TEXT-BOOK OF NV)RMAL HISTOLOGY INCLUDING AN ACCOUNT OF THE DEVELOPMENT OF THE TISSUES AND OF THE ORGANS. BY GEORGE A. PIERSOL, M.D., PROFESSOR OF ANATOMY IN THE UNIVERSITY OF PENNSYLVANIA. WITH FOUR HUNDRED AND NINE ILLUSTRATIONS, OF WHICH THREE HUNDRED AND FIFTY-EIGHT ARE FROM ORIGINAL DRAWINGS BY THE AUTHOR. SEVENTH EDITION. \\< ;' : ' ' PHILADELPHIA AND LONDON: J. B. LIPPINCOTT COMPANY. 1904. Copyright, 1893, by J. B. LlPPlNCOTT COMPANY. Copyright, 1899, by J. B. LlPPlNCOTT COMPANY. ELECTROTYPED AND.PRINTED BY J. B. LlPPlNCOTT COMPANY, PHILADELPHIA, U.S.A. PREFACE. IN the preparation of these pages the aim of the author has been to present descriptions which should include the salient features of the various structures with sufficient fulness to impress important details without wearying minutiae : many years of teaching have con- vincingly shown that too great conciseness of statement, on the one hand, and too great elaboration of detail, on the other, are alike unsatisfactory to the student in his efforts to gain an adequate and lasting knowledge of minute anatomy. The recognition of the underlying morphological relations of the tissues alone can bring the appreciation of the broad principles requisite for the elevation of histology from a maze of barren details to a study full of interest and suggestion. In order that these wider bearings may become apparent, a brief account of the embryological processes and the histological differentiation concerned in the de- velopment of the tissues and the organs has been added to the descriptions of the adult structures. The desirability of keeping the size and scope of the volume within the limits adapted to its primary purpose of text-book has forbidden the systematic consideration of embryological data, and much of interest relating to the earlier stages of development has been necessarily omitted. In adopting the character of the illustrations choice has been influenced by the reflection that the mission of such drawings is instruction, and that the illustrations best accomplishing that end are of most value for the object at hand. With the exception of those taken from other, duly acknowledged sources, the drawings have been made by the author in nearly all cases with the aid of the camera lucida or from photo-micrographs. While sufficiently dia- grammatic to be efficient aids in the comprehension of the text, the drawings are faithful likenesses of the original preparations; the latter as far as possible have been taken from human tissues. iii 258238 IV PREFACE. For manifest reasons, references and bibliography have been omitted, except in connection with statements where mention of the name of the authority has seemed desirable. The author wishes to express his obligation to the writings of Kolliker, Ranvier, Schwalbe, Waldeyer, Retzius, Stohr, Flemming, O. Hertwig, Schaefer, Golgi, Ram6n y Cajal, and others, as well as to many papers found in the Archiv fur mikroskopische Anatomic and other journals. G. A. P. UNIVERSITY OF PENNSYLVANIA, PHILADELPHIA, September 30, 1893. CONTENTS. CHAPTER I. PAGES THE CELL AND THE TISSUES 11-25 The elementary tissues ; The typical cell ; Protoplasm — arrangement and structure ; The nucleus and the nucleolus ; The paranucleus ; The centrosome and the attraction-spheres ; Vital manifestations of the cell ; Direct cell-division ; Indirect cell-division — karyokinesis ; Maturation and fecundation of the ovum ; Segmentation of the ovum ; The tissues— cellular and intercellular constituents ; The blastodermic layers and their derivatives. CHAPTER II. THE EPITHELIAL TISSUES 26-34 Varieties of epithelium ; Squamous epithelium ; Columnar epithelium ; Modified epithelium ; Glandular epithelium ; Neuro-epithelium ; Endothelium ; Development of epithelium ; Development of endothelium. CHAPTER III. THE CONNECTIVE TISSUES 35-57 Forms of connective tissue ; Cellular elements ; Intercellular constituents — white fibrous and yellow elastic tissue ; Mucoid tissue ; Tendon ; Elastic tissue ; Development of fibrous and elastic tissue ; Adipose tissue ; Hyaline cartilage ; Elastic cartilage ; Fibro-cartilage ; Development of cartilage ; Bone — spongy and compact ; Structure of compact bone ; vi CONTENTS. PAGES The periosteum ; The marrow of bone ; Development of bone ; Endochondral bone ; Periosteal bone ; Summary of bone-development. CHAPTER IV. THE MUSCULAR TISSUES 58-68 Non-striated muscle — distribution and structure ; Striated muscle-structure ; Arrangement of muscle-fibres ; Cardiac muscle ; Development of muscular tissue. CHAPTER V. THE NERVOUS TISSUES 69-82 Nerve-cells ; Nerve-fibres — structure ; Medullated nerve-fibres ; Non-medullated nerve-fibres ; Nerve-trunks—structure ; Supporting tissues of nerve-centres ; Ganglia — structure ; Development of nervous tissues. CHAPTER VI. THE PERIPHERAL NERVE- ENDINGS . . 83-93 Terminations of sensory nerves ; Special sensory nerve-endings ; Tactile cells ; Tactile corpuscles ; End-bulbs ; Nerve-endings in non-striated muscle ; Nerve-endings in striated muscle ; Nerve-endings in tendon ; Nerve-endings in blood-vessels ; Nerve-endings in glands ; Neuro-epithelium of the sense-organs. CHAPTER VII. THE CIRCULATORY SYSTEM . . 94-114 The arteries ; The veins ; The capillary blood-vessels ; The heart ; Development of the blood-vessels ; Development of the heart ; The blood ; The colorless blood-cells ; The colored blood-cells ; Effect of reagents on human blood ; Blood-crystals ; Development of the blood-corpuscles. CONTENTS. VH CHAPTER VIII. THE LYMPHATIC SYSTEM "S^SS The lymphatic spaces ; The lymphatic vessels ; The lymphatic tissues ; Simple lymph-follicles ; Compound lymph-glands ; The spleen ; The thymus body ; The serous membranes ; The synovial membranes ; Development of the lymphatic system ; Development of the spleen ; Development of the thymus body. CHAPTER IX. Mucous MEMBRANES AND GLANDS 136-143 Mucous membranes — structure ; Glands — varieties ; Tubular glands ; Saccular glands ; Glandular epithelium ; Glandular ducts ; Mucous glands ; Serous glands ; Changes due to functional activity ; Development of glands. CHAPTER X. THE DIGESTIVE TRACT , . 144-190 The oral cavity ; The teeth ; Development of the teeth ; -^ The tongue ; The papillae of the tongue ; The salivary corpuscles ; The tonsils ; The pharynx ; The oesophagus ; The stomach ; The glands of the stomach ; The intestines ; The intestinal villi ; The intestinal glands ; The glands of Lieberkiihn ; The glands of Brunner ; The solitary glands ; The agminated glands, or Peyer's patches ; The liver ; The gall-bladder ; The accessory digestive glands ; The parotid gland ; Vlll CONTENTS. The submaxillary gland ; The sublingual gland ; The pancreas ; Development of the digestive tract ; Development of the accessory digestive glands. THE URINARY CHAPTER XI. 191-206 The kidney ; The renal sinus and the ureter ; The urinary bladder ; The urethra ; Development of the urinary organs. CHAPTER XII. THE MALE REPRODUCTIVE ORGANS 207-223 The testicle ; Spermatogenesis ; The epididymis ; The semen ; The penis ; The prostate gland ; The glands of Cowper. CHAPTER XIII. THE FEMALE REPRODUCTIVE ORGANS 224-245 The ovary ; The ovum ; The escape of the ovum ; The parovarium ; The paroophoron ; The oviduct ; The uterus ; The vagina ; The genitalia ; The glands of Bartholin ; The mammary glands ; Milk; Development of the reproductive organs. CHAPTER XIV. THE RESPIRATORY ORGANS 246-260 The larynx ; The trachea ; The bronchi ; The lungs ; The pleura ; The thyroid body ; Development of the respiratory organs ; Development of the thyroid body. CONTENTS. ix CHAPTER xv. PAGES THE SKIN AND ITS APPENDAGES 261-281 The skin ; The nails ; The hair ; The sebaceous glands ; The sweat-glands ; Development of the skin and its appendages. CHAPTER XVI. THE CENTRAL NERVOUS SYSTEM 282-335 The membranes of brain and cord ; The spinal cord ; The medulla ; The pons ; The crura cerebri ; The cerebellum ; The cerebral cortex ; The hippocampus major ; Tne fascia dentata ; The fimbria ; The septum lucidum ; The corpus striatum ; The optic thalamus ; The corpora quadrigemina ; The olfactory lobe ; The white matter of the cerebrum ; The pituitary body ; The pineal body ; The suprarenal body ; Development of the nervous tissues. CHAPTER XVII. THE EYE AND ITS APPENDAGES , . 336-376 The cornea ; The sclera ; The choroid ; The ciliary body ; The iris ; The irido-corneal angle ; The retina ; The optic nerve and entrance ; The crystalline lens ; The vitreous body ; The blood-vessels of the eye ; The lymphatics of the eye ; The nerves of the eye ; The eyelids ; The Meibomian glands ; The conjunctiva ; The lachrymal apparatus ; The capsule of Tenon ; Development of the eye. CONTENTS. CHAPTER XVIII. PAGES THE ORGAN OF HEARING 377-401 The external ear ; The tympanic membrane ; The middle ear ; The ear-ossicles ; The Eustachian tube ; The internal ear ; The saccule and the utricle ; The semicircular canals ; The cochlea ; The ductus cochlearis ; The scala vestibuli ; The scala tympani ; The ductus endolymphaticus ; The development of the ear. CHAPTER XIX. THE NASAL Mucous MEMBRANE 402-406 The respiratory region ; The olfactory region ; Development of the nasal fossae. APPENDIX. THE MOST USEFUL HISTOLOGICAL METHODS 407-429 Fixation of the tissue Fixation reagents ; Preservation of the tissue ; Staining ; Staining solutions ; Embedding ; Interstitial embedding ; Paraffin method ; Celloidin method ; Section-cutting ; Cutting ribbon-series ; Fixing sections to the slide ; Mounting sections ; Finishing, labelling, and storing slides ; Outline of standard method ; Weigert's staining method ; Golgi's silver method ; Golgi's gold method ; Silver staining ; Staining chromatin filaments ; Injecting capillary blood-vessels. INDEX 431 LIST OF ILLUSTRATIONS. FIG. PACK 1. Colorless blood-cell u 2. Typical cell — ovum of cat 12 3. Structure of the cell 13 4. Cells exhibiting the paranucleus (Plainer) 14 5. Segmenting ova of ascaris megalocephala (Boveri) 14 6. Direct cell-division of colorless blood-corpuscle 15 7. Karyokinesis — diagram of close skein (Rabl- Schiefferdecker) 16 8. Karyokinesis — diagram of loose skein (Rabl- Schiefferdecker) 16 9. Karyokinesis — diagram of polar field (Rabl- Schiefferdecker) 17 10. Karyokinesis — diagram of migration of segments (Rabl) 18 11. Karyokinesis — epidermal cells from larva of newt 19 12. Segmenting ova, showing centrosomes and attraction-spheres (Boveri) . 20 13. Large marrow-cell with multiple nuclei . . 20 14. Maturation and fecundation of ovum (O. Hertwig) 22 15. Blastodermic layers of rabbit embryo 24 16. Squamous epithelium 28- 17. Stratified squamous epithelium in section 28- 18. Isolated cells of stratified squamous epithelium 2$ 19. Prickle-cells from epidermis 29 20. Simple columnar epithelium . . 29 21. Stratified columnar epithelium 29 22. Ciliated epithelium 30* 23. Isolated elements of ciliated epithelium 30 24. Goblet-cells 31 25. Pigmented epithelium 31 26. Glandular epithelium 32 27. Rod-epithelium (Heidenhain and Schiefferdecker) 32 28. Isolated neuro-epithelium 32 29. Endothelium 33. 30. Endothelium showing stomata . 34. 31. Young connective-tissue cell 36 32. Embryonal connective tissue 36- 33. Subcutaneous areolar tissue 37 34. Special connective-tissue elements 37 35. Pigmented connective-tissue cells 37 36. Pigment-cell 38. 37. Plate-like connective-tissue cells . 38 38. Cell-spaces of dense connective tissue 38 39. Branched connective-tissue cells 38. 40. White fibrous tissue 39 41. Elastic fibres isolated ( Schiefferdecker) 39 42. Young connective-tissue cells 40 43. Tendon in transverse section 4! xi xii LIST OF ILLUSTRATIONS. FIG. PAGB 44. ' Primary bundles of tendon 41 45. Primary tendon-bundles in section 42 46. Elastic fibres in transverse section 42 47. Elastic fibres forming fenestrated membrane 42 48. Subcutaneous tissue with fat-cells 43 49. Hyaline (costal) cartilage 44 50. Hyaline cartilage with perichondrium .... 45 51. Elastic cartilage 46 52. Fibro-cartilage 46 53. Transverse section of dried bone 47 54. Longitudinal section of dried bone 48 55. Lacunae and canaliculi of dried bone 48 56. Bone-cell within lacuna 49 57. Fragments of bone, showing Sharpey's fibres 49 58. Cells of bone-marrow 50 59. Primary embryonal cartilage 51 60. Developing bone — centre of ossification 52 61. Developing bone — zone of calcification 53 62. Developing bone — trabeculae of endochondral bone 54 63. Developing bone — conversion of osteoblasts into bone-cells 54 64. Developing bone — periosteal and endochondral bone 55 65. Developing bone — longitudinal section of embryonal phalanx 55 66. Developing bone — showing Howship's lacuna 56 67. Isolated involuntary-muscle cells 59 68. Involuntary-muscle cells 59 69. Involuntary muscle in transverse section 60 70. Involuntary muscle in longitudinal section 60 71. Voluntary-muscle fibres 61 72. Voluntary-muscle fibres in section 62 73. 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 fibrillae 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 (Schieffer decker) . 81 LIST OF ILLUSTRATIONS. FIG. 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 (Schieffer decker} 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 1 10. 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 1*17 141. Elements of adenoid tissue 118 142. Diffuse adenoid tissue 119 143. Simple lymph-follicle 119 144. Section of lymph-gland v 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 trabeculae 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 LIST OF ILLUSTRATIONS. *IG- 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 ( Stbhr) 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. XV FIG. PAGR 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 I71 212. Section of human large intestine i72 213. Peyer's patch from small intestine of cat i72 214. Section of small intestine of child 173 215. Section of injected small intestine of cat 174 216. Section of liver of hog i76 217. Section of human liver 177 218. Diagram of structure of liver . , 177 219. Section of injected human liver I78 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 XV1 LIST OF ILLUSTRATIONS. 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 foetus 277 312. Developing skin from foetal kitten 279 313. Developing hair from foetal kitten 279 314. Section of skin of foetal kitten 279 315. Degenerating hair-follicle from human scalp 280 316. Section of skin of human foetus 281 317. Brain-membranes of child 282 318. Section of human spinal cord from cervical region . 285 LIST OF ILLUSTRATIONS. 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 ( Testuf) ............. 296 330. Diagram of decussating tracts of medulla ( Testut-Duval) ....... 297 331. Diagram of medulla through olivary bodies (Testut-Duval} ...... 297 332. Diagram of sensory decussation of medulla (Testut-Duval) ...... 298 333. Diagram of medulla through olivary bodies (Testut-Duval} ...... 298 334. Section of medulla of child . . . .- ............... ... 299 335. Section through human pons (Tes tut- Stilling} ............. 302 336. Section through human cerebral peduncle (Krause] .......... 303 337. 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-Meynerf} ........ 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 .................... .,,o 354. Corpora amylacea from human brain ........... ..... . 330 355. Section of human suprarenal body .................. 3<5I 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) ................... 333 360. Germ-cells and spongioblasts (His) .................. 334 361. Spongioblasts from neural tube (His) ................. 334 362. Section of human cornea .................. ,,-r 363. Fibrous tissue of cornea of ox .................... 338 364. Corneal corpuscles of calf ...................... 333 365. Corneal spaces of calf ..................... ' 330 366. Corneal spaces of calf 367. Plexus of corneal nerves 368. Section of walls of human eyeball ,,,g 340 369. Section of human choroid ................... ,42 370. Human choroid from surface ............... 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 xviij LIST OF ILLUSTRATIONS. 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) 352 377. 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 373 389. Developing lens and optic cup of rabbit embryo 373 390. Choroidal fissure in developing eye of rabbit embryo 373 391. Developing eye of rabbit embryo 375 392. Section through developing eye of rabbit embryo 376 393. Section of human external auditory canal (Rudinger) 378 394. Human tympanic membrane and malleolus (Rudinger) 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 ( Testut) 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 4ot>. 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 small irregularly round or oval mass of finely granular gelatinous substance — the protoplasm or Cell-COntentS Colorless blood-cell exhibiting amoeboid movement. — in some part of which a smaller and often indistinct spherical body — the nucleus — lies embedded. In the embryonal condition, ii 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 throughout the greater part of the cell usually appears as a finely granu- lar semi-fluid or gelati- nous substance, in which minute granules, the microsomes, as well as other particles of extraneous matters, lie embedded. The most superficial zone of the protoplasm — known as the exoplasm — is de- void of microsomes. The structure of protoplasm is now recognized as far more complicated than was formerly supposed, comprising a highly elastic and extensible portion — the spongioplasm — and an Typical cell, — ovum of cat : a, protoplasm ; b, 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 interstitial, seemingly less active substance — the hyaloplasm. The active contractility which has been generally credited to the spon- gioplasm has been 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- minous substances alone the property of '£^^^±7^ Contractility resides; the plastin, On the wall ; c, chromatin filaments, between other hand, offers great resistance to ±*£-JS±? *"*" 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 usually 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, substance, the nuclear matrix. The nuclear membrane is composed of amphipyrenin. The nuclear fibrils consist of particles of a deeply staining proteid substance, chromatin, supported by delicate achromatic threads of linin, along which the chromatin is arranged as irregular beads or thickenings. 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 present, little is definitely established. The nucleolus is highly NORMAL HISTOLOGY. refracting, and, when subjected to appropriate stains, takes on a color differing from both nuclear fibrils and protoplasm ; it contains a substance known as pyrenin. The nucleolus lies closely approxi- mated to, but separated from, the nuclear fibrils, being especially evident in such elements 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 r6le in the life-history of the cell ; its true value, however, has yet to be determined. In addition to the parts of the cell readily recognized, the presence of a very small, constant, round, highly-refracting body — the cen- trosome — has been established within the cytoplasm. This body is so minute and inconspicuous that it is not easily distinguished ; the fact that the centrosome is itself surrounded by a clear area, FIG. 4. FIG. 5. B A, cell from pancreas of salamander: n, nucleus; /, paranucleus. B, sexual cell of leech : «, nucleus ; /, paranucleus ; c, centro- some. (After Plainer.) U Segmenting ova of ascaris megalocephala : n, nucleus ; a, centrosome, surrounded by attraction-sphere ; /, po- lar body. (After Boveri.) named the attraction-sphere, will often aid in its detection. While the centrosome has 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 it becomes most conspicuous, since its division and subsequent migration often inaugurate the complex cycle of nuclear changes. Certain investigators have described the occasional presence of an irregularly spherical body, lying within the protoplasm in the vicinity of the nucleus, to which the name accessory nucleus, or paranu- cleus {Nebenkern of the Germans), has been applied. According to Platner, the paranucleus is an extrusion of the nucleus, and is sub- ject to great variation in size and appearance ; the existence, nature, and function of this body are at present still uncertain, and need fur- ther investigation. THE CELL AND THE TISSUES. 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 simplest organisms, Or of the least dif- 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. FIG. FIG. 8. the brilliant investigations of Flemming, Strasburger, v. Beneden,. Schleicher, Rabl, and others have added much to the accurate knowledge of the life-history of the cell. The entire process of indirect cell-division may be divided con- veniently into three stages, which, however, gradually follow one another without sharp demarcation. These stages are : (i) the Pro- phases, embracing the preparatory changes of the nuclear constitu- ents ; (2) the Metaphase, during which the accurate division of the chromatin is effected ; (3) the Anaphases, in which distribution and rearrangement of the newly apportioned chro- matin takes place. Coincidently with the com- pletion of the new nuclei, the cell-protoplasm undergoes division, so that each daughter - cell consists of the new nu- cleus surrounded by a definite area of proto- plasm. These final changes constitute the Telophases. When the cell under- goes a complete and typi- cal mitotic division, the following changes occur : (i) The centrosome in- creases in size and, if not already existing double, divides into two ; the nu- cleus enlarges, while the chromatin greatly in- creases, the fibrils becom- ing contorted to form a dense convolution, whose twisted threads run gener- ally 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, becoming less convoluted, and forming irregularly-arranged loops, known as the (3) Loose skein. The skeins, sometimes composed of the con- tortions of one long fibre, at others of several shorter ones, separate at their peripheral turns, so that a definite number of distinct loops, or chromosomes, are formed ; the closed ends of these are directed 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 AND THE TISSUES. towards a common centre, around which, but removed some little distance, they become arranged. The enclosed clear space is the polar field. The centrosome early undergoes division, when not already double within the cytoplasm, and lies close to the nuclear membrane. The new centrosomes, enclosed within the attraction spheres, soon begin to separate, each receding from its original position through an arc of 90° towards the opposite poles of the cell. During the formation of the skeins and the division of the centro- somes the nuclear membrane disappears and the chromosomes lie free within the cell-protoplasm. Coincidently with the foregoing changes delicate striae make their appearance around each centro- some, the radiating figure thus produced constituting the amphi- aster. The rays bridging the space separating the centrosomes are so disposed 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 ; these achromatin figures constitute the nuclear spindle, and occupy the polar field. The cromatin fibrils, now staining intensely, grow thicker and shorter, and arrange themselves so that the closed ends of the loops encircle the polar field, giving rise, when seen from the 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 dif- ferences, therefore, between the wreath and the aster depend upon the point of view, and not upon variations in the arrangement of the fibres. The completion of these preparatory changes marks the termination of the prophases ; the suc- ceeding metaphase is initiated by an important change leading to the reapportionment of the chromatin. (5) Each of the loops, or chromosomes, un- dergoes longitudinal cleavage, splitting up into double the number of segments : these are now entirely rearranged during the anaphases, the first step being: (6) A rapid separation into two groups, pass- ing towards the poles of the future new nuclei, as indicated by the foci of the nuclear spindle. Around these points as centres, a delicate radial marking — the polar striation — appears. The halves of the longitudinally cleft fibrils are so disposed that one of each pair of sister-segments passes along the guiding lines of the GP Rearrangement and cleavage of V-segments : A , from the side . B. from the polar field, P ': GP, anti-pole. (After Rabl-Schieffer decker. ) 18 NORMAL HISTOLOGY. 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 out- ward 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 segments. With the completion of migra- tion the cardinal features of the division of the nucleus have been established, since the anaphases are but repetitions, in inverse order, of the changes already instituted. Following the stage of the equa- torial plate, the fibrils group themselves about the poles of the spindle and form FIG. 10. 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.) (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. * The term "equatorial plate" has been employed by some authors to indicate the later phases of the aster stage. THE CELL AND THE TISSUES. In recapitulation, the above changes may be tabulated as follows : Resting Mother-Nucleus. Prophases : The inauguration of division is marked by migration and division of centrosome, increase of chromatin, resulting in the formation of The Mother- Skein (Spirem) : a. Close skein, — Disappearance of nucleoli. Disappearance of nuclear membrane. FIG. ii. R 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 ; //, daughter-stars ; / and J, segments grouped about new polar fields (in J the protoplasm exhibits constriction) ; A", daughter-skeins, — division of nucleus complete with slight consiriction of cell-body ; L, completed division of nucleus and protoplasm. b. Loose skein, — Separation of skein into segments or chromosomes. Appearance of polar field around the centrosomes. Rearrangement of chromosomes around polar field. The Mother- Wreath, or Aster: Appearance of nuclear spindle. Metaphase : Longitudinal cleavage of chromatin segments. 20 NORMAL HISTOLOGY. Anaphases : Migration of segments {Metakinesis}. Segments pass towards the poles of the new nuclei. Equatorial plate produced by massing of migrating segments. Separation of segments into polar groups. Appearance of connecting filaments. Daughter- Wreaths, or Asters. Telophases : Beginning division of cell-protoplasm. 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. 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. B D Segmenting ova of ascaris megalocephala : A , cell Large marrow-cell : the nu- contains nucleus, two centrosomes (c), surrounded by cleus has undergone repeated attraction-spheres, and adherent polar body (/) ; 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. (After 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. Not infrequently under such conditions the nucleus undergoes repeated abortive division, resulting in the production of irregular lobulated or cleft forms embedded within the common protoplasmic mass. 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 (Mimosese, 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 formation of the polar bodies ; of these latter, usually two are extruded. The nucleus which appears within the Maturation and fecundation in ova of ascaris megalocephala, : I, n, nucleus of ovum before matura- tion ; s, entering spermatozoon ; II, nucleus («) has passed to periphery of cell preparatory to di- viding ; s, spermatozoon now within the ovum ; ///, nucleus dividing into first polar body (p) ; m, male pronucleus resulting from spermatozoon ; IVjpyp1 ', first and second polar bodies, the last still in process of formation ; m, male pronucleus ; Vt 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. Her twig.} ovum after the formation of the polar bodies is the female pronu- cleus. Upon the completion of these phenomena, maturation has taken place and the ovum is prepared for the reception of the male sexual element. Under favorable conditions the spermatozoa reach THE CELL AND THE TISSUES. 23 the ovum, when a single element penetrates the envelopes of the egg and is received within the protoplasm of the female cell. The head of the spermatozoon, which alone passes within the ovum, be- comes transformed into the male pronucleus. Subsequently the latter approaches the female pronucleus, the fusion of the two pro- nuclei being followed by the appearance of a new nucleus of seg- mentation, so called from the fact that within this body cleavage of the ovum is first inaugurated. The segmentation nucleus con- tains the chromatin contributed by the sexual elements of both parents — the fundamental fact in the consideration of heredity. 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. /// Modified, a. Ciliated; b. Goblet; c. Pigmented. IV. Specialized, 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- mejnbrane, 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. 2? 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 cesophagus ; 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 cesophageal opening'of stomach to anus, as well as in the larger ducts of the glands com- municating with this tube ; ducts of mammary glands ; 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 ; seminal vesicles ; olfac- tory 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 bronchiae ; 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 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 FIG. 18. 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. 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. TFeTextent 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 ''trajisitionaL" 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- thelium from intestine : the free ends of the cells present a peculiar striated border - zone. Highly magnified. Stratified columnar epi- thelium from vas defer- ens : the deepest layer consists of small cells, between which the co- lumnar cells extend. 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 jrge_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. 3! 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 5° C. , and permanently impaired by an elevation above 50° 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 eleidiniin 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. FlG. 25. Pigmented epithelium from outer layer of ret- . ina : the nuclei («) still uninvaded. 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 FIG. 26. FIG. 28. Glandular epithelium : Rod-epithelium : a, b, c, isolated epithelial cells from uriniferous small acinus from a serous tubules of rat (after Heidenhairi) ; d, rod-epithelium from submax- racemose gland. illary duct of dog. (After Schiejferdecker.} 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 Presses. The outer segment re- tory cells ; j, sustentacuiar ceives the stimuli from external impressions, while the inner, centrally-directed, segment stands in close anatomical relation with the nerve-fibres. THE EPITHELIAL TISSUES. 33 ENDOTHEtHJM. 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 well as of the numerous lymphatic spaces 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 Endothelium from peritoneal surface of diaphragm, , , i j 1 i stained with silver : n, nucleus of endothelial plate ; s, the blood-VeSSelS are elOn- one of the intercellular clefts or stigmata. 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 NORMAL HISTOLOGY. FIG. 30. 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 cisternae of frog, stained with silver: a, one of the true stomata, lined with guard-cells ; b, intercellular cleft ; n, 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 and elastic tissue, as in the sclera, fasciae, etc. 5. Dense white fibrous tissue, as in tendon and the 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 and glands. NORMAL HISTOLOGY. FIG. 31. Connective-tissue cell from young subcu- taneous tissue : w, wing-like expansion seen in profile.. 1 1 . The elastic reticulum of organs. 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 "fixed" or connective-tissue cells proper and the migratory or ' ' 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 Embryonal connective tissue: the inter- abOut by the extension Or retraction cellular substance is only slightly differen- , of the protoplasmic processes. FIG. 32. 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. THE CONNECTIVE TISSUES. In addition, occasional peculiar granule-cells (the "Mast- zellen" of the Germans) must be recognized. These elements often appear spherical in form, and are distinguished by the con- spicuous granularity of their protoplasm, the granules possessing a strong affinity for dahlia and basic aniline stains. The granule-cells occur in especial pro- fusion in the vicinity FlG- 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 FIG. 34. Subcutaneous areolar tissue : c, c, some of the connective-tissue corpuscles ; w, migratory cells ; v, plasma-cell ; e, elastic fibres. FIG. 35. pigment-cells, 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. Special connective-tissue elements : p, vacuolated plasma-cells ; g, granule- cells. Pigmented connective-tissue cor- puscles from the choroid. NORMAL HISTOLOGY. FIG. 36. 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- Pigment-ceii from newt's skin. eluding 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 were formerly regarded as composed of melanin derived from the coloring-matters of the blood ; recent investigations, however, render it probable that, while apparently 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 characteristic tint appearing only when the pigment-gran- ules are massed. Exceptionally the colored particles are taken up by the cells as pre-existing pigment-granules ; more usually, how- ever, they are produced within the protoplasm of the cell by elabo- ration from special substances held in solution. 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. FIG. 38. Plate - like connective- tissue cells found in ten- don. Cell-spaces of dense con- nective tissue in which the Connective - tissue (corneal) corpus- :les : these cells occupy the spaces cells lie : silvered ground- within the ground-substance, substance ; from the cornea. 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 lacuna, lie the connective-tissue corpuscles, generally only partially filling the cavities, Imcf being usually Especially applied to one wall of the space after the manner of an endothelial covering. These interjas^icular cjejts within the ground-substance may be regarded as the radicles of the lymphatic system, in some localities, as in the peritoneunT, standing in close relation with both the Ivmphatic and the bloodchannels. The intercellular of horous constituents oTconnective tissue are of two kinds — white fibrous and yellow elastic tissue. "White fibrous tissue ordinarily occurs as wavy bundles of varying thickness, com- posed of silky fibrils of such fineness that, under ordinary amplifica- tion, they present no appreciable thickness ; these bundles sometimes run parallel, as in tendon, but more frequently interlace, forming coarser or finer mesh-works, as seen in the omentum and subcu- taneous tissues. When examined after teasing, the ultimate fibrils of the white fibrous tissue appear as a FIG. 40. confused mass of delicate interlacing lines, but in their undisturbed relation they lie parallel, whatever may be the general disposition of the bundles. Fibrous tissue yields^ gela- tin on boiling in water, and swells up and becomes in- distinct on treat- ment with acetic acid. Yellow elastic tissue, on the con- trary, occurs usually as a net-work of dis- tinct fibres lying among the bundles of the white fibrous tissue. Examined in detail, the elastic fibre appears highly refracting and White fibrous tissue : one end of the bundle has been teased to display the component fibrillae. Elastic fibres isolated ; from the ad- ventitia of the aorta. (After Schief- ferdecker.} 4O NORMAL HISTOLOGY. homogeneous, and possesses a definite width throughout its length, although the several fibres forming the same net-work may vary in thickness ; not infrequently slight triangular thickenings are found at the points marking the union of several fibrils. Loosened from their attachments, the elastic fibres assume a wavy, bent or coiled condition, highly characteristic. Elastic fibres do not yield gelatin when boiled, but contain elastin, which is probably enclosed within a sheath of great delicacy, but of considerable resistance towards reagents. The most immature, and morphologically the youngest, form of connective tissue is mucous tissue, a typical example of which is found in the jelly of Wharton, in the umbilical cord. Here the stellate cells still retain their embryonal characters, and, by the union of their processes, form a protoplasmic net-work throughout the tissue ; the meshes of this net-work are occupied by a semi-gelatinous, indifferent, and but slightly differentiated intercellular substance, containing few fibres and occasional wandering cells. All gradations of density between the immature mucous and the more resistant areolar tissue are supplied by the various stages of development. Ordinary connective or areolar tissue, as found be- neath the skin and in many other localities, comprises both white fibrous and elastic tissue. The former usually occurs as wavy bundles, which interlace to form a felt-work of varying compactness ; it is probable that the bundles are confined by a delicate sheath, strengthened by trans- versely and spirally wrapped fibrils, whose positions are marked as con- strictions, after the treatment of the bundles with acetic acid. The indi- vidual fibrils composing the bundles lie embedded within and held together Connective-tissue cells from young urn- by a Soft homogeneous gFOUnd-Sub- biiicai cord: processes of cells unite to stance, securely uniting them ; in the form protoplasmic net-work ; fibrous ele- . '" ments slightly developed. denser tissues the ground-substance contains intercommunicating cell- spaces and canaliculi, the surrounding areas appearing as a homo- geneous matrix. The elastic fibres, in varying number and size, form a net-work throughout the tissue. The fixed connective-tissue corpuscles lie embedded among or directly applied to the surface of the bundles of white fibrous tissue, forming, in such cases, an im- perfect wrapping or covering ; within the interfascicular clefts are the wandering cells. The density of the tissue depends largely upon the amount and THE CONNECTIVE TISSUES. arrangement of the white fibrous element, while its extensibility is determined by the proportion of elastic tissue present. When the former occurs in well-defined bundles, felted together into FIG. 43- interlacing lamellae, dense and resistant structures result, as fasciae, the cornea, etc. ; in such structures the cement- substance within the interfas- cicular clefts is usually hol- lowed out to form the spaces occupied by the connective- tissue cells and their pro- cesses. Peripheral part of a tendon in section : a, external fibrous investment sending partitions between the stellate figures represent the stained contents of the interfascicular clefts Tendon represents a dense secondary groups (b) of the tendon-fibres; the small connective tissue, composed almost entirely of white fibrous tissue arranged in parallel bundles of varying thickness. The primary bundles, made up of the ultimate fibrillae, are held tog-ether to form larger secondary ones, which latter are enveloped in a delicate sheath covered by endothelial plates; the secondary bundles are bound together and grouped by connective-tissue septa, which are extensions of the thick external sheath wrapping the entire tendon. The larger septa support the blood and lymphatic vessels. The flattened connective-tissue corpuscles, or tendon-cells, occur in rows within the clefts, between the primary bundles, upon and between which the thin, plate- like bodies and wings of the FlG- 44- tendon-cells expand. Seen from the surface, these cells appear as quadrate bodies, whose oval nuclei are frequently so disposed that those of two neighboring cells are in close proximity, lying near the ad- jacent ends of the cells, from * - at j these are seen from the surface ; at o and p, which arrangement It follows oblique and profile views. that each pair of nuclei is sep- arated by the greater part of the length of two cells. Viewed in profile, the tendon-cells show as narrow, irregularly rectangular bodies; while when examined in transverse section the same cells appear as stellate bodies, whose extended arms, passing often in several planes, represent the sections of the wing-plates. Each cell P Primary bundles of white fibrous (tendon) tissue, on and between which the flattened tendon-cells lie : at NORMAL HISTOLOGY. occupies a corresponding space within the cement-substance, just as do the cells of other dense forms of connective substances. Elastic fibres are almost, if not en- FlG- 45- tirely, wanting in tendon. Elastic tissue, as usually encountered as an element of areolar tissue, occurs in slender fibres; where, how- ever, the elastic tissue be- comes the dominating con- stituent, as in the ligamentum nuchae or ligamenta subflava of man, the fibres assume much greater size, becoming coarse and of considerable diameter. On transverse sec- tion of such tissue the robust individual elastic fibres appear as irregularly angular or polyhedral areas ; these are of variable size and held together by a small quantity of areolar tissue. The fibres of elastic tissue may become broad and flattened out, and so closely placed that they assume the form of a reticulated elastic membrane, as Henle' s fenestrated membrane of the larger arteries ; again, the tissue may assume the form of a FIG. 47. continuous elastic sheet, as Des- cemet's membrane of the cornea. The development of the white fibrous tissue is still a FIG. 46. Primary tendon-bundles in section : b, the tendon- tissue; s, interfascicular clefts occupied by granular material and the tendon-cells (a) applied to the bundles. Elastic fibres in transverse section ; from the ligamentum nuchae : a, are- olar tissue separating the groups of the elastic fibres ; b, the individual elastic fibres in section. Elastic fibres closely placed, form- ing the fenestrated membrane ; from the aorta. subject of much uncertainty. It may be regarded, however, as established that it is through the agency of the cells, indirect although their influence may be, that the fibres of connective tissue originate. Two methods are recognized in the production of the fibres. The doctrine of the direct mode assumes the transformation of the eel] THE CONNECTIVE TISSUES. 43 protoplasm into the white fibrillae, the periphery of the cell-body becoming the fibres. While such conversion certainly occurs as a primary process (Hemming), 'it is probable that the indirect mode, whereby the fibres originate within an indifferent matrix, also con- tributes to the production of fibrous tissue ; likewise that the young fibres increase in size by independent growth. Regarding the de- velopment of the elastic fibres, strong evidence supports the view that the fibres are produced by the fusion of longitudinally- disposed rows of minute particles, which appear within the indiffer- ent intercellular matrix as the derivatives of the cells. Adipose tissue must be regarded as a member of the group of connective substances, since the accumulation of oily matters within the protoplasm of connective-tissue cells is responsible for the highly FIG. 48. Fat-cells embedded in subcutaneous areolar tissue : f, fat-cells ; n, nucleus ; c, connective-tissue corpuscles ; iv, migratory cells ; e, elastic fibres ; b, capillary blood-vessel. characteristic appearance of the tissue. Whether the fat-cells are developed from elements especially set apart for this role, or whether they are but modjfied orgUoaiy connective- tissue cells, is still a dis- puted point ; there are, however, strong reasons for holding the latter view as correct. Examined after the usual preparatory manipulations, and in places where the cells maintain their individual forms, as in the omentum, adipose tissue is seen to be made up of relatively large, clear, oval or spherical sacs. The transparent contents are limited by a delicate envelope, composed of cell-membrane and an extremely thin layer of protoplasm ; on one sjgle of the sac a local accumulation marks the position of the nucleus. Fat-cells occur usually in groups, supported and held together by areolar tissue, through which ramifies a rich, vascular net-work. In localities possessing considerable masses of adipose tissue, as beneath the scalp and the skin, the cells are grouped into lobules, and these 44 NOI^IAL HISTOLOGY. again into larger masses, or lobes; where aggregated and closely pressed together, the normal spherical shape of the individual fat- sacs gives way to a polyhedral form. Adipose tissue possesses a rich vascular supply, an arteriole passing to each lobule, there to break up into capillary net-works, which surround the individual sacs. The development of adipose tissue is probably not confined to any particular kind of connective-tissue cell, but may involve any of the corpuscles. The granule-cells, however, seem to bear a close relation to the production of fat-tissue. In those elements about to become fat-cells, a few oil-drops appear within the protoplasm ; these increase in size, coalesce, and gradually encroach upon the cell-contents, pushing the nucleus towards the periphery. This displacement progresses with the increasing volume of the accumulating oil, until, finally, the once slender cell is trans- formed into a distended vesicle, whose protoplasm is expanded to an almost invisible layer immediately beneath the cell-wall, containing, at one side, the flattened and displaced nucleus, which now appears, in profile, as an attenuated crescent. Observations on starved animals show that after the withdrawal and disappearance of the fatty matters, the cells are capable of resuming the usual appearance and properties of connective-tissue corpuscles. - — s^ — CARTILAGE. Cartilage represents a dense connective tissue in which the intgr- cellular substance has undergone great condensation. Depending upon the variation in the character of the matrix between the cells, three varieties of cartilage are recognized — hyaline, elastic, and fibrous. Regarded in their re- lationship to the denser connective tissues, the order of enumeration should be reversed, the fibrous variety standing next and differing but little from tendon. Since FIG. 49. Hyaline cartilage from the rib : the cell lie embedded within the lacunae, either singly, in pairs, or in groups ; matrix exhibits differentiation around the cell-spaces as more L « f-i ' ' -j-U «• deeply staining areas. ^ ' ^P1" 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 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 >cejls ; these are irregularly oval or angular nucleated protoplasmic bodies, which, during life, probably 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 lacunae 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 (j>) attached : y, zone of youngest cartilage-cells; m, hyaline matrix enclosing the lacunae contain- ing the cartilage-cells ; /, space from which the cell has been lost. NORMAL HISTOLOGY. ^jfr* [brans layer of dense fibre-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. 51. FIG. 52. 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. 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 pjrimary close aggregation of the embryonal cells, which early indicates the position of the future ^artimge, 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 comoact. Although the spongybone 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 lamellae. 48 NORMAL HISTOLOGY. FIG. 54. Longitudinal section of dried bone : h, Haversian canals opened lengthwise and bordered by the longitudinally-cut lamellae. 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 l^one-marrow, comprising a delicate connective- tissue reticulum, rich in cells, blood-vessels, and lymphatics. The areas between the Haversian systems are rilled 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 FlG- 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. The lacunae and canaliculi of dried bone under high amplification. THE CONNECTIVE TISSUES. 49 FIG. 56. In dried bone the spaces are filled with air, the lacunae 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 A bone-cell lying within the lacuna of the osseous matrix : decalcified and stained. FIG. 57. ' facets. This important structure is composed of two portions — an outer, 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 bon« : A, surface ; B, oblique view ; s, Sharpey's perforating fibres ; /, the lacunae. ijO 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 Kolliker 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 FIG. 58. c u u • r tint, finally becoming of a straw color, owing to the accumulation of fat within the marrow-cells. Depend- ing upon this difference, two varieties — the red marrow and the yellow marrow — are recognized : it is to be remembered that the red Elements of ted marrow; stained and highly magni- . . fied. a, various forms of marrow-cells; b, eosinophilic HiarrOW IS genetically the cell ; c , mast-cell ; d giant-cell ; e, nucleated red blood- Older and represents the cells; r, red blood-cell. . ,. .* 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 / £t/' t THE CONNECTIVE TISSUES. *u4^cU**^5 B O- ^^ ^ xvT^txWv/. >n^W-' . meshes of the tissue contain great numbers of soft, plastic connective- tissue elements, the marrow-cells, which, while closely resembling the leucocytes, differ from the blood-cells in possessing a nucleus larger but less rich in chrqmatin. Larger eosinophilic cells, modifications of the marrow-cells, are also encountered. Additional huge multinu- cleated elements exist as the giant-cells, or myeloplaxes (Robin) ; these are of interest as being especially concerned in the absorption of osseous tissue, being identical with the osteoclasts (Kolliker). Developing nucleated red blood-cells— the erythroblasts — are im- portant constant elements. Mast-cells, with eosinophilic granules, are also found as occasional constituents of the red marrow. 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, enclosingtn ~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- r •(• , • •. i • i M • senting one of the carpal bones : p, Of OSSlficatlOn Within the Cartilage, It IS perichondrium, or primary periosteum; termed CndOChondral bone ; when *» nutr'ent canals extending from the formed directly from and beneath the periphery- 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 JP #* *>'••» j^; R*'-(S %>«= -vi • <&' '•*=*>. ••• v; ws£i?&~yv; V •" ^ -r' •'*' ••-•>> '" e>~&' V/ -t/tx? 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. FlG- Developing bone— both periosteal and endochondral : f, outer fibrous, o, inner osteogenetic layer of perios- teum; /, trabeculae of periosteal bone covered by the osteoblasts ; e, endochondral bone ; m, primary marrow- cavities. Developing bone — longitudinal section of embryonal phalanx : e, the primary cartilage of the extremities of the bone ; a, zone of enlarged and vertically-dis- posed cartilage-lacunae ; c, zone of calcifi- cation ; t, trabeculae of calcified cartilage covered with new bone; m, marrow- cavity ; b, periosteal bone formed directly beneath the overlying periosteum,/. arrange themselves over the surfaces of the cartilage-trabecube or the periosteal fibres respectively, and soon are surrounded by osseous 56 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 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 exhibits an indistinct fibrillated structure in which the subsequent deposit Developing bone— portion of of lime salts — principally the phosphate and trabecula undergoing absorp- carbonate takes place. tion : b, bone-cells; c, osteo- -\-ITI i i blasts ;m, bone-matrix ; *, muiti- When, on the contrary, bone or carti- nucieated osteociast lying within lage is absorbed, it is through the agency the^bsorption-pit, or lowship's Qf ^ g^^ the QSteOClaStS, Or choU- 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 : 1. 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 net-work of spongy bone. 9. Conversion into compact bone by partial absorption of tra- beculse to form Haversian spaces ; secondary deposit of concentric lamellae within these spaces forming Haversian systems of compact bone. THE CONNECTIVE TISSUES. 57 10. Absorption of inner lamella of compact bone as the shaft increases in diameter by the deposition beneath the periosteum ; production of enlarged medullary cavity. 1 1 . 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. 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, iresiculae seminales, prostate body, Cowper's glands, cavernous and spongy bodies of penis. 5. The Female Generative Organs: in oviducts, uterus, and vagina ; in the erectile tissue of external genitals ; in the broad and the round ligaments, and in the erectile tissue of the 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 trabeculae of spleen ; sometimes in the trabeculae 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 FIG. 68. At* long and 4-8 /* wide. The cells found in arteries are short FIG. 67. Isolated involuntary-muscle cells from intestine of man. Involuntary-muscle cells from mesentery of newt: n, nuclei:; f, axial fibre; m, transverse markings on surface of cell ; B, muscle-cell with forked extremity. and flat, being but 25-45 /* l°ng and 9-12 /* wide; the largest ele- ments are found in the gravid uterus, where they reach a length i ^ (micron) = the loooth part of a millimetre. 6o NORMAL HISTOLOGY. FIG. 69. of over 500 it and a breadth of 20 //. 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 usually 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- 7°- 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 fibrous connective tissue ; how- ever, the numerous more or 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. 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. Involuntary muscle in longitudinal section : the muscle-cells are often cut obliquely, and hence appear shorter than when isolated. ,^ 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 syjnpathetic^system, likewise penetrate the intercellular spaces and terminate between tKe 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 oi' me striated muscular tissue, and corresponds to the spindle fibre-cell of the involuntary variety. The fibre of striped muscle comprises (a} the sarcolemmOj (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, 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 jremains of the indifferent protoplasm whicri has hot undergone conversion into the highly specialized muscle-substance of the fibre. In qjammaliaa muscle the nuclei lie always upon the surface of the sarcous substance of the fibre and immediately beneath the sarco- l> FIG. 71 j >^ 5^... • . Voluntary-n\uscle fibres, somewhat broTceii- *z^ter treatment with watef, showing the sarcolemma (s) in several places. NORMAL HISTOLOGY. 62 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 alternafe light and dark transverse markings, or striae, to which the tissuejowes 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. 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 Krause. 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 jribrillsp were formerly considered by Kolliker as the normal elements of the fibre ; the dark prisms of these fibrillae correspond to the ^arcous__elejn^Dts, which were regarded by Bowman as the component units/H muscular tissue. The transverse cleavage of thelibre following the action of diluted mineral acids, , 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. THE PERIPHERAL NERVE-ENDINGS. 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 are considered as special sensory nerve - endings. They contain muscle- fibres and the terminal arborizations of the nerve surrounded by an en- velope of connective tis- sue. 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, FIG. 112. **i.<^££ $$ T^.% Ear) of the ajjs-cyfinder; X, the of which is separated at *„- A^, the fibres; R, node of Ranrier. Q2 NORMAL HISTOLOGY. These tendon-spindles appear as sharply-defined, greatly-elon- gated, elliptical masses (in the rabbit .25-. 75 mm. long and .O2-.oi 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 fibrillae, 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 FlG- IJ3- 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 pan{^ ancj partly SUrrOUnded by (z>), from the mesentery of rabbit ; gold prep- x J 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. 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. 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. HE 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- ^v signed to facilitate the interchanges be- FIG. it tween the nutritive current which they and the tissues through which they The arteries possess three coats — the inner, or intima, the middle, or media, amd the external, or adventitia. Since these coats vary in relative thickness and FIG. 116. Section of human artery of medium size : /, the intima, consisting of the endothelium (e), the sub-endothelial tissue (j), and the internal elastic membrane (_r) ; M, the media, com- posed of the involuntary muscle and the bundles of elastic tissue (y) ; A , the adventitia, containing irregular elastic trabeculae (2). Endothelium of artery of frog : the vessel has been treated with silver, hence the boundaries of the endothelial plates are indicated by the dark lines of stained cement-substance. Sev- eral pseudo-stomata appear as minute dark areas between the cells. in details of structure with the size of the vessel, it is usual to classify "THE *>x.^ 95 arteries as small, medium, and large. The first group includes the terminal branches near transformation into capillaries, the second, all the named arteries of the body, except those which, as the aorta or the pulmonary artery, are recognized as belonging to the third group of large arterial vessels. The inner coat, or intima, as seen in a typical artery of medium size, comprises three layers : (a) an endothelial lining, madeup^v*^*^ of long, lanceolate, nucleated plates, united by a sinuous line of cement-substance and placed parallel to the axis of the vessel ; (£) a sub-endothelial layer of delicate fibrous connective tissue, with branched corpuscles ; (c) a band of elastic tissue— the internal elastic membrane — which forms the most prom- inent part of the intima, appearing in sections of medium-sized ar- teries as a clear, FIG. 117. glistening, and usually corrugated band separajtin^, the tissue of the inner coat from that of the media. The sub-endothe- lial tissue, which separates the en- dothelium from the internal elastic membrane, is wanting in the smaller arterioles, but appears in vessels Portion of the intima of the human aorta, silver stained : the larger stellate figures are the cell-spaces in the ground-substance be- tween the elastic bundles and contain the connective-tissue corpuscles. Portion of the elastic tissue of the intima of the human aorta; the fibres are so broad and so closely grouped that they constitute an elastic sheet — the fenestrated membrane of Henle. of medium size as a longitudinally disposed layer, becoming more conspicuous with the increased calibre of the artery. In tubes of ^ L large diameter, as in the aorta, the sub-endpthelial tissue appears as oi a stratum composed of layers made up of fibrous tissue, elastic net- works, and flattened connective-tissue cells. Likewise, the elastic tissue of the intima increases in amount and in complexity, in the • large arteries the broad elastic fibres becoming fused together to form an almost continuous sheet — the fenestrated membrane of Henle. The middle coat, or media, is the muscular tunic, and consists principally of circularly disposed bundles of non-striated muscle-cells ; these elements, .when isolated, appear as broad, nucleated, irregular spindle-cells, presenting ragged outlines. In many arteries, con- spicuously the 'subclavian, the inner portion of the media con- tains additional muscle-cells longitudinally disposed. In the smaller arteries the muscular tissue constitutes almost the entire media, but an insignificant amount of intermuscular fibrous connective tissue FIG. 119. Muscle-cells isolated from g5 NORMAL HISTOLOGY. being present ; with the increase in the size of the vessel, however, the quantity of such tissue becomes greater, in addition to which bands of elastic tissue also make their appearance between the muscle-bundles. In the large vessels the fibro-elastic tissue forms a considerable portion of the media; in the aorta the elastic tissue occurs as robust circularly arranged bands, supplemented by oblique and longitudinal tra- beculse of similar nature ; these elastic fibres, together with the accompanying fibrous tissue, constitute the predominating structure, the muscle being less conspicuous in places than the intermuscular fibro-elastic strata. Owing to this generous admixture of fibrous tissue, the large arteries, while possessed abso- lutely of a greater amount of elasticjtissue, have walls relatively less contractile than those of the the media of human artery, smaller jirteries, whose media is composed of almost pure muscular tissue^ The external coat, or adventitia, is the most resistant tunic of the vessel, its characteristic strength being due to the generous amount of component fibro-elastic tissue. The fibrous tissue is arranged as closely- felted bundles, irregularly placed and intermingled with longitudinal bands of elastic tissue ; numerous flattened con- nective-tissue cells lie between the bundles applied to the fibrous trabeculse. The mesh-work is closer and the amount of elastic tissue greater next the media than towards the outer surrounding con- nective tissue into which the adventitia insensibly blends^--In the larger arteries the middle ancKouter coats are separated by a band of ^condensed elastics-tissue — the external elastic membrane. Cer- tain arteries present peculiarities in their coats ; as examples of such varia- tions may be noted the slight develop- ment of the sub-endothelial tissue of the intima of the external iliac, renal, mesen- teric, and cceliac arteries, the appear- ance of longitudinal muscle-cells within the intima of the aorta, and the presence of longitudinally dis- i r section of aorta of child : 7, flf, 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. ** <*i+*Z2r* ?, in which the coals A, small human artery, in which the cc are reduced each to a single layer of cells ; the media here consists of only one layer of muscle-cells (m), 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 (m), 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 98 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. isj^jcfwyr' The ^dventitia, often the thickest coat of the vein, consists oi / stout netTwoTi^s composed of bands of fibro-elastic tissue ; in some veins additionaVjmndles of^ plain muscle occur>vithin this tunic. jnong the venous trunks possessing well- 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. Thfi^striated car- f^djai^muscular tissue is continued for a short distancejft'-fhe walls of those parts of the venae cavae and of the pulmonai'^yejiis^mn^^ 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- E£>^ ^Wx^^M^t^HE CAPILLARIES. The capillaries establish the ojily^commmiication, with few excep- tions, between the arteries and the veins, and, further, provide the ate anatomical relation between the mitntiye _ current and the ues of the body necessary for the maintenance of~the integrity 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 tie of the genital organs, in the spjeen, 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 : 1, M, and A, respectively intima, media, and adventitia. /, in THE CIRCULATORY SYSTEM. 99 *7 <-£» Capillary blood-vessels from mesentery T^_ 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 fA ; the smallest are found in the brain, retina, and muscle ; the largest in bone-marrow, dentinal pulp, and the liven The closest meshes ^ Fi afe found in the aif-yesicles of theiuligv' 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 theTnterchanges maintaining nutrition. x 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. ^^<^nxtx5uCa/C cn^=^ 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 lymphmd tissue. The intimate relation existing between the endotEelium of the vessels and the surrounding connective-tissue corpuscles is well exhibited in young growing tissues, as the omentum. ___ ,J 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 TirniftTof 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- \ 100 NORMAL HISTOLOGY. ^ tion oTthe walls of the medium- and large-sized arteries and veins. These vessels arise some distance from the area which They supply, frequently coming from a different branch or, as in the case of the veins, from a neighboring arterial stem. Thgjierves of blood-vessels are mainly derived from the sym- pathetic system, and hence are principally of the non-medullated kind ; a few 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 fibrillse 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 Section of human heart show- connective-tissue layer of the endocardium ing endocardium : a, endotne- . » . Hum; b, subendotheiiai con- is continuous with the penmysium 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 nective-tissue stroma in outer layer (c), containing net-work of elastic fibres (e) ; d, trans- versely-cut bundles ; ft mus- cular tissue. elastic fibres. THE CIRCULATORY SYSTEM. 101 auriculp-ventricular valves is thicker than that of the ventricular "surface. The roots or attached portions of these valves possess thickenings — the annul! 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 tendineae the papillary muscles extend for some distance, in addition to which isolated muscle-bundles aje also sQjnetim^ present. The semilunar valves possess a thin ^ . ^ V Ir^tS fL '** ****^ elastic layer on the \ yr FIG. 125. arterial surface, aug- \ \ \ \ d 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^ fibro-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- 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. m 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 (f), 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, /, media, k, adventitia, of the pulmonary artery ; the adventitia is continuous with the principal fibrous layer of the endocardium ; in, cardiac muscle ; n, areolar tissue. 102 NORMAL HISTOLOGY. IG. 126. 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 niuscle-fibres are enveloped within a ^ej.im.ysium 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 fibre-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^lood-vessels deeply impress the fibres, and in some 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. 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 dependently, and, for a time, are distinct and dis- 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 Developing capillary blood-vessels within the omentum large trunks which have of y°unS rabbit: a, a, elongated protoplasmic processes i r , • • i . 1 connecting the walls of the newly-formed capillary (c) been lormed COinCldently with the angioblastic connective-tissue corpuscles (*). 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 heart however, develop in- IO4 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 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- entiates into the muscular tissue of the cardiac wall, but for some time the endo- Belial and muscular layers continue as independent tubes, the inner endothelial i- • • i_ 1 linmg appearing as a shrunken cast repro- FIG. 128. ~- m Section of a part of the develop- tube, within which lie several of the primary nucleated red blood- ceils W; m, the slightly differ- entiated mesoblastic cells, which ducing the contours of the larger muscular ,e muscular tissue. Qrgan The twQ tunjcs are connected by numerous bridging bands, which increase in number and size with the progress of the development of the organ ; these primary tra- beculae 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. 105 FIG 129 THE BLOOD. 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 are not peculiar to the blood,, since they originate in lymphoid tissues and bone- marrow and are car- ried into the blood-current, in which fluid they usually are ob- served. Critical examination of suitably stained preparations of human blood shows that the colorless cells include several varieties which are character- ized by differences of size, nu- cleus, and granularity. These varieties are : i. Small lymphocytes, which are about the same size as the red blood-cells, or some- what smaller, and contain a nucleus relatively so large that almost the entire cell is occupied leucocyte; c> transition form; rf, poiymorphonu- by this body. The protoplasm clear cells: e, eosinophilic leucocyte; r.redcorpus- is confined to a thin inconspicu- ous envelope and is usually devoid of granules. This variety may be regarded as the youngest form, and probably originates solely within lymphoid tissue. 2. Large mononuclear leucocytes, two or three times larger than the red cells, are frequently of an oval form and contain a nu- cleus which stains less intensely than in the younger cells, owing to its comparative^ poverty in chromatin. The protoplasm of these leu- cocytes contains but few, if any, pale granules. 3. Transitional leucocytes, which represent more advanced stages of development, are characterized by a nucleus exhibiting vary- ing degrees of indentation} so that the nucleus often appears kidney- Leucocytes in normal human blood, stained and highly magnified : a, small lymphocytes ; b, large I06 NORMAL HISTOLOGY. shaped or of a horseshoe form. The protoplasm resembles that ( the large mononuclear cells, presenting ordinarily no granularity, few eosinophile granules, however, sometimes being distinguishabl 4. Polymorphonuclear leucocytes constitute the form mo< frequently encountered, and probably represent the fully develope condition of the leucocyte. These elements are distinguished b the variously distorted nucleus, which, being fairly rich in chrc matin, presents a striking figure in stained preparations. Th segments usually retain connection by delicate threads of chromatin exceptionally the bridges become broken, in which case the ten ' ' polynuclear' ' is appropriate. Occasionally cells may be observe containing granules which stain deeply with eosin. Such * ' eosinx philic' * leucocytes probably represent later phases of developmen According to Ehrlich's teaching, the lymphocytes and the leuc< cytes are to be regarded as distinct varieties of cells, the former bein derived from lymphoid tissues and thelatter from bone-marrow. Ehrlich has classified the granules occurring within the leucocyte into the following four groups, according to their affinity for "acid, ' * basic, " or " neutral' ' stains : 1. a-granules, which are coarse and highly refracting, appearin fresh blood as minute fat particles. These granules possess strong affinity for eosin and acid stains ; hence they are known i ^eosinophile and oxyphile. •" • 2. y-granules, which are coarse, intensely basophilic, and occur i the mononuclear c ' mast' ' cells. 3. S-granules, which are fine, basophilic, and are seen in the pob morphonuclear leucocytes. 4. s-granules, which exhibit an affinity for neutral staining mi: tures and are neutrophilic. These constitute the most abundant ar important variety of granules in the polymorphonuclear cells. THE COLORED CELLS OF THE BLOOD. The adult mammalian red blood-cell represents a condition c .^^trogresslon, since in its development it has suffered the loss of i nucleus and a profound metamorphosis of its protoplasm, chang< of such importance that some authorities dispute the propriety c regarding the mammalian red blood-corpuscles as true cells. T\ presence or absence of the nucleus within the colored corpuscL together with its general form, furnishes a basis for a division of a vertebrate bloods into — A. Those having nucleated, oval red corpuscles : includin fishes (except cyclostomata, which have round, discoidal cells, as tf lamprey), amphibians, reptiles, and birds. B. Those having non-nucleated, round, discoidal red coi THE CIRCULATORY SYSTEM, ID/ jmscles : including mao, and qther mammals, except the camel family, which have \valt non-nucleated red blood-cells. Human blood-cells : TV, color- less corpuscle, surrounded by red cells ; those at r exhibit a partially-formed rouleau. vai Since an oval_cor£uscle on""*b>eing 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. ri^^^c^Ct^^ ^Lu^^^^^ The human colored blood-cell, or erythrocyte, is a small disk, about 8 PL in diameter, and exhibiting individually a faint greenish- yellow tinge. The well-known color of the blood appears only when great numbers of 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 somewhat thickened : in consequence of this peculiar "biscuit" form, all planes of the 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 jtructure 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 strorna, extensible and pliable to a high degree, and (ft) the c6Io7m^matter7"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 rea 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 IO8 NORMAL HISTOLOGY. very evident, and correspond in appearance and structure with those of other cells, a nucleus 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 ^S^ ; 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 //, or about i-32ooth 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 h^man blood, as determined by the hsemacytometer, 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 FIG. 131. Red blood- cells of man and of am- phiuma, magnified to the same extent to show the size of the human cor- puscles in comparison with that of the largest known blood-cell. THE CIRCULATORY SYSTEM. are more §e_n§itive 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 tcPThfluences acting on the corpuscles outside the body. If fresh blood be exposed to a current of air, subjected to unduejDressure 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. Q Reactions of human blood- cells with various reagents: A, effect of treatment with water upon the white (iv) 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 (j) 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. ' ( 110 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 ^A 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 approacKIng~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 cel^and becomes conspicuous as a minute accumulation adhering to one edge of the corpuscle. Where .strong solutions of tannic acid are employed, the^haemioglobin is coagula£ea 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, covered at once, and examined with a high power, numbers of small, colorless, circular disks will be seen on careful observation ; these are the blood-platelets of Bizzozero, sometimes called the third corpuscular ele- ments of the blood. They are very unstable, prone to disintegration, and are variable in size, possessing an average diameter of about one-third of that of the red cells ; they occur singly, but show a marked disposition to run together in groups preparatory to 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. \ human red blood-cells and blood-platelets (/) ; g , minute fatty (?) particles, which occur isolated or in masses ; B, fibrin filaments, among which lie par- tially disintegrated blood-plate- lets. THE CIRCULATORY SYSTEM. UI 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 red cells, the blood-platelets being regarded by many as only fragments of the former. 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 micrpcytes 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- J34- 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 H^min crystals from dried 111, . human blood. ljs 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 112 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 tissue and the bone-marrow 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 aggregations of lymphoid and marrow 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 y-* — p— . :*- . r , 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. The term "(^lanpy," as applied to compound lymph-nodules, is an inaccuracy sanctioned by long usage. 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 ; 6, lymphoid cells ; c, ex- panded connective - tissue plate. zf&o;^^ THE LYMPHATIC SYSTEM. HQ 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 trabeculae, 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 mucosae 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 central parts of such nodules, as well as of the Cortical follicles of the larger glands, are usually occupied by germ-centres, areas composed of lymphoid tissue of looser Diffuse lymphoid tissue occu- pying deeper layers oF nvucosa 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. texture containing large cells exhibiting mitotic figures. The affe- rent lymph-vessels conveying the lymph to the simple follicles break up at the periphery of the nodule into branches, which dis- tribute 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 b^ the aggregation and partial fusion of a o»£S^ T^ 5? 4^ •i -u^-^-i i " ^a Section of lymph-gland from child, showing general arrangement of lymphoid tissue and lymph- sinuses: a, capsule from which trabeculae (b, b) extend ; c, masses of dense adenoid tissue composing the cortical follicles ; d, the same, of the medullary cords ; e, lymph-sinuses. 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 FIG. 147. the cortical follicles constitute one continuous mass of dense lymphoid FIG. 146. 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 (/). Portion of human lymph-gland, showing de- tails of structure : a, lymph-sinus ; b, adenoid tissue ; c, trabeculae ; d, coarser reticulum of lymph-sinus ; e, expanded connective-tissue plate applied to fibres ; f, 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 which break up into the delicate reticulum constituting the supporting framework in whose meshes the lymphoid cells are held. 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. The nerves include both the medullated and the pale fibres. In certain localities, especially in the prevertebral retroperitoneal and cervical regions, in the vicinity of the abdominal aorta, vena cava, adrenal and renal vessels, along the brim of the pelvis and in the root of the mesentery, are found minute organs known as hem- olymph glands (Warthin). They lie embedded within the fat and connective tissue and are usually the size of a mustard-seed or pea ; exceptionally they are larger. The hemolymph glands are lymph-nodules modified by the presence of blood-spaces and the slight development or absence of the lymph-sinuses. The blood- spaces often include a peripheral blood-sinus with irregular cen- tral extensions, the lymphoid tissue being correspondingly reduced to trabeculae surrounded by the vascular channels. All degrees of development of the blood-spaces exist, from the type of the ordinary lymph-nodule on the one hand to that of the spleen on the other. Warthin subdivides the hemolymph glands into two groups, the splenolymph and the marrowlymph glands, which he regards as transitional forms standing between the lymphatic nodule on the one side and the spleen and the lymphoid marrow respectively on the other. 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 " °^^ 1 1 1 r, 1 rLrL, 1 rl. 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 alveolar periosteum, the peridentinal membrane, 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. 10 146 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 fibrous tissue intimately united and subsequently impregnated with calca- reous salts. Piercing the ground- substance and appear- ing under low amplifica- FIG. 174. Longitudinal section of molar tooth of kitten : a, pulp-cavity, continued by canals (./") to apices of roots ; d, dentine ; e, en- amel ; c, cementum ; p, alveolar periosteum ; «, 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 2.0-2.6 /Jt, 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. 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 Schreger'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 outer margin of the dentine, traversed by some of the dentinal tubules. The walia,of these spaces pre- FIG. 175. FIG. 176. Interglobular spaces of dentine from dried human tooth : t, t, 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. sent numerous minute spherical projections, the dentinal globules, produced during calcification of the dentine. 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 148 NORMAL HISTOLOGY. FIG. 177. bundles which cross one another, producing the alternate dark and light radial prism-stripes of Schreger. 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 uncalcified enamel and 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 crust a 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 lacunae. 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 ; perforating fibres of Sharpey are also present in small numbers. 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). -a. THE DIGESTIVE TRACT. 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 fibrillae 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 (t) begins its growth into mesoderm (m). ISO NORMAL HISTOLOGY. the ridge. These secondary dental bulbs are the first indications of the enamel organs of the temporary teeth. After the establish- FIG. 180. FIG. 181. Model of jaw of human embryo of 40 mm. : rt rf arch of increased epithelium constituting dental ridge; /, local thick- enings corresponding to positions of future enamel sacs. (After Rose.) 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. FIG. 183. ec. THE DIGESTIVE TRACT. , ,. j 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 enamel organ, however, sub- serves another important pur- pose, since its inner and outer layers grow towards the base of the dentinal papilla and invest the young mesoder- mic tissue with a two-layered envelope, the epithelial sheath. This structure plays an important role in deter- mining the form of the future tooth, since the young dentine is deposited along its inner sur- face. Vestiges of this sheath ap- pear as isolated epithelial nests. The enamel organ itself under- goes a differentiation into three distinct layers : the outer layer, directly COntinUOUS for a long densed mesoderm, whose summit is enveloped by time with the Prtodermir Cells the invaginated enamel organ (^) ; ec, oral epi- ' WltJ thelium, still attached by the atrophic isthmus (a) Of the Oral Cavity, is COmpOSed with the enamel organ, whose outer (A), middle Of One Or tWO layers Of low (0, and inner (^) layers are differentiated ;^, * beginning of enamel organ for permanent tooth. 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. c/. Section of jaw of cat embryo ; the dental papilla is seen as a projecting conical mass (/) of con- 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, bt bone. distinctly columnar, constituting the inner layer of the enamel organ containing the beautiful enamel cells. The outer and inner layers FIG. 185. 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 of 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 in- ner layer, the adamantoblasts, alone produce the enamel. This process consists essentially of a gradual deposition on the inner '/•'f/A(\ 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 Section of developing tooth from cat embryo: layer of enamel increases by the m, mesodermic tissue condensed in dental pa- addition of increments deposited pilla (/). at whose summit osteoblasts (d\ are c • . . , , r forming young dentine (,); inner layer (a) of from Within OUt, the latest-formed enamel organ is engaged in producing layer of enamel always lying immediately • , i , .-, -, c . 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. Subsequent deposition of lime-salts imparts to the enamel its remarkable harclness. 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 young enamel (8) ; e, middle, h, outer layer of enamel organ. THE DIGESTIVE TRACT. 153 FIG. 186. 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 the newly-formed dentine is 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./ Section of developing tooth from cat em- bryo, portion of preceding figure more highly magnified : tn, mesodermic elements consti- tuting pulp-tissue ; /.layer of odontoblasts en- gaged in producing dentine (K) ; 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 lingualae, 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. papillae. The papillae are of three kinds : the filiform or conical, the fungiform, and the circumvallate. 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 A ^y^^^^. at the Posterior Part of tne dorsum of the tongue. Each consists of a large flattened fungiform papilla surrounded by a deep furrow and a secondary encircling ridge or wall — an arrangement which has suggested the name. The upper 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 Section of human tongue showing conical papillae: a, connective tissue of mucosa, which forms core of papillae; b, b, partially abraded epithelium; Amasses of epithelial cells filling interpapillary recesses. Section of tongue of child, showing a fungiform papilla; the connective-tissue stroma is covered by the epithelium. THE DIGESTIVE TRACT. !^ 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. 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 (gt g1) ; 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 foliatse, 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-nore^ 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 cell^. 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 provided 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 papilla of child. The oval structure is limited to the epithelium (e) lining the furrow, encroaching slightly upon the adjacent connec- tive tissue (f ) ; o, taste-pore through which the taste-cells communicate with the mucous surface. NORMAL HISTOLOGY. r as the free surface. The inner or central ends of the gustatory cells are prolonged as slender nervous processes, which are often beset with minute swellings or varicosities.) These processes end in close association, but not continuity, with the terminal axis-cylinders : composing the intrabulbar ramifications of the fibres prTrieglosso- pharyngeal nerve, the nerve of the special sense of taste. The submucous and interfascicular tissue of the tongue con- tains 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, al- though a group of small mucous glands (Nuhn's) is found near the tip. The ducts of those at the root of the tongue are sometimes 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 spherical masses of denser structure. Among the formed elements observed in the saliva the so-called salivary corpuscles are conspicuous. These are spherical bodies, some- what larger than the leucocytes, and possess a distinct 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. FIG. 191. Salivary corpuscles from human saliva: x, group of corpuscles near epithelial cells; y, cor- puscle which has burst, allowing granules to es- cape; z, salivary cor- puscle highly magnified, showing granules and nucleus. 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 FIG- 193- latter vessels, in turn, take up the smaller trunks having their FIG. 192. Section of tonsil of dog : a, epithelium of mucous membrane passing into central recess (6), where it becomes infiltrated with lymphoid cells (e) ; 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. FIG. 194. NORMAL HISTOLOGY. The nerves supplying the mucous membrane — the glosso-pharyn- 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 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- pletely infiltrated with lymphoid cells, so that the demarcation between the epithelium and the subjacent adenoid tissue is often obscure. 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 occuV~m-4arge 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. Section of child's tonsil, showing the details of the epithelium and part of the lymphoid tissue from preceding figure under higher amplification. THE DIGESTIVE TRACT. THE PHARYNX. 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- ~~ereci with stratified squamous cells similar to those lining the oral cavity. The tunica^prqrjria, or stroma of the mucosa, is formed r-* of a felt-work of fibrous bundles, together with a variable, in certain parts large, quantity of elastic tissue. The subepithelial surface of . r.- 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 faucial 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 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 OESOPHAGUS. 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 mucosas ; 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; e1 ', 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 !62 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. 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- 197- are more cuboidal, and assume a columnar or pyramidal form as they approach the fundus. The chief or central cells bound the lumen FIG. 196. '. 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 (b) ; h, blood-vessels ; c, cf, 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 the 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 i2>u^v 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 r FIG. K 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. Pari.f>taJ. nr acid cells do not occur in the pvloric % lands ^ being- onfined tojjue-mre-^ephc 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 of peptic dog, highly magnified : a, a, the central or chief cells next the lumen (c) ; b, b, the parietal or acid cells connected with the lumen of tube by short lateral branches which extend to the cells. THE DIGESTIVE TRACT. 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. — rlit! iiiUs»i~dlari" mucosae oc- cupies the deepest layer of the FIG. 201. Section of pyloric glands from human stomach : a, motuh 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- y£I^ Longitudinal section of child's stomach passing through pyloric nrifice : 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. j 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 4s 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. • siderabie 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.j203. 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 (£) ; 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. 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. 1 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 Stohr.) 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 !68 NORMAL HISTOLOGY \ ^^A^^i and to the gastric glands; the exact mode of termination of these nerve-fibrillae 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 specialisations 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 _ • FlG- 2°5- 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 valvulae 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. THE DIGESTIVE TRACT. FIG. 206. 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 mucosse, 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. Transverse section of follicles of large intestine of dog : the individual tubules are separated by the fibrous stroma of the mucosa. I/O such FIG. 208. NORMAL HISTOLOGY. 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-caecal 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 (k) ; c, basement membrane ; d, plate-like connective-tissue elements of core ; e, e, blood-vessels; _/", 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 Lieberkuhn. 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. I/I Longitudinal section of large intestine of child : a, a, simple tubular glands ; b, submucous tissue ; c and d, circular and longitudinal layers of muscle. FIG. 211. conversion into goblet-cells. Lieberkiihn's glands lie between the bases of the villi, but are found upon the valvulae conniventes, FIG- 210. since the latter depend on the elevation of the submucosa for their formation, the mucosa being reflected over the pro- jecting underlying tunic. In the lower part of the large in- testine the glands of Lieber- ktihn 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 submucosa 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 ; ^ mucosa containing the SUbmUCOUS tissue through villi (/) and the follicles of Lieberkuhn (/ ), and pierced by the mucosa to open on the the ducts (^of the g,lands of BrunnJ <*> with;n the.'ub- l mucosa (c) ; 6, musculans mucosa: ; d, . V., the portal or interlobular vein, which breaks up into the capillary net- work of the lobule; H. V., central intralobular vein, a branch of the hepatic; H. A., he- patic artery, supplying nutrition to the in- terlobular structures and terminating in the lobular capillary net- work ; B.D., the inter- lobular bile-duct which takes up the bile- capillaries at the periphery of the lobule. NORMAL HISTOLOGY. secreting hepatic tissue, comprising the liver- cells, the bile -capil- laries, the minute channels through which the bile elaborated within FIG. 219. Section of injected human liver, the capillaries having been filled from the central vein (a) ; b, branches of portal vein. the lobule is carried off, together with lymph-radicles and a very small amount of delicate areolar tissue. The liver-cells are irreg- ular polyhedral elements (17— 25 p) in whose finely granular FIG. 221. protoplasm, devoid of cell-mem- brane, one or more round nuclei lie embedded. Numerous oil- drops of various sizes, as well as pigment - granules, very com- monly are present within the FIG. 220. Hepatic cells isolated from human liver : a, Section of uninjected human liver : a, cords of oil-drops ; b, slight concavity produced by liver-cells lying between the blood-channels (b}. blood-vessels protoplasm. The variations in the apparent granularity of the cells depend, as in other glands, upon the condition of functional activity : THE DIGESTIVE TRACT. 179 FIG. 222. Section of centre of lobule of human liver: a, intralobular vein, into which the capillaries (i>) converge ; c, hepatic tissue. the nearer complete exhaustion, the less emphasized are the granules and the smaller and darker the cells. The meshes of the capillary net-work are usually only suffi- ciently wide to accommodate a few liver-cells, in consequence of which arrangement almost every hepatic ele- ment is bounded directly on at least one side by a capillary blood-vessel, a relation con- ducive to free interchange between the blood and protoplasm of the cells. With few excep- tions every liver-cell exhibits a slight con- cavity on one border, which denotes the position of contact and impression by the blood-vessels. In uninjected organs the hepatic tissue ap- pears made up of irregular, branching, and anastomosing cords of cells, which form close net-works, the intervening clear clefts being the lumina of the blood-capillaries. According to Disse's studies, the liver-cells do not lie immediately in contact with the capillaries, but are separated from the latter by delicate perivascu- lar lymphatic channels which envelop the blood-capillaries. In livers still retaining their primitive type of the tubular gland the bile-capillaries appear as minute ducts placed centrally within the cords of the hepatic cells, the biliary passages representing lumina of tubular acini lined with secreting glandular epithe- lium. In man, however, the liver-cells are often bordered on all sides, ex- cept on that lying next the blood- vessels, by the delicate bile-canaliculi, the latter never interposing between the cells and the blood-channels. The bile-capillaries,exist as narrow (1-2 fji) clefts between adjacent liver- cells, maintaining about the same diameter throughout the lobule ; at the periphery the intercellular channels pass into the larger, though still small, interlobular bile- ducts. The hepatic cells between which the bile-capillary takes its course become replaced at the periphery of the lobule by the low epithelium of the bile-duct, the basement-membrane present in the latter fading away into the delicate connective tissue holding together the cords of liver-cells. FIG. 223. Section of liver of frog, exhibiting tubu- lar character of gland : a, blood-channels containing corpuscles ; b, lumina of hepatic cylinders which correspond to bile-capil- laries ; c, pigment-cell. i8o NORMAL HISTOLOGY. FIG. 224. The existence of a distinct independent wall to the bile-capillaries has been the subject of much conflicting testimony; according to some, these vessels are with- out distinct walls of their own, while other authorities regard the existence of a deli- cate special wall consisting of a homogeneous structureless membrane as established. The presence of a distinct membranous wall seems ques- tionable ; when it is recalled that the bile-capillaries really represent lumina of modi- fied tubular glands, there seems to be no greater neces- Section of rabbit's liver in which the bile-capillaries gjj-y for or probability of the (£) have been injected and appear as dark lines between . the ceils :c, blood-channels. existence of a membrane to limit the lumen of the bile- tubule than in the case of other glands. The direct transforma- tion of the secreting hepatic cells into the epithelium of the bile- duct at the margin of the FIG. 225. lobule further opposes the assumption of such limiting membrane, while examination of livers in which the tubu- lar type of the acini is re- tained fails to show such structures within the lumina of the tubes. Emerging from the lobule at the periphery to pass into the adjacent interlobular con- nective tissue, the small bile- ducts empty into the larger ones, which bear the branches of the hepatic blood-vessels company. The interlobular bile-vessels gradually in- crease in size, owing to the repeated union of the smaller tubes, until the larger trunks unite to form the hepatic duct. While the walls of the smaller bile-ducts consist of columnar epithelium strengthened by fibrous con- nective tissue mixed with elastic fibres, those of the large vessels Section of liver of dog, including portion of lobule and interlobular connective tissue (a) ; b, portal vein ; c, hepatic artery ; d, bile-ducts ; e, small peripheral bile- vessel ; gt blood-channels ; h, hepatic tissue. THE DIGESTIVE TRACT. lgl 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 FIG. 226. 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- Transverse section of large bile-duct tance in determining the arrangement J^±±S^S±SS of the hepatic tissue. The blood brought areoiar tissue, 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. 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 well 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- uies, each of which, in turn, is composed of groups of the ultimate saccules or acini. THE DIGESTIVE TRACT. The large excretory duct of the parotid gland, or Stenson's duct, contained within the interlobular connective tissue, is composed of a fibre-elastic tunica propria, lined by a simple FIG. 227. 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 coarsely granu- lar, while after functional activity and in the ex- hausted condition they are smaller, darker, and finely granular, the threads 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- Section 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. 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 acini are of the same nature, since quite usually small crescentic groups of granular cells lie immediately next the basement-membrane at the pe- FIG. 229. riphery of the acinus, where they have been crowded by the larger mucus - filled ele- ments. These crescentic groups consti- tute the demilunes of Heidenhain or the crescents of Giannuzzi, which are aggregations of cells belonging to the serous type, similar to those of the parotid acini. The submaxillary is, therefore, a Section of human subiinguai muco-serous or " mixed" gland. The ex- gland : among the clear cells 11-111 i lining the mucous acini are cretory tube of the subiinguai gland, or the nests (g, g) of granular eie- duct of Bartholin, consists principally of a ments which constitute the rl - . . ...,.,. demilunes of Heidenhain. fibro-elastic tunica propna, 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. jg* 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. THE PANCREAS. The pancreas is, as aptly described by its German name, ' ' Bauch- speicheldriise," the abdominal salivary gland, belonging to the serous type, and closely corresponding in structure and in the nature of its secre- , FlG- po- 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, and a peripheral clear zone. 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 1 86 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 zones 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 granules occupy almost the entire cell, the clear zone being confined to a narrow belt most removed from the lumen ; towards the close of a period of functional activity, on the contrary, the granules occupy the smaller part of the cell, while the clear zone is expanded to a broad peripheral area ; during fasting the clear and the granular zones 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, the bodies of Langerhans or interlobular masses, seem 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 possibly represent groups of special cells concerned in the elabo- ration of some particular pancreatic ferment. 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 ; b, the usual acini. THE DIGESTIVE TRACT. lg« as in the case of the salivary glands, is still undetermined; the fibrillae 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 Transverse section of nine-day rabbit embryo, show- r i 1 ing formation of primitive gut (g) by approximation of irom tne primary Oral reCeSS, ventral plates composed of visceral layers of mesoderm Or StOmodaeum, by a parti- and entoderm (<•); m, m, body-cavity bounded by tion, the pharyngeal plate, and visceral she£ 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 1 88 NORMAL HISTOLOGY. FIG. 233. 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 fcetal 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 fcetal 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, B1 , neural canal and brain vesicles; /#, ectodermic invagination which contributes the lining of anterior part of future oral cavity ; p, 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. 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 probably connected with the development 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 as three diverticula, one dorsal and two ventral, which extend from the duodenum into the primitive mesen- NORMAL HISTOLOGY. tery. The organ first lies parallel to the sagittal axis of the body, afterwards changing its position so as to lie transversely, resulting in the approximation and subsequent fusion of the originally distinct rudiments as well as the ducts. The presence of more than one pan- creatic duct in certain 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 extending 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. IQI 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 the primary pyramids : inij*! adultk however^t.heir 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 general relations of macroscopic details : A, renal artery ; U, ureter ; C, one of the calices into which a papilla projects ; i, cortex containing labyrinth (/) and medullary rays (m) ; 2, medulla ; M, Malpighian pyramids, some obliquely cut -at 3 ; b, bound- ary layer; B, columns of Bert in ; 4, masses of adipose tissue; 5, branches of renal artery. (After ffenle.) FIG. 235. 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. t^v-c^X^L^-- T££^ 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 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 Berlin, 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, 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 (I) containing the Malpighian bodies (x) ; in places (xf) the glomerulus has fallen out, leaving the empty capsule ; b and v , sections of blood-vessels. 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 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 TIG. 236. • 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- 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 glomerulus ; /, outer layer of Bowman's cap- sule, the nuclei of whose cells show at g ; h, uriniferous tubule in transverse section, /, in oblique section 194 NORMAL HISTOLOGY. FIG. 237. LABYRINTH IMED, 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's loop, 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. Yl t^rCAM^^^V THE URINARY ORGANS. !95 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. CXx^-i (\ 196 NORMAL HISTOLOGY. Medullary ray contains Medulla contains : ( Spiral tubules ; < Ends of arched collecting tubules ; I Straight collecting tubules. ( Descending limbs of Henle 's loops ; \ The loops ; ] Ascending limbs of the loops ; v. 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. i. 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. 238. 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 vessels of the tuft ; e, nuclei of capillaries ; n, constricted neck marking passage of capsule into convoluted tubule; ^..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. 197 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 v Section of kidney of amphiuma : the peritoneal surface (b, b) exhibits one of the nephrostomata (, capillaries filled with red blood-cells. 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. NORMAL HISTOLOGY. 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 FIG. 241. 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 : -w, large collect- ing tubules ; x andy, descending and ascending limbs of Henle's loops ; z, loops of Henle ; v, blood-vessels. THE URINARY ORGANS. 199 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- Transverse section of papillary region of medulla of hu- C, large collecting scending limbs of anes. 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 m*n ,kidney' m?re h^hly ******* • c> larse collecting & tubules ; x and y, descending and asc< Small tWlgS are given off for Henle's loops ; v, blood- vessels. 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 Bertin, 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 arterise rectse 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 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. FIG. 243. The arteries supply- A-_ c. k .. ing the medulla enter as straight vessels, the arterise rectse, 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 the medulla, along with the arteries, to reach the pelvis, where they join with their fellows to form the renal veins. The lymphatics of Section of injected kidney of dog, showing g> neral 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 (/, /') ; e,f, afferent and efferent ves- sels of glomeruli (g) ; h, intertubular capillary net-works ; /, peripheral venous trunks, which collect the blood from sub- capsular net-works (k). 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 fibrillae and their relations to the secreting cells are still uncertain. THE URINARY ORGANS. <$£^*****^*- 201 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 insverse section of human ureter: a, irregular lumen, lined by mucous membrane, which con- :>f epithelium (b), tunica propria (c), and submucous tissue ( mother-cells undergoing division ; d, daughter-cells, Oi Cycle side bv Side spermatoblasts ; e, partially-developed spermatozoa ; ft , surrounding intertubular connective tissue. 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: (i) 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, Section of testicle of doB, including . . ... part of seminiferous tubule : a, zone of the derivatives Of the SpermatOgeniC Cells parietal cells containing sustentacular of the outer zone, and, in turn, the parents <*ements (/)= *. mother -ceils; c, of a numerous progeny of smaller daugh- ter-cells. The latter constitute the spermatids, from the metamorphosis of which the spermatozoa are later directly derived. The inner zone of the tubule is frequently occupied by fan-shaped groups of 14 FIG. 252. daughter-cells ; d, free nuclei of sper- matoblasts and developing sperma- tozoa. 210 NORMAL HISTOLOGY. developing spermatozoa, embedded within the inner end of the supporting cell of Sertoli. Spermatogenesis varies among the different classes of vertebrate animals ; the account here given refers to man and the higher mammals. The originally round spermatids promptly 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 intimate union with the centrally projecting protoplasm of the sustentacular cells. Such appearances, probably FIG. 253. FIG. 254. Section of testicle of musk-rat, ex- hibiting early stage of spermatogenesis : a, membrana propria ; 6, 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). partly the result of mechanical forces, at present are regarded as indicating an important role on the part of the sustentacular cells in the production of the spermatozoa, an assumption seemingly 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, Kolliker has always held, as likewise 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 d6bris in which the groups of developing spermatozoa lie embedded. THE MALE REPRODUCTIVE ORGANS. 211 Critical study convinces that the nucleus, together with the cen- trosome of the spermatoblast, is the chief factor in the formation of the spermatozoon. 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 (L^x^yu^^f us mu ' j 1 m thelium. ^The deeper layer of the mucous membmne 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 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 FIG. 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 the muscles being effected by the investment of the Longitudinal section of epiglottis of child : a, laryngeal surface ; b, glossal surface; c, plate of elastic cartilage ; d, acini of mucous glands. structures, the attachment of tendinous tissue directly continuous with 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. THE RESPIRATORY ORGANS. 249 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 FIG. 285. ciliated columnar epithelium, among whose elements lie num- bers of goblet-cells. The current established by the ciliated epithe- lium tends to expel mucus or other 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 elasticffibres 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 Section embracing trachea and oesophagus of child : a, b, tracheal and oesophageal surfaces ; c, tracheal epithelium ; d, stroma of mucosa ; e, submucosa ; .//mucous glands; /, part of ring cartilage ; g; its perichondrium ; /, fibrous tissue ; k, fibro-muscular tissue of oesophagus ; /, oesophageal epithelium. 250 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 B'RONCHI. 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 ; et submucosa ; _/", acini of mucous glands ; h, blood-vessels ; *, 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. According to Miller, the distal extremity of the terminal bronchus communicates with sev- eral spherical cavities, the atria. Each of the latter in torn opens into a group of larger and less regular spaces, the air-sacs, into which di- rectly open the ultimate air-spaces, the alveoli or air-cells. The latter open not only into the air-sacs and atria, but also beset the alveolar ducts as minute saccula- tions that impart an ir- regular contour to the air-tube. 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 bundles of non- striped muscle. The mucous glands and the cartilaginous plates are wanting 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 approaching the atria. The walls of the irregular atria suffer still further reduction, the fibrous coat becoming greatly thinned, while the mucosa is reduced to panments of air-passage : B, ... . c ri i .• .• terminal bronchus; A, atrium; a delicate tunica propna of fibro-elastic tissue, 5.>air.saC)intowhichopenair. in which bundles of non-striped muscle may ceils (C). Branches of pulmo- nary artery follow bronchus ; remain. those of puimonary vein iie at The epithelium of the smaller passage, at periphery. (Miller.-) first low cuboidal in character, rapidly assumes a flat polygonal type ; towards the air-sacs large flat plates appear among the smaller polygonal cells, and become more numerous as these terminal divisions of the air-passages are neared. FIG. 287. Diagram of terminal com- 252 NORMAL HISTOLOGY. Within the irregularly round air-sacs the epithelial lining consists of the large flat endothelioid plates, or respiratory epithelium, between which elements diminutive groups of the smaller polygonal cells appear. In the air-cells, 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 several atria, and the subsequent origin from these of the air-sacs and the alveoli, 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 groups of the alve- oli, are often defined with great distinct- ness by the pigment accumulated within the connective tis- sue separating the adjacent lobules. Section of human lung: a, atria and air-sacs cut in various direc- 1 he Ultimate aiT- tions; b, alveoli separated by interacinous partitions (c) ; d, masses cells Ol" alveoli of of connective tissue containing accumulations of pigmented par- , . tides (#). the lung represent theaciniof racemose glands, the similarity being especially marked in the uninflated organ, which still retains its glandular character. Opening into the cavity of the expanded air-sacs and the less uncertain atria, the FIG. 288. THE RESPIRATORY ORGANS. 253 FIG. 289. alveoli are placed closely side by side, and by mutual pressure be- come polyhedral. Around the opening or base of the alveolus, where it communicates with the air-sac wall, 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 alveoli 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 cells lie scattered as 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 closed alveoli, 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 pseudo-stomata may exist ; they usually con- nect 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 alveoli 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 two alveoli and atrium : a, small polyhedral epithelial cells covering distal part of atrium ; b, nbro-elastic framework ; c, large flattened epi- thelial plates lining alveoli, among which lie small groups of the small cells rf. 254 NORMAL HISTOLOGY. FIG. 290. completely surrounds the alveolus and constitutes the septum be- tween the adjoining air-cells, 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 alveolus. The capillary net-work within the walls of the alveoli 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 the veins, bronchioles, nerves, and lymphatics, within the thicker tracts of interlobular connec- tive tissue ; the smaller twigs extend, among the groups of the air-sacs, embracing the openings into the alveoli with more or less complete rings, from which pass the capillaries enveloping the air- cells with net-works on all sides. Between the adjoining alveoli lies Section of injected and inflated lung of cat : Only a Single layer of Capillary « air-sacs enclosed in dense capillary net-works vessels wnich, hoWCVCr, are not (b) ; c, larger interlobular branches of pulmonary . artery. . 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-cells, the scanty connective-tissue framework and the capillary net- work constituting their entire bulk, the alveoli belonging to differ- ent, although neighboring, end-tubules 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- THE RESPIRATORY ORGANS. 255 nary artery follow the air-tubes to their ultimate distribution, the arterioles extending along the respiratory bronchial tubes and terminal ducts as far as the interatrial 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 terminal ducts the pulmonary arterioles give off twigs which form net-works around the air-cells 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-cells. 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 256 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 existing in this region, less rigidly adherent. The endothelium of the parietal portion Section of human pleura cover- possesses cells more expanded and thinner ing surface of lung : a, endothe- * Hum; b, fibre-elastic stroma ; m, than those covering the surface of the lung; cut bundle of muscle-ceils; /, the eiements [n this latter position vary in peripheral layer of pulmonary .....'. -11 , • ,.»_ i_ n r 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. 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 ; bt 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 fj. 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 2 eg 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 Section of thyroid body, exhibiting de- , . . , i rj^, tail of the acini, which are cut in various thlS questionable Organ. The inter- directions : c, colloid material distending alveolar tissue contains elements closely the larger acini ;/', interacinous connective •, , • •, -,•> tissue ;%, biood-vesseis. 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 cesophageal 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. 294. 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; bt body- cavity ; m, mesoder- mic tissue. FIG. 295. Portion of section of thirteen-day rabbit embryo, including developing lungs ; mesodermic pulmo- nary masses, L, L', are covered with primary pleural endothelium and penetrated by bifurcations of primary bronchi (/, /) ; 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- 260 NORMAL HISTOLOGY. FIG. 296. 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 (/) still connected with pharyngeal entoderm (e) ; nt, surrounding meso- derm. FIG. 297. 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. Portion of section of four- teen-day rabbit embryo, in- cluding lateral thyroid area (t) which is stilf attached to fourth inner pharyngeal furrow (/) ; m, surrounding mesoderm. 261 / THE SKIN AND ITS APPENDAGES. 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: a, stratum corneum ; b, stratum lucidum ; c, stratum granulosum ; d, stratum Malpighii ; e, f, papillary and reticular layers of corium ; g, stratum of adipose tissue ; h, t, spiral and straight portions of duct of sweat- gland ; k, coiled portion of sweat-gland ; I, vascular loops occupying papillae of 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 ol 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 FIG. 300. 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 Epidermis of human skin separated from corium, viewed from beneath : a, thickened areas filling de- pressions between papillae ; b, pits receiving papillae 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 ; f, 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. 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, probably identical with keratohyaline, staining intensely in certain dyes, and resulting from the cornification of parts of the epithelial elements occupying the outer layer of the stratum Malpighii. 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 imperfect, the stratum lucidum is wanting, while the superficial cells rapidly dry. Pigment-granules are widely distributed throughout the epider- mis, but it is especially within the deeper layers of the stratum Mal- pighii that accumulations are found to which the dusky hue of the skin of many races is due. The pigment-granules usually originate within the epithelial elements ; in some cases, however, they are FIG. 301. *«lgk.. ;..-• .^.v, fejw ••£<••••:•"<••:: ..&» ..•.:•.•• ^ .- ^ :vtmss:* 264 NORMAL HISTOLOGY. conveyed to the epidermis by means of migratory cells. 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 coriurn, 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 (b) ; the deepest layers of epidermis (c) contain the pigment. THE SKIN AND ITS APPENDAGES. 26t 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-bedf, the^>ostenor 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 coriurn and that portion of the epidermis corresponding to the stratum Malpighii. The corium consists of the usual bundles of fibre-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 ectoderrmTorlgin. These slenHerfle^TDle" 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 ; ft 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 ; «, 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 epitKelial 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 /JL 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. mi A , human hair ; the upper half of the figure represents the super- ficial horny cells (A) 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 ; b, thin fibre-cells of cortical substance. THE SKIN AND ITS APPENDAGES. 269 The medulla is composed of rows of irregular cuboidal or spherical cells, 15-20 n 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 ; ft hair-bulb; h, hair-pa- 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. 306. Transverse sections of hair-follicles from human scalp : a, hair ; b, cuticle of hair; c, d, inner and outer root- sheath ; e, glassy membrane ;ft fibrous sheath; g, surrounding connective tissue of corium ; ht 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. 27 1 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 n 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 outer cells of the root- FIG. 308. Transverse section of hair-follicle from human scalp, more highly magnified : a, substance of hair, condensed at periphery (b) • 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 loogitudinal 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 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 fj. 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 inner 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, .I-.3 mm. in length, which usually contains numerous con- nective-tissue-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 which 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 OJ 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. 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 wTnch open into the hair-fQllicles 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. THE SWEAT-GLANDS. The sweat or sudoriparous glands are modified simple tubular glands which extend from the free surface of the integument, where 18 Seciion of portion of seba- ceous gland from human scalp, including part of acinus : a, membrana propria ; b, periph- eral layer of cuboidal cells; ct elements in which fatty meta- morphosis is beginning ; d, cells filled with fatty particles and exhibiting marked intra-cellular net-works ; et nuclei of ctlls. 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 posTtTorTllTe gland-tube ends as a greatly convdluTect 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 v) ; 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 iree 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 /j. 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. 2/5 FIG. 310. 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 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 /i, of which about 30 // are contributed by the epithelial lining, and about half as much by the fibrous and muscular tunics ; the remaining 20 /* 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. 270 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 sterns 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 fibrillse which are traceable with certainty as far as the glassy membrane and probably end within the external root-sheath. AND ITS APPENDAGES. FIG. 311. THE DEVELOPMENT OF THE SKIN 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 . , , . the remains of the epitrichial layer ; a, two layers of the ectoderm probably mesodermic tissue forming corium. already indicating the corneous and Malpighian strata of the future epidermis, although the precise Section of developing skin from human foetus of three and a hair months : «Jayer of cuboidal cells «p- resenting stratum Malpighii : b, polyhe- drai dements forming superficial layers; '. outermost flattened piaies, probably 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 fcetal 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. 2/9 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. FIG. 313. Section of skin of foetal 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. Section of skin of foetal kitten, showing ecto- dermic tissue (a) starting to grow into mesoderm (6) 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- 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 mesoderm. 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, f, hairs in different stages of their development ; gt 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 fcetal 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')\ b, inner root-sheath ending in atrophic area at b' ; c, outer root- sheath ; e, glassy membrane ; ft lateral projection marking attach- ment of arrector pili muscle (g ) ; h, 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 of 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. Section of skin of human foetus, showing devel- oping sweat-glands. The latter grow as epithelial cylinders from the stratum Malpighii of the epi- dermis into the underlying corium ; the character- istic coil appears later. 282 NORMAL HISTOLOGY. CHAPTER XVI. THE CENTRAL NERVOUS SYSTEM. I) THE MEMBRANES. THE spinal cord and the brain are surrounded by their enveloping membranes, the dura, the arachnoid, and the pia ; these afford additional protection and support the blood-vessels in their course to the nervous tissue. The dura consists of interlacing bundles of dense fibre-elastic tissue, in the interspaces between which lie numerous plate-like connective-tissue cells ; many irregular granular elements resem- bling plasma-cells occupy the more superficial layers. The narrow clefts between the fibrous bundles represent lymph-spaces. The smooth unattached surfaces of the dura are clothed with a single layer of endothelial plates, while the attached sur- faces, on the contrary, are rough and without endothelium, but covered with fibrous processes for attachment. The inner sur- face of the visceral layer forms the outer wall of the subdural space, the inner boundary of which is contributed by the op- posed surface of the arachnoid ; the two surfaces, while usually in apposition, are united by very few intervening bands of connective tissue. In some places the outer dural layer is less intimately united with the bone than usual, which arrangement produces the epidural spaces ; a more or less perfect endothelial lining exists at such points. The dural layers vary in vascularity in different regions ; in addi- tion to the intradural venous sinuses, on either side of the supe- rior longitudinal sinus smaller venous clefts, the parasinoidal spaces, occur ; into these the cerebral veins directly open, the entrance of the veins into the sinus being thus indirect. The arteries of the dura in many places are surrounded by perivascular lymphatic Section of membranes from brain of child : D, A , P, respectively the dura, the arachnoid, and the pia; a, subdural space; b, meshes of sub- arachnoidean space; c, blood-vessel within the pia sending branch into cerebral cortex, d. THE CENTRAL NERVOUS SYSTEM. 383 channels ; these canals open into the sub- or the epi-dural spaces on the one hand, and stand in close relation with the blood-vessels on the other. The veins of the dura are of much greater size than the corresponding arteries. The nerves of the dura are not numerous, but consist of both medullated and pale fibres, chiefly distributed to the walls of the blood-spaces. The arachnoid is a connective-tissue membrane of great delicacy, the component fibres being loosely held together rather than arranged as distinct bundles. The free surfaces of the membrane, including the numerous trabeculae on its inner side, are covered with endo- thelium. The arachnoid lies closely applied, but slightly attached, to the inner surface of the dura, while between the arachnoid and the pia the considerable subarachnoidean space exists. Scattered over the outer surface of the arachnoid small villous elevations project into the subdural space ; a core of connective tissue, covered by a reflection of the endothelium, constitutes these structures. In various situations, but particularly in the neighborhood of the superior longitudinal sinus, the arachnoidal villi become hypertrophied and form the Pacchionian bodies : these press against the opposed dural surface and push the latter before them where least resistant ; such points occur where the lamina of the dura separate. The arachnoidal projections encroach upon the dura to such a degree that its tissue is largely absorbed, the cauliflower excrescence being separated from the venous current by an extremely thin layer. In localities where the projections press against the bones, conspicuous depressions on the inner cranial sur- face mark the positions of the Pacchionian bodies ; these latter not infrequently contain small, hard, calcareous concretions, the * ' brain-sand. ' ' The arachnoid contains neither blood-vessels nor nerves. The pia is the vascular membrane, and consists of two lamellae, an outer layer, rich in blood-vessels, and an inner stratum, less vascular, but closely associated with the nervous tissue, to which it contributes a partial supporting framework. The pial stroma is composed of interlacing fibro-elastic bundles, between which lie the numerous blood-vessels, surrounded by perivascular lymphatics ; the vessels, invested by delicate prolongations of both connective tissue and lymph-sheath, pass into the nervous tissue. The free sur- face of the pia is covered by endothelium, as are also the trabeculae subdividing the subarachnoidean space and connecting the arach- noid and the pia. The pia of the cord is composed of coarser fibres than that of the brain. The dura and the arachnoid do not follow the irregularities of NORMAL HISTOLOGY. the surface of the nervous masses ; the pia does, dipping down into the fissures and penetrating, as part of the velum interpositum, into the interior of the brain. The inner layer of the pia is closely united to the surface of the cord and the brain, while the vascular tunic in places is less accurately adapted : thus the entire pia enters the anterior median fissure of the spinal cord, while the inner layer alone takes part in the formation of the posterior median septum, or "fissure." Branched pigment-cells are not uncommon in the outer layer of the pia ; these are especially well developed on the anterior sur- face of the medulla, although frequently found in other positions along the cord and at the base of the brain. A few non-medullated nerve-fibres have been traced within the pia. THE SPINAL CORD. The spinal cord, or medulla spinalis, hangs, enveloped by its membranes, within the vertebral canal, and extends from the lower border of the skull, where it becomes continuous with the medulla above, to the lower border of the first lumbar vertebra below ; from this level the conical end of the cord, the conus medullaris, is continued into the attenuated filum terminale, the nervous matter disappearing about the middle of this structure. While the several di- visions of the cord are distinguished by individual peculiarities, certain general features of arrangement are common throughout its length. The cord is formed of symmetrical halves partially separated in the mid-line in front by a cleft, the anterior median fissure, and behind by an ingrowth of dense neuroglia tissue which constitutes the posterior median fissure, but is really only a fibrous sep- tum. Each half of the cord contains a crescentic mass of gray matter ; the convexities of the crescents face, and are connected by a horizontal bridge, the gray commissure, the gray matter of the cord thus collectively forming an H-like mass. The horns of the crescents are not equal, the anterior cornua being broad and robust, while the posterior cornua are more slender and pointed and ex- tend almost to the outer surface. The exterior of the cord is invested by a dense neurogliar layer, from which numerous fibrous septa extend into the substance of the cord, dividing the white matter into certain pyramidal areas. The anterior or motor roots of the spinal nerves are formed by bundles of fibres which escape from the gray matter ; these bundles pass from the anterior cornu to the surface of the cord associated in groups, their exit being indicated by slight furrows. The position at which the posterior or sensory root appears on the surface, on the contrary, is marked by a distinct indentation. THE CENTRAL NERVOUS SYSTEM. 285 These furrows marking the anterior and the posterior roots, to- gether with the penetrating processes from the pia, divide the white matter of each half of the cord into definite areas or tracts. The anterior median fissure penetrates a little more than one-third of the diameter of the cord, and does not quite reach the bridge of gray substance, but leaves an intervening band which connects the white matter of the two halves ; this constitutes the white commissure in- cluded between the gray bridge behind and the anterior median fissure in front. The part of the cord embraced between the anterior median fis- FIG. 318. -w Section of spinal cord from cervical region of child : a, anterior "median fissure ; b, posterior median septum ; c, d, anterior and posterior horns ot gray matter ; e, f, anterior and posterior nerve-roots ; f, lateral reticulum of gray substance into white matter ; k, median and antero-lateral groups of ganglion-cells ; 2, central canal ; k, /, gray and white commissures ; A, Z,, /*, anterior, lateral, and posterior columns ; G, column of Goll ; B, column of Burdach. sure and the anterior root is the anterior column ; the large area bounded by the anterior root, the gray matter, and the posterior root forms the lateral column ; while the field included between the posterior root and the posterior median septum corresponds to the posterior column. Since the first two divisions are very closely associated both as to their position and as to their constit- uents, they are very frequently regarded as a single column, the antero-lateral. Each of these principal segments is subdivided into secondary tracts, distinguished by names indicating the gen- eral course or the destination of the component nerve-fibres. 286 NORMAL HISTOLOGY. The anterior column includes two tracts : the direct pyram- idal tract (TurcKs column), next the median fissure, and the FIG. 319. Diagram showing principal divisions of white matter of spinal cord: A, P, anterior and posterior horns of gray matter ; DP, direct pyramidal tract ; GB ', anterior ground-bundle ; CP, crossed pyramidal tract; DC, direct cerebellar bundle; GT, Gowers's or ascending antero-lateral tract, blending anteriorly with descending antero- lateral tract ; L, Lissauer's column ; BG, column of Burdach (fasciculus cuneatus) and column of Goll (fasciculus gra- cilis) ; LGB, lateral ground-bundle. anterior ground-bundle, or anterior radicular zone, which is continuous with the adjoining area of the lateral region. The lateral column contains a number of important tracts, two of which are especially prominent, the crossed pyramidal and the direct cerebellar. The latter lies as a narrow zone at the margin of the cord, and extends from the posterior root about half-way to the anterior root. The crossed pyramidal tract appears as an oval area which lies next the cerebellar path and in front of the pos- terior root. The remainder of the lateral column is occupied by a number of smaller tracts, concerning which uncertainty still exists. These may be grouped into two segments : an outer peripheral, in- cluding the ascending antero-lateral tract, or tract of Gowers, and the descending antero-lateral tract, and an inner zone, next the gray matter, the lateral ground-bundle ; the latter, in con- junction with the similar anterior tract, constitutes the antero-lat- eral ground-bundle. The posterior column is divided by a fibrous septum into the inner triangular segment, the column of Goll, next the median septum, and an outer area, the postero-lateral tract, or Burdach's column, lying between Coil's tract and the posterior horn and root. THE CENTRAL NERVOUS SYSTEM. 28/ Lissauer's column appears as a small area capping the apex of the posterior cornua ; it consists of fibres from the lateral part of the posterior nerve-roots, which, proceeding from the cells of the spinal ganglia, are passing to higher levels of the cord. The framework of the spinal cord consists of the penetrating pial processes, which divide the white matter into numerous areas as well as convey the blood-vessels into the nervous tissue. From the large fibrous partitions finer secondary trabeculse are given off ; these, in turn, divide and subdivide until they become lost as delicate fibrils among the nervous elements. In addition to the framework of connective tissue contributed by the pia, the specialized sup- porting tissue of the nervous system, the neuroglia, is distributed throughout the cord, filling up the coarser meshes of the connective- tissue reticulum and intimately uniting the more important nervous elements. The neuroglia occurs immediately beneath the outer pial invest- ment as a condensed peripheral zone, from which prolongations accompany the pial septa, as well as intermingle with FlG- 32°- the nerve-fibres ; among the latter lie the charac- teristic spider-cells, sending their long, deli- cate processes between the fibres. The white matter of the cord is made up seem- ingly of great numbers of small round nucleated ele- ments, held together by the supporting neuroglia. These apparent cells are the nerve - fibres in transverse section, the supposed nuclei being really the cut axis-cylinders ; an irregularly concentric striation is usually present around the axis-cylinder, this appearance being produced by the partial distortion of the medullary substance. The nerve-fibres of the cerebro-spinal axis possess no neurilemma, the surrounding neuroglia affording the necessary protection. The individual nerve-fibres composing the white matter of the cord vary greatly in diameter (1-27 /*) ; while the thick and the thin fibres are found side by side in all regions of the cord, certain columns are characterized by the predominance of thick fibres, 9 Portion of white matter of human spinal cord : a, large nerve-fibres in section ; b, smaller fibres ; c, supporting neuroglia ; d, spider-cell ; e, connective-tissue trabecula containing blood-vessel,/; g, spaces from which sections of nerve-fibres have been lost. 288 NORMAL HISTOLOGY. while other tracts contain mostly small ones. With reservation, it may be assumed that motor fibres are generally the largest (15- 20 //): hence the nerves issuing from the anterior cornua contain principally fibres of large size ; the posterior sensory nerves and the sensory tracts, on the contrary, contain chiefly small fibres, although a number of fibres of large diameter are usually present. The largest fibres occur within the direct and crossed pyramidal tracts ; the smallest, within the column of Goll. The white commissure in man forms a continuous nervous lamella, .3-. 5 mm. in thickness, which separates the gray com- missure from the bottom of the anterior median fissure ; in many animals the white commissure is incomplete, being represented by isolated commissural bundles found only at certain levels. The gray matter, while presenting the general H-form through- out the cord, differs in the details of its arrangement in the several regions. The gray mat- ter shares in the in- creased size which char- acterizes the cervical and lumbar enlargements, its amount being absolutely as well as relatively greatest in the lumbar region. Typical cervical sec- tions are distinguished by their large size, great transverse diameter, and large H of gray matter, the anterior cornua of which are robust and broad, while the poste- rior horns are slender. Sections from the tho- racic region are smaller than those from either above or below, and present an almost circular outline ; the gray matter possesses crescents only slightly curved, with slender horns both in front and behind. Cross-sections of the lumbar cord are recognized by being broad, having a deep anterior fissure, and possessing a large, thick H which greatly encroaches upon the white matter. The latter diminishes relatively, as well as absolutely, on reaching the conus medullaris, where it is reduced to a mere shell. The gray matter of the halves is united by the gray commissure, Section of spinal cord from thoracic region of child : V, D, ventral (anterior) and dorsal (posterior) median fissures; C, column of Clarke. THE CENTRAL NERVOUS SYSTEM. 28g in the middle of which lies the minute central canal, the direct FIG. 322. Section of spinal cord from lower part of lumbar region of child : V, D, ventral and dorsal median fissures. continuation of the ventricular cavities of the encephalon and the remains of the large neural canal of early foetal life. That part of FIG. , Portion of section of spinal cord of calf, including central canal and commissures : a, b, anterior and posterior median fissures ; c, central canal, lined with ciliated epithelium,^/ e, surrounding substantia gelatinosa ; f, gray commissure ; g, white matter ; h, white commissure ; «, decussating nerve-fibres ; k, nerve-fibres in section. the gray commissure lying in front of the central canal constitutes 19 2QO NORMAL HISTOLOGY. FIG. 324. the anterior gray commissure, while that behind the canal is the posterior gray commissure. The histological elements entering into the composition of the gray matter include the nerve-cells, the nerve-fibres, the sub- stantia spongiosa, the substantia gelatinosa, and the blood- vessels. The most conspicuous elements of the gray matter are the gan- glion-cells. These are especially numerous in the apices of the anterior horns, where they form almost con- tinuous columns. The motor cells are largest, those found in the anterior cornu being distinguished by their great size (65-130 A), as well as by their numerous branched pro- cesses. The ganglion- cells of the anterior cornu are disposed in groups, of which there may be recognized usually a small median group, occupying the inner part of the horn, but wanting in the lumbar region, and a conspicuous large an- tero-lateral group, which Anterior horn of gray matter of human spinal cord : g, H^S in the OUter angle of gray matter containing stellate ganglion-cells ; , white fa^ hom * the posterior matter penetrated by bundles (r) of root-fibres. outer angle, where the an- terior cornu is broad and well developed, contains often additionally a postero-lateral or an external group. The ganglion-cells of the posterior horn are much smaller (15-20 pi) and irregularly distributed to the outer side of the cornu and within the substantia gelatinosa. In certain regions of the cord, principally from the eighth cervi- cal to the third lumbar nerve, much less markedly in the upper cervical and in the sacral region, a distinct cluster of nerve-cells exists at the juncture of the posterior root and the gray commissure, which marks the position of the vesicular column of Clarke. The gan- glion-cells of this tract vary in size (30-90 M), but possess an average diameter of 70 //, thus standing midway between the largest motor and the smallest sensory elements ; the neurits of these cells pass THE CENTRAL NERVOUS SYSTEM. 29I laterally into the white matter and constitute the nerve-fibres of the direct cerebellar tract. The lateral horn when well developed, as in the intermedio- lateral tract of the tho- also con- of small, .._ _.„, ..„„_ ^^T~£ p^T '£% ^tU " FIG. 325. racc regon, tains groups frequently bipolar, cells (20—30 JJL) which re- semble the isolated cells of the posterior cornu. In addition to the groups of nerve - cells described, isolated clus- ters of "outlying" ganglion - cells exist beyond the gray sub- stance, within the white matter of the antero- lateral and posterior columns. The composition of the gray matter is very intricate, including as it does not only nerve-fibres of various sizes, both medullated and non - medullated, and countless fibrils of varying thickness de- rived from the processes of the ganglion-cells, but also the universally present substantia spongiosa, the modified neuroglia of the gray matter, which contributes additional nuclei and fibrils of its own. The recent advances in our knowledge concerning the processes of nerve-cells have introduced new elements of complexity, for it must be remembered that, in addition to the richly-branched protoplasmic processes, the axis-cylinders contribute numerous fibrils both as the collateral fibres and as the net-works of fine terminal fibres in which the axis-cylinder processes of cells of the second type end. The relation between the various nerve-fibres and the cells of the gray matter is a question of great difficulty ; the researches of Golgi, Ram6n y Cajal, Kolliker, and others within the last few years have established that the protoplasmic processes probably neither anas- tomose with one another nor unite with nerve-fibres : likewise, that the axis-cylinder processes of certain cells are directly continued jtb** ^^ Portion ot anterior horn of gray matter of spinal cord of calf : g, multipolar ganglion-cells lying within pericellular lymph- spaces (/) ; r, r, bundles of nerve-fibres (f) passing from gray matter to form anterior roots ; w, white matter ; /, portions of isolated processes of nerve-cells ; n, larger processes in section ; v, blood-vessel. 292 NORMAL HISTOLOGY. as nerve-fibres, these being especially the cells of the anterior horn, which are prolonged into the large motor nerves. FIG. 326. Diagram illustrating the probable relations between the celis and the fibres and the principal tracts of the spinal cord ; the left half of the figure exhibits the communications of the several varieties of nerve-cells : A, P, anterior and posterior cornua of gray matter ; PR, posterior root-bundles ; DP, direct pyramidal tract ; CP, crossed pyramidal tract ; DC, direct cerebellar path ; GB, Gowers's tract ; a, motor cells passing directly into fibres of anterior roots of spinal nerves ; b, various cells of the antero-lateral column, including elements of Clarke's column (b'} and of substantia Rolandi ; some give off collateral branches of remarkable size ; c, commissural cells ; d, cells to posterior column ; e, Golgi cells of posterior horn. The right half of the diagram shows the communications established by means of the collateral fibres. (After Lenhossik.) The posterior root-fibres are afferent processes of the nerve-cells situated within the spinal ganglia. On gaining the posterior columns of the cord, the sensory fibres divide into ascending and descending branches, from which collateral twigs are given off at various levels. The collaterals, after a longer or shorter course, pass horizontally into the gray matter, and terminate, in the majority of cases, in arborizations closely related to the nerve-cells of the posterior horn. These latter cells supply the links of communication between the sensory and motor roots, thereby establishing the paths for spinal reflexes. In some cases the sensory fibres traverse the gray matter and end directly in relation to the cells of the anterior horn. While many of the cells of the posterior horn are confined to the gray mat- ter, others send their nerve-processes into the surrounding white matter to form particular tracts of nerve-fibres. THE CENTRAL NERVOUS SYSTEM. 203 The accompanying diagram, after Lenhosse"k, illustrates the vari- ous groups of nerve-cells now recognized as taking part in the com- position of the gray matter, as well as the assumed communications established by the collateral fibres within the cord. In addition to the nerve-cells and the fibres, the gray matter is everywhere pervaded by the supporting and uniting substantia spongiosa ; this ground-substance is composed of neuroglia fibres and richly-branched neuroglia cells, the latter being rather more nu- merous than in the white matter. Covering the posterior cornu and immediately surrounding the central canal of the cord, the ground-substance is modified to become the apparently almost homo- geneous substantia gelatinosa ; the mass capping the posterior horn, the substantia gelatinosa Rolandi, contains some few fusi- form nerve-cells and presents a striation produced, in part at least, by the course of the posterior root-fibres. The zone of clear ground- matrix surrounding the central canal of the cord, the substantia gelatinosa centralis, markedly differs from that on the posterior cornu, in being composed principally of closely-felted neuroglia fibres ; in certain regions (cervical and dorsal) the gelatinous sub- stance encroaches somewhat upon the gray commissure. The central canal occupies the gray commissure, being contin- uous with the cavity of the fourth ventricle above, and ending blindly below in the upper half of the filum terminale. The canal does not occupy the centre of the gray commissure, since it lies rather ven- trally to that point, especially in the lower part of the cord. The columnar epithelium lining the canal is an extension of that of the cerebral ventricles. In children, and in many animals at all ages, the surface of the cells directed towards the lumen is clothed with cilia ; the opposite ends of the cells terminate in long slender processes, which extend deeply into the surrounding struct- ures. The lining cells represent the spongioblasts, which in the embryonic cord closely crowd around the central canal and send long delicate fibres from their outer ends through the cord as far as the pia, while from their inner surface the hair-processes, the cilia, pro- ject into the central canal. The epithelium, with the subjacent neuroglia layer on which the cells rest, constitutes the ejjendvma. The form and size of the central canal, which represents the remains of the primitive neural tube, vary in the different divisions : in the upper cervical region its cross-section is somewhat quad- rilateral, from the level of the fifth cervical nerve becoming oval or slit-like, with the cleft placed parallel with the commissure. In the dorsal region the canal gradually approaches the circular form, while in the lumbar it once more becomes a compressed oval, with, however, the long diameter coinciding with the sagittal plane. 294 NORMAL HISTOLOGY. The canal of the sacral cord and of the conus medullaris assumes a _L-form, consisting of a ventral wider arm and a narrow dorsal ex- tension ; an irregular dilatation in the lower part of the conus has received the name ventriculus terminalis. The cords of chil- dren and of many animals contain a completely pervious central canal ; in the human cord in later life this is usually more or less occluded, although much variation exists in this respect. The upper cervical, lower lumbar, and sacral regions usually contain, even in the adult, a partially pervious tube. Overgrowth of the lining cells, as well as of the subepithelial substantia gelatinosa, is the prin- FIG. 327. Section of spinal cord of human embryo stained by Golgi silver method ; the left half of the figure exhibits the neuroglia-cells, while the right shows the elements constituting the framework of the epen- dyma. (After Lenhosstk.) cipal factor in the closure of the central canal, which, however, must be regarded as a normal change and not a pathological process. The blood-vessels of the substance of the cord are arranged in two groups : those entering at the periphery, including the larger branches which follow the connective-tissue septa ; those de- rived from the arteria sulci, given off from the anterior spinal artery and lodged within the anterior median fissure, from which branches are distributed to the gray matter. Of the numerous arteries which enter at the circumference, the finer usually terminate THE CENTRAL NERVOUS SYSTEM. 295 within the white substance, while the coarser alone penetrate into the gray matter, the outer zone of which they in part supply. The vessel occupying the posterior median septum, the arteria fis- surae posterioris, is the most important of the peripheral branches : twigs also accompany the anterior and posterior root-bundles. At the bottom of the anterior median fissure the arteria sulci divides into two sulco-commissural branches, which, diverging slightly, enter the gray matter to the inner side of the base of the anterior horn. After a short course within the gray substance, these vessels break up into a number of twigs, which soon form close cap- illary net-works within the anterior and middle parts of the gray FIG. 328. Section of injected spinal cord of child : s, sulcal branch of anterior spinal artery occupying anterior median fissure ; c, c, sulco-commissural vessels from sulcal artery passing to gray matter to form dense net-work ; p, posterior spinal artery, sending off twigs to white matter ; around margin of cord numerous peripheral vessels enter white substance to form open net-work. crescents ; a branch of some size passes backward to supply the region corresponding to Clarke's column. The sulco-commissural artery likewise gives off vertical anastomosing branches, one passing brainward, the other caudalward, to unite with similar off- shoots from the corresponding arteries of different planes. The veins follow in general the course of the corresponding arteries : some of the blood, however, brought by the sulcal artery is carried off by the peripheral veins. THE MEDULLA. The differences between the medulla and the spinal cord are rather of arrangement than of any great variation in structural 296 NORMAL HISTOLOGY. elements, since the tissues of the cord are prolonged into the medulla, where the increased importance of parts before relatively incon- spicuous, together with the addition of new masses of nervous matter, brings about the redisposition of the structures continued from the cord. The changes taking place in the transition of the cord into the medulla consist primarily in a modification of th^ gray matter ; the principal factors are the gradual increase in the size of the tracts of the posterior column and the decussation of fibres from the lateral column destined to aid in forming the anterior pyra- mids. The changes wrought by the first FlG- 329. factor are earliest indicated, and affect par- ticularly the posterior cornua of the gray substance, while the second modifies the anterior horns. An intimation of the changes to follow is seen in sections as low as the first, or even second, cervical nerve in the thick- ened club-shaped accumulation of gray matter representing the posterior cornu, connected by an extended and attenuated stalk with the chief mass. With the pro- gressive increase in the size of the columns of Goll (funiculus gracilis) and the col- umns of Burdach (funiculus cuneatus} the posterior horns are displaced more and more laterally and ventrally until the cornua with their supporting necks lie nearly horizontally, forming almost a right angle with the posterior median septum. The increased mass of the substantia gelatinosa not only approaches the surface, but gradually displays its growth by the formation of the projection known as the funiculus of Rolando, which, higher up, expands into the tubercle of Ro- lando. The greater size which the tracts of the posterior column assume is produced by the accession of masses of new gray matter, the nucleus gracilis and the nucleus cuneatus. These gray nuclei are at first narrow, but become more robust as the medulla is ascended. The ascending fibres of the posterior cord columns (Goll and Burdach) end in arborizations closely related to the cells of the nucleus gracilis and cuneatus ; from these nuclei new fibres spring which pass partly to the cerebellum of the same and the opposite side, as the posterior and the anterior external arcuate fibres, and partly to higher levels by way of the mesial fillet, as the decussating deep arcuate fibres. With the opening out of the central canal of the cord into the fourth ventricle the gray matter lying originally dorsally to the canal Diagram of spinal cord indicating the paths taken by fibres of crossed pyramidal tract (6) to gain the an- terior columns (a), and by fibres of posterior column (s) higher up to form sensory decussation. (After Testut.) THE CENTRAL NERVOUS SYSTEM. 297 becomes laterally displaced, while the remains of the base of the anterior horn come to the surface of the ventricular floor, and assist in forming the projection of the funiculus teres. A longitudinal column of large nerve-cells occupies part of this, forming the nucleus from which the numerous bundles of the roots of the hypoglossal nerve arise. The changes affecting the anterior cornuaof the cord are produced primarily by the decussation of those fibres of the lateral column FIG. 331. Diagram of lower end of medulla at level of decussation of anterior pyramids : a, anterior pyramidal tracts ; b, posterior median septum ; c, fibres of crossed pyramidal tracts crossing (d) to anterior pyramid of opposite side ; e, anterior horn of gray matter isolated by decus- sating fibres ; f, remains of bases of anterior horns ; g, nucleus gracilis ; h, enlarged and displaced posterior horns of gray matter. (After Testut-Duval.) Diagram of medulla through lower part of olivary body : a, anterior pyramidal tract ; 3, posterior median groove ; c, gray matter representing bases of anterior cornua, the latter lying isolated at e, forming nucleus lateralis ; d, decussating fibres of formatio reticularis ; g, nucleus gracilis ; h, gray matter of bases of posterior horns ; k, nucleus cuneatus ; t, remains of posterior horns, substantia gelatinosa of Rolando ; /, ascending root of tri- facial nerve ; m, pneumogastric, n, hypoglossal, nerve ; o, nucleus dentatus of olive ; /, mesial accessory olive ; s, sensory portion of anterior pyramids. (After Testut-Duval.) which contribute to the formation of the anterior pyramids. The fibres of the crossed pyramidal tract, in taking the shortest course to reach the point of decussation, cut obliquely through the gray substance in such a manner that the anterior cornu becomes broken up, its caput being entirely separated ; the remaining portion of its base forms a small mass of gray matter lying ventro-laterally to the central canal. The isolated segment of the anterior cornu is pushed to the side by the development of the pyramid, and, higher up, by the additional displacement caused by the appearance of the olivary body between the caput cornu and the pyramid ; in conse- quence the separated part is displaced both laterally and dor- sally, and becomes the lateral nucleus, taking up a position in close relation with the now ventrally situated posterior horn. By the penetration of transverse and longitudinal fibres the greater part NORMAL HISTOLOGY. of the separated area is broken up into a coarse net-work containing nerve-cells and intersecting fibres — the formatio reticularis. Above the level of the decussation of the pyramids, a second or sensory decussation is seen, formed by the crossing fibres pro- ceeding from the nerve-cells within the funiculus gracilis and cunea- tus. On gaining the opposite side, some of the decussating fibres (internal arcuate) turn sharply brainward and pass to higher levels as a longitudinally coursing tract, known as the mesial fillet. Other fibres, the anterior external arcuate, after crossing, appear ven- a Section of medulla at level of sensory decussation : a, anterior pyramidal tracts ; b, posterior median septum ; c, h, gray matter representing bases of anterior and posterior cornua ; e, iso- lated anterior horns ; f, bundles of sen- sory fibres displacing posterior horn ; g, nucleus gracilis ; /, posterior horn, substantia gelatinosa of Rolando ; k, nucleus cuneaius; /, decussating sen- sory fibres crossing to the opposite median tract ; nt, root-fibres of hypo- glossal nerve. (After Testut-Duval.} n Diagram of medulla through olivary bodies : a, anterior pyramidal tracts ; b, floor of fourth ven- tricle ; c, remains of gray matter of base of anterior horns, nucleus of hypoglossal nerve ; c', accessory hypoglossal nucleus ; d, decussating fibres of for- matio reticularis ; e, nucleus ambiguus ; g, gray matter of posterior funiculus, including h, which represents base of posterior horn ; z, substantia gelatinosa of Rolando ; j, ascending root of tri- facial nerve ; k, restiform nucleus ; /, funiculus solitarius ; mt root-fibres of pneumogastric nerve ; n, hypoglossal nerve; o, nucleus dentatus of olive; p, q, dorsal and mesial accessory olivary nuclei ; r, external arcuate fibres ; s, sensory portion of anterior pyramid. (After Testut-Duval.*) trally and wind over the anterior pyramid and inferior olive to gain the restiform body in their course to the cerebellum. Additional decussating fibres pass from the inferior olivary body of the opposite side to the cerebellum by way of the restiform body. A third set of arcuate fibres, the posterior external, passes from the posterior funiculi of the same side to the cerebellum by way of the restiform body. In addition to the longitudinal fibres contributed by the deep arcuate bundles, the continuation of tracts from the antero-lateral column furnish longitudinal fibres of the formatio reticularis. In the upper part of the medulla, a group of longitudinal fibres constitute a distinct tract, the posterior longitudinal bundle. THE CENTRAL NERVOUS SYSTEM. 399 On reaching the inferior olivary bodies, new groups of ele- ments are introduced ; of these the most important is the nucleus of the olive, or corpus dentatum. This consists of a wavy sheet of gray matter so disposed that it forms collectively a compressed ovoid capsule or shell, closed externally, but open towards the median side, through which hilurn the nerve-fibres gain access to FIG. 334. Section of medulla of child through olivary bodies : a, anterior median groove ; b, raphe ; c, formatio reticularis ; d, gray matter of nucleus dentatus of olive ; e, dorsal accessory olivary body ; f, root-fibres of hypoglossal nerve ; g, nucleus arciformis ; h, external arcuate fibres ; i, anterior pyramidal tract ; k, remains of nucleus lateralis ; /, substantia gelatinosa of Rolando and fibres of ascending trifacial root ; m, n, gray matter of posterior funiculus ; o, funiculus solitarius ; p, nucleus ambiguus ; q, root-fibres of pneumogastric nerve ; r, s, hypoglossal and vagus nuclei ; /, nerve-cells of posterior funiculus ; «, posterior medullary velum closing in fourth ventricle, IV. the interior. The considerable tract of nerve-fibres entering the hilum constitute the olivary peduncle, having crossed the raphe from the tracts of the opposite side. After gaining the interior of the olivary body, they diverge towards the lamina of gray matter, which they traverse in their course to the restiform body and thence to the cerebellum. These olivary bundles form part of the lateral arcuate fibres, but consist, for the most part, of nerve-fibres of smaller diameter than those composing the internal arcuate fibres. Two additional small areas of gray substance are seen in NORMAL HISTOLOGY. close proximity to the corpus dentatum : these are the dorsal or outer and the mesial or inner accessory olivary nuclei, the first of which lies behind the olivary nucleus, near and parallel to its wavy band, while the second lies almost across the open end of the corpus dentatum. Attention has already been directed to the tract of large nerve- cells which lies near the median line and represents the nucleus of the hypoglossal nerve. In the lower part of the medulla, before the central canal opens out into the ventricle, a group of numerous smaller cells lies close but dorsally to the nucleus just mentioned ; as the central canal approaches the surface the tissues forming its former dorsal border become gradually laterally displaced, in consequence of which this group of nerve-cells then comes to lie outside of the hypoglossal nucleus. These cells form a continuous column throughout almost the length of the medulla, constituting a common receptive nucleus of the pneumogastric and glosso- pharyngeal nerves. The four principal tracts of the medulla are made up chiefly of the continuations of the columns of the cord ; without entering into a detailed account of these structures, a brief outline of the most important of the constituents of the tracts may here find place. 1. The anterior pyramid is composed of two sets of fibres : the continuation of the direct pyramidal tract of the anterior column of the cord, which does not take part in the decussation of the pyra- mids, and the continuation of the crossed pyramidal tract of the lateral column. The proportion of the crossed to the uncrossed fibres varies greatly ; while usually from three to ten per cent, of the pyramidal fibres pass directly into the anterior columns of the spinal cord, total decussation of these fibres takes place in about eleven per cent., in such cases the anterior pyramidal tract being evidently wanting. In only about sixty per cent, is a symmetrical disposition of the two pyramidal tracts on each side observed. 2. The lateral tract claims all the fibres of the lateral column not included in the crossed pyramidal and the direct cerebellar tract, together with the external anterior or ground-bundle, since the latter really is a part of the adjacent tract of the lateral column. The antero-lateral fibres enter beneath and at the side of the anterior pyramid and pass under the olivary body and the arcuate fibres to take part in making up the formatio reticularis ; the sensory fibres derived from the posterior columns after crossing in the sensory decussation pass brainward and aid in forming the mesial fillet. 3. The restiform body contains constituents from a number of sources ; these may be arranged in two groups, — those derived THE CENTRAL NERVOUS SYSTEM. from the cord and the medulla and those arising from the pons. The first group comprises : (a) The direct cerebellar tract of the lateral column. (•£) The posterior external arcuate fibres from the nucleus gracilis and nucleus cuneatus of the same side. (V) The anterior external arcuate fibres from the nucleus gracilis and nucleus cuneatus of the opposite side. (d) The internal arcuate fibres from the inferior olive of the oppo- site side. O) Fibres from the lateral nucleus of the medulla. The pontine group includes : (/) Fibres from the superior olive of the opposite side. (£•) Fibres from the acoustic nucleus of the same side. 4. The posterior pyramid is the upward prolongation of the postero-median column of the cord. On approaching the lower angle of the fourth ventricle, this column, or the funiculus gracilis, exhibits the pronounced thickening of the clavus, which contains the nucleus gracilis and then merges into the restiform body. THE PONS. The pons, as may be inferred from the mutual relations of the sev- eral divisions of the brain which it connects, consists very largely of bundles of nerve-fibres ; in addition to these, areas of gray mat- ter, the pontine nuclei, supplement the nerve-fibres in making up its mass. On section the pons exhibits two portions, the dorsal and the ventral. The latter contains the principal decussating tracts connecting the cerebral cortex and cerebellum, and constitutes a robust mass of transverse fibres ; through this the longitudinal bundles of the anterior pyramids of the medulla force their way in their course from the cerebrum. In the lower half of the pons the pyramidal fibres are collected into two closely- packed groups of bundles, one on either side of the mid-line, which are enveloped in front and behind by a layer of transverse fibres ; higher up, above the middle of the pons, the pyramidal tracts become separated by the penetrating transverse bundles into a number of fasciculi. Among the transverse tracts, therefore, are recognized the ventral or super- ficial bundles and the dorsal or deep bundles, the latter forming the corpus trapezoideum. Small multipolar cells are found widely distributed in the ventral region of the pons within the gray matter which occupies the interfibrillar interstices. The dorsal portion of the pons consists largely of structures rep- resenting the continuation of parts already encountered below, espe- cially of the formatio reticularis and of the dorsal tracts of gray substance. In addition to the gray matter scattered throughout 302 NORMAL HISTOLOGY. the reticulum, other localizations represent important nuclei of cranial nerves. The sheet of gray matter lying in the lower half of the ven- tricular floor is continued over the pons, and there gives rise to nuclei connected with the V, VI, VII, and VIII nerves. While the details of the sections must vary with each plane, the general dis- position of the structures is shown in sections passing through at about the middle of the fourth ventricle. In such sections the dorsal FIG. 335. Section through upper part of human pons : i, fourth ventricle ; 2, valve of Vieussens lined with ependyma; 2', white matter of anterior medullary velum; 2", gray matter of Hngula ; 3, descending root of trifacial nerve ; 4, substantia ferruginea ; 5, posterior longitudinal bundle ; 6, formatio reticu- laris ; 7, groove indicating boundary between tegmentum and ventral part of pons ; 8, superior cere- bellar peduncle; 9, mesial fillet; 9', lateral fillet; 10, transverse fibres of pons; n, longitudinal fibres ; 12, raphe ; V, trifacial nerve. (After Testut-Stilling.) or tegmental portion of the pons bears a resemblance to the me- dulla, the gray dorsal stratum giving rise to fibres which pierce the reticulum in their course to the free surface. At a somewhat higher level, lateral groups of pigmented nerve- cells occupy the floor of the fourth ventricle ; these cells are so dark that they collectively present an area visible to the unaided eye, the substantia ferruginea ; seen through the stratum of white fibres forming the immediate floor of the ventricle, this area appears of a bluish-gray or slate-color and constitutes the locus coeru- leus. Close to this pigmented area, lying to its mesial side and near the raphe", an angular tract, known as the posterior longitudinal bundle, extends beneath the gray matter of the ventricle, just at the dorsal border of the reticular formation. This fasciculus, also prom- THE CENTRAL NERVOUS SYSTEM. 303 inent at higher levels, establishes important communications between the nuclei of several cranial nerves. THE CRURA. The crura cerebri, or cerebral peduncles, resemble the pons in general arrangement, since they consist of a ventral portion, the crusta pedunculi, or the cerebral peduncle proper, made up FIG. 336. Section through human cerebral peduncles at point of emergence of oculo-motor nerve : C, crusta, separated from tegmentum ( Tg) by sub- stantia nigra (5) ; R, raphe dividing formatio reticularis ; F, longitudinal bundles of latter ; O, groups of nerve-cells connected with origin of oculo- motor fibres (Om) ; Tf, cells connected with origin of trifacial nerve ; A , aqueduct of Sylvius; CQ, anterior corpora quadrigemina. (After Krause.) exclusively of ascending and descending fibre-tracts, and of a dorsal portion, the tegmentum, which contains the prolongation of the formatio reticularis and of the dorsal stratum of the gray substance 304 NORMAL HISTOLOGY. of the medulla and the pons. On transverse section of the crura, it is seen that the tegmental halves are united, while the two peduncular portions are widely separated and are attached to the tegmentum alone ; the oblique line of this juncture is indicated within the section by a deeply pigmented area, the substantia nigra. The crusta is hemi-cyliridrical in section, but the encroachment of the substantia nigra reduces the area devoted to the ascending and descending fibres to a narrow crescent, whose convexity corre- sponds to the external outline of the peduncle, while the concavity embraces the dark field. Since the tracts of ventral nerve-fibres of the peduncle greatly exceed the pyramidal bundles of the pons, it is evident that many additional fibres have arisen within the peduncles. On reaching the cerebral hemispheres in their course upward, the tracts of the crusta become continuous with the fibres constituting the internal capsule. The substantia nigra, separating the crusta and the tegmentum, forms a tract of gray matter extending from the upper border of the pons forward as far as the mammillary bodies ; while it gradually diminishes in its forward course, the mesial edge of the mass becomes thickened in the vicinity of the oculo-motor groove. The area owes its exceptional color to irregular groups of deeply pigmented multipolar cells embedded within a finely granular ground-sub- stance. The tegmentum forms only part of the great nuclear tract continued through the dorsal portion of the oblongata, the pons, and the peduncle into the subthalamic region ; as in the other localities, so here, the stratum of gray matter lying beneath the floor of the neural tube and the formatio reticularis are its principal constit- uents. In addition to the gray matter distributed throughout the reticulum, groups of nerve-cells are situated along the floor of the Sylvian aqueduct ; some of these are of importance as the nuclei of the bundles of the oculo-motor and the pathetic nerve. Near the middle of the formatio reticularis, on either side of the raphe", lies a conspicuous group of large pigmented nerve-cells, the tegmental or red nucleus, so called on account of its brown or reddish hue. The formatio reticularis of the tegmentum differs little from the similar structure at lower levels. In general, the fibres contained within the crusta connect with the motor areas of the cerebral cortex, while those of the tegmentum usually terminate in or about the thalamus. THE CEREBELLUM. The cerebellum consists of a peripheral or cortical layer of gray substance which encloses the various tracts of nerve-fibres composing THE CENTRAL NERVOUS SYSTEM. 305 the white matter of the medulla, together with certain additional gray nuclei embedded within the latter. On section, each leaflet of the cerebellum is seen to be made up of (i) a central core of white medullary substance, which blends into (2) the granule layer, characterized by its "rust-color," external to which follows (3) the FIG. 337. 2- Section of human cerebellum, slightly magnified to show general arrangement : w, white matter of medulla ; g, o, granule and molecular or outer layer, between which lies layer of Purkinje's cells (/>). outer or molecular stratum ; between the latter and the granule layer lies (4) the single row of ganglion-cells which constitutes the layer of the cells of Purkinje. The granule layer forms a zone conspicuous on account of the great number of small deeply-staining cells which it contains. It varies in thickness, being broadest at the summit of the laminae and narrowest at the bottom of the fissures. Towards the outer layer the zone is sharply defined, but it fades away on the median side into the medullary substance. The nerve-cells of the granule layer are of two kinds, — the small and the large ganglion-cells. The former are small (6-7 p) round elements, stain deeply, but possess so little protoplasm that the greater part of the cell is formed by the nucleus. These cells, the principal elements of this layer, are arranged in irregular groups ; they are multipolar, and have, according to recent investigations, 306 NORMAL HISTOLOGY. branched protoplasmic as well as nervous or axis-cylinder processes ; while the former ramify among the cells of the granule layer, the delicate nervous processes extend into the outer, molecular layer, where they usually end by dividing into longitu- dinal T-branches which stretch horizontally parallel with the boun- daries of the zone. The processes of these cells are so delicate, as well as so masked by the surrounding elements, that their existence has been established only after the introduction of the recent methods of Golgi, the results of whose investigations have been confirmed by Ramon y Cajal, Kolliker, and others. Other nervous elements of the granule layer are the sparingly-distributed multipolar cells, much larger than the ones just considered, which resemble in struct- ure and size the cells of Purkinje, and, like them, possess richly- branched protoplasmic processes extending within the molecular FIG. 338. 0 G Diagram representing cellular constituents of cerebellar cortex ; Golgi's silver staining : IV, white matter ; O, G, outer and granule layers of gray matter; a, large cell of granule layer confined to gray substance ; b, b' , small nerve-cells of granule layer (exaggerated for convenience), also limited to gray matter; c, cell of Purkinje, sending axis-cylinder into granule layer and richly-branched processes towards periphery ; e. similar cell seen in profile ; f, small nerve-cell of outer layer, limited to gray matter; g, nerve-cell of outer layer, whose axis-cylinder process forms basket works (d, r. (After Schae/er-Mtynert.) tion of the improved methods (Weigert's) for tracing medullated fibres, much remains to be learned regarding the course and the distribution of many tracts connecting the central nuclei with the cerebral cortex. The great mass of the cerebral medulla is composed of fibre- tracts, which may be grouped into three systems : 1. The association fibres, connecting parts of the same hemi- sphere. 2. The commissural fibres, uniting parts of the two hemispheres, THE CENTRAL NERVOUS SYSTEM. and represented by the fibres of the corpus callosum and of the anterior commissure. 3. The projection fibres, streaming from the entrance of the brain-stalks, or cerebral peduncles, secondarily also from the basal nuclei, to spread out in the various parts of the cerebral cortex and thus constitute the conspicuous corona radiata. The association fibres consist of bundles of various length, which unite : (a) adjoining convolutions, passing from the medulla of one, beneath the intervening fissure, into the white matter of the neighboring gyrus ; (£) adjacent convolutions, but not immedi- ately adjoining ; (V) more distant parts of the hemisphere. The most important of these longer tracts are : 1. The fasciculus uncinatus, connecting the inferior frontal convolution with the uncinate gyrus of the temporal lobe. 2. The fasciculus longitudinalis inferior, connecting the an- terior part of the temporal with the apex of the occipital lobe. 3. The fasciculus longitudinalis superior, connecting the middle of the frontal partly with the occipital and partly with the apex of the temporal lobe. 4. The cingulum, extending along the corpus callosum within the gyrus fornicatus. 5. The fasciculus perpendicularis, connecting the inferior parietal with the fusiform lobe. 6. The fornix, connecting the uncinate process of the hippo- campal convolution with the thalamus by means of the continuations effected by the fimbria behind and the bundle of Vicq d'Azyr, from the mammillary body to the thalamus, in front. The majority of the commissural fibres, which connect similar regions on the two sides, take part in the formation of the great transverse bridge, the corpus callosum ; these fibres, the pro- longations of the axis-cylinder processes of the cortical ganglion- cells or of the collateral processes derived from the projection fibres, pass to all parts of the cerebral surface, with the exception, probably, of the anterior portions of the temporal lobes and the olfactory tracts, which parts are connected by the fibres of the anterior commissure. On either side of the closely-packed bundles con- stituting the immediate bridge the fibres spread out in a fan-like course to reach their destination. The projection or peduncular fibres include many of the most important tracts by means of which communication between the presiding cortical centres and the more deeply lying nuclei and paths is established. The bundles of the crusta on reaching the sub- thalamic region become continuous with the internal capsule and spread out into the conspicuous corona radiata. The fibres which 328 NORMAL HISTOLOGY. gain the cortex, however, do not correspond exactly with those enter- ing the cerebrum as the peduncular bundles, since some of the latter are deflected and pass to the caudate and the lenticular nucleus from the internal capsule ; on the other hand, the peripherally-streaming bundles are augmented by fibres which come from the thalamus and the subthalamic region. The peduncular tracts continued to the cortex consist principally of the pyramidal fibres, the fibres from the caudate and lenticular nuclei, and the fibres to the temporo-occipi- tal region from the optic thalamus and the pons. The tracts of the tegmentum largely contain fibres related to the connections of the thalami, the cerebellum, and the corpora quadrigemina ; regarding the exact course and communications of these bundles much still remains to be determined. Two small but remarkable organs, the pituitary and the pineal body, are closely associated in their genetic relations with the cere- brum, since the first of these bodies originates partly and the second entirely as a diverticulum from the cavity of the primary inter-brain. THE PITUITARY BODY. The pituitary body, or hypophysis cerebri, consists of two portions, the large anterior oral and the small posterior cerebral division. These are entirely distinct both in structure and in de- velopment, since tjie anterior lobe is derived as a diverticulum from the primitive oral cavity, and, as such, is lined with the oral ectoderm, while the posterior lobe descends as an outgrowth from the floor of the primary inter- FlG- 351- brain, its stalk remaining as the infun- dibulum. In the embryo temporarily, and in many lower vertebrates permanently, the tissues composing the posterior lobe assume a distinctly nervous type ; in the higher animals, however, this character is lost, the lobe remaining small and rudi- mentary and its cavity undergoing obliter- ation ; the primary nervous character of section of human pituitary body: the cerebral lobe disappears as the in- C, portion of posterior or nervous L . lobe; P, portion of anterior or grOWth of the COnnCCtlVC tlSSUC and glandular lobe, consisting of tubular the blood-VCSSCls takes place. The TC- acini (a) ; s, connective-tissue septa ; . . v, biood-vesseis. mains oi the immature nervous elements are sometimes recognized in the branched and spindle pigmented cells found in this part of the pituitary body, as well as in the partially-preserved cavity lined with ciliated columnar cells. THE CENTRAL NERVOUS SYSTEM. The anterior lobe, larger and darker than the preceding, for some time remains connected by its tubular ectodermic stalk with the primitive oral cavity ; later the tube becomes atrophic and finally disappears, the end of the oral diverticulum then lying iso- lated and separated from the buccal cavity. The single primary tube undergoes repeated division, producing compartments which appear in the adult organ as slightly convoluted tubular acini. The tubules are held together by vascular connective tissue, and contain polyhedral epithelial cells, with spherical or oval nuclei, irregularly disposed and often almost filling the alveoli ; the lumina of the tubules are sometimes occupied by colloid masses resembling those of the thyroid gland. THE PINEAL BODY. The pineal body, epiphysis, or conarium, since the compara- tively recent investigations of Spencer and of de Graaf, although known and described previously for centuries, is now regarded as a rudimentary sense-organ. These investigators independently demonstrated that the structure seen in man and the higher FIG. 352. animals is the rudiment of what was a functionating sense-organ in the extinct reptiles, and even in certain living members of the same class strongly resembles an imperfect invertebrate eye in its early embryonal condition. In the light of our present knowledge, therefore, this pe- culiar body must be looked upon as representing an im- perfect organ of special sense, whether as an additional visual structure — the "pineal eye" as an organ for the percep- B Sagittal section through part of head of lizard embryo, showing so-called pineal eye: P, special- ized isolated extremity of pineal diverticulum from brain-vesicle (B) ; b, c, so-called retinal and len- ticular areas of its walls ; a, ectoderm ; d, remains of diverticulum undergoing division into tubules (d') ; f, blood-vessels ; e, mesodermic tissue. tion of warmth still remains to be determined. In man and other mammals the pineal body, instead of oc- cupying its morphologically normal position on the superior surface of the brain, is covered over by the greatly developed cerebral hemispheres, so that its final position is well towards the base of the encephalon. The organ at no time in the higher ani- 330 NORMAL HISTOLOGY. FIG. 353- Section of human pineal body : a, a, acini lined and partially filled with epithelium and cal- careous concretions (s) ; f, inter- tubular fibrous tissue. FIG. 354. mals assumes the characters of a sense-organ to the extent seen in the lower types. The adult human pineal body is composed of a number of tu- bular compartments or alveoli, which are separated by septa of connective tissue and lined by polyhedral epithelial cells ; in many places the tubules are almost oc- cluded by epithelium, together with aggre- gations of gritty calcareous matter, the so-called " brain-sand." The brain-sand, or acervulus cerebri, consists of irregu- larly round mammillated or mulberry-form concretions of variable size, composed of animal matter combined with earthy salts (calcium carbonate and phosphate with magnesium and ammonium phosphate). These deposits are not limited to the in- terior of the pineal body, but are encountered on its exterior and on the peduncles, as well as in the choroid plexus and in other parts of the brain-membranes ; the concretions occur at all ages, even before birth, and within the perfectly normal organ. Other bodies, the corpora amylacea, occur as round discoidal masses, and exhibit a distinct concentric striation ; they are regarded as amylaceous in nature, since they respond to the tests for such substances, staining violet with iodine and sulphuric acid. These bodies are almost constant within both the gray and the white matter consti- tuting the walls of many parts of the brain-cavities ; the olfactory tract is a particularly favorite situation, along this region the amylaceous corpuscles occurring with especial profusion. THE SUPRARENAL BODY. The close relations of this organ with the nervous system, as evidenced by its early history, the profusion of its nervous elements, and the results of pathological processes, entitle the suprarenal body to place, provisionally at least, within the present chapter. The parenchyma of the organ, composed of a peripheral zone, the cortex, and a central area, the medulla, is invested by a fibrous capsule of considerable thickness. From this envelope numerous connective-tissue septa penetrate deeply into the soft cellular substance, which is thus broken up into cylindrical masses. The cortex consists of aggregations of irregularly rounded or Corpora amylacea from lateral ventricles of human brain. THE CENTRAL NERVOUS SYSTEM. 331 FIG. 355. polygonal cells (13-17 /*), whose granular protoplasm frequently contains fat-particles in addition to clear nuclei. The arrangement of the cortical elements varies at different levels, the resulting disposition giving rise to the three divisions of the cortex recognized as the zona glomerulosa, the zona fas- ciculata, and the zona reticularis. The cells forming the first of these are grouped as oval masses, those of the middle layer are disposed as long cylindrical groups, and those of the third stratum are irregularly arranged as anastomosing cords supported within a reticulum of connective tissue. The zona reticularis is distinguished from the other cortical layers by the pigmented condition of its cells. The various groups of cellular elements are separated from one another by delicate fibrous septa, continuations from the outer connective-tissue envelope ; the larger septa support the capillary net- works which surround the groups of cells. The medulla contains granular, fre- quently feebly-pigmented, polygonal cells arranged as cords and irregular net - works within a framework of highly vascular connective tissue. Nu- merous ganglion - cells occupy the central portions of the medulla, along with a rich net-work of non-medullated nerve-fibres and the con- spicuous venous channels. The blood-vessels of the organ divide within the capsule into numerous smaller branches, which enter the parenchyma along the fibrous septa ; capillary net-works surround the cell-groups of both cortex and medulla. The veins of the medulla are of large size and unite to form trunks which make their exit at the central hilus ; the larger radicles are accompanied by longitudinal bundles of non-striped muscle. The nerves of the suprarenal body are remarkable for their num- ber and size ; they bear the arteries company within the septa to reach the medulla, where they form an intricate plexus composed chiefly of non-medullated fibres. Ganglion-cells occur along Section of human suprarenal body : a, fibrous capsule ; b, zona glomeru- losa ; c, zona. fasciculata ; d, zona reti- cularis ; e, medullary cords ; ft venous channel ; g, ganglion-cells'. NORMAL HISTOLOGY. the course of the nerve-trunks, and are found within the medulla in considerable numbers. The lymphatics are represented by delicate canals within the fibrous septa which communicate with the intercellular clefts of both cortex and medulla on the one hand, and with the larger lymph-ves- sels within the capsule on the other. THE DEVELOPMENT OF THE NERVOUS TISSUES. The consideration of the general changes involving the primary neural tube and its cephalic expansions, the brain-vesicles, by which are produced the various portions of the cerebro-spinal axis, belongs to embryology, and lies without our present purpose ; an account of the histogenesis of the nervous tissues, however, is of much interest in indicating the true relations of the structural components of the great nervous, masses. The essential parts of the nervous system, including the nerve- cells, the nerve-fibres, and the neuroglia, are developed from the ectoderm alone, and all result from the differentiation and speciali- zation of the walls of the primary neural tube. This canal is formed by the gradual closure of the early furrow, the medullary groove, of the FIG. 356. invaginated ectoderm along the dorsal line ; by the approxi- mation of the upper or dorsal edges of the involution the furrow is converted into a tube, the sides, or medullary plates, of the extreme ante- rior and posterior segments of which are the last to unite. Even before the closure of the groove has been completed a differentiation of two impor- tant regions is indicated; these are the areas giving rise to the segmental ganglia and to the general axial nerves. The area for the latter is represented by the lining of the neural tube, that for the former by the inconspicuous cell-groups lying on either side of the line of closure. The primary wall of the neural tube consists of a single layer of columnar epithelial cells, whose nuclei occupy the middle third of the elements, leaving an outer and an inner free zone ; within the latter appears very early a second variety of cell, which is distinguished by its large spherical form and conspicuous nucleus. The Section of nine-day rabbit embryo, showing open neural tube : e, ectoderm invaginated and thickened within neural canal («) ; m, mesoderm ; b, body- cavity ; g, still open gut, lined by entoderm (K). THE CENTRAL NERVOUS SYSTEM. 333 round cells invading the inner zone represent the ancestors of the nervous elements— both cells and fibres — and are the germ-cells, while the columnar cells produce the neuroglia FlG- 357- and are the spongio- blasts. The development of the nerve-cells proceeds from the germ -cells, which, as shown by the karyokinetic figures within their nuclei, undergo ac- tive proliferation, the resulting progeny being the neuroblasts, from which the nerve - cells are directly derived. The germ-cells are confined to the zone next the brain-cavity, which thus indicates the position of greatest formative energy. The neuroblasts at first occupy the innermost zone, next the cerebral cavity, but soon migrate towards the outer boundary of the wall, at the same time becoming pyriform and elongated. The young nerve-cells for a long time possess but a single process, Section of ten-day rabbit embryo, showing closed neural tube : n, neural canal ; s, area from which segmental gan- glia develop ; m, mesodermic tissue ; g, gut-tube ; vt z>, primitive aortae ; /, pleuro-pericardial cavity. FIG. 358. FIG. 359. Primary wall of neural tube composed of single layer of epithelium («) ; b, b, germ -cells occupying inner zone. (After Portion of inner zone of wall of neural tube in which round germ-cells («, «) and partially-developed neuroblasts (nf, n') lie among the surrounding spongio- blasts. (After His.) which grows out to become a nerve-fibre, and therefore represents the axis-cylinder, or nerve-process; the protoplasmic pro- 334 NORMAL HISTOLOGY. cesses, whose ramifications later present such striking pictures, are subsequently acquired, after the lapse of considerable time. FIG. 360. Portion of wall of neural tube, exhibiting germ-cells (g) among the differentiating spongioblasts (s). (After Hzs.) FIG. 361. The development of the neuroglia depends upon the special- ization of the columnar elements, the spongioblasts. The epithelial cells elongate, their protoplasm at the same time undergoing vacuolation and partial absorption, resulting in the production of an elongated framework of connected slender trabeculse. The extremities of the changed epithelial elements, or spongioblasts, greatly dif- fer ; the inner ends of the cells extend to the inner boundary, where they are united to form a continuous sheet, the membrana limitans interna, and the outer processes break up into irregular branches, which ultimately form a close reticulum. The early spongioblasts ex- tend the entire thickness of the neural wall, but with the subsequent increase in this structure their attachments become Spongioblasts from neural tube; broken, the spongioblasts then lying free their expanded upper ends unite to , •>• •> constitute the internal limiting mem- among the surrounding nervous elements. brane next the brain-cavity; their The general growth of the tisSUCS is aC- "P int° redCUlUm' companied by great extension and sub- division of the neuroglia fibres, which eventually become the nucleated masses of fine, bristle-like processes THE CENTRAL NERVOUS SYSTEM. constituting Deiters's or spider cells. The spongioblasts im- mediately around persistent parts of the neural canal retain their inner connection and form a continuous layer of lining elements, which later constitute the ciliated columnar epithelium of the ependyma. The development of the nerve-fibres includes the origin of two sets of primary fibres — those derived from the nerve-cells of the medullary tube and those growing out from the cells of the ganglia. All nerve-fibres are formed as the direct exten- sions and continuations of the processes of the neuroblasts. In the case of those proceeding from the neural canal the fibres grow peripherally and the cells remain attached to their central ends, thus early establishing the relations afterwards existing between the motor cells and the fibres ; those originating from the ganglia, on the other hand, grow in two directions, towards the periphery and towards the nervous axis, representing the sensory paths. . The early nerve-fibres consist for some time of the axis-cylin- der alone, the neurilemma and the medullary substance being not only much later acquisitions but also contributions from the meso- derm. The neurilemma first envelops the ectodermic axis-cylin- der as a delicate sheath, and subsequently within this envelope the myeline of the white matter of Schwann is deposited. The ap- pearance of this coat is often very late, and takes place at different times for the various tracts of nerve-fibres, although the period at which the several groups acquire their medullary substance is con- stant and definite for each set. The young fibres soon collect into groups, which represent the early nerve-trunks, whose further growth proceeds in a straight path corresponding with the general direction of the component axis-cylinders ; a course once established is maintained until arrested by some obstacle or modified by changes in the position of the parts with which the nerve has formed attach- ments. The terminations of the growing nerves are abrupt, the finer ramifications appearing only after the trunk has undergone repeated branchings. 336 NORMAL HISTOLOGY. CHAPTER XVII. THE EYE AND ITS APPENDAGES. THE EYEBALL. THE bulbus oculi consists of three coats: i, the external fibrous tunic, comprising the sclerotic and the cornea, upon which devolves the maintenance of the form of the organ ; 2, the middle vascular tunic, made up of the choroid, the ciliary body, and the iris, to which the principal vascular supply of the eye is distributed : 3, the inner nervous tunic, the retina, which receives the termi- nal expansion of the optic nerve and contains the specialized neuro- epithelium concerned in the perception of the visual stimulus. The aqueous humor, the crystalline lens, and the vitreous body are en- closed by these coats, and represent the refractive media of the eye. Referred to their embryonic origin, the several parts of the eye may be grouped under two headings, — those developed from the ectoderm and those derived from the mesoderm. The mem- bers of the first group may be subdivided into (a) structures derived directly from the ectoderm, including the lens and its anterior epi- thelium, and the epithelium of the cornea and of the adjacent scleral surface, and (&) structures derived secondarily from the ectoderm through the optic vesicles protruded from the involuted ectoderm of the cerebral vesicles ; to this class belong the primary retinal tissues, including the pigment-layer, as well as the atrophic retinal layers continued over the posterior surface of the ciliary body and the iris. All other parts of the eyeball, comprising the remaining portions of the sclera, the cornea, the iris, the ciliary body, the choroid, and the vitreous body, as well as the connective-tissue ingrowths of the retina, are developed from the mesoderm. THE CORNEA. The cornea consists of five layers : 1 . The anterior epithelium. 2. The anterior limiting membrane. 3. The substance proper. 4. The posterior limiting membrane. 5. The posterior endothelium. The anterior epithelium, the only part of the cornea derived from the ectoderm, all others being mesodermic, is stratified squa- THE EYE AND ITS APPENDAGES. 337 mous in character ; it is thinnest over the central part of the cornea, where its six to eight layers of cells together measure about 45 /*, at the periphery reaching almost double that thickness. The deepest cells are columnar in form with their outer ends somewhat rounded off, while their bases are slightly expanded and conform to the surZ face of the basement-membrane upon which they rest. Succeeding the deepest layer the elements become broader and polyhedral, many pos- FIG. 362. sessing the protoplasmic threads char- acteristic of prickle-cells. The su- perficial strata are composed of flattened cells which lie parallel to the surface and contain oval nuclei. The anterior limiting mem- brane, membrane of Bowman, or lamina elastica anterior, corre- sponds to a highly-developed base- ment-membrane, being continuous with the tissue of the substantia pro- pria, of which it is a special conden- sation. The structure is especially conspicuous in the human cornea, where it appears as a seemingly ho- mogeneous glassy layer, about 20 M in thickness in the middle of the cor- nea, gradually diminishing towards the periphery. The resolution of this lamina into delicate connective- tissue fibrillse after treatment with suitable reagents demonstrates its true nature as a specialized portion of the substantia propria. The fibrous stroma, or the sub- stantia propria, constitutes the chief bulk of the cornea, and is made up of parallel lamellae composed of in- terlacing bundles of fibrous connective tissue. The exact num- ber of corneal lamellae is inconstant, since this depends upon the extent to which the artificial separation of the tissue is carried. The interlacing bundles of the white fibrous tissue composing the lamellae are united by the interfibrillar cement substance, and cross one another obliquely at various angles, the adjacent bundles being intimately united by bands, the fibrse arcuatse, which pass from one bundle to the other ; the arcuate fibres are especially prominent 22 Section of human cornea : a, anterior epithelium ; c, anterior limiting membrane ; b, b, fibrous substantia propria, containing corneal corpuscles (f) lying within cor- neal spaces ; d, posterior limiting mem- brane ; e, endothelium lining anterior chamber. 338 NORMAL HISTOLOGY. in the anterior lamellae. The substantia propria resembles the matrix of cartilage in yielding chondrin on boiling, therein differ- FIG. 363. Interlacing bundles of fibrous tissue constituting substantia propria from cornea of ox ; interstitial injection with silver nitrate. ing from the sclera, which, like the usual connective tissues, produces gelatin. The cellular elements, the corneal corpuscles, are plate-like or stellate connective-tissue cells, whose branched processes unite FIG. 364. Corneal corpuscles from calf; gold preparation. with those from adjacent cells to constitute a protoplasmic reticu^ lum throughout the tissue. The corneal cells and their processes lie within a system of intercommunicating lymphatic spaces THE EYE AND ITS APPENDAGES. 339 FIG. 365. 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 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. The posterior limiting membrane, membrane of Descemet, or poste- rior elastic lamina, ap- 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 FIG. 366. Corneal spaces from calf: silver preparation. 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 foetus, 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 FIG. 368. of loose connective tissue, the lamina suprachoroidea, the extensive interfascicular clefts of which form part of the sub- scleral lympl\-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 trabeculae join one another at various angles, and include the imperfectly sep- arated compartments of the gen- eral lymph-space. The larger partitions convey the numerous vascular and nervous trunks in their course to and from the choroid. The deeply-pigmented tissue cf the innermost layer of the sclera, next the subscleral space, constitutes the lamina fusca, and is covered with the endothe- C 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. 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 fibrillae 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 : 1. 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 (b) ; c, capillary layer, 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 vense vorticosse, 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 FIG. 370. Human choroid seen from its inner surface, exhibiting surface view of cap- illary net-work, or choriocapillaris (c, c) ; bt 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 ol a narrow 344 NORMAL HISTOLOGY. zone, about 10 n 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 //. 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 : i, the ciliary ring; 2, the cili- 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 Section of human ciliary processes ; 7. in- « , r , r , terstitial connective-tissue stroma, covered by prolonged frOIX! the maSS of the retinal layers (/?) ; f, o, inner clear and outer ciliary mUSCle J the character of pigmented layers of cells; f fibrous tissue of , i u V u 11 processes. tne 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 i mm. , they abruptly end at the base of the iris, sinking FIG. 371. THE EYE AND ITS APPENDAGES. 345 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 fj. 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. Section through ciliary region of human eye : A, cornea; a, b, c, its epithelium, substantia propria, and endothelium ; C, scleral conjunctiva, terminating at d; B, sclera/ e, sclero-corneal juncture ; D, iris ; E, ciliary body covered by pigment-layer, /; k, fibrous stroma of ciliary processes ; /J bands of pectinate ligament; g, spaces of Fontana ; s, canal of Schlemm; v, venous channels; m, 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. 346 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 choroidese. 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 Miiller, 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 retina. The various components of the iris and their morphological relations may be grouped as follows : 5. Pigment-layer, < -of OPTIC VESICLE. 1 . Anterior endothelium. 2. Anterior boundary layer, ~\ Continuation of the tissues of the 3. Vascular stroma-layer, uveal tract proper, constituting 4. Posterior boundary layer, ) the stroma-zone. ' a. Anterior layer of pig- 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; b, 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, w.th anterior epithelium beneath; /, 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 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 i 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 i 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 vorticosse. 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 i mm. in width, and the ill-developed radially-disposed bundles extending from the pupil towards the ciliary margin and forming an incomplete and very inconspicuous layer, the dilator pupillae. The posterior boundary layer, or vitreous lamella, appears as a glassy structureless membrane, about 2 p. 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. 349 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 stroma-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 350 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 trabeculse 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 lamellje (d) ; c, endothelium continued over iris (i) ; f, elastic lamellae separating Schlemm's canal (S) from spaces of Foniana (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. lies a flattened annular channel, the canal of Schlemm ; the inner wall of this canal is formed by intersecting delicate lamellae whose loose disposition effects but incomplete isolation of the channel from the adjacent spaces of Fontana. Schlemm's canal, which may be regarded as a venous channel, is connected with the anterior ciliary veins ; the communication thus established between the anterior chamber and the venous radicles is important as allowing the escape of the aqueous humor. 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 : (i) the pars optica retinse, including the entire posterior segment and end- ing at the ora serrata; (2) the pars ciliaris retinse, 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- tinse, 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 retinse, 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-epitlielial and the cerebral layer. The relations of these divisions to the individual retinal layers may be expressed : Layer of rods and cones ; 1 B Neuro.epithelial Limiting membrane ; layer Outer nuclear layer ; II. Inner layer of optic Outer reticular layer ; vesicle. | Inner nuclear layer ; Inner reticular layer ; Ganglion-cell-layer ; Nerve-fibre-layer. C. Cerebral layer. 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 352 NORMAL HISTOLOGY. fibres of Miiller, 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 nai row irregular stalks giving 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 ; ff, layer of ganglion-cells ; /, fibre-layer ; K, limitans interna. a, supporting fibres of Miiller; b, c, rod- and cone- visual cells; d, bipolars belonging to rod-cells ; e—i, bipolars belonging to cone-cells ; k-in, horizontal nerve-cells ; n, centrifugal nerve-fibres ; o-t, ganglion-cells connected with optic fibres ; a-e, spongioblasts or amacrines arranged in layers ; £, $, 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. 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 M), 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 (£) an outer layer of the rod- and cone-bipolars forming the ganglion retinse. 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 M til- ler's fibres (y) ; b, fibre-layer; c, layer of ganglion-cells (z) ; d, e, inner reticular and inner nuclear layer ; f, g, 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. 354 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 fibrillse 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 fj. in length and 2 p. 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. 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 356 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 ft) 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 tne 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 External surface FIG. 378. M 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 ; z>, section of a blood-vessel ; M, 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. 358 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. B Section of human retina through ora serrata : A, B, visual and ciliary portion of retina; a, vacuoles; b, robust fibres of Miiller; 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 Miiller, 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- c o m e 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 /i), 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. Occasionally the medullated fibres retain their medullary substance after their passage through the lamina cribrosa, such conditions presenting very striking ophthalmoscopic appearances. Transverse section of human optic nerve : d, dural sheath : a, arachnoidean sheath ; /, pial sheath; n, bundles of nerve- fibres separated by fibrous septa (e). FIG. 381. Section of human optic nerve under higher magnU fication : b, bundles of nerve-fibres enveloped in con- nective-tissue sheaths (jc) ; n, neuroglia nuclei; xt nuclei of interfascicular connective tissue (/); v, blood- vessels. 360 NORMAL HISTOLOGY. The lamina cribrosa consists of five to eight lamellae, composed of transversely extending fibrous trabeculse, 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 a1 ' , a! ; b, layers of retina terminating at edge of optic papilla ; c, choroid ; d, sclera, continued across optic nerve as lamina cribrosa ; e, g, t, respectively pial, arachnoidean, and dural sheaths, including subdural and subarachnoidean lymph-spaces; /, I', 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. 361 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 /* 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. 362 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 fJL 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 FIG. 384. 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 of 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 120° down and outward ; in the posterior star the rays form an angle of 60° with those of the anterior surface, so that the figures of both surfaces THE EYE AND ITS APPENDAGES. 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 /-O 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 (/) ; f, connective tissue of ciliary processes (g) ; h, canal of Schlemm ; k, trabeculae 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) ; s, spaces of Fontana ; t, 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 fibrillse 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 foetal 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. 366 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 : 1. 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. 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 palpebrse, which are partly inserted into the areolar tissue — fascia palpe- 368 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. :m 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 ; /, Moll's glands; tn, tn, cut fibres of orbicular muscle ; m1 ', 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. 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 . i 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 is less squamous in type and resembles 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 NORMAL HISTOLOGY. Additional minute lymphoid nodules and mucous glands occur within the conjunctival fornix. The ocular conjunctiva pre- sents changes in the vicinity of the transitional folds, where the epithelium loses its columnar character and assumes the stratified squamous type in its further extension. 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 conjunctivse 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. ^l 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- 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. , . ., 111 Section of human lachrymal gland: The nerves distributed to the glandu- a> acini> limited by basement-mem- lar tissue pass between the acini and form branes (»*) and lined by secreting ceils (P-) ; /, 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 B Section through head of ten-day rabbit em- bryo, exhibiting primary optic vesicle (O) 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 FlG- 388. FIG. 389. 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, 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. Sagittal section through developing eye of eleven- Trie Retina. The layers Of and-a-half day rabbit embryo, exhibiting choroidal . . fissure (C) through which mesodermic tissue (m) the OptlC Vesicle Very SOOn ex- reaches interior of secondary optic cup : o, i, outer hibit marked difference in their and inner layers of 0Ptic veside : *> lens-sac- 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 FIG. 390. 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 ar^ 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. 375 FIG. 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 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 tunicae vas- culosse. 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 (p) nearly effaced by apposition of invaginated anterior segment (r> with posterior wall (/)) ; /, lens-sac, com- pletely closed and separated from ecto- derm ; t, tissue within secondary optic cup derived from surrounding meso- derm (/«). NORMAL HISTOLOGY. of the rudimentary portions of the optic cup, whose double-layered lip corresponds in position with the pupillary margin. The vitreous humor is derived from the mesodermic tissue occu- pying the interior of the optic cup. FIG. 392. This tissue appears very early, in consequence of the ingrowth of the mesoderm through the cho- roidal fissure ; the early vitreous possesses delicate branched cells as well as numerous blood-vessels, and corresponds to soft embry- onal connective tissue ; later the corpuscles and blood-vessels dis- appear and the mass assumes its characteristic semi - fluid almost structureless condition. The pe- ripheral zone of the vitreous un- dergoes condensation and forms the hyaloid membrane, which in the ciliary region becomes thick- ened and constitutes the suspen- sory ligament of the lens, or the zone of Zinn. The eyelids develop as folds of integument above and below the corneal area ; these grow towards one another and finally fuse, all epidermal demarcation for a time disappearing. Shortly b e f o r e birth the centre of the epithelial layer undergoes degeneration and the lids become permanently separated. The epithelium of both the tegumentary and conjunctival sur- faces is derived from the ectoderm, as are also such epidermal appendages as the hairs and the glands, the Meibomian glands corresponding to sebaceous follicles in their formation. Section through developing eye of thirteen- day rabbit embryo : e, ectoderm ; /, lens, con- sisting of anterior nucleated division repre- senting thin front wall of lens-sac and greatly thickened posterior division, completely filling cavity of sac by elongated fibres whose nuclei present crescentic zone («) ; /, posterior pig- mented layer; r, specialized anterior retinal layer ; i, point where layers of optic vesicle be- come continuous ; n, extreme peripheral section of tissue of primitive optic nerve connected wiih vascular tunic (v) occupying posterior surface of lens; m, surrounding mesoderm, which at t grows between lens and retina. THE ORGAN OF HEARING. -~~ CHAPTER XVIII. THE ORGAN OF HEARING. t THE complicated organ of hearing of man and the higher animals, reduced to its essential factors, consists of two parts, — the system of intercommunicating epithelial tubes, certain parts of whose walls are differentiated into special structures for the perception of the sound- waves, and the elaborate conducting apparatus for the transmis- sion, direct and indirect, of the sound-impulses to the perceptive structures. THE EXTERNAL EAR. The external ear, including the pinna and the external audi- tory canal, possesses a bony or cartilaginous -basis over which extend the integument and a layer of subcutaneous tissue. The cartilage is of the yellow, elastic variety, forming a thin, tough, yielding plate, displaying the various depressions and elevations seen on the outside ; the lobule, however, contains no cartilage, but only tough fibrous tissue and fat. The skin covering the pinna corresponds with the surrounding integument ; within the auditory canal, however, it presents some change. The skin covering the cartilaginous division of the meatus, together with part of the roof of the bony division, is char- acterized by its thickness, the subcutaneous tissue also constituting a layer of considerable depth, which includes some fat and many bundles of dense fibrous tissue. Fine hairs, with relatively very large sebaceous glands, occur in all parts of this surface, as do also the ceruminous glands, which constitute conspicuous structures and closely correspond to the glands of Moll within the eyelid, being, like them, modified sweat-glands. Their long, narrow ducts during early life open with the sebaceous glands into the hair-follicles, but later acquire independent orifices. The ceruminous glands pos- sess a well-marked basement-membrane, within which lies a single layer of cuboidal epithelial cells, with a thin, longitudinal stratum of non-striped muscle-cells interposed. The secreting cells contain numerous brown particles, but the presence of fat is question- able, the fatty constituents of the cerumen being probably contributed by the adjoining sebaceous glands. The coiled masses of the gland- tubes are situated within the subcutaneous tissue, where they some- times reach as far as the cartilage or the bone. NORMAL HISTOLOGY. The skin covering the greater part of the bony canal, on the contrary, is very thin and intimately united to the periosteum. Hairs and glands are want- FIG. 393. ing in this part of the canal, as they are also in the integument reflected over the external sur- face of the tympanic membrane. The membrana tympani consists of three layers : (i) the central ground-stratum, or lam- ina propria, composed of fibrous connective tissue, (2) the cutaneous layer reflected over the external surface of the drum, and (3) the mucous layer covering the inner side of the membrane as the repre- sentative of the lining of the tympanic cavity. The tegumental layer con- sists of the usual epidermis and connective- tissue corium, the latter being only about half as thick as the epithelial layer. Section of bony portion of human external audi- tory canal : s, cutaneous layer closely united with periosteal fibrous tissue ; o, osseous tissue of wall. (After Rudinger.} The central connective-tissue ground-plate, or lamina pro- pria, constitutes the fibrous basis of the tympanic membrane and represents its mesodermic portion. This layer consists of closely- felted bundles of fibrous tissue arranged as two strata, the outer or radial fibre-layer, composed of fibrous bundles, which in their general course radiate from the periphery of the tympanum towards the point of attachment of the head of the malleus, and the inner or circular fibre-layer, consisting of concentrically-disposed bundles, whose greatest development is at the periphery in the vicinity of the annular attachment of the membrana tympani. The mucous layer is a part of the general lining of the middle ear, and consists of a thin connective-tissue tunica propria or groundwork, composed of delicate bundles of fibro-elastic tissue, upon which rests the epithelium ; the latter consists of a single layer of low cuboidal polyhedral cells without cilia. The blood-vessels supplying the tympanic membrane are derived from two sources, the one set proceeding from the branches of the external auditory canal to end in capillaries which ramify within the THE ORGAN OF HEARING. 379 cutaneous layer, the other group coming from the vessels of the tympanic cavity to break up into the net-works distributed to the mucous layer. The lymphatics of the tympanum correspond in their arrange- ment with the principal strata of the membrane. In the corium of the skin-layer lies a close net-work of capillary lymphatics ; these increase in size towards the periphery, where they are collected into larger trunks, which in turn empty into the lymphatic channels of the FIG. 394. Section through human malleus and tympanic membrane : i, 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 nbro-cartilage. (After Rudinger.) 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 380 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 //) 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 trabeculse 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 //.) 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 . i 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. by a single layer of low polyhedral cells, is very thin and inti- mately united with the delicate periosteal layer ; numerous fibres, trabeculae, 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 layer 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 FIG. 395. 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 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 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 tubae 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. 383 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 fibro-elastic tissue, whhch 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 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 cribrosae and acusticse 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 fJL. 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. Section through membranous labyrinth of cat, showing specialized areas within ampulla (A) and utricle (B) : a, surrounding bony wall separated from membranous tube (d) by layer of areolar trabeculse (d) ; c, crista acustica covered with specialized epithelium (/); e, e' , bundles of nerve-fibres; g, ordinary epithelium; h, layer of otoliths overlying neuro-epithelium of macula acustica (f) ; /', 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. columnar, and progressively increase in length until they measure 30—35 t*. 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 V- l°ng) projects into the endolymph ; this conical process, how- ever, is resolvable into a number of agglutinated finer hairs or rods. The free surface of the neuro- epithelium within the saccule and the utricle is covered by a remark- able structure, the so-called otolith membrane. This consists of num- berless small crystalline bodies, the otoliths, or ear-stones, embedded within a soft gelatinous ground-sub- stance. The otoliths are minute crystals of calcium carbonate, 1-15 /* length, usually six-sided prisms in Section of wall of utricle through mac- ular region, from rabbit, showing otoliths (a) embedded within granular substance (g) : h, hair-cells with processes (/) ex- tending between sustentacular elements (s) ; n, nerve-fibres within fibrous tissue (/) passing towards hair-cells and be- coming non-medullated at basement- membrane (m). with slightly-rounded angles. The nerve-fibres proceed to the acoustic areas and unite beneath the epithelial 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 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 acusticse. 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 FIG. 398. off numerous connecting bundles of fibrous tissue ; in other parts of the circumference of the canal only widely- separated , occasional trabeculae bridge across the perilymphatic space to aid in maintaining the position of the membranous tube. The inner surface of the periosteum, the tra- beculae, 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 cristse acusticse, 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- beculae (d, d) ; e, blood-vessel. THE ORGAN OF HEARING. 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 transverse ridge, or septum trans versum. 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 cristse 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- The sustentacular elements resemble those ^T"L^t± of the maculae of the saccule and the utricle, tissue supporting single extending the entire thickness of the epithelial l^LleiM^ 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 NORMAL HISTOLOGY. 388 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 (, 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. 399 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 FIG. 407. NORMAL HISTOLOGY. 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 maculse 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- 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 (m), within which large lymph-spaces later appear ; c, con- densed cartilaginous capsule ; n, bundles of nerve-fibres. THE ORGAN OF HEARING. 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 stapes is probably developed from the second visceral arch ; the peculiar form of the stapes results from the perforation of the original cartilaginous plate by a small artery which later disappears. 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. 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 Section through mucous membrane of respiratory region of child's Wnicn nose: a, ciliated epithelium; b, tunica propria; c, submucous con- SfOblet-CClls are nective tissue ; d, mucous glands ; e, duct of glands opening on free . —,, surface ; s, biood-vesseis. interspersed. The tunica propria of this region is composed of fibrous-1 connective tissue containing clefts occupied by many leucocytes, me 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 THE NASAL MUCOUS MEMBRANE. 403 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 Section through olfactory mucous membrane from child's nose : at 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. 405 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 fibrillse enclosed within the neurilemma ; on reaching the epithelium the fibres break up into their component fibrillae, which pass as naked, often varicose, axis- cylinders towards the elements of the neuro-epithelium. The olfac- tory nerve-fibres are connected peripherally with the olfactory cells within the nasal mucous membrane. After passing into the cranium they terminate in rich arborizations in relation to the peculiar glomer- uli already noted in connection with the olfactory lobe. 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. 4C>6 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 H1STOLOG1CAL 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 vvill 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 : 1. Fixation of the tissue. 2. Preservation of the fixed tissue. 407 408 . 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. i. 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. Miiller's Fluid. Potassium bichromate 2.5 gm. Sodium sulphate i.o gm. 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 Muller'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 Muller'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 Muller* s fluid, being kept in an oven from 8 to 10 days at a temperature of 35° 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 may be cut within 24 hours. Small pieces of tissue, so placed either by 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 4io 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 Miiller'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 decalcijication and softening ; APPENDIX. 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 h&matoxylin stand pre-eminent on account of their general applicability and their certainty. The relative merits of carmine and hsematoxylin 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 formulae, 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"1 s h&matoxylin, given below, which answers admirably for bulk-staining. The liability to fade, the possibility of overstaining, and the necessity of using water for differentiation are among the disadvantages of hsematoxylin 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- 412 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 (Grenacher). Carmine, best . 2.5 gm. Borax 4.0 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. 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 Haematoxylin. (1) Haematoxylin, 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 i 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 overstaining 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. 414 APPENDIX. c. Alum-Hsematoxylin (Bohmer). (1) Haematoxylin, crystals 35 gm. (2) Alcohol, absolute 10 c.c. (3) Potash-alum 10 gm. (4) Water, distilled 30 c.c. Dissolve i 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 blue, 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 i 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 and 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. 4! 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 50° 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 50° 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 55° 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. 416 APPENDIX. tissues at a temperature whose variations are included within the limits of 50° to 52° 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 no 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. 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 41 8 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 i 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. 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 entire length of the blade 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. 42O 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 expansion 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 arable {Flogel- Schultze) and collodion-clove oil (Schallibaum) mixtures. The gum-arabic method is carried out as follows : of a saturated 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 c.c. 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 422 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. 423 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, pressure, 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. 1. 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 50° 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. 1 6. Fix sections to slides by gum or collodion-clove oil. 17. Remove paraffin by benzole, succeeded by turpentine. 1 8. 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 c 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 hamatoxylin 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 uniil 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 i part ; Solution of Rochelle salt ( 10 per cent.) i part, for 24 hours in oven at 40° C. b. Transfer to — Saturated solution neutral cupric acetate i part ; Distilled water i part, for 24 hours. 426 APPENDIX. c. Transfer to 80 per cent, alcohol — ^-i hour. ci. 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. HaO) 7 c.c. I Distilled water „ 100 c.c. TJ f Haematoxylin, crystals i gm. \ Absolute alcohol 10 c.c. e. Stain sections for 12 to 24 hours in mixture composed of 9 volumes of A -\- i 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. -j- xylol i 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.) ....... 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 i part, and mounted in balsam ; cover with cover-glass. APPENDIX. 427 Even in successful preparations only a limited number of cells will be well shown ; this, however, is rather an advantage than otherwise, since diagrammatic pictures are obtained of the various elements in turn. The method is an impregnation, not a true stain, defining outline, but not histological structure. The method is also applicable to the demonstration of minute canals, as the bile capillaries and glandular ducts. 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 translucent — usually 15—25 minutes. b. Transfer Gold chloride .5 gm. Water, distilled 100 c.c. for 25 to 45 minutes ; rinse off in distilled water. c. Transfer to i 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 absolutely 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 — a. 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 (^-i minute) until the clouds of color cease to be copiously given off; then— d. Transfer to fresh absolute alcohol for i 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. carmine solutions. One of the most convenient and efficient inject- ing fluids is — Soluble Berlin blue (Grubler) 3 gm. Distilled water 600 c.c. This fluid runs well, does not extravasate, and may be used cold ; perfectly fresh animals, immediately after killing, are the most favor- able subjects for the manipulation. A smoothly-working hand- syringe (200-300 c.c. capacity), with appropriate stop-cock and can- ulse, 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. A. 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, in. fibrin, in. granules of Max Schultze, in. haematoblasts, in 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. Blocd-crystals, in. -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 lamellae, 48 compact, 47. development of, 51. endochondral formation of, 52. ground lamellae, 48. Haversian canals, 48. Haversian spaces, 54. Howship's lacunas, 56. interstitial lamellae, 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 43' 432 INDEX. 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. 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 haematoxylin, 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. Miiller'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. cristae acusticae of semicircular canals, 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 of maculae acusticae, 385. internal, 383. ligamentum spirale, 389. maculae acusticae of, 384. mastoid cells, epithelium of, 380. membrana tectoria, 395. membrane of Reissner, 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 endolymphaticus, 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, u. Embedding, interstitial, 414. simple, 414. Embryonal cell, n. 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, 350 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, viireous 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. G. 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. hemolymph, 122. lachrymal, 371. Lieberkiihn'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 tendinese, 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. Hemolymph glands, 122. Howship's lacunae, 56. Hyaloplasm, 13. Hydatid, sessile, 244 stalked, of Morgagni, 230. Hypophysis cerebri, 328. 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. Lieberkiihn'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, 1 68, 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, 20:1. sinus of, 201. tubes of Bellini, 195." uriniferous tubules of, 195, 196. Kleinenberg's solution, 410. Krause's views regarding muscle, 63. L. Labia majora, 236. minora, 236. Lachrymal canals, 371. gland, 371. Lanugo, 280. Larynx, 246. blood-vessels of, 248. cartilages of, 248. }ymphatics of, 248. nerves of, 248. vocal cords of, 246. Leucocytes, 105. Lieberkiihn's follicles, 170. Ligamentum nuchae, 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, 1 1 8. 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, 230. galactophorous ducts, ^40 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, 83. 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, HI. 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 of, 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. Nebenkern, 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, 93. 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 framework ot 79. Neuroblasts, 81, 333. Neuro-epithelium, 93. Neuroglia, 79. cells, 79. Nipple, 240. sNucleolus, 14. Nucleus, 13. caudatus, 319. fibrils of, 13. lenticularis, 320. membrane of, 13. segmentation, 23. structure of, 13. Nymphae, 236. CEsophagus, 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. Penonyx, 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, 269. 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 coeruleus, 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, I'j structure of, 12. Purkinje's ganglion-cells, 308. basket-works of, 310. R. Reissner's membrane, 389. Reproduction of the cdH, 15. Reproductive organs, table of homologies of, 245 Respiratory organs, 246. Rete Malpighii, 262. Ribbon sections, 420. Rollett's views regarding muscie, 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. 438 INDEX. Skin, hair-follicles, 269. hair-papillae, 272. lymphatics of, 276. muscles of, 272. nerves of, 277. panniculus adiposus, 265, papillae of, 264. pigment of, 263. sebaceous glands, 273. stratum corneum, 263. stratum granulosum, 263. stratum lucidum, 263. stratum Malpighii, 263. structure of hairs. 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 antero-lateral, 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. T. 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, 146. membrane of Nasmyth, 148. odontoblasts, 152. pulp, 148. Schrager's lines, 147. stripes of Retzius,.i48. 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 of, 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, n. elements of, 23. Tongue, 153. blood-vessels of, 156. glands of, 156. lymphatics of, 156. mucous membrane of, 152. nerves of, 156. papillae 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. V. Vagina, 235. development of, 244. Vas deferens, 213. ampullae of, 213. Vasa vasorum, 99. Veins, 97. adventitia of, 98. intima cf. 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. THIS BOOK IS DUE ON THE LAST DATE STAMPED BELOW AN INITIAL FINE OF 25 CENTS WILL BE ASSESSED FOR FAILURE TO RETURN THIS BOOK ON THE DATE DUE. THE PENALTY WILL INCREASE TO 5O CENTS ON THE FOURTH DAY AND TO $1.OO ON THE SEVENTH DAY OVERDUE. SEP 1 8 1940 MAR - 7 1949 AUG 29 1932 16 1933 F, MAY 5 V" MM* 21 '935 AlH^B •51 OCT 14 '935 FEB221938 5 1938 MAY MAY 3 - '949 NOV 2 3 1951 J) BIO. UNIVERSITY OF CALIFORNIA LIBRARY*'1