria of cornea; b, posterior limiting membrane, splitting at corneal margin into delicate lamella (rf) ; c, endothelium continued over iris (z) ; f, elastic lamellae separating Schlemm's canal (S) from spaces of Fontana (s, s) and giving attachment to fibres of ciliary muscle (h). by an imperfect layer of endothelium, are more conspicuous in the eyes of some of the lower animals (horse; ox, pig, sheep), where they are far better developed than in man. Within the sclera, close to its inner border and the corneal juncture, THE EYE AND ITS APPENDAGES. 351 lies a flattened annular channel, the canal of Schlemm ; the inner wall of this canal is formed by intersecting delicate lamellae whose loose disposition suggests an incomplete isolation of the channel from the adjacent spaces of Fontana. The nature of the canal of Schlemm, whether a venous or a lymphatic channel, has long been a subject of discussion ; *the weight of evidence warrants re- garding it as a venous canal, between which and the lymph-clefts represented by the spaces of Fontana free communication un- doubtedly exists. THE RETINA. The inner nervous tunic of the eyeball includes the retina alone, which extends from the optic entrance throughout the posterior seg- ment of the ball and as far forward as the pupillary margin of the iris. This extensive tract, corresponding in its morphological limits to the secondary optic vesicle, falls into three divisions : (1) the pars optica retinae, including the entire posterior segment and end- ing at the ora serrata; (2) the pars ciliaris retinae, covering the posterior surface of the ciliary zone and processes and extending from the ora serrata to the base of the iris ; and (3) the pars iridica re- tinae, passing over the posterior surface of the iris from the base to the anterior edge of the pupil, where it terminates as a slightly-thick- ened margin, which corresponds to the free lip of the double-layered optic cup. The retina proper, or pars optica retinae, consists of an inner and an outer lamina, which correspond to the inner and outer layers of the optic vesicle ; the outer lamina includes the pigment-layer alone, while the inner lamina embraces the remaining layers of the retina. The inner lamina permits further subdivision of its structures into the neuro-epithelial and the cerebral layer. The relations of these divisions to the individual retinal layers may be expressed : /. Outer layer of optic 1 Pigment.layer. A. Pigment layer, vesicle. ) r Layer of rods and cones ; 1 B Neuro.epitheKal J Limiting membrane ; layer. I Outer nuclear layer ; II. Inner layer of optic I Outer reticular layer ; -. vesicle. Inner nuclear layer ; Inner reticular layer ; \ C. Cerebral layer. Ganglion-cell-layer ; Nerve-fibre-layer. J The retinal structures consist of two parts, — the nervous ele- ments and the supporting neuroglia. The supporting tissues contribute a considerable part of the entire retina, but differ in their amount in the several layers. The most conspicuous constituents of the supporting framework are long neuroglia-fibres, the radial or2 NORMAL HISTOLOGY. fibres of Muller, which extend through the entire thickness of the retina. The expanded inner ends of the supporting fibres are so closely applied that they produce a seemingly continuous mem- brane, the so-called membrana limitans interna. The radial fibres rapidly diminish in diameter beyond their bases, and are con- tinued as narrow irregular stalks gi\*ng off lateral branches in pro- fusion to the reticular layers ; within the inner nuclear layer each fibre presents an irregular nucleated enlargement, and gives off lateral processes for the support of the nervous elements of the inner nuclear layer, as well as to each of the succeeding layers. At the Fig. 376. Diagram illustrating the relation of the retinal elements. A, layer of rods and cones; B, limitans externa ; C, outer nuclear layer ; E, outer reticular layer (between the two (D) Henle's fibre-layer) ; F, inner nuclear layer ; G, inner reticular layer ; H, layer of ganglion-cells : /, fibre-layer ; K, limitans interna, a, supporting fibres of Muller ; b, c, rod- and cone-visual cells ; d, bipolars belonging to rod cells ; e-i, bipolars belonging to cone-cells ; k-tn, horizontal nerve-cells ; «, centrifugal nerve-fibres ; o-t , ganglion-cells connected with optic fibres; a-e, spongioblasts or amacrines arranged in layers; 4, d, diffuse amacrines ; rj, nervous amacrine. (Kallius after Ramon y Cajal.) inner border of the rods and the cones the expanded ends of the neu- roglia-fibres form the external limiting membrane, delicate pro- cesses extending from the latter between the bases of the rods and the cones, which they surround and embrace as the "fibre-crates." In addition to the long radial fibres, richly-branched neuroglia- cells occur within the outer reticular layer to the fibre-complex of which they contribute. Within the meshes of the framework just described the ner- vous elements of the retina are distributed in a manner charac- teristic for each layer : a brief consideration of these is therefore necessary. THE EYE AND ITS APPENDAGES. 353 Fig. 377. Ik The nerve-fibre-layer contains the continuations of the optic fibres which, after having lost their medullary substance in their passage through the lamina cribrosa, radiate as naked axis-cylin- ders to all parts of the retina as far as the ora serrata. The fibre- layer is thickest at the edge of the optic disk and thinnest at the extreme retinal periphery. Sooner or later the fibres forsake their peripherally-directed course, and, bending sharply, pass almost per- pendicularly to the ganglion- layer and other strata. The ganglion-cell-layer consists of a single row of large multipolar nerve- cells (15 to 30 fi), whose axis-cylinder processes are directed towards the fibre- layer ; their branched pro- toplasmic processes, when well developed, pass into the inner reticular zone, to meet the arborizations of the cone- bipolars. The ganglion- cells in the central part of the retina are densely packed in the macula, constituting overlying rows, but towards the periphery they are less plentiful, and at the ora ser- rata infrequent. The inner reticular layer presents a characteristic retic- ulated tissue composed of neuroglia net-works and the rich arborizations of various nerve-cells ; the processes origi- nate from both the elements of the ganglion-layer and the cells of the adjacent nuclear stratum. The internal nuclear layer includes a number of distinct ele- ments, and presents two subdivisions : (a) an inner layer of nerve- cells, the spongioblasts, or amacrines, and (6) an outer layer of the rod- and cone-bipolars forming the ganglion retinae. The "spongioblasts" are not concerned in the production of the sus- tentacular tissue, as their name — given under erroneous ideas regard- ing their function — would imply, but are nervous elements whose branched protoplasmic processes are resolved within the inner reticular layer into arborizations. The cone-bipolars send their 23 Section of human retina : a, internal limiting mem- brane formed by apposition of expanded basis of Mai- ler's fibres (;>) ; b, fibre-layer ; c, layer of ganglion-cells (z) ; d, e, inner reticular and inner nuclear layer ; /, gt outer reticular and outer nuclear layer; h, outer limit- ing membrane : i, layer of rods and cones ; k, portion of pigment-layer ; v, x, blood-vessels. •554 NORMAL HISTOLOGY. axis-cylinder processes into the inner reticular layer, to end at various levels in arborizations in relation with the terminal filaments of the ganglion-cells ; their protoplasmic processes extend as far as the outer reticular layer, where they terminate in ramifications beneath the cone-cells. The protoplasmic processes of the rod- bipolars end beneath the rod-cells, their axis-cylinder processes penetrating the inner reticular stratum, to end in close relation with the ganglion-cells. The outer reticular layer appears as a narrow zone made up of an intricate net-work of fine fibres with sparingly distributed nuclei. The fibrillae are derived from the neuroglia and from the processes of nerve-cells, among which are the horizontal cells whose axis-cylinder processes extend horizontally within the layer, often for considerable distances, to end beneath the visual cells. The outer nuclear layer and the layer of rods and cones, the remaining strata of the inner lamina of the retina, together constitute the neuro-epithelium. Since the rods and the cones and the outer nuclear layer are parts of a single lamina of tall neuro-epithelial elements, the visual cells, of which they are respectively the outer and inner segments, these strata must be regarded as subdivisions of the one broad zone, and not as independent retinal layers. The outer and inner segments are sharply separated by the intervening membrana limitans, through the openings in which the rods and the cones protrude. The constituents of the neuro-epithelium are, therefore, the rod-visual cells and the cone-visual cells, supported by the sustentacular tissue. The rod-visual cells are composed of two parts, the one situ- ated without the limitans, including the non-nucleated and highly- specialized segments, the rods, and the other within the limitans, consisting of slender varicose elements, the rod-fibres, provided with fusiform enlargements, the rod-spherules, which contain the nuclei of the visual cells. The rods are slender cylindrical struct- ures, about 60 ft in length and 2 (i in breadth, composed of two chemically and optically distinct parts, the outer and inner seg- ments. The outer segments of the rods are cylindrical, apparently homogeneous, highly-refracting bodies, which, after certain reagents, exhibit a disposition to break up into thin transverse disks. The outer segments of the rods are further distinguished as being the exclusive seat of the peculiar visual purple or rhodopsin. The inner segments of the rods are slightly broader and less regularly cylindrical, and present a finely granular appearance, the parts of the segments nearest the membrana limitans possessing a peripheral longitudinal striation. THE EYE AND ITS APPENDAGES. 355 The inner segments of the rod-visual cells include the rod- fibres and their nucleated expansions, the rod-granules. The rod-fibres are slender, greatly extended, and often varicose, and reach from the membrana limitans into the external zone of the outer reticular layer. Each rod-fibre represents the greatly attenu- ated protoplasmic body of a visual cell, the situation of whose nucleus is indicated by the ellipsoidal enlargement. These enlarge- ments, the rod-granules, vary in position, sometimes lying near the outer end, at other times close to the middle or the inner extremity of the fibres. The granules are almost entirely occupied by the nuclei of the visual cells, which are covered by an extremely thin layer of the cell-protoplasm. The nuclei of the cells are oval in form, about 6 fi in length, and characterized by a remarkable differentiation of their substance into lighter and darker transverse bands. The cone-visual cells consist also of two parts, the outer di- visions, the cones, situated beyond the membrana limitans, and the inner portions including the cone-fibres and their nucleated cone- granules. The cones, like the rods, present inner and outer seg- ments, which in physical and chemical properties resemble the corresponding parts of the rods ; the cones, however, are little more than half (32-36 /*) the length of the rods. The inner segments of the cones are much wider than their outer divisions, and appear as truncated conical bodies whose sides are not absolutely straight, but slightly convex. The outer part of these segments is occupied by an ellipsoidal group of fine longitudinal fibrillae, the fibre -body, which corresponds with the similar structure sometimes present within the rods. The inner segments of the cone-visual cells, representing the bodies of the elongated cells, include the cone-fibres and their granules. The cone-fibres differ from the rod-fibres in being broader at the inner ends and more regular in their general contour ; the cone-granules always lie, except in the macular region, next the membrana limitans. The distribution of the two kinds of visual cells varies in the different retinal regions ; the arrangement prevailing throughout the greater part of the retina is such that the adjacent cones are separated by three or four rods, the latter far outnumbering the cones. On approaching the macula the number of cones increases, the cones being so closely placed that they are separated by only a single row of rods ; within the fovea itself the rods entirely disappear, the entire percipient layer being composed of cones alone. On the other hand, towards the periphery the number of these visual cells diminishes, and at the ora serrata the cones are widely separated, while the relative number of rods is very large. The ,eg NORMAL HISTOLOGY. conclusion inferable from the distribution of these elements in the hu- man retina, that the cones are the essential perceptive instruments, is not applicable as a generalization, since in many of the lower animals the cones are in the minority or even entirely wanting (hedgehog, shark, sturgeon), and the rods predominate ; it seems, however, probable that the highest acuity of vision requires the presence of cones. The entire number of cones in the human retina has been computed at something over three and one-half millions (Salzer), while the rods are supposed to aggregate one hundred and thirty millions. The pigment-layer represents the outer lamina of the embry- onal optic vesicle, and consists of a single layer of polyhedral epi- thelial cells containing pigment-granules in varying amount. These cells ( 1 2-1 8 /jl) are usually six-sided, but may have fewer or more borders ; the cells in the vicinity of the ora serrata are of exception- ally large size and dark color. The elements of the pigment-layer exhibit a differentiation into an outer zone next the choroid, free from pigment and containing an oval nucleus, and an inner zone loaded with pigment-granules. The inner part of the pigment-cells includes protoplasmic pro- cesses directed towards the layer of neuro-epithelium, between the rods and the cones of which they extend for a variable distance ; the depth to which the pigment-granules penetrate along the pro- cesses between the cells depends upon the influence of light, since under strong illumination the granules wander along the protoplas- mic processes as far as the inner segment of the rods and the cones, while in eyes kept in the dark for some time before death the intercel- lular processes remain uninvaded. The structural details above described represent the construction of the retina throughout the greater part of its extent : two regions, however, present such marked variations from the typical arrange- ment as to call for brief special mention ; these are the macula lutea and the ora serrata. The macula lutea and the contained fovea centralis corre- spond to the posterior pole of the visual axis, and are distin- guished physiologically by the acuity of vision, which here attains its highest degree. The macula lutea is characterized, in addition to its yellow color, by a distinct thickening of certain of the retinal layers and by the absence of the rod-visual cells within its area. The distinctive color of the macula depends upon the presence of diffuse yellowish pigment within the layers internal to the visual cells, the latter elements remaining colorless ; in consequence of this arrangement the fovea, in which the neuro-epithelium alone exists, is devoid of pigment, and therefore appears as a light spot within the colored area. THE EYE AND ITS APPENDAGES. 357 The increased thickness of the retina at the macular margin depends almost entirely upon the extraordinary development of the layer of ganglion-cells, which progresses until a stratum from seven to nine cells deep replaces the usual single row. The fovea, on the other hand, is produced by the hollowing out of the centre of the macula consequent upon the gradual thinning, to almost suspension, of the retinal layers lying internal to the Diagrammatic section of the human fovea. Magnified 375 diameters. (Golding-Bird and Schafer.) — 2, ganglion layer; 4, inner nuclear layer; 6, outer nuclear layer, the cone-fibres forming the so-called external fibrous layer of Henle; 7, cones; v, section of a blood-vessel; ]\I, membrana limitans externa ; og, ig, outer and inner granules (cone-nuclei and bipolars) at the centre. outer nuclear zone ; the centre of the foveal depression, the fun- dus foveae, consists chiefly of the neuro-epithelium. Within a central area the fovea is devoid of blood-vessels. The ora serrata marks the termination of the optical part of the retina and the transition into its anterior continuations, the pars ciliaris and the pars iridica. The ora is distinguished, in addition to its irregular serrated border, by the abrupt diminution in the thickness of the retina, brought about by the sudden termina- tion at this point of many of its layers. The regular diminution in the retinal thickness proceeds gradually from the fundus towards the periphery, when, on reaching a point near the ora serrata, many layers end abruptly, the ciliary continuation measuring only about one-third of the thickness of the adjacent retina. ^c8 NORMAL HISTOLOGY. The nerve-fibre and the ganglion-cell layer having already ended before reaching the ora, the sudden reduction is caused principally by the abrupt termination of the two reticular strata. The Fig. 379. Section of human retina through ora serrata : A, B, visual and ciliary portion of retina; a, vacuoles; b, robust fibres of Muller; c, remains of nuclear layers; d, termination of supporting fibres ; e, transformation of inner nuclear layer into colum- nar cells within continuation of pigment-layer. region of the ora serrata is also noteworthy on account of the re- markable development of the radial fibres of Muller, which here occur not only in unusual numbers but also of exceptional strength. Beyond the ora serrata the retinal laminae are continued as the pars ciliaris and the pars iridica retinae. These prolongations consist of an outer and an inner lamina. The outer layer is the direct and only slightly modified extension of the retinal pigment ; the inner lamina, the attenuated representative of the remaining retinal layers, consists of a single row of slender colum- nar cells, which originate at the ora by the transformation of the elements of the inner nuclear layer. A delicate cuticle, the limitans interna, extends over the posterior surface of both the ciliary body and the iris ; this membrane is a true cuticular for- mation, and begins at the ora as a new structure not present within the optical part of the retina. THE OPTIC NERVE. The optic nerve corresponds to a highly-developed single fu- niculus, enveloped by stout connective-tissue sheaths, which are prolongations of the brain-membranes. Externally the optic nerve is invested by a robust fibrous membrane, the dural sheath, de- rived directly from the dura ; this covering extends the entire length of the nerve, and on the entrance of the latter into the eyeball be- comes continuous with the outer part of the sclera. The surface of the optic nerve is closely invested with the pial sheath, an extension of the pia, while between the latter and the dural covering lies a delicate partition from the arachnoid, constituting the arach- noidean sheath. The clefts included between these sheaths con- THE EYE AND ITS APPENDAGES. 359 Fig. .380. stitute the subdural and the subarachnoidean lymph-spaces of the optic nerve, which communicate with the corresponding inter- cranial cavities. On reaching the eye- ball the tissue of the dural sheath passes uninterruptedly into the outer two-thirds of the sclera ; the greater part of the pial sheath blends with the inner third of the sclera, some of its fibres, however, joining the choroid. The arachnoidean sheath unites with the dural, in consequence of which arrangement the subdural and sub- arachnoidal spaces be- Transverse section of human optic nerve : d, dural sheath : a, arachnoidean sheath ; /, pial sheath; n, bundles of nerve- fibres separated by fibrous septa (e). come continuous at their ocular extremities. The trunk of the optic nerve, about 3 mm. in diameter, consists of a great number (almost 800) of bundles of medullated nerve-fibres separated by- intervening fibrous partitions, offshoots from the pial sheath. Each bundle is composed of small medullated fibres (2 fi), which are without neu- rilemma. On reaching a level corre- sponding with the confluence of the sheaths of the nerve with the sclera, the optic fibres pass through the sieve - like lamina cribrosa and lose their medullary coat, contin- uing to their retinal distribution as naked axis - cylinders. Fig. 381. :jm ■I ^ fe^e ■ & . Section of human optic nerve under higher magnu fication : b, bundles of nerve-fibres enveloped in con- nective-tissue sheaths (jr) ; «, neuroglia nuclei; x, nuclei of interfascicular connective tissue u) ; v, blood- vessels. Occasionally the medullated fibres retain their medullary substance after their passage through the lamina cribrosa, such conditions presenting very striking ophthalmoscopic appearances. 360 NORMAL HISTOLOGY. The lamina cribrosa consists of five to eight lamellae, composed of transver&ely extending fibrous trabecular, the direct pro- longations of the scleral tissue. These bands bridge across what otherwise would be a canal, and unite in such manner that the openings occupied by the nerve-bundles present less area than the intervening fibrous tissue. The fibrous lamellae, additionally con- nected with one another by vertical bands, pass from the margins of the scleral ring to the connective tissue supporting the blood-ves- sels within the optic nerve. The lamina cribrosa marks the nar- Fig. 382. 9 e Longitudinal section through optic entrance of human eye : a, a, bundles of optic fibres, which spread over retina at a', a' ; />, layers of retina terminating at edge of optic papilla ; c, choroid ; d, sclera, continued across optic nerve as lamina cribrosa ; e,g, i, respectively pial, arachnoidean, and dural sheaths, including subdural and subarachnoidean lymph-spaces; /, /', retinal vessels cut longi- tudinally. rowest diameter of the optic nerve, the loss of the medullary substance, together with the decrease in the neuroglia, reducing the size of the nerve about one-half. On arriving at the margin of the optic papilla, the bundles of nerve-fibres bend over its edges, con- stituting a thick layer, which rapidly thins away during its radial distribution over the retinal area. The centre of the optic papilla not infrequently presents a funnel- shaped depression, at the bottom of which the retinal vessels enter ; this depression, variable in size and form, but always retain- ing sloping walls, is known as the physiological excavation, as distinguished from those possessing the vertical or overhanging walls indicative of grave pathological change. At some distance (15-20 mm.) from the eyeball the retinal blood- vessels pierce the exterior of the optic nerve to take up a central THE EYE AND ITS APPENDAGES. 36l position, surrounded by connective tissue, which they maintain until their final branching on the papilla. The blood-vessels of the retina constitute an independent sys- tem composed of end-arteries ; the only communication between the retinal and ciliary vessels is established within the sclera, close to the optic nerve, by means of minute scleral and choroidal branches. The larger retinal vessels are situated within the inner part of the fibre-layer and supply twigs to the cerebral division alone, the epithelial portion being non-vascular and deriving its nutrition from the adjacent choriocapillaris. The capillaries are arranged as two net-works, an inner and an outer. The inner net-work lies within the fibre-layer, is wide- meshed and derived directly from the division of the retinal vessels; the outer net-work, situated within the inner nuclear layer, is dependent upon the former, since its capillaries are derived from the branches given off from the inner vascular reticulum. The retinal arteries and veins are surrounded by adventitious sheaths, the spaces included between these sheaths and the walls of the vessels constituting perivascular lymph-clefts. THE CRYSTALLINE LENS. The crystalline lens comprises two genetically distinct portions, the lens-substance and the lens-capsule. The lens-substance consists of the epithelium of the lens and the lens-fibres — both epithelial structures directly derived from the invaginated ectoderm. The epithelium of the lens, the representative of the anterior wall of the primary lens-vesicle, consists of a single layer, of low polyhedral cells, about 20 fi in diameter, whose granular proto- plasm contains an oval nucleus, also often vacuoles. These cells lie immediately beneath the anterior capsule and extend backward as far as the equator, at which point the epithelial cells are trans- formed into the lens-fibres. A thin subcapsular stratum of albuminous substance exists as a connecting medium between the epithelium and the capsule, the same substance being continued be- tween the posterior lens-capsule and the lens-fibres behind. Be- neath the epithelium a subepithelial stratum of somewhat simi- lar albuminous substance unites the epithelium and the lens-fibres and occupies the cleft representing the remains of the original cavity of the lens-vesicle ; sometimes a few drops of fluid — the liquor Morgagni — occupy this subepithelial stratum. The lens-fibres are greatly elongated modified epithelial cells, whose ancestors constituted the posterior wall of the lens-sac, but whose more recently formed fellows result from the transforma- Fig. 383. -62 NORMAL HISTOLOGY. tion of the peripherally situated anterior epithelium at the equator. They are elongated compressed six-sided prisms varying in size with their position ; those at the periphery of the lens are the largest (12 mm. in length by 10-12 (j. in breadth), their size decreasing towards the centre. In the young lens all the fibres contain oval nuclei, but in the adult organ only those recently formed lying in the vicinity of Portions of human crystalline lens: A, section through periphery at equator ; a, anterior capsule ; b, anterior epithelium converted into lens-fibres (I) at equator (z) ; n, nuclei of young lens-fibres. B, fragment of anterior capsule with adherent epi- thelium, viewed from under surface ; h, capsule ; e, epithelial cells. Fibres of human crystalline lens : A , portions of young isolated fibres ; B, fibres in transverse section. the equator possess these. The fibres constituting the softer cortical zone have smooth straight contours, while those of the central part display a finely-serrated outline and are with- out nuclei. The lens-fibres are united by albuminous cement- substance, which, after suitable maceration, is dissolved, so that the fibres may be readily isolated ; since the amount of the cement-sub- stance is less between the broader than between the narrow surfaces of the fibres, after suitable maceration the lens evinces a disposition to separate into concentric lamellae, somewhat after the fashion ol an onion. The apposition of the ends of the fibres takes place along definite lines which appear on the anterior and posterior surfaces of the lens as stellate figures, the lens-stars. In the simpler con- ditions of the new-born child, as well as in most mammalia, each star consists of three rays, one of which in the anterior star is directed upward, while the others are disposed at an angle of 1200 down and outward ; in the posterior star the rays form an angle of 6o° with those of the anterior surface, so that the figures of both surfaces THE EYE AND ITS APPENDAGES. gg, together constitute a six-rayed star. In the adult lens, however, the typical arrangement of the rays is greatly complicated by the addition of secondary lines which obscure the figures. The capsule of the lens is a strong transparent elastic mem- brane completely enclosing the lens and, at the periphery, intimately uniting with the suspensory fibres of the zone of Zinn. The an- terior capsule covering the front lens-surface is thicker (11-15 fi) than the corresponding posterior capsule (5-7 //), the maximum thickness being at the centre of the anterior lens-surface and the minimum at its posterior pole. The zone of Zinn, zonula ciliaris, or suspensory ligament of the lens, is the radially plicated, modified anterior continuation of the hyaloid membrane of the vitreous body. At the ora ser- rata the hyaloid becomes intimately united to the posterior surface of the ciliary body as far as the ciliary processes, from whose sum- Fig. 385 Section through anterior segment of human eye, including cornea, sclera, iris, ciliary body, and lens : a, b, substantia propria of cornea (C) and of sclera (S) ; c, sclero-corneal juncture ; d, conjunc- tival tissue; e, stroma of iris (I);/, connective tissue of ciliary processes (g) ; h, canal of Schlemm ; k, trabecule connecting sclera and ciliary body; /, section of blood-vessel; m,n, o, meridional, radial, and circular fibres of ciliary muscle; /, continuation of hyaloid membrane into ligament (r) of lens (L) ; j, spaces of Fontana ; /, muscular tissue of pupillary sphincter; u, pigment-layer mark- ing termination of retinal layers at pupil. mits thickened bands bridge across the intervening space and become attached principally to the anterior surface and to the periphery of the lens. Owing to the plication of the ciliary body over which the 364 NORMAL HISTOLOGY. hyaloid is reflected, its surface is marked by radiating folds, which at the edge of the ciliary processes become converted into the stiff fibres distinguishing the free part of the zonula. These fibres form two series, the one comprising the fibres springing from the sum- mit of the ciliary processes, the other consisting of those fibres which take their origin in the depressions between the ciliary pro- cesses ; the fibres extending from the valleys pass to the anterior surface of the lens, where they blend with the outer lamella of the anterior capsule, while those springing from the summits of the processes are inserted into the periphery and the immediately ad- joining parts of the posterior capsule. The narrow annular cleft, triangular in section, bounded in front by the zone of Zinn, mesially by the lens, and behind by the mem- brane of the vitreous body, constitutes the canal of Petit. Owing to the constrictions produced by the shorter bridging fibres, the canal presents a series of alternate constrictions and dilatations, which, on inflation, map out the position of the canal by a ring of bead-like enlargements. THE VITREOUS BODY. The vitreous body occupies the space between the lens in front and the retina behind ; it consists of the vitreous substance en- closed by the glassy hyaloid membrane, which in front, where it supports the lens within the patellar fossa on its anterior surface, comes in direct contact with the posterior capsule. The substance of the vitreous body is remarkable, in addition to its beautiful transparency, for its great fluidity, consisting of 98.6 per cent, of water, the remaining small portion being made up of solids, including its organized parts. Histologically, the adult vitreous substance corresponds to connective tissue containing an enormous watery infiltration whose fixed elements have undergone degener- ation. In its embryonal condition the vitreous body is composed of delicate gelatinous or mucoid mesodermic tissue containing numerous frail stellate cells. The formed elements of the vitreous are of two kinds, fibres and cells. The fibrous elements occur in the superficial part of the vitreous, in the vicinity of the ora serrata, as fibrillae of extreme delicacy, which take part in the formation of the zone of Zinn. Other fibrous structures are present as the remains of the minute blood-vessels permeating the vitreous in its embryonal condition. The cells of the vitreous body belong to the category of wan- dering corpuscles or leucocytes, the fixed connective-tissue cells being wanting in the matured organ. In the central part of the vitreous body, the central or hyaloid THE EYE AND ITS APPENDAGES. 365 canal extends from the optic papilla to the vicinity of the posterior lens-capsule ; during fcetal life it transmits the hyaloid artery, and afterwards contains the remains of the supporting connective tissue, and, rarely, the atrophic artery itself. The canal is defined by a thin membranous wall, the continuation of the hyaloid membrane. The existence of other additional small lymphatic spaces has been demonstrated within the periphery of the vitreous body. The minute arrangement and ultimate distribution of the blood- vessels in the various parts of the eye have already been described in connection with the individual structures ; it here remains to out- line briefly the general relations of the larger trunks. The blood-vessels of the eyeball belong to two distinct systems, the retinal and the ciliary, which are connected by meagre anasto- moses only around the optic nerve entrance, otherwise they remain entirely separate. The retinal system is formed by the ramifications of the reti- nal artery and vein, which constitute the permanent circulation within the nervous layer. During fcetal life an additional transient supply, represented by the hyaloid artery, is distributed to embryo- nal structures which disappear before birth. The ciliary system consists of the ramifications of the short, the long, and the anterior ciliary arteries and their complementary veins, and furnishes the blood-supply to the bulbar conjunctiva, the sclera, the choroid, the ciliary body, and the iris, and indirectly aids in maintaining the nutrition of the cornea, the lens, and the epithelial division of the retina. The short ciliary arteries supply principally the choroid, and form the choriocapillaris, at the same time giving off twigs, before piercing the sclerotic coat, to the posterior segment of the sclera and to the dural sheath of the optic nerve. The long ciliary arteries pierce the sclera and pass in the horizontal meridian between the scleral and choroid coats as far forward as the ciliary body, in which they form the larger arterial circle of the iris ; additional recurrent twigs are given off to the choroid and the ciliary muscle. The larger arterial circle sends branches to the ciliary processes and to the iris, as well as a few twigs to the choroid. The anterior ciliary arteries pass to the anterior segment of the ball, and pierce the sclera near the corneal margin to gain access to the ciliary muscle behind the canal of Schlemm. Before entering the eyeball they send branches to the anterior segment of the sclera, to the scleral conjunctiva, and to the corneal limbus. From the branches which pierce the eyeball twigs communicate with the larger arterial circle of the iris, and supply the ciliary muscle and the fore part of the choroid. o(56 NORMAL HISTOLOGY. The venous vessels of the eyeball culminate in two principal sets, the posterior and anterior ciliary veins. The former, or the venae vorticosae, collect the blood from the iris, the ciliary processes, part of the ciliary muscle, and the choroid, and on emerging from the sclera receive also the episcleral veins ; they, therefore, drain the entire territory supplied by the ciliary arteries, except a part of the region nourished by the anterior ciliary arteries. The lymphatics of the eyeball constitute the anterior and pos- terior lymph-tracts, which do not comprise definite lymphatic vessels, but a series of intercommunicating lymph-spaces varying in size from the microscopic tissue-spaces to the anterior chamber. The anterior lymph-tract includes : i. The systems of the lymph-spaces within the cornea and the sclera. 2. The anterior chamber of the eye, containing the aqueous humor, which possesses in small number the usual histological ele- ments of lymphatic fluid, the leucocytes. The anterior chamber com- municates with the posterior chamber through the cleft between the iris and the lens, and indirectly, by means of the spaces of Fontana, with the canal of Schlemm. 3. The canal of Petit, connected by means of the interfascicular clefts with the posterior chamber, and thus indirectly with the ante- rior, these three spaces standing in close relation. The posterior lymph-tract includes two groups, the lymphatics of the retina and of the vitreous body and those of the pericho- roidal space. The constituents of the first group are : 1. The hyaloid canal of the vitreous, which empties into the lymph-clefts of the optic nerve. 2. The perivascular lymph-channels surrounding the retinal vessels, which likewise pour their contents into the lymph-spaces of the nerve. 3. The lymph-clefts of the optic nerve, terminating within the subarachnoidean space of its sheaths. The perichoroidal space, lying between the scleral and the choroid coat, drains the choroid and communicates with the sac enclosed by Tenon's capsule ; the perivascular lymphatics sur- rounding the venae vorticosae lead from the perichoroidal cleft into Tenon's space, from which channels connect with the supra- vaginal space, embracing the optic nerve ; finally, communications exist between this space and the great intercranial lymphatic cavities. Connections between the lymph-clefts of the optic nerve and the perichoroidal space probably also exist in the vicinity of the optic entrance. THE EYE AND ITS APPENDAGES. ^57 The nervous supply of the several parts of the eye has already been considered in detail ; it remains to add a short description of their general relations. The long and short ciliary nerves pierce the sclerotic coat in the vicinity of the optic nerve and pass between the sclera and the choroid, giving off branches for the supply of the latter, and unite to form the ciliary ganglionic plexus on the outer part of the ciliary body. From this plexus twigs pass to the tissues of the ciliary muscle, the iris, and the cornea, to be distributed in the manner already described. THE APPENDAGES OF THE EYE. THE EYELIDS. The eyelids are protecting folds which include between their tegumental and mucous surfaces connective tissue, muscular and glandular structures. The constituents of the eyelids are arranged as general layers from without inward, these being : (i) the integu- ment and subcutaneous tissue, (2) the muscular layer, (3) the median connective tissue, (4) the tarsal plate, and (5) the con- junctiva. The skin covering the external surface of the eyelid is thin, thrown into folds, and beset with fine hairs and small sweat-glands ; the corium possesses slightly-developed papillae, except at the edge of the lid, where the fibrous tissue is denser and displays more conspic- uous elevations. The constant occurrence of pigment-cells within the corium is a noteworthy peculiarity. The loose subcutaneous tissue is rich in elastic fibres, but fat is wanting, or, if present, is found only in meagre amount. At the outer border of the margin of the lid large stiff hairs, the cilia, ex- tend obliquely outward ; they are arranged as two or three rows, their hair-follicles extending deeply into the corium and being sup- plied with small sebaceous glands. The life of the cilia is short, being about four months in duration ; as a result, hairs in all stages of growth are usually included among the eyelashes. The muscular bundles of the orbicularis palpebrarum constitute the layer next the subcutaneous tissue. At the lower margin of the lid the muscle-bundles are divided by the outer structures occupying this region ; an especially robust bundle separated by the lashes lies near the posterior margin of the lid-edge and constitutes the ciliary or marginal muscle of the lid. The succeeding connective-tissue layer is composed largely of the fibrous extensions of the tendon of the levator palpebrae, which are partly inserted into the areolar tissue — fascia palpe- ^68 NORMAL HISTOLOGY. bralis — and partly attached to the upper edge of the tarsus ; the tarsal portion contains bundles of non-striped muscle, which col- lectively form the lid-muscle of Miiller. The tarsus consists of a semilunar plate of dense fibrous tissue Fig. 386. Section of human eyelid: a, a, skin; b, subcutaneous tissue; c, cilium ; d, median connective tissue; e, tarsal plate containing Meibomian glands {h)\f, tunica propria of conjunctiva covered by its epithelium (g) ; i, duct of Meibomian glands ; j, Moll's glands; m, »i, cut fibres of orbicular muscle ; m' , marginal bundle of same; n, sections of sweat-glands ; o, hairs ; /, anterior boundary of tarsus. lying immediately in front of the conjunctiva, and extending as a firm but elastic lamina from the sharply-defined palpebral border deeply into the substance of the lid. The tarsus is composed of closely-felted bundles of dense fibrous tissue, whose tough THE EYE AND ITS APPENDAGES. 360 resistant mass gives form and support to the softer tissues of the lids and partly covers the Meibomian glands embedded within its sub- stance. The Meibomian or tarsal glands constitute a series of about thirty elongated tubulo-acinous structures embedded within the substance of the tarsal plate, nearer the anterior than the poste- rior surface. Each gland consists of a long vertical duct, whose general course is perpendicular to the margin of the lid ; into this canal numerous short lateral tubular acini open. Since the ex- tremities of the glands occupy the outer arched border of the tarsus, these structures are longest in the middle of the lid and progressively shorten towards either end. The ducts open on the straight pal- pebral border as a row of minute orifices situated parallel to, but at some little distance from, the sharply-defined inner palpebral border. In their histology the Meibomian glands so closely re- semble the sebaceous follicles of the skin that they must be re- garded as modifications of these structures ; their secretion consists of a fatty substance similar to the sebum lubricating the integu- ment. The ducts of these glands, about . 1 mm. in diameter, are lined by an epithelium possessing the character of the surrounding epi- dermis, while the acini (.08-. 15 mm.) contain several layers of poly- hedral cells, most of which are in various stages of fatty degen- eration. In the upper part of the tarsus, especially in the nasal half, additional branched tubular glands lie partially surrounded by the fibrous tissue ; these structures correspond in composition to the tear-glands, and are known as the accessory lachrymal glands. The conjunctiva constitutes the innermost layer and surface of the lid, being continuous at the base of the lid with the bulbar con- junctiva and at its palpebral border with the integument. The con- junctiva consists of the epithelium covering the free surface and the connective-tissue matrix, or tunica propria. The epithe- lium covering the inner surface of the lid is stratified columnar ; at the margin of the lid the columnar epithelium passes over into the squamous cells of the epidermis. The surface of the conjunctiva covering the tarsal plates is smooth, but beyond its epithelium forms irregular pockets, which in section somewhat resemble glands. Numerous lymphoid cells within the reticulated tunica propria, in certain localities, strongly suggest the presence of diffuse aden- oid tissue ; the amount of such lymphoid tissue is subject to much individual variation ; it is, however, usually best marked in the retrotarsal portions of the conjunctiva. Circumscribed lymph- follicles are occasionally observed, although these structures are less constant in man than in many of the lower animals — dog, cat, sheep, or ox. 24 ,y0 NORMAL HISTOLOGY. Additional minute lymphoid nodules and mucous glands occur within the conjunctival fornix. The ocular conjunctiva pre- sents no marked differences until near the corneal margin, where the epithelium loses its columnar character and assumes the stratified squamous type in its reflection over the cornea. The edge of the lid presents two borders, the outer, rounded off and tegumental in character, and the inner, distinguished by its sharply-defined margin and dense fibrous structure. In addition to the orifices of the Meibomian glands, the palpebral border is pene- trated by the ducts of the glands of Moll, structures properly regarded as modified sweat-glands. The vertical fold of conjunctiva occupying the inner canthus, the plica semilunaris, represents the third eyelid, or membrana nictitans, of the lower animals. In exceptional cases the base of the fold contains a minute plate of hyaline cartilage ; a small race- mose gland, the homologue of the Harderian gland, is also some- times present at the base of the semilunar fold. The lachrymal caruncle within the inner canthus is an isolated and modified island of skin, possessing an epithelium, a corium, and subcutaneous tissue similar to the adjacent integument ; the epithelium, however, is without the stratum corneum. The caruncle contains adipose tissue, fine hairs with relatively large hair-follicles, and modified sweat-glands closely resembling the glands of Moll. A small amount of involuntary muscle usually exists in the car- uncle, and sometimes a few additional fibres of striped muscle. The blood-vessels of the eyelids pass from the outer and inner angles towards the centre of the lid, forming an arch, the arcus tarseus, along the edge of the lid, and a second anastomosis, the arcus tarseus externus, at the upper margin of the tarsal plate ; from these arterial bows smaller twigs are given off, which, in addition to supplying the integument, the Meibomian glands, and the glands of Moll, form the conjunctival capillary net-work ; additional branches pass to the fornix conjunctivae and to the conjunctiva of the eyeball. The lymphatics of the lid are arranged as two sets : the close- meshed conjunctival net-work within the tarsal mucous membrane, and the wide-meshed peritarsal net- work on the front of the tarsus at its upper border. The first set include the lymphatics running near the palpebral border, as well as the narrow channels surrounding the Meibomian glands. The conjunctival lymph-vessels communi- cate with the peritarsal net-work by means of the coarse reticulum within the tarsus surrounding its glands, as well as by direct connec- tions established by the twigs which pierce the tarsus to join the net-work within the conjunctiva. The peritarsal lymphatics possess valves. THE EYE AND ITS APPENDAGES. ,7I The nerves of the eyelids form the rich marginal plexus close to the palpebral border ; the trunks taking part in the formation of this plexus before their union give off branches to the orbicular muscle and the skin, as well as additional twigs for the supply of the conjunctiva. From the plexus itself fibres are distributed to the hair-follicles of the cilia, the Meibomian glands, the tarsal conjunc- tiva, and the tissues of the edge of the lid. The ultimate nervous distribution includes the formation of subepithelial net-works of fine non-medullated fibres, together with the special endings, the spherical end-bulbs, occurring within the bulbar conjunctiva. THE LACHRYMAL APPARATUS. The lachrymal apparatus includes the lachrymal gland and the system of canals carrying off the fluid secreted under usual con- ditions. The lachrymal gland represents the serous racemose type, closely resembling the true salivary glands in structure ; the organ differs from the usual racemose gland in the independent course and the number of its ducts, of which about a dozen are usually present. It appears, therefore, more accurate to regard the lachry- mal gland as a group of closely-placed small individual racemose glands rather than as a single organ. The ducts of the lachrymal gland are lined by simple columnar epithelium . The structure of the acini and the relations of their groups corre- G' jta,, spond to those of the serous salivary glands, the secreting cells possessing similar spherical forms and granular pro- toplasm. The blood-vessels of the lachrymal gland form the usual capillary net-works supplying the acini and their secreting cells. ^t-., i- -1 t i 11 Section of human lachrymal gland: The nerves distributed to the glandu- a> acinif limited by basement-mem- lar tissue paSS between the acini and form branes (*») and lined by secreting cells i , ,1,1 i (g) ; i, interacinous connective tissue. net-works beneath the basement-mem- brane ; their ultimate relations to the secreting cells are uncertain. The lachrymal canals or canaliculi consist of three coats — the epithelium, the tunica propria, and the muscular tissue. The epithelium is stratified squamous, and forms a layer about .12 mm. in thickness, in which the deepest cells are columnar and the superficial greatly flattened. The tunica propria is composed of bundles of fibrous tissue among which lie especially rich circularly- disposed elastic net-works. Outside the tunica propria the lachry- 372 NORMAL HISTOLOGY. mal canals are surrounded by a layer of striped muscle derived from that part of the orbicularis known as Horner's muscle ; this tissue is arranged as small bundles, which possess a general longitu- dinal course parallel with the axis of the greater part of the lachry- mal canals. The vertical papillary division of the tube, however, lies at right angles to the muscle-bundles, which, consequently, seem to enclose this part of the canal within circular or sphincter fibres ; some of these occupy the edge of the lid and surround the puncta with muscular loops. The mucous membrane of the lachrymal sac and of the naso- lachrymal duct is connected with the periosteum of the neighbor- ing bony surfaces by loose areolar tissue, within which is lodged a rich venous plexus. The mucous- membrane of the lachrymal sac and of the duct partakes largely of the nature of lymphoid tissue, consisting of a connective-tissue reticulum infiltrated with lymphoid cells. From the tear-sac to the nasal termination of the duct the lining epithe- lium is stratified columnar in character, with the occasional pres- ence of cilia within the lower part of the tube. The eyeball is separated from the surrounding structures within the orbit by the intervention of a fibro-elastic membrane or fascia, the capsule of Tenon, covered by a continuous layer of endothe- lial plates ; the enclosed episcleral space, or space of Tenon, communicates with the perichoroidal space on the one hand and with the supra- vaginal cleft on the other. In effect, the capsule of Tenon corresponds to a synovial sac, whose lubricated surfaces of contact facilitate the movements of the eyeball. DEVELOPMENT OF THE EYE. The earliest indication of the visual organ is the optic vesicle, a large diverticulum extending on either side from the primary anterior brain-vesicle, and later becoming connected by a constricted stalk with the interbrain, or thalamencephalon. In the early stage the optic vesicle lies in contact with the ectoderm reflected over the prominently protruding optic diverticulum, the sur- rounding mesoderm at first showing no differentiation. Shortly after the optic vesicle has reached the surface ectoderm the latter exhibits proliferation and thickening opposite the external pole of the vesicle. This ectodermic area, the earliest trace of the future crystalline lens, soon becomes depressed, the invagination progressing until the pit- and the cup-stage give place to the closed vesicle, which finally separates from the ectoderm and lies beneath the surface as the lens-sac. Simultaneously with the progress of these changes in the ectoderm, THE EYE AND ITS APPENDAGES. 373 Section through head of ten-day rabbit em- bryo, exhibiting primary optic vesicle (0) pro- truding from fore-brain (B) and coming in con- tact with surface ecto- derm (e) : m, surround- ing mesoderm. Section through develop- ing eye of eleven-day rab- bit embryo : B, fore-brain connected by stalk with optic vesicle (o), whose anterior wall is partly in- vaginated ; /, thickened and depressed lens-area. the anterior segment of the primary optic vesicle undergoes an important invagination, whereby the front wall of the sac is pushed into the cavity of the vesicle until eventually the anterior and posterior walls are in apposition and the included cavity is largely obliterated. The new space within the indented anterior walls of the sac constitutes the second- ary optic vesicle and corre- sponds to the later vitreous chamber. These important changes probably are not en- tirely attributable to the me- chanical influence exerted by the developing lens-sac on the closely-applied optic vesicle, but must be referred also to deeply-lying formative forces. The invagination of the optic vesicle is not confined to the anterior pole, but takes place likewise along the under side of the sac as well as along the optic stalk ; in consequence the vesicle is imperfectly closed below, the cleft, or choroidal fissure, Fig- 39°- thus established affording an entrance for the surrounding mesodermic tissue which takes part in the production of the primary vascular structures oc- cupying the vitreous chamber. The relations of the parts to the fissure are well shown in frontal sections, where the cleft appears as a conspicuous break in the continuity of the walls of the vesicle. The Retina. The layers of the optic vesicle very soon ex- hibit marked difference in their rate of growth, since the an- terior depressed lamina rapidly overshadows the posterior layer by its much greater thickness and more active proliferation. The posterior wall becomes reduced in thickness, owing to the increase in the size ,. — ' <-!;--& i&c, j \j -13- ■= ■ Sagittal section through developing eye of eleven- and-a-half day rabbit embryo, exhibiting choroidal fissure (C) through which mesodermic tissue (;«) reaches interior of secondary optic cup : o, t, outer and inner layers of optic vesicle ; /, lens-sac. 374 NORMAL HISTOLOGY. of the sac, and later is distinguished by the appearance of deeply- pigmented granules, which mark the beginning of the pigment- layer of the retina, to the formation of which the posterior lamina of the optic vesicle is entirely devoted ; the pigment is first seen in the vicinity of the lip of the cup, from which point the colored par- ticles spread towards the posterior pole. The invaginated anterior lamina becomes greatly thickened and differentiates into the remaining highly-specialized layers of the retina. The process by which these are formed corresponds in the main points with the differentiation of the nervous centres, the re- sulting tissues being of two kinds, the supporting neuroglia and the nervous elements. The retinal lamina early • presents a narrow inner zone, dis- tinguished by its meagre nuclei as contrasted with the richly-nu- cleated broad outer division ; this latter, next the pigmented lamina, with many strata of nuclei, differentiates into an outer layer characterized by small, deeply-staining nuclei, and an inner layer of larger elements. The outer layer subsequently divides into three strata, the outer nuclear, the outer reticular, and the inner nuclear, while the inner layer produces two zones, the inner reticular and the ganglion-cell. The rods and cones appear later as minute hemispherical eleva- tions on the outer surface of the external limiting membrane, and at first possess their inner segments alone, the outer members later growing out from the inner. At birth in many animals (as cats, rabbits, etc.) the rods and cones are wanting, and even in man they are rudimentary ; the macula at birth is still undifferentiated. The nerve-fibres of the retina are derived probably from two sources, from the neuroblasts of the retina itself and from those of the interbrain. The hollow optic stalk becomes solid and con- verted into the primary optic nerve, which acquires its nerve-fibres from the ingrowing and outgrowing processes of the retinal and the cerebral elements. The retinal blood-vessels develop within mesodermic tissue, which spreads over the inner surface of the nervous layer at a com- paratively late period ; the vessels first appear around the optic nerve and spread peripherally. They are not connected primarily with the central vessels of the retina, but with branches entering at the periphery of the nerve (O. Schultze). The crystalline lens proceeds from the ectodermal vesicle already noted. The walls of this sac very early exhibit marked va- riation in thickness, the anterior lamina being relatively thin and composed of a single layer of cuboidal cells, which persist as the flattened polyhedral epithelium of the anterior lens-capsule. THE EYE AND ITS APPENDAGES. <>jc The posterior wall of the lens-sac plays the active role in the formation of the lens-substance, since the production of the lens- fibres is entirely due to the transformation of its greatly-elongated cells. After the obliteration of the original cavity of the sac has been Fig. 391. completely effected by the apposition of the enormously-thickened posterior wall and the anterior lamella, the lens further increases in size by the addition of new fibres at the equator, where the metamorphosis of the epithelial elements into the lens-fibres is continually taking place. The anterior and posterior cap- sules of the lens are genetically dis- tinct from the lens-substance, since they are mesoblastic in origin ; for a time they are closely associated with the tran- sient lamellae of vascular mesodermic tissue which invest the surfaces of the lens and constitute the tunicse vas- culosae. The development of the fibrous tunic — the sclera and the cor- nea— proceeds from the surrounding mesoderm, which undergoes condensation immediately around the ectodermic structures representing the retina and the lens. The mesodermic tissue at the sides of the anterior segment grows be- tween the epidermis and the lens, and constitutes a layer of consid- erable thickness ; subsequently this sheet becomes unequally divided by the appearance of a cleft, the primary anterior chamber, into two laminae of unequal thickness ; of these the anterior and thicker becomes the cornea and the posterior and thinner the connective tissue of the iris and the transient vascular tunic of the lens. The mesodermic corneal stratum undergoes specialization into the substantia propria, the anterior and posterior limiting mem- branes, and the endothelium, the anterior epithelium alone being ectodermic. The choroid and the iris are closely associated in their origin with the mesodermic tract producing the fibrous tunic, the rich vascular net-works characterizing the choroid appearing relatively late. The iris does not grow forward until the anterior chamber begins to form, when it proceeds, as a blunt continuation of the choroidal tract ; while the stroma of the iris is contributed by the mesoderm, the pigment-layer is derived from the extension Section through developing eye of eleven-and-a-half-day rabbit embryo : B, fore-brain connected with optic vesi- cle (t> pT^ ■M m m Section through human malleus and tympanic membrane : 1, bony tissue of manubrium, containing medullary canal (2) ; 3, hyaline cartilage of malleus ; 4, 5, lamina propria of tympanic membrane attached to malleus ; 6, cutaneous layer ; 7, mucous membrane covering hammer ; 8, blood-vessel ; 9, fragment of fibro-cartilage. (After RudiTtger.) external auditory canal. Within the mucous stratum a much less important lymphatic net-work exists, which communicates at the periphery with the lymphatics of the mucosa of the tympanic cavity. Suitable silver staining shows the existence of lymph- spaces in certain places, in both the fibrous layer and the mucous membrane. The nerves of the membrana tympani follow the blood-vessels in their distribution so far that thej* also comprise two sets destined for the cutaneous and mucous layers. The nerves of the cutaneous stratum, chiefly derived from the tympanic branch of the auriculo- temporal, pass behind the manubrium of the malleus to divide at the ,gQ NORMAL HISTOLOGY. lower third of the process into two terminal twigs. In addition to these central nerves, small stems enter the drum-membrane at various points at the periphery, both sets of twigs taking part in the formation of a wide-meshed ground-plexus. From the latter fine pale fibres pass to the blood-vessels which they surround, while other fibres extend to the superficial part of the layer, where, be- neath the epidermis, they constitute a subepithelial plexus. The nerves of the mucous layer originating in the tympanic plexus are largely distributed to the lymphatics as well as to blood-vessels ; an additional subepithelial plexus bears close relations to the epi- thelium ; a few fibres extend into the fibrous tissue of the lamina propria. THE MIDDLE EAR. The middle ear, the entodermic division of the auditory appa- ratus, comprises the tympanic cavity, with its extension into the mastoid cells, and the Eustachian tube, together with the series of minute ear-ossicles. The walls of the tympanic cavity consist of the surrounding bony structures with their periosteum, over which is reflected the mucous lining, indirectly continuous with that of the pharynx. The mucous membrane, closely united with the underlying periosteum, not only covers the inner surface of the membrana tympani, but is also reflected over the ear-bones and their ligaments as well as over the nerves and blood-vessels crossing the cavity. The mucosa con- sists of a thin fibrous tunica propria (50-60 ft) which in places resembles the reticulum of adenoid tissue and includes leucocytes ; the mucous layer is intimately blended with the denser fibrous struct- ure of the periosteum. Connected with the trabeculae of the mu- cosa peculiar oval bodies are occasionally encountered, which are composed of an axial band and concentric lamellae of connective tissue ; these bodies are normal but probably not constant constit- uents of the middle ear. The epithelial lining (18-21 fi) of the tympanic cavity differs in character in the several regions ; over the ear-ossicles, the tympanic membrane, and the promontory, as well as within the mastoid cells, the epithelium consists of a single layer of low cuboidal po- lygonal cells without cilia ; over the remaining parts of the mid- dle ear a layer of ciliated columnar cells exists. In those places where nerve-trunks or blood-vessels are covered, the greatly-thick- ened mucosa forms local ridges, within which the trunks are en- closed. Small tubular glands, about .1 mm. in length, occur in the mucous membrane of the anterior part of the tympanic cavity ; they are sparingly distributed and subject to individual variation. The mucous lining of the antrum and the mastoid cells, clothed THE ORGAN OF HEARING. ^3j by a single layer of low polyhedral cells, is very thin and inti- mately united with the delicate periosteal layer ; numerous fibres, trabecular, or lamellae pass between neighboring surfaces and partially occlude the spaces within the bone, thereby reducing the lumina and still further adding to the complexity of the mastoid cells. The secondary tympanic membrane, closing the fenestra ro- tunda, consists of three layers, a central fibrous lamina propria, which is covered on the tympanic surface by a reflection of the mu- cous membrane, and on the other side by the extension of the lining of the vestibular perilymphatic space. The lamina propria, the unossified part of the wall of the labyrinth, is composed of ra- dially-disposed bundles of fibrous tissue passing from the indented point of its base towards the periphery. The mucous stratum is formed of a thin fibrous tunica propria invested by a single layer of flattened non-ciliated polyhedral epithelial cells, similar to those covering the neighboring promontorium. The innermost stratum of the membrane is composed of a thin laver of sub- endothelial fibrous tissue, over which extends the single layer of endothelial plates. The larger blood-vessels supplying the mucous lining of the tympanum lie within the deeper periosteal layer of the mucosa and give off smaller branches, which pass superficially to form a capillary net-work beneath the epithelium. The vessels distributed to the mucosa covering the promontorium are remarkable for the absence of anastomoses, the arteries dividing into twigs possessing rela- tively large lumina ; the terminal arterioles pass very rapidly into venous radicles, so that intervening capillaries scarcely exist, in places being entirely wanting. The lymphatics of the tympanic mucous membrane form a sys- tem of channels within the deep periosteal layer, where the lymph- vessels are supplemented by spherical enlargements and lateral dila- tations. The reticular connective tissue of the mucosa exhibits local accumulations of lymphoid cells, which strongly suggest the presence of lymphatic nodules. The principal nerves of the tympanum, derived from the tym- panic plexus, run within the periosteal layer of the mucosa, and are composed almost entirely of medullated fibres. From the deeper trunks fine twigs pass towards the surface and form a wide-meshed plexus, which contributes delicate bundles of pale non-medullated fibres to a subepithelial net-work. Along the course of the larger trunks and their immediate branches groups of ganglion-cells occur in exceptional cases, these being found in proximity with the epithelium. The ear-ossicles consist of compact bone, in which Haversian _g2 NORMAL HISTOLOGY. canals and concentric lamellae are present in the thicker parts, as the head and the base of the short process of the malleus. All surfaces of contact, including the articular facets, are invested by hyaline cartilage. The cavity of the ambo-malleal articulation is sub- divided by a minute intra-articular plate of fibrous cartilage. An investment of cartilage covers the malleus on all parts of the sur- face of its attachment to the tympanic membrane, the perichondrium becoming firmly united with the fibrous tissue of the lamina propria. The entire base of the stapes also is covered with a plate of car- tilage directly applied to the fenestra ovalis ; the space intervening between the stapes and the margin of the oval window is occupied by the ring of fibrous tissue constituting the annular ligament. The Eustachian tube consists of two parts, — the supporting framework, composed partly of bone and partly of cartilage, and the mucous membrane. Neither FlG,' 395\ the osseous nor the cartilaginous tissue of the canal constitutes a com- plete wall, since the tube is imperfect, being completed by the fibrous and other tissue which bridges the cleft left by the insufficient hard parts. Within the canal formed by the os- seous, cartilaginous, and fibrous tissues the soft tube of mucous membrane lies, its lower division supplemented by a stratum of submucous tissue, its upper part closely united with the periosteum of the bony walls. The epithelium lining the Eu- stachian tube is ciliated stratified columnar in type, the cells clothing the pharyngeal division of the tube being tall columnar elements, while those lining the upper bony part are low cuboidal, although ciliated, and resemble the epithelium of the tym- panum. The tunica propria presents a stratum of loose connective tissue, rich in cells and defined from the sub- mucous tissue by a denser layer; in many places the reticular connec- tive tissue is infiltrated with lymphoid cells and constitutes an adenoid structure. The profusion and distribution of this lymphoid t—li Section through cartilaginous portion of human Eustachian tube : i, bent plate of cartilage with its hook (i') ; 2, fibrous tissue with fat (3) ; 4, tubo-pharyngeal fascia ; 5, dilator tubx muscle ; 6, mucous membrane of tube with prominent fold (6') below ; 7, mucous glands ; 8, lumen of tube expanding above into so-called safety-tube (8') ; 9, connective tissue uniting tube with base of skull ; 10, le- vator palati muscle. (After Testut.) THE ORGAN OF HEARING. ,3, tissue vary greatly with age ; in early childhood it is present almost in all parts of the tube, but in adolescence it is plentiful only in the lower third, in the upper third being entirely wanting and in the middle third very sparingly distributed. Small mucous glands are also present, and open on the surface of the mucosa within the depressions between the longitudinal folds ; these glands may exist throughout the length of the tube, but they occur with constancy only towards its pharyngeal end. The submucous layer is well developed in the cartilaginous division of the tube, particularly in the outer membranous wall ; it consists of loosely-arranged nbro-elastic tissue, which supports the mucous glands and the larger vessels and nerves, and often contains a considerable mass of fat. The blood-vessels supplying the tubal mucous membranes are derived from the pharynx and from the tympanum ; the larger longi- tudinal stems run within the submucosa or the deep periosteal layers and send twigs into the mucosa to form capillary net-works. The nerves derived from the pharyngeal and tympanic plexuses occupy the deeper layers of the mucosa ; the twigs given off from the larger trunks form a plexus within the superficial parts of the tunica propria, fine non-medullated fibrillae passing to the epithelial structures ; ganglion nerve-cells are found at the nodal points within the plexus. THE INTERNAL EAR. The internal ear in its fully-developed condition consists of two concentrically arranged parts, the bony and the membranous labyrinth, separated by an intervening space containing the peri- lymph. THE SACCULE AND THE UTRICLE. While the bony labyrinth in the cochlea and the semicircular canals quite closely repeats the general arrangement of the corre- sponding parts of the enclosed membranous tube, the central divis- ion of the osseous capsule, the bony vestibule, differs somewhat in its details from the enclosed membranous compartments. These are two almost completely separated vesicles of un- equal size, the anterior and smaller sacculus and the posterior and larger utriculus ; the compartments communicate indirectly with each other by means of the ductus endolymphaticus, while the saccule connects additionally with the cochlear division of the membranous labyrinth through the narrow canalis reuniens, the utricle directly opening into the semicircular canals. The bony wall of the vestibule is lined by a very thin perios- teum, composed of a felt-work of resistant fibrous tissue, in which pigmented connective-tissue cells are not infrequent. From 284 NORMAL HISTOLOGY. this peripheral lamella trabeculae extend across the intervening perilymphatic space to the fibrous wall of the membranous laby- rinth. The endothelium of the inner surface of the periosteum invests the fibrous trabeculae as well as the outer or perilymphatic surface of the membranous labyrinth. The walls of the saccule and the utricle consist of the con- nective-tissue lamella, composed of the bundles of fibrous tissue and the delicate epithelium. At the positions where the filaments of the auditory nerve enter the maculae cribrosse and acusticae the fibrous stratum is best developed and densest, forming a layer .15 to .20 mm. thick. Within other parts of the vestibule, especially in the roof of the utricle, the thickness of this layer may be reduced to 5-6 fl. The lining of the saccule and the utricle consists everywhere, except at the maculae acusticae, of a single layer of thin flattened polyhedral cells. Over the regions receiving the terminations of Fig. 396. a • Section through membranous labyrinth of cat, showing specialized areas within ampulla (A) and utricle {B) : a, surrounding bony wall separated from membranous tube (A) by layer of areolar trabeculae {d) ; c, crista acustica covered with specialized epithelium (f)\ e, e' , bundles of nerve-fibres ; g, ordinary epithelium ; h, layer of otoliths overlying neuro-epithelium of macula acustica (/) ; i, blood-vessel ; k, fibrous layer ; /, adipose tissue. the nerve-fibres, the maculae acusticae, on the contrary, the epi- thelium undergoes marked alteration, changing from the indifferent covering cells into the highly-specialized neuro-epithelium. At the margin of these areas the cells are at first cuboidal, then low THE ORGAN OF HEARING. ,gc columnar, and progressively increase in length until they measure 30-35 >>. in contrast with their usual height of 3-4 //. The character and arrangement of the cells of the acoustic areas in the saccule and the utricle are the same, including two kinds of elements, the sustentacular or fibre cells and the hair-cells. The sustentacular cells are elongated irregularly cylindrical, and extend the entire thickness of the epithelial layer to rest upon the well-developed basement-membrane by their expanded or divided basal processes. The oval nuclei are frequently wider than the average diameter of the cells, and produce corresponding enlarge- ments in the contour of the elements ; the nuclei occupy various levels within the inner half of the cells, but are never situated beyond ; the cell-contents appear faintly granular, and contain yellowish pigment-particles. The hair-cells are broader but shorter than the sustentacular ele- ments, and reach from the surface only to about the middle of the epithelium, where they terminate in rounded margins ; these cells possess large spherical nuclei, which usually lie well towards the slightly-expanded inner ends. The protoplasm of the hair-cells is granular, and contains yellow pigment ; the outer part, next the free surface, exhibits a differentiation into a cuticular zone, cov- ering the outer ends of the cells. From the free border of each cell a seemingly single stiff robust hair (20-25 I1 l°ng) projects into the endolymph ; this conical process, how- ever, is resolvable into a number fig. 397. of agglutinated finer hairs or rods. ■■9A'0 The free surface of the neuro- €M'$W''Wz'&s? ~-y--^^ epithelium within the saccule and the utricle is covered by a remark- able structure, the so-called otolith SWift§ iSflfelSiM^ membrane. This consists of num- $M-f(*fM_Q berless small crystalline bodies, the otoliths, or ear-stones, embedded .^^^^^^ within a soft gelatinous ground-sub- stance. The Otoliths are minute Section of wall of utricle through mac- 1 r i • ular region, from rabbit, showing otoliths Crystals Ot Calcium Carbonate, I-I5 (1 {o) embedded within granular substance in length, usually six-sided prisms te) :/<, hair-ceils with processes (/) ex- « 1 1 . 1 1 , , ,-r,, tending between sustentacular elements With Sllghtly-rOUnded angles. The (s) ■ n> nerve-fibres within fibrous tissue nerve-fibres proceed to the acoustic (;) Passins towards hair-ceiis and be- . . . , , . , ,. , coming non-medullated at basement- areas and unite beneath the epithelial membrane (;«). layer in a plexus, from which fine bundles of fibres pass towards the surface ; the nerve-fibres usually lose their medullary substance in their transit through the base- ment-membrane and enter the epithelium as naked axis-cylinders. 25 3g5 NORMAL HISTOLOGY. After ascending about half-way to the free surface the fibres break up into their fibrillae, many of which are distributed to the hair-cells, with which they probably stand in close relation, while others pass as free axis-cylinders between the epithelial elements to a higher level. The blood-vessels of the saccule and the utricle form a wide- meshed capillary net-work within the fibrous wall of the membranous sacs, the vascular supply being especially rich within the maculae acusticae. THE SEMICIRCULAR CANALS. The inner surface of the bony capsule constituting this part of the osseous labyrinth is lined by a thin periosteum similar to that of the vestibule already described. Along the line of attachment of the membranous canal this layer sends off numerous connecting bundles of fibrous tissue ; in other parts of the circumference of the canal only widely- separated, occasional trabeculse bridge across the perilymphatic space to aid in maintaining the position of the membranous tube. The inner surface of the periosteum, the tra- becular, and the outer face of the fibrous tunic of the membranous canals are invested by the endothe- lium which forms the immediate lining of the perilymphatic space. The walls of the membranous semicircular canals closely re- semble those of the saccule and the utricle, being made up of an outer fibrous lamella and an inner epi- thelial lining. The fibrous coat is further differentiated into an external layer of felted connective- tissue bundles, containing many cells, and an inner, more compact, almost homogeneous layer, which corresponds to a highly-developed basement-membrane. The epithelium of the semicircular canals, supported by the outer fibrous coat, consists throughout the greater part of its extent of a single layer of flattened polyhedral cells (12-18 /->.) similar to those lining the saccule and the utricle. The areas receiving the terminal filaments of the auditory nerve, the cristae acusticae, are distinguished by specialization of the Section of wall of cat's semicircular canal : a, epithelial lining of canal ; b, basement-membrane ; c, fibrous tunic united with osseous lamella (_/") by tra- beculse (d, d) ; e, blood-vessel. THE ORGAN OF HEARING. *$j epithelium to constitute the perceptive apparatus of the semicir- cular canals. These specialized areas are limited to the floor of the ampullae, in which position the fibrous wall of the canal is distinguished by a local thickening forming the FlG- 399- transverse ridge, or septum transversum. On approaching the base of the crest the epi- thelial cells become more columnar, being much taller and narrower than those of the general sur- face. The specialized cells crowning the sum- mits of the cristas acusticae, like other examples of neuro-epithelium, consist of elements of two kinds, the sustentacular or fibre cells and the hair-Cells. Surface view of mem- ry-., . . 11.1 branous semicircular The sustentacular elements resemble those canal of cat . x> fibrous of the maculae of the saccule and the utricle, tissue supporting single extending the entire thickness of the epithelial lh&J>cJls(j,). r layer and presenting an elongated narrow irregular cylindrical body, with prominent projecting oval nucleus. The hair-cells, or auditory cells, reach only part-way to the basement-membrane and bear on their free surfaces enormously long hair-processes, the auditory hairs, which project at least as far as the middle of the lumen of the ampulla. The auditory hairs spring from the ends of the cells by minute conical expansions, and under high amplification are resolvable into a number of finer com- ponent hairs. The nuclei of the auditory cells usually lie within dilated rounded inner extremities of the cells, with which also the terminations of the auditory nerve come in close relations. In sections of the ampullae in tissue preserved with approved reagents the inner free ends of the auditory hairs are embedded within a peculiar dome-like structure, the cupola, regarding whose nature, and even existence during life, opinions greatly differ. As usually seen in well-preserved tissue, this structure appears as a faintly-striated cuticular formation covering in the ends of the hair-processes. The fibres of the auditory nerve pass into the septum trans- versum, where they unite into net-works from which finer diverging fibrillae pass into the overlying epithelium after losing their medul- lary substance. Small groups of naked axis-cylinders extend be- tween the epithelial cells and separate into the individual fibrillae, some of which are applied to the bases of the hair-cells, while others apparently seek their ultimate distribution at higher levels. The blood-vessels supplying the semicircular canals comprise those destined for the bony capsule and those distributed to the ,gg NORMAL HISTOLOGY. membranous structures. These vessels form a wide-meshed capillary net-work within the fibrous tunic of the canals and the ampullae, which supplies both the endo- and perilymphatic surfaces. THE COCHLEA. The cochlea consists of the tapering bony tube wound spirally about its axis and containing the highly-specialized but much smaller epithelial canal, the ductus cochlearis. This latter tube, Fig. 400. Longitudinal section of cochlea of guinea-pig : a, bony capsule ; b, central shaft or modiolus ; c, lamina spiralis ; d, canal of modiolus containing bundles of nerve- fibres (e) ; /, terminal bundles ; g, basilar membrane ; h, spiral ligament ; 1, limbus ; j, membrane of Reissner ; /, Corti's organ ; m, spiral ganglion ; n, blood-vessels ; V, T, M, respectively scala vestibuli, tympani, and media. triangular in transverse section, is attached along its base to the outer wall of the bony tube, and along its narrow opposite border to the projecting osseous spiral lamina ; in consequence of this arrange- THE ORGAN OF HEARING. ,30 ment the perilymphatic space, instead of constituting a single cavity in which the epithelial tube is suspended, is divided into the scala vestibuli above and the scala tympani below, which com- municate respectively with the vestibule and the tympanum. The ductus cochlearis, or scala media, consists, like other por- tions of the membranous labyrinth, of the epithelial tube, the oldest part of the cochlea representing the specialized outgrowth from the primary ectodermic otic vesicle, and the supporting fibrous tunic derived from the differentiated surrounding mesoderm. The ductus cochlearis is triangular in section ; its base or ex- ternal wall is attached to the outer wall of the bony capsule, its apical border is joined to the end of the osseous spiral lamina, and the converging sides are formed by the delicate membrane of Reissner above and the basilar membrane below, which separate respectively the scala vestibuli and the scala tympani from the scala media. The vestibular wall of the cochlear duct is formed by Reiss- ner's membrane, an extremely fragile partition dividing the duct from the scala vestibuli ; the membrane begins on the vestibular border of the lamina spiralis, about .2 mm. inside the free edge of the crista, and extends at an angle of about forty-five degrees until it meets the outer bony wall. Reissner' s membrane consists of three layers : an extremely thin central, almost homogeneous connective-tissue stratum, one side of which is covered by the endothelium of the vestibular surface and the other by the epi- thelium of the cochlear duct. Notwithstanding the extreme thin- ness of this layer, the presence within it of sparingly distributed capillary blood-vessels has been demonstrated. The vestibular endothelium consists of a single layer of delicate plates, which here and there enclose pigment. The surface towards the duct is cov- ered by the general ectodermic lining of the canal, represented by a single layer of flat polyhedral epithelial cells. The three layers contribute equally to the 3 n representing the entire thickness of the membrane. The outer wall of the cochlear duct rests against a greatly thick- ened crescentic cushion of connective tissue, whose convex border is intimately united with the bony wall, and whose generally concave margin looks towards the cochlear duct. This area of con- nective tissue, the ligamentum spirale, extends both above and below the boundary of the cochlear duct, its two horns forming part of the outer walls of the adjacent vestibular and tympanic canals. The concave surface of the ligamentum spirale is interrupted opposite the level of the tympanic wall of the cochlear duct by a pro- jecting ridge, the crista basilaris ( Schwalbe), to which the basilar 390 NORMAL HISTOLOGY. membrane or tympanic wall of the duct is attached. Near the base of the basilar crest the outer wall of the cochlear duct is marked by an additional smaller projection, the prominentia spiralis, or accessory spiral ligament, distinguished usually by the presence Fig. 401. Section of single turn of cat's cochlea : SV, SM, ST, scala vestibuli, media, and tympani; a, osseous tissue projecting as spiral lamina (6) ; c, basilar membrane attached to spiral liga- ment (d) on outer wall ; e, concave surface lined by flat cells (q) interrupted by spiral promi- nence (_/") containing blood-vessel ; g, stria vascularis ; //, Reissner's membrane covered by epithelium (/) of cochlear duct and by endothelium (a) of scala vestibuli ; i, limbus from which extends membrana tectoria (k) overhanging Corti's organ ; m, tunnel of Corti; r, s, inner and outer hair-cells ; /, cells of Claudius ; n, spiral ganglion ; o, nerve-bundles ; v, blood-vessel. of several small blood-vessels. The part of the wall lying be- tween this prominence and the point of attachment of Reissner's membrane is occupied by a peculiar vascular structure, the stria vascularis. The epithelium covering the outer wall of the cochlear duct varies in different positions ; the usual low flat cells become higher and more cuboidal within the area corresponding to the stria vas- cularis ; over the prominence the cells again become flat and poly- hedral, but increase in height on approaching the basilar membrane. The stria vascularis is remarkable on account of the existence of capillary blood-vessels within an epithelial structure. The presence of numerous vessels within the area is readily established, THE ORGAN OF HEARING. 391 likewise the undoubted epithelial character of the innermost cells next the endolymph, but uncertainty exists concerning the true nature — whether epithelium or endothelium — of the cells filling the intercapillary spaces and lying between the epithelial layer and the adjacent connective tissue. The tympanic wall of the cochlear duct consists of two por- tions,— the limbus, which includes the wall from the attachment of Reissner's membrane to the end of the lamina spiralis, and the basilar membrane, which extends from the end of the bony spiral lamina to the basilar crest on the outer wall. The limbus corresponds to a conspicuous local increase in the periosteum and the fibrous coat at the point where the apical border of the cochlear duct is attached to the bony spiral lamina. The greatest thickening of the periosteal tissue occurs within the half of the limbus next the membrane of Reissner, the half adjoining the basilar membrane exhibiting an abrupt decrease in the layer, marked by a sharp edge overhanging the sulcus spiralis, the con- cavity formed by the receding border of the suddenly-diminished stratum ; the upper and lower edges of the recess constitute the superior and inferior labia. The thicker portion of the limbus between the membrane of Reissner and the superior labium is remarkably modelled, since its surface is broken by clefts and furrows, which become deeper as well as larger towards the margin of the superior labium ; this peculiar arrangement culminates in the deeply-cleft edge of the superior labium, where irregular tongue-like processes separated by lateral clefts form the so-called auditory teeth, the entire number of which in the human cochlea has been estimated at about 2500. The epithelium covering the limbus differs in various parts ; flat polyhedral cells cover the elevated portions, including the auditory teeth, the intervening furrows and clefts being clothed by columnar elements. The epithelium lining the sulcus spiralis consists of a single layer of low cuboidal or flattened polyhedral cells continuous with the investment of the auditory teeth on the one hand and with the highly-specialized elements of Corti's organ on the other. The basilar membrane, the outer zone of the tympanic wall, stretches from the end of the osseous spiral lamina to the basilar crest of the spiral ligament of the outer wall. The membrane bears upon part of its surface directed towards the cochlear duct the re- markably modified neuro-epithelium constituting the organ of Corti, and is consequently divided into the inner zona tecta, over which this end-organ lies, and the outer zona pectinata, covered with the more usual epithelium. 392 NORMAL HISTOLOGY. The basilar membrane includes three distinct layers, — the epithe- lium, the substantia propria, and the tympanic lamella. The substantia or membrana propria consists of almost homoge- neous connective tissue, and represents an enormously-developed basement-membrane beneath the highly-specialized epithelium of the tympanic wall. This stratum is covered by a layer of peculiar con- nective tissue, the tympanic lamella, directly continuous with the tympanic periosteum. The lamella contains numbers of fusiform cells of immature character interspersed with fibres ; in this position the differentiation of the mesodermic cells Fig. 402. lining the tympanic canal has never ad- vanced to the produc- tion of typical endo- thelial plates, the free surface of the lamella being invested by the short fusiform cells alone. The epithelium covering the basilar membrane within the inner zone forms the remarkable organ of Corti, the highest ex- ample of specialization of neuro - epithelium anywhere encountered. The organ of Corti extends the entire length of the cochlear duct, with the exception of a short distance within the blind terminal sacs at the two ends of the canal, where the neuro-epithelium is wanting. In general it consists of a series of epithelial arches formed by the interlocking of the ends of two converging greatly modified epithelial cells, the pillars or rods of Corti, upon the inner and outer sides of which rest groups of neuro-epithelium ; the tri- angular space included between the converging pillars of Corti above and the basilar membrane below constitutes the tunnel of Corti, which is, therefore, only an intercellular space of unusual size, containing probably a soft semi-fluid intercellular substance serving to support the nerve-fibrils traversing the space. Examined in detail, the pillars or rods of Corti prove to be com- posed of two parts, the denser substance of the pillar proper and a thin imperfect protoplasmic envelope, which presents a 6 Section of Corti's organ from guinea-pig's cochlea : 57", scala tympani ; TC, tunnel of Corti ; a, bony tis-ue of spiral lamina ; b, fibrous tissue covering same continued as substantia propria of basilar membrane ; c, c' , protoplasmic envelope of Corti's pillars (e, e') ; d, endothelial plates ; f, heads of pillars contain- ing oval areas ; g, head-plates of pillars ; h, h' , inner and outer hair-cells; m, membrana reticularis; k, I, cells of Hensen and of Claudius; n, nerve-iibres ; i, cells of Deiters. THE ORGAN OF HEARING. 393 triangular nucleated thickening at the base directed towards the cavity of the tunnel. Each pillar possesses a slender slightly-S-shaped longitudinally- striated body, whose upper end terminates in the triangular head, and whose lower extremity expands into the foot resting upon the basilar membrane. The inner pillar is shorter, more perpendicular, and less curved than the outer ; its head exhibits a single or double concave articular facet for the reception of the corresponding convex surface of the head of the outer rod. The cuticular sub- stance of both pillars adjoining the articular surfaces is distinguished by a circumscribed seemingly homogeneous oval area of different nature. The upper straight border of the head of both pillars is prolonged outwardly into a thin process or head-plate, that of the inner rod lying uppermost and covering over the head and inner part of the plate of the outer pillar ; the head-plate of the latter is longer and projects beyond the termination of the plate of the inner Fig. 403. Diagrammatic view of Corti's organ : A , inner pillars of Corti (with head-plates a) ; B, outer pillars ; C, tunnel of Corti ; D, basilar membrane; E, inner hair-cells; 1, 1', membrana reticularis; 2. 2'. 2'', rows of outer auditory hairs projecting between phalanges (4-4"; ; 5, terminal plates ; 6-6", outer hair-celis ; 7-7", cells of Deiters ; 8, cells of Claudius. (After Testut.) rod as the phalangeal process, uniting with the adjacent pha- langes of the cells of Deiters to form the membrana reticularis. The inner pillars of Corti are more numerous but narrower than the outer elements, from which arrangement it follows that the broader outer rods articulate with two and sometimes three of the inner pillars, the number of the latter in man being estimated by Retzius at 5600, as against 3850 of the outer rods. 394 NORMAL HISTOLOGY. Immediately within the arch of Corti, resting upon the inner rods, a single row of specialized epithelial elements extends as the inner hair-cells. These elements, little more than half the thickness of the epithelial layer in length, possess a columnar body, whose dark granular protoplasm contains an oval nucleus ; the outer somewhat constricted end of the cells is limited by a sharply- defined cuticular zone, from the free surface of which project, in man, some twenty fine rods or " hairs." The inner hair-cells are less numerous, as well as shorter and broader, than the correspond- ing outer elements ; their numerical relation to the inner rods of Corti is such that to every three rods two hair-cells are applied. The inner sustentacular cells extend throughout the thickness of the epithelial layer, and exhibit a slightly-imbricated arrangement as they pass over the sides of Corti' s organ to become continuous with the lower cells of the sulcus spiralis. The cells covering the basilar membrane from the outer pil- lar to the basilar crest comprise three groups : those composing the outer part of Corti' s organ, including the outer hair-cells and cells of Deiters, the outer supporting cells, or cells of Hensen, and the low cuboidal elements, the cells of Claudius, investing the outermost part of the basilar membrane. The outer hair- cells are far more numerous than the corre- sponding inner elements, and in man and apes are disposed in three or four rows, alternating with the peculiar end-plates or " pha- langes" of Deiters's cells which separate the ends of the hair-cells and join to form a cuticular net-work, the membrana reticularis, through the openings of which the hair-cells reach the free surface. The inner row of these cells lies directly upon the outer rods of Corti, so placed that each cell, as a rule, rests upon two rods ; the cells of the second row, however, are so disposed that each cell lies opposite a single rod, while the third layer repeats the arrangement of the first ; in consequence of this grouping these elements, in con- nection with the ' ' phalanges," appear in surface views like a checker- board mosaic, in which the oval free ends of the auditory cells are included between the peculiar compressed and indented octag- onal areas of the end-plates of Deiters's cells. The outer auditory or hair cells are cylindrical in their general form, terminating about the middle of the epithelial layer in slightly- expanded rounded ends near which the spherical nuclei are situated. The outer sharply-defined ends of the cells are distin- guished by a cuticular border supporting about twenty fine, rigid auditory rods or " hairs" which project beyond the level of the membrana reticularis. The sustentacular elements, the cells of Deiters, have much THE ORGAN OF HEARING. 395 in common with the rods of Corti, being specialized epithelial cells which extend the entire thickness of the epithelial stratum to terminate in the peculiar end-plates or phalanges. It follows that while the free surface of Corti' s organ is composed of both auditory cells and sustentacular cells, the elements resting upon the basi- lar membrane are of one kind alone, — the cells of Deiters. The bodies of the latter consist of two parts, — the elongated cylindri- cal chief portion of the cell, containing the spherical nucleus and resting upon the basilar membrane, and the greatly-attenuated pyramidal phalangeal process. A system of communicating intercellular clefts, the spaces of Nuel, lies between the auditory and supporting cells ; these are occupied by a semi-fluid inter- cellular substance, like the tunnel of Corti, which they connect. The membrana tectoria, or Corti's membrane, stretches from the upper lip of the limbus above the sulcus spiralis and Corti's organ as far as the last row of the outer hair-cells. The membrane is a cutic- ular production originally formed by the cells covering the region of the auditory teeth and the spiral sulcus ; at first it rests upon the epithelial cells, but later it becomes separated from those lying external to the free edge of the auditory teeth and assumes its conspicuous posi- tion over the organ of Corti. The membrane seems to be composed of fine resistant fibres held together by an interfibrillar cement-sub- stance. During life the membrane is probably soft and gelatinous and much less rigid than its appearance after reagents indicates. The outer sustentacular cells, or cells of Hensen, form an outer zone immediately external to the last Deiters' s cell ; these ele- ments resemble the inner sustentacular cells, but differ somewhat in form and arrangement. In consequence of their oblique positions the bodies are not only greatly elongated but also imbricated. The cells of Claudius are the direct continuations of Hensen's cells, and pass uninterruptedly into the low columnar elements covering the remaining part of the basilar membrane. These cells possess clear faintly granular protoplasm, in which pigment- granules are frequently seen as well as spherical nuclei. At the outer extremity of the basilar membrane these cells are continuous with the epithelium covering the upper surface of the basilar crest. The nerves of the cochlea, branches of the cochlear division of the auditory nerve, present an intricate arrangement, the exact mode of their ultimate termination being still in many points un- certain. With the exception of bundles for the supply of the first turn, which run in channels leading directly to the peripheral spiral canal, the cochlear nerves pass into the central canal of the modiolus, from which a series of large-sized lateral branches diverges at quite regular intervals through canals communicating with the 306 normal histology. peripheral spiral canal within the base of the bony spiral lamina. Within the peripheral canal the nerve-fibres are augmented by- numerous nerve-cells, continuing along the spiral canal as the ganglion spirale. From this numerous twigs are given off, which pass along the canals within the spiral lamina towards its margin, the twigs meanwhile subdividing to form an extensive plexus con- tained within corresponding channels in the bone. At the edge of the spiral lamina bundles of fine fibres are given off, which escape at the foramina nervina and enter the epithelium close to the inner .rod of Corti. During or before their passage through the foramina the nerve-fibres lose their medullary substance and proceed to their destination as fine, naked axis-cylinders. The radiating bundles pass within the epithelium to the inner side of the base of the inner pillar, where they divide into two sets of fibrillae, one going to the inner hair-cells, the other passing between the inner pillars to reach the tunnel. After crossing this space the fibrillae escape between the outer rods into the epithe- lium lying on the outer side of the arch. The further course of the fibrillae seems to be such that some fibrillae extend between the outer pillar of Corti and the first row of hair-cells, while succeeding groups of fibrillae course between the rows of Deiters's cells to reach the remaining hair-cells. The exact relation between the nerve- fibrils and the auditory cells, as to whether the fibrillae actually join the cells or only come in close contact, is yet a matter of uncertainty, although renewed investigations render it still improbable that direct anatomical continuity exists. The ductus and saccus endolymphaticus possess walls which closely correspond with those of the saccule and the utricle, com- posed of a thin connective-tissue tunica propria supporting the lining of ectodermic epithelium ; the latter consists of a single layer of flat polyhedral cells. The duct lies within the bony aqueduct, closely united with the periosteal lining, unsurrounded by an extension of the perilymphatic space ; in a few localities a meagre layer of loose connective tissue forms a less intimate bond between the periosteum and the fibrous coat of the duct. The cochlear perilymphatic spaces, the scalae vestibuli et tympani, include within their walls the same tissues that bound similar cavities within other parts of the internal ear. The perios- teum of the bony cochlea constitutes the fibrous tunic, which is usually covered on the surface in contact with the enclosed perilymph by a single layer of endothelial plates ; in some localities, however, as on the tympanic surface of the basilar membrane, the lining cells retain their primitive mesodermic character, never becoming fully differentiated into endothelium. THE ORGAN OF HEARING. 397 The blood-vessels supplying the cochlea constitute two groups, — the branches distributed to the membranous cochlea and the numerous twigs destined for the bony capsule. The cochlear branch of the auditory artery, just before its passage through the bony wall, divides into fifteen to twenty twigs, which pass either directly through canals to supply the lowest turn of the cochlea or into the modiolus. The vessels within the central canal of the modiolus, after supplying the nerve-trunks and the spiral ganglion with nutritive twigs, send off lateral branches, which form two remarkable masses of coiled vessels, the glomeruli cochleae ; from the larger of these, situated somewhat above the point of origin of the bony spiral lamina, arterioles proceed to Reissner's membrane and to the limbus, breaking up to form the capillary net-works of these structures. The smaller glomeruli, within the base of the partitions separating the adjoining cochlear turns, send off branches forming two independent capillary systems. These are the net-works within the basilar membrane and those of the stria vascularis, which, while having a common origin, do not communicate. The capillaries of the membranous cochlea are collected into two principal trunks, the vas prominens on the outer wall and the vas spirale beneath the basilar membrane opposite the inner rods of Corti ; from these channels the blood is conveyed to the larger venous trunk, the vena spiralis modioli, lying below the spiral ganglion within the base of the osseous spiral lamina. The lymphatics of the internal ear are represented by the large lymph-spaces included between the membranous labyrinth and its bony capsule, — the perilymphatic spaces of the semicircular canals, the utricle, the saccule, and the cochlea. These large inter- communicating spaces are in direct exchange with the subarach- noidean and probably also the subdural intra-cranial lymph-cav- ities. The demonstrated communication between the cavity of the endolymph and the subdural space by means of the saccus endolymphaticus brings the contents of the membranous labyrinth into closer relations with the lymphatic system than was formerly recognized. THE DEVELOPMENT OF THE EAR. The development of the ear includes the formation of two mor- phologically distinct divisions, the membranous labyrinth, the essential auditory structure, and the accessory parts, comprising the middle ear, with its ossicles and associated cavities, and the external auditory canal and the pinna. The developmental history of the organ of hearing proper in its early stages is largely an account of the growth and differentiation ,Qg NORMAL HISTOLOGY. of the ectodermic otic vesicle, since from this is produced the im- portant membranous tube, the enveloping fibrous and osseous structures being comparatively late contri- Fig. 404. butions from the mesoderm. The internal ear first appears as a thick- ening and soon after depression of the ectoderm within a small area on either side of the cephalic end of the neural tube at a level corresponding to about the middle of the future medulla. This auditory pit is widely open for a considerable time and distinguished by the great thickness of its depressed wall, which contrasts strongly with the adjacent ectoderm. After a time the lips of the pit approximate until by their final union the cup-like depression is converted into a closed sac, the otic vesicle. The otic vesicle, after severing all con- nection with the ectoderm, gradually re- cedes from the surface in consequence of the growth of the intervening mesodermic layer ; it next loses its spheroidal form and becomes pear-shaped, with the smaller end directed dorsally. This diverticulum is the first appearance of the recessus vestibuli, a divi- sion of the embryonal laby- Fig. 405. Section through developing ear of nine-and-a-half-day rabbit em- bryo : e, ectoderm thickened and invaginated to form auditory pit ato; in, surrounding still undif- ferentiated mesoderm ; n, lining of neural tube ; v, blood-vessel. Sagittal section through developing ear of ten-day rabbit embryo : o, otic vesicle becoming pear-shaped, due to formation of recessus vestibuli (r) ; m, surrounding mesoderm. Section through developing ear of twelve-day rabbit embryo : v, primitive vestibule, from which extend (r) recessus labyrinthi and (s) semicircular canal above and (c) cochlear canal below ; n, neural tube with thickened ventral lining ; m, mesoderm. rinth disproportionately conspicuous compared with its permanent representative, the ductus endolymphaticus. THE ORGAN OF HEARING. 300 The semicircular canals next form as tubular projections from the vesicle and rapidly assume great prominence ; the superior vertical canal appears first, and the external or horizontal canal last. The growth of the epithelial diverticula is later accom- panied by a condensation of the surrounding mesoderm, which differentiates into an external layer, the future cartilaginous and later bony capsule, and an inner layer of fibrous tissue. The latter suffers partial atrophy and absorption, in consequence clefts appear among the delicate bundles, an arrangement permanently represented by the fibrous walls and intervening trabeculae of the spaces occu- pied by the perilymph surrounding the membranous canals. Within the ampullae, which early develop, the epithelial lining undergoes specialization, accompanied by thickening of the mesodermic wall within circumscribed areas to form the cristae acusticae. Coincidently with the development of the semicircular canals a diverticulum — the cochlear canal — appears at the lower anterior end of the membranous sac ; this tube, oval in section, grows for- ward, downward, and inward, and represents the future cochlear duct, or scala media. After attaining considerable length, further elongation is accompanied by coiling and the assumption of the permanent disposition of the tube. The epithelium of the cochlear tube early exhibits a distinction, the cells of the upper surface of the somewhat flattened canal be- coming attenuated, while those on the lower wall undergo thick- ening and further differentiation ; the flattened cells form the covering of Reissner's membrane and the outer wall, and the taller elements are converted into the complicated structures of the tympanic wall of the scala media, including the crista, the sulcus, and the organ of Corti. The development of these structures includes the differentiation of two epithelial ridges ; from the inner and larger of these is derived the lining of the sulcus spiralis and the overhanging mem- brana tectoria, and from the outer and smaller ridge is produced the elaborate and complicated organ of Corti. The crista appears between the sulcal cells and the cochlear axis as a thickening of the spiral lamina. The cochlear outgrowth of the primary otic vesicle forms the membranous cochlea, or scala media, alone, the walls of the adjacent divisions, the scala vestibuli and scala media, resulting from the changes within the surrounding mesoderm. The latter differentiates into two zones, an outer, which becomes the car- tilaginous, and finally osseous, capsule, and an inner, lying immediately around the membranous canal, which for a time consti- tutes a stratum of delicate connecting tissue between the denser 400 NORMAL HISTOLOGY. Fig. 407. :\ capsule and the ectodermic canal. Within this layer clefts appear, which gradually extend until two large spaces bound the mem- branous cochlea above and below. These spaces, the scala vestibuli and the scala tympani, are separated for a time from the scala media by a robust septum consisting of a mesodermic layer of considerable thickness and the wall of the ectodermic tube. With the further increase in the dimensions of the lymph-spaces the par- titions separating them from the cochlear duct are correspondingly reduced, until, finally, the once broad layers are rep- resented by frail and attenuated struct- ures, the membrane of Reissner and the basilar membrane, which con- sequently include an ectodermic stratum, the epithelial layer, strength- ened by a mesodermic lamina, rep- resented by the substantia propria and its endothelioid covering. The main sac of the otic vesicle from which the foregoing diverticula arise constitutes the primitive membra- nous vestibule, and later subdivides into the saccule and the utricle. This separation begins as an annular constriction of the primitive vestibule, incompletely dividing the vesicle into two compartments ; the ductus endolymphaticus unites with the narrow canal connecting these vesicles in such man- ner that each space receives one of a pair of converging limbs, an arrangement foreshadowing the permanent relations of the parts. Even before the subdivision of the primitive vestibule is established the vestibular end of the cochlear canal becomes constricted, so that communication between this tube and the future saccule is main- tained by only a narrow passage, the canalis reuniens. The de- velopment of the maculae acusticae of the saccule and the utricle depends upon the specialization of the epithelium within certain areas associated with the distribution of the auditory nerves. The nerve-fibres form their ultimate relations with the sensory areas by secondary growth into the epithelial structures. From the foregoing it is apparent that the membranous laby- rinth is genetically the oldest part of the internal ear, and that it is in fact only the greatly modified and specialized closed otic vesi- cle surrounded by secondary mesodermic tissues and spaces. The middle ear is derived from the expanded and metamor- M Section through developing cochlea of twenty-one-day rabbit embryo : e, sections of ectodermic cochlear duct, or scala media, surrounded by delicate mes- odermic tissue (;«), within which large lymph-spaces later appear; c, con- densed cartilaginous capsule ; n, bundles of nerve-fibres. THE ORGAN OF HEARING. 40I phosed outer end of the first pharyngeal pouch, or inner visceral furrow, the Eustachian tube representing the inner segment. The tympanic membrane results from the changes affecting the septum between the outer and inner first visceral furrows ; this par- tition, originally thick, consists of a mesodermic middle stratum, covered on its outer and inner surfaces respectively by the ecto- derm and the entoderm. The external and the middle ear at no time communicate, but are normally separated by the septum in question. The ear-ossicles are developed in connection with the primitive skeleton of the visceral arches ; the malleus and the incus rep- resent specialized parts of the cartilaginous rod of the first arch. The development of the stapes, on the contrary, is probably not connected with the visceral skeleton, but owes its formation to the ossification of the tissues at the fenestra ovalis. The development of the external ear results from the changes taking place within the first outer visceral furrow, or gill-cleft, and the tissue immediately around its external orifice. From the gill-cleft originates the external auditory canal, and from the margins of its orifice the pinna is formed. 402 NORMAL HISTOLOGY. Fig. 408. CHAPTER XIX. THE NASAL MUCOUS MEMBRANE. The mucous membrane lining the nasal fossae consists of two prin- cipal divisions, that of the respiratory and that of the olfactory region ; the latter alone is concerned in the sense of smell. The mucous membrane of the respiratory region is dis- tinguished from that of the olfactory area by its thickness, over the inferior turbinals it reaching 4 mm., and by the presence of venous net- works of such size that the structure appears as if com- posed of cavernous tissue. The epi- thelium of this region is stratified ciliated columnar in type, within the superficial layer of which numerous goblet-cells are interspersed. The tunica propria of this region is composed of fibrous connective tissue containing clefts occupied by many leucocytes, the latter frequently invading the superimposed epithelium ; occasional nodules of lymphoid tissue are also encountered in various parts of the mucosa. The surface of the tunica propria is smooth, since the usual subepithelial papillae are here wanting. The mucous membrane of the respiratory region is further dis- tinguished by numerous small racemose glands, which open on the free surface by funnel-like pits, readily recognized by the unaided eye, and lined for some distance by epithelium corresponding to that of the adjacent surface. These glands are mixed in character, since some acini secrete serous fluids, while others elaborate mucous products. The glandular structures occur with especial frequence over the inferior turbinated bones, although on the lateral Section through mucous membrane of respiratory region of child's nose : a, ciliated epithelium ; b, tunica propria ; c, submucous con- nective tissue ; d, mucous glands ; e , duct of glands opening on free surface ; f, blood-vessels. THE NASAL MUCOUS MEMBRANE. aq^ walls and on the lower part of the nasal septum they are present in large numbers. As already mentioned, the veins of the mucosa are so wide and plentiful that the layer in which they lie appears like cavernous tissue. The mucous membrane lining the accessory spaces of the nasal fossae — the sphenoidal, the frontal, and the maxillary sinuses and the ethmoidal cells — closely resembles that of the respiratory region, being covered by a stratified ciliated epithelium, which rests upon a thin tunica propria closely united with the periosteum. These tracts are chiefly distinguished from the respiratory surface by the marked reduction in the thickness of the mucous membrane, which within these spaces is seldom more than .02 mm. The meagre supply of glands is another point of difference, the glandular struct- ures within these spaces being represented by small and sparingly distributed groups often exhibiting peculiar modifications of the racemose type. The olfactory region is distinguished macroscopically from the respiratory portions of the nasal fossae by the yellowish-brown tinge of its mucous membrane as contrasted with the rosy hue of that covering the adjacent region ; the more deeply colored tract indicates in only a general way the boundaries of the olfactory region, since the limits of the two do not closely correspond, the brownish area in man being usually somewhat less extensive than the entire surface possessing the structure of the ol- factory mucous membrane. The latter is also dis- tinguished by its greater thickness and by the absence of ciliated cells. The olfactory mucosa consists of the epithelium and the tunica propria, the characteristic appearances of the tissue depending upon the peculiari- ties of the former, another example of neuro-epithelium. This epi- thelium consists of two kinds of cells, the sustentacular and the olfactory elements. The sustentacular or support cells present Fig. 409. Section through olfactory mucous membrane from child's nose : a, zone of oval nuclei belonging to sustentacular cells ; b, zone of spherical nuclei of olfactory elements ; c , basilar cells ; d, subepi- thelial tissue ; e, glands of Bowman. 404 NORMAL HISTOLOGY. an outer cylindrical division, containing an oval nucleus, situated always near the inner end of the more expanded part of the cell, and yellowish pigment, together with numerous granules arranged more or less markedly in longitudinal rows. The outer ends of the supporting cells are modified into a cuticular zone, the membrana limitans olfactoria, sometimes exhibiting vertical markings. The nuclei of the sustentacular cells form a regular band, the zone of oval nuclei, which lies next the free surface, and strongly con- trasts with the adjoining broad zone of round nuclei of the olfac- tory cells. The inner portions of the sustentacular elements are very narrow, irregular in outline, and terminate generally in cleft or branched processes in close relation with the underlying basal cells. The olfactory cells lie among the supporting elements as incon- spicuous, elongated, and attenuated bodies, whose variously-placed spherical nuclei, covered by a thin stratum of protoplasm, consti- tute the widest parts of the cells ; in consequence these elements appear like spherules from the outer and inner poles of which thin rod-like processes extend towards the free surface and the base- ment-membrane. The nuclei of the olfactory cells lie at all levels, forming the broad zone of round nuclei. The deepest part of the epithelial stratum is made up of a closely- set zone of small nucleated cells, resting upon the tunica propria on the one hand, and sending irregularly-branched processes among the overlying elements on the other. These basilar cells consti- tute a protoplasmic net-work, whose extensions and continuities are at present inadequately determined. The tunica propria of the olfactory region consists of a moder- ately loose felt-work of bundles of fibrous connective tissue, inter- mingled with numerous delicate elastic fibres. The outermost zone of the tunica propria is condensed to form a very slightly developed basement-membrane, upon which rests the epithelium. Em- bedded within the mucosa branched tubular glands, or Bowman's glands, exist in great abundance ; these structures possess a duct of sufficient length to extend through the epithelial layer, the remaining portions of the tube constituting the body and fundus of the gland. The epithelial cells lining the secreting part of the tube contain brownish pigment, which aids in producing the characteristic color of the olfactory mucous membrane. Although formerly regarded as serous in type, it is probable that Bowman's glands must be included within the mucous group. These glands, which in places consti- tute an almost continuous layer of secreting tissue, are much more generously distributed than those within the respiratory region. The blood-vessels supplying the nasal mucous membrane are especially distinguished by the size and profusion of the veins. THE NASAL MUCOUS MEMBRANE. aQc The arterial stems lie in the deeper layers of the tunica propria, from which twigs are sent into the more superficial stratum, where, imme- diately beneath the epithelium, a subepithelial capillary net-work is formed ; other twigs break up into capillaries which surround the glands. The veins are remarkable for their size and number, in many places, particularly over the posterior part of the inferior tur- binated bone, giving to the entire tunica propria the character of cavernous tissue. The lymphatics are represented by numerous vessels which con- stitute a net-work within the deeper parts of the tunica propria and around the lymphoid nodules ; in addition to these, within the olfac- tory region wide-meshed net-works of perineurial lymph-chan- nels extend throughout the mucosa of the olfactory region. The olfactory mucous membrane is further provided with a rich sys- tem of intercommunicating lymph- spaces within the groundwork of the tunica propria, which empty into the larger lymphatic net- works of the deeper layers. The nerves of the nasal mucous membrane are of two kinds, those providing common sensation and those concerned in the special sense of smell ; the relations of the latter with the neuro- epithelium are of much interest, but at the present time by no means definitely determined. The larger filaments of the olfactory nerve lie against the bony walls, partially embedded within corresponding grooves, and give off smaller arching bundles, which pass within the mucous membrane towards its epithelial surface. The twigs, even within the mucosa in many places, are enclosed by perineurial sheaths prolonged from the intercranial investment of the olfactory nerve. The fibres of the latter are without the medullary sub- stance, being bundles of the axis-cylinder fibrillar enclosed within the neurilemma ; on reaching the epithelium the fibres break up into their component fibrillae, which pass as naked, often varicose, axis- cylinders between the elements of the neuro-epithelium. It is highly probable that the nerve-fibrillae come into close contact, even if not into actual continuity, with the inner ends of the olfactory cells ; whatever the exact actual relation, a very intimate relation between the nerves and percipient elements may be assumed. Additional twigs from the trifacial, composed of medullated fibres, are also distributed to the olfactory region, without, however, coming in relation with the olfactory cells. The development of the nasal mucous membranes proceeds from the ectoderm, the earliest indication of these structures ap- pearing as the olfactory plates, two areas of thickened ectoderm immediately above the primitive oral cavity and in contact with the wall of the fore-brain. 406 NORMAL HISTOLOGY. The olfactory plates are converted into the nasal pits by the growth and elevation of the surrounding parts on all sides except the under surface, along which the nasal pits for a time directly com- municate with the primary mouth. In addition to the differentiation of the surrounding tissues into the structures of the external nose, the close relation of the primary nasal surface with the brain-vesicle disappears with the changes of position produced by the develop- ment of the fore-brain and growth of the tissues forming the cranial case, particularly the development of the olfactory ganglion from the olfactory plate. The complicated surfaces of the nasal fossae are due primarily to the appearance of the superior, middle, and inferior turbinal folds on the lateral wall of the nasal recess. Each fold comprises the dupli- cation of ectoderm enclosing a core of mesoderm ; the latter becomes the turbinal cartilages and finally the corresponding osseous plates. The differentiation of the olfactory region from the general lining of the nasal fossae takes place coincidently with the growth of the olfactory nerve-fibres ; the details of the histogenesis of these structures, however, are still but imperfectly determined. The special organs of taste and of touch, including the taste- buds and the tactile corpuscles, have been already considered in connection respectively with the tongue and with the peripheral nerve-endings and the skin. appendix: INCLUDING THE MOST USEFUL HISTOLOGICAL METHODS. The advances made during the last few years in the preparation of tissues for microscopical examination have been so important, that no one proposing to undertake practical histological investigations, normal or pathological, can afford to ignore methods of work which, although somewhat exacting, yield results far superior to the older processes. With the increased facilities for producing thoroughly good and accurate preparations the current standard of excellence has advanced, and results formerly viewed with complacency are now often regarded as incomplete and correspondingly unsatisfactory. The activity of the last half-dozen years has resulted in greatly multiplying the details of histological technology, since each worker determines what new procedures or modifications of existing methods are advantageous for his own special purposes. Useful, and for the advanced worker indispensable, summaries of the ever-increasing methods of microscopical investigation are to be found in the volumes especially devoted to technology ; of such works in English the excel- lent " Microtomist's Vade-Mecum," by Bolles Lee, may be recom- mended, supplemented by the notices of new methods presented in the current issues of the Journal of the Royal Microscopical Society. In the present place, however, no attempt will be made to discuss even incompletely many of the methods finding use at the hands of various investigators ; but, on the contrary, only a few processes will be described which extended use has proved to be thoroughly trust- worthy and satisfactory. The student undertaking such work for the first time is strongly advised to persevere with the paraffin method, as here described, since, when properly employed, it may always be depended upon to yield the most gratifying results. Failures, sure to beset the beginner, should be carefully analyzed and be made to yield the experience which will guard against their repetition. The manipulations necessary for the conversion of the fresh tissue into the finished preparation are : i. Fixation of the tissue. 2. Preservation of the fixed tissue. 407 4o8 APPENDIX. 3. Staining of the tissue in toto. 4. Embedding in paraffin. 5. Sectioning. 6. Fixing sections to the slide. 7. Mounting. 8. Finishing, labelling, and storing. 1. Fixation of the Tissue. By "fixation" is understood the killing of the tissue so rapidly that its elements are retained exactly as they were while living when first met by the fixing reagent ; thus, for example, extended cells should remain extended after death, or rapidly-effected changes, as those of karyokinesis, should be retained in the stage in which first encountered, and not be allowed to com- plete their cycle, and consequently disappear, as when the tissue slowly dies. It is evident that absolutely fresh and, for many investi- gations, still living tissues are essential for satisfactory results where the condition of the cells is a matter of importance, as in the study of the structure of the nucleus or of the protoplasm. While so evidently desirable, the fulfilment of this condition in the case of human tissues is often a matter of impossibility, or, at best, of extreme difficulty, the restrictions imposed upon immediate autop- sies rendering it usually almost impossible to secure the more delicate tissues while their cells are still alive. Fortunately, however, for the majority of investigations, the exact condition of the cell is a matter of less moment than its general form and its relations to the surround- ing elements ; for such purposes the slow death of the cells may work no serious detriment to the usefulness of the tissue, but it is to be accepted as a histological maxim, that the fresher the tissue and the more accurate the fixation of its elements, the more valuable and satisfactory will be the preparation. When, then, really fresh material is to be prepared for subsequent histological examination, it is to be subjected, without previous wash- ing in water, first to the action of some fixation fluid ; the choice of the reagent to be employed must be determined by the purposes in view and the character of the tissue. a. Muller's Fluid. Potassium bichromate 2.5 gm. Sodium sulphate i.ogm. Water 100 c.c. This fluid, when properly employed, is probably the most generally useful fixation reagent ; for successful results, however, strict attention to the manner of its employment is imperative. The quantity of fluid must always be largely in excess of the volume of the tissue APPENDIX. 409 treated, and the tissue should not be in pieces over 2 cm. in thickness ; the fluid should be changed as soon as it becomes turbid, sometimes within the first hour, and subsequently renewed as often as may be necessary to maintain perfect transparency . Tissues are usually allowed to remain in Miiller's fluid for a considerable time, two weeks being the minimum, while they may be permitted to lie much longer, usually, without disadvantage ; it is advisable, however, to remove specimens after six weeks, and preserve them in spirit. The tissue is transferred from the Miiller's fluid to water, and thor- oughly washed in the running stream from 4 to 6 hours, until all excess of the fluid has been removed ; it is then placed in 70 per cent, alcohol and kept in the dark, the spirit being renewed whenever strongly tinged by the removed fluid ; as long as discoloration occurs an occasional change of alcohol is desirable. Where the interstitial methods of embedding are followed, no great amount of hardening is necessary or even desirable, in which case the tissues are best stored in 80 per cent, spirit, where they may lie until needed. Portions of the nervous system which are subsequently to be stained after the Weigert process may be fixed with advantage in warm J fuller's fluid, being kept in an oven from 8 to 10 days at a temperature of 350 C. b. Absolute Alcohol. For glands, skin, blood-vessels, etc., absolute alcohol affords a rapid and admirable means of fixation, and possesses the additional quality of simultaneously hardening the tissue, a matter sometimes of great convenience, since the specimen maybe cut within 24 hours. Small pieces of tissue, so placed either bv sus- pension or support on cotton that they do not come in contact with the bottom or the sides of the glass (to which they otherwise adhere), are treated from 12 to 24 hours, the alcohol being invariably changed at the end of the first three hours, whether cloudy or not. After fixation the tissue is preserved in 80 per cent, spirit. It is to be noted that the action of 95 per cent, alcohol is entirely different from that of the absolute, with the weaker spirit the shrinkage being great and the fixation imperfect ; it cannot, therefore, be substituted. c. Flemming's Solution. Chromic acid (one-per-cent. solution) 7.25 c.c. Osmic acid (two-per-cent. solution) 2.50 c.c. Glacial acetic acid, at least 25 c.c. Where the structure of the protoplasm or the nucleus is to be in- vestigated, or where for any purpose an accurate picture of the cells is desirable, Flemming's stronger solution (given above) will be found the most trustworthy reagent at our command. Two drawbacks limit 4I0 APPENDIX. its use : its very limited power of penetration, which necessitates the tissue being cut in layers not over 2-3 mm. thick, and the consider- able expense attending the use of large quantities of the fluid. The mixture should be made up each time just before using, and cannot be employed a second time. The living tissue is placed within the solution in a glass-stoppered bottle, and allowed to remain, without changing, 24 hours ; then transferred to running water 1-2 hours, after which it is placed in 70 per cent, alcohol, and, after several changes, preserved in 80 per cent, spirit. d. Picro-Sulphuric Acid (Kleinenberg's) Solution. Picric acid, saturated watery solution 200 c.c. Sulphuric acid, pure 4 c.c. resulting in dense precipitate ; after one hour filter, and dilute with three volumes (600 c.c.) of distilled water. This solution is an admirable and trustworthy reagent for embryos and other delicate structures, its principal objection being the time required to remove the yellow tinge of the picric acid. The embryos are placed directly, without washing, into the fluid, where they remain 5 hours — if very large the time may be extended to 10-12 hours, with a renewal of the fluid ; they are then transferred to 70 per cent, alcohol, which is repeatedly changed until discoloration no longer takes place ; preserve in 80 per cent, alcohol. 2. Preservation of Tissues. In connection with fixation, the subsequent preservation of tissues in 70 per cent, spirit has been indi- cated ; when, however, the condition of the specimen, as when ob- tained some time after death, or other considerations, render fixation useless, it becomes necessary to preserve the tissue from further change. To this end Midler's fluid may also be advantageously employed, observing the precautions already pointed out, followed after some weeks by alcohol. In many cases, however, when fixation is no longer possible, alcohol offers the most convenient method of preser- vation, possessing as it does the merits of simplicity and of rendering the tissue receptive to all forms of staining. In the employment of alcohol for hardening, the tissue should be passed through a series of gradually-increasing strength ; beginning with 60 per cent, spirit for 2-3 days, with renewals when turbid, the tissue is placed successively, at intervals of 3-4 days, into 70 per cent., 85 per cent., and 95 per cent, alcohol, finally, after sufficient hardening, to be preserved indefinitely in 80 per cent, spirit. In those cases where bone or calcareous matters are present, fixation and hardening must be followed by decalcification and softening ; APPENDIX. ,xl this is most conveniently and quickly accomplished by placing the fixed and partially-hardened tissue in a large quantity of dilute nitric acid, varying in strength from 3 to 9 per cent. The fluid should be changed daily for three days, subsequently every second day. The completion of the decalcification may usually be determined by judi- ciously passing a fine needle into the tissue. After suspending the acid solution, whose too prolonged action may result very disastrously for the softer parts, the tissue is thoroughly washed for some hours in running water, and then placed in alcohols of gradually-increasing strength to complete the hardening. 3. Staining. Since the introduction by Gerlach, now some forty years ago, of a means of differentially coloring tissues, the list of staining methods has gradually been extended, until their description at the present time would cover pages ; notwithstanding the multipli- cation of formulae and their claimed advantages for particular purposes, all ordinary investigations may be satisfactorily carried on with the aid of a very limited selection. Among the important stains, carmine and hematoxylin stand pre-eminent on account of their general applicability and their certainty. The relative merits of carmine and heematoxylin are well defined by their respective advantages. Carmine is, as usually now employed, a pure nuclear stain, pos- sessing great penetrating properties, and hence being well adapted for staining tissues and small animals in toto, — a matter of much importance in many lines of work requiring serial sections ; further, carmine is permanent, remaining bright and unfaded after years of exposure, does not overstain, and produces preparations admirably adapted to the needs of the improved methods of photomicrog- raphy. Haematoxylin, on the other hand, is more than a nuclear stain, yielding, when successfully employed, beautifully crisp pictures of cellular structure seldom, if ever, equalled by carmine; its applicability in its usual formulas, however, is limited to staining sections, since its powers of penetration are feeble. This latter defect may be overcome by employing the stain in the form of Delafield' s heematoxylin, given below, which answers admirably for bulk-staining. The liability to fade, the possibility of overstating, and the necessity of using water for differentiation are among the disadvantages of haematoxylin as usually employed. The student is strongly advised to adopt carmine as his staple stain, reserving haematoxylin as a valuable, and sometimes indispensable, supplementary means of bringing out parts of cells not satisfactorily displayed in carmine preparations. In the order of procedure given above, staining follows the preser- 4I2 APPENDIX. vation of the tissue and precedes the embedding and sectioning, this arrangement being based on the supposition that the tissue is to be stained in bulk and cut in paraffin : with this sequence in view, the specimen is removed from the 80 per cent, spirit and placed directly in the staining solution, which, for all the ordinary purposes for which carmine is employed, is best made up as : a. Borax-Carmine {Grenadier). Carmine, best 2.5 gm. Borax 4-° gm- Water 100 c.c. Alcohol (70 per cent. ) 100 c.c. The carmine and borax are thoroughly rubbed up in a mortar and dissolved as far as possible in the previously-heated water, the alco- hol being subsequently added. The fluid may then be filtered, but it is preferable not to do so ; the solution is set aside for at least two weeks, and then carefully decanted. The exact length of time required to stain sufficiently a block of tissue throughout evidently depends upon the size and density of the specimen ; it is, however, seldom safe to trust to an immersion of less than 24 hours' duration, and if the object be of large size and compact texture, say a piece of kidney 2 cm. in thickness, it should be allowed to remain in an ample quantity of the stain for at least three days. The vessel containing the fluid and tissue must be well stoppered, a wide-mouthed bottle or tightly-covered capsule being the most suitable receptacle. From the carmine the tissue is directly transferred, without the slightest washing in -water, into a large quantity of acid alcohol, made by adding strong hydrochloric acid to 70 per cent, alcohol in the proportion of 5 drops of acid to every 100 c.c. of spirit. The object of the acid solution is to effect differentiation and fixation of the color ; for this purpose the tissue should remain at least 24. hours, and, if of the size and character above supposed, twice as long — until the frequently-changed acid alcohol no longer becomes tinged. If the staining has been successful, the block of tissue now appears of a brilliant deep uniform red ; if inspection shows inequality of tint or insufficient color in the central parts of the mass, the staining will not be satisfactory and should be repeated. Failure in bulk staining is due to an unfavorable condition of the tissue or to an improperly-prepared staining fluid, and not to the method, which extended experience shows is always capable of yielding the most gratifying results, whose brilliancy and differentiation compare favor- ably with those of any carmine staining of individual sections. Where it is preferable to stain the sections after cutting, the same APPENDIX. 4I., carmine fluid may be employed, the sections, either loose or fixed to the slide, being immersed from 15 to 20 minutes, and then directly transferred to 10 per cent, acidulated 70 per cent, alcohol for about 5 minutes, followed by thorough washing in 70 per cent, spirit. Where the tissue is robust, the acid solution for differentiation and fixing may be made with water in place of the alcohol, water being also used for the subsequent washing ; it is an advantage, however, for delicate structures to avoid transfers from alcohol to water, keep- ing as far as possible the sections in alcoholic solutions of about the same strength. b. Delafield's Hsematoxylin. (1) Hematoxylin, crystals 4 gm. (2) Alcohol, absolute 25 c.c. (3) Ammonia-alum, crystals . 52 gm. (4) Water 400 c.c. (5) Glycerin 100 c.c. (6) Methyl-alcohol 100 c.c. Dissolve 1 in 2, and 3 in 4 ; mix, when a slightly-colored fluid is produced ; let stand for 4 days, protected from dust, but with free access to air and light, at the end of which time the fluid has turned to a deep bluish purple. Filter, and add 5 and 6 ; a part of the am- monia-alum falls out in small crystals. After several hours filter again, and then keep in a tightly-stoppered bottle at least four or five weeks before using. This tediously-prepared stain possesses the great advantage of penetrating and staining well tissues in bulk, for many purposes being a valuable adjunct to carmine staining. The strong solution above given is diluted with distilled water, and the tissue allowed to remain until of a very dark blue color, when it is placed in distilled water for 24 hours to effect differentiation and remove excess of color ; it is then transferred to 70 per cent, alcohol for subsequent treatment. The action of the stain must be watched, as overstating may readily occur ; should the coloring be too intense, this may be remedied by soaking in dilute hydrochloric acid, the action of the latter being arrested at the proper time by water, which at the same time restores the tissue to its former blue color, the acid having previously turned it reddish or brown. It is very important to remove every trace of acid, to prevent subsequent fading ; to this end thorough washing after the use of acid is imperative. An avoidance of overstaining in the first place is much more desirable than any subsequent correction. In addition to the purposes of staining in bulk, this haematoxylin fluid works well after fixation in chromic acid or Flemming's solution, yielding excellent preparations of chromatin filaments in such tissues. .I4 APPENDIX. c. Alum- Hematoxylin (Bohmer). (i) Hematoxylin, crystals .35 gm. (2) Alcohol, absolute 10 c.c. (3) Potash-alum 10 gm. (4) Water, distilled 30 c.c. Dissolve 1 in 2 = A ; dissolve 3 in 4 — B ; A is added to B, drop by- drop, and allowed to stand in the light for several days before filtering. For staining sections, dilute with distilled water, several drops of the stain to a watch-glass of water usually producing the requisite rich bluish-purple solution. The sections remain in the diluted stain until colored dark bhie, this usually requiring 5-8 minutes, although the exact time depends upon the condition of the tissue and the strength of the staining fluid employed ; the sections are transferred to distilled water and allowed to soak from 5 to 10 minutes, by which time they have become a bright rich blue ; a too intense color and a light lilac tint are alike to be avoided. The tissue having been stained in bulk with either borax-carmine or Delafield's haematoxylin, it is now ready for the important manipu- lation of embedding. 4. Embedding. This may be simple or interstitial, the former affording a general support to the tissue by grasping its surface with- out penetrating the tissue, the latter supporting not only the surface, but also, in consequence of the complete infiltration of the specimen, every part of the object. For the purposes of hasty examination, the simple embedding often answers perfectly, and is preferable on account of economy of time and labor ; where, however, really fine preparations are desirable, the additional labor involved by the more elaborate process is amply repaid by the character of the resulting preparations. The most satisfactory mass for simple embedding consists of paraffin 2-3 parts -\- tallow 1 part ; the melted mass is poured around the piece of tissue, which has been previously fixed in position by a carefully-inserted pin within a paper mould. The mass should cool slowly, and the sections should be cut with both knife a?id block flooded with strong spirit. Interstitial Embedding, by which every portion of the entire tissue-mass is held together and sustained, each isolated fragment being retained in its relative position and preserved in the mounted preparation, has given the histologist of to-day a command of his tissues incomparably superior to anything that his predecessors pos- sessed, and enables him to secure complete series of objects whose minuteness and frailty precluded perfect preparations by the older methods. APPENDIX. 4IC The important processes of interstitial embedding are two, paraffin and celloidin being the substances respectively used to infiltrate the tissue ; of these the paraffin method must be regarded as the most perfect, and, with few exceptions, to be preferred whenever thin per- fect sections are of importance, especially where preservation of sequence is desirable. Paraffin Method (Klebs). The essential point of this process is thorough and complete im- pregnation of the tissue with the embedding mass ; it is conse- quently necessary to saturate the tissue with some fluid with which the paraffin is perfectly miscible, the fluids usually employed to this end being chloroform or turpentine oil ; in order, however, to insure the free entrance of these fluids within the tissue, it is first necessary to free the tissue of all traces of water still contained in the alcohols of 70 or 80 per cent. It is, therefore, necessary to place the tissue from the usual 80 per cent, preserving spirit as follows : * a. Into 95 per cent, alcohol from 12 to 24 hours. b. Into absolute alcohol from 24 to 48 hours, until complete dehy- dration has been secured ; this step is of the utmost importance for the success of all the subsequent manipulations, since if dehydration be imperfect infiltration will be unsuccessful, and the tissue will cut badly. c. Into pure chloroform from 6 to 8 hours, or until the chloroform has replaced the absolute alcohol ; an indication of the completion of this interchange is furnished by the position of the tissue, since as soon as the tissue continues to lie beneath the surface of the chloro- form, or sinks towards the bottom of the bottle, it may be concluded that the alcohol has been completely replaced by the chloroform. d. Into a saturated solution of paraffin in chloroform from 2 to 3 hours ; the solution may be kept slightly warmed. e. Into pure melted paraffin, which has a melting-point of about 500 C. ; the paraffin is best contained in a small open porcelain cap- sule placed within a water-oven so regulated as to maintain a constant temperature of about 500 C. : while undesirable, congealment of the surface of the paraffin due to reduction in temperature is no great misfortune, the retarded evaporation of the chloroform being the principal evil ; a rise of the temperature to which the tissue is sub- jected to a point beyond 550 C, on the contrary, is usually disastrous, the tissue being shrunken and distorted to a degree which renders it valueless. It is, therefore, desirable to keep the paraffin and the * In the appended data it is still assumed that the tissue being treated is of the consistence and volume represented by a piece of kidney 2 cubic cm. in size. .r5 appendix. tissues at a temperature whose variations are included within the limits of 500 to 520 C. The tissue must remain in the melted paraffin until every portion of it has been completely filled with the embedding mass and all the chloroform has been driven off. This latter point is a matter of importance in insuring the proper consistence of the paraffin for satis- factory cutting, since when the paraffin contains traces of chloroform it is too soft and friable to yield the best results. In order to deter- mine whether all the chloroform has been driven off, a clean thin iron rod is heated and plunged into the melted paraffin, care being taken that the rod is not too hot when immersed, lest the tissue be over- heated. So long as traces of chloroform are present, bubbles follow the introduction of the heated rod ; when bubbles 710 longer appear, all the chloroform has been driven off. After the complete dissipation of the chloroform, the tissue is trans- ferred for a few minutes to a second capsule containing fresh, unused, melted paraffin of such consistence as is best adapted to sectioning under the conditions of season and particular object in view ; the quantity of melted paraffin should amply suffice to fill the mould which is to be employed in the next manipulation. f. Embedding the Tissue. For this purpose some form of mould must be devised, which may be the simple paper box, made by fold- ing over a block the sides and ends of a piece of sized paper some 4 cm. wide by 8 cm. long ; more convenient are the adjustable metallic embedding frames furnished by dealers, those made by Jung, of Heidelberg, and sold by various firms in this country, being par- ticularly serviceable. When the paper box is used, it should be fixed to a loaded cork before the paraffin is poured into it; when the metallic frame, it must closely rest upon a piece of polished glass. In either case, the mould is placed in a broad dish, whose depth somewhat exceeds the height of the sides of the mould when resting in position for use. The mould and dish being ready, the capsule containing the fresh paraffin and specimen is removed from the oven, and the paraffin poured at once into the mould, which should be completely filled ; after this has been done, the tissue is seized lightly with the slightly- warmed forceps, and rapidly transferred to the mould ; a warm needle should be at hand with which to arrange the tissue, so that the pro- posed plane of section shall lie parallel to one of the smaller ends of the mould, while its principal axis corresponds with the bottom upon which the tissue rests. As soon as the specimen is properly placed — and this is often a matter of great consequence — steps should be taken to harden the paraffin as rapidly as possible. To this end, the dish supporting the APPENDIX. 4I- mould and specimen should be filled with cold water until the latter is just on the point of overflowing the sides of the mould, great care being taken that this does not happen before the surface of the enclosed lake of melted paraffin has congealed, otherwise the paraffin becomes partially displaced by the water, which will be found later within large cavities in the block. As soon as the film on the.surface has completely formed, the water is allowed to cover the mould entirely ; the dish may then be placed under the tap, and a gentle stream of water aid in cooling off the mass. No attempt should be made to remove the block from the mould until the entire mass has become thoroughly hardened ; when this has occurred, and the embedded object with its surrounding mass has been freed, the paraffin should appear almost transparent and of a bluish tint, and not milk-white, as is usually the case when the paraffin is impure or when the block has been cooled slowly. After trimming off" the superfluous embedding material and exposing the surface to be sectioned, the tissue is ready for cutting. Objects may be preserved within the paraffin indefinitely, the method affording an admirable and convenient means of keeping tissues for any length of time and always ready for immediate sectioning and mounting. Celloidin Method {Duval-Schieffer decker). This method has but one point in common with the paraffin process — the tissue is infiltrated with the embedding mass ; while paraffin is cut dry, celloidin must be cut under or flooded with spirit. Celloidin is particularly adapted for certain lines of work in the central nervous system and the special senses, and possesses the advantages over paraffin of requiring less attention and no heat for its successful manip- ulation. The retention of the supporting mass, the rather thicker sections, and the impossibility of cutting ribbon-series, on the other hand, are points of unfavorable comparison with the paraffin method. The celloidin should be prepared as two solutions, a thin and a thick: the celloidin — either as chips or in cake — is dissolved in equal parts of absolute alcohol and ether, about 5 grammes, in small pieces, being placed in 100 c.c. of the mixed solvent ; the resulting solution will be very thin, and maybe labelled "A" ; a second solution should be made containing enough celloidin to secure the consistence of a thick syrup; this is "B." The celloidin does not dissolve with great readiness, days often being required for the preparation of the solutions ; these should be very carefully guarded against evapora- tion, and a small quantity of the absolute alcohol and ether added from time to time to maintain the proper degree of fluidity. The tissue, previously thoroughly dehydrated by absolute alcohol, is soaked in a mixture of equal parts of absolute alcohol and ether 27 4l8 APPENDIX. from 24 to 48 hours and then transferred to the "A" or thin celloidin solution, in which it remains for several days, until entirely permeated with the mass ; the tissue is then placed in the thick " B" solution, where it stays until the thinner fluid has been replaced by the thicker. Meanwhile, corks of suitable size should be soaking in the mixture of equal parts of absolute alcohol and ether ; one of these is selected, its end slightly roughened, and finally moistened with a few drops of the mixture just before the tissue with an envelope of the thick celloidin solution is placed in position for cutting on the cork, care being taken that the stratum (1-2 mm.) of celloidin lies between the tissue and the cork. After a few moments a fresh layer of celloidin is added, and this process is repeated until the tissue is completely surrounded with a stratum of the embedding mass ; or the tissue may be completely embedded, after being attached to the surface of the cork, by fastening a piece of writing-paper to the sides of the cork and at once filling the resulting mould with the fluid celloidin. The mass of fresh celloidin should remain undisturbed until the sur- face has hardened sufficiently to prevent all possibility of shifting, when the cork with the tissue is transferred to a vessel containing 75 per cent, spirit to harden, where it remains, completely immersed, from 1 to 3 days or longer ; at the expiration of this time the block has gained a consistence suitable for sectioning. The cutting can be done either free-hand or by the microtome, but it must be done while both knife and tissue are flooded with 70 per cent, alcohol. The sections are transferred to 70 per cent, spirit for subsequent treatment ; if already stained, they are passed into 95 per cent, for dehydration, cleared in xylol, bergamot oil, or cedar oil (but not in clove oil, as this dissolves the celloidin), and mounted in balsam ; if, on the other hand, the tissue has not been stained in bulk, the sec- tions are treated with the selected stain, alcoholic or aqueous, and subsequently dehydrated, cleared, and mounted. 5. Sectioning. While for the purposes of immediate examination or of temporary preparation free-hand sections often suffice, yet no one seriously undertaking histological investigation can afford to ignore the advantages possessed by the approved microtomes of the present day, without which accurate work is impossible. After an extended experience with many forms of these instruments, the writer unhesitatingly recommends the sliding microtome, as made by Schanze, of Leipsic, as the best all-round instrument to be had, the medium-sized . " model B" of this maker supplying an ideal tool capable of executing all forms of cutting in the most satisfactory and convenient manner. The little sliding student's microtome made by the Bausch and Lomb Optical Company answers as a very satisfactory APPENDIX. 41q substitute for the more convenient and accurate foreign instrument. A word of caution may be added against regarding all forms of sliding microtomes as equally efficient, since the satisfactory working of such tools is largely dependent upon details of their construction and workmanship. While theoretically more accurate, the beautifully- made Thoma microtomes with the "Naples" holder are much less convenient than the Schanze instruments, and are less desirable than the latter for general use. Where much ribbon-cutting is carried on, the Minot automatic microtome will be found a most valuable time- and labor-saving device ; equally perfect ribbon-series can be pro- duced on the Schanze, but with much less rapidity. Assuming that some satisfactory form of sliding microtome is at command, and that the tissue has been embedded interstitially in paraffin, the method employed in cutting will depend on whether isolated sections or a series are desired. For very many purposes the separate sections are all that is needed, their relative position and sequence being preserved by systematic arrangement as they are cut. In making such individual sections, the knife should be placed obliquely to the tissue, the exact angle being such that the e?itire 'length of the plate is successively brought into use. It will be found necessary to adopt some means of preventing the rolling up of the sections as they are cut, this tendency being especially pronounced with the harder grades of paraffin ; after this has occurred, the sec- tions are usually useless. The simplest and most effective means of overcoming this difficulty is to hold a small red sable brush over the edge of the knife, and, as the latter enters the block, lightly hold the section as it is being cut from curling over and rolling up ; the manip- ulation requires some little dexterity, but when once acquired sup- plies a simple "section smoother" equally as efficient as any of the more elaborate mechanical devices. In cutting paraffin sections, no fluid is needed, both block and knife being kept perfectly dry. The knife should be wiped occasionally with a clean cloth, to remove any particles of the embedding mass that may adhere ; especial attention must be given to the edge and under surface of the blade, as some- times a minute adherent fragment will cause cracks across the entire surface of the subsequent sections. The forceps or a brush serve to transfer the sections from the knife-blade to the adjacent tray lined with perfectly clean paper, upon which the sections may remain for a long time if properly guarded against high temperature and dust. The average thickness of satisfactory paraffin sections is about .01 mm. ; large sections are usually somewhat thicker, small delicate objects, as embryos, readily yielding sections not much over half as thick (.005 to .008 mm.) ; it should not be forgotten that a keen blade and proper paraffin are essential to first-class results. 420 APPENDIX. In cutting celloidin or other specimens requiring to be flooded while sectioned, the knife is likewise placed obliquely ; the sections are removed with a soft wet brush and transferred to alcohol ; rolling up of such sections does not occur. Cutting ribbon-series is a modification of the usual procedure, and possesses great advantages where the possession of a complete series of sections arranged in their natural sequence is important ; not only for embryological studies, where it has become a necessity, but for many other purposes, ribbon-cutting is to be preferred. The success of the manipulation depends largely upon the proper consistence of the paraffin, since the latter must be of just such hardness that while firm enough to enable the sections as cut to push before them those already in the chain, it must be sufficiently soft to enable the op- posed edges of the sections to adhere together, and thus form the "ribbon." Preparatory to cutting the paraffin block is trimmed as accurately as possible into rectangular form, and so clamped in the microtome that the longer sides of the rectangle are exactly parallel to the edge of the transversely-set knife, the latter being placed at right angles to its slide-ways. When the first section is cut it is not removed, but allowed to lie upon the blade ; the knife being returned to its first position, the tissue is raised the proper distance (generally .01 mm.), and a second section is made, which, if the paraffin is of the proper character, will adhere to the first, while the latter is pushed ahead for a distance equal to the second section ; in this manner each section in turn drives those previously cut before it, all adhering by their opposed edges and forming a ribbon whose length is often limited only by the wishes and the convenience of the worker. Care must be taken to keep the cutting edge, especially its under surface, free from particles of par- affin, since the presence of these will lead to furrows and cracks in the sections. The sides of the block corresponding to the knife- edge must also be kept exactly parallel, otherwise the ribbon will be curved instead of straight. In case the paraffin in which the tissue lies is too hard, the sections breaking apart instead of adhering, ele- vating the temperature of the workroom or judiciously holding the block in the vicinity of a flame for a short time will usually afford relief; or the entire block may be coated with softer paraffin, which is subsequently trimmed off from all but the two adhering sides. As the ribbons are completed they are placed in covered • trays upon clean sized paper, protected from dust and high temperature. 6. Fixing sections to the slide constitutes the next step after cutting when tissues have been embedded in paraffin, whether pre- APPENDIX. 421 viously stained or not ; the object of the manipulation is to replace the support afforded by the paraffin by attaching the sections to the slide before removing the embedding substance. In this point paraf- fin is much more accurately and conveniently worked than celloidin, since the latter is removed from the sections with much less facility than paraffin. The ideal fixing solution is yet to be devised, those at present employed being all defective in some particular. The desiderata are secure attachment of the sections to the slide in all solutions necessary for the various manipulations of staining and mounting, and complete expansioyi of the sections before their final adhesion to the slide : this latter consideration is of great importance in large sections or in mounting ribbon-series, since it is practically impossible to cut these without some slight compression or wrinkling; if mounted without being perfectly expanded, the preparations are marred by distorting folds, which in lines of accurate work, where reconstructions are sometimes necessary, are serious defects. The most satisfactory fixing solutions are the gum arabic (Flogel- Schultze) and collodion-clove oil (Sch'dllibaum) mixtures. The gum-arabic method is carried out as follows : of a satttrated aqueous solution of best gum arabic (a crystal of thymol being added to prevent the growth of fungi) about 12 drops are added to 30 ex. of distilled water and thoroughly shaken. The slide is flooded with the solution, care being taken that the fluid does not run over the edges, and the sections are floated on the liquid, every part of the sections being separated from the slide by the stratum of solution : when all the sections are arranged, the slide is transferred to a warm- ing-plate and very gently heated to a temperature never as high as the melting-point of the paraffin, the object being to enable the sections to expand while swimming on the gum solution; this they do in a most satisfactory manner within a few minutes, the sections spreading out perfectly flat even when previously wrinkled. After expansion the excess of the fluid is drained off, and, if neces- sary, the sections finally rearranged ; the slides are then placed in a suitable place to dry, where evaporation is favored but protection from dust is afforded. It usually is best to allow the sections to lie overnight to insure complete drying, as if water be still present the sections will not properly clear up. The disadvantages of the method are the long time required to insure complete evaporation of the fluid and the inability of sections so fastened to withstand watery solutions, which dissolve the gum and loosen the sections. These objections, however, are more theo- retical than real, and are more than compensated by the superior preparations secured by this method ; in the exceptional cases where it is necessary to apply aqueous solutions, advantage may be taken .22 APPENDIX. of the modification introduced by Gray, who uses a weak gelatin solution in place of the gum arabic, and, after the sections have ex- panded and are fastened in their proper positions, soaks the slide in a very weak solution of potassium bichromate, which, in the presence of light, renders the gelatin film insoluble in water, and hence capable of resisting aqueous stains. To those desiring accurate preparations, these methods are strongly recommended as preferable to the more rapidly applied and generally used Collodion and Clove-Oil Mixture. This is made by adding i part of collodion to 3 parts of clove oil ; the mixture should be made up in small quantities, as it becomes less reliable with age. The slide is lightly painted over with the mixture and the paraffin sections placed in position ; the sections cannot be moved after touching the mixture, hence care must be exercised in their placing. When the slide is full, it is gently warmed until the fumes of the clove oil ap- pear ; meanwhile the paraffin melts and the section sinks down into the film of the mixture, from which the clove oil is driven off, leaving the tissue attached to the slide by the film of collodion alone ; this union is not attacked by any of the aqueous, alcoholic, or other solu- tions ordinarily used. The ability of resisting many fluids, together with its simplicity and rapidity, has long rendered the method a favorite, and, for very many cases, deservedly so, due care being exercised in heating the slide to avoid injury to the tissue. In spite, however, of these considerable advantages, the inability of securing perfect extension of the sections is a shortcoming which for accurate investigations is fatal ; when, therefore, accurate preparations are de- sired, it should be discarded for the gum or the gelatin method. The sections being securely fixed to the slide by one of the foregoing meth- ods, the paraffin on the slide must be removed, as preliminary to — 7. Mounting the sections for preservation. The paraffin is best removed by immersing the slide in benzole or xylol for a few mo- ments and then transferring to turpentine for a short time. The sections having cleared up in these fluids are ready for the applica- tion of the mounting medium, the balsam. The slide is removed from the turpentine, drained, and hastily wiped on the back and edges, care being taken not to touch the sections ; a drop of pure balsam is then placed on the centre of the slide and the latter held for a few moments over a spirit flame to liquefy more thoroughly the balsam, when the cleaned cover-glass, previously caught by the for- ceps and passed for a moment over the spirit flame, is lowered into position ; this manipulation should be executed with steadiness and evenness, avoiding as far as possible the imprisonment of air-bubbles. Should these, however, appear after the cover is in place, they need APPENDIX. a2\ cause no concern, as they usually spontaneously disappear during the next twelve hours unless imprisoned within some enclosed recess of the tissue ; rough treatment, by strongly and repeatedly pressing on the cover-glass in the attempt to displace air-bubbles, is disastrous to thin sections, and should never be practised ; gentle ftressztre, however, should be made after the cover is down, to press out super- fluous balsam, but this must be done with care and judgment. The balsam should entirely fill up the space beneath the cover and form a slight border outside ; this edging of balsam is useful, as it dries much sooner than the medium beneath the cover and adds very materially to the strength of the preparation. The freshly-mounted slides should be placed in the horizontal position and allowed to dry some days before being much handled, although if necessary a preliminary study of them can be made at once. No attempt should be made to clean them until the balsam has well hardened and all danger of moving the cover-glass disap- peared ; the excess of the mounting medium is then removed with a sharp knife and the slide finally cleaned by a cloth moistened with benzole. 8. Finishing, labelling, and storing the slides depend largely upon the individual taste and wishes of the worker ; while the earnest investigator has little time for useless ornamentation, the small amount of labor involved in having slides clean, neat, and properly labelled is well compensated by the convenience and satisfaction of handling such preparations. Labels should always be attached as soon as practicable, and should indicate all data likely to be of interest ; when labels are placed on both ends of the slide, one should be re- served for noting points of especial interest shown by the preparation. In preparing slides on which an entire series is mounted, marking each with a diamond saves much vexatious delay, which otherwise is often experienced in determining the proper sequence. Finished preparations are best preserved in some form of cabinet or case, the exact character of which is of little consequence so long as the slides are protected from dust and light and lie flat ; cabinets with well-made drawers are attractive and convenient, but usually expensive. In recapitulation of the foregoing manipulations, already considered in detail, the steps necessary to convert the fresh tissue into the finished preparation may be presented as AN OUTLINE OF THE STANDARD METHOD. i. Fixation of fresh tissue in large quantity of Miiller's fluid; renewal when turbid ; tissue remains 2-3 weeks. 2. Thorough washing in running water — 2-5 hours. 424 APPENDIX. 3. Transfer to 70 per cent, alcohol ; keep in dark ; change alcohol whenever it becomes deeply tinged, until it remains colorless. 4. Stain in excess of borax-carmine — 24-48 hours. 5. Transfer directly, without washing, from stain to acid alcohol — 24-48 hours. 6. Wash well in 70 per cent, alcohol, several times renewed — 24 hours. 7. Transfer to 80 per cent, alcohol — 24 hours. 8. Transfer to 95 per cent, alcohol — 24-48 hours. 9. Dehydrate in absolute alcohol — 24-48 hours. 10. Transfer to pure chloroform until tissue sinks — 6-8 hours. 11. Transfer to saturated solution of paraffin in chloroform — 6 hours. 12. Transfer to pure melted paraffin, kept at constant temperature of about 500 C. , until all chloroform is driven off— 6-8 hours. 13. Transfer to fresh melted pure paraffin of consistence for em- bedding— 10-15 minutes. 14. Embed tissue in mould ; cool rapidly. 15. Section in microtome, first suitably trimming block for cutting. 16. Fix sections to slides by gum or collodion-clove oil. 17. Remove paraffin by benzole, succeeded by turpentine. 18. Drain off excess of turpentine, apply balsam, and cover. 19. Place freshly-mounted slides in horizontal position. 20. Clean up and permanently label when thoroughly -dry ; store in suitable cabinet. While the duration of the several manipulations as indicated in the above summary represents the time usually required by ordinary objects, yet the individual character of the tissue must be considered in each case, as density exerts much influence on the rapidity with which the fluids penetrate. When it is desirable to stain the tissue after sections have been cut, the above manipulations must be modified ; steps 4, 5, and 6 in such case are omitted and the tissue is at once dehydrated. Re- moval of the paraffin from the fixed sections on the slides (17) by benzole is at once succeeded by the following manipulations : a. Transfer to 95 per cent, to remove the benzole — 5-10 minutes. b. Transfer to clean 95 per cent, alcohol to insure complete absence of benzole — 5 minutes. c. Transfer to 80 per cent, alcohol — 5 minutes. d. Transfer to 70 per cent, alcohol — 5 minutes. e. Stain in borax-carmine solution — 10-15 minutes. f. Differentiate in acid alcohol (10 per cent. ) — 6-10 minutes. g. Wash in 70 per cent, alcohol, renewed — 10-15 minutes. h. Transfer to 80 per cent, alcohol — 15 minutes. APPENDIX. 425 i. Transfer to 95 per cent, alcohol — 15 minutes. j. Dehydrate thoroughly in absolute alcohol — 15 minutes. k. Clear sections in oil of turpentine — 5 minutes. 1. Mount in balsam as indicated above in 18. When hematoxylin is used as the stain, the steps e, f, and g are omitted and replaced by — ee. Transfer to distilled water — 5 minutes. ff. Stain in properly-diluted hsematoxylin fluid until sufficiently dark — 8-10 minutes. gg. Wash well in distilled water to remove excess of stain and to differentiate — 10 minutes ; then dehydrate by the ascending series of alcohols included by h to j as above. The foregoing methods are those to be employed as the standard processes, since for the great majority of specimens they yield results perfectly satisfactory and trustworthy ; sometimes, however, special lines of investigation demand other treatment in order to bring out particular features. Several of those most important for the study of the nervous system are here given. Weigert's hsematoxylin method is of great value in exhibiting the presence and course of medullated nerve-fibres on account of the peculiar staining of the medullary substance ; the method takes ad- vantage of the tenacity with which this part of the nerve-fibre retains the color, appearing slate-blue or black, while the other parts of the nervous tissues become pale ; the tissue is first overstained and then decolored. The fresh spinal cord or the brain is hardened in a large excess of potassium bichromate (5 per cent, solution), repeatedly renewed, for several weeks, and then directly transferred to 80 per cent, alcohol, kept in the dark, and frequently changed until the fluid is no longer discolored ; as the tissue is usually cut in celloidin, the next step is the dehydration by 95 per cent, and absolute alcohol, followed by the usual process of the celloidin embedding. After this has been ac- complished, and the tissue is on the cork ready for cutting, the entire block is transferred to — a. Saturated solution neutral cupric acetate 1 part ; Solution of Rochelle salt (10 per cent.) 1 part, for 24 hours in oven at 400 C. b. Transfer to — Saturated solution neutral cupric acetate 1 part ; Distilled water 1 part, for 24 hours. 426 APPENDIX. c. Transfer to 80 per cent, alcohol — }4-i hour. d. Cut sections ; knife and tissue wet with 80 per cent, alcohol. The later method of Weigert directs the preparation of the fol- lowing staining solutions : { Lithium carbonate (1.2 gm. : 100 c.c. H2O) 7 c.c. I Distilled water 100 c.c. f Haematoxylin, crystals 1 gm. I Absolute alcohol 10 c.c. e. Stain sections for 12 to 24 hours in mixture composed of 9 volumes of A + 1 volume of B. f. Wash thoroughly in distilled water. g. Transfer to 90 per cent. — 15 minutes, h. Transfer to 95 per cent. — 15 minutes. i. Transfer to anilin oil-xylol (anilin oil 2 vol. + xylol 1 vol.) — 5 minutes. j. Transfer to pure xylol — 5 minutes. k. Mount in balsam. The exact degree of color must be determined by experience and the individual taste of the worker ; the Weigert method in any of its forms is a stain particularly for the medullated nerve-fibres, the cellular elements being better displayed by carmine or other haema- toxylin dyes. Cox-Golgi method for displaying the nerve-cells of the central nervous system possesses the advantages of simplicity and relative certainty over the older silver impregnation methods of Golgi. Small pieces of nervous tissue, not over from two to three centi- metres cube, are placed in a mixture composed of — Solution of potassium bichromate (5 per cent. ) 20 c.c. Solution of corrosive sublimate > 5 per cent 20 c.c. Solution of potassium chromate (5 per cent, i 16 c.c. Distilled water 44 c.c. and allowed to remain until ready for cutting, the fluid being changed after the first, third, and seventh days, and subsequently each week for a month, if necessary. When ready for sectioning, the tissue is transferred directly to 95 per cent, alcohol for two hours and then embedded in celloidin by successive treatment with alcohol-ether, thin and thick celloidin solutions. After cutting, the sections are cleared in a mixture of — Xylol 3 parts, Phenol 1 part, and mounted in balsam ; cover with cover-glass. APPENDIX. 427 e. Wash in 80 per cent, alcohol — %—i hour. f. Dehydrate in absolute alcohol. g. Clear in turpentine oil, or first in clove oil. h. Balsam or damar. In case the sections are not sufficiently dark after cutting, the pre- cipitate can be blackened by treatment with solution of sodium sulphate. Golgi's gold method is useful for displaying naked axis-cylinders and ultimate nerve-fibrillse, as well as special nerve-endings : the method possesses the advantage of being relatively certain and rapid in its action, especially if the reduction be facilitated by heat. Soak the fresh tissue in — a. Arsenious acid .5 gm. Water, distilled 100 c.c. until it becomes tra?ishice?it — usually 15-25 minutes. b. Transfer to — Gold chloride .5 gm. Water, distilled 100 c.c. for 25 to 45 minutes ; rinse off in distilled water. c. Transfer to 1 per cent, arsenious acid solution and expose to sunlight until reduction follows and the tissue appears of a deep purple or red color ; this reduction may be hastened by gently heat- ing over water-bath for some 10 to 15 minutes, until the tissue be- comes deeply colored. d. Wash thoroughly in water. e. Transfer to alcohol for dehydration, or to 50 per cent, glycerin, as the case may demand respectively for balsam or glycerin mounting. Silver staining is an important means of bringing to view the boundaries of epithelial and endothelial cells by the deposit of reduced silver particles within the intercellular cement-substance ; in the typical silver staining only the cell boundaries are shown as dark brown or black lines, the protoplasm being almost colorless. In intensely stained specimens of very fresh still living tissue the protoplasm and nuclei are sometimes colored. The silver method also tinges the interfibrillar ground-substance of dense connective tissue, bringing to view the cell-spaces as clear areas within a colored field. The absohdely fresh tissue is carefully rinsed in distilled water, without rubbing the surfaces, and then transferred to .5-1 per cent, solution of silver nitrate from 2 to 10 minutes, depending on the thickness of the object ; the then milky tissue is washed and exposed 428 APPENDIX. in distilled water to sunlight in a porcelain dish until it becomes dark brown ; the reduction is arrested, when sufficiently advanced, by thorough washing in water to which a few grains of sodium chloride have been added. The stained tissue may be mounted either in glycerin or in balsam, soaking in dilute and later strong glycerin, or dehydration and clearing, being the subsequent respective manipu- lations. Staining chromatin filaments for the display of karyokinetic figures and other studies of cell-structure can be successfully carried out only after accurate fixation of the cells, for which purpose the stronger Flemming's solution will be found most trustworthy. The tissue after such treatment is embedded in paraffin and cut, the fixed sections on the slide being subsequently stained by saffranin or by Delafield's haematoxylin. When karyomitosis is the especial object of study, preparations made by stripping off the epidermis of suitable animals {very young larval newts being excellent) are more favorable than sections, as the cells are preserved intact and contain the entire chromatin figures, and not merely the parts included within the planes of the section. Place small pieces of such tissues in — 3. Saffranin 2 gm. Alcohol, 50 per cent 60 c.c. 24-48 hours. b. Wash off in water for a few moments. c. Transfer to acidulated absolute alcohol {10 drops of pure hydro- chloric acid to 100 c.c. of absolute alcohol) for a few moments \TA— 1 minute) until the clouds of color cease to be copiously given off; then — d. Transfer to fresh absolute alcohol for 1 to 2 minutes. e. Clear in clove oil and mount. Care must be taken not to remove too much color by prolonged action of either the acidulated or the plain absolute alcohol, since the preparation can be almost entirely bleached by inattention to this point. In a successful preparation the chromatin figures are brilliantly stained of a bright red, while the other parts of the cells are almost uncolored. Injection of capillary blood-vessels requires considerable ex- perience, and at best an element of uncertainty enters into every attempt, since the condition of the tissues, particularly of the vessels, largely influences the manner in which the fluid runs. While car- mine-gelatin injections make very attractive pictures, a successful blue mass possesses many advantages when used in connection with APPENDIX. 429 carmine solutions. One of the most convenient and efficient inject- ing- fluids is — Soluble Berlin blue ( Griibler) 3 gm. Distilled water 600 c.c. This fluid runs well, does not extra vasate, and may be tised cold ; perfectly fresh animals, immediately after killing, are the most favor- able subjects for the manipulation. A smoothly-working ha?id- syringe (200-300 c.c. capacity), with appropriate stop-cock and can- ulae, is the best instrument, since the educated hand of the operator forms the best judge of the amount of pressure that may safely be applied. When the injection is completed the vessels should be ligated and the tissue placed in 70 per cent, alcohol or Miiller's fluid for fixation and subsequent hardening. In the case of the lungs, after injecting the blood-vessels, the tissue should be moderately dis- tended by forcing the preserving fluid into the organ through the air-tubes. In conclusion, it may be repeated that the object in appending these pages treating of microscopic technology is to present in detail a few methods which will be found satisfactory and thoroughly trust- worthy for the great majority of histological investigations. The student is urged to persevere with those here given until he has re- peatedly carried the manipulations to a successful issue by producing the really beautiful results of which these methods are capable. INDEX. Absolute alcohol, use of, 409. Accessory digestive glands, 182. development of, 189. Acervulus cerebri, 330. Achromatin, 13. Adenoid tissue, 118. Adipose tissue, 43. Agminated glands, 173. Alum-haematoxylin (Bohmer), 414. Amoeboid movement, 12 Amphiuma. red blood-cells of, 108 Aqueduct of Sylvius, nuclei of floor of, 304. Arachnoid, 283. villi of 283. Areolar tissue, 40. Arrector pili, 272. Arterial glands, 114. Arteries, 94. adventitia of, 96. intima of, 95. media of, 95. small, 97. structure of, 94. Association fibres of cerebrum. 327. Attraction-spheres. 14. Auerbach, plexus of, 73. Axis-cylinder, 73. processes, 70 B. Baillarger's stripes, 311. Bartholin's glands, 237. Basement-membranes, 137. Berlin-blue injecting, 429. Blastoderm, 23. Blastodermic layers, 24, 25. Blood, 105. elementary particles, m. fibrin, m. granules of Max Schultze, m. haematoblasts, m. Blood-cells, colored, 106. colored, human, 107. colorless, 105. division of, 112. effect of reagents upon, 108. origin of colored, 112. origin of colorless, 112. primary embryonal, 113. reproduction of colorless, 106. size of, 108. Blood-crystals, m. -islands of Pander, 103 Blood-platelets, no. Blood-vessels, 94. capillary, 99. development of, 103 lymphatics of, 100. nerves of, 100. perilymphatic clefts, 100 Bone, 47. circumferential lamella;, 48. compact, 47. development of, 51. endochondral formation of, 52. ground lamellae, 48. Haversian canals, 48. Haversian spaces, 54. Howship's lacunas, 56. interstitial lamella;, 48. marrow, 50. marrow-cavity, 48. osteoblasts, 55. osteoclasts, 56. perforating fibres of Sharpey, 50. periosteal formation of, 54. periosteum, 49. red marrow, 50. spongy, 47. summary of development of, 56. varieties of, 47. Borax-carmine (Grenacher), 412. Brain-sand, 283, 330. Bronchial tubes, 250. Brunner's glands, 171. Canal of Schlemm, 351. Capillary blood-vessels, 99. Carmine staining, advantages of, 411. Carotid gland, 114. Cartilage, 44. cells, 45. development of, 47. elastic, 46. fibrous, 47. hyaline, 44. of bronchial tubes, 250. of Santorini, 248. of trachea, 249. of Wrisberg, 248. perichondrium of, 46. varieties of, 44. Cells, embryonal, n. goblet, 31. granule, 37 431 432 Cells, irritability of, 21. motion of, 21. pigment, 37. plasma, 36 typical, 12. wandering, 36. Cell-division, direct, 15. indirect, 16. Cell-wall, 12. Celloidin method, 417. Central nervous system, 282. Centrosome, 14, 19. Cerebellum, 304. cells of Purkinje, 308. granule layer, 305. molecular layer, 309. nuclei of the roof, 310. white matter of, 310. Cerebral cortex, blood-vessels of, 319. pyramidal cells of, 312, 313. stratification of, 311. Cerebrum, 311. association fibres of, 327. claustrum, 320. commissural fibres of, 327. cornu Ammonis, 312. corpus striatum, 319. fascia dentata, 318. fibre-tracts of, 326. fifth ventricle, 319. fimbria, 318. hippocampus major, 315. nerve-fibres of, 314. nucleus caudatus, 319. nucleus lenticularis, 320. optic thalamus, 320. peduncles of, 303. projection fibres of, 327. septum lucidum, 319. white matter of, 326. Ceruminous glands, 275. Charcot's prostatic crystals, 222. Choroidal fissure of eye, 373. Chromatin, 13. figures, staining of, 428. Ciliary motion, 30. effects of reagents upon, 31. Claustrum, 320. Clitoris, 237. Coccygeal gland, 114. Coelom, 133. Colostrum, 242. Conarium, 329. Connective tissue, 35. arrangement of cells of, 38. cellular elements of, 36. development of, 42. ground-substance of, 40. juice-canals of, 39. migratory cells of, 36. mucoid, 40 spaces of, 39. varieties of, 35. wandering cells of, 36. white fibrous, 39. INDEX. Connective tissue, yellow elastic 39 Conus medullaris, 284. Cornea, 336. Corneal corpuscles, 338. Corpora amylacea of brain, 330. geniculata, 322. mammillaria, 323. quadrigemina, 321. Corpus callosum,' 327. striatum, 319. subthalamicum, 321. Cowper's glands, 222 Crescents of Gianuzzi, 141. Crura cerebri, 303. crusta of, 303, 304 fibres of crusta, 327. substantia nigra, 304. tegmentum of, 303, 304. Cutis anserina 272. D. Debove's endothelium of intestine, 169 Decidua, uterine, 233. Delafield's hematoxylin, 413. Demilunes of Heidenhain, 141. Dentine, 51. Derivatives of blastodermic layers, 25 Direct cell-division, 15. Duct, endolymphatic, 396. galactophorous, 240. Gartner's, 230, 245. Muller's, 242. of thyroid body, 257. Wolffian, 204, 242. Dura mater, 282. nerves of, 283. perivascular lymphatics of, 282. venous sinus of, 282. £. Ear, 377. accessory spiral ligament, 390 ampulla of semicircular canals, 387 auditory pit, 398. auditory teeth, 391. basilar membrane, 391 canalis reuniens, 383. cells of Claudius, 394, 395. cells of Deiters, 394, 395 cells of Hensen, 394, 395. ceruminous glands of, 377. cochlea, 388. cochlea, blood-vessels of, 397. cochlea, nerves of, 395. cochlea, perilymph-spaces of, 396. Corti's organ, 392. crista basilaris, 389. crista acusticae of semicircular canals, 386 development of, 397. ductus cochlearis, 388, 389. ductus endolymphaticus, 383, 396 Eustachian tube, 382. external auditory canal, 377. external cartilage of, 377. fenestra ovalis, 382. INDEX. 433 Ear, hair-cells, 394. hair-cells ol maculae acusticae, 385 internal, 383. ligamentum spir.de, 389. maculae acusticae of, 384. mastoid cells, epithelium of, 380. membrana tectoria, 395. membrane of Keissner, 389. middle, epithelium of, 380 middle, glands of, 380. ossicles, 381, 382. otic vesicle, 398. otolith-membrane, 385. otoliths, 385. pillars of Corti, 392. prominentia spiralis, 390. saccule, 383. saccus endolymphaiicus, 396. secondary tympanic membrane, 381. semicircular canals, 386. spaces of Nuel, 395. spiral lamina, 388. stria vascularis, 390. sulcus spiralis, 391. tympanic cavity, 380. tympanic membrane, 378. tympanum, lymphatics of, 379. tympanum, nerves of, 379. utricle, 383. Ear-stones, 385. Ectoderm, 24. derivatives of, 25. Elastic tissue, 42. Elastin, 40. Eleidin, 272. Elementary tissues, n. Embedding, interstitial, 414. simple, 414 Embryonal cell, 11. Endochondral formation of bone, 52. Endogenous cell-division, 20. Endothelium, 33. development of, 34. stomata of, 33. Entoderm, 24. derivatives of, 25. Epididymis, 213. development of, 243. globus major of, 208, 212. tube of, 213. Epidural spaces, 282. Epiglottis, 248. glands of, 248. Epiphysis, 329. Episcleral space, 372. Epithelium, 26. ciliated, 30. classification of, 26. columnar, 29 development of, 27, 34. distribution of, 27. germinal, of ovary, 224. glandular, 31. modified, 30. of mucous membranes, 136. 28 Epithelium of sense-organs, 32. pigmented, 31. prickle-cells, 29. rod, 32. squamous, 27. transitional, 29. varieties of, 26. Eponychium, 278. Epoophoron, 230. Equatorial plate, 17. Erythroblasts, 113. Eustachian tube, 382. Eye, 336. anterior chamber of, 366. blood-vessels of, 365. canal of Petit, 366. canal of Schlemm, 351 capsule of Tenon, 366, 372. choriocapillaris, 343 choroid, 342. choroidal fissure, 373. ciliary body, 344. ciliary muscle, 345. ciliary processes, 344. color of iris, 349. conjunctiva, 369. cornea, 336. crystalline lens, 361. development of, 372. fovea centralis, 356. hyaloid canal, 365. hyaloid membrane, 364. irido-corneal angle, 349. iris, 346. iris, color of, 349. lachrymal canals, 371. lachrymal caruncle, 370. lachrymal gland, 371. lamina cribrosa, 360. lamina fusca, 341. lamina suprachoroidea, 341. . ligamentum pectinatum iridis, 35a lymphatics of, 366. macula lutea, 356. membrana nictitans, 370. naso-lachrymal duct, 371. nerves of, 367. optic nerve, 358. optic nerve, excavation of, 360. optic nerve, sheaths of, 359. optic vesicle, 372. ora serrata, 357. perichoroidal space, 366. plica semilunaris, 370. retina, 351. retina, morphology of, 351. retina, pigment-layer of, 356. retina, visual cells of, 354. sclera, 341. spaces of Fontana, 350. suspensory ligament of lens, 363. tapetum cellulosum, 343 tapetum fibrosum, 343. Tenon's space, 366. venae vorticosae, 343, 366. 434 Eye, vitreous body, 364. vitreous lamina, 344. zone of Zinn, 363. Eyelids, 367. blocd-vessels of, 370. development of, 376 glands of Moll, 370 lymphatics, 370 Meibomian glands, 369. nerves of, 371. tarsus, 368. F. Fallopian tube, 230. Fat, 43. Fat-cells, 43. Female pronucleus, 22. Fenestrated membrane of Henle, 95. Finishing and storing preparations, 423. Fixation of tissues, 408. Fixing sections to the slide, 420. Flemming's solution, 409. Foramen caecum, 257. Galactophorous ducts, 240. Gall-bladder, 182. Ganglia, structure of, 80. Gartner's duct, 230. Genitalia, female, 236 Germ-cells of neural tube, 333. Germinal epithelium, 224. spot, 227. vesicle, 227. Giraldes's organ, 214. Glands, 137. arterial, 114. Bartholin's, 237. blood-vessels of, 141. Brunner's, 171. carotid, 114. coccygeal, 114. compound saccular, 138. compound tubular, 137. Cowper's, 222. development of, 142. epithelium of, 32. Harder's, 370. lachrymal, 371. Lieberkuhn's, 170. Littre's, 203. lymphatics of, 142. Moll's, 370. Montgomery's, 240. mucous, 140. Naboth's, 233. nerves of, 142. racemose, 138. secreting cells of, 141. serous, 140. simple saccular, 138. simple tubular, 137. solitary, 172. structure of, 138. Tyson's, 219. unicellular, 137. INDEX. Glands, varieties of, 137. Golgi's gold method, 427. silver method, 426. Graafian follicles, 226. number of, 228. Grandry's tactile corpuscles, 84. Granule-cells, 37. Growth, 15. H. Haematoxylin staining, advantages of, 411. Weigert s method, 425. Hair, 268. color of 269. development of, 279. lanugo, 280. race peculiarities of, 267, renewal of, 280 structure of, 268 Hair-follicles, 269. root-sheaths of, 270. structure of, 271. Hassall's corpuscles of thymus, 128. Haversian canals, 48. Heart, 100. annuli fibrosi, 101. blood-vessels of, 102. chordae tendineae, 101 corpus Arantii, 101. development of, 104. endocardium, 100. fibres of Purkinje, 101. lymphatics of, 103. muscular. tissue of, 102. nerves of, 103. pericardium, 102. structure of, 100. valves of, 100. Howship's lacuna;, 56. Hyaloplasm, 13. Hydatid, sessile, 244. stalked, of Morgagni, 230. Hypophysis cerebri, 328. I. Indirect cell-division, 16. Injecting capillary blood-vessels, 429. Internal capsule, 327. Intestines, 168. agminated glands, 173. blood-vessels of, 175. Brunner's glands of, 171. chyle vessels of, 169. duodenal glands of, 171. glands of, 170. goblet-cells of, 169. Lieberkuhn's follicles of, 170. lymphatics of, 175. mucosa of large, 169. mucosa of small, 168. muscular coat of, 174. muscular coat of large, 174. muscularis mucosae of, 174. nerves of, 176. Peyer's patches, 173. solitary glands of, 172. INDEX. 435 Intestines, submucosa of, 174. valvulae conniventes, 168. villi of, 168, 169. K. Karyokinesis, 15. Kidney, 191. blood-vessels of, 199. Bowman's capsule, 193. capsule of, 193. columns of Bertini, 192. connective tissue of, 193. development of, 204. divisions of, 191. glomeruli of, 193. Henle's loops, 195. labyrinth of, 192. lobules of, 191. lymphatics of, 200. Malpighian bodies, 193. Malpighian pyramids, 192. Malpighian tuft, 193. medulla of, 192. medullary rays, 192. nerves of, 200. papillae of, 191. pelvis of, 201. sinus of, 201. tubes of Bellini, 195. uriniferous tubules of, 195, 196. Kleinenberg's solution, 410. Krause's views regarding muscle, 63. Labia majora, 236. minora, 236. Lachrymal canals, 371. gland, 371. Lanugo, 280. Larynx, 246. blood-vessels of, 248. cartilages of, 248 lymphatics of, 248. nerves of, 248. vocal cords of, 246. Leucocytes, 105. Lieberkiihn's follicles, 170. Ligamentum nuchse, 42. Liver, 176. bile-capillaries of, 178, 179. bile-ducts of, 180. blood-vessels of, 181. cells of, 178. development of, 189. fibrous tissue of, 176. glands of bile-ducts, 181. Glisson's capsule, 176. interlobular vessels of, 177. intralobular capillary net-work, 177. lymphatics of, 181. multinucleated cells of, 189. nerves of, 182. perivascular lymphatics of, 179. Lung, 252. air-sacs, 252. Lung, alveolar passages, 251. blood-vessels of, 254. connective tissue of, 254. development, 259. infundibula, 251. lobules of, 252. lymphatics of, 255. nerves of, 255. pigment within, 254. terminal bronchus, 251. Lunula of nail, 265. Luschka's gland, 114. Lymph, 117. capillaries, 116. corpuscles, 117. corpuscles, sources of, 118. perineurial channels, 117 perivascular sheaths, 117 Lymphatic glands, 119. blood-vessels of, 120 compound, 120. simple, 119. spaces, 115. system, 115. system, development of, 133. tissues, 118. tissues, diffuse, 119. tissues, elements of, 118. vessels, 117. M. Male pronucleus, 23. Mammary glands, 238. ampullae, 240. areola, 240. blood-vessels, 241. during lactation, 239. galactophorous ducts, 240 lymphatics, 241. nerves, 241. nipple, 240. rudimentary, 241. Maturation of ovum, 22. Medulla, 295. anterior pyramid, 300. arcuate fibres, 298, 299. clavus, 296. corpus dentatum of olive. 299. cuneate tubercle, 296. decussation of anterior pyramids, 297. external cuneate nucleus, 297. fibre-tracts of, 300. formatio reticularis, 298. funiculus Rolandi, 296. funiculus teres, 297. hypoglossal nucleus, 297. lateral tract, 300. nucleus cuneatus, 296. nucleus gracilis, 296. nucleus lateralis, 297. posterior pyramid, 301. restiform body, 300. spinalis, 284. Meissner's tactile corpuscles, 85, Melanin, 38. 436 INDEX. Membrana nictitans, 370. propria of mucous membranes, 137. Membrane of Descemet, 339. Merkel's tactile corpuscles, 84. Mesoderm, 24. derivatives of, 25. Mesogastrium, 190. Mesothelium, 133. Metabolism, 15. Metakinesis, 18. Microcytes of blood, in Milk, 241 colostrum corpuscles, 242. secretion of, 239. Mitotic cell-division, 16. Mounting sections, 422. Mouth, 144. blood-vessels of, 145 lymphatics of, 145. mucous membrane of, 144 nerves of, 145. Mucous membranes, structure of, 136. Muscle, 58. blood-vessels of, 67. cardiac, 66. development of, 67. involuntary, 59. nerves of, 67. non-striped, distribution of, 58. striped, 61. voluntary, 61. Miillerian duct, 242. Miiller's fibres of retina, 352. Miiller's fluid, 408. Myeloplaxes of Robin, 51. N. Nails, 265. development of, 278. growth of, 278. lunula, 279. regeneration rr, 279. structure of, 266. Nasal mucous membrane, 402. blood-vessels of, 404. Bowman's glands, 404 development of, 405 glands of, 402. lymphatics of, 405. nerves of, 405. olfactory division of, 403. olfactory epithelium, 404. respiratory division of, 402. Nasmyth's membrane, 148. Naso-lachrymal duct, 371. Nebenkeru, 14. Nephrostomata, 197. Nerve-cells, 69. of first type, 70. of second type, 71. processes of, 70. Nerve endings, 83. classification of, 88. cylindrical end-bulbs, 86. in blood-vessels, 92. Nerve-endings in glands, 92. in non-striated muscle, 89. in striated muscle, 90. muscle-spindles, 91. of Langerhans, 84. sensory, 83. spherical end-bulbs, 85. tactile cells, 84. tendon spindles, 92. Nerve-fibres, 72. medullated, 73 non-medullated, 74. of spinal cord, 288. Nerve-trunks, 77. blood-vessels of, 78. endoneurium, 77. epineurium, 78. funiculus, 77. Henle's sheath of, 78. lymphatics of, 78. nerves of, 78. perineurium, 77. Nervi nervorum, 78. Nervous system, 282. Nervous tissues, 69. development of, 81. supporting fr imework 01, 79. Neuroblasts, 81, 333. Neuro-epithelium, 93. Neuroglia, 79. cells, 79. Nipple, 240. Nucleolus, 14. Nucleus, 13. caudatus, 319. fibrils of, 13. lenticularis, 320. membrane of, 13. segmentation, 23. structure of, 13. Nymphae, 236. (Esophagus, 160. muscular tissue of, 161. Olfactory bulb, 324. glomeruli, 325. lobe, 323. tract, 323. Optic thalamus, 320. Organ of Rosenmiiller, 230. Ovary, 224. blood-vessels, 229. corpus luteum of pregnancy, 229. development of, 244. germinal epithelium, 224. interstitial cells, 228. lymphatics of, 229. nerves of, 229. primary egg-tubes, 244. primordial ova, 244. stroma, 225. tunica albuginea, 225. Oviduct, 230. Ovula Nabothi, 233. INDEX. 437 Ovum, 227. escape of, 228. germinal spot, 227. germinal vesicle, 227. maturation, 22. segmentation of, 23. P. Pacchionian bodies, 283. Pacinian corpuscles, 86. Pancreas, 185. development of, 189. Panniculus adiposus, 265. Paradidymis, 214. development of, 243. Paranucleus, 14. Parasinoidal spaces, 282. Paroophoron, 245. development of, 245. Parovarium, 230. development of, 244. Peduncular fibres, 327. Penis, 216. arteries of, 218. cavernous venous channels of, 217. corpora cavernosa, 216. corpus spongiosum, 218. erectile tissue of, 218. glands of Tyson, 219. helicine arteries of, 218. lymphatics of, 219. nerves of, 219. Perichondrium, 45. Perionyx, 278. Periosteal bone, 54. Peripheral nerve-endings, 83. Peyer's patches, 173. Phagocytes, 106. Pharynx, 159. glands of, 159. mucous membrane of, 159. Pia mater, 283. pigment-cells of, 284. Picro-sulphuric acid solution, 410. Pigment-cells, 37. Pigment of hair, 2C9. of skin, 263. Pineal body, 329. eye, 329- Pituitary body, 328. Plasma-cells of Waldeyer, 36. Plastin, 13. Pleura, 256. blood-vessels of, 256. nerves of, 256. Plexus of Auerbach, 167. of Meissner, 167. Polar bodies, 22. field, 16. Pole-corpuscle, 14. Pons, 301. locus cceruleus, 302. nuclei of, 301. posterior longitudinal bundle, 302. substantia ferruginea, 302. Preparation of tissues, order of manipulations, 407. Preservation of tissues, 410. Primary body-cavity, 133 neural tube, 332. Primordial ova, 244. sexual cells, 243. Projection fibres, 327. Pronucleus, female, 22 male, 23. Prostate gland, 219. acini of, 220. amyloid concretions of, 216. blood-vessels of, 222. concretions of, 222. involuntary muscle of, 220. lymphatics of, 222. nerves of, 222. secretion of, 222. Prostatic crystals, 216. sinus, 221. Protoplasm, reticulation of, 13. structure of, 12. Purkinje's ganglion-cells, 308. basket-works of, 310. R. Reissner's membrane, 589. Reproduction of the cell, 15. Reproductive organs, table of homologies of, 245. Respiratory organs, 246. Rt-te Malpighii, 262. Ribbon sections, 420. Rollett's views regarding muscle, 63. Root-sheaths of hair-follicle, 271 S. Saffranin staining, 428. Salivary corpuscles, 156. Sebaceous glands, 273. Sebum, 273. Section-cutting, 418. Segmentation nucleus, 23. Segmentation of ovum, 23. Semen, 273. Serous membranes, 128 blood-vessels of, 130. classification of, 128. development of, 133. ground-substance of, 130. nerves of, 131. structure of, 129. Sexual cords, 243. glands, indifferent, 243. Sharpey's fibres of bone, 50. Silver staining, 427 Sinus pocularis, 221, 244. Skin, 261. arrector pili, 272. blood-vessels of, 276. corium, 264. development of, 277. eleidin granules, 263. epidermis, 262. epitrichial layer, 263. 43§ INDEX. Skin, hair-follicles, 269. hair-papillae, 272. lymphatics of, 276. muscles of, 272. nerves of, 277. panniculus adiposus, 265. papilla; of, 264. pigment of, 263. sebaceous glands, 273. stratum corneum, 263. stratum granulosum, 263. stratum lucidum, 263. stratum Malpighii, 263. structure of hair.-, 268. sweat-glands, 273. Somatopleure, 133. Spaces of Fontana, 350. Spermatic crystals, 216. duct, 213. Spermatozoa, 215. vibrations of, 215. Spinal cord, 284. anterior column, 285. anterior gray commissure, 290. anterior ground-bundle, 286. anterior median fissure, 285. anterior radicular zone, 286. ascending anterolateral, 286. blood-vessels of, 294. Burdach's column, 286. central canal of, 293. Clarke's column, 290. connective tissue, framework of, 287. crossed pyramidal tract, 286. descending antero-lateral, 286. direct cerebellar tract, 286. direct pyramidal tract, 286. ependyma of, 293. filum terminale, 285. ganglion-cells, 290. Coil's column, 286. Gowers's tract, 286. gray commissure, 285. gray matter, arrangement of, 288. lateral column, 286. mixed lateral tract, 286. neuroglia of, 287. outlying ganglion-cells, 291. posterior column, 285. posterior median fissure, 285. structure of gray matter, 290, 291. substantia gelatinosa, 293. substantia gelatinosa Rolandi, 293. substantia spongiosa of, 291. Tiirck's column, 286. ventriculus terminalis, 294. white commissure, 288. white matter of, 287. Spirem, 16. Splanchnopleure, 133. Spleen, 122. blood-vessels of, 125. development of, 134. lymphatics of, 126. Malpighian corpuscles of, 124. Spleen, nerves of, 126. pulp-tissue of, 124. Spongioblasts, 81, 333. Spongioplasm, 12. Staining, 411. chromatin figures, 428. Standard technique, outline of, 423. Stomach, 162. acid cells of, 163. blood-vessels of, 166. development of, 187. lymphatics of, 167. mucous membrane of, 162. muscular coat of, 166 nerves of, 167. peptic glands, 162. pyloric glands of, 164. serous coat of, 166. submucosa of, 165. Stratum Malpighii, 263. Subarachnoidean space, 283. Substantia gelatinosa of spinal cord, 293. Substantia spongiosa of spinal cord, 291. Suprarenal body, 330. Sweat-glands, 273. muscle of, 275. number of, 275. secretion of, 275. Synovial membranes, 131. blood-vessels of, 132. Haversian fringes of, 132. nerves of, 132. structure of, 131. Tapetum cellulosum of choroid, 343. Tapetum fibrosum of choroid, 343. Taste-buds, 155. Teeth, 145. cementum, 148. crusta petrosa, 148. dental papilla, 150. dentinal fibres, 147. dentinal tubules, 146. dentine, 146. development of, 149. enamel, 147. enamel organ, 150. incremental lines of Salter, 147. interglobular spaces, r46. membrane of Nasmyth, 148. odontoblasts, 152. pulp, 148. Schrager's lines, 147. stripes of Retzius, 148. Tegmentum of cerebral peduncles, 328. Tendon, structure of, 41. Tendon-cells, 41. Tenon's capsule, 372. Testicle, 207. blood-vessels of, 214. coni vasculosi, 208, 213. development of, 243. hydatids of, 214. interstitial cells, 212. INDEX. 439 Testicle, lymphatics ot, 214. mediastinum ot, 207. nerves of, 214. seminiferous tubules, 208. Sertoli's columns, 209. spermatoblasts, 209. spermatogenesis, 210. straight tubules, 212. tunica albuginea, 207. tunica vaginalis, 207. vasa efferentia, 208, 213. Thymus body, 126. blood-vessels of, 128. corpuscles of Hassall, 128. development of, 134. lymphatics of, 128. nerves of, 128. Thyro-glossal duct, 257. Thyroid body, 257. colloid secretion of, 258. development of, 260. Tissues, constituents of, 11. elements of, 23. Tongue, 153. blood-vessels of, 156. glands of, 156. lymphatics of, 156. mucous membrane of, 152. nerves of, 156. papilla of, 153. Tonsils, 158. Trachea, 249. blood-vessels of, 250. cartilages of, 249. glands of, 249. lymphatics of, 250. nerves of, 250 Tunica propria of mucous membranes, 136. U. Ureter, 201. development of, 204. Urethra, 203. development of, 206. female, 203, 237. glands of, 203, 238. male, 203. Urinary bladder, 202. development of, 206. Uterus, 232. blood-vessels of, 234. cervix, 232. development of, 244. menstrual changes, 233. muscular coat of, 234. Uterus masculinus, 221, 244. Vagina, 235. development of, 244. Vas deferens, 213. ampullse of, 213. Vasa vasorum, 99. Veins, 97. adventitia of, 98. intima of, 97. media of, 98. valves of, 98. variations in coats of, 98. Vital manifestations of the cell, 15. Vitelline membrane, 227. Vitellus, 227. Vocal cords, 246. W. Wandering cells of connective tissue, 36. Weigert's staining method, 425. White fibrous tissue, 39. Wolffian body, 204, 242. Wolffian duct, 204, 242. Wolffian tubules, 242. Y. Yellow elastic tissue, 39. THE END. COLUMBIA UNIVERSITY This book is due on the date indicated below, or at tbe expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special ar- rangement with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE 3IC j ■ -- R C28'638>MEO I I IB mm iM I. -. '' •'* :,vv.v'