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A TEXT-BOOK OF
HISTOLOGY

A TEXT-BOOK OF

H ISTOLOGY

BY

HARVEY ERNEST JORDAN, A.M., PH.D.

PROFESSOR OF HISTOLOGY AND EMBRYOLOGY, UNIVERSITY OF VIRGINIA

AND

JEREMIAH S. FERGUSON, M.Sc., M.D.

FORMERLY ASSISTANT PROFESSOR OF HISTOLOGY, CORNELL UNIVERSITY
MEDICAL SCHOOL, NEW YORK CITY

WITH FIVE HUNDRED AND NINETY-FOUR ILLUSTRATIONS IN THE TEXT,

AND FOUR PLATES

NEW YORK AND LONDON
D. APPLETON AND COMPANY

1916

COPYRIGHT, 1916, BY
D. APPLETON AND COMPANY

PRINTED IN THE UNITED STATES OF AMERICA

PREFACE

In the preparation of this text-book of Histology we have kept fore-
most in mind the needs of medical students as we have come to under-
stand them in our experience as teachers of the subject. These needs
have been suggested by the common difficulties we have discovered on
the part of the average student. It has been our effort to lessen these
difficulties in the most practical way. Our experience has demonstrated
to us the efficacy of the methods here pursued.

The bulk of the subject matter of Histology is now relatively stable.
With respect to this nucleus our problem has largely been one of the best
means of presentation. The secret of success in the acquisition of his-
tologic data is of course fundamentally an interest in the subject. In-
terest can best be stimulated by a revelation of relationships to future
more clearly conceived practical ends; and it can best be sustained by
the possession of principles and generalizations that serve at least pro-
visionally to coordinate the mass of seemingly unrelated facts. These
considerations force an approach to the subject of Histology largely from
the viewpoint of function. The known or believed function dependent
upon the structure described is therefore briefly indicated whenever this
seems desirable. With the same e^d in view comparative anatomic and
embryologic facts are frequently presented.

Since Embryology usually constitutes a separate course of the med-
ical curriculum, the development of tissues and organs is discussed only
to the extent deemed absolutely essential for a proper appreciation of
structure. Since the anatomy of the Nervous System likewise properly
constitutes a separate course, only the nervous tissues are here described,
including the microscopic structure of the spinal cord, the cerebral cor-
tex and the cerebellar cortex. A description of the structure of the
brain stem is not included. An effort has been made to include the
results of the latest investigations especially as regards cytologic data,
particularly in relation to the genital glands. The organs of internal
secretion are treated under a single head, and rather more fully, in view
of their now evident importance, than has hitherto been the case.

The illustrations have been taken from various sources, duly cred-

PKEFACE

ited including more than 300 originals our one object having been
to best elucidate the structures described. Photomicrographs of actual
sections, combined with interpretive drawings and diagrams, appear to
us the ideal illustrative procedure.

The majority of the photomicrographs are taken from Ferguson's
"Normal Histology and Microscopical Anatomy." For a number we are
indebted to our friend and colleague, Professor Albert H. Tuttle of the
University of Virginia.

An attempt is made to adapt the book somewhat to prevailing non-
uniform demands, by putting the more essential and what we regard as
additionally desirable in different type.

References to the recent literature are inserted for the student who
may wish to consult the more important original works upon which the
later developments of Histology have advanced.

We gratefully acknowledge our indebtedness for illustrations and
data taken from the recent and earlier literature, and our obligations to
the publishers for their kindly help and courtesy.

HARVEY ERNEST JORDAN
JEREMIAH S. FERGUSON.

CONTENTS

CHAPTER PAGE

I. INTRODUCTION PROTOPLASM CELL ..... 1

II. EPITHELIAL TISSUES . 30

III. CONNECTIVE TISSUE CARTILAGE BONE .... 49

IV. MUSCULAR TISSUE ..... 90

V. NERVOUS TISSUES . ...... 119

VI. PERIPHERAL NERVE TERMINATIONS END ORGANS . . . 159

VII. THE BLOOD VASCULAR SYSTEM 176

VIII BLOOD 203

IX. THE LYMPHATIC SYSTEM ...... 225

X. Mucous MEMBRANES GLANDS . . . . . .251

XI. THE SKIN . 262

XII. THE RESPIRATORY SYSTEM ....... 292

XIII. THE DIGESTIVE SYSTEM .... . 320

XIV. THE URINARY SYSTEM ... . 423

XV. THE REPRODUCTIVE SYSTEM . 455

XVI. THE DUCTLESS GLANDS : ENDOCRIN GLANDS . . 548

XVII. THE NERVOUS SYSTEM 587

XVIIL THE EYE 626

XIX. THE EAR . .... .682

XX. HISTOLOGIC TECHNIC 720

LIST OF ILLUSTRATIONS

FIGURE PAGE

1. Various spheroidal cells ........ 1

2. Ameba proteus in motion ....... 3

3. Paramecium caudatum .... ... 4

4. A generalized cell ......... 5

5. A unicellular flagellate animal (Tetramitus chilomonas) . . 6
6. Egg of a clam (Cumingia tellinoides) . . 7

7. Primary spermatocyte of a turtle (Cistudo Carolina)
8. Spermatid of opossum in early stage of metamorphosis into a sper-
mium .......

9. Cells from the newly-hatched rainbow trout, treated according to
Meves' technic for the demonstration of mitochondria (plasto-
somes) ........ .9

10. Two cells from the mesenchyma of the newly-hatched rainbow trout 9
11. Intracellular network, or ' trophospongium ' within a Purkinje cell

of the cerebellum of Strix flammea . . 10

12. Diagram illustrating the various theories of protoplasmic structure 11
13. Egg of the blood starfish (Henricia sanguinolenta) in later growth

period ...... 11

14. Pancreas cell of turtle, filled with zymogenic granules . . 12

15. Motor nerve cell from the ventral horn of the spinal cord of the ox 12
16. Interstitial cell from the testis of a twenty-one year old man.

Showing granular and filamentous mitochondria . . 13

17. A neuron (giant pjo-amidal cell, or cell of Betz) from the cerebral

cortex of man, showing the neurofibrils ..... 13

18. Developing fat cells . . . . . . . .13

19. Columnar ciliated epithelial cells. Showing canalicular apparatus 14
20. Successive stages in the movement of an ameba . 15

21. A leukocyte from human blood in active ameboid motion . . 16
22. Three cells from the epididymis of the rabbit . . . .16

23. Ciliate and flagellate cells .... 17

24. Successive steps in amitotic division in tendon cell of new-born

mouse ........ 18

25. Successive stages in the amitotic division of the ciliated cells lining

the vasa efferentia of the epididymis of the mouse . . .19

ix

x LIST OF ILLUSTRATIONS

FIGURE PAGE

26. Multinuclcated giant cell, from the yolk-sac of a 10 mm. pig embryo 19
27. Spermatocyte of Pyeris crategi, a butterfly, showing a cilium at-
tached to the centrosome ...... 20

28. Diagrams illustrating successive stages of mitosis ... 21

29. Cells from epidermis of the salamander ... 22

30. Successive stages of mitosis in the root tip of the dogtooth violet

(Erythronium americanum) . 23

31. Successive stages in the maturation, fertilization and segmentation

of the star-fish (Asterias forbesii) egg . . . 26

32. Transverse section of a frog embryo, showing the three germ layers 27
33. Group of epithelial cells from the Malpighian layer of the skin 30

34. A villus of the human placenta, showing a peripheral syncytium of

irregular thickness . . . . . 31

35. Cells from the pancreas of Necturus, containing secretory granules

and basal ergastoplasmic filaments . . 31

36. Various forms of cells ........ 31

37. Polyhedral epithelium, from a section of the human liver . . 32
38. Goblet and columnar cells from the large intestine of the cat . . 32
39. Columnar epithelium from the pyloric region of the human stomach 33
40. 'Terminal bars' of cement substance as seen between the epithelial
cells of a tubular secreting gland in the pyloric region of the
human stomach . 34

41. Semidiagrammatic illustration of endothelium lining a large artery 37
42. Mesothelium (surface view) from the mesentery of a rat . . 38
43. Cuboidal epithelium from the rete testis of the rabbit ... 39
44. Tip of a villus of the synovial membrane from the knee-joint of an

old man ..... . 39

45. Columnar ciliated epithelium from the epididymis of a rabbit . 40
46. A group of cells from a transection of an acinus of the human pan-
creas; glandular epithelium . 41
47. Goblet cells as seen in a transection of a crypt of the large intestine

in man ........ 42

48. Diagram showing the arrangement of the columnar and goblet cells

of figure 47 . . 42

49. Stratified epithelium from the human esophagus . . 43

50. Epidermis of the skin of the finger tip, showing extreme keratization

of the epithelium . . ...... 45

51. Pseudostratified columnar ciliated epithelium from a bronchial tube

of man .......... 46

52. Diagram showing the manner in which all the epithelial cells of
pseudostratified ciliated epithelium reach the basement mem-
brane ...... . . 46

53. Transitional epithelium from a transection of the ureter of an infant 47

LIST OF ILLUSSTEATIONS x j

FIGtTRB PAGE

54. Isolated cells which may appear in human urine . 48

55. Embryonal connective tissue, early stage . 49
56. Embryonal connective tissue at a later stage than is represented in

figure 55 49

57. Subcutaneous areolar connective tissue of guinea pig . 50

58. Plasma cells of connective tissue from the human breast . 51
59. -Spindle-shaped connective tissue cells from the stroma of the human

ovary ... 51
60. Pigmented cells from the choroid coat of the ox's eye . 52
61. Granule cells from the fibrous connective tissue of the human mam-
mary gland .... . 52
62. Gelatinous connective tissue from the umbilical cord of a new-born

infant ... 54
63. Reticulum of a cervical lymph node of man, from a thin section from

which the lymphatic corpuscles had been partially washed out . 55
64. Dense fibrous tissue from the tendon of one of the ocular muscles of

a child . 57
65. Longitudinal section of tendon of human finger . . 58
66. Portion of tendon from a cow . 58
67. Transverse section of portion of tendon of human finger . 59
68. Piece of tendon from tail of white mouse . ... 59
69. Isolated tendon cells ... 60
70. Coarse elastic fibers from the ligamentum nuchae of the ox . .60
71. Transection of a fasciculus of the ligamentum nuchae of the ox,
showing the very large elastic fibers embedded in a very delicate
network of collagenous fibers . 61
72. Portion of ligamentum nuchae of ox . 61
73. Portion of a fat lobule from the areolar connective tissue surround-
ing the esophagus of a cat 62
74. A group of fat cells from the subcutaneous tissue of a young rabbit 63
75. Fat cells from a teased preparation of adipose tissue of man 63
76. Adipose tissue . 64
77. Developing adipose tissue from the subcutaneous tissue of an infant 64
78. Reticulum from the mucosa of the f undus region of the dog's stomach 65
79. Section through a small lymph gland of a dog 65
80. From a section through the medulla of a cervical lymph node of man 66
81. Transection of a plate of hyaline cartilage, from the trachea of a

child . 68
82. Cells and matrix of hyaline cartilage from the wall of a large bronchus

of man ... 69
83. Elastic cartilage from the human epiglottis, showing the large ovoid

cartilage cells and the very delicate reticulum of elastic fibers 70

84. Fibrocartilage, showing a group of oval cartilage cells ... 71

Xii LIST OF ILLUSTEATIONS

FIGURE PAGE

85. Notocbordal tissue . ...... 72

86. Transection through the compact bony wall of a human meta-

carpal bone ...... 73

87. Longitudinal section of ground bone from the shaft of the human

femur . . . . ... 74

88. Isolated bone cell shrunk away from wall of its lacuna . 75

89. An Haversian system, including the central canal, several lamellae,

lacunae and canaliculi .... ... 75

90. Transverse section of Haversian canal, with contents ... 76
91. The primary changes in intracartilaginous bone formation . . 80
92. A longitudinal section of the two distal phalanges from the finger

of a five-months' human fetus . . ... 81

93. Reconstruction of cartilage into bone ..... 82

94. Trabecula of primary enchondral bone, showing a central deep-
staining core of calcified cartilage and a peripheral layer of osteo-
blasts . ... .83

95. Trabecula of primary bone from the finger of a human fetus 84

96. Intramembranous bone formation in the lower jaw of a sheep fetus 87
97. Smooth muscle cells ........ 91

98. Smooth muscle cells from the pig's stomach .... 92

99. Smooth muscle cells from the wall of the human intestine . . 92
100. Smooth muscle cells from the wall of the human intestine . . 93
101. Two stages in the histogenesis of smooth muscle, from the wall of

the esophagus of a pig embryo . . . .94

102. A group of myoblasts from the heart muscle syncytium of a 48-hour

chick embryo ......... 95

103. Cardiac muscle of guinea-pig, showing several branches, cross

striations (ground membranes) and a number of intercalated disks 95
104. Cardiac muscle cells from the pig's heart, isolated in equal parts of

alcohol, glycerin, and water ...... 96

105. Cardiac muscle of the human heart; the abundant branches are

plainly shown ... 97

106. The central portion of figure 5, more highly magnified ... 98
107. Transection of a group of cardiac muscle fibers from a papillary

muscle of the human heart ... . .98

108. Developing muscle fibers from the heart of a human fetus at

seven months ... ... 99

109. Cardiac muscle fibers ... . 100

1 10. Diagram of a striped muscle fiber, according to Heidenhain . . 101
111. Six-lobed nucleus from the heart muscle of Limulus, showing the

continuity of the nucjear wall with the telophragmata . . 101
112. Seven nuclei, the product of amitotic division, lying in an undifferen-

tiated mass of sarcoplasm, from the heart of Limulus . . 102

LIST OF ILLUSTEATIONS xiii

FIGURE PAGE

113. Longitudinal section of a trabecula of Limulus (King crab) heart
muscle, showing an intercalated disk separating a contracted
from an uncontracted portion . 103

114. Semidiagrammatic illustrations of various types of intercalated disks 104
115. Successive stages of skeletal muscle histogenesis in mammals . 105
116. Transverse section of a striped muscle fiber of a newly-hatched rain-
bow trout, showing the process of myofibril increase by radial
longitudinal splitting . . . . . . . .105

117. Striated muscle fibers ruptured by teasing, showing the sarcolemma 106
118. Isolated fragments of striated muscle fibers, unstained . 107

119. Striated muscle fibers of the dog, seen in transection . . 107

120. A portion of a striated muscle fiber seen in longitudinal section . 108
121. A small portion of a muscle fiber of a crab showing beginning separa-
tion into fibrils . . ... . 108

122. Fibrils from the wing muscles of a wasp . . . 109

123. Longitudinal section of a portion of a striped muscle trabecula of
Limulus, showing a nucleus of serrated contour with the telo-
phragmata attached to the serrations . . . 109

124. Striated fiber from a leg muscle of the sea spider (Anapodactylus
maxillare), showing the complexly striped condition characteristic
of insect muscle ..... .110

125. Semidiagrammatic drawing, representing the appearance of the
same fiber from the leg muscle of a beetle in ordinary and polarized
light .... .110

126. Lateral contractive wave of Cassida equestris . .111

127. Striated muscle fibers of the dog . . .112

128. Striated muscle of a cat seen in transection . . . .113

129. Motor end-plate on an intercostal muscle fiber of a young rabbit . 115
130. Portion of a transection of a large tendon . . .116

131. Transverse section of tendon of tail of adult mouse . 116

132. Portion of a muscle fiber from the tail of a 5 cm. frog tadpole . 117
133. Diagram of a neuron . . . 120

134. A unipolar ganglion cell of a frog ... .122

135. Multipolar ganglion cell from the ventral horn of the gray matter of

the spinal cord of the ox ... .122

136. Pyramidal multipolar nerve cell from the cerebral cortex of a mouse 123
137. Isolated nerve cells from the spinal cord of man . .1:24

138. Various types of nerve cells of the cerebellar cortex . . 125

139. Three types of nerve cells supplying respectively cardiac (1), smooth

(2) and (3) striated muscle . .126

140. A nerve cell from the trapezoid nucleus in the midbrain of a rabbit 127
141. A neuron (giant pyramidal cell, or cell of Betz) from the cerebral

cortex of man, showing the neurofibrils . . . . .128

Xiv LIST OF ILLUSTRATIONS

FIOURE PAGE

142. Intracellular network (trophospongium) within a Purkinje cell of

the cerebellum of Strix flammea ... . 128

143. Golgi cell, type I ... 129

144. Golgi nerve cell, type II ........ 130

145. Isolated nerve fibers from a frog ...... 133

146. A small portion of a transect ion of the sciatic nerve of a dog . . 134
147. A group of large meclullated fibers from a nerve in the peritracheal

areolar tissue of the cat . . . . . . .134

148. Nerve fibers . 135

149. Cross and longitudinal sections of the same funiculus of non-
medullated nerve fibers (turned up at the left), showing the
perineurium and the relationship of the neurolemma nuclei to the
axis cylinder bundles of neurofibrils . . . 136

150. Cross-section of the trunk of the human vagus -nerve, some distance
below the nodose ganglion, showing medullated and non-medul-
lated fibers . . 137

151. Successive stages in the degeneration process exhibited by the distal
stump of a medullated axon (from sciatic nerve of adult dog) fol-
lowing section ......... 138

152. Regenerative stages in the proximal stump of the cut sciatic nerve

of the dog, several millimeters above the level of section . .139
153. Transection of the spinal cord of an embryo chick . . . 140
154. Transection of the spinal cord of a child, fifth lumbar segment . 141
155. Portion of gray substance from the anterior horn of the spinal cord
of man, showing nerve cell bodies, dendrons, medullated and non-
medullated portions of axons, and neuroglia .... 142

156. Transverse section through the white substance of the human spinal

cord . . . .142

157. Neuroglia from the spinal cord of a fetal pig .... 143

158. A long-rayed astrocyte . ..... 144

159. A short-rayed astrocyte, or mossy cell ..... 144

160. Neuroglia cell with adjacent fibers, from the pineal body of a yearling

sheep ... . 145

161. Neuroglia cells and fibers from the spinal cord of an elephant . 146
162. Transection of the sciatic nerve of a dog ..... 147

163. Diagram of the origin and relations of the peripheral motor and

sensory neurons . . . .... 148

164. Bipolar cell from a spinal ganglion . . . 149

165. Transformation of bipolar cells into unipolar cells in the Gasserian

ganglion of the pig . .149

166. Section through the dorsal root ganglion of the first thoracic nerve

of a cat .......... 150

167. A nerve cell from a section of a human Gasserian ganglion . . 150

LIST OF ILLUSTRATIONS xv

FIGURE PAGE

168. Schematic representation of the relations of the structures com-
posing a spinal ganglion . . 151
169. Common atypical, though probably perfectly normal, nerve cells

from the spinal ganglion of the dog . 152

170. Sympathetic neurons . . 154

171. The sprouting of an axon by a neuroblast from the spinal cord of

a frog embryo . . .156

172. The sprouting of an axon by a neuroblast from the spinal cord of a

frog embryo . 156

173. Nerve endings in the epithelium of the larynx . 160

174. Tactile cells in the epithelium of the groin of a guinea-pig . .160
175. Schematic representation of a taste bud . . . 161

176. Taste bud from the human tongue . .162

177. Tactile corpuscle of Meissner from the skin of the human toe . 163
178. Tactile corpuscle of Meissner .... . . 164

179. Tactile corpuscle of Meissner ..... . 164

180. Ruffini's end organ . . . .... 165

181. End bulb of Krause from the margin of the ocular conjunctiva . 165
182. Genital corpuscles from the clitoris of a rabbit . . .166

183. A lamellar corpuscle from the mesentery of a cat . . 166

1*4. A lamellar corpuscle from the pleura of a child . .167

185. Lamellar corpuscle from the mesentery of a kitten . 167

186. A lamellar corpuscle in longitudinal section, showing a network of

spiral elastic fibers . .168

187. Axial section of a corpuscle of Herbst from a duck's tongue . . 16S
188. A papilla of the duck's tongue, containing a corpuscle of Grandry . 169
189. Golgi-Mazzoni corpuscles from the subcutaneous tissue of the tip

of the finger . . . 170

190. Motor nerve endings in striated muscle . 171

191. A muscle spindle from the psoas magnus of man . 172

192. Middle third of a terminal plaque in the muscle spindle of an adult cat 17.'>
193. Neurotendinous end organ or tendon spindle of Golgi . . 174

194. Nerve endings in cardiac muscle, from the heart of a cat . 17.")

195. Nerve endings in smooth muscle, from the intestine of a cat . .175
196. A small artery from the connective tissue of the anterior cervical

region of man . . . . . . . . .177

197. The external carotid artery of a child . . . .179

198. Transection of the wall of the aorta of a child .... 179

199. Part of a cross-section of the femoral art cry of a dog . . . 180
200. Transection of the celiac axis of man .... 181

201. A group of small blood-vessels . . 182

202. Semi-diagrammatic illustration of small branch of pulmonary artery

of ox . . 183

1

XVI LIST OF ILLUSTRATIONS

FIGURE PAGE

203. Semi-diagrammatic illustration of dividing small branch of pul-
monary artery of guinea-pig . ... 183

204. The capillary network connecting an arteriole and venule of the

omentum of a young rabbit . . . 185

205. Capillary vessel of the frog's mesentery . . . 185

206. Two sinusoidal vessels from the medulla of the human adrenal . 186

207. Precapillary venule and arteriole . . 187

208. Transection of an arteriole and venule .... 188

209. Transection of the wall of the human vena cava . . . 189

210. A 13 mm. human embryo . 192

211. ' Vasof ormative ' cells from the mesentery of a rabbit seven days old 193

212. The parietal layer of the pericardium of a child . . 196

213. The endocardium . 197

214. Radial sections of the mitral valve, from the heart of a man . . 198
215. Human heart, opened from the right to show the atrioventricular

bundle of His . 199
216. Reconstruction of the sino ventricular system (bundle of His) of

the calf's heart . 200
217. Oxalatcd plasma of human blood clotted with thrombin, showing

fibrin needles ... ... 204

218. From a freshly prepared, unstained specimen of human blood . 205

219. Blood cells from a specimen of freshly drawn unstained human blood 206

220. Showing the action of water upon the red blood corpuscle . . 206

221. Five nucleated red cells (erythrocytes) from the blood of a frog . 207
222. Three nucleated red blood cells (erythrocytes) from the marrow of a

human rib . ... 207

223. A group of cells from normal human blood . . . 208

224. A group of blood platelets, from the human blood . . . 209
225. Outline drawings of living polymorphonuclear leukocytes of rabbit,
from a drop of blood mixed with Ringer's solution to which a

small amount of hirudin had been added to prevent coagulation . 211
226. Section of bone marrow from skull of 25 mm. turtle embryo (Chely-

dra serpentina), showing three main stages in the hemopoiesis . 212
227. Hemoglobin crystals . . .213
228. Crystals of chlorid of hematin or hemin . . 213
229. Wall of yolk sac of a 13 mm. human embryo (Fig. 210), showing a
small blood island and several small blood-vessels contain-
ing erythrocytes . . .... 215

230. Large blood island from yolk sac of a 13 mm. human embryo . 216
231. Diagrammatic illustrations of successive stages in the transforma-
tion of the mammalian erythrocyte to form the erythroplastid . 218
232. Successive stages in the elimination of the erythroblast nucleus,

from homoplastic cultures of blood of a 32 mm. pig embryo . 218

LIST OF ILLUSTRATIONS XVii

FIGURE PAGE

233. From a section of rod marrow of a human bone . . 220
234. Types of cells from a smear preparation of the marrow of a human

rib 221

235. Subcutaneous lymphatic vessel of a fetal pig 227
236. The growing end of a developing lymphatic vessel in the subcutane-
ous tissue of a fetal pig

237. Lymphatic and blood vessels in the hilum of a human lymph node . 229
238. Lymphatic capillary from the spermatic cord of a dog, showing nerve

endings

239. Transection of the pericardium of a child . . 232
240. Section of a vascular synovial villus from the knee joint of a

child . 233

241. A lymph nodule, solitary follicle, from the large intestine of man . 234

242. Diagrammatic illustration of a lymph node . . 236

243. Transection of a cervical lymph node of a dog . 237

244. Transection of a mesenteric lymph node of a man . . . 237
245. Diagram of the blood vessels of a lymph node

246. Hemolymph node of the sheep . 240

247. Horizontal section through the faucial tonsil of a child . . 241

248. From a crypt of a dog's tonsil . . . 243

249. The lingual tonsil of man 244
250. Portion of spleen of cat, showing capsule and two splenic nodules

with central arteriole . . 246

251. Diagram of a lobule of the spleen . . 247

252. The origin of a vein in the splenic pulp . . . 248
253. Types of cells from a smear preparation of the pulp of the human

spleen

254. Diagram of a mucous membrane having simple tubular glands 252

255. Diagrams of the principal types of glands . . 253
256. Transection of three secreting tubules of the submaxillary gland of

man . 255

257. Model of a reconstruction of the lacrimal gland of man 258
258. Reconstruction of a mucous gland from the respiratory region of the

nasal mucosa of a child 259
259. Reconstruction of an intralobular duct dividing into its terminal

intercalary ducts and acini . 259
260. Epidermis of the foot 263
261. Section of thin skin from abdomen of negro, showing the distribu-
tion of the pigment granules in dermal and epidermal cells 264
262. Section of thin skin from abdomen of light brown mulatto 264
263. Skin from sole of human foot, showing spiral ducts of two sweat

glands opening through the epidermis 266

264. Transection of the epidermis of the foot ..... 267

xviii LIST OF ILLUSTRATIONS

FIGURE PAGE

265. Three early stages in the histogenesis of the skin . . . 270

206. From a section of the abdominal integument of an infant . . 272

267. Several coils of a sudoriparous gland of the human finger . 273

268. Terminal phalanx of finger- of human fetus . . . 275

269. Transection through the margin of a finger nail . . . 276
270. Longitudinal vertical section of the young nail and nail-bed of an

infant ... . .277

271. Five stages in the development of a human hair . 278
272. From a section of the skin of an infant's arm, showing small im-
mature hair follicles in transection . . 280
273. From a section of the human scalp . . . 282
274. Transection of a hair near the middle of the root sheath . . 284
275. Regeneration of a hair ...... . 287

276. Sebaceous glands in the scalp of a child . . . 288
277. Section of a sebaceous gland from the human scalp, through point

of opening into a hair follicle (obliquely cut) . . . 289
278. Cells from the central portion of figure 277, showing two successive

stages in sebum formation by process of fatty metamorphosis of

the cytoplasm ....... . 289

279. Reconstruction of the cutaneous blood vessels . . . 290
280. Photograph of Azoux model, showing nostril, pharynx, larynx and

related structures ..... . 292

281. From a section of the mucous membrane of the respiratory region

of the human nose ........ 294

282. The olfactory mucosa of a cat ....... 296

283. The olfactory mucous membrane ...... 297

284. Vertical section of the olfactory mucosa of a kitten . 298
285. Diagram of the relations of the neurons of the olfactory nerve and

olfactory bulb . . 299

286. A vertical section through the lateral wall of the human larynx . 301

287. Transection of the wall of a child's trachea . 302
288. Mucus-secreting, tubulo-alveolar gland of the human tracheal

mucosa .......... 303

289. A bronchus from the human lung ... . . 305

290. Diagram of primary lobule of lung (lung unit) .... 307

291. From a section of a child's lung ...... 308

292. From a section of a child's lung ...... 309

293. From a section of a child's lung ... .310

294. Diagram of the three pulmonary lobules connected with a terminal

bronchiole . . . . . . . . . .311

295. Two alveoli of a child's lung . . . . . . .312

296. Transection of the pleura of an infant . . . . .313

297. From a section of the pleura of man ...... 313

LIST OF ILLUSTRATIONS x j x

FIGURE PAGE

298. From the lung of a child . . .315

299. From the lung of a dog whose blood vessels had been injected wit h

a gelatinous mass, and appear black . 316

300. From the central portion of figure 299 . 317

301. From a section through the lip of an infant . 321

302. Axial section of a human molar tooth . 322
303. Diagram of an axial ground section of tooth, .showing the several

stripes of the dentin and the enamel . 323
304. From a longitudinal section of the neck of a child's tooth and the

adjacent alveolus ... . 324
305. From a section of a human tooth which had been ground to extreme

thinness . ..... . 325

306. Section of fang parallel to the dentinal tubules, human canine . 326
307. Dentin from a ground section of a human molar, showing the den-
tinal tubules cut across ... . 327

308. Enamel prisms in transection . . 328
309. A group of enamel prisms cut longitudinally, from the incisor tooth

of the rat, showing their irregularly beaded character and the cross

striations ........ . 329

310. From a section of a human tooth which had been ground to extreme

thinness .......... 330

311. Developing tooth from a human embryo 17 mm. long . .331

312. Dental anlages from a human fetus 40 mm. long . . 332
313. Two stages in the early development of the teeth, from a 25 mm. pig

embryo .......... 332

314. Developing tooth from a human fetus 30 cm. long . . 333

315. A developing tooth from an infant's jaw . . 334

316. A portion of Fig. 315, near the apex of the developing tooth . 335

317. Odontoblasts and dentin of the tooth of a new-born cat 336
318. View of dorsum of tongue, showing the various papillae, the tonsils

and the fauces .......

319. One lateral half of a coronal section of a dog's tongue . . . 339

320. Filiform papilla? of the dog's tongue . . 340
321. A filiform and a fungiform papilla, from an injected specimen of

tongue of cat ..... . 341

322. Circumvallate papillse of the human tongue . 342
323. Two foliate papillse from a rabbit's tongue, showing numerous

taste buds along their lateral margins ... . 343

324. Diagram of the alimentary canal of man . . . 345
325. Surface view of Auerbach's intramuscular nerve plexus, from the

esophagus of a cat . . 346
326. Photomicrograph of a transverse section through upper third of cat's

esophagus ........ . 349

XX LIST OF ILLUSTRATIONS

FIGURE PAGE

327. Photomicrograph of a longitudinal section through the lower third

of the human esophagus, showing a group of esophageal glands . 350

328. From a section of the superficial glands of the human esophagus . 351

329. Section through the stomach wall of man (pyloric region) . . 352

330. The mucosa of the fundus region of the dog's stomach . . 354

331. Longitudinal section of the fundus glands of man . . . 355
332. Transections of three glands of the fundus region of the human

stomach ......... 356

333. A pyloric gland, from section of the dog's stomach . 357

334. Portion of gastric gland from the fundus region of the stomach . 357

335. Secretory capillaries of the fundus glands of the dog's stomach . 358

336. The mucosa of the pyloric region of the human stomach . 359

337. Blood vessels and lymphatics of stomach ..... 361

338. Termination of sympathetic nerve fibers . ... 362

339. Schematic diagram illustrating probable relationship of sympathetic

neurons in myenteric and submucous plexuses . . . 363
340. Section through the commencement of the duodenum at the pylorus 364
341. From a longitudinal section through the duodenum of a cat . 365
342. The central portion of a Peyer's patch in the ileum of a dog's in-
testine .......... 367

343. Diagram of small intestine, showing the topographical relationship

of the intestinal glands (crypts of Lieberkiihn) to the villi . . 368

344. Longitudinal section of villus ... . . 369

345. Several villi from the small intestine of the dog, in longitudinal

section .......... 370

346. Reconstruction model of a Brunner's gland, from the human

duodenum .......... 372

347. The blood-vessels of the small intestine of a dog, drawn after an

injected preparation . . . 373

348. Intestinal mucosa of a frog during the absorption of fat . . 375

349. -Apex of an intestinal villus of a rabbit which had been fed with milk 376
350. Section of large intestine of dog, showing intestinal glands (crypts

of Lieberkiihn) cut longitudinally . . . 378
351. Section of portion of large intestine of dog, showing the intestinal
glands (crypts of Lieberkiihn) cut across, their lining including

columnar and goblet cells ... . 379

352. Transection of the vermiform appendix of man . . 380
353. Semidiagrammatic representation of a small mucous gland from the

oral mucosa of a rabbit . 382
354. Corrosion model of an interlobular duct and its branches, from the

human submaxillary gland . . 383
355. Intercalary ducts and acini of the human submaxillary gland, corro-
sion model . 385

LIST OF 1LLUSTEATIONS xx i

FIGURE PAGE

356. A group of mucous acini, from the human submaxillary gland . 386

357. From the sublingual gland of man . 387

358. Mucous acini of the ivtrolingual gland of the rat . 388
359. Diagram of the arrangement of the colls in a mixed salivary

gland . . 389
360. Diagrams of parotid gland, submaxillary gland, sublingual gland,

and pancreas . 3.V.I
361. From a section of the human parotid gland . 390
362. From a section of the human submaxillary gland . 3!H
363. Reconstruction model of the sublingual gland of man . . 392
364. Nerve endings in a salivary gland . 393
365. Early stages in the development of the pancreas, illustrating condi-
tions in the 5 and 7 weeks old human embryos . 394
366. From a section of the human pancreas, showing several lobules and

the broad interlobular bands of connective tissue . 395
367. Drawing of an intercalary duct with three branches ending in acini

to form centro-acinial cell groups . . 396

368. Reconstruction model of the human pancreas . . 396

369. Acini of the human pancreas . 397
370. Pancreatic acinus of cat cut transversely near fundus, showing the

basal (prozymogen) filaments of the cells . 398

371. Cells from pancreas of Necturus . 399

372. Two adjacent acini from the guinea-pig's pancreas . 399
373. Section of an acinus from the guinea-pig's pancreas, showing the

basal mitochondrial content and the central zymogcn granules . 400
374. Intercalary duct with branches, from pancreas of guinea-pig,
showing highly branched tubules connected with the duct and

with the islet . 400

375. Pancreatic islet . 401

376. From the human pancreas . 402
377. Section of a pancreatic islet from injected specimen of cat's pancreas

to show the profuse blood supply . . 404

378. A lobule of the pig's liver; the central vein lies in the middle figure . 405
379. Diagram of liver lobules, the upper two cut transversely, the lower

longitudinally . 406
380. From a section of the turtle's liver, showing the tubular arrange-
ment of the parenchyma . 407
381. The reticulum of the dog's liver . 408
382. Stellate cells of von Kupffer in the liver of a dog . 409
383. A lobule of the pig's liver in longitudinal section, showing the rela-
tion of the central and sublobular veins and the arrangement
of the hepatic cells . 410
384. A lobule of the human liver, seen in trunsection . .411

xxii LIST OF ILLUSTRATIONS

FIGURE PAGE

385. Section of liver tissue showing the liver cell-cords, and the sinusoids

lined with endothelium . . .412

386. Diagram of four adjacent liver cells . .413

387. Bile capillaries of the hepatic lobule, from the liver of a cat . . 413
388. Showing the connection between the intralobular and interlobular

bile ducts in the cat's liver . . . .414
389. Types of cells from a section of the normal human liver . 414
390. Human liver cells, showing enlarged intracellular canaliculi, a con-
dition characteristic of jaundice . 415
391. Diagram of a portal canal, including a branch of the portal vein,
hepatiq artery, hepatic (bile) duct, lymphatic and non-mcdul-
lated nerve trunks . 415
392. From a section of the rabbit's liver whose blood vessels had been
injected with a carmin stained gelatin mass; somewhat more than
a single lobule is represented . .416
393. A sublobular vein of the pig's liver . . 418
394. Intralobular nerve fibers in a rabbit's liver . 420
395. From a section through the wall of a dog's gall-bladder . 421
396. Reconstruction of the wall of a dog's gall-bladder . 421
397. Longitudinal section of kidney . . . 424
398. Diagram of the structure of the kidney . 425
399. Reconstruction of a uriniferous tubule of an infant . 426
400. Diagram of uriniferous tubule of a mammal . 428
401. Reconstruction of a glomerulus of the human kidney . . . 429
402. From the cortical labyrinth (pars convoluta) of the human kidney 430
403. From the cortex of the human kidney, showing a transection of a

cortical ray in the lower left-hand corner

404. From a longitudinal section of a convoluted tubule of the guinea-
pig's kidney

405. Cross section of a proximal convoluted tubule from the kidney of
a mouse, showing basal filaments breaking up into granules (vu-

trally, and the central striated border of the cells . . 433
406. A group of tubules from a transection of a renal pyramid of the

human kidney; the section passes through the boundary zone . 439

407. The distribution of the left renal artery . 441

408. From the cortex of the human kidney . 442

409. Nerve endings in a convoluted tubule of the frog's kidney . 444

410. Cast of the pelvis, infundibula and calices of the kidneys of a man . 445
411. Transection of human ureter .... .44(1

412. Transitional epithelium of dog's ureter . 447

413. Transection of the wall of a child's bladder . 449

414. The mucosa of a child's bladder in the contracted state of the organ 450

415. Transitional epithelium of dog's bladder . 451

LIST OF ILLUSTRATIONS xx jji

FIGURE PAGE

416. Epithelial cells from the bladder of the rabbit .... -!.">_>

417. Transection of the female urethra ..... I.",.;

418. Diagram of a male genitalia ..... 4.").")

419. Diagram of female internal genitalia . . 4.~>ii
420. Diagrams illustrating the metamorphoses of the indifferent urogeni-

tal sj^stem into the male and female systems . . i.~>7
421. Diagrams illustrating the process of maturation in the male and

female gametes . .462

422. Primary spermatocyte of a grasshopper, Hippiscus tuberculatus,
showing the compact accessory chromosome among the paler

mossy prophase euchromosomes, and the idiosome ' . . 4ii4

'423. Chromosome groups of Schistocerca damnifica . . 473
424. Diagram illustrating the behavior of the chromosomes during the

first and second maturation divisions ..... 474

425. The testicle with its system of efferent passages . . . 480

42G. Seminal tubule of a man in transection . . 481

427. Sertoli cells of the human testis . 482
428. Portion of a transection of a seminiferous tubule from the human

testis, illustrating the various stages in spermatogenesis . . 4s:!
429. Successive stages in the metamorphosis of the spermatid into the

spermatozoon . . . . 484

430. Diagram of human spermatozoon . . 485
431. Spermatozoa of various animals . 486
432. Spermatozoa from the semen of man . 487
433. Agroupof interstitial cells from the testis of a thirty-five year old negro 488
434. Interstitial cells from the human testis . 4v.)
435. A small portion of the wall of an efferent ductule of the testicle . 491
436. Efferent ductules of the rabbit's epididymis . 491
437. Several coils of the rabbit's epididymis in transection . . . 492
438. Transection of the ductus deferens of a dog . . 494
439. From a section through the wall of a seminal vesicle of man . 4 '.),">
440. Model of a reconstructed prostate gland of man . . 496
441. Several alveoli of the human prostate gland, seen in section . 498
442. Portion of prostate gland of an old man, showing the prostatic con-
cretions ...... . . 499

443. Prostatic genital corpuscles . . . 500
444. Reconstruction of a bulbo-urethral (Cowper's) gland of man . 501
445. From a section of the bulbo-urethral (Cowper's) gland of man . 501
446. Transection of a child's penis, just back of the glans . . 503
447. Helicine artery in section, from the urethral bulb of man . . 504
448. The erectile tissue of the penis . . 505
449. Section of ovary of adult cat, showing five vesicular (( Ininfian) folli-
cles, four with the cumulus oophorus and the enclosed ovum . 508

XXIV LIST OF ILLUSTRATIONS

FIGURE PAGE

450. From the ovarian cortex of an infant, showing many ova in the

primary follicular stage . . 509
451 . Ovum, containing a yolk nucleus ('Dotterkern') at the left and above

the nucleus . . . . 511

452. From a section of the ovarian cortex of a new-born kitten . . 513
453. A primary ovarian follicle of the human ovary . .514
454. A vesicular (Graafian) follicle of the human ovary, somewhat more

advanced than the preceding . . 515

455. A nearly ripe Graafian follicle from the ovary of a dog . 516
456. Photomicrograph of a section of cat's ovary, showing two primary

follicles and one vesicular ... . . 517

457. Section through the peripheral portion of a corpus luteum, showing

lutein cells . . . .520

458. Portion of corpus luteum of rabbit . . . . 521

459. A corpus albicans, from a section of the human ovary . . 522

460. From a thick section of the ovary of a woman .... 523

461. Transections of the human oviduct . . . 524
462. From a transection of the ampulla of the oviduct, showing the struc-
ture of the mucosa ........ 525

463. Transection of the uterus of an ape . . ... 527

464. Transection through the body of the human uterus . . . 529

465. From a transection of the uterine mucosa . . . 530
466. From the cervix uteri of a girl of sixteen years, showing the cervical

glands in section ..... . 531

467. A gland of the human cervix uteri in longitudinal section . . 532
468. From a section of the human uterine mucosa at the first day of men-
struation ...... . . 534

469. A group of decidual cells from the human uterus during the early

stages of pregnancy ........ 535

470. Chorionic villi from the human placenta at full term . . . 536

471. Chorionic villus at various stages of development . . 537

472. Vaginal mucosa ..... . 538

473. Transection of a labium minus of an infant .... 540

474. From the actively secreting mammary gland of a woman . . 542
475. Model of a reconstruction of an intralobular duct and its acini from

the active mammary gland of a woman ..... 543

476. Portions of several adjacent lobules, and a lactiferous duct, of the

active mammary gland . . . 544

477. From a section of the human mammary gland in the resting condition 545

478. From a section through the human adrenal .... 550

479. Photomicrograph of suprarenal gland of dog . 551
480. More highly magnified region of the preceding section, to show the

capsule, zona glomerulosa, and a portion of the zona fasciculata . 552

LIST OF ILLUSTRATIONS xxv

FIGURE PAGE

481. Reconstruction of a dog's adrenal ...... 555

482. Section of part of an accessory suprarenal (chromophil) body, new-
born child ... ... . 556

483. From a section of the human thyroid gland . 558

484. Diagram of pharynx of human embryo showing the origins of the

anlages of the thymus, thyroid and parathyroids (epithelial bodies) 560
485. From the border of a mass of aberrant thyroid tissue of man, occur-
ring in the region of the parathyroid glands . . . 562
486. Human parathyroid tissue, moderately magnified . . 564
487. A section through several lobules of the thymus of an infant . . 566
488. A thymic corpuscle from the thymus of an infant . . . 567
489. Carotid gland of an ape ... . . 569

490. From a section of the coccygeal gland of man . . . 570

491. Median section through the anlages of the hypophysis cerebri of a 10

mm. cat embryo . . 571

492. Sagittal view of a wax reconstruction of the hypophysis cerebri of

the adult cat ....... 574

493. Pars tuberalis, hypophysis of cat ...... 576

494. Pars infundibularis, hypophysis of cat . . . . 576

495. Pars distalis, hypophysis of cat .... . 577

496. Section of hypophysis cerebri of dog, showing portions of pars distalis
of anterior or buccal lobe, residual lumen, pars tuberalis (pars
intermedia), pars neuralis, and capsule . . 578

497. Field from the center of a normal canine (puppy) pars anterior . 579
498. Semidiagrammatic representation of a median longitudinal section

through the epiphysis of a 17 cm. sheep fetus . . . .581

499. Cells from the pineal body of a 11 cm. sheep fetus . . . 582
500. Photomicrograph of a peripheral portion of the pineal body of a 21
cm. sheep fetus, showing several cysts and vascular trabeculse,
and an enormous number of intracellular melanic granules . 583

501. Photomicrograph of peripheral region of pineal body of a yearling
sheep, to show the character of the parenchyma, the neuroglia cells
and fibers, and the interneuroglia cells ..... 584

502. Two neuroglia and three interneuroglia cells from the pineal body

of a lamb .......... 584

503. Cells from pineal of yearling sheep ...... 585

504. Section of pineal body of an old sheep, showing 'brain sand' (acer-

vulus) in the parenchyma ...... 586

505. Human embryo 2 millimeters long . . . 587

506. Transection through the Graf Spee embryo shown in figure 505 . 588
507. Three successive stages in the process of closure of the medullary
(neural) groove to form the medullary (neural) canal and neural
(ganglionic) crests ........ 588

xxvi LIST OF ILLUSTKATIONS

FIGURE PAGE

508. Cell lining the neural canal of the newly-hatched rainbow trout,

showing mitochondria in an embryonic nerve cell . . . 589

509. Section through medullary plate of a rabbit embryo . . . 589
510. Section through medullary plate of closing neural groove of rabbit

embryo ... . . . 590

511. Section through wall of later neural tube of rabbit embryo, showing
a stage in the differentiation of the ependyma cells and the forma-
tion of a myelospongium . . . 590
512. Section of wall of forebrain of four-day chick embryo . . 591
513. Diagram of a transection of the spinal cord of an early embryo, show-
ing the migration of neuroblasts toward the marginal veil, and
the ventral nerve root . .591
514. Transection of the spinal cord of a human embryo of four weeks . 592
515. Transection of the spinal cord of an embryo chick . 593
516. Reconstruction of the anterior portion of the body of a chick, the

head distinctly differentiated, seen from the surface . 593

517. Transection of the spinal cord of a child, seventh cervical segment . 595
518. Diagram of the fiber paths of the spinal cord . .518

519. Transection of the spinal cord of a child, third sacral segment . 600

520. Transection of the spinal cord of a child, fifth lumbar segment . 600

521. Transection of the spinal cord of a child, eighth thoracic segment . 601

522. Transection of the spinal cord of a child, fourth cervical segment . 604

523. Median sagittal section through the brain . . . 605

524. From a section of the cerebcllar cortex of man .... 606

525. A Purkinje cell from the human cerebellar cortex . 607

526. A Purkinje cell from the cerebellar cortex of the rabbit . . 608

527. Diagram of the cerebellar cortex . ... 610

528. Motor region of the cerebral cortex in man . . . 612

529. Large pyramidal cell of the cortex . . 613
530. Scheme of the motor area of the cerebral cortex, showing the 'effect

of various staining methods ... ... 614

531. Cortex of human brain illustrating the systems and plexuses of nerve

fibers ...... ... 615

532. Human cortex cerebri, motor area . ... 616

533. Human cortex cerebri, parietal lobe . 617

534. Human cortex cerebri, olfactory region . . 619
535. Section of the spinal cord and its membranes, from the upper thoracic

region ........ 621

536. Dissection of eyelids and lacrimal apparatus . . 626

537. Horizontal section of the right eyeball 627

538. The anterior segment of a child's eye; meridional section . 629

539. From a meridional section of the human cornea . . 630

540. Corneal corpuscles of the frog .... 632

LIST OF ILLUSTRATIONS

XXV11

FIGURE PAGE

541. Conical cells, isolated . ..... 633

542. From a meridional section of the choroid coat . 637

543. The ciliary body and the adjacent structures; meridional section . 639

544. The developing eye in meridional section; diagrammatic . 645

545. Schematic reconstruction of the developing eye . . 646

546. The retina of a child's eye; meridional section . . . 647

547. Pigmented epithelium of the retina, viewed in transection . . 647

548. Isolated rod and cone visual cells of the pig . 648
549. Diagram of the rod and cone visual cells, and their respective bipolar

neurons ...... ... 649

550. A rod and cone visual cell from the fundus of the human retina,

outside the macula lutea . .... 650

551. Two cones from the human retina .... . 650

552. From the human retina . . . ... 651

553. Diagrams of the human retina, showing the relationships to each

other of the retinal neurons, and their disposition in the different

layers . ........ 652

554. From a meridional section of a child's eye, showing the layers of

the retina at a point midway between the macula lutea and the

ora serrata ... . . ... 653

555. Horizontal cell from the retina of a calf . . . 655

556. Two amacrine cells from a transection of the retina of a calf . 656

557. A nerve cell of the large ganglion cell layer; from the retina of a cat . 657

558. A fiber cell of Miiller, or sustentacular cell, from the dog's retina . 658

559. Transection through the fovea centralis retina? . . . 660
560. Developing rod and cone visual cells, from the retina of a 345 mm.

(6 mos.) human fetus . .... .661

561. Two early stages in the development of the rod and cone visual cells

in the chick ......... 662

562. Diagram illustrating Balfour's theory to account for the inversion

of the visual cells of the vertebrate retina . 663

563. Entrance of the optic nerve . . . 664

564. Lens fibers .......... 667

565. The nuclear zone at the margin of the crystalline lens of a child's

eye, showing the transition of the lens epithelium to the lens fibers

and the attachment of the suspensory ligament . . . 668

566. Schematic representation of the intrinsic blood vessels of the eye . 671

567. Vertical section through the upper eyelid ..... 675

568. Arterial supply of the eyelid . . 678

569. Section through a lobule of the lacrimal gland of man . 680
570. Portions of two adjacent lobules of the lacrimal gland of the rabbit,

showing two stages in secretory activity of the tubules . 681

571. Transection of the lobule of the external ear of an infant 683

Xxviii LIST OF ILLUSTEATIONS

FIGURE PAGE

572. From the external acoustic meatus of man .... 684

573. Transection of the tympanic membrane of a child . . . 687

574. Section through the margin of the tympanic membrane of a child . 688

575. The auditory ossicles ........ 689

576. The cavity of the tympanum, viewed from above . . . 690

577. Transection of the Eustachian tube; diagrammatic . . . 692

578. The bony labyrinth .. 694

579. Diagram of the membranous labyrinth in lateral view . 695

580. Diagram of the right membranous labyrinth .... 696

581. The isolated membranous labyrinth ...... 696

582. Transection of the margin of the macula acustica sacculi of a guinea-
pig . . 697
583. Nerve endings in the macula acustica of a guinea-pig . . . 698
584. Transection of a human semicircular canal .... 700

585. Axial section through the cochlea of a fetal calf . . . .701

586. Axial section through a turn of the cochlea of a guinea-pig . . 702
587. A radial section through Corti's organ in the first turn of the human

cochlea .......... 707

588. Diagram of the organ of Corti . . . . . . .711

589. Axial section through Corti's organ of the guinea-pig, showing the

terminal nerve fibrils . . . . . . . .713

590. Scheme of the vascular supply of the internal ear . .714

591. Scheme of the vascular terminations in the wall of the cochlear

canals .......... 715

592. Semidiagrammatic illustrations of successive stages in the develop-
ment of the internal ear of the chick . . . . .718

593. Wax reconstructions of three early stages in the development of the

internal ear (membranous labyrinth) of man .... 718

594. A method of preparing a paper box for paraffin embedding . . 737

. PLATES

A. Successive stages in the spermatogenesis of Schistocerca damnifica . 465
B. Successive stages in the spermatogenesis of Schistocerca damnifica

(continued) ..... ... 467

C. Successive stages in the spermatogenesis of Schistocerca damnifica

(continued) . . ..... 469

D. Successive stages in the growth, maturation, and fertilization of the

egg of the starfish, Asterias forbesii . . . . . .471

A TEXT-BOOK OF
HISTOLOGY

A TEXT-BOOK OF HISTOLOGY

CHAPTER I

INTRODUCTION PROTOPLASM CELL

INTRODUCTION

Definition of Histology. Histology is the science of tissue struc-
ture, plant or animal. It concerns itself, therefore, chiefly with the
structural characteristics and interrelationships of the component ele-
ments of tissues. These elements are the cells, and the material con-
necting or separating the cells, the intercellular substances. A tissue
consists of cells associated in the performance of
a specific function. A cell may be defined in a
preliminary way as the unit of organic structure
and function. The minuter details of histology
involve also cell anatomy or cytology. Here we
meet witli the essential substance of the cells, the
protoplasm, or bioplasm, the 'material basis of life/
We also meet with the chief 'organ' of cells, the
nucleus. A completer definition of a cell may
accordingly be given as a circumscribed mass of
protoplasm containing a nucleus (Fig. 1). A com- FIG. 1. VARIOUS
plete histologic description embraces, therefore, SPHEROIDAL CELLS

details of the" relationships of the component cells f *> fr m ovai T

of a child; 2, sperm-

ot a tissue and of the protoplasmic structure, and atocyto; and 3, sperm-
nuclear characteristics of the types of cells in- atid, from the testicle

Yoked. Histology includes further a knowledge of f . a rab . bit - . Hema '

. c tern and cosm. X

tissue origin and development, or lustogenesis, and 759.

of cell origin and development, or cytogenesis.
Cells are the 'building stones' of tissues ; tissues combine to form organs ;
organs are associated into systems. Histology is accordingly a part of
general anatomy; it is tissue anatomy ; that part of histology \vhich con-
siders the relationships between tissues in organs is sometimes spoken of
as microscopic anatomy.

2 1

2 INTRODUCTION PROTOPLASM CELL

Historical Development of Histology. Modern human histology
had its origin in the work of Bichat (1771-1801). He did not employ
the microscope; but his careful and extensive studies of the minute
anatomy of tissues gave the impulse and general outline for later studies
by means of the microscope through which mammalian histology has
grown to a relatively complete science. Great impetus was given also by
the announcement of the 'cell theory' by Schleiden and Schwann in 1839,
namely, the statement that all tissues are composed of structural units,
or cells. Other epochal steps in histologic science w r ere the recognition of
the nucleus by Robert Brown in 1831, and of protoplasm by v. Mohl
in 184G. Cytology arose almost as an incident to embryology. It traces
its origin to the work of 0. Hertwig on the fertilization of the sea
urchin's egg (1875). It is the infant anatomic science, its late develop-
ment being due, largely, to its dependence upon the optical and me-
chanical refinements of the microscope. It deals with fundamental
structures within the limits of visibility, and is destined to grow to vast
proportions, as the already voluminous literature on 'mitochondria'
('plastosomes') in part foreshadows.

Relation of Histology to Other Biologic Sciences. Histology
aims to complete anatomic knowledge. It is thus the complement of
gross anatomy. It furnishes also essential preliminary data for the
understanding of pathology; abnormal structure and function become
fully intelligible only in the light of normal histology. It is funda-
mental also to physiology, the science of normal function.

A certain function demands a specific structure; structure and func-
tion sustain reciprocal relationships. Normal function depends upon
the normal structure of the cells involved in the function; abnormal
function, or disease, is associated with altered cellular structure. His-
tology gains enormously in interest and value to the student who will
always keep well in mind the function that a certain structure under
consideration is called upon to perform. Embryology also to a consid-
erable extent builds upon histologic and cytologic data.

PROTOPLASM

Chemical Constitution. The unit of both structure and function
is the cell. The essential constituent of cells is protoplasm. Protoplasm
may be thought of as a physicochemical mechanism. Chemically, it is a
very complex aqueous mixture of substances, containing the elements,

PEOTOPLASM

carbon, oxygen, hydrogen, nitrogen, and small quantities of sulphur,
phosphorus, calcium, sodium, chlorin, magnesium, potassium and iron.
The prineipnl compounds of protoplasm are proteins, which furnish
the main source of energy expended in function; carbohydrates; fats;
and water, which constitutes ahout three-quarters of its weight. It is
believed by one school of biologists (mechanists) that if we had the

:, - . '

';,- '

' ' .'"'',

.
gft :

T \>'-.'*+ V (5?rt% 'V* ; j u . .. ;

(ii

Vv^

:|IIiP

V'-<^ '';

\ -'.-I*:?;-'-?.

; "-,'. --* '- "

c.v

A

FIG. 2. AMEBA PROTEUS IN MOTION.

c.v., contractile vacuole; /.c., food vacuole; n., nucleus; w.v., water vacuoles. The
arrows indicate the direction of the protoplasmic flow. Note the peripheral non-
granular ectoplasm, and the granular endoplasm. (From Calkins' "Biology,"
H. Holt & Co., after Sedgwick and Wilson.)

formula for the proper stereo-isomeric association of the elements and
compounds of protoplasm, life could be artificially produced; another
school of biologists (vitalists) assume an additional 'vital principle' as
a prerequisite for life.

Physical Constitution. Physically, protoplasm is a granular semi-
fluid or gelatinous substance. It possesses properties characteristic of
both solids and liquids. It is an aggregate of colloids and cri/xt<tllui<lx.
The physicochemical laws which govern the crystalloids and colloids
underlie the properties of living matter. An organism is essentially

1

INTRODUCTION PROTOPLASM CELL

an aqueous solution, holding in suspension colloidal substances of great
complexity. Crystalloids arc divisible into two groups: electrolytes and

non-electrolytes. The one (salts,
acids, bases) in solution conduct
the electric current, the others
(urea, sugar) do not. Colloids ex-
ist in two states, a liquid or sol
state, and a semi-solid or gel state.
There exists no sharp line of di-
vision between colloids and crystal-
loids ; these terms designate phases
or states rather than substances;
between them lie all kinds of inter-
mediate grades. Protoplasm is a
sol ; and since its fluidity is due to
water, it is commonly classed as a
liydrosol. It passes readily into a
gel condition, thus becoming a liy-
drogel. In living protoplasm this
metamorphosis is a reversible proc-
ess. Agents which effect an irre-
versible gelation of protoplasm
tend to bring life to a standstill.
Fixation, or killing, of tissue for
microscopic study consists in a sep-
aration of the more solid part of
colloidal protoplasm from a more
liquid part. Death is histologically
such a process of coagulation. Liv-
ing protoplasm may be studied to
good advantage in the one-cell ani-
mal forms, Ameba (Fig. 2) or

TfflCHOCYSTS

5" Cfl/Vfli.3

MlCRONUCLEUS

MACRONUCLEUS

Gasrmc

pSRlSTOME
MOUTH AW GULLET

CONTRACTILE VAOJOLE.

FIG. 3. PARAMECIUM CAUDATUM.

Note the peripheral cilia and the gran-
ulo-alveolar character of the protoplasm.
(From Calkins' "Biology," H. Holt
&Co.)

Paramecium (Fig. 3). These and
other equally favorable protozoan
forms are readily available from hay infusion cultures, and can be profit-
ably employed for the demonstration also of the simpler modes of proto-
plasmic activity, and of the changes suffered by protoplasm in passing
from the living to the dead condition. Since protoplasm is commonly
organized into cells, the next step demands a knowledge of a typical or
generalized cell.

THE CELL

THE CELL

General Statements. A generalized cell is of spheroidal shape (un-
modified by pressure) and contains certain 'organs' and a variety of fun-
damental and secondary elements (Fig. 4). A cell (or protoplast;
Hanstein) is a mass of protoplasm endowed with vital properties. The
confines of such a cellular mass of protoplasm exist in a cell meinbranr.

* ' i >.... \ v \ fTfsSK! 1 , " -\

yTr--/^T?-Kv\?%---:s

S*r^>t-^>< v >Mi

v^33kg^5w w^n^-.

r \%WK Ml X>^-:;

V.m^fe^W;^i^<%^-:y

X . -*. :;,..."/.. : . < f ..**.-/ -,' \ .-.-* * . S

FIG. 4. A GENERALIZED CELL.

a, exoplasm; fe, endoplasm; c, spongioplasm; d, hyaloplasm; e, microsomes; /,
chromidia; g, centrosome (centriole) ; /;, centrosphere, surrounded by astrosphere; i, cell
membrane; j, deutoplasmic granule; k, fluid vacuole, or oil drop; I, mitochondria or
plastosomes; m, nuclear membrane; n, nucleolus; o, linin; p, karyosome; q, chromatin
(net knot); r, foreign inclusions, pigment, etc. (metaplasm).

This represents a differentiation product of protoplasm; when robust
as in plant cells, it forms a cell wall. In certain cells, e.g., white blood-
cells, it is apparently lacking; however, in these so-called naked cells the
peripheral layer of protoplasm is more condensed and most probably
subserves the osmotic function of a distinct membrane. In fact, the
surfaces of protoplasm possess the properties of semipermeable mem-
branes, probably lipoid in nature. An essential organ of the cell is the
nucleus. It is trophic in function, the center of oxidation processes.
In certain protozoa this is represented by scattered nuclear materials

G

INTRODUCTION PROTOPLASM CELL

or granules (Fig. 5). The .si) ape of the nucleus is spherical; typically
it has a central location, but it frequently assumes eccentric positions.
It is physically denser and more elastic than the extranuclear protoplasm.
Its periphery simulates, or perhaps consists of, a membrane, the nuclear
irall. Whether as a membrane it be complete or reticulated, whether of
nuclear, cvioplasmic or composite origin, are undecided points. Recent

investigations on the nuclear membrane indicate
that it is fenestrated; such conditions would per-
mit of an easy escape of nuclear material into the
cytoplasm.

Nucleus. The protoplasm composing the nu-
cleus is known as nudeo plasm or karyoi>lasm;
that constituting the remainder of the cell, the
(yloi>!<tvi. The nuclear constituents include a more
fluid ground substance or nuclear sap (Tcaryo-
lijmiih : paralinin), throughout which extends a
delicate reticulum of linin threads (Fig. 4).
Upon these linin or achromatin threads are sup-
ported, more abundantly at the points of inter-
section of the mesh, granules (chromioles) and
masses (net-knots], of a substance, staining deeply
in the basic dyes, the chromatin. Spheroidal net-
knots are known as karyosomes. The linin is
said to be achromatic. Whether it is chemically
different from chromatin or simply more atten-
uated chromatin is disputed. The 'chromatic' gran-
ules themselves undergo changes in stainability :
on the basis of reaction to acid and basic dyes,
this substance is divided into oxy chromatin (lan-
tanin} and basichromatin. Limn and chromatin
are regarded by some as different phases in the
elaboration of the same substance. The nucleus in-
cludes, furthermore, usually one, frequently more,
nucleoli. These do not grade into the nuclear sap. like the nuclear
network, but are limited by a sharp line of demarcation. They may be
achromatic, when they are known as plasmosomes, or they may take on
chromatin, becoming cJiromatin nucleoli. It is uncertain whether the lat-
ter are identical in all cases with the karyosomes. The difference among
nucleoli is more probably one of degree of abundance of chromatin. The
nucleus is the metabolic organ of the cell; without a nucleus a cell may

FIG. 5. A UNI-
CELLULAR FLAG-
ELLATE ANIMAL
(TETRAMITUS
CHILOMONAS).

Showing the nu-
clear material dis-
tributed as granules
throughout the cell.
(Redrawn from
Calkins.)

THE CELL

continue to live for a time, but it can neither grow nor undergo progres-
sive differentiation. All changes in enucleated protoplasm are regn-ssi\e.
leading to death. The nucleus is also largely the reproduct i\e center, as
will be described below. The nucleolus phiys the role, among other pos-
sible functions, of a center of storage, perhaps also elaboration, of chro-
matin. Xuclear protoplasm, more especially the chromatin, is relatively
rich in phosphorus.

Astral System. Another organ of a typical cell is the aster, asirnJ
system or all faction x/ilicrc. Its substance is collectively known as arclio-
plasm. It usually lies outside of,
but close to, the nucleus ; in cer-
tain cells it is intranuclear, e.g.,
spermatocytes of Ascaris. It con-
sists centrally of a granule, the
centrosome; in this, in certain in-
stances, may be differentiated cen-
trally a smaller granule, the cen-
triole; when the latter appears,
the more outlying portion of the
centrosome is designated the cen-
tro plasm. The centrosome may
divide into two, becoming a diplo-
some, or in some instances it
may become multiple, when it is

FIG. 6. EGG OF A CLAM (CUMINGIA

TELLINOIDES).

Showing the first maturation spindle
with centrosomes and chromosomes at
metaphase, and the disappearing nucleolus
() at the right, X 1000.

known as a pluricorpuscular cen-
trosome. Surrounding the cen-
trosome is a clearer, minutely
granular sphere, the centrospliere;
radiating from this peripherally are delicate astral rays, collectively
known as the astrosphere (Fig. C). Structurally the aster is subject to
considerable variations in different cells. On account of its relation to
cell division, it is regarded as the dynamic center of the cell ; viewed thus
its substance is known as kuin/ihixm. The attraction sphere may or may
not be visibly present; in all living cells it, or its analogue, is generally
believed to be potentially present.

Cytoplasm. The cytoplasm may be divided into a thin peripheral or
cortical layer of less granular protoplasm, the exo plasm (ectoplasm),
and the main central mass, the endoplaxm. In certain highly differen-
tiated cells the exoplasm is not discernible. In others, at certain stages
in the development it contains the products of differentiations, when it is

8

INTKODUCTION PROTOPLASM CELL

FIG. 7. PRIMARY
SPERMATOCYTE OF
A TURTLE (CiSTUoo
CAROLINA).

Showing chromatic
spherules ('chromidia')
apparently in process
of extrusion from the
nucleus. X 1500.

known as 'deuteroplasm' (Studnicka). The endoplasm is commonly
described as consisting of a more fluid, finely granular ground substance,

the hyaloplasm (paraplasm, interfilar mass, para-
mitome, encliylema, cytolymph), containing a del-
icate denser reticulum, or cytoreticulum, with
polygonal or spheroidal meshes. The substance of
the reticulum is called spongioplasm (mitome;
filar m.ass). It is held by some to be continuous
with the linin mesh of the nucleus. The granules
of the ground substance, both free of and attached
to the spongioplasm, are called microsomes. Ac-
cording to one interpretation the spongioplasm
arises by coalescence of microsomes. A more re-
cent interpretation regards both network and
granule as simply more condensed portions of the
hyaloplasm. The cytoplasm may contain, besides
the aforementioned fundamental constituents, nu-
tritive materials including yolk granules or glo-
bules (deutoplasm) ; vacuoles, foreign enclosures, e.g., bacteria, etc., and
pigment (metaplasm) ; plastids (in plant cells) ;
chromidia (Fig. 7), masses of chromatic gran- # '

ules, presumably of nuclear origin, and probably
the raw material for certain differentiation prod- * v *

ucts; and mitochondria or plastosomes. **.

Mitochondria. 'Mitochondria' is at present
a comprehensive term for a collection of probably
very different substances. These are destined to
bulk very large in immediate cytological investi-
gations. They may prove to be very important
elements of the more fundamental protoplasmic
structure and function. In the germ cells of
vertebrates, as in undifferentiated cells generally,
they are for the most part, granular (chondrio-
somes) (Fig. 8) ; in the somatic differentiated
cells filamentous or rod-shaped (chondriomites;
clntndrioconts; pseudochromosomes) (Figs. 9
and 10). Both chromidia and irojilioxpoiifjiuni.
(a canalicular network of the cytoplasm, prob-
ably concerned with circulation of nutritive material or secretion prod-
ucts) (Fig. 11) have been identified with mitochondria. Trophospon-

FIG. 8. SPERMATID OF
OPOSSUM IN EARLY
STAGE OF METAMOR-
PHOSIS INTO A SPER-

MIUM.

Showing granular
mitochondria, vi, in the
cytoplasm, n, nucleus,
,*, archoplasmic sphere.
X 2000.

THE CELL

9

gium at least is a distinct structure, and chromidia more probably also,
though by some regarded ;is the elements from which the filamentous
mitochondria are formed. Mitochondria have been credited with most

a b c d

FIG. 9. CELLS FROM THE NEWLY HATCHED RAINBOW TROUT, TREATED ACCORDING
TO MEVES' TECHNIC FOR THE DEMONSTRATION OF MITOCHONDRIA (PLASTOSOMES).
a and 6, cartilage cells; c, young blood cell; d, epithelial cells from the intestine.
X 2000.

various functions, e.g., formation of presecretion and excretion granules,
and the formation of various kinds of fibrils. M. Heidenhain regards the
chondriosomes as vegetative organs of the cells subserving metabolism.

FIG. 10. Two CELLS FROM THE MESENCHYMA OF THE NEWLY HATCHED RAINBOW

TROUT.

The one to the left (a) at late anaphase of mitosis, showing mitochondria (plasto-
somes). Meves' technic. X 2000.

Our knowledge is as yet too limited to speak with assurance either as to
their origin, complete function, or fate. One thing only is certain,
namely, that they are actual constituents of the cytoplasm of practically

10 INTRODUCTION PROTOPLASM CELL

every type of cells, at certain, perhaps all, stages of development and
active function. They have been seen and studied even in living plant

cells (Maximmv). and in animal cells grown in
artificial media they were observed by M. E. and
W. H. Lewis (Amer. Jour. Anat., 17, 3, 1915)
to move, to change shape, to divide into granules
and again to reunite into filaments facts which
render inadmissible their interpretation in fixed
material as lipoid precipitation products (Faurier-
Fremier), and strongly suggest their connection
FIG. 11. INTRA- w ^h metabolic activity. They have the chemical
CELLULAR NET- composition of a lipoid (probably a phosphatid)
WORK, OR TROPH- un ^ ec [ ^o an albuminoid base. It has been sug-

OSPONGIUM,' WITH- 1,1,1 -, 41

IN A PURKINJE gested that they are a support to, and the region
CELL OF THE CERE- of, oxidation. Chambers suggests that they 'may
BELLUM OF S TR ix be expressions of changes in the physical states of

FLAMMEA.

(-, , -, , Af , the cytoplasmic colloids.
Golgi s stain. (After J

Golgi.) Schreiner's findings in developing fat cells sug-

gest a nutritive significance.

STRUCTURE OF PROTOPLASM

Four main types of protoplasmic structure are generally recognized:
(1) the homogeneous; (5) the granular; (3) the alveolar or foam type;
and (4) the fibrillar, (a) reticular or sponge type and (b) filar (Fig.
12). The type of protoplasm of a particular cell may vary with the
stage of development and function. In successive stages of development
and differentiation the protoplasm of the same cell may pass from the
apparently homogeneous, through the granular and granulo-alveolar. to
a granulofibrillar type. Homogeneous protoplasm, as for example the
ectoplasmic layer of ameba, is more probably to be interpreted as com-
posed of minute, perhaps ultramicroscopic, colloidal granules ('colloidal
biogens'). Young and undifferentiated cells commonly have a granular
cytoplasm. In general it may be said that the actual fundamental type
of protoplasm is the granular. This changes into the alveolar type by
the appearance of spherules among the granules. The contents of the
alveoli constitute the alveolar substance; the inter-alveolar sap, the hya-
loplasm; the granules, the microsomes; and the walls of the alveoli may
be identified with the spongioplasm of the reticular type of protoplasm.
Another interpretation of alveolar protoplasm regards the content of the

FIG. 12. DIAGRAM ILLUSTRATING THEORIES OF PROTOPLASMIC STRUCTURE.

1, alveolar structure; granules occur only at the angles formed by the alveoli. 2,
filar structure, showing filar and interfilar substance. The centrosome (a diplosome)
is represented in this portion; it is surrounded by a clear attraction sphere. 3,
granular structure; coarse microsomes irregularly disposed. This portion contains
three foreign bodies which have been included by the cell, a streptococcus, a crys-
tal, and a spheroidal pigment mass. 4> the alveolar walls are formed by regularly
arranged microsomes; a vacuole is shown in this section. -5, reticular structure.

The cell is inclosed by a cell membrane, and contains a central nucleus in which are
shown the nuclear membrane, indistinct linin fibrils, deeply stained chromatin in
coarse threads and irregular masses (karyosomes), and a centrally situated nucleolus
or plasmosome.

FIG. 13. EGG OF THE. BLOOD STARFISH IN LATER GROWTH PERIOD.
Showing a stage in the change of an earlier granular to a later alveolar condition
of the cytoplasm. The nucleus contains many spherical nucleoli of various sizes.
The space (a) is a fixation artifact. X 1500.

11

12

INTRODUCTION PROTOPLASM CELL

alveoli as hyaloplasm. The microsomes may in part be closely associated
with the alveolar walls, perhaps forming them and the spongioplasm by

the process of coalescence. The so-called alveolar
protoplasm is in reality of the granulo-alveolar type.
The spherules probably arise, at least in part, by a
process of liquefaction of some of the granules. The
alveologranular is probably the commonest type of
protoplasm. The process of transformation of the
granular into the alveolar type can best be demon-
strated in young growing eggs of invertebrates. Fig.
13 shows an egg in which the perinuclear protoplasm
is predominantly alveolar, the more peripheral por-
tion granular. The metamorphosis is apparently
under the control of the nucleus.

Other commonly described types of protoplasmic
structure may be interpreted in terms of mechanical
(extraneous; artificial) alterations in the alveolar type. Thus a reticular
type may be derived from the alveolar through modification ( by pressure,

n

'

FIG. 14. PANCREAS
CELL OF TURTLE,
FILLED WITH ZY-
MOGENIC GRAN-

ULES.

n, nucleus, with
nucleolus. X 2000.

FIG. 15. MOTOR NERVE CELL FROM THE VENTRAL HORN OF THE SPINAL CORD

OF THE Ox.

Showing Nissl granules in the cell body and its dendritic processes. The non-
granular process at the left is the axon. p, pigment. (From Barker's "The Nervous
System," after von Lenhosse'k.)

STKUCTl 'UK OF I'KOTOI'LASM

13

or distortion) of the spherical alveoli into polyhedral or irregular eorn-
partments. Likewise the phrillar or fihir types may he interpreted as
similar more extensive modilicaiions resulting in ruptures of the alveoli
and consequent finer or coarser indiscriminate aggregations of spongio-

FIG. 16. INTERSTITIAL CELL FROM THE
TESTIS OF A TWENTY-ONE YEAR OLD
MAN, SHOWING GRANULAR AND FILA-
MENTOUS MITOCHONDRIA.
After Winiwarter.

FIG. 17. A NEURON (GIANT PYRAMIDAL
CELL, OR CELL OF BETZ) FROM THE
CEREBRAL CORTEX OF MAN, SHOW-
ING THE XEUROFIBRILS.

Bielschowsky technic. X 500.

plasmic fibrils, or as the result of the coalescence of granules to form
fibrils. The distinction between fundamentally granular and alveolar
protoplasm, and secondarily derived types of granular and reticular
(fibrillar) protoplasm must be emphasized. In the performance of spe-
cific functions, certain cells elaborate secretory gran-
ules (gland cells, Fig. 14'; nerve cells, Fig. 15; cells ^>
with crystalloids, Fig. 16) ; others produce various
types of fibrils (e.g., nerve cell. Fig. 17 ; connective
tissue cells, and muscle cells) ; others elaborate fat
spherules (e.g., Fig. 18) ; and still others a canalicu-
lar (trophospongium) apparatus (Fig. 19).

FIG. 18. DEVEL-
OPING FAT CELLS.

The fat droplets,
after extraction
with alcohol and
ether, appearing as
vacuoles. Hematein
and eosin. X 550.

The foregoing description of protoplasmic struc-
ture pertains largely to the 'fixed' (dead) condition. In
this connection the terminology employed will continue
useful. But recent more refined physiochemical studies
of living protoplasm have aroused considerable skepti-
cism, respecting the verity of actual specific structures corresponding to the
designations applied, more especially the spongioplasmic and linin network.^
Perhaps the most that can be said with certainty regarding the fundamental
structure of protoplasm is to describe it as a 'granular gel.' Kite's studies

14 INTRODUCTION PROTOPLASM CELL

(Anier. Jour. Phys., 32, 2, 1913) of the' physical properties and molar struc-
ture of protoplasm in various cells, by combined methods of microdissection
and vital staining, have led to clearer conceptions in this field. Kite ac-
cepts the interpretation of protoplasm as an emulsoid, the real structural

units of which are the colloidal particles; and he con-
ceives of the optical image as the result of the com-
bination of the physical phenomena of reflection, re-
fraction, diffraction, absorption, dispersion, interfer-
ence, and a scattering action on light. Living proto-
plasm is an apparently homogeneous and viscous
hydrogel, holding in suspension in the form of gran-
ules ('microsomes') minute masses of denser gels, and
liquid globules ('alveoli') which show many of the

optical properties of an oil drop. The 'network' and
FIG. 19. COLUMNAR ij^.i i i--, i ^-ii

CILIA/TED EPITHE- granules of the nucleus Kite regards as optical phe-

LIAL CELLS, SHOW- nomena, areas of greater concentration in the nuclear
ING CANALICULAR gel, not separated from, but grading into the sur-
APPARATUS. rounding diluter gel of the 'nuclear sap.' Spindle

After Holgrem. fibers were successfully dissected out of the proto-

plasm as distinct, relatively rigid threads. These con-
clusions are in the main in accord with those deduced from the earlier
physiochemical studies of protoplasm and colloids by Hardy and others.
M. R. and W. H.' Lewis (op. cit.) also find no sign of a reticular or of an
alveolar structure in either cytoplasm or nucleus in cells studied in tissue
cultures. They describe both cytoplasm and nucleus as 'finely granular
almost homogeneous in appearance.'

VITAL PROPERTIES OF CELLS

Living protoplasm is capable of certain specific reactions (physiologi-
cal processes) or functions. These reactions are spoken of as vital prop-
erties or attributes of protoplasm. They are general properties of living
matter. They include primarily (1) metabolism; (2) irritability; (3)
contractility; (1) reproduction.

(1) Metabolism. Metabolism is that property of living proto-
plasm by virtue of which it can elaborate from raw food material the
complex chemical compounds of protoplasm (anabolic phase, construc-
tive metabolism, assimilation), and convert the same into kinetic energy
for the performance of specific functions (katabolic phase, destructive
metabolism, dissimilation), e.g., secretion and excretion. Metabolism
generally involves growth and differentiation. Development also is

VITAL I'l.'Ol'MirriKS OF CELLS 15

fundamentally a metabolic process, and in essence consists of 'a progres-
sive differentiation of complex and specialized structures and functions
from relatively simple and geiierali/ed beginnings' (('onklin ) .

(2) Irritability. Irritability, or sensitivity, is a fundamental or
general property of protoplasm. It is characterized by a capacity to
receive and make response to stimuli, by changes of vital processes. Its
prerequisite is the protoplasmic property of con<lnc/iri///. and its expres-
sion in many instances depends upon tbe property of conlriic/iliti/. In
a comprehensive sense, stimulus is every alteration in the external vital
condition (Verworn). The reaction to stimuli may exhibit itself in
one of three modes: functional, nutritive, and formative (A r erworn).

'

FIG. 20. SUCCESSIVE STAGES IN THE MOVEMENT OF AN ARIEBA.

The cells contain a nucleus, a contractile vacuole and protoplasmic granules.
(After Verworn.)

Stimuli are of various sorts, e.g., thermal, mechanical, chemical, photic,
solar, galvanic (or electric), fluid, current, gravity. The simplest re-
sulting reactions, expressed in unicellular forms in terms of orientation
(tropism) or contact (taxis) represented by automatic responses or
reflexes in higher forms are respectively thermotropism, stereotropism
(barotaxis; thigmotaxis), chemotropism, phototropism, heliotropism,
galvanotropism, hydrotropism, rheotropism, and geotropism. Eesponse
may be either toward or away from the source of stimulus. In the case
of the electric current or water currents, for example, simple organisms
may orient themselves, or protoplasm may move, in line with or opposite
to the current ; these opposite reactions are called positive and negative
troi>ixntx respectively. Eesponses involve fundamentally metabolic
changes.

(3) Contractility. Motion results from response to certain stim-
uli, that is, by reason of irritability; and it is dependent upon the vital
phenomenon of contract Hit//. Motion is of various types, predominant
among which are (a) ameboid, (b) ciliary, (c) molecular, (d) circula-
tory (streaming; protoplasmic), and (e) muscular.

16

INTRODUCTION PROTOPLASM CELL

FIG. 21. A LEUKOCYTE FROM HUMAN BLOOD IN

ACTIVE AMEBOID MOTION.

The figures indicate the successive forms assumed
by the cell. Drawings were made at intervals of one
minute. X 500.

---

(a) Ameboid n/o/ilih/ is exemplified in the movements of an ameba;
hence the name. This consists essentially in the formation of a proto-
plasmic process or pseudopodium, into which the main mass of proto-

plasm flows, thus pro-
ducing progression (Fig.
20). The movement of
the white blood-corpus-
cles is of this sort (Fig.
21).

(b) Ciliary motility
is characteristic of hair-
like processes of certain
cells; such processes or

cilia represent essentially permanently differentiated delicate pseudo-
podia. The method of cilium formation is illustrated in its simplest
form in the transient vibratory processes that arise under certain condi-
tions on leukocytes (Fig. 225). In metazoa generally ciliated cells are
attached, motion being limited to the cilia, which are located 011 the free
border. The function of cilia is to pro-
pel secretions toward the surface. The
motion is wavelike and always in one
direction. The cilia are generally at-
tached to a double row of granules, the
'basal bodies' (Fig. 22), perhaps parti-
tion products of the centrosome. In
Protozoa, e.g., Paramecium (Fig. 3),
the entire surface of the cell may be
ciliated; the function of the cilia here
being progression, and the direction of
stroke is reversible. Certain cilia are
non-motile, e.g., in the epididymis,
where they are closely clumped into
brushlike masses (Fig. 25). The func-
tion of such cilia is, in part at least, to
furnish a means for the elimination of

secretions. Flagellnte motion is to be regarded as a variety of ciliary
motion. A flagellum is commonly regarded as a more robust cilium.
The purpose of flagella is to propel the cells to which they are attached.
I'-iially in higher animals the number of flagella is limited to one to a
cell. The best examples of flagella are furnished by spermatozoa (Fig. 2.'! ) .

FIG. 22. THREE CELLS FROM THE
EPIDIDYMIS OF THE RABBIT.

The non-ciliated cell has a diplo-
some at its free border. The ad-
jacent ciliated cells have in place a
double row of 'basal granules' to
which the cilia are attached. (After
v. Lenhossek.)

VITAL PROPERTIES OF CKLLS 17

(c) Molt'cit/iir iiiijlilili/ is a dancing or oscillatory mo\ement of the
granules in living protoplasm. Such granules may he non-living matter,
pigment, etc. This type of motion is also called broiniitm nntrcninil .
It is probably purely a physical phenomenon. It may be simulated by
mixing finely divided carmin Avith glycerin.

(d) Circulatory or streaming movement is present in various de-
grees in probably all living protoplasm. It is only when it is rapid
that it becomes easily discernible. It is readily demonstrable in certain
cells, e.g., chara and nitella; also less readily in certain protozoa (Para-
mecium). It must most probably be interpreted as a form of respira-
tion. It is characterized by a flowing

or streaming of the protoplasmic gran-
ules in a definite direction.

(c) The reason for listing IHHXI-H-
lar as a separate type of motility is
mainly its predominance in animals
and the fact that it does not apparently
fully conform to any of the above types.

It is characterized by a reversible FlG . 2 3.-CiLiATE AND FLAGELLATE

process of contraction of specially dif- CELLS.

ferentiated muscle fibrils. It perhaps A, ciliated cells isolated from the

most closely resembles streaming motil- trachea of a cat; B, human sperma-

-, T4. i T i s tozoa 1. in surface view; 2. in

ity. It leaas to least confusion, m view profile Examined fresh in normal

of our present lack of definite knowl- saline solution, x 550.
edge regarding the physical and chem-
ical phenomena underlying muscular motion, to speak of it as a distinct
type. It will be further discussed under Muscle.

(4) Reproduction. The essence of reproduction is cell multiplica-
tion. A living cell has the power of producing other cells like itself.
Viewed philosophically, cells may conceivably arise in two different ways:
(1) from non-living material, spontaneous generation (abiogenesis) ; (2)
from preexisting cells by division. Science has quite generally accepted the
aphorism 'omnis cellula e cellula' (Virchow) as an expression of the
whole truth. However, full acceptance of the doctrine of evolution logi-
cally compels belief in spontaneous generation : this not in any such
crude form as that frogs may arise from the mud of rivers, or insects
from dew or dung, but that given the conditions (conceivably possible
somewhere in the universe to-day) prevalent when life first appeared as
the original mass of living protoplasm, the 'cytode' or 'cytoblastema,' the
inorganic may continually be passing into the primarily organic, e.g.,

18

INTRODUCTION PROTOPLASM CELL

monera (Haeckel), but not perceptible under our present means of
search and observation. This is the position urged by one of the leading
physiologists and histologists (E. A. Schaefer) of our day, following
Spencer of the preceding generation.

However, in histology we need be concerned only with the derivation
of cells from preexisting cells. This proceeds in one of two ways: (a)
direct, amitotic, or akaryokinetic ; and (b) indirect, mitotic. or karyokin-
etic. The difference between the two inheres in a difference in behavior
on the part of the nucleus (or karyon). Comparative studies of the

FIG. 24. SUCCESSIVE STEPS IN AMITOTIC DIVISION IN TENDON CELL OF NEW-BORN

MOUSE.

(After Nowikoff. X 800.)

lower groups of animals and plants have revealed a fairly complete series
of intermediate stages. On the basis of these facts it is believed by some
(e.g., Strasburger) that amitosis is the primitive method of cell
multiplication, mitosis the derived or more highly specialized type.
Others regard amitosis as the derived, not the primitive form of
division.

Cell division is presumably due to the fact that the area of the
surface increases as the square, the volume as the cube, of the diameter.
In consequence, the periphery becomes more favorably placed with respect
to the nutritive medium than the more central portions. The time then
arrives when the center must suffer nutritive want or when the nucleus
becomes unable to exert its trophic functions at the distance of the ad-

VITAL PROPERTIES OF CELLS

19

vancing periphery. Division of such an enlarged cell into i\vo smaller
cells reestablishes the original and more favorable nuclco-cytoplasmir
dimensional relationship.

(a) AMITOSIS. In typical amitosis the nucleolus first heroines bi-
lobed and then divides ( Fig. 24). This is followed by nuclear division.

^

FIG. 25. SUCCESSIVE STAGES IN THE AMITOTIC DIVISION OF THE CILIATED CELLS
LINING THE VASA EFFERENTIA OF THE EPIDIDYMIS OF THE MOUSE. X 1500.

- i . .

each resulting nucleus enclosing one of the nucleoli. Nuclear division is
followed by cytoplasmic division. A centrosome is generally neither
active nor even visible during this process. This typical condition is
rarely realized. It was first described by Kemak (1841) for blood-cells.
Usually nuclear division is in-
dependent of nucleolar fission,
which may be lacking (Fig.
25). The nuclear fission pro-
ceeds variously by a medial or
submedial annular constric-
tion, or by progressive linear
indentation of some portion of
the surface. In certain in-
stances the division takes place
inside of the original nuclear
membrane. The nuclear prod-
ucts may be of unequal size,
and multiple (Fig. 26). Gen-
erally cytoplasmic division lags FlG ' 26. MULTINUCLEATED GlANT CELL,
n T n , . . . FROM THE \ OLK-SAC OF A 10 MM. PIG

tar behind nuclear division, or EMBRYO. X 2000.

may even fail to appear, thus

producing hi- or multinucleate cells. Amitosis effects a mass division of
the nucleus ; neither spireme nor chromosome nor achromatic spindle, so
conspicuous in mitosis, appear. Until quite recently amitosis was gen-
erally regarded as a relatively rare and unimportant process. It was

^"""K ' ""^

r ' X

6

,-. *

20 I XTBODUCTION PEOTOPLASM CELL

supposed to be associated only with highly specialized and pathological
conditions leading inevitably to death. Cells once having suffered ami-
totic division were believed not to be capable of thereafter dividing mitot-
ically. The work of Child (Biol. Bull., 1907) has shown, however, that
it is probably of very wide occurrence. Instances have been described in
most of the animal groups, including the vertebrates. Child has shown
its occurrence in regions of rapid growth, as in various embryonic tissues,
e.g., blastoderm of chick (Patterson), and where a secretion is elaborated
or in places of reserve formation. These facts may be harmonized with
its occurrence in starving, degenerating tissues on the basis of a common

underlying condition, namely,
relative scarcity of nutritive

r material. Wicman conceives

of amitosis as due to scarcity
of oxygen supply.

Where mitosis and amitosis
are simultaneously present, it
is more frequently the cells
with the large nuclei, sur-
rounded bv a considerable
*

B amount of undifferentiated cy-

toplasm, that divide by mitosis.
The factors underlying amito-
** sis most probably exert their

FIG. 27. SPERMATOCYTE OF PYEKIS CRA- fi na i e ff ec t indirectly through
TEGI. A BUTTERFLY, SHOWING A CILIUM . ... , . a
ATTACHED TO THE CEXTROSOME. mitial "^uence upon the ceil-

(After Meves.) trosome. The best experi-

mental evidence in favor of

this view is supplied by Xathansolm who grew Spirogyra, normally
dividing by mitosis, in a 1 per cent, solution of ether in water, when
the cells divided amitotically. On transference to pure water, the cells
again divided mitotically. The ether seems to have exerted a 'stupe-
fying' effect upon the kinoplasm (centrosome material), compelling
division by amitosis. Amitosis is now generally conceded to be of
wide occurrence under certain conditions and in certain cells, but it is
still quite unanimously disbelieved to occur in germ cells. In the lat-
ter it has perhaps not yet been certainly demonstrated to occur in cells
actually in the germ cycle. In Mammalia amitosis can be demonstrated
in the intermediate layers of stratified squamous (skin), transitional
(bladder) and certain ciliated (epididymis, Fig. 25) epithelia; in the

H

FIG. 28. DIAGRAMS ILLUSTRATING SUCCESSIVE STAGES OF MITOSIS.

A-F, prophase; G, metaphase; H, anaphaso; I-J, telophase. a, achromatic
spindle; c, centrosome; ep, equatorial plate of chromosomes; if, interzonal fibers;
n, nucleolus. (After Wilson.)

21

22

INTRODUCTION PEOTOPL ASM CELL

medulla of the adrenal, and in decidual cells. In ciliated epithelia this

mode of division is perhaps associated with a partition of the centro-

some in the formation of cilia. This will be further discussed under

a Ciliated Epithelia.

This view is sup-
ported by the fact
that the flagella of
spermatozoa arise
from the centro-
some, and the ob-
servation that in
certain cells the
centrosome of mi-
totic spindles de-
velops cilia (Fig.
27).

(b) MITOSIS.
This is the prevail-
ing type of cell di-
FIG. 29. CELLS FROM EPIDERMIS OF THE SALAMANDER. vision. For con-
Three cells are in process of division by mitosis, a, venience of descrip-
prophase; 6, anaphase. The second cell above b, whose {ion ^] ie process
cell body is in process of fission, presents a stage of the 1-1 e

telophase. (After Wilson.) which mus

course be thought

of as continuous, may be divided into (1) prophase; (2) metaphase; (3)
anaphase; and (4) telophase. An alternative and preferable terminology
employs the words anaphase (prophase), mesophase (metaphase) and
kataphase (anaphase and telophase). These phases involve coincident
changes in the nucleus and the archoplasm (attraction sphere, Fig, 28, A
to J). Mitotic figures can be seen in all rapidly growing tissues. The
process is an essentially similar one throughout the plant and animal
kingdoms; variations relate only to details associated chiefly with the
archoplasm. The most favorable locations for study of mitosis are the
growing tips of roots of certain plants, e.g., onion, hyacinth, dogtooth
violet, amphibian tissue (particularly skin and blood-cells), and the
testes of grasshoppers. Mitosis in germ cells involves certain specialized
features, and calls for additional theoretical consideration; hence the
description of these maturation mitoses will be reserved for the chapter
dealing with the ovaries and testes, where a complete account will follow.
Among the simplest types of mitosis, and those best adapted for labora-

FIG. 30. SUCCESSIVE STAGES OF MITOSIS IN THE ROOT TIP OF THE DOGTOOTH VIOLET

(ERYTHRONIUM AMERICANUM).

a, resting nucleus; 6, close spireme; c, loose spireme; d, segmented spireme; e, late
prophase;/and g, metaphase; h and i, anaphase;jW, telophase (showing mid-body or
cell plate) ; m and n, daughter cells, n, with resting nuclei. X 1500.

23

24: INTRODUCTION PEOTOPLASM CELL

tory study, at least as an approach to the subject, is that shown in the
root tip of the dogtooth violet (Fig. 30, a to n). The cells and the mi-
totic figures are here so large that all the major details can be easily
recognized by use of the usual dry high power lenses of the microscope.
(1) Pro phase. This stage can again be subdivided into that (a)
of the resting nucleus; (b) of the nucleus with close spireme; (c) of the
nucleus with the loose spireme; and (d) of the segmented spireme.
Coincident with these nuclear changes, the centrosome in animal cells
divides into two (diplosome) ; these moieties move apart toward opposite
poles of the nucleus and build a spindle (amphiaster) between them-
selves. Meanwhile the nuclear membrane begins to disappear, only a
remnant distant to the achromatic spindle persisting at the end of the
prophase. In the root tip cell of the dogtooth violet and in plant cells
generally, the spindle appears in less conspicuous fashion than in animal
cells. A centrosome is apparently lacking. The first indications of the
spindle are the polar caps of faint radiations which grow medially to build
the spindle. The resting nucleus (Fig. 30, a) is characterized by a
random, granular, nuclear reticulum with net-knots and one or several
nucleoli. This reticulum becomes changed into a delicate, deeply chro-
matic, probably continuous, close spireme (Fig. 30, b). By process of
shortening and thickening, 'this changes into the loose spireme stage
(Fig. 30, c). The nucleoli have meanwhile contributed chromatic sub-
stance to the spireme, but may persist for some time longer as achro-
matic, ultimately fragmenting or dissolving, bodies. On closer inspection
the close spireme is seen to consist of a series of granules (chromomeres) ;
during the loose spireme stage these become split, thus giving rise to
a double row of granules. The loose spireme passes into the succeeding
stage (segmented spireme, Fig. 30, d) by transverse segmentation into a
number of rods or chromosomes. At this stage all indication of chro-
momeres is generally again lost, the chromosomes appearing as compact,
deeply staining rods of various shapes.

The number of chromosomes is believed to be constant for all cells of
a species. This belief rests upon data of actual counts in various insects and
other lower animals and certain plant forms. Here the number is rela-
tively small, and the individual chromosomes are large and can in conse-
quence be readily counted. (Certain qualifying statements must be made
in the chapter which includes a discussion of sex determination.) Attempts
have recently been made to throw doubt upon the matter of a specific chro-
mosome constancy, but it is only fair to note that these attempts have
dealt with relatively unfavorable material, where exact chromosome counts

VITAL PKOI'HIi'TlKS OF CELLS

are extremely difficult if not at present actually impossible. It may be
noted in passing also, tb.it the chromosomes are believed by many to be the
bearers of the determiners of hereditary characters a point to be further
discussed below.

(2) Metapliase. This is a relatively brief stage in mitosis. It
includes the period when the chromosomes are arranged upon the spin<il>'
in the equatorial plate. Seen in polar view this is called the nintinxh'r
stage (Fig. 30, e). In this stage the chromosomes split longitudinally.
In dogtooth violet the number of chromosomes is twenty-four. A com-
mon form of chromosome is the U-shaped type. The point of attachment
to the spindle is the apex of the bent chromosome (Fig. 30, f). In the
more rapidly growing cells the double or split condition of the chromo-
somes has remained discernible since the preceding telophase, a true
resting stage having been omitted. At metaphase the already longi-
tudinally split chromosomes are completely divided, and the sepa-
rated moieties (daughter chromosomes) drawn toward opposite poles
(Fig. 30, g).

(3) AnapJiase. The limits of this phase are indefinite (Fig. 30,
h to j). It may be said to include all stages between that when the
separation of the daughter chromosomes, resulting from the longitudi-
nally splitting of the mother chromosomes, is completely consummated,
and that when the groups of daughter chromosomes drawn to either pole
are still distinct. Seen in side or oblique view the later stages of this
phase present a double star arrangement of chromosomes hence
diaster stages (Fig. 30, i). The daughter chromosomes, an equal
number at either pole, were drawn apart by activity of the outer-
most of the spindle fibers (called man/It' fibers) presumably by process
of contraction. The inner or 'interzonal fibers' constitute the centra I
spindle.

(4) Telopliase. Meanwhile a plate of granules (cell plate: mill-
body) has appeared in the equatorial region of the spindle. This marks
the plane of the future division (Fig. 30, j and k). In animal cells, an
annular constriction appears peripherally in the cell membrane. This
proceeds centrally throughout telophase until ultimately the mother-cell
is divided into two daughter-cells. The constriction of the cells in divi-
sion is generally interpreted as a phenomenon of alteration in surface
tension. Coincidently with the steps of this process, the chromosome-
and centrosomes (archoplasm material in plants) pass through the stages
of the prophase, but in inverse order : segmented spireme. loose spireme.

T.b.l.

. hi. S.I.

r.S.

FIG. 31. SUCCESSIVE STAGES IN THE MATURATION, FERTILIZATION AND SEGMENTA-
TION OF THE STARFISH (ASTERIAS FORBESII) EGG.

a, first maturation spindle (m.s.l) and the spermatozoon (s); 6, formation of the
first polar body (p.b.l) and the residual substance of the nucleus (r.s.); c, second
maturation spindle (m.s.2) ; d, female pronucleus ( 2 ) ; e, union of male ( $ ) and female
pronuclei (the male pronucleus is derived from the spermatozoon) ; /, first segmenta-
tion spindle; g, two-cell stage of division, d and e are less highly magnified.

26

HISTOGENESTS

27

close spireme, resting daughter nucleus with its daughter centrosome
and ultimately a nucleolus (Figs. :><>, k, 1, in, n). Where a cell plate
appears, division is consummated without constriction. In certain
pathological tissues, e.g., cancers, the cells divide in various
atvpical ways, involving the formation of tri- and multipolar spin-
dles.

HISTOGENESIS

Every higher organism begins as a fertilized egg or zygote; this in-
volves the fusion of a male (spermatozoon) and a female (egg) germ cell
(Fig. 31, a and e). The result of the fusion is a mingling of approxi-
mately equal parts of
paternal and mater-
nal chromatin (pre-
sumably the basis of
specific heredity) ; a
large mass of mater-
nal cytoplasm and
nutritive substance
with a small, but
perhaps important
mass of male cyto-
plasm; and a coinci-
dent stimulus to de-
velopment. The fer-
tilized egg divides by
mitosis into two
spheroidal cells the
typical embryonic
form orblastomeres
(Fig. 31, f and g),
and each of these

FIG. 32. TRANSVERSE SECTION OF A FROG EMBRYO,
SHOWING THE THREE GERM LAYERS.

a, neural crest; b, neural groove; c, neural plate; d>
ccelom; e, ectoderm;/, mesoderm; g, entoderm; h, somite;
i, notochord; j, parietal niesoderm; k, visceral meso-
derm; I, yolk; central opening, the primitive intestine.
(Drawing by G. A. Pagenstecker.)

again into two, the
segmentation process
continuing until the adult organism results as an aggregation of innumer-
able cells. This process of growth through cell multiplication is accom-
panied by cell differentiation, which constitutes histo genesis. The first
outstanding stage in the differentiation is that when the three funda-

INTRODUCTION PEOTOPLASM CELL

mental germ layers: ectoderm (ectoblast; epiblast), mesoderm (meso-
blast), entoderm (endoblast; hypoblast) have appeared (Fig. 32). Back
of this of course must lie a more fundamental differentiation, perhaps
already present in the unfertilized egg, a predelineation of adult struc-
ture destined to develop from localized egg materials. By the process of
histogenesis all the adult tissues arise from the several germ layers. This
matter is summarized in the following table :

ADULT TISSUE DERIVATIVES FROM

ECTODERM

Epidermis and its de-
rivatives : hair, nails,
and epithelium of se-
baceous, sweat and
mammary glands.

Epithelium of mouth
and its derivatives :
enamel, taste buds,
epithelium of salivary
and other b u c c a 1
glands, and anterior
portion of hypophysis.

Epithelium of anus,
and distal portion of
the male urethra.

Epithelium of nos-
trils and communicat-
ing glands and cranial
sinuses.

Epithelium of con-
junctiva and associated
ducts and lacrimal
glands. The lens, and
the epithelium of the
pars nervosa, ciliaris
and iridica retinae.

Epithelium of mem-

MESODERM

Epithelium of urinif-
erous tubules, renal
pelves and ureters.

Epithelium of the
seminiferous tubules
and the associated ex-
cretory ducts of the tes-
tis; epithelium of ovi-
duct and uterus; prob-
ably also the sex cells.
The cortex of the su-
prarenal gland. All
muscular tissue ; con-
nective tissue; vascular
tissue (blood and
lymph vessels and
cells), and lymphoid
organs in general.

Epithelium (meso-
thelium) of pleurae,
pericardium and peri-
toneum ; of the tendon
sheaths, joint cavities
and bursae; and of the
chambers of the eye,
and the p e r i 1 y m p h
spaces of the internal

ENTODERM

Epithelium of diges-
tive tract (including
pharynx; excluding
mouth and anus) and
associated glands:
pharyngeal, esophageal,
gastric, intestinal, pan-
creas and liver, with
gall-bladder.

Epithelium of middle
ear (tympanum) and
auditory (Eustachian)
tube. Epithelium of
respiratory system, be-
yond nostril. Epithe-
lium of thyroid, para-
thyroids, and the thy-
mic reticulum and cor-
puscles.

Epithelium of female
urethra, proximal part
of male urethra, and of
the urinary bladder.

Epithelium of pros-
tatic and Cowper's
glands in the male,
and of the glands of

CVTOMORPIIOSIS

ECTODERM

branous labyrinth of
internal ear, and lining
of external ear.

Epithelium lining
the central canal of the
spinal cord, and the
ventricles of the brain.

All neurons and neu-
roglia of the nervous
system.

Certain ductless
glands : pineal, posteri-
or (nervous) portion of
hypophysis, medulla of
suprarenal, and the
chromaffin system or
paraganglia.

Possibly smooth mus-
cle associated with
sweat glands, and in
iris of eye.

MKSOIIKKM

EXT<>ni:i;\l

ear (scake tympani and
vestibuli).

iJarthnlin
male.

in the fe-

Nuclei pulposi of
vertebra 1 , remains of
the embryonic noto-
chord.

CYTOMORPHOSIS

From the standpoint of the individual cells of tissues, histogenesis
involves progressive and regressive changes. This process may be desig-
nated as cytomorphosis (Minot). The gradual acquirement of definite
form by development is known as morphogenesis. Cytomorphosis in-
cludes several successive steps: (a) undifferentiated or embryonal stages;
(b) differentiated stage, during which the cell acquires and maintains its
maximum differentiation expressed structurally by a definite shape and
specific content and performs its specific function; (c) regressive, when
the function gradually wanes, and finally fails (reflected in coincident
protoplasmic alterations), the cell concerned suffering death and ulti-
mately removal from the body.

With this preliminary general view of protoplasmic organization and
function (general cytology) we are prepared to approach histology proper.

CHAPTER II

EPITHELIAL TISSUES

TISSUES

A tissue in the histologic sense is a collection of similarly specialized
cells united in the performance of a particular function, e.g., liver tissue.
In certain tissues the cells are joined together by an intercellular cement
substance, e.g., epithelia, a secretion product of the cells themselves.
Through this cement may extend the so-called 'intercellular bridges' or
cytodesmata (Fig. 33), the minute intervening spaces forming delicate

' - - ! --' -. *W T ^ F J*S ; J'

'*&&^ '

FIG. 33. GROUP OF EPITHELIAL CELLS FROM THE MALPIGHIAN LAYER OF

THE SKIN.

The intercellular bridges are very distinct. Hematein and eosin. X 1,000.

canaliculi, presumably for mediating the transfer of nutritive material
from cells more favorably placed with respect to the source of supply to
those less favorably located, e.g., epidermis; these bridges arise through
process of vacuolization in the exoplasm of adjoining cells, the walls
of the original vacuoles persisting as 'bridges/ Through such bridges,
fibrils may extend from cell to cell. Practically every tissue contains

30

TISSUES

31

also connective tissue elements for unification and support: also vascular
and nervous constituents. Tissues in which the cell boundaries are ab-
sent are known as t>yn<-y1i(i (Fig. 34). A syncytium may obviously arise

through nuclear proliferation in the ab-
sence of cytoplasmic division, or as the
result of the disappearance of original
cell boundaries. We mav distinguish

m

.

,

FIG. 34. A VILLUS OF THE HUMAN
PLACENTA, SHOWING A PERIPH-
ERAL SYNCYTIUM OP IRREGULAR
THICKNESS.
The connective tissue inclosed

by the syncytium contains three

capillary vessels. Hematein and

eosin. X 500

^W^V ^- -

i~ . !

A

FIG. 35. CELLS FROM THE PANCREAS OF
NECTURUS, CONTAINING SECRETORY GRAN-
ULES AND BASAL ERGASTOPLASMIC FILA-
MENTS. (After Matthews.)

the following fundamental tissues : (a) epithelial; (b) connective; (c)
muscular; (cl) nervous; and (e) vascular.

Lymphoid tissue may be regarded as still another fundamental tissue;

FIG. 86. VARIOUS FORMS OF CELLS.

a, squamous epithelium from the tongue; b, a columnar cell from the small intestine;
c, a polyhedral or spheroidal cell from the liver; d, a smooth muscle cell from the mus-
cular coat of the stomach. X 550.

or it may be 'included under vascular tissue. In fact from the genetic
viewpoint, vascular may be included under connective tissue, since both
arise from the mesenchyma.

32

EPITHELIAL TISSUES

Representatives of all of the fundamental tissues are generally found
in all histologic preparations, or tissues in a general sense. Cells vary
greatly both from the standpoints of shape and contents in the various
tissues both depending upon the types and phases of function. The
more usual form variations include: (a) spheroidal, spherical (e.g., em-
bryonic cells and egg cells, Fig. 1, chap. I), polyhedral (spherical cells
modified by pressure from adjacent cells, e.g., liver cells, Fig. 37) ; (b)
scalelike or squamous (e.g., super-
ficial cells of mucous membrane of
mouth, Fig. 36, a) ; (c) columnar,
prismatic or cylindrical (e.g., cells
lining intestine, Fig. 38, b). Col-
umnar cells, when very short, are

FIG. 37. -- POLYHEDRAL EPITHELIUM,
FROM A SECTION OF THE HUMAN
LIVER.

The central blood papillary contains
one leukocyte, and its wall contains the
nucleus of a flattened endothelial cell.
Hematein and eosin. X 550.

FIG. 38. GOBLET AXD COLUMNAR CELLS
FROM THE LARGE INTESTINE OF THE
CAT.

A, Goblet cells; B, isolated columnar
cells. X 900.

usually designated cubical or culoidal (e.g.. bronchioles and rete testis,
Fig. -43) ; intermediate lengths may be designated either tall cuboidal or
short columnar ; when modified by confinement in an alveolus into a
pyramidal shape as in glands, they may be called pyramidal or 'glandu-
lar' (Fig. 46). Glandular cells, moreover, are characterized also by an
internal differentiation commonly expressed in the form of granules or
filaments. Columnar cells may be further modified by the appearance of
cilia into ciliated epithelium (e.g., trachea, bronchial tube, Fig. 53), or of
mucus into goblet cells or 'unicellular glands' (e.g., intestine, Fig. 38, a) ;
or as specialized receptors for stimuli of special sense they may become
modified as neuro-epithelium (e.g., certain cells of eye, ear, nose and
tongue).

EPITHELIAL TISSUES 33

EPITHELIAL TISSUES

Epithelia are cellular membranes covering' the surfaces and lining
the internal cavities of the body. They serve for protection, secretion, ex-
cretion, and the reception of stimuli. The constituent cells may be of any
of the above enumerated forms. The spheroidal types, however, are
found only in embryonal membranes. The term spheroidal epithelium
is sometimes employed to designate masses or solid columns of spheroi-
dal cells, such as appear in the sex cords of the developing testis and
ovary, and in the early stages of glands. They are in general, outgrowths
or evagination from embryonic or undifferentiated epithelia.

An epithelium may consist of a single
layer of cells, when it is called non-strat-
ified or simple epithelium. A complete
description, however, must include the
name of the preponderating type of cell,
e.g., simple columnar epithelium, or si in-
pie squamous epithelium, as the case may
be. Moreover, an epithelium may consist FIG. 39. COLUMNAR EPITHE-

P 1 i -, i LIUM FROM THE PYLORIC RE-

of several or many layers, w.hen it becomes GIQN QF THE HUMAN STOMACH .

a complex or stratified epithelium. The (Profile view.)

uppermost type of cells gives the name to Hematein and eosin. X 550.

stratified epithelium; for example, in the

epidermis the outermost cell is of .the squamous type, though the middle

cells are polyhedral, and the innermost columnar ; hence called stratified

squamous epithelium (Fig. 49).

In the stratified epithelia the superficial cells arise through cell divi-
sion in the deeper layers, and if they become detached by abrasion, dis-
integration, or by other physiological or pathological processes, they may
be replaced by cell reproduction occurring in the lower layers. When
but a single layer of cells is present, as in the simple epithelia, loss of
cells over large areas will obviously become more difficult of replacement
by cell division. Hence it is that repair of extensively destructive patho-
logical conditions involving such epithelial tissues becomes exceedingly
difficult and often impossible, as, for example, in the alveoli of the lung.

Each epithelial cell is to some extent a secreting cell. Sometimes
secretion is its chief function, as is the case with goblet cells, which
might well be called 'unicellular glands,' and which secrete abundant

mucus. The same is true of those cells which form the parenchyma of
4

34

EPITHELIAL TISSUES

secreting glands, such as the salivary glands, kidney, and liver. In many

cpithelia, however, secretion is a subsidiary function, protection being

the primary purpose.

In all epithelia a cement substance is present between the cells.

Tliis becomes especially abundant and dense between the distal ends of

the cells of columnar epithelium, and
is here known as terminal bars (Fig.
40). Cement substance has the pe-
culiar property of precipitating sil-
ver nitrate from solutions, which
turns black on exposure to sunlight.
This furnishes an especially favor-
able technic for demonstrating cell
boundaries. All epithelia, simple or
stratified, rest upon a homogeneous
basement membrane or membrana
propria, frequently a product of the

FIG. 40. 'TERMINAL BARS' OP CEMENT
SUBSTANCE AS SEEN BETWEEN THE
EPITHELIAL CELLS OF A TUBULAR
SECRETING GLAND IN THE PYLORIC
REGION OF THE HUMAN STOMACH.

The columnar epithelium is seen in
profile at a; at b, the free ends of the
cells are seen. Hematein. X 550.

cells themselves but occasionally of
connective tissue origin, and a sub-
jacent connective tissue supporting
membrane or tunica propria (or
corium). The latter only contains

blood and lymph vessels from which the epithelial cell must draw nour-
ishment by process of absorption, and transfer through 'intercellular
bridges.' It furnishes support also for the nerve supply. We may now
consider briefly the usual types of simple and stratified epithelia. The
main facts are summarized in the appended outline :

CLASSIFICATION OF EPITHELIA

I. SIMPLE (NON-STEATIFIED) EPITHELIA those which com-
pose a membrane but one cell in thickness.

1. Squamous,
composed of
flattened,
scale-like
cells.

(a) Lining closed cavities.
Pavement epithelium

or (1) endothelium; heart, arteries, capillaries, veins,
and lymphatic vessels.

(2) mesothelium ; serous membranes.

(3) mesencliymal epitln limn : synoviul membranes,

bursae, and tendon sheaths, lining of the anterior

EPITHELIAL TISSUES

35

1. Squamcms,

((imposed of
flattened,
scale-like
cells.

2. Columnar.

chamber of lh<> eye, and of the perilymph spaces
of the internal ear.

(b) Lining the alveoli of the lungs, some tulniles of

the kidney, the middle ear, and the membranous
labyrinth of the internal car.

(c) As the superficial cells of stratified epithelium

(i-idc infra).

(a) Lining the mucous membrane
of the alimentary tract stom-
ach, small intestines, large in-
testines, gall-bladder.

(b) Lining the ducts of all secret-
ing glands liver, pancreas, sali-
vary, lacrimal, and mammary
glands, testicle, prostate, kidney,
etc.

(c) The deepest layer of cells in
stratified epithelium is composed
of columnar-shaped cells, which,
however, differ in structure from,
the true columnar type.

f (A) Plain

(B) Modified
(1) Ciliated

(2) Pyramidal
or 'glandular'

(3) Goblet*

(a) Lining the uterus and ovi-
ducts.

(b) Lining portions of the ventri-
cles of the brain and central
spinal canal of the embryo and
infant. (In later life these cells
lose their cilia.)

The secreting cells of all tubular
glands kidney, pancreas, sali-
vary glands, intestinal glands,
etc.

(a) Respiratory tract nasal,
pharyngeal, tracheal, and bron-
chial mucous membranes.

(b) Alimentary tract stomach,
small and large intestines.

* Cells whose protoplasm has been converted into raucinogen.
be considered unicellular, mucus-secreting glands.

They may

36

EPITHELIAL TISSl'KS

2. Columnar.

Xeuro-epi-
t helium.

f (a) Eye the rod and cone cells
of the retina.

(b) Ear in the cristse and mac-
nine of the labyrinth and in Cor-
ti's organ.

(c) Xose in the olfactory mucous
membrane (true neuron).

(d) Tongue in the taste buds.

II.

1. Squamous.

2. Columnar
(Pseuclo-
stratified
columnar).

3. Transitional.

COMPLEX (STEATIFIED) EP1THELIA those whose cells
form several superimposed layers.

Forms the epidermis of the skin,
and covers the free surface of
those mucous membranes which
clothe all orifices in direct con-
nection therewith viz., the con-
junctiva and cornea; the exter-
nal auditory canal; part of the
nasal mucous membrane ; mouth,
pharynx, and esophagus; epi-
glottis and vocal cords; anus, as
high as the internal sphincter;
vagina and external portion of
the urethra.

Superficial cells,
squamous;
deeper, polylie-
dral; the deep-
est, columnar
in shape.

Superficial cells,
columnar;
deeper cells,
polyliedfal or
spindle-sliaped.

(a) Non-ciliated
(rare)

(b) Ciliated.

Superficial cells
only somewhat
flattened; next
deeper layer,
pear-shaped;
deepest layers,
polyhedral.

(a) Part of vas deferens.

(b) Eespiratory tract; nasal mu-
cous membrane and passages
connected therewith, tear-ducts,
auditory tube, etc., larynx,
trachea, and bronchi.

Genital tract; epididymis and vas
deferens.

Found only in the urinary system
viz.. pelvis of the kidney, ure-
ter, bladder, and first portion of
the urethra.

NON-STRATIFIED Kl'ITIIELIA

37

I. NON-STRATIFIED EPITHELIA

1. SiMi'u: SQUAMOUS

(Pavement E [lilli cTnim}

This variety of epithelium comprehends two main groups: (1) the
endofhelia, lining the vascular system, and (2) the mesotliclia of the
serous memhranes lining the large internal closed cavities pleurae, peri-
cardium and peritoneum. This distinction is ,.

somewhat arbitrary hut nevertheless useful, and
derives justification in that endothelia arise in
the first instance from syncytial mesoderm (mes-
enchyme) and mesothelium from epithelial meso-
derm.

But according to Bremer (Amer. Jour. Anat.,
16, 4, 1914), at least some of the earliest blood-
vessels in man also arise from true mesothelial
cells. Mesothelium lines the extra-embryonic
body cavity and is reflected over the yolk-sac and
body-stalk. In the latter location Bremer de-
scribes ingrowths of mesothelium into the mesen-
chyme, from which endothelium and blood-cells
develop.

This classification should include also another
group of closed cavities, namely, the tendon
sheaths, bursa?, joint or synovial cavities, cham-
bers of the eye, and the sea la? tympani and vesti-
buli of the internal ear. These cavities arise as
splits, or by the union of isolated spaces, in the
mesenchyma, the mesenchymal lining cells taking FlG 4 i._s EMIDIAGRAM .
onepithelioid characters and arranging themselves MATIC ILLUSTRATION

in the form of a membrane. In their method of OF ENDOTHELIUM LIN-
, . ,. ,, ING A LARGE AR-

(lerivation these cells resemble more closely the TERY

earliest endothelia 1 anlages. The most satisfac-

tory disposition of this group of epithelia seems to be to classify them

as 'false' or 'mesenchymal' epithelia, as proposed by F. T. Lewis.

Such epithelia have been experimentally produced by the introduc-
tion of small sheets of celloidin and masses of paraffin into the subcuta-

38

EPITHELIAL TISSUES

neons tissue and cornea respectively, of laboratory animals : the connective
tissue cells became changed into large flat cells, disposed in the manner
of a mesothelium. These results suggest the conclusion that the meso-
thelial cells of pleura, pericardium and peritoneum may be regenerated
in the event of destruction from exposed connective tissue cells of the
subepithelial stroma (TF. C. Clarke, Anat. Rec., 8, 2, 1914).

The individual squamous cells are flat plates bulging at the center
where the oval nucleus is located, with serrated borders. In surface view

FIG. 42. MESOTHELIUM (surface view), FROM THE MESENTERY OF A RAT.
Silver nitrate and hematein. X 550.

the endothelial cell is oblong, the long axis parallel with the long axis of
the vessel (Fig. 41), while the mesothelial cell is polygonal in outline
(Fig. 42). In sections through the nucleus, these cells in side view
present a flat spindle-shaped appearance.

Mesothelia exhibit small intercellular spaces, the stigmata. They
have been regarded as openings between the body cavities and lymph
spaces and vessels; but are more probably transient structures, perhaps
artifacts. Abdominal mesothelia of lower forms, e.g., frog, contain also
permanent openings, or stomata, surrounded by specialized guard cells.

XOX STRATIFIED KI'ITII Kl.l A

39

2. SIMPLE COLC.MXAU KiTniKLtr:\t
(a)

FIG. 43. CUBOIDAL EPITHELIUM FROM THE
RETE TESTIS OF THE RABBIT.

a, epithelium; b, connective tissue. Hema-
tein and eosin. X 550.

This type of epithelium consists of columnar or cylindrical elements
(Fig. 39). in transverse section presenting polygonal, frequently hex-
agonal, outlines (Fig. 40). It

may be tall, medium or low ^ ^ ' ** O ^ ^

columnar epithelium, depend-
ing upon the height of the in-
dividual cell of the particular
membrane. The lower types
may be designated cuboidal
epithelia (Fig. t3). The phe-
nomenon of polm-ili/ is partic-
ularly well exhibited by a tall

columnar cell, a condition inhering in a structural and functional differ-
entiation between the attached, or
proximal,, and the free, or <//*////, end
of the cell, dependent in a final an-
alysis in larger measure upon dis-
tance from source of the nutritive
and oxvgenative stream in the blood.

J O

The nucleus is generally located
nearer the proximal end ; this end,
moreover, tapers to a point and is
occasionally bifid; and it contains
the presecretion (ergastoplasm, pro-
zymogen, etc.) granules, rod lets and
librils in secreting epithelia (Fig.
35). The distal border is frequently
striated (cuticular margin, striated
border, Fig. 38, b), an appearance
due to the presence of minute canals,
or more frequently, short pseudo-
podia, mediating absorption or the
elimination of secretion. Striated
borders are particularly prominent
cells of the intes-
of the

FlG. 44. TlP OF A VlLLUS OF THE

SYNOVIAL MEMBRANE FROM THE
KNEE-JOINT OF AN OLD MAN.
The core contains capillaries em-
bedded in a compact, delicately fibrillar
stroma. A distinct basement mem-
brane appears in certain regions. The
epithelium is of the low columnar or
cuboidal type.

in the columnar
tine. In the

secreting cells

40 EPITHELIAL TISSUES

kidney the marginal processes are more prominent and divergent, forming
'brush borders.' Where the cell membrane becomes greatly thickened on
the free surface of a columnar cell, it is termed a rntxlti. Also, in neuro-
epithelial cells, the free border mediates reception, the attached pole
transmission, of stimuli.

(I)) Modified Columnar Epithelium

(1) Ciliated Epithelium. Here the columnar cells carry upon
their free surface a group of delicate hairlike processes called cilia, or a
single flagclliini (flagellate cells of lower forms), which during life are

capable of a rapid vibratory or undu-
< < latory motion, a further expression of
cell polarity. The direction of this
ciliary motion is constant and is such
as to produce a definite current within
the fluids which bathe the surface of
these cells whose direction is invariably
from within toward the external surface
of the body. In the human body the
cilia occur almost exclusively upon the
FIG. 45. COLUMNAR CILIATED EPI- free extremities of columnar cells

THELIUM FROM THE EPIDIDYMIS ( FigS. 45, 51 ail<l 52 ) . Ill SOlllC of tllC

OF A RABBIT. . ,,

lower animals, as for example in the

o epithelium;6 connective tissue; momh f tl f nj flre f d }

c, cilia. A leukocyte is seen between

the bases of the columnar cells, upon polyhedral and pear-shaped cells.
Hematein and eosin. X 550. In simplest form cilia are pseudopod-

like extensions of the cytoplasm of the
cell body, and may be regarded as modifications of its exoplasm.

The ciliated border is separated from the protoplasm of the cell body
by a fine chromatic line, which on higher magnification resolves into a
number of knob-like segments, the basal granules (Fig. 22, Chap. I). The
cytoplasm and nucleus of ciliated epithelium, except for the peculiarities
dependent upon the formation of cilia, is similar to that of the simple
non-ciliated columnar cells. Their cytoplasm as in other types, may
contain vacuoles, pigment granules, metaplasm, and even secretory
granules, e.g., epididymis.

(2) Glandular Epithelium. This type derives its name from the
fact of the predominance of the glandular function. This condition is

NON-STEATIFIED KI'ITIIKI.IA

41

structurally expressed in M'gn'gaf ion of the presecretion bodies (gran-
ules, rods, threads) in the ha sal end of the cell, and of the secretion
products (granules, spherules, and mucous or serous fluid) in the distal
end (Fig. 35). Morphologically it represents simply a modified colum-
nar cell, its pyramidal shape resulting from mechanical factors due to
its disposition in saccular or spherical acini, the periphery of the cen-
tral lumen of which is much less than the periphery of the acinus,
necessitating the modification in shape of the individual cells (Fig. 4>i).
The cells of glandular epithelium usually lack cuticular borders. Pyram-
idal or glandular epithelium is found in tulndes of the kidney, salivary
glands, the pancreas, in the secreting
glands of the gastric and intestinal
mucous membrane, in the mucous
glands of the esophagus, pharynx,
bronchial tubes and oral and nasal

FIG. 46. A GROUP OF CELLS FROM
A TRANSECTION OF AN ACINUS OF
THE HUMAN PANCREAS; GLANDU-
LAR EPITHELIUM.

Hematein and eosin. X 550.

cavities, and in the secreting glands of
the skin.

(3) Goblet Cell Epithelium. A
further important and very widespread
modification of columnar cells in epi-
thelia concerns the elaboration and
storage of mucous secretion, giving to
the loaded cells a goblet form (Figs. 47
and 48) . Goblet cells may occur among

either the plain or ciliated columnar cells. They are most abundant in
the intestinal tract but are also to be found in the stomach, bronchial
tubes, trachea, nasal mucous membrane, and in the ducts and tubules of
mucus secreting glands. In such epithelial membranes certain columnar
cells, if not indeed all of these cells, are destined to secrete mucus. The
cytoplasm of such cells is converted into a glairy mass of a peculiar vitre-
ous appearance, which occupies an increasing proportion of the free ex-
tremity of the cell. This 'mucinogen,' when acted upon by alcohol, is
precipitated within the cell, and then forms fine basophilic fibrils or gran-
ules which stain deeply with the muchematein and mucicarmin solutions
of P. Mayer. At the base of the goblet cell, its nucleus is embedded in a
minute mass of unaltered granular cytoplasm.

The accumulation of mucus (mucinogen) within the cytoplasm ex-
pands the cell, finally ruptures its wall in the direction of least resistance,
and thus permits its mucous content to exude upon the free surface,
leaving behind the small granular protoplasmic cell remnant attached to

EPITHELIAL TISSUES

the basement membrane. The further history of these cell remnants is
Miim-what doubtful. They are possibly ivsorbed or removed, and finally
replaced through mitotic division of adjacent cells. There is, however,
some evidence to show that after function they are still capable of further

FIG. 47. GOBLET CELLS AS SEEN IN
A TRANSECTION OF A CRYPT OF THE
LARGE INTESTINE OF MAN.

Sections of five goblet cells are seen
among the columnar cells which line
the tubule. Muchematein and eosin.
X 550.

FIG. 48. DIAGRAM SHOWING THE AR-
RANGEMENT OF THE COLUMNAR AND
GOBLET CELLS OF THE PRECEDING
FIGURE.

The goblet cells are represented as
being empty; their unaltered basal por-
tions containing the nucleus are dis-
tinctly seen.

growth, whereby they may regain their original form and become again
able to pass through the same stages of secretory activity.

(4) Nemo-epithelium. The cells of neuro-epithelium are colum-
nar elements specially differentiated to form nerve end-organs. They
are usually elongated cells having a bulging nucleated center, their free
extremity either projecting beyond the epithelial surface as a bundle of
fine cilia or as a slender non-ciliated process which terminates within a
pore-like opening directly connected with the free surface. Their at-
tached extremity, tapering to a fine process, is in relation with the
terminal arborization of the axis cylinder of a nerve fiber. jSTeuro-epithe-
lium is found only in the several organs of special sense, and will be more
fully described as a part of these several organs. (See chapters of the
Eye, the Ear, the Olfactory Organ, the Tongue, and on the Nerve End-
Organs.)

STRATIFIED EPITHELIUM

43

II. STRATIFIED EPITHELIUM

1. STRATIFIED SQUAMOUS EPITHELIUM

This variety of epithelium occurs as a membrane of varying thickness
but always comprising several cell layers. A straight line perpendicular
to its free surface would penetrate from five to thirty or more epithelial
cells. But while there is a wide diversity in the thickness of the epithelial
layers, the character of the cells at any given level is very nearly con-

FIG. 49. STRATIFIED EPITHELIUM FROM THE HUMAN ESOPHAGUS.
a, basement membrane; 6, connective tissue. Hematein and eosin. X 410.

stant. Thus the deeper cells, those nearest the basement membrane, are
nucleated, of soft consistence and may contain mitotic figures, indicating
that it is at this level that cell reproduction is most active. Toward the
surface of the membrane the cells become progressively of firmer con-
sistence, so that the most superficial ones present a horny appearance as
a result of the gradual keratization of the cytoplasm during the progress

44 EPITHELIAL TISSUES

of the cell toward the surface. The keratization is apparently dependent
upon surrounding physical conditions, for it is much more marked in
the skin, which from constant and rapid evaporation is comparatively
dry, than in the mouth, esophagus, or conjunctiva, where the epithelium is
constantly moistened by glandular secretions; the margins cf the lips,
eyelids, etc., present an intermediate state of keratization.

With these chemical changes in the composition of the cytoplasm
there are corresponding changes in its nucleus. In the deeper cells, the
nucleus is oval or spherical and highly chromatic. Toward the surface,
the nucleus becomes more and more flattened and more and more obscured
by the cornification of the cell protoplasm. In the most superficial cells
it is usually impossible to demonstrate the nuclei, except by acting upon
their protoplasm with strong reagents such as caustic alkalies, soda or
potassa.

But the most characteristic change in the cells of stratified epithelium
is the progressive transition in shape undergone during their passage
from the deeper layers to the free surface. Xew cells, resulting from indi-
rect division of the cells in the deeper layers, are by continued reproduction
gradually pushed toward the surface, whence they are constantly being-
desquamated in small scaly masses. The pressure exerted in this process
tends to gradually flatten these cells so that their vertical diameter, that
perpendicular to the surface, becomes progressively shorter the nearer
they approach the free surface ; on the other hand, their transverse diam-
eter, that parallel to the surface of the epithelial membrane, is correspond-
ingly increased. The deepest cells of the stratified epithelium those
which rest upon the basement membrane are elongated in their vertical
diameter and possess an irregularly columnar shape. Their nuclei are
likewise elongated, oval or elliptical in shape. In the skin of brunettes
and the dark-skinned races, and in the epithelium of the skin of the
scrotum, perianal region, and areolae of the breasts, these cells contain
small granules of the pigment to which the color of the cuticle is largely
due. This columnar cell layer is then described as the layer of pigment
epithelium. Superficial to these, but still in the deeper layers, are poly-
hedral cells with spherical nuclei, which are known as prickle cells be-
cause of their proi. .inent intercellular bridges. Superficial to the prickle
cells, the epithelial cells become progressively more flattened, until at the
surface, they are mere scales. This gradual transition from columnar
and polyhedral cells below, to thin flat scales on the surface is character-
istic of all stratified epithelium.

The thin superficial scales resemble very closely in shape and appear-

STRATIFIED EPITHELIUM

45

ance the squamous epithelium previously described. The deeper cells have
a finely granular cytoplasm and distinct nuclei except when obscured by
the appearance of keratin within their protoplasm. Many of these cells
contain coarse granules of clcnlni and keratoliyalin substances chemi-
cally intermediate between the unaltered and keratixed protoplasm.

As stated, the formation of kcni/i// within these cells is more active
in those membranes which are comparatively dry from exposure to the
Consequently, it is most active in the epidermis of the skin. If

air.

stratified epithelium is at all times well moistened, as, for example, in the

FIG. 50. EPIDERMIS OF THE SKIN OF THE FINGER TIP, SHOWING EXTREME KERATIZA-

TION OF THE EPITHELIUM.

a, keratized epithelium; 6, Malpighian or germinal layer; c, connective tissue.
Hematein and eosin. X 50.

mouth and esophagus, the formation of keratin is slight, and the soft
polyhedral cells compose the major portion of the epithelial membrane
which then has only a thin superficial covering of flattened scaly cells.
In the comparatively dry epidermis, on the other hand, the flattened
horny cells frequently occupy more than half the thickness of the epithe-
lial layer (Fig. 50) . In the superficial squamous cells of moist membranes
the nucleus can always be readily demonstrated, e\ . n in the keratized
cells of the extreme surface. Cells of the intermediate layers, especially
those just above the prickle cell layer, frequently show nuclei in process of
amitotic division. This condition is presumably associated with an early
stage of degeneration dependent upon a scarcity of nutriment due to
the relatively greater distance of these cells from the source of supply.

46

EPITHELIAL TISSUES

It will assist in the understanding of the structure and morphological
characteristics of the several layers of cells to think of the superficial

squamous cells in terms of the innermost
columnar cells, modified during the pas-
sage to the surface by mechanical (pres-
sure), physical (desiccation), and chem-
ical (kcratization) factors.

PSEUDO-STKATIFIED COLUMNAR
EPITHELIUM

FlG. 51. P S E U D O - STRATIFIED

COLUMNAR CILIATED EPITHE-
LIUM FROM A BRONCHIAL TUBE

OF MAN.

a, a goblet cell ; ft, cilia ; c , super-
ficial cytoplasmic layer; d, deeper
nucleated layer, the nuclei of the
columnar cells are somewhat more
deeply stained than those of the
basal cells; e } basement mem-
brane;/, connective tissue. Hema-
tein and eosin. X 550.

The superficial cells only of this va-
riety of epithelium are columnar in
shape, and except in one or two unim-
portant places are always ciliated. The
deeper extremities of these columnar
cells taper to a point, and extend all the
way to the basement membrane. Be-
tween the tapering ends of these cells
small spindle-shaped and spheroidal cells
are closely packed. The several varieties
of cells thus appear to be superimposed, though
all actually rest upon the basement membrane.
The 'superficial' cells of this variety extend
throughout the entire thickness of the mem-
brane. Hence this form of epithelium may in
one sense be called 'simple' rather than 'strat-
ified.' The distribution of this variety of the
epithelium is practically identical with that of
ciliated cells. The deeper extremities of the
columnar cells are occasionally bifid or even
somewhat varicose in order the more closely to
fit between the spindle-shaped and spheroidal
cells of the deeper portion. The nucleus of these
latter cells is usually situated a little below the
middle of the columnar cell, so that all the nuclei
of the epithelial membrane lie within its deeper
half, thus giving to this portion a more deeply
chromatic appearance when observed in stained sections under low mag-
nification. The superficial half of the epithelial layer contains only

FIG. 52. DIAGRAM

SHOWING THE MAN-
NER IN WHICH ALL
THE EPITHELIAL
CELLS OF PSEUDO-
STRATIFIED ClLIATED
EPITHELIUM REACH
THE BASEMENT MEM-
BRANE.

Letters as in the pre-
ceding figure.

STRATIFIED EPITHELIUM

47

the cytoplasmic portion of the columnar colls with their ciliated bor-
ders.

This typo of epithelium is frequently designated simply 'stratified
columnar'; and in fact in certain instances under conditions of further
modification involving a separation of the taller cells from the Itascmcni
membrane, it passes, over more or less extensive areas in the respiratory
and male genital tracts, into actual .stratified columnar epithelium.
Toward the proximal end of the male urethra the epithelium is of the
true stratified columnar (non-ciliated) type.

3. TRAXSITIONAL EPITHELIUM

This variety resembles somewhat stratified squamous epithelium in
that it is composed of several cell layers, the deeper cells of which are
more nearly polyhedral but are somewhat flattened upon the free sur-
face, but differs in having a smaller number of cell layers in which
respect it is 'transitional'
between simple and strat-
ified squamous epitheli-
um and in the charac-
ter of the superficial
cells. Transitional epi-
thelium is not usuallv

\j

more than from three to
ten cells deep, four to six
being the rule. The
number of cell layers and
the consequent actual
thickness of epithelial
membranes is to a cer-
tain extent dependent
upon their state of ten-
sion during life ; thus the
transitional epithelium of

the urinary bladder is much thicker when the organ is collapsed than dur-
ing distension.

The deepest cells are polyhedral, and these form the greater portion
of the membrane. Only the more superficial layers differ therefrom.
Those polyhedral ceils which lie in the midregion of the epithelial layer
possess a peculiar flask or pear shape, with well-rounded bodies and a

FIG. 53. TRANSITIONAL EPITHELIUM FROM A TRAN-
SECTION OF THE URETER OF AN INFANT.

(7, epithelium; b, connective tissue. Hematcin and
eosin. X 550.

48

EPITHELIAL TISSUES

broad tapering process which is embedded between the adjacent cells of
the deeper layers. The rounded extremities of the pear-shaped cells fit
into peculiar indentations in the deeper surface of the superficial layer
of epithelial cells, producing peculiar concave facets, which are specially
characteristic of the detached superficial cells of transitional epithelium.
The superficial cells, while someAvhat flattened, usually have a thick-
ness equal to one-sixth to one-third their transverse diameter. In this
respect they differ markedly from the superficial scaly cells of stratified
squamous epithelium and are easily distinguished therefrom, even in the

B

FIG. 54. ISOLATED CELLS WHICH MAY APPEAR IN HUMAN URINE.

A, from the vagina of a woman (stratified squamous epithelium); B, from the
ureter of a child (transitional epithelium); a, cells from the deep layers; b, superficial
cell. Moderately magnified.

isolated condition in which they are frequently found in the urine.
The concave facets on their under surface, as well as the peculiar pyri-
form shape and small size of the deeper cells, are sufficient to distinguish
the transitional cells from those of stratified epithelium.

There is little, if any, formation of keratin in transitional epithelium.
This is possibly explained by the fact that, as it occurs only in the
urinary system, this form of epithelium is always well moistened. Differ-
entiation of this variety of epithelial tissue, though neglected by some
authors, becomes most important in the clinical examination of urine
where it is necessary to determine the origin of individual cells. Transi-
tional cells from the bladder are easily distinguished from the stratified
squamous cells of the vagina, urethra, or epidermis.

CHAPTER III

CONNECTIVE TISSUE CARTILAGE BONE

CONNECTIVE TISSUE

General Statements. While in the epithelial tissues the cells are
developed chiefly at the expense of the intercellular elements, in the
connective or supporting tissues the conditions are the reverse. The
intercellular elements are here developed out of all proportion to the
connective tissue cells. The cells of these tissues therefore are scanty,
the ground substance considerable, and within the latter a new element,
the connective tissue fiber, makes its appearance. The fibers are of three

*' K

FIG. 55. EMBRYONAL CONNECTIVE
TISSUE, EARLY STAGE.

Highly magnified. (After Mall.)

<=

" '"

I o M

^ ? -^o *..

FIG. 56. EMBRYONAL CONNECTIVE TIS-
SUE AT A LATER STAGE THAN Is REP-
RESENTED IN FIG. 55. (After Mall.)

varieties: ichite or collagenous fibers, elastic fibers, and n'lici/Jitm. In
any given location either of these varieties may predominate to such an
extent as to determine the character of the mature tissue, while in the
immature forms of connective tissue it is the cellular elements which
attain the greatest prominence.

The minute structure of connective tissue is subject to great and
important changes during its development. Beginning as it does with
the primitive mesoderm, connective tissue is originally a cellular struc-
ture. The cells of primitive connective tissue, the fibrobl*t*. not only
increase in number by cell division but also secrete an intercellular
ground substance of semifluid consistence. The fibroblasts fuse with each
5 49

50

CONNECTIVE TISSUE CAETILAGE BONE

other and finally form a syncytial tissue, the inrxcrlii/nin. in which
there promptly occurs a differentiation of the cytoplasm with the forma-
tion of an endoplasm and an exoplasm; and within the latter the fine
fihrils soon make their appearance, according to Meves, by processes
of fusion and chemical alteration of mitochondria (chondrioconta).
This process continues, new ground substance and fibers being con-

Ft,

M'z Knlf Kl Elf PI?

Plb

Eo:
Kl

Fb

Fb

Mz

Kl Kolf

Elf

FIG. 57. SUBCUTANEOUS AREOLAR CONNECTIVE TISSUE OF GUINEA PIG.

(Maximow.)

Elf, elastic fiber; Kolf, collagenous (white) fiber bundles; Fb, fibroblast (lamellar
cell); Mz, mast cell; Wz, resting wandering cell (clasmatocyte); Plz, plasma cell; Kl,
clasmatocyte ('macrophage'); Eos, eosinophil. X 1750.

stantly formed at the expense of the endoplasm, until finally the remnant
of the latter again forms isolated cells. The culmination of these changes
results in the mature fibrillar connective tissue in which the cells are
shrunken and scarce, though still apparently capable of assuming renewed
activity on demand of altered conditions. The definitive fibrils result in
part from a longitudinal splitting of the coarser primitive fibers, collage-
nous (Mall), elastic and reticular.

Embryonic connective tissue is therefore typically cellular as com-
pared with the mature type; its ground substance is abundant but the
fibers, whose development is as yet incomplete, are scanty. Such embry-

CONNECTIVE TISSUE

51

onie connective tissue is round not only in the fetus but also in early child-
hood and in the adult, especially during regeneration of destroyed areas
of connective tissue, and in other more or less pathological conditions.

i-: TISSUE CELLS

FIG. 58. PLASMA
CELLS OF CONNEC-
TIVE TISSUE FROM
THE HUMAN BREAST.

Hematein and eosin.
X 750.

Connective tissue cells not only vary in number as they approach ma-
turity, but in their structure and appearance as well. The cells of em-
bryonic connective tissue are comparatively large, are frequently stellate
from the presence of numerous interlacing and
sometimes anastomosing branches, and their cyto-
plasm has a typical reticular or granular appear-
ance. In the later stages of their development
ameboid motion has been observed in such cells,
and within the limits of the tissue in which they
are developed, they are presumably endowed with
the power of locomotion.

In the neighborhood of developing blood-ves-
sels plasma cells of large size and irregular shape
are frequently seen. The cytoplasm of these cells

is of considerable volume, is finely granular, stains readily in most dyes,
especially the basic varieties, and is prolonged into broad protoplasmic
branches of considerable length. Both in the cell body and in the proc-
esses vacuoles are so numerous as to give the cell a typically reticular

appearance, a peculiarity which is emphasized
^ by the removal of the contents of the vacuoles,

as frequently happens in the preparation of
microscopical specimens. Plasma cells are
found in considerable numbers in the mucous
membrane of the intestinal tract and in the
subcutaneous tissue, where they are frequently
of spheroidal form.

In the denser forms of mature connective
tissue, where the cells are apparently subjected

to more or less compression between the firm bundles of fibers, the con-
nective tissue cells lose their typical embryonal stellate form and become
somewhat fusiform; they are then known as the spindle cells of connec-
tive tissue. Such cells occur in great abundance in the stroma of the
ovary and the mucosa of the uterus and oviduct.

In the mature tissue of the adult many of the cells become more or

FIG. 59. SPINDLE-SHAPED
CONNECTIVE TISSUE
CELLS FROM THE STROMA
OF THE HUMAN OVARY.

Hematein and
X 550.

eosm.

CONNECTIVE TISSUE CARTILAGE BONE

r

L_ .

FlG. GO. PlGMENTED CELLS FROM THE

CHOROID COAT OF THE Ox's EYE.

Unstained; hence, only the pigment
granules appear in the figure. 1, gran-
ules contained within the cytoplasm; 2,
free granules which have escaped from
cells injured during the process of teas-
ing; 3, the non-pigmented nuclei.

less flattened and are often closely applied to, or even wrapped around.

the fiber bundles. These lamellar cells have a small nucleus, a consider-
able rim of cytoplasm, which fre-
quently has a shrunken appearance,
and sometimes a few short cytoplas-
mic processes. The branching stel-
late forms, however, are characteris-
tic of the younger connective tissues.
In certain locations a deposit of
pigment granules occurs within the
connective tissue cells. Such pig-
ment cells are usually found where
protection against light seems desir-
able, and are most abundant in the
choroid coat and iris of the eye.
The pigment granules are entirely
confined to the cytoplasm of the
cell ; the nucleus is never invaded by
the deposit. These granules belong
to the melanin series of pigments.
The cytoplasm of certain cells found in connective tissue contains

coarse basophil granules, which stain with dahlia and similar basic

dyes. This type is known as lasopliil granule cells,

or mast cells (Mastzellen of the German authors).

The granules of other granulocytes are readily stained

with acid dyes, such as eosin (eosinopliil, acidopliil

or o.i'i/jiliil granulocytes). According to the observa-
tions of II. B. Shaw (Jour. Anat. and Physiol.,

1901), certain of the granule cells abound in those

locations where fat is deposited, and have a special

relation to the development of the fat cells of adipose

tissue. These granulocytes of fibro-elastic connective

tissue are apparently identical with those of the blood.

Lymphocytes and phagocytic leukocytes are also pres-
ent in connective tissue.

It is a disputed point whether the granulocytes of

connective tissue different-late from fibroblasts or

from lymphocytes; the weight of evidence seems to incline to the latter

position. Plasma cells seem more probably altered fibroblasts but have

also been regarded by some as lymphocyte derivatives. The so-called

i

FIG. 61. GRANTLE
CELLS FROM THE
FIBROUS CON-
NECTIVE TISSUE
OF THE HUMAN
MAMMARY GLAND.

A, a basophile
cell; B, an eosino-
phile cell. Henia-
tein and eosin. X
750.

CONNECTIVE TISSUE 53

testing-wandering' cells, or Vlasmatoevtes,' are perhaps to be regarded
as varieties of basophilic granulocytes characterized priiieipally bv the
presence of irregular protoplasmic processes. According to Kite (Jour.
Infec. Dis., 15, 2, l'.H4) the Ylasinatocytes' described for the frog by
Eanvier in 1<S!)1 are lymphocytes which have protruded pseudopods.
Evans classifies them with the 'macrophages' of Metschnikoff.

TYPES OF CONNECTIVE TISSUE

The proportions and character of the cells and fillers present in
any given connective tissue, to a certain extent determine its character.
If the collagenous fibers of connective tissue are closely packed in dense
parallel bundles, the elastic fibers being comparatively insignificant in
number, the type of connective tissue may then be said to be dense
fibrous or white fibrous tissue.

In elastic tissue on the other hand, the yellow elastic fibers are highly
developed, the white fibers forming only insignificant and very delicate
sheaths which inclose the coarser elastic fibers.

Again, it is the variety of delicate connective tissue fiber known as
reticulum which preponderates in reticular tissue, and if the meshes
of this reticular network become infiltrated by lymphocytes, which then
multiply by division until they exceed the other tissue elements, the con-
nective tissue is then said to be of the lymphoid or adenoid variety.
Large numbers of the fixed cells of areolar connective tissue may change
into fat cells, the tissue as a whole then forming adipose tissue. In all
we distinguish the following varieties of connective tissue: (1) embry-
onal; (2) mucous; (3) reticular; (4) loose fibre-elastic or areolar; (5)
dense fibrous; (G) dense elastic ; (7) cartilage; (8) bone.

Embryonal Connective Tissue. Embryonal connective tissue (Figs.
55 and 56) occurs not only in fetol and infantile life, but also during the
regeneration of destroyed connective tissue areas and in pathological
neoplasms. It is distinctly cellular in character. Its cells are spindle-
shaped and stellate, are much branched, and through their larger proc-
esses they frequently anastomose.

The fibers are extremely fine; they are not usually arranged in bun-
dles, but form a delicate network which permeates the ground substance
in every direction. In the very immature types the fibers are all of the
collagenous variety; delicate elastic fibers appear later. The fluid ground
substance forms an abundant mass of tissue juice which occupies the
meshes of the fibrous net. The earliest developmental stages are ideiiti-

54

CONNECTIVE TISSUE CARTILAGE BOX E

cal with mesenchyma ; from the viewpoint of progressive differentiation
it properly heads the li<t of connective tissues.

Mucous Connective Tissue. Mucous, gelatinous or mucoid connec-
tive tissue occurs only in the umbilical cord, where it forms the 'jelly of
Wharton/ and in the vitreous humor of the eye. Its semifluid ground
substance is of a gelatinous consistence and forms the greater portion of
the tissue; in the vitreous humor there is little else.

The cells are mostly of the branched lamellar variety, are few in nuni-

FIG. 62. GELATINOUS CONNECTIVE TISSUE FROM THE UMBILICAL CORD OF A NEW-
BORN INFANT.

Safranin and water blue. X 410.

her in the vitreous, but more abundant in the umbilical cord. In the
vitreous humor also, there arc very few fibers; those which are present
are very line and form a delicate reticulum. In the umbilical cord the
fibers are more abundant, and possess a tendency to form bundles which
are disposed in parallel cylindrical layers around the large blood-
vessels. Elastic fibers are wanting. This type lacks also nerves, blood-
vessels and lymph-vessels; the two large umbilical arteries and the
umbilical vein have no vascular connection with the mucous tissue of
the cord.

The essential chemical body in -nine us is muciii, a glycoproteid. The
most typical mucous substance is the secretory content of goblet cells.
The mucus of embryonic and gelatinous connective tissue is closely

CONNKCTIVK TISSUE

similar. I. ess closely similar 'ni'icnu>' substances of the more compact
connective tissues arc properly designated, mucuidx.

Reticular Tissue (Hr/iculum). lieticular tissue occurs as the
stroma of adenoid tissue in the lymphatic glands and other lympiioid or-
gans, and according to Mall (Johns Hopkins Hosp. Eep., IS'.Mi). is found
also in the membrana propria of the secreting tubules of the stomach.
intestine, kidney, testis. and thyroid, and in the marrow of hone and the
walls of the pulmonary air sacs.

Like the other connective tis-
sues, reticular tissue consists of
cells, fibers, and ground substance;
the latter, however, is no more
than a fluid ti*x/ie juice which, at
least in the lymphoid organs, is
identical with the lymph. The
fibers are extremely fine and are
arranged in slender bundles, which
freely anastomose to form a deli-
cate close-meshed reticulum. In-
dividual fibers can he readily dem-
onstrated in these bundles onlv

J

after the action of alkalies, diges-

O

tion by artificial gastric juice, or
by other methods of dissociation,
yet on careful examination indica-
tions of fibrillar structure can be
seen in the reticulum of fresh tis-
sue and in ordinary microscopical

preparations. The chemical reactions of the reticular fibers are similar
to those of collagenous fibers except that the former are much less readily
digested by artificial gastric juice.

Flattened connective tissue cells clasp the bundles of reticular fibers ;
they are mostly found at the intersections of the anastomosing bundles.
This fact was accountable for the former theory, which regarded reticu-
lar tissue as formed by the anastomosing branches of stellate cells. The
careful investigations of Carlier (Jour. Anat. and Physiol., 1895) and
others have shown the true nature of the lamellar cells and their under-
lying fiber bundles.

The fibers of reticular tissue very closely resemble the collagenous
fibers of areolar tissue, but differ from them in having a clearer, more

FIG. 63. RETICULUM OF A CERVICAL
LYMPH NODE OF MAN, FROM A THIN
SECTION FROM WHICH THE LYMPHATIC
CORPUSCLES HAD BEEN PARTIALLY
WASHED OUT.

a, polynuclear lymphatic corpuscle; b,
larc;e mononuclear cell; c, connective tis-
sue cells of the reticular tissue; d, fibrous
bundle of the reticulum; e, small mono-
nuclear lymphocyte. Hematein and
eosin. X 500.

56 CONNECTIVE TISSUE CARTILAGE BONE

highly refractive appearance. Their digestion in pepsin begins only after
an interval of two hours, while white fibers are digested in a few minutes;
llicy also stain less readily than white fibers and yield retirulin. which
differs somewhat from the gelatin of white fibrous tissue. The intimate
histologic relation between the reticular and white fibrous tissue is shown
by the fact that the two tissues are frequently continuous and exhibit
similar staining reactions.

Mall (Amer. Jour, of Anat., 1902) has attempted to show that reticu-
lar tissue should be considered as that form of connective tissue which
has been least differentiated from the embryonic mesenchymal type.
He accordingly considers the cells of the reticulum as formed by the un-
dilferentiated endoplasm, and the reticular fibers as representing the
specialized exoplasm of this most primitive type of true connective
tissue. In the liver, the reticulum arises from the endothelial cells of von
Kuppfer instead of from mesencliyme (Mall}.

Loose Fibro-elastic or Areolar Connective Tissue. Loose fibro-
elastic or areolar connective tissue (Fig. 57) is the most widely distrib-
uted of all the varieties; it fills all otherwise unoccupied spaces within
the body, and in all microscopical sections areolar tissue is almost in-
variably to be found. It is also known as loose connective tissue in con-
tradistinction to the more compact or dense varieties. This tissue con-
nects the skin with the underlying structures, maintains the position and
relation of adjoining muscles, surrounds the heart and its great vessels,
envelops the abdominal viscera as submucous and subserous sheets, occu-
pies the spaces of the mediastinum, and fills similar intervals between
the various organs in all parts of the body. Areolar tissue of course
varies in the degree of its laxity or density.

The ground substance of areolar tissue is a coagulable fluid, the tixxiic
juice. Solutions of silver nitrate injected into the interstices of areolar
tissue coagulate its tissue juice or ground substance and darken it
slightly. It is then seen to be permeated by broad lymphatic channels,
which are lined by delicate endothelioid mesenchymal cells ( W. G. Mac-
Callum, Arch. f. Anat., 1902 ; alvo Bull. Johns Hopkins Hosp., 1903).

Both collagenous and elastic fibers occur in areolar tissue, the former
being far in excess of the latter. The comparatively loose reticular ar-
rangement of the fibers of fibro-elastic tissue affords a most favorable
opportunity for the study of these connective tissue elements.

The collagenous or white fibers in mature tissues are invariably ar-
ranged in bundles which interlace with ojae another to form an open net-
r/ork. Each bundle consists of a number of verv fine fibers whose

CONNECT I VK TISSl'K 57

course is characteristically wavy or undulating. Though tin- individual
iilicrs rarely branch, the liber bundles frequently anastomose with one an-
other. The white libers are readily stained with most 'acid' dyes, and
possess a special affinity for acid fuchsia. Chemically they consist of the
albuminoid collagen , which on boiling in water yields gelatin, and is
readily dissolved by boiling in dilute acids or alkalies. Collagen fibers
are digested by artificial gastric juice in five or ten minutes but are

FIG. 64. DENSE FIBROUS TISSUE FROM THE TENDON OF ONE OF THE OCULAR

MUSCLES OF A CHILD.

Hematein and eosin. X 550.

scarcely altered after several hours when acted upon by solutions of pan-
creatin. After boiling, however, white fibers are readily digested by pan-
creatin.

The elastic fibers of areolar tissue, in comparison with the collagenous
fibers, are few in number. They occur as isolated fibers never in bundles
which frequently branch and anastomose, forming in this way a very
fine net with wide meshes, within which are the interlacing bundles of
white fibers. The elastic fibers exist under a certain tension during life,
so that their course under favorable conditions is invariably straight.
When areolar tissue is removed from the body this tension is frequently
relieved and the elastic fibers then curl up, especially at their free ends.

58

CONNECTIVE TISSUE CARTILAGE BONE

Under these conditions they are no longer straight, but present a grace-
fully curved contour. The elastic fibers also possess a glassy, shining, or
highly refractive appearance, the collagenous fibers by comparison look-
ing dull and opaque.

Elastic fibers stain but slightly with most dyes; they are readily
colored by orcein and by Weigert's elastic tissue stain (resorcin-fuchsin),
both of which serve as specific dyes for these
fibers, coloring the fibers dark brown or
black. Elastic fibers are not dissolved by
dilute acids or alkalies even when boiled, and
are only digested by artificial gastric juice
after a lapse of several hours; they are, how-
ever, readily digested in faintly alkaline solu-
tions of pancreatin. They consist of the al-
buminoid body, elastin, which on boiling does
not yield gelatin. Both collagenous and elas-
tic fibers arise by a similar process involving
transformation of the exoplasm of their re-
spective fibroblast progenitors into a fibrillar

conn. t. c.

FIG. 65. LONGITUDINAL SECTION OF TENDON OF
HUMAN FINGER.

Only the nuclei of the tendon cells are conspicu-
ous, scattered in rows among the collagenous fibrils.
The rows of nuclei mark the boundaries of the
primary bundles. X 750.

FIG. 66. PORTION OF
TENDON FROM A Cow.

conn. I. c., connective tis-
sue cells (tendon cells) seen
from the side and, in one case,
from the surface. (From
Dahlgren and Kepner's "Ani-
mal Histology," Macmillan
Co.)

structure. Whether the fibers arc deposited as such or arise by coales-
cence of more fundamental granular dements is a disputed point.

The cells of areolar tissue are few in number, but may include any
of the several varieties, though lamellar and spindle cells together with
leukocytes form the more common types. Many of the lamellar cells are

CONNECTIVE TISSUE

59

closely applied 1<. or even wrapped around the bundles of white fibers.
Fat cells occur in considerable numbers in all areolar tissue and in some
places are aggregated into large groups which form lobules of fatty
tissue.

Dense Fibrous Tissue. In dense fibrous tissue the ground substance
is comparatively deficient. Large bundles of collagenous fibers are ar-
ranged in approximately parallel rows, and are so closely packed as to

FIG. .67. TRANSVERSE SECTION OF PORTION
OF TENDON OF HUMAN FINGER.

a, three-winged cell; b, four-winged cell;
c, primary bundle, completely ensheathed by
the wings of tendon cells, and divisible into
still smaller bundles of collagenous filters
outlined by finer processes of the wings.
The individual fibers are not shown. Gold
chlorid. X 1000.

Tendon fibre --

'

Nucleus of a /

tendon cp?/.-fc- xS^| '
surf nc f rit-ir I

~\V

!$/

Ridges o rp// l,_-1 ^
due fo pcessKre'p' ^- I

"^

i

Tendon cells seen ^L- f-r
/;-on ed^e \

FIG. OS. PIECE OF TENDON FROM
TAIL OF WHITE MOUSE.

Between the bundles of connec-
tive-tissue fibrils are cells arranged
in rows. Some are seen in surface
view, and others in optical section.
X -400. (From Szymonowicz-Mac-
Callum, "Histology and Microscopic
Anatomy.")

form a dense, firm, highly resistant tissue. Its scanty connective tissue
cells are of the lamellar variety and are usually arranged in rows which
occupy the interstices between the parallel fiber bundles.

Dense fibrous tissue occurs typically in tendons; in these the connec-
tive tissue cells often have a peculiar quadrate shape and are arranged
in rows of exceptional regularity (Figs. G4-07). These should be studied
in dissociated tendinous tissue. It also forms the ligaments, the fascia 1 ,
the muscular sheaths (aponeuroses), and the enveloping capsules of many
of the viscera. Thus it surrounds the liver, kidney, lymphatic nodes, and
other organs; it also forms the valves of the heart, the tendinous rings

60

CONNECTIVE TISSUE CAETILAGE BONE

B

FIG. 69. ISOLATED TENDON CELLS.

A, with two 'wings'; B, with four 'wings.' (From Maximow, after Tourneau.)

X 1000.

which surround the cardiac orifices, and the chorda tendineae which are
attached to its valves; and in general, it is found wherever great firmness

and resistance are required.

Elastic fibers in this tissue are

relatively few in number and are so

*

obscured by the dense bundles of white
fibers as to be scarcely demonstrable
except by means of the specific stains.
Tendon will lie further discussed in
connection with striped muscle.

Dense Elastic Tissue. I n this
form of tissue the elastic fibers are de-
veloped at the expense of the colla-
genous fibers. The ground substance
is insignificant in amount, and the
connective tissue cells are scanty and
are confined to the white fibrous
sheaths in which the elastic fibers are
enveloped. The elastic fibers are of
very large size (10 to 15 /t) as com-
pared with those of other forms of
connective tissue. But except for their
larger size, these fibers have the same
peculiar characteristics as the elastic
fibers of areolar tissue. In their
straight course, frequent branches, and
their glistening, highly refractive appearance, as also in their character-
istic reactions to specific dyes and other reagents, these fibers are identical

FIG. 70. COARSE ELASTIC FIBERS

FROM THE LlGAMENTUM NuCH.E
OF THE Ox.

Isolated by teasing. Partly dia-
grammatic. X about 250.

CONNECTIVE TISSUE

FIG. 71. TRANSECTION OF A FASCIC-
ULUS OF THE LlGAMENTUM NUCH.E

OF THE Ox, SHOWING THE VERY
LARGE ELASTIC FIBERS EMBEDDED
IN A VERY DELICATE NETWORK OF
COLLAGENOUS FlBERS.

Picro-fuchsin. X 550.

with the elastic fibers of the other
types of connective tissue.

The elastic fibers are bound to-
gether by delicate sheaths of very line
collagenous fibers, and are united iulo
bundles by coarser bands of fibrous
tissue. Elastic tissue is found in the
ligamenta flava, the stylohyoid liga-
ment and in the ligamentum micha;
('whitleather') of quadrupeds. In
these locations it occurs in consider-
able quantity and has a peculiar yel-
lowish color; it is for this reason that
it is frequently described as yd loir
elastic tissue. It occurs also as fen-

estrated membranes in arteries. These are formed by a coalescence of

neighboring fibers. In the process of
occlusion of the postfetal ductus ar-
teriosus of the pig by increase in the
amount of the elastic tissue in the
wall of the artery, the new elastic
fibers arise both from latent fibro-
blasts and by delamination of fibers
from preformed elastic tissue (-7. s> .
^cliaeffer, Jour. Exp. Med., vol. 19,
1914).

Adipose Tissue (Fat Tissue).
Wherever areolar tissue occurs, adipose
tissue may also be found ; its distribu-
tion is therefore identical with that of
areolar tissue. It forms a consider-
able mass, panniciilnx (n1ii>osns, be-
neath the skin of many parts. In it
are embedded the kidneys, adrenals,
and many lymphatic nodes. The mes-
entery and omentum are freely sup-
plied with fat. The same tissue is
found in the grooves of the heart wall
and it also occupies the spaces of the mediastinum.

Adipose tissue is composed of lobules or groups of fat cells which are

FIG. 72. PORTION OF LIGAMENTUM

NUCH.E OF Ox.

conn. t. c., connective tissue cells.
(From Dahlgren and Kepner.)

62

CONNECTIVE TISSUE CAKTILAGE BONE

supported by fibrous bauds and septa and are abundantly supplied with
small blood-vessels.

The fat cells arise from the connective tissue cells by a deposit
of fat droplets within the cytoplasm of the latter. These droplets
continue to increase in number and fuse with each other to form globules

ct.c

ct. c

FIG. 73. PORTION OF A FAT LOBULE FROM THE AREOLAR CONNECTIVE TISSUE SUR-
ROUNDING THE ESOPHAGUS OF A CAT.

cap., capillary; ct. c., nucleus of a connective tissue cell; /. c., fat cell showing
nucleus; tr., trabecula of fibro-elastic connective tissue. X 500.

of increasing size, until the cytoplasm finally becomes so excavated as to
form a mere limiting membrane or cell wall (Fig. 74). The nucleus is
pushed to one side in this process and is flattened against the cell mem-
brane; it is usually embedded in a remnant of granular cytoplasm. Be-
ing thus distended with fluid fat, the cell acquires a spheroidal shape.
The routine specific stains for fat are osmic acid, which colors the

CONNECTIVE TISSUE

63

FIG. 74. A GROUP OF FAT
CELLS FROM THE SUBCU-
TANEOUS TISSUE OF A
YOUNG RABBIT.

Cells a show stages in de-
velopment; cell b is cut tan-
gentially through the nucle-
ated pole. X

fat globules black; sudan ITT, which gives a
red reaction : and scharlack K (fettponceau),
which also stains fat red. For the successful
application of these stains it is required that
the tissue has not been previously subjected
t<> treatment involving the use of alcohol or
ether, since these reagents extract fat from
the cells. Fat, in cooling, solidifies and pre-
cipitates delicate threads, the margarin crys-
tals.

During periods of starvation or malnu-
trition, at which time fat decreases greatly
in volume, many of the fat cells return to a
condition which approximates their former
state. As the fat is removed the cytoplasm
of the cell increases in amount, but assumes
a peculiar fluid appearance and is not read-
ily colored by the usual dyes. These cells,
which still contain a number of fat droplets,
are known as 'serous' fat cells.

The origin of the fat cell is still somewhat in doubt. It was for-
merly thought that it might
result from a deposit of fat
within any of the connective
tissue cells. A second theory
maintains that it arises only
from a special fat-forming
connective tissue cell. The
demonstration of large num-
bers of peculiar ovoid granular
cells within areas where fat
cells were undoubtedly form-
ing in fetal and young sub-
jects, and the demonstration
of similar cells in areas show-
ing fat formation in adult tis-
sues, has lent support to the
hypothesis that these granular
cells are the only progenitors of the fat cells (Shaw, Jour. Anat. and
Physiol., 1901). According to Weiskotten and Steensland (Anat. Eec.,

FIG. 75. FAT CELLS FROM A TEASED PREP-
ARATION OF ADIPOSE TISSUE OF MAN.
X HO.

CONNECTIVE TISSUE CAETILAGE BONE

FIG. 76. ADIPOSE TISSUE.

The fat cells have been blackened by osmium
tetroxid. X 110.

8, 2, 1914) fat cells
can arise also by a
process involving the
enclosure of free fat
spherules by endothe-
lial cells. They suggest
that fat cells may be
modified endothelial
rrlls rather than mod-
ified fibroblasts.

The forerunners of
the original smallest
fat droplets are gran-
ules (Altmann, 1890).
In the subcutaneous
tissue of Myxine (Hag-
fish) embryos, Schrei-

ner (Anat. Anz. 48, 7, 1915) has described the process of fat elaboration

in minute detail. The pre-fat granules originate from rod-like chromidia

('mitochondria') by process

of segmentation. The chro-
midia arise as nucleolar buds

which wander through the

nucleus and traverse the nu-
clear membrane as spherical

granules. These 'primary

granules' elongate into rods,

and subsequently segment into

'secondary granules,' which

liquefy and coalesce to form

the definitive fat spherules.

This important investigation

suggests a functional role for

mitochondria in terms of a

nutritive material upon which

FIG. 77. DEVELOPING ADIPOSE TISSUE FROM
THE SUBCUTANEOUS TISSUE OF AN INFANT.

The fat has been removed by immersion in
alcohol and ether. The polygonal outlines of
the fat cells are well shown. Within many of
them is seen the finer cytoplasmic network by
which the inclosed droplets of fat were in-
vested; this network had not been completely
replaced by the accumulation of fat. Hema-
tein and eosin. Photo. X 325.

cell metabolism and differen-
tiation may depend.

Lymphoid Tissue (Ade-
noid Tissue}. Lymphoid tissue is a reticular tissue the meshes of whose
network are occupied by a closely packed mass of lymphocytes, cells with

FIG. 78. RETICULUM FROM THE MUCOSA OP THE FUNDUS REGION OP THE DOG'S

STOMACH.

The section was made parallel to the surface and the glandular tissue removed
by shaking in water. Picro-carmin. X 125. (After Mall.)

Fat

L/ympJi sinus

Cortical

_ :>y/Sx. ' 'VTViciHi

\ ^\ substance

te'/ ! \ Ns^ i

!

Capsule

Medullary cords

Follicles Hilus with vessels \ '^Trabeculas

entering Medullary substance

FIG. 79. SECTION THROUGH A SMALL LYMPH NODE OF A DOG. X 20.
(From Szymonowicz-MacCallum, "Histology and Microscopic Anatomy.")

i

65

G6

CONNECTIVE TISSUE CARTILAGE BONE

a deeply staining nucleus enveloped by a narrow shell of homogeneous
slightly basophilic cytoplasm. The lymph cells (lymphocytes) are so
closely packed that it is almost impossible to distinguish the fine threads
of the reticular stroma, except in those portions where some of the
lymphatic cells have been washed out or displaced in the preparation of

the specimen.*

The density of the lymphoid
tissue varies much, however, in dif-

'j >-'-=!/' - -jfMi;Hft*Aik ferent organs and even in different
toAHHKte&fflXI Portions of the same organ. The

FIG. 80. FROM A SECTION THROUGH THE
MEDULLA OF A CERVICAL LYMPH NODE

OF MAN.

a, a 'cord' of dense lymphoid tissue;
b, looser lymphoid tissue of the medullary
sinuses; c, the margin of a fibrous tra-
becula; d, nucleus of the connective tis-
sue reticulum; e, endothelial lining of the
lymphatic sinus. Hematein and eosin.

denser accumulations of lymphoid
corpuscles may form either ovoid
lymph nodules or follicles, or long
dense trabeculae, the lymphatic
cords, which are surrounded by
looser portions of lymphoid tissue.
Lymphatic corpuscles are fre-
quently infiltrated into the connec-
tive tissue of the mucous mem-
branes, where they form irregular
collections, which may be termed
diffuse lymphoid tissue, in contra-
distinction to compact lymphoid
tissue, which occurs in the lymph
nodes, tonsils, thymus, and spleen,
and in the aggregate and solitary
nodules of the intestinal canal.
Diffuse lymphoid tissue is found in
the mucous membranes of (A) the
respiratory tract nose, nasophar-
ynx, larynx, trachea, and bronchi ;

X 475.

and (B) the alimentary tract

mouth, tongue, pharynx, esophagus, stomach, and intestines.

In the basement membranes of certain tubular glands e.g., sweat,
kidney, tear and mammary and in the peripheral portion of the large
cells of the umbilical cord, Mallory (Jour. Med. Res., 1903 and 1905)

* Mall 's technic for this purpose consists in injecting gelatin into a fresh
lymph organ (e. g., spleen), freezing the tissue, and placing thin sections into
warm water when the lymphocytes are largely carried away by the dissolving
gelatin leaving the reticulum free.

CARTILAGE 67

has discovered robust fibers extending also from cell to cell, resembling
somewhat white fibers, but unrelated by transition elements to, and dif-
fering microchemically from, collagenous fibers. They are said to be
similar to the fibrils of neuroglia cells of nervous tissue and to the
border or myoglia fibrils of plain muscle cells.

BLOOD AND NERVE SUPPLY OF THE CONNECTIVE TISSIKS

The connective tissues, but especially the areolar variety, form a
supporting substance through which the various blood and lymphatic
vessels and nerve trunks are distributed to all portions of the body.
Within the connective tissues these vessels are everywhere present, and
from them the connective tissue itself receives its supply of capillary
vessels and terminal nerve fibrils.

The vascular supply of the connective tissues is very abundant.
Small arteries, which are derived from the main trunks, form a capillary
plexus throughout the tissue, the capillaries finally reuniting to form the
venules.

It is in this capillary plexus that the fluid portions of the blood exude
into the surrounding perivascular lymphatic or tissue spaces of the con-
nective tissue. The tissue juices which arise in this manner are most
active agents in the physiological processes of assimilation. From the
tissue juice spaces, lymph reenters the abundant capillary lymphatic
vessels to be finally returned to the venous blood. This transfer is
mediated by process of filtration and osmosis, the tissue spaces being
generally regarded as closed spaces making no direct connection with
the lymphatic terminals. Of the several varieties of connective tissue,
the adipose possesses the most abundant blood supply ; the lymphoid, on
the other hand, is most richly supplied with lymph.

Abundant nerves are distributed to the connective tissues, some of
which, the sympathetic nerves, supply its blood-vessels while others,
medullated, terminate in special forms of sensory nerve end-organs.

CARTILAGE

Cartilage is a dense, firm, but elastic substance, resembling connective
tissue in that it is developed from similar mesodermal cells. It contains
a ground substance, the cartilage matrix, and at times, fibers which
may be either collagenous fibers or elastic. The presence, absence, or

68

CONNECTIVE TISSUE CARTILAGE BONE

character of these fibers determines the variety of cartilage. Three
varieties are thus distinguished: hyaline cartilage, in which no specific
fibers can ordinarily be demonstrated within the matrix ; elastic cartilage,
whose matrix is permeated by elastic fibers; and fibrocartilage, whose

matrix contains collagenous fibers.

FIG. 81. TRANSECTION OF A PLATE OF HYALINE CARTILAGE, FROM THE TRACHEA OF

A CHILD.

The margin of the fibrous perichondrium can be seen on either side of the plate of
cartilage, in the upper right hand corner and lower left hand corner of the figure.
Hematein and eosin. Photo. X 400.

Hyaline Cartilage. This is the most abundant of the three varie-
ties, commonly known as gristle. It is found in the respiratory system,
forming the cartilages of the nose, larynx, trachea, and bronchial tubes;
in the costal cartilages of the ribs; as articular cartilages covering the
mils of long bones; and in the fetus, where in the course of development
of the bones, the entire skeleton, excepting only the flat bones of the skull
and face, at first consist of hyaline cartilage. In most of these loca-
tions the cartilage occurs as platelike masses, which are invested by a vas-

CARTILAGE

69

cular membrane of dense fibre-elastic tissue. This membrane is the
pericliondrium. The inner portion of this membrane is richly supplied
with small cells, and it is from this cell layer, the chondrogenetic layer,
that the cartilage is presumably developed.

The cartilage blastema is essentially mesenchyma. The chondro-
genetic cells of this p re cartilage multiply, and deposit about themselves
the structureless mass which first forms merely a capsule to the cell,
but which as it increases in amount, separates the various cells by
wider areas and becomes the cartilage matru: The cells, which in the
perichondrmm are small and
decidedly flattened, likewise in-
crease in size during this proc-
ess, and become more nearly
spherical, so that those cartilage
cells which lie near the center of
the cartilaginous plates are
spheroidal in shape, while those
toward the surface are more and
more flattened or elongated,
their long axes gradually re-
volving from a perpendicular
position in the center of the
plate to one parallel w 7 ith the
pericliondrium at the surface.
Each cartilage cell is inclosed
within a small space or lacuna.
which during life it entirely fills.

Cell multiplication in carti-
lage is peculiar in that cell di-
vision occurs within a firm capsule and results in the formation of two
daughter-cells, which at first lie within the same encapsuled space. These
two cells may each again undergo division within the same space with
formation of four new cells. As a result of this peculiar method of cell
division the cartilage cells are arranged in groups of two, four, or even
eight cells. Each of the cells in the group deposits its capsule, and thus
forms a matrix about itself, so that the increasing space thus produced
between the cells of a group may separate them until they become com-
pletely isolated cartilage cells each within its own lacuna. In this way
the matrix of the cartilage is produced. Enlargement of n cartilage plate
occurs through a combination of interstitial and perichondrial growth.

FIG. 82. CELLS AND MATRIX OF HYALINE
CARTILAGE FROM THE WALL OF A LARGE
BRONCHUS OF MAN.

The grouping in pairs and fours, and the
tendency to produce a so-called 'capsule,'
are especially noticeable. Hematein. X550.

CONNECTIVE TISSUE CARTILAGE BONE

The matrix of hyaline cartilage is devoid of fibrous or cellular structure.
Chemically it consists of collagen, chondromucoid and albuminoid sub-
stances. Von Korff (1914) interprets hyaline matrix as being composed
of matrical fibrils masked by a homogeneous cementing substance.

During life, or if the tissue is examined in the fresh state, the car-
tilage cell entirely fills the lacuna in which it lies. But shortly after death
shrinkage of these cells begins, so that after some hours a considerable
space intervenes between the cell and the wall of its lacuna. It has been
supposed that this space was occupied during life by lymph. It would,

however, seem more probable
that it is partially the result of
post-mortem shrinkage of the
cell.

Frequently, and especially in
developing cartilage, concentric
lines may be seen surrounding
each lacuna. These lines have
been described as the 'cell cap-
sule.' They appear only to in-
dicate the successive layers of
material which have been de-
posited by the cell, and which
have fused together to form its
surrounding matrix.

Cartilage arises from a mes-
enchymal syncytium in which
the matrix is formed from the
exoplasm of the syncytial tissue,

the cartilage cell representing its endoplasm. The so-called capsule of
the cartilage cell would accordingly represent the partially modified bor-
der line between the original endo- and exoplasm, and would thus cor-
respond to similar conditions which are observed in other forms of devel-
oping connective tissue.

Cartilage cells frequently contain small droplets of fat, and these may
coalesce until the cell is completely transformed into a fat cell. Isolated
masses of adipose tissue, resulting from the transformed groups of carti-
lage cells, thus make their appearance within the cartilaginous plates. This
fatty metamorphosis is most marked in the elastic variety of cartilage.

By coloration with iodin, glycogen granules may also be demonstrated
in the cartilage cells. *

FIG. 83. ELASTIC CARTILAGE FROM THE
HUMAN EPIGLOTTIS, SHOWING THE LARGE
OVOID CARTILAGE CELLS AND THE VERY
DELICATE RETICULUM OF ELASTIC FIBERS.

Ehrlich's triacid stain. X 550.

CARTILAGE 71

Elastic Cartilage. Elastic cartilage occurs in the external ear, in
the auditory tube, in the epiglottis and in the cuneiform and corniculate
cartilages and the vocal processes of the arytenoid cartilages of the
larynx. It is essentially hyaline cartilage the matrix of which has
become permeated with delicate elastic fibers forming a dense interlacing
network. The large spheroidal cartilage cell lies in a lacuna bounded
by a capsule and surrounded by a layer of hyaline matrix free of elastic
fibers. The plates of elastic cartilage, like those of the hyaline variety,
are surrounded by a dense fibrous perichondrium. Neither blood-vessels,
nerves, nor lymphatics are distributed within the matrix of elastic car-
tilage.

Fibrocartilage. This tissue forms the interarticulai cartilages of the
lower jaw, the clavicle, and the knee; composes the iutervertebral disks
and the other cartilaginous symphyses of
the body ; lines the tendon grooves of the
bones, and forms the glenoid ligament of
the shoulder and the cotyloid ligament
of the hip. Fibrocartilage is intermedi
ate in structure between hyaline carti

lage and such very dense fibrous tissue FlG ' S^-FIBROCARTILAGE, SHOW-

ING A GROUP OF OVAL CAR-
as occurs in the tendons of muscles. At TILAGE CELLS.

the attached margins of the cartilaginous

.... r rom the sermlunar cartilage of

plates its tissue is continued by imper- the knee of man. Hematein and

ceptible gradations into the surrounding eosin. X 550.

fibrous connective tissues. Like the

other forms of cartilage, this variety is also non- vascular and devoid of

nerves.

Microscopically, fibrocartilage differs from such dense white fibrous
tissue as is found in the ligaments and tendons, in that the meshes of
the dense fibrous tissue of fibrocartilage are everywhere permeated by a
hyaline matrix in which here and there are small groups of ovoid car-
tilage cells. Each cartilage cell is occasionally surrounded by a charac-
teristic, concentric, lamellar appearance of the adjacent matrix, the so-
called 'capsule/ Plates of fibrocartilage, unlike the other varieties, are
not surrounded by a perichondrium.

A peculiar sort of connective tissue of eutodermal origin is found
in the nuclei pulposi of the invertebral disks. It is the sole adult
vestige of the embryonic axis, the notochord. According to Williams
(Amer. Jour. Anat., 8, 3, 1908), who carefully studied its cytomorphosis
in the pig, "It is primarily cellular and epithelial; later it becomes a

72 CONNECTIVE TISSUE CAETILAGE BONE

syncytial network with a mucin-like substance in its vacuoles ; and finally
it becomes cellular and closely resembles cartilage.* 7

The Perichondrium. The perichondrium is a dense fibrous mem-
brane which surrounds each individual plate of cartilage. It is continuous
with the surrounding connective tissue, and is well supplied with blood-
vessels and lymphatics ; it may also contain terminal nerve fibrils.

The cartilage itself is an absolutely bloodless and nerveless tissue.
Neither are lymphatic channels demonstrable within the cartilage matrix.

\

*** -5. -", -- '"^Ss'v ' 'L' '- '.,,

Y**#"^$ -'':' -. '>::

"V3-. ...:(:"':.,; .- ;v--: *J^ -. ; ;... J*

KKVr

;. t .

r

'-/

-" - ..:-. ,; '-:... .

FIG. 85. NOTOCHORDAL TISSUE.

A, from pig embryo of 150 mm.; the syncytium contains many mucin-filled spaces.
X 800. B, from nucleus pulposus of an adult pig; the three cells shown are greatly
vacuolated. X 452. (After L. W. Williams, Amer. Jour. Anat., 8, 3, 1908.)

After long maceration or artificial digestion the matrix assumes a granu-
lar or fibrous appearance, and small channels have been demonstrated
within it, which have been said to connect the various lacuna?; but it is
evident that these appearances were possibly the result of artificial de-
structive processes and could not therefore be considered as evidences of
the presence of such structure in living cartilage.

BONE

General. Bone is a firm calcareous tissue which is found only in
the skeletal system. In the flat bones it forms a double layer of fense
osseous tissue between which is a narrow space, bridged across at fre-
quent intervals and thus subdivided into a number of compartments, the

BONE

73

marrow cavities. This central stratum presents a spongy appearance as
compared with the denser periphery; it is therefore said to contain
spongi/ or cancellous bone, while the more superficial lamella? contain
compact bone.

In the long bones a similar condi-
tion exists in the epiphyses, which
consist of a Avail of compact bone
within which the marrow cavity is
subdivided by bony partitions into
numerous compartments. The epi-
physis consists, therefore, of spongy
bone. The shaft or diaphysis of the
bone, however, contains a single large
marrow cavity whose walls, except for
a thin layer at either end, consist en-
tirely of compact bone. A little
spongy structure is present for some
distance at either end of the shaft, in
that portion which adjoins the mar-
row cavity.

The ends and facets of the bones
are covered by a disk of hyaline car-
tilage, which forms the articulating
surfaces of those bones which enter
into the formation of the movable
joints. These articular cartilages are
peculiar in that they are not covered
by a perichondrium, and their deeper
cells, which adjoin the bone, are so
arranged that their long axes are per-
pendicular to the free surface, as is
the case in the central portion of free
cartilaginous plates. Toward the free
surface of the cartilage the long axis
of the cell lies more nearly parallel to
the surface, as is likewise the case at
the surface of cartilaginous plates

elsewhere. In the long bones of younger individuals a plate of hyaline
cartilage is found also at the epipliyseal lines between the epiphysis and
the diaphysis. This plate, which extends through the entire axis of the

y&jv&L,

K^ggs^^-

imfM^SP
pp^ fcv
g*&

e&s*

FIG. 86. TRANSECTION THROUGH THE
COMPACT BONY WALL OF A HUMAN
METACARPAL BONE.

a, outer circumferential lamellae; b,
inner circumferential lamellae; c,
Haversian canals; d, interstitial lamel-
lae; e, lacunae, with delicate radiating
canaliculi. From a thin section of
ground bone. X 90. (After Kolli-
ker.)

74

CONNECTIVE TISSUE CARTILAGE BONE

m

mfji
f : ;

y>

w.

ilii

bone, becomes ossified later in life. It represents the line of growth, and
is the last portion of fetal cartilage to be transformed into adult bony
tissue.

Periosteum. All those portions of the bone which are not covered by
an articular cartilage are supplied with a membranous coat of fibrous
tissue, the periosteum. The outermost layer of this membrane consists

of interlacing bundles of dense fibrous
tissue in which are the larger blood-
vessels, whose branches are distributed
to the underlying bone. The inner
portion of this layer forms a firm
fibre-elastic stratum, which in older
individuals is closely attached to the
surface of the bone. The periosteum
of developing and growing bone, how-
ever, contains a third or innermost
areolar layer, in which are small
blood-vessels, fine connective tissue
fibrils, and numerous small osteogenic
cells, the osteoblasts. After growth
of the bone has ceased, the deepest
layer of the periosteum contains few
small blood-vessels and only occa-
sional osteoblasts. These cells, how-
ever, are present in sufficient numbers
to accomplish the regeneration of the
bone after destruction of its osseous
tissue.

The medullary surface of the bone
is likewise supplied with an osteo-
genic membrane of fibrocellular tis-
sue, similar to the innermost layer of

the periosteum; it is known asi the periosteum interiium, endosteum, or
membrana medullaris.

Compact Bone. Compact bone, such as that composing the shafts
of the long bones, consists of concentric lamellce of calcified fibrous tissue
which constitute the Haversian systems, together with groups of parallel
laminae,, which are interposed between adjacent Haversian systerns and
are known as the interstitial or ground lameUce. Many of the interstitial
lamella? are the remains of Harversian systems which have been partially

#*'mv

i&l&Fl

' * Tr T" -I'-f * " -fr " ." v >\ i-f-^Lf^f-

' * 1 fe^w !

^i'll^^

FIG. 87. LONGITUDINAL SECTION OF
GROUND BONE FROM THE SHAFT OF
THE HUMAN FEMUR.

a, Haversian canals; 6, lacunae; c,
canaliculi. X 100. (After Kolliker.)

\

BONE

75

FIG. 88. ISOLATED BONE CELL,
SHRUNK AWAY FROM WALL
OF LACUNA AT I.

(Schafer, after Joseph.)

absorbed during the development of the bone. In a section through
the shaft of a long bone the I !;i \ersian systems are found in the middle of
I lie wall, while superficial to them and just within the periosteum are a
number of lamella? which may be traced
much or all of the way around the cir-
cumference of the cylindrical shaft, and
which are known as the external circum-
ferential or periosteal lamella;. On the
inner surface of the compact bony wall is
a similar group of parallel laminae which
adjoin the marrow cavity, and are known
as the internal circumferential or endos-
(cii I lamella'. In their finer structure
the circumferential lamellae are exactly
similar to the cylindrical bony lamella of
the Haversian systems.

HAVEKSIAN SYSTEM. A Haversian system contains a small central
canal (0.05-0.1 mm. dia.), which is occupied by connective tissue, marrow
cells derived from the marrow cavity during the process of development,

small blood-vessels, nerve fibers, and
perivascular lymphatics. Concen-
trically arranged around the Haver-
sian canal are parallel layers of
dense fibrous tissue, the Haversian
lamellce. The fiber bundles of this
tissue form an interlacing network
whose bundles frequently cross each
other at right angles and whose in-
terstices are occupied by a solid cal-
careous mass, consisting chiefly of
the phosphates (about 30 per cent.)
and carbonates of calcium. From
four to twenty such calcareous lam-
ella? are found in each Haversian
system. The organic substance of

bone consists chemically of collagen, osseomucoid and small amounts of
other albuminoid bodies.

Both in and between the lamella 1 are many small ovoid spaces which
are partially filled by small flattened cells, the bone cell*; these spaces
are known as the lacuna 1 . From each lacuna minute canals, the canaliculi,

FIG. 89. AN HAVERSIAN SYSTEM,
INCLUDING THE CENTRAL CANAL,
SEVERAL LAMELLA, LACUNA AND
CANALICULI.

CONNECTIVE TISSUE CARTILAGE BONE

radiate in all directions, thus placing the lacuna in open communication
with its neighbors, and eventually with the lymph spaces of the cen-
tral Haversian canal. The branching processes of the bone cells fre-
quently project for a short distance into the canaliculi. These cyto-
plasmic branches are more numerous in newly formed bone, later they
are retracted and the cells become more or less shriveled in appearance.
The Haversian system, being developed about a central canal which
marks the course of a blood-vessel, necessarily acquires a slender columnar
shape, its long axis being usually disposed in a direction nearly parallel
to that of the bone of which it forms a part. The Haversian canals fre-
quently branch to permit a corre-
sponding division of their blood-ves-
sels, and all of the Haversian canals
are connected either directly or indi-
rectly with the periosteum, the nu-
trient foramina, or the marrow cavity
thus forming a complete connected
system between marrow cavity and
surface from the blood-vessels of
which their vascular supply is de-
rived.

INTEESTITIAL LAMELLA. The in-
terstitial lamellae are likewise com-
posed of dense interlacing bundles of
calcified fibrous tissue, within and be-
tween which are lacunae, canaliculi,
and bone cells, all disposed in a man-
ner exactly similar to their arrangement within the concentric lamella?
of the Haversian systems. Coursing through the interstitial and circum-
ferential lamellae are Volkmanns canals, which are similar in origin, con-
tents, and function to the Haversian canals but which are not surrounded
by concentric lamella?. Volkmann's canals frequently arise as branches of
the Haversian canals which wander out, as it were, into the interstitial
lamellae.

CIRCUMFERENTIAL LAMELLA. The circumferential lamella? do not
differ in structure from the other osseous lamellae. They possess the
same arrangement of laminated calcareous connective tissue, with Is^cunae,
canaliculi, and bone cells, as in the concentric and interstitial lamellae.
Even more than elsewhere, however, the outer circumferential lamella 1 are
firmly bound together by collagenous and elastic fibers which pass from

FIG. 90. TRANSVERSE SECTION OF
HAVERSIAN CANAL, WITH CONTENTS.

a, arteriole; v, venule; /, lymphatic;
n, non-medullated nerve fibers; c,
bone cell. (After Schafer.)

BONE 7?

the periosteum into and through the superficial lamella'; Ihese are known
as the perforating fibers of Miar/try. Similar fibers connect together the
concentric and interstitial lamella. The perforating elastic fibers are
frequently surrounded by an envelope of fibrous connective tissue.

Bone Marrow. Bone marrow consists of a variety of connective
tissue, largely reticular, which is rich in fat cells and blood-vessels and
which also contains osteogenic and hemogenic elements, the marrow
cells or myelocytes. According to the relative proportion of these ele-
ments marrow is said to present two types, the yellow and the red marrow.
The yellow marrow consists almost entirely of fat, with only occasional
bands of true marrow tissue. The red marrow contains very little fat,
but is so abundantly supplied with blood and marrow cells as to closely
resemble a very vascular lymphoid tissue. The embryonic medulla of all
bones contains fetal red marrow, but in later life the larger masses in
the medulla of the shafts of the long bones are, in man, changed to the
yellow variety. The red marrow, however, persists in the epiphyses of
the long bones and in cancellous bone generally; it is especially charac-
teristic of the marrow cavities of the ribs, vertebrae, base of the skull, and
sternum. It is the source of supply of blood-cells in the adult.

EED MARROW. Eed marrow consists of fibrous and reticular tissues
which are infiltrated by marrow cells and richly supplied with small
blood-vessels. The smaller veins possess exceedingly thin walls, readily
pervious to the blood-cells. The walls are so delicate that it becomes
very difficult to determine with certainty whether or not their endothe-
lium, as also that of the capillaries, may be occasionally absent, thus
placing the blood-stream in direct communication with the pulp of the
bone marrow.

The hemogenic elements of marrow will be described under the
subject of blood development, where red marrow must again be con-
sidered. At this point it is only necessary to describe the osteogenic
elements. These are (1) the osteoblasts, or bone builders, and (2) the
osteoclasts, or bone destroyers. The osteogenic process as a whole is of
course dependent upon the blood, with all its hemal elements.

OSTEOBLASTS. These are cells which may assume various shapes
depending upon their spatial relationship to the bony substance. When
free they are of round or slightly oval shape; lining the marrow cavity
or covering the bone as portions of the periosteum or applied to spicules
of cancellous bone they may become considerably flattened. The nucleus
is generally round or oval, deeply chromatic and granular. As spheroidal
cells they have an average diameter of about 8 microns. They are with

78 CONNECTIVE TISSUE CARTILAGE BONE

difficulty distinguished from lymphocytes except when characteristically
arranged as a membranous coat upon the surface of bony walls or
spicules. They become the bone cells of compact bone. Osteoblasts and
lymphocytes are genetically closely related, both being relatively slightly
differentiated mesenchymal cells. In the bone marrow of the turtle
osteoblasts may differentiate into leukocytes. It seems probable that
persistent fetal osteoblasts of adult red marrow may function as parent
blood-cells.

OSTEOCLASTS. These are giant multinuclear cells, often containing
as many as ten to twenty or more nuclei. They are believed to be the
cells by whose agency bone is destroyed during the processes of develop-
ment and growth. They are very similar to, perhaps identical with, the
polykaryocytes of hemogenic foci which are concerned with the process of
blood-cell formation. The genetic relationship of these marrow giant
cells to the leukocyte series and their full significance for the osteogenic
and hemogenic processes are not completely elucidated.

Blood Supply. Marrow, and especially the red variety, is richly
supplied with blood. The nutrient or medullary artery penetrates ob-
liquely through the nutrient foramen to the marrow cavity of a long
bone where it divides into an ascending and descending branch and
supplies an abundance of small arteries to all portions of the medulla.
The terminal arteries end in broad capillary vessels whose wide lumen
and delicate endothelial walls determine their character as sinusoids. It
was formerly thought that the endothelial walls of these vessels were here
and there deficient, and although recent investigations discredit the
former observations, the all-important fact remains that the endothelial
walls are pervious to both red and white blood-cells. Neither is this the
only location where the red as well as the white cells may, under certain
conditions at least, penetrate the endothelial walls of the blood-capillaries.

Efferent veins return the blood from the sinusoidal -capillaries of the
marrow. These veins, passing as companion veins to the medullary
artery through the nutrient foramen, or independently through separate
foramina, as also those of the bony tissue, are not supplied with valves.
Outside of the bones, however, these same veins contain abundant valves.

The Lymphatics. The lymphatics of bone occur in great abundance
in the periosteum, and as perivascular spaces penetrate the canals of
Havers and Volkmann and thus reach the medullary cavity. The exist-
ence of lymphatics within the marrow, other than in the sheaths of the
blood-vessels, is doubtful.

The Nerves. The nerves accompany the blood-vessels in all portions

BONE 79

of the bone and marrow and form a rich perivascular plexus which is
distributed to the walls of the vessels; occasional side fibrils are also dis-
tributed to the marrow. Nerve endings have not been demonstrated in
compact bone nor in the articular cartilages. In the periosteum terminal
nerve fibrils are supplied to the musculature of the blood-vessels, and
other sensory fibrils end in lamellar corpuscles.

Development of Bone Bone tissue makes its appearance relatively
late ill fetal life. The long bones are first mapped out by masses of
hyaline cartilage. The entire skeleton, with the exception of the flat
bones of the face and those of (lie vault of the skull, is thus primarily
formed by plates of fetal cartilage. The process by which these cartilag-
inous plates are transformed into bone is known as intracartilaginous or
enclwndral ossification. The process is essentially one of replacement
of cartilage by bone, not one of change of cartilage into bone. The
resulting bones are known as substitution bones.

The flat bones of the face and skull (including the interparietals,
parietals, frontals, squamosals, tympanics, median pterygoid plate of the
sphenoid, nasals, lacrimals, malars, palatine, vomer, maxilla, and a
portion of the mandible) are formed directly from the mesenchymal
blastema without the intervention of cartilage. This method of bone
formation differs somewhat from the above and is known as intramem-
b ranous ossificatio n .

INTRACARTILAGINOUS OSSIFICATION. This process begins with the
formation of plates of hyaline cartilage whose shape corresponds more or
less closely with that of the future bone. This type of fetal cartilage
differs from the hyaline cartilage of the adult only in the irregular form
and distribution and greater abundance of its cartilage cells.

Each plate of fetal cartilage is enveloped by a layer of embryonal
fibrous tissue, the fetal perichondrium. The outer portion of the fibro-
cellular layer is destined to become the periosteum of the future bone;
its innermost portion contains many small round cells, which from their
intimate relation to bone production, are known as osteoblasts. The
inner portion of the perichondrium forms the osteogenic layer of the
future periosteum.

Centers of Ossification. Ossification of the cartilage begins at one or
more points which are called centers of ossification. In the long bones,
in which the process of bone formation can be most readily traced, there
are usually three such centers, one near the middle of the cartilaginous
plate, from which the diaphysis is formed, and one epiphysial center at
each extremity. The centers for the epiphyses make their appearance

80

CONNECTIVE TISSUE CARTILAGE BONE

much later than that for the shaft of the bone, for the most part not
until some months after birth, and from an extension of marrow from
the primary center.

Enlargement of the Cartilage Cells. The first indication of begin-
ning bone formation is evidenced by an enlargement of tlie cartilage cells
which promptly arrange themselves in rows or columns that radiate from
the center of ossification (calcification). This process is accompanied
by absorption of the adjacent cartilage matrix, so that the enlarged car-

C
B

FIG. 91. THE PRIMARY CHANGES IN INTRACARTILAGINOUS BONE FORMATION.

A, metatarsus; B and C, phalanges of human fetus. In A, the earliest enlarge-
ment of cartilage cells at the center of ossification is shown. B and C are successively
later stages. The bones are cut in longitudinal section. Carmin hematoxylin stain.
X 27. (After Toldt.)

tilage cells are contained within broad spaces or areolcc. The cartilage
cells now appear to undergo a gradual but progressive absorption; their
cytoplasm becomes shrunken and granular and finally disappears, even
the nucleus at last succumbs to the process.

Calcified Cartilage. The absorption of the cartilaginous matrix pro-
ceeds more rapidly in those portions which separate the individual cells
in the columns than in those other portions which intervene "between
the adjacent rows of cartilage cells. While the former portions are
entirely absorbed, remnants of the latter remain, and in them calcium
salts are deposited in an irregular manner. Calcified cartilage, the most
primitive of the calcareous tissues, is thus formed.

FIG. 92. A LONGITUDINAL SECTION or THE Two DISTAL PHALANGES FROM THE
FINGER OF A FIVE-MONTHS' HUMAN FETUS.

Kn, cartilage showing calcification and resorption; ek, enchondral bone; M,
marrow cavity; pk, periosteal bone. X 15. (From Sabbtta's "Histology.")

SI

82

CONNECTIVE TISSUE CARTILAGE BONE

:.-. -- -,.;-""*. A,.*^ i&y

;-' : ' . "----, \ t7 '" ; --*:",-....' -;'

/; :.*'.* ' /-' ' y\

\

,1"

^|'- "^ ,^

if

SiS^. .,

^.jsiili

Primordial Mar-
row ('a cities. The
absorption of the
cartilage matrix re-
sults in the forma-
tion of broad spaces
into which osteo-
genic buds of prim-
itive marrow tissue
push their way from
the perichondrium.
Thus the primordial
marrow cavities are
formed. The fetal
marrow which now
occupies these cav-
ities is derived from
the osteogenic layer
of the primitive peri-
osteum. The oste-
ogenous tissue of this
layer, containing os-
teoblasts, osteoclasts,
a n d developing
blood-vessels, grows
into the cartilage in

the form of budlike
cords which are pre-
ceded by absorption
of the adjacent car-
tilage matrix. This
so-called 'eruptive
tissue promptly
reaches the center of
ossification 411 d bur-
rows its way into the
enlarged cartilage
lacunas whose cells are now replaced by jirimari/ osteogenic marrow. The
destruction of cartilage is initiated and maintained by agency of the
osteogenic tissue, presumably through specific cells, the so-called clion-

FIG. 93. RECONSTRUCTION OF CARTILAGE INTO BONE.

car. c., cartilage cells in successive stages of degenera-
tion; ost, osteoblasts; gi. c., giant cells (osteoclasts); 6,
young bone; bl. c., blood cells. (From Dahlgren and
Kepner.)

BONE

83

droclasts, the morphological marks of identification of which are not yet
known. According to some investigators (e.g., Eetterer, 1900) the car-
tilage cells do not disintegrate but pass into the marrow cavity where
they become osteoblasts.

Primary Bone. The osteoblasts which thus gain access to the pri-
mary marrow cavities, now arrange themselves along the surface of the
remnants of calcified cartilage and
begin the deposit at their proximal
surface of the fibrous tissue and
calcareous salts which compose the
primary bone. The osseous matrix
is commonly assumed to be the
product of a transformation of the
exoplasm of the osteoblasts. Many
of the osteoblasts apparently be-
come entangled in this newly
formed tissue and form the bone
cells. The fetal cartilage is thus
transformed into a spongy mass of
primary osseous tissue whose spic-
ules are formed by a core of calci-
fied cartilage upon which are de-
posited successive layers of bony
tissue with their included lacuna?
and bone cells. In sections stained
with hematoxylin and eosin, the
central strand of calcified cartilage
is colored blue, the primary bone,
red.

Axial sections of long bones at
this stage of ossification show all
the above changes in regular suc-
cession from the fetal hyaline car-
tilage at the extremities to the primary bone with its marrow cavities in
the center. The process of ossification steadily progresses toward the ends
of the bone, the line of enlarged cartilage cells constantly advancing
farther and farther from the original center of ossification.

Absorption of the Neivly Formed Bone. It is at this stage, however,
that the giant cell osteoclasts become most active and the absorption of
the newly formed bone progresses rapidly. The osteoclasts collect along

FIG. 94. TRABECULA OF PRIMARY
ENCHONDRAL BONE, SHOWING A
CENTRAL DEEP-STAINING CORE OF
CALCIFIED CARTILAGE AND A PER-
IPHERAL LAYER OF OSTEOBLASTS.

Osteoblasts have become incorpora-
ted within the bone as bone cells. From
the finger of a human fetus.

84

CONNECTIVE TISSUE CARTILAGE BONE

the surface of the spicules of primary bone in considerable numbers and
appear to sink into little recesses which they form within the bony
tissue. The little bays which are thus formed in the primary bone are
the lacuna of Hoivship. The continued absorption soon breaks down
and removes the trabeculae and partitions of spongy bone and forms a
central medullary cavity of constantly increasing size.

Pericliondrial Ossification. Coincident with these changes within the
cartilage the osteogenic tissue which forms the inner layer of the peri-

chondrium produces succes-
sive layers of bony tissue
upon the surface of the fetal
cartilage. This process of
pericliondrial (periosteal)
ossification proceeds in a
manner similar to that by
which bone is formed in
membrane which is not
closely applied to cartilage.
Pericliondrial bone for-
mation is essentially of the
intramembranous type. In
essence there is no valid dis-
tinction between endochon-
dral, pericliondrial and
membrane bone develop-
ment, since each involves
calcification of a fibrillar
matrix by agency of the
same cell, the osteoblast. At
irregular intervals the osteo-
clasts collect and the pri-
mary pericliondrial bone is

absorbed. Into these cavities buds of vascular osteogenic tissue push
their way to form canals of considerable length. Upon the surface of the
canals which are thus hollowed out of the pericliondrial bone, the Haver-
sian spaces, the osteoblasts deposit successive concentric layers of bony
tissue and the Haversian systems make their appearance. Finally, upon
the surface of the periosteal bone successive layers of newly formed bony
tissue compose the external circumferential lamella', while upon the
wall of the medullary cavity a similar endosteal layer of bone-forming

FIG. 95. TRABECULA OF PRIMARY BONE FROM
THE FINGER OF A HUMAN FETUS.

Three giant cells (osteoclasts) are shown at
the right, two resting in Howship's lacunae.

BONE 85

cells deposits the internal circumferential lamellae. The Havrrsian canals
are actually continuations of the marrow cavity, and the larger are cvi-n
lined by endosteum.

With the formation of the perichondrial bone the lateral expansion
of the organ by endochondral bone formation necessarily ceases. Hence-
forth increase in diameter of the bone is only produced by continued
absorption internally of the compact bony wall and the formation of new
bone beneath the periosteum by frequent repetitions of the processes of
periosteal (perichondrial) ossification as already described. The rem-
nants of those Haversian and circumferential lamellae which are only
partially absorbed in this process form the interstitial lamellae of the ma-
ture bone. In the long bones and in flat cartilage bones ossification at
first proceeds in the perichondrium, endochondral ossification appearing
only later ; in the short bones ossification is endochondral until the carti-
lage is entirely replaced by bone.

Epiphysial Ossification. During the processes of eudochondral and
perichondrial ossification within the shaft of the bone, the epiphysial
cartilages continue to grow. Finally, however, ossification begins in the
epiphysis, osteogenic tissue having pushed in from the primary center of
the diaphysis, and proceeding in the same manner as in the shaft,
results in the formation of primary spongy bone, some of which is ab-
sorbed and replaced by more compact bony tissue, as occurs in the wall
of the diaphysis. In its central portions the tissue retains its spongy
arrangement and but few Haversian systems are formed. It is thus
that the cancellous bone of this part, as also of the ends of the diaphysis,
is formed.

At the point where the expanding centers of ossification of the shaft
and epiphysis are about to meet, a line of unossified cartilage, the
epiphysial line, persists until growth of the bone is complete. It is by
growth of this cartilaginous disk, with continued formation of cartilage
mainly on its inner surface, and its concomitant replacement by bone,
that the bone increases its length. After ossification of this epiphysial
synchoiidrosis at about the twenty-first year, growth in length must
cease. Meanwhile the perichondrium has become periosteum.

The following is a resume of the various stages of endochondral ossifi-
cation :

1. Formation of the fetal hyaline cartilages from precartilage mesen-

chyme blastema.

2. Enlargement of the cartilage cells with a rearrangement into

radiating cell rows at the center of ossification.

86 CONNECTIVE TISSUE CARTILAGE BONE

3. Absorption of the cartilage matrix between the cells of the rows

and finally also of the cells themselves. Calcification of per-
sistent remnants of cartilage matrix between the rows of
cells.

4. Eruption of the subperiosteal osteogenic tissue, invasion to center

of cartilage plate, and the formation of primary marrow cavi-
ties at the center of ossification.

5. Gradual extension of the above processes followed by a deposit

of primary bone by the osteoblasts upon the calcified cartilage
spicules. Coincident osteoblastic deposit of perichondrial bone
beneath and within the perichondrium of the cartilage plate.

6. Absorption of portions of the primary bone by the osteoclasts to

form the large central marrow cavity or medulla. The ab-
sorption involves both the endochondral and the perichondrial
bone and is accompanied by a further deposit of new bone
at the periphery. In the perichondrial bone cylindrical axial
channels are formed, in which the deposit of new bone pro-
duces the Haversian systems of the compact bony tissue.

INTRAMEMBKANOUS OSSIFICATION. This is the simpler and more
direct method of bone formation. In principle it is identical with peri-
chondrial ossification. Endochondral bone development differs from it
only in respect of the additional processes involved in the removal and
replacement of the hyaline cartilage.

Membrane bones, including the flat bones of the face and the vault of
the cranium, arise directly in the mesenchyma. The first indication of
ossification is the enlargement and rounding up of a group (or groups)
of mesenchyme cells, and their association in the form of an irregular
membrane. Among the cells appear bundles of delicate collagenous
fibrils, the osteogenic fibers (Sharpcy), radiating beyond the limits of
the cell group. The cells of this initial ossific group begin to function
as osteoblasts and deposit osseous matrix among the fiber bundles.
This original osseous trabecula marks approximately the center of the
future bone. The surrounding loose mesenchyma has meanwhile become
increasingly vascular. Vaguely outlining the peripheral limits of the
definitive bone appears a relatively thick layer of denser, more cellular
mesenchyma, the cells in general maintaining a fusiform shape. This
represents the primitive periosteum of the forming bone. The bone takes
shape internally by the appearance of numerous trabecula?, which arise
in the manner described for the initial spicules and then unite into a

BONE

87

bony sponge-like structure em-losing vascular mesenchyma, the primary
marrow. The spicules of the niticellous bone contain numerous bone cells
the representatives of original osteoblasts which have become enmeshed
in their own product of osseous matrix and are covered with an epithe-
lioid membrane of a single or donUe In \er of osieohlasis. which contribute

. ._

'!

... -

. ...

I

" ' ^

.v*vp '-.',.. *

f!

'
. -

.

f 9

,

.
-

.

s> ' f * ' '

i c ' - -V

r-

.

v- - .-...

-

. a ? *.* -

I . ... # -

M X .,, - ^ t)

FIG. 96. INTRAMEMBRANOUS BONE FORMATION IN THE LOWER JAW OF A SHEEP

FETUS.

a, bone; b, primary marrow cavity; c, osteoblasts; d, growing point of the primitive
bone, beyond which primary marrow is developing in the connective tissue of the
mesoblast. X 300. (After Bohm and von Davidoff.)

to the further growth of the bony trabeculae. The marrow includes
besides osteoblasts and the specific marrow cells somewhat less numerous
than in the primary marrow of endochondral bone numerous osteoclasts
under whose absorptive agency, assisted by the productive activity of
the osteoblasts, the inner conformation of the growing bone continually
alters its details. Peripheral osteoblasts, arising from the inner layer
of the periosteum, produce the more compact external plates of the bone.

CONNECTIVE TISSUE CARTILAGE BONE

In the flat bones of the skull, the central oancellons bone is designated
diploc, the peripheral compact bone, tables. Membrane bones lack Haver-
sian systems.

The conditions which determine that certain bones may arise directly
in mesenchyrna while others must pass through a cartilaginous stage are
obscure.

It is commonly believed that periosteum is essential for bone regenera-
tion, and its preservation is aimed at where new growth is desired after
osteotomy. But according to W. Macewen ("The Growth of Bone,"
Maclehose & Sons, Glasgow, 1912), who has made a comprehensive ex-
perimental study of osteogenesis in regenerating bone in dogs, the perios-
teum functions simply as a confining, nutritive, and protective membrane,
but has no osteogenic significance. His observations lead him to conclude
also that in the long bones the osteoblasts are derived from proliferating
cartilage nuclei freed from the disappearing matrix. Under more favor-
able conditions regeneration is said to occur through direct osteoblastic
activity, under less favorable conditions a cartilaginous transition stage
intervenes. He deduces from his experiments that "diaphyseal bone is re-
produced by proliferation of osteoblasts derived from preexisting osseous
tissue, and that its regeneration takes place independently of the perios-
teum.^ The periosteum is conceived as being an important factor in de-
termining the conformation and growth limit of bone.

JOINTS

Joints are divisible into two main types, the movable and the 'im-
movable,' or (1) dlartliroses and (2) synarthroses. These and their
several modifications call for histologic description. Synarthroses include

(a) syndemoses, or joints in which the connecting substance is a dense
fibro-elastic tissue joining the bones immovably as in the articulation of
the skull (sutura), or where it consists of ligamentous tissue permitting
slight movement as between the lower ends of the tibia and fibula; and

(b) synchondroses, in which the connection is effected by cartilage,
either hyaline (e.g., between the epiphyses and diaphysis of young bones)
or fibrous (e.g., the in vertebral disks of the vertebral column).

In relation with diarthroses are in several instances (mandibular,
lower radio-ulnar, costosternal, sternoclavieular, acromioclavicular)
intra-articular menisci of fibrocartilage ; here the articular cartilages of
the bones concerned are also of the fibrous variety. The semilunar car-
tilages of the knee and the glenoid cartilage of the shoulder joint are also

JOINTS

of the fibrous type. These cartilages serve to deepen the sockets in which
the upper ends of the femur and h inner us move and are known as
adaptation cartilages or labra glenoidalia.

The joint cavity of a diarthrosis is enveloped in a capsule consisting
of two layers, an outer fibre-elastic continuous with the periosteum and
an inner cellular layer, the synodal membrane, consisting of epithelioid
cells forming a mesenchymal epithelium. The function of the synovial
membrane is to secrete a lubricating fluid, the synovia, consisting of about
i>4 per cent, water with small amounts of mucoid substances and oil.
In the large joints the synovial (serous) membrane is thrown into villus-
like folds (Fig. 240). The covering cellular membrane is occasionally
imperfect; the cells vary from the flattened, typical mesothelial cells, to
the cubic variety (Fig. 44), and rest directly upon a vascular, frequently
fatty, fibrous stroma.

CHAPTER IV
MUSCULAE TISSUE

GENERAL CONSIDERATIONS

Muscular tissue consists essentially of protoplasm in which the gen-
eral vital property of contractility has become predominant. However,
the path of contraction is practically limited to one direction, the long
axis of the cell. This phenomenon of contractility results from the dif-
ferentiation of specially contractile fibrils, the myofibrils, from the pro-
toplasm of embryonic muscle elements, the myoblasts. The protoplasm
of the muscular tissue is called sarcoplasm. Adult muscular tissue may
be divided into three classes: smooth, cardiac, and striped. All three
types arise from mesoderm, with the exception of the dilator and sphinc-
ter muscles of the iris of the eye, and the muscle of the secretory portion
of the sweat gland both of the smooth variety which are generally be-
lieved to be of ectodermal origin. In lower forms, muscle tissue may be
largely derived from the ectoderm and even from the entoderm.

The smooth muscle is in general limited to the viscera ; it is not under
the control of the will, hence also called involuntary muscle. The cardiac
type is limited to the heart, and to the middle layer of the roots of the
aorta, pulmonary artery, and pulmonary veins. It is striped, but like
smooth muscle, controlled by the sympathetic nervous system; therefore
independent of the will, hence also of involuntary type. So-called striped
or skeletal muscle is practically limited to the skeleton, and subserves the
function of skeletal movement. This group includes also the muscles
of the eyeball, the ear, the upper third of the esophagus, diaphragm,
and tongue. It is under the control of the will, hence designated volun-
tary. The striped muscle of the diaphragm and the esophagus is appar-
ently only partially voluntary.

It is obvious from the above that there is demanded a more specific
terminology: involuntary smooth (unstriped) ; involuntary striped (car-
diac) ; and voluntary striped (skeletal). The three types pass through
very similar, perhaps identical, earlier stages of histogenesis. The essen-

90

GENERAL CONSIDERATIONS

91

tial difference seems to be one of degree
dill'civntiation. In general, skeletal mus-
cle is most highly differentiated, cardiac
muscle being intermediate between
smooth and the voluntary striped type.

For a proper understanding of the
structure of these three types it is neces-
sary that we now consider the process of
muscle histogenesis. The student should
gather the several criteria by which he
may distinguish between smooth, cardiac,
and skeletal muscle, both in transverse
and longitudinal sections.

HISTOGENESIS AND STRUCTURE

Smooth Muscle. As stated above, the
germ layer involved in muscle histogene-
sis is the mesoderrn. Smooth muscle is
derived chiefly (exception: arrectores pil-
orum) from the visceral or splanchnic
layer. This is at first an epithelial struc-
ture of a single layer of cells, the prim-
itive mesothelium. The cells subsequent-
ly proliferate and change their shape in
general to a fusiform type. Intercellular
connections (cytodesmata) are either
maintained or established, and the tissue
is permanently more or less in a syncytial
condition. These so-called intercellular
bridges are particularly pronounced and
can be readily demonstrated in the tunica
media of the blood-vessels of the umbilical
cord. It must be emphasized, however,
that the outlines of the genetic units in
smooth muscle are always distinct, where-
as in striped, especially the cardiac type,
the outlines of the original myoblasts are
lost.

FIG. 97. SMOOTH MUSCLE
CELLS.

A, an isolated cell from the
cat's intestine. The nucleus is
surrounded by coarsely granular
sarcoplasm, continuous periph-
erally with the finely granular
interfibrillar sarcoplasm. The
innermost myofibrils may er-
roneously suggest a cell mem-
brane. The fusiform element is
invested by a true cell mem-
brane, or sarcolemma. X 750.
B, oblique transverse section of
a cell from the muscularis mu-
cosse of the cat's esophagus.
The perinuclear sarcoplasm has
contracted away from the nu-
cleus leaving a clear space limited
by a sharp line, external to which
lies the perinuclear granular sar-
coplasm. Hematoxylin and
eosin. X 750.

MUSCULAR TISSUE

The early myoblast, of short spindle shape with central oval nucleus,
contains a granular cytoplasm, limited hy a delicate membrane, the
sarcolemma. The granules may be called myochondria; whether identi-
cal with cytomicrosomes or with mitochondria, whether of cytoplasmic

FIG. 98. SMOOTH MUSCLE CELLS FROM THE PIG'S STOMACH.
Isolated in equal parts of alcohol, glycerin, and water. Unstained. X 410.

or of nuclear origin, are disputed points. No evidence of a distinct
spongibplasm is discernible. This observation tends to invalidate the
teaching of certain histologists, that the contractile fibrils (myofibrils)
represent modified spongioplasmic threads arranged in rectilinear meshes.

FIG. 99. SMOOTH MUSCLE CELLS FROM THE WALL OF THE HUMAN INTESTINE.
Longitudinal section. Hematein and eosin. X 665.

Moreover, it has been established by direct observation (McGill. et al.)
that the myofibrils arise through process of alignment and subsequent
fusion of the myochondria. McGill ( Internat. Monatschr. Anat. u. Phys.,
Bd. 24, 1907) recognizes two types of myofibrils, namely, stouter periph-
eral border fibrils (myoglia) which may pass beyond the limits of a
cell and form intercellular bridges; and the more central, or myo/ibrils

HISTOGENESIS AND STRUCTURE 93

proper, which are limited to the cells proper and are considerably more
delicate. It is believed that border fibrils may subsequently arise by
fusion of the more delicate fibrils.

The function of the border fibrils is disputed, some claiming that
they serve to straighten the cell following contrac-
tion produced by the central fibrils, others claim- Q
ing that they have a contractile role similar to the
central myofibrils. Whatever their complete func- ^
tion may be, they certainly seem to bind, together
with the connective tissue, the individual cells into @ -
a compact tissue in which coordinated movement,

as in peristalsis of the intestine, becomes possi-

FIG. 100. SMOOTH
ble an obviously important condition. MUSCLE CELLS

The oval or rod-shaped nucleus retains its cen- FROM THE WALL OF

tral location, and is surrounded by a mass of gran- THE HUMAN INTES-
TINE.

ular, relatively undifferentiated sarcoplasm, con- ~,

Iransection. Hema-

taining mitochondria, lipoid, and glycogen gran- te in and eosin. x 750.
ules. It changes its shape with the phase and

degree of contraction, occasionally even assuming a short, spiral form.
It has been shown (McGiU, Amer. Jour. Anat, 9, 4, 1909) that during
contraction the nucleus decreases markedly in length and increases in
thickness; and that the uniformly distributed chromatin granules stream
toward the poles, where they collect in coarse strands. This structural
intranuclear change is apparently unaccompanied by any change in
volume.

Smooth muscle cells vary greatly in size from the shortest of about
50 microns, to some of 500 microns in length in the pregnant uterus.
When in the contracted condition, they show a number of broad, more
deeply staining contraction bands, very conspicuous in the smooth mus-
cle of the lower portion of the esophagus. As seen in transverse section
these fibers vary in size from a mere point u-p to their maximum diame-
ter, according as the section happens to pass through the end or through
the middle of a fiber. Because of its central location, the nucleus
is only found in the larger transections.

Smooth muscle fibers may be joined together in interlacing groups
as in the wall of the uterus or bladder; or they may form broad mem-
branous layers as in the wall of the alimentary tract; or again,
they may form small isolated bundles, as in the skin. In any case,
the muscle bundles are united by a delicate network of connective
tissue.

94

MUSCULAE TISSUE

Smooth muscular tissue occurs chiefly in the walls of the hollow or
tubular viscera. Its distribution may be classified as follows :

(1) In the alimentary tract : lower portion of the esophagus, stom-
ach, small and large intestines.

(?) In the respiratory system: trachea and bronchial tubes.

(-">) In the genito-urinary xiixh'm: ureter, bladder, urethra, penis,
prostate, vagina, uterus, oviduct, and ovary.

(4) In the vascular xi/x/cm: ar-
teries, veins, and the larger lymphatic
vessels.

(5) In the ducts of all secreting
glands: gall ducts and gall bladder,
and the ducts of the pancreas, sal-
ivary glands, testicle, etc.

(6) It is also found in the cap-
sules of the spleen and lymphatic
nodes, in the skin, and in the intrin-
sic muscles of the eye.

Small numbers of branching cells
have been described in the walls of
the urinary bladder and the large
arteries.

Cardiac Muscle. Heart muscle
likewise takes origin from splanchnic
mcsotlielium, which soon becomes
modified into a loose-meshed syncy-

FIG. 101. Two STAGES IN THE His-
TOGENESIS OF SMOOTH MUSCLE,
FROM THE WALL OF THE ESOPHAGUS
OF A PIG EMBRYO.

A, 10 mm. stage of development.
The central nucleus of the mesenchy-
mal syncy.tium has become enlarged
and is enveloped by a greater mass
of cytoplasm. It represents a myo-
blast; the peripheral myochondria have
become aligned preparatory to fusion
to form a muscle fibril. B, 21 mm.
stage of development. Four adjacent
myoblasts, with peripheral stouter
myoglia fibrils and central more deli-
cate myofibrils. X 1500.

quently acquire a cross striation.

tium. in which all trace of the orig-
inal cellular element is lost. The
myoblast areas of stellate and irreg-
ular form contain a central oval nu-
cleus and a finely granular cytoplasm.
In a manner similar to that described
for smooth muscle histogenesis, the
myochondria form myofibrils which
extend for great lengths throughout
the sarcoplasmic meshwork. In car-
diac muscle the mvofibrilla? subse-

Adult muscle consists of stouter mus-
cle fibers or trabeculse joined into an intricate close meshwork, by means
of less robust branches. The nuclei retain their axial position in the

HISTOGENESIS AND STRUCTURE

95

fibers and are surrounded by an oval aiva of undifferentiated granular
>a ivoplasm. The cardiac libers and their brandies contain peripheral
nivofibrils, which during growth of the muscle arise by longitudinal
splitting of the original fibrils and take position progressively toward the
center. Cardiac- muscle thus consists of a slender axial core of undilTer-
eiitiated sarcoplasm swelling to an oval, more expansive mass where the

FIG. 102. A GROUP OF MYO-

BLASTS PROM THE HEART
MUSCLE SYNCYTIUM OF A
48 HOUR. CHICK EMBRYO.

Showing myofibrils, myo-
chondria and mitochondria.
The latter are the deeper
staining granules. Meves'
technic. X 2000.

FIG. 103. CARDIAC
MUSCLE OF GUINEA
PIG, SHOWING SEV-
ERAL BRANCHES,
CROSS STRIATIONS
(GROUND M E M -

BRANES) AND A Xuil-

BER OF INTERCALATED
DISKS.

Zimmerrnann's tech-
nic-. X 1000.

nuclei arc located ; this core is surrounded by successive rows of myofibrils
arranged in groups representing Cohnheim's fields in transverse section;
and the whole is invested by a delicate sarcolemma. The striations of
the fiber result from the fact of a transverse alignment of identical areas
in adjacent fibrillw a correspondence which indicates a definite func-
tional stimulus to a structural modification ( Fig. !(>.">). The sarcoplasni
contains mitochondria (Fig. 1<"'^), lipoid, albuminoid (interstitial gran-

96 MUSCULAR TISSUE

ules of Kolliker), and glycogen granules. Fat granules, 'liposomes'
(Bell) of probably nutritive significance, and varying greatly in amount
according to the functional condition of the individual, are normally
present in cardiac muscle (J-lnllurd, Amer. Jour. Anat., 1-4, 1, 1912).
This fatty content can be demonstrated by the several mierochemical
technics for lipoids. According to Meves, Duesberg, and others, the myo-
fibrils of striped muscle differentiate from the mitochondria of the myo-
blasts; but since mitochondria can be demonstrated in highly developed

FIG. 104. CARDIAC MUSCLE 'CELLS' FROM THE PIG'S HEART, ISOLATED IN
EQUAL PARTS OF ALCOHOL, GLYCERIN, AND WATER.

Unstained. (The nuclei are somewhat darker than they actually appear.) X 410.

fibers (Fig. 116) it seems improbable that mitochondria have anything
directly to do with the development of muscle fibrils.

It has been claimed that heart muscle and striped muscle generally
can be interpreted in terms of muscle cells, and intercellular myofibrillae,
in analogy with connective tissue (Baldwin). But the presence of a con-
tinuous axial core of undifferentiated sarcoplasm, lack of a definite cell
membrane separating this sarcoplasm from the outlying myofibrillas, in-
ability to separate such 'cells' by dissociation methods, and the extension
of the telophragma to the nuclear wall, seem to render this view unten-
able.

The myofibrils must be further considered. No distinction between
border fibrils and central fibrils, as in smooth muscle, is possible in car-
diac muscle. But the myofibrils undergo greater differentiation. This

HISTOGENESIS AND STRUCTURE

expresses itself in an alternation of light and dark disks ('bands,' 'seg-
ments/ 'stripes'), said to consist of isotropic and anisotropic substances
respectively. While the disks are conspicuous both in fresh and stained
tissue, the demonstration of their physical properties under the polari-
scope is a matter of difficulty. Indeed with crossed Nichols the entire

FIG. 105. CARDIAC MUSCLE OF THE HUMAN HEART; THE ABUNDANT BRANCHES

ARE PLAINLY SHOWN.
Longitudinal section. Hematein and eosin. Photo. X 120.

fiber appears lighter than the field, showing the presence of anisotropic
materials (granules) scattered throughout the fiber, but a definite band-
ing corresponding to the light and dark disks of fresh muscle is not
apparent in all striped muscle. It seems more probable that, though
anisotropic granules are more abundant in the dark disk, they are not
absent in the lighter disk; moreover, they are more or less definitely
aggregated in the dark disk according to the phase of contraction. The

98

MUSCULAR TISSUE

a en

FIG. 106. THE CENTRAL PORTION OP THE
PRECEDING FIGURE, MORE HIGHLY MAG-
NIFIED.

a, intercalated disk; en, endothelial nuclei
of a capillary; Nuc, nucleus of muscle syn-
cytium. Hematein and eosin. X 500.

lighter disk, or intermediate disk of Krause, is commonly designated by
the letter J (Isotrope streife) ; the dark disk, or transverse disk of
Briicker. by the letter Q (Querscheibe). On closer inspection the J

disk is seen to be bisected by a
dark disk or membrane, the
ground membrane of Krause.
designated by the letter Z
(Zwischenscheibe) . Indeed
this is the most conspicuous
stripe, and gives to the mus-
Nuc cle, as seen under ordinary
low magnification, its band-
ed appearance in uncontracted
fillers. The term teloplirmima
has recently been employed by
Heidenhain for this mem-
brane. The myofibrils are in-
timately connected with it.
Similarly, the Q disk is bi-
sected by a narrow light disk, the median disk of Hensen (H), which in
turn is said to be bisected by the intermediate membrane of Heidenhain,
or mesophragma (M, Mittelscheibe). Both telo- and mesophragmata
(inophragmata) are supposed to unite with the sarcolemma peripherally,
and to be structurally similar. The telophragma is in intimate connec-
tion both with the sarcolemma
and the nuclear membrane. But
the mesophragma, at least in
striped muscle of certain forms,
e.g., Limulus, is not a true
membrane to which the fibrils
are attached in the manner of
the telophragma. Indeed it re-
mains an open question whether
heart muscle actually possesses
a mesophragma.

The portions of a fibril, or
sarcostyle, included between
successive telophragmata, con-
stitute structural units, the sar-
comeres, or uiokommaia (Heidenhain, Fig. 110). In macerating fluids

FIG. 107. TRANSECTION OF A GROUP OF
CARDIAC MUSCLE FIBERS FROM A PAPIL-
LARY MUSCLE OF THE HUMAN HEART.

Hematein and eosin. X 550.

HISTOGENESIS AND STRUCTUEE !)!

fractures occur at the Z lines. These membranes extend completely across
the fiber, through the axial strand of sarcoplasm a siirnilicant fad con-
troverting the cellular idea of cardiac muscle originally advanced b\-
Apathy. The interstitial granules of Kolliker ( sa rcosomes of Uetzius)
scattered throughout the Q and J disks in
striped muscle, both cardiac and skeletal, M

are designated the Q and J granules re- ^

spectively ( Holmgrei i ) .

INTERCALATED DISKS. A unique char-
acteristic of cardiac muscle pertains to the ^

presence of the intercalated disks, 'junc-
tional lines/ or bands of Eberth. These

arc barely visible in ordinary histologic Fl J' 108 -" - DEVELOP MUSCLE

, FIBERS FROM THE HEART OF A

preparations, but can be rendered conspic- HUMAN FETUS AT SEVEN

nous by the special technics of Heiclenhain MONTHS.

and of Zimmermann. In gross appear- Fibrillae are well developed at

,1 . , the periphery: the undifferenti-

ance they are of several sorts: straight ate / cy l opla y s ' m in the center

bands, step-like forms, and serrated forms, presents a clear appearance and

The bands (disks) may extend completely in some cases is partially occu-
,2! . ,,, P pied by the nucleus. Hematein

across a fiber, or only the width of a single ^nd e0 g in x 750

fibril (granule type) ; the step form may

consist of one or many groups of steps and risers, the 'risers' being the
height of one or, occasionally, several inokommata ; the saw-tooth type
also may be of small or greater extent, and of the height of one or several
inokommata. All three types may be arranged in rings or even longer or
shorter spirals. The intercalated disks are peripheral in position, extend-
ing for varying depths, but never completely through u fiber, and never
central to the axial sarcoplasm. They are occasionally on the same level
with the nucleus. They have been found in the heart of representatives
of all the animal groups to, and including, teleost fishes (Jordan and
Steele). They are present sparsely and in simple form also in the heart
of Limulus. They are probably a morphologic incident of the rhythmic
contraction of cardiac muscle. They appear only late in fetal life, toward
the end of the last week of gestation in the guinea pig.

The earliest disks are all of the coarsely granular band type. Subse-
quently they increase in number and complexity, the older stages being
characterized by occasional saw-tooth forms. Once formed, they are
evidently for the most part permanent structures, undergoing modifica-
tion largely through mechanical factors. On closer inspection, under
the higher powers of the microscope, they are seen to consist of units

100

MUSCULAR TISSUE

A B

FIG. 109. CARDIAC MUSCLE
FIBERS.

A, portion of a fiber from a
macerated preparation of a
cat's heart, drawn according
to its appearance in the opti-
cal longitudinal plane. Two
nuclei are shown, connected
by a continuous axial strand
of coarsely granular sarco-
plasm. The sarcolemma ap-
pears festooned between suc-
cessive ground membranes.
There is no evidence of a cell
membrane separating the cen-
tral granular from the periph-
eral non- or finely-granular
sarcoplasm. X 1000. B,
median longitudinal section
of a fiber from the ventricle
of an adult white mouse.
Note the continuity of the
axial sarcoplasm. Hematox-
ylin and eosin. X 1000.

corresponding to portions of a single fibril.
These units may be granular or compact.
The units are bisected or bounded on one side
by the Z membrane. Association of the units
in transverse lines gives rise to the band
forms; they may be drawn into spirals by
longitudinal traction of the fibers involved;
unequal transverse and oblique tractions
probably produce the step forms; the saw-
tooth form arises by process of longitudinal
splitting of fibrils, enlargement of fibers, and
the various tensions characteristic of hyper-
trophying fibers. The exclusive type of
hypertrophied heart muscle is the more or
less complex saw-tooth type. The practically
exclusive type of atrophied heart muscle is
the 'comb type/ a type produced from a band
type by a modification involving longitudinal
tension (Fig. 114, d). In brief, the unit of
structure is a modified focus on a myofibril,
in essence involving an accumulation of gran-
ules about the Z membrane. Such foci asso-
ciated in various ways produce the various
types of bands and steps, the latter in part
due also to external mechanical factors, the
extreme condition of such effect being saw-
tooth forms.

A significant point concerns the similarity
between the phylogenetic and ontogenetic de-
velopment of intercalated disks : that is, below
birds, as in all fetal hearts, only simple bands
appear ; in birds as in young hearts, step forms
are present; only in mammals and in old
hearts do the more complex types appear.
What then is the meaning of these disks ? Any
interpretation must be more or less tentative
at present. It is easier to say what they prob-
ably are not, than what they probably are.
They were originally interpreted as cell boun-
daries, or intercellular cement lines (Schweig-

HISTOGENESIS AND STRUCTURE

101

ger-Seidel) ; this interpretation has recently been again supported by
Zimmermanii. This interpretation would mean that from a syncytium a
cellular tissue has secondarily arisen by the appearance of cement, lines,
secondary cells having been formed in a syncytium, irrespective of the
original genetic units. A number of facts render this interpretation inad-
missible, chief among which are their occasional supernuclear position, and
their peripheral location. A more recent interpretation conceives of them
as places where the muscle fiber grows, that is, as sarcomeres in the mak-
ing (Heidenhain). Among the countervailing facts to such interpretation
are chiefly the absence of transition stages, their relative scarcity at the
period of greatest growth of the heart, and their continued abundance in
full-grown, even aged, hearts. The suggestion has occasionally been made
that they are somehow related to a phase of contraction. This seems the

J 2

Q

I

C I

Id

I J

Telophragmo.
J granule

Q-granule

Mesophragma
Q-granule

J granule
J-gra n ule

Transverse
fiber net-
work

Transverse
fiber net-
work

FIG. 110. -- DIAGRAM OF A
STRIPED MUSCLE FIBER, AC-
CORDING TO HEIDENHAIN.

The transverse fiber network
may be a trophospongium.

FIG. 111. --SIX-
LOB E D NUCLEUS
FROM THE HEART
MUSCLE OF LIM-
u L u s , SHOWING
THE CONTINUIT\
OF THE NUCLEAR
WALL WITH THE
TELOPHRAGMATA.

X 1300.

more likely interpretation. Since the discs are largely permanent when
once formed, and undergo subsequent modification, they must represent an
irreversible condition of the contraction phase. The interpretation of the
disks as irrecersiUr contraction Itaiiclx rests largely upon the similarity be-
tween the simplest types and the 'contraction bands 1 <if Rollet. both char-
acterized by accumulation of dark staining granules about the Z membrane.
In the older hearts, where they are mechanically modified, and in diseased
hearts, as in hypertrophies, where probably a chemical modification is also
8

102

MUSCULAR TISSUE

suffered, they represent lines of weakness. These are the locations of frac-
ture in fragmented and segmented pathological hearts a significant point
in relation to 'heart failure/

Heart muscle is syncytial in structure, and the myofibrillas pass unin-
terruptedly through the intercalated disks. These facts are of special im-
portance because of their bearing on the opposed theories of the origin and
conduction of the stimulus to the heart beat, the myogenic and the neuro-

genic. A complete cellular structure with actual ce-
ment lines, combined with the fact that the atria are
apparently completely separated from the ventricles by
intervening connective tissue, was once urged as a
strong argument against the validity of the myogenic
theory of heart beat the theory which proclaimed the
adequacy of heart muscle to initiate and conduct the
stimulus to contraction without the intervention of
nerve elements, that is, to beat automatically and inde-
pendently of the nervous system. The neurogenic
theory, which holds that nerve elements are essential
for the conduction of stimuli for contraction, on the
other hand, seemed contradicted by the observation that
in the chick the heart beat rhythmically before the ap-
pearance of nerve fibers. However, there remained the
possibility that nerve fibers were actually present but
(indemonstrable by the method employed; also that
while nerves might be imnecessary for maintaining
rhythmic contraction during embryonic life, they
nevertheless became necessary in fetal and adult life.

FIG. 112. SEVEN
N UCLEI, THE
PRODUCT OF
AMITOTIC DIVI-
SION, LYING IN
AN UNDIFFEREN-
TIATED MASS OF
SARCO PLASM,
FROM THE HEART

OF LlMULUS.

The telophrag-
mata are seen span-
ning the space be-
tween the nuclear
membrane and the
next adjacent myo-
fibril. X 700.

The discovery of the atrioventricular bundle of
His (1893) at first added apparently the strongest
evidence to the support of the application of the myo-
genic theory of heart beat in the mammalian heart.
This is a muscular bundle which effects an intimate
connection between the atria and the ventricles. (Tt
will be further described with the Heart.

An important matter is the observation that the
final ramifications of the bundle of His are identical with the so-called
Pur jink e fibers. These have long been known, especially in the sheep's
heart, where they are unusually large and abundant. They are limited
to a region directly under the ventricular endocardium. They are coarser,
less branched, with fewer intercalated disks, almost, exclusively of the
band type, than aiv the fibers of the myocardium proper. They would

HISTOGENKSIS AND STRUCT T I,' K

103

seem In represent a younger or less highly differentiated stage of muscle
fiber. In cross section they are of greater diameter, with fewer peripheral
myofibrils and a far greater amount of central undifferentiated sarco-
plasm, rich in glycogen. According to Lange (Arch. mikr. Anat,, Bd.
84, 1914) the Purjinke fibers cannot, however, be regarded as remains of
embryonic muscle cells, since they are clearly distinguishable already in
very young mammalian embryos; they constitute the
non-nervous apparatus for conducting stimuli to heart
beat.

The myogenic theory accordingly seemed well es-
tablished. It was apparently strongly supported by the

experiments of Erlanger (1906), who clamped the

bundle in the dog's heart and produced a condition of

'heart block' a disturbance of the coordinated rhyth-

micity of the atria and ventricles without, however,

interfering with the conduction of impulse, since there

resulted no stoppage of contraction in the ventricles.

But the subsequent discovery of abundant nerve fibers

and ganglion cells (Tawara, Wilson, McGill) in the

bundle, intimately related to the cardiac fibers, robbed

this experiment of its specific applicability and seemed

for a time to force an interpretation favoring the neu-

rogenic theory. Carlson, moreover, demonstrated its

validity for the Limulus heart, in which, after the

removal of its ganglion, it could not be made to beat.

But more recently Burrows (1911) has shown that

single cells of a 14- to 18-day embryo chick heart,

grown in artificial culture media, may begin to beat

automatically and rhythmically an observation which
would seem to settle the point that heart muscle may
beat rhythmically in the absence of nerve supply or
even nerve stimulus.

Furthermore, Hooker (Jour. Exp. Zool., 11, 2, 1911) showed that in the
frog larvae in which the nervous system was entirely removed, the cardiac
muscle will differentiate and function normally, independently of nervous
control. The myogenic theory is further supported by the fact that it has
been possible to revive the excised heart of man to rhythmic activity 20
hours after death (Flack, "Further Advance in Physiology," Ed., Hill, 1909),
whereas the longest time that a nerve cell is known to survive (in the intes-
tine) is 3 l /2 hours (Cannon and Burkett, Amer. Jour. Phys., vol. 32, p. 347,
1913). In the superior cervical ganglia, nerve cells may survive 1 hour,
while in the brain the maximum time of survival is aid to be 15

FIG. 113. LONGI-
TUDINAL SECTION
OF A TRABECULA
OF LIMULUS
(KING CRAB)
HEART MUSCLE,
SHOWING AN IN-
TERCALATED
DISK SEPARAT-
ING A CONTRACT-
ED FROM AN UN-
CONTRACTED
PORTION.

Nitric acid-alco-
hol fixation (Zim-
mermann's tech-
nic), iron-hematox-
ylin stain. X 1300.

104

MUSCULAR TISSUE

Any interpretation of the intercalated disks as actual intercellular struc-
tures (cement substance) would seem inconsistent with the myogenic theory
of the heart beat, which now seems largely to prevail. The present status
of the matter seems to be that the origin of stimulus to heart beat in
vertebrates is myogenic, in invertebrates probably neurogenie. The differ-
ence may inhere in the absence in the hearts of invertebrates of a muscular
coordinating structure analogous to the atrioventricular bundle of verte-
brate hearts.

FIG. 114. SEMIDIAGRAMMATIC ILLUSTRATIONS OF VARIOUS TYPES OF INTERCALATED

DISKS.

a, from guinea pig's heart; 6, from chipmunk's heart; c, from monkey's heart;
d, from monkey's heart; e, from guinea pig's heart;/, from chipmunk's heart. X 1200.

Voluntary Striped or Skeletal Muscle. The unit of structure of
skeletal muscle is essentially the same as that described for cardiac mus-
cle, namely, a myofibril or sarcostyle. The fiber is likewise divisible into
successive sarcomores or inokommata. A difference in detail inheres in
a greater definiteness of striation, and a greater complexity, due to the
presence generally of an additional disk in the J stripe. This stripe
or accessory disk of Merkel and Rollet (N line; nebenscheibe) bisects the

HISTOGKNESIS AND STRUCTURE

105

portion of the .) disk lietween Ilie Z line and Hit- succeeding Q disk.
Jt is interpreted more or less tentatively ly Heidenhain as due to a linear
arrangement of J granules. The median segment of the J disk, that is,

the portion between the N line and
the Z line, is called the terminal <lixh-
of Engelmami (E disk; endscheibe).
This complex condition of striping is
conspicuous only in certain insect
muscles (e.g., leg and wing muscles
of wasp, etc.) where powerful activity
or great rapidity of beat is required.
Tn general, complexity of striation of
conspicuous character corresponds
with a relatively greater irritability
and a capacity for more powerful or
relatively more rapid function.

Another difference between skel-
etal and cardiac muscle pertains to
the diameter of the fiber and tbe posi-
tion of the nucleus. In skeletal mus-

FIG. 115. SUCCESSIVE STAGES OF
SKELETAL MUSCLE HISTOGENESIS
IN MAMMALS.

a, myoblast with fine cytoplasmic
granules (myochondria), from a 13
mm. sheep embryo; 6, myoblast
with homogeneous myofibrils, from
a 10 mm. guinea-pig embryo; c,
myoblast with cross striped fibrils,
from a 8.5 mm. rabbit embryo.
(From Heidenhain, after Godlew-
ski.)

FIG. 116. TRANSVERSE
SECTION OF A STRIPED
MUSCLE FIBER OF A
NEWLY-HATCHED RAIN-
BOW TROUT, SHOWING
THE PROCESS OF MYO-
FIBRIL INCREASE BY RA-
DIAL LONGITUDINAL
SPLITTING.

Mitochondria are seen in
the peripheral sarcoplasm
and around the nucleus at
the right. Meves' technic.
X 2000.

cle the fiber has a greater diameter, is more nearly circular in cross sec-
tion, the myofibrils are scattered throughout its diameter, and the nuclei
are peripheral, lying just beneath the sarcolemma. The nuclei are envel-

106

MUSCULAR TISSUE

FIG. 117. STRIATED
MUSCLE FIBERS RUP-
TURED BY TEASING,
SHOWING THE SARCO-
LEMMA.

a, ruptured end of the
muscle fiber; B, a bundle
of fibrils projecting from
the torn end; in, a muscle
fiber; n', a nucleus of the
muscle cell; at p, the
muscle substance has
shrunken away from the
sarcolemma; s, sarcolem-
ma. Moderately magni-
fied. (After Ranvier.)

oped in a small amount of granular sarcoplasm.
The .sarcolemma is a homogeneous, plastic, non-
nucleated membrane, the representative and
product of the cell membrane of the original
xnyoblasts.

In routine laboratory preparations only the
Z, Q, and J stripes are conspicuous. Meigs
(Zeitschr. allg. Phys., 8, 1, 1908) recognizes at
most only three different substances in striped
muscle sarcostyles (fresh wing muscle of fly) :
i), Z, and M. He regards J and H as optical
effects dependent upon the reflection of light by
the Z and M membranes.

Asai (Arch. mikr. Anat., 8G, 1, 1914) records
the absence, of both Z and M membranes in the
wing muscles of certain insects (Coleoptera) and
the analogous (pectoral) muscles of birds and
bats.

The perinuclear sarcoplasin contains filar and
granular mitochondria. Both the perinuclear
and interfibrillar sarcoplasin contain also fat
granules and globules (liposomes), interstitial
granules of Kolliker and glycogen.

Heidenhaiii (Anat. Anz., 44, 11-12, 1913) has
conclusively shown that in the trout embryo the
progenitor (the manner of whose origin is un-
known) of the definitive myofibrillae is a single,
stout, deeply staining column, close to the nuclear
wall externally, which undergoes a succession of
radial and concentric longitudinal divisions. This
observation would seem to dispose of the assump-
tion of a direct mitochondrial origin of myofibril-
lae in this form at least, in the manner of the
current descriptions. And this conclusion is
strengthened by the demonstration of mitochon-
dria throughout the earlier development (Fig.
116).

Skeletal muscles develop from a portion of
the mesodennic segments or primitive somites,
called the nti/otoiiu'x. The -m-yob/axlx pass through

FIG. 118. ISOLATED FRAGMENTS OF STRIATED MUSCLE FIBERS, UNSTAINED.

The one above is from the end of a fiber; that on the right shows at one end a,
tendency to cleavage into transverse disks. X 360.

FIG. 119. STRIATED MUSCLE FIBERS OF THE DOG, SEEN IN TRANSECTION.

The areas of Cohnheim are indistinctly outlined. Hematein and eosin. X 490.

107

108

MUSCULAR TISSUE

the early histogenetic changes already described for cardiac muscle. In
the frog, irritability was shown by Hooker to follow closely upon differen-
tiation of the fibrillae, and the establishment of nervous connections.
The adult skeletal muscle fiber is a multinucleate structure. Is this
condition the result of fusion of distinct myoblasts, or of growth of a
single myoblast accompanied by nuclear proliferation? Both interpreta-
tions have been advanced; many observational data tend to show that

FIG. 120. A PORTION
OF A STRIATED MUS-
CLE FIBER SEEN IN
LONGITUDINAL, SEC-
TION.

The alternate light
and dark cross stria-
tions are well shown.
h, light line, Hensen's
line, in the middle of
the dark disk Q. z,
dark line, Kratise's
membrane or Dobie's
line, in the middle of
the light disk. Hema-
tein. X 1200. (After
Bohm and von David-
oflf.)

FIG. 121. A SMALL
PORTION OF A MUS-
CLE FIBER OF A
CRAB SHOWING BE-
GINNING SEPARATION
INTO FIBRILS.

Drawn from a pho-
tograph. X 600. (After
Schafer.)

a skeletal muscle fiber represents a myoblast which has elongated and
multiplied its nuclei. In the trout embryo, however, considerable fusion
of myoblasts occurs. The mode of nuclear division appears to be at first
mitotic, and subsequently amitotic. In the tongue a small number of
branched fibers have been described.

Striped muscle fibers differ in the relative amounts of myofibrillar and
sarcoplasmie content. When the myofibrillse are relatively preponder-
ant and the interstitial granules sparse, the fiber is known as 'light';

HISTOGENESIS AND STRUCTURE

109

when the sarcoplasm, with its interstitial granules, is relatively. abundant,
'dark.' In the latter fibers many of the nuclei may be (cut rally located.

<I^S

#

FIG. 122. FIBRILS FROM THE WING
MUSCLES OF A WASP.

A, contracted; B, stretched; C, un-
contracted. The alternate dark and
light disks are prominent; the mem-
brane of Krause in the light disk, and
the line of Hensen in the dark disk are
well shown. Very highly magnified.
(After Schlifer.)

FIG. 123. LONGI-
TUDINAL SECTION
OF A PORTION OF
A STRIPED MUS-
CLE TRABECULA
OF LIMULUS,
SHOWING A NU-
CLEUS OF SER-
RATED CONTOUR
WITH THE TELO-
PHRAGMATA AT-
TACHED TO THE
SERRATIONS.

The nucleus lies
in an undifTerenti-
ated mass of sarco-
plasm containing
below a deutoplas-
mic granule. The
adjacent myofibrils
simulate a cell mem-
brane. Fleming's
fluid, iron-hematox-
ylin. X 2000.

Most mammalian muscles contain both types of fibers, but with the
'light' greatly in excess. When a muscle consists chiefly of 'light' fibers
it is a 'white' muscle; when the 'dark' fibers are abundant it may be

110

MUSCULAK TISSUE

called 'red' muscle. The former variety, for example the biceps muscle,
acts more energetically but is more easily fatigued ; the latter, like the

muscles of mastication, respiration, the eyeball, and
cardiac muscle, are functionally characterized by
slower activity but less ready fatigue. The intersti-
tial granules accordingly seem to be of nutritive sig-
nificance. They are generally more abundant in the
J than in the Q segments. The J granules are of
spherical form and smaller than the oval Q granules.
Striped muscle fibers contain also a trophospongium
(Holmgren). Adult muscle cannot regenerate, but is
replaced by scar tissue. A young fiber is said to be
able to regenerate, the process involving movement of
proliferating nuclei toward the cut surface. Muscle
growth, as with exercise, depends upon enlargement

IHUlH

FIG. 124. S T R i A T E D
FIBER FROM A LEG
MUSCLE OF THE SEA
SPIDER (ANAPODAC-
T Y L u s MAXILLARE),
SHOWING THE COM-
PLEXLY STRIPED CON-
DITION CHARACTER-
ISTIC OF INSECT MUS-
CLE.

Q, anisotropic disk; J,
iso tropic disk; M, mem-
brane of H e i d e n h a i n
(m eso phr ag ma) ; Z,
membrane of Krause (telo-
phragma) ; H, median disk
of Hensen; N, accessory
disk of Merkel; E, terminal
disk of Engelmann. X
1000.

ZJQJZJQJZJQJZ

B

FIG. 125. SEMIDIAGRAMMATIC DRAWING, REP-
RESENTING THE APPEARANCE OF THE SAME
FIBER FROM THE LEG MUSCLE OF A BEETLE IN
ORDINARY AND POLARIZED LIGHT.

A, appearance in ordinary light; B, appearance
in polarized light. (After Meigs.)

of the muscle fiber, consequent upon a multiplication of fibrillge by process
of longitudinal splitting, and their individual enlargement.

MUSCULAR CONTRACTION

111

MUSCULAR CONTRACTION

The physics and chemistry of muscle constituents are too inadequately
known to permit anything like a confident description of the mechanism
of contraction. It has been suggested that muscular contraction is essen-
tially a reversible coagulation process. The rapidity of the process seems
a fatal objection to this
explanation. A plaus-
ible interpretation fol-
lows the analogy afford-
ed by the action of cat-
gut suspended in water,
the temperature of which
suddenly raised by

Sarcolemma

is

passage of ami electric
current, namely, a swell-
ing and consequent
shortening of the fiber
(Eiigelmann). In mus-
cle, the myofibrillse may
be conceived of as cor-
responding to the catgut
of the experiment, the
semifluid sarcoplasm to
the water, and the nerve
impulse to the electric
current. The rapidity
of muscular activity,
however, again seems a
difficulty. However, the
optical changes under-
gone by a contracting
muscle give evidence in
favor of such interpreta-
tion. The fibrillae short-
aiid thicken in con-

Doyere's hillock

en

FIG. 126. LATERAL CONTRACTIVE WAVE OF CASSIDA

EQUESTRIS. (After Rollet.)

The formation of the contraction band is well seen,
at the left, as thick black lines. (From Szymonowicz-
MacCallum," Histology and Microscopic Anatomy.")

traction, and there is a

rearrangement of the optically different substances of the fiber; the dark
granules aggregate about the Z line, so that it seems to have disappeared
a change which involves also the disappearance of the original Q stripe.
We may be fairly certain that the explanation of muscular contraction must
be sought for in physical and chemical changes in the myofibril, it being

113

MUSCULAR TISSUE

the essential contractile element, the sarcoplasm serving largely as a nutri-
tive substance. However, it should also be mentioned that it has been held
that the sarcoplasm may be the essential contractile substance.

Meigs questions the pertinency of Engelmann's 'artificial muscle' in
his catgut experiment, and the validity of the suggested hypothesis of con-
traction as a thermodynamic phenomenon. He regards contraction as
the result of a rise in osmotic pressure and the consequent imbibition
of fluid caused by the breaking down of larger into smaller molecules
within the sarcostyles. According to Roaf (Proc. Roy. Soc., Series B. 88,
1914) contraction can be explained on the hypothesis that lactic acid is
set free, and that this combines with certain proteins to form salts, with
a consequent rise of osmotic pressure.

We must now consider the muscle as a whole. For this purpose
we may select any well-known muscle, for example, the biceps. A muscle

as seen in transverse section
is enveloped in a moderately
dense, fibre-elastic mem-
brane, the epinti/xitiin (ex-
ternal perimysium) ; this
gives off septa which sep-
arate the muscle into a
larger or smaller number of
bundles, depending upon its
size, each bundle, or fascicu-
lus, being again separately
closely enveloped in a fibro-
elastic covering, the peri-

FIG. 127. STRIATED MUSCLE FIBERS OF THE

DOG.

The blood-vessels have been filled by injection
with a gelatinous mass and are represented in
black. One whole fasciculus and one fiber from
an adjacent fasciculus have been included, a,
perimysium; b, endomysium; c, a large vein seen
in transection. The section was not stained.
X 53.

mysium (internal perimy-
sium). Each fasciculus is,
moreover, again subdivided

into larger and smaller collections of muscle fibers, each bundle imper-
fectly separated from its fellows by septa from the perimysium, the endo-
nii/xiiiiH.. The ultimate subdivisions of the endomysium completely en-
velop each fiber and blend with the sarcolemma. This brings us to an
individual fiber. Each fiber is enclosed in a sarcolemma. The myofibrilla?
are collected into larger and smaller bundles, Ki'illiker'x columns, sepa-
rated from each other by semifluid, granular sarcoplasm; these collec-
tions in cross section are known as the areas of Cohnheim. They repre-
sent the definitive division products of the original group of fibrils (Heid-
enhain). The ultimate histologic units are the myofibrilla^ or sarcostyles.

MUSCULAR CONTRACTION 113

But these may consist of still more delicate fibrils; in Limulus muscle,
for example, the myofibrils may be resolved into successively finer iibrils
to the limits of visibility.

Heart muscle can be similarly, but less precisely divided, the endo-
cardium and epicanliuiii corresponding to the epimysiuni. Fasciculi and
perimysium are not so readily distinguished, but the eudomysium is re-

.. ..

.

.

-. : . :>

. . s~

*.'* ' ' . - ' ' .
. .

. i .;-.-'. ... . = -4_

. . . .-m ' -,-.--

\ :*......-.;

' M& * W * *

FIG. 128. STRIATED MUSCLE OF A CAT SEEN IN TRANSECTION.

The blood-vessels have been injected and are black in the figure. At a an artery is
contracted and empty. The heavy black vessels are veins and arterioles; the small
black dots are capillaries in transection. One whole fasciculus is represented and is
surrounded by a delicate perimysium of connective tissue. Between the muscle
fibers is the still more delicate endomysium. The larger vessels are almost exclusively
found in the perimysium. The section was not stained. X 80.

lated to cardiac muscle in a manner essentially similar to that described
for skeletal muscle.

The student should have well in hand the several criteria for the
differentiation of the three types of muscle, both in transverse and
longitudinal sections; and of smooth muscle from the dense white
fibrous connective tissue. In brief, cross sections of skeletal striped muscle
can be readily distinguished on the basis of their greater diameter and
the peripheral position of the nucleus. Both cardiac and smooth muscle

114 MUSCULAE TISSUE

have a central nucleus and peripheral fibrillge; but the fibers of the
cardiac muscle are more or less polygonal in outline and more constant
in size, excepting occasional branches, while the smooth cells are circular
in outline and of very diverse diameters, depending upon the different
levels at which the section passes through adjacent fusiform cells. In
longitudinal sections the cardiac muscle can be easily recognized by its
branching character and the presence of intercalated disks ; smooth mus-
cle by the fusiform character of its associated cells. Smooth muscle is
frequently difficult to distinguish from compact, white fibrous connective
tissue. When both are present in the same section, stained with the
routine hematoxylin-eosin technic, the two exhibit a slight difference in
staining reaction. The smooth muscle commonly stains a deeper red;
the collagenous fibers have a lighter orange tinge. Moreover, from a
morphological standpoint, while portions of the white fibrous connective
tissue may appear spindle-shaped, thus simulating the unit of smooth
muscle structure, the associated nuclei of enveloping connective tissue
cells are peripheral to the bundle, whereas the nucleus of smooth muscle
is of course in the center of the analogous structure, the muscle cell.

BLOOD SUPPLY

The blood-vessels of voluntary striped muscle distribute their larger
trunks within the connective tissue of the epimysium. The smaller
branches penetrate the endomysium and supply a rich capillary plexus
with long rectangular meshes. This network of capillaries surrounds
the muscle fibers so completely that each fiber is placed in relation with
four or five capillary vessels which run parallel with the long axis of the
fiber. The blood supply of cardiac muscles is in general similar, but
even more abundant and intimate, with respect to its terminal meshes.
The blood supply of smooth muscle is relatively meager.

Numerous lymphatics occur in the perivascular connective tissue.
These lymphatic vessels are especially abundant in cardiac muscle.

NERVE SUPPLY

Skeletal muscle is innervated both by cerebrospinal and sympathetic
nerves, supported in the connective tissue envelopes and septa. The
former include both sensory and motor fibers ending in muscle spindles

TENDONS

115

and motor end-organs respectively. These endings will be further de-
scribed under Peripheral Nerve Terminations. The sympathetic or 'ac-
cessory fibers' (Fig. 129) relatively sparse and delicate, and in close
relationship to the motor fibers and endings terminate in special 'end-
plates/ close-meshed networks of generally oval outline. Boeke (Anat.
Anz.,44, 15-16, 1913) sug-
gests that they may me-
diate the maintenance of
muscle tone.

Cardiac muscle is sup-
plied only with sympa-
thetic motor fibers. These
terminate on the muscle
fibers in brushes of fibrils,
but without highly spe-
cialized endings. Sensory

FIG. 129. MOTOR END-PLATE ON AN INTERCOSTAL
MUSCLE FIBER OF A YOUNG RABBIT.

The motor nerve fiber m is accompanied by an
accessory (sympathetic) fiber, a/. (After Boeke,
Anat. Anz., 44, 15, 1913.)

fibrils from the vagus are

distributed to the cardiac

endomysium. Each smooth

muscle cell, likewise, is supplied with a sympathetic fibril, ending in

minute knobs or plates.

According to Malone (Amer. Jour. Anat., 15, 1, 1913), the three types
of muscle are innervated by three histologically distinct types of nerve
cells, representing specific functional differences. The cells supplying
heart muscle are from the standpoint of size and granular (chromophilic)
content, intermediate between those supplying smooth and those supply-
ing skeletal striped muscle. (See Fig. 139 below.)

TENDONS

A tendon, taken as a whole, is invested by a dense fibro-elastic mem-
brane, the peritenoneum (peritendineum), or vagina fibrosa. Where
tendons play in bony grooves this may be modified into a tendon sheath,
the peritenoneum acquiring a mucous cavity, when it becomes known as a
vagina mucosa. Septa from the external peritoneum penetrate the
mass and divide the tendon imperfectly into irregular columns, the ter-
tiary bundles. These are further divisible into more regular aggregations
of fibrils, completely enveloped by an internal peritenoneum, and are the
tendon fasciculi. These correspond to the muscle fasciculi enveloped by

116

MUSCULAR TISSUE

FIG. 130.

OF A TRANSECTION
TENDON.

OF A LARGE

a, fibrous capsule with circular, and at b, longitudinal
bundles of connective tissue; c, d, and e, fibrous septa be-
tween the fasciculi of the tendon; I, lymphatic cleft.
Moderately magnified. (After Schafer.)

perimysium. In the
mouse, tendons con-
sist of from 1 to 11
fasciculi ; in the
chick from 2 to 5
(Loevy, Anat. Anz.,
45, 10-11, 1913).
Each fasciculus con-
sists of elementary
bundles of collage-
nous fibrils, envel-
oped by a complete
sheath formed bv

/

the anastomosing
processes of the ten-
don cells (cells of
Eanvier). The cell
bodies lie between
these primary bun-
dles; they are connected to each other by their processes, forming an
'endotheliaP tube (Ranvier), the cells of which have a characteristic
mesothelial appearance in sil-
ver nitrate preparations.

In the tendons of the tail
of the mouse, Loevy describes {('. ^

the cells as flat, rectangular,
and rhomboidal ; they are
parallel to the long axis of
the tendon, two of their sur-
faces extended into flat plates
or wings which effect a union
with 'wings' of adjacent cells.
A cell may have from 2 to 4
wings. The wings or plates
have been interpreted as elas-
tic in nature, but do not re-
act to specific stains for clas-
tic tissue. Each cell contains
a spherical or oval deeply
staining nucleus; the nuclei

c.R.

FIG. 131. TRANSVERSE SECTION OF TENDON
OF TAIL OF ADULT MOUSE.

It consists of four secondary bundles or fas-
ciculi, s.b.; p.b., primary bundle; p., peritenon-
eum; c.R., tendon cell (cell of Ranvier).
(After Loevy, Anat. Anz., 45, 10, 1913.)

TENDONS

117

of two successive cells are so placed as to be immediately adjacent. Ac-
cording to Loevy the fibrils are developed from fibroblasts; the definitive
tendon cells, which form the primary bundles, arise from cells of llnii-
vier. Both come from mesenchyme cells, but the fibroblasis entirely
disappear, while the cells of Eanvier persist as the characteristic winged
tendon cells.

Ligaments, fascia, and aponeuroses are very
similar to tendon, but are less compact and contain
more elastic tissue.

Bursae are mesothelium-lined sacs in connec-
tion with the large diarthroses and certain locations
where tendons are subject to friction.

Tendons are supplied with blood-vessels and
sensory nerve endings, in a manner very similar to
skeletal muscle.

The exact manner of the attachment of striped
muscle to tendon is still disputed. According to
certain investigators (0. tichultze, Arch. f. mikr.
Anat., Bd. 79, 1912), the myofibrils and tendon
fibrils are directly continuous through the sarco-
lemma. Others (Baldwin, Morph. Jahrb., Bd. 45,
1912) hold that the muscle ends sharply, remain-
ing striped to its termination, and that the rounded
or pointed end is completely enveloped by the sar-
colemma (Fig. 132). The muscle fibers are de-
scribed as being dovetailed into the tendon, the ten-
don fibrils being attached to the sarcolemma. This
is the more commonly accepted interpretation; but
it seems probable that both types of muscle-tendon
connections occur in different muscles, for in cer-
tain muscles the cross striations become gradually
more vague toward the tendon, and the point of

transition from muscle to tendon is by no means sharply marked. More-
over, the fact that certain ligaments and aponeuroses arise normally by
transformation of muscle adds support to the idea of muscle-tendon con-
tinuity.

Baldwin distinguishes two general types of muscle termination with

respect to tendon : one in which the long axes of tendon and muscle

fiber coincide; a second in which they meet at an angle. In neither type

does he recognize a direct continuity between muscle and tendon fibrils.

9

FIG. 132. PORTION
OF A MUSCLE FI-
BER FROM THE TAIL
OF A 5 CM. FROG
TADPOLE.

Each cone-shaped
sarcolemma process
has attached to it a
tendon fibril. Two
of the processes de-
rive fibrillse from a
large fibroblastic cell
situated among the
tendon fibrillae. (Af-
ter Baldwin.) xiooo.

118 MUSCULAR TISSUE

In the first type the sarcolemma presents pointed ends, to which the ten-
don fibrils are attached; in the second, the sarcolemma presents a flat
surface which rests directly against the attached structure, whether
fascia, periosteum, or ligaments.

CHAPTER V
NERVOUS TISSUES

GENERAL CONSIDERATIONS

Nervous tissue comprehends those tissue elements which are peculiar
to the nervous system. In the protoplasm of nervous tissue proper
(neuroplasm) the fundamental properties of irritability and conductivity
have become predominant. The nervous system includes the cerebro-
spinal comprising the central (brain and spinal cord) and the periph-
eral (cerebral and spinal nerves) portions and the sympathetic divi-
sions. For convenience we may speak also of the central and peripheral
nervous systems., the latter including the sympathetic division. The
essential unit of structure, comparable to the cell of other tissues, is
here the neuron, or neurocyte. A neuron is a nerve cell in the broadest
sense of the term. It consists of the cell body (nerve cell of the older
writers, cyton), together with all of its processes. These latter are
divisible into two varieties, the axon and the dendrons (dendrites).

The neurons are among the largest cells of the body. Their cell body
is of variable size, in some cases extremely minute, at other times
sufficiently large to be readily observed with the unaided eye. Their
processes, usually of considerable number, vary in length from a milli-
meter or less, up to half the height of man. It is therefore obviously
impossible to study microscopically at one time the entire course of
these longer processes. This circumstance renders it advisable to retain
the term nerve fiber of the older writers to designate, not as was the
former conception, a histological entity, but rather that portion of those
long processes of the nerve cell which pursues its course, as a rule,
outside of the gray matter of the central portion of the cerebrospinal
division.

On this basis we may divide the neuron into the nerve cell and the
nerve fiber. The former term includes the cell body, or cyton, with its
dendrons and the proximal portion of its axon; the distal portion of
the axon forming the essential part of a long nerve fiber. The nerve cells

119

S,L-

-ax.

FIG. 133. DIAGRAM OF A NEURON.

a h, axon hillock; a x, axon; c, cytoplasm, the Nissl granules have been stained;
d, dendrons; m, myelin sheath of the nerve fiber; m', muscle fiber; n, nucleus; n',
nucleolus; n of >i, nucleus of the neurolemmaof the nerve fiber; n R, node of Ran-
vier; s /, collateral; s L, segment of Lantermann; tel, telodendrion or terminal
arborization which here forms a motor end-plate. (After Barker.)

120

THE NEEVE CELL 121

are found throughout the gray matter of the central portion and in the
peripheral ganglia of the cerebrospinal division and in the sympathetic
ganglia. Nerve fibers occur in the white matter of the central portion
and in the nerve trunks and ganglia of the peripheral portions of the
nervous system.

In the peripheral nervous system the nervous tissues are chiefly
supported by the connective tissues, but in the central portion a special
form of supporting tissue, the newoglia, is also found. This is de-
scribed below.

THE NERVE CELL

(Cyion, Cell Body, Perikaryon, Ganglion Cell}

This term, as already stated, includes the cell body with its den'
drons and the proximal portion of its long axon. The cell bodies vary
in size from 4 /< to 200 /* in diameter. Their shape is chiefly dependent
upon the number of their dendritic processes. Unipolar nerve cells, with
but a single process, are flask-shaped or pyriform ; bipolar cells, whose
processes are usually derived from opposite extremities, are most fre-
quently fusiform; multipolar nerve cells, from the considerable number
of their processes, are irregularly stellate.

Nucleus.- The cytoplasm of the cell is finely granular and contains
a large vesicular nucleus which, as a rule, is exceutrically situated. The
appearance of this large nucleus is quite characteristic of the nerve cell
as distinguished from the cells of other tissue. The nuclear membrane
is distinct and highly chromatic. The contents of the nucleus, however,
except for the large spherical nucleolus which is quite constantly present,
is noticeably deficient in chromatin. Those few small karyosomes which
are present are mostly adherent to the inner surface of the nuclear mem-
brane. The achromatic nucleoplasm forms the greater portion of the
nucleus. Occasionally the chromatin forms still finer granules, and is
more equally distributed throughout the nucleus. A large, chromatic,
centrally situated nucleolus is nearly always present.

Cytoplasm. The finer structure of the cytoplasm of the nerve cell
is the subject of considerable difference of opinion. The studies of
Nissl have shown that it is divisible into a substance which is readily
stained by methylene blue, thionin, etc. (the stainable substance of Nissl,
tigroid of von Lenhossek), and an apparently homogeneous substance
which is not so readily stained (the unstainable substance of Nissl).

6 a

FIG. 134. A UNIPOLAR GANGLION CELL OF A FROG.

a, cell body; b, axon; c, dendron. Methylene blue. Highly magnified. (After von

Smirnow.)

FIG. 135. MULTIPOLAR GANGLION CELL FROM THE VENTRAL HORN OF THE GRAY
MATTER OF THE SPINAL CORD OF THE Ox.

a, axon; b, dendrons. (From Barker, after Dieters.)

122

THE NERVE CELL

123

Nissl's substance, chromopkilic
or tigroid substance, occurs in the
form of flake-like granules of vary-
ing size and irregular shape. Their
disposition within the cytoplasm is
subject to considerable variations
in different nerve cells, but accord-
ing to Nissl it is fairly constant in
cells of the same location for any
given species. The amount also of
the chromophilic substance is sub-
ject to variation depending upon
the functional condition of the in-
dividual. It has been shown that
the substance is greatly diminished
by fatigue (Dolly) and after sur-
gical shock (Crile). In general
also, the longer the axon the great-
er the amount of chromophilic sub-
stance. Chemically, it is a nucleo-
proteid. There is considerable his-
tologic evidence to indicate that it
has a nuclear origin, appearing
first in the form of 'chromidia,'
and it is accordingly sometimes
designated as cytocliro matin. Miihl-
man has shown, however, that
tigroid nuclein is soluble in weak
soda solutions while nucleus nu-
clein is not. It has been suggested
(Heidenhain) that it may perhaps
have an accessory nuclear function.
According to Held it is present as
a diffuse continuous substance, co-
agulated in the form of flakes and
granules in fixed tissues.

Those nerve cells in which the
Nissl substance is abundant are
said to be in a pyTcnomorplious,
those in which it is scanty in an

FIG. 136. PYRAMIDAL, MULTIPOLAR
NERVE CELL FROM THE CEREBRAL
CORTEX OF A MOUSE.

a, axon; d, dendrons; c, collaterals.
Golgi technic. (Barker, after Ram6n
y Cajal.)

124

NERVOUS TISSUES

apyknomorphous condition. The Nissl granules are apparently used up
during functional activity of the nerve cell.

The brain-cells show a strong affinity for adrenalin, the secretion of
the suprarenal glands; this fact leads Crile (1914) to strongly suspect
that the Nissl substance is a volatile, extremely unstable combination of
certain elements of the brain-cells and adrenalin because the suprarenal

FIG. 137. ISOLATED NERVE CELLS FROM THE SPINAL CORD OF MAN.
x, axon. Carmin. X 160. (After Sobotta.)

glands alone do not take the Nissl stain, and the brain deprived of
adrenalin does not take Nissl stain.

Nissl substance disappears in case of lesion of the neuron, but re-
appears in abundance after temporary injury and recovery of the cell.
Such disappearance after section of the axon (axonal reaction) is accom-
panied by a swelling of the neuroplasm and the peripheral migration of
the nucleus, after from ten to fifteen days.

Concerning the finer structure of the unstainable substance of Nissl,
comparatively little is known. With varying methods of fixation this
portion of the cytoplasm has been found to show very fine fibrils (neuro-

THE NERVE CELL

125

fibrils, Fig. 141) ( Schultze, Flemming, Apathy, Bethe) and fine acidophil
granules (neurosomes of Held; probably mitochondria). Besides these
structures there remains a homogeneous ground substance or hyaloplasm,
which, though of extreme physiological importance, in the usual histo-
logical preparations presents no structure. Centrosomes and attraction
spheres have been frequently observed in the nerve cells of the lower
vertebrates, and occasionally in those of
mammals.

The cytoplasm of many nerve cells con-
tains a characteristic brownish-yellow pig-
ment, whose fine granules have a tendency
to accumulate in the vicinity of the nu-
cleus.

Mitochondria also have been reported in
ganglion cells of the rabbit (Schirokogoroff,
Anat. Anz., 43, 19 and 20, 1913). Cowtlry
(Amer. Jour. Anat., 17, 1, 1914) describes
granular and rod-like mitochondria in the
spinal ganglion cells of a number of verte-
brates, including man. They are said to
occur throughout the entire neuron, axon
as well as dendrons. They are regarded as
fundamental constituents of the neuro-
plasm. It is suggested that they are con-
cerned with the metabolism of the neuro-
cyte.

Neurons are incapable of division ; de-
stroyed neurons cannot be replaced; the axon, however, may regener-
ate.

End fibrils of other neurons have been demonstrated within the cyto-
plasm of the nerve cell. Apathy has likewise demonstrated that fibrils
occasionally pass from one neuron to another, so that we no longer con-
sider that a neuron, though a structural unit, is in all cases anatomically
independent of all other neurons. The present status of this much dis-
cussed question seems to be comparable to that of the cell, as a histological
unit of structure, which though formerly thought to exist independently
of other cell units, has since been found to be frequently connected, as
by the intercellular bridges of epithelium and of smooth muscle. The
neurons of the nervous system therefore, while being usually related to
one another by contiguity or by contact only, may occasionally be more

FIG. 138. VARIOUS TYPES OF
NERVE CELLS OF THE CERE-
BELLAR CORTEX.

1, cell of Purkinje; the cyto-
plasm contains large flakes of
Nissl substance; 2 and 3, small-
er nerve cells, 'granule cells.'
Nissl's stain. X 1200.

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126

THE NERVE CELL

127

directly connected by fibrilhe, which pass from Ihe processes of one
neuron to the cell body or processes of a second neuron (Apathy, Bethe),
or by 'concrescence,' as described by Held.

The nerve cells are surrounded by a narrow interval which separates
them from the surrounding tissue. This is presumably a lymphatic or
tissue juice space. Holmgren has demonstrated also the presence, within
the cytoplasm of the nerve cell, of minute canaliculi which form an intra-

FIG. 140. A NERVE CELL FROM THE TRAPEZOID NUCLEUS IN THE MIDBRAIN OF A

RABBIT.

a, axon; 6, axons of other nerve cells which terminate in relation and apparently
fuse with the cytoplasm of the cell body; c, points of fusion or zones of concrescence;
d, dendrons which have been cut off close to the cell body; e, neuroglia. The cyto-
plasm shows a neurofibrillar network and Nissl granules. Iron hematoxylin. Very
highly magnified. (After Held.)

cellular network, more abundant near the surface of the cell, and which
he has termed juice canaliculi, or trophospongium. These canaliculi
may possibly account for the peculiar iutracellular network which Golgi
has demonstrated in the periphery of the nerve cell, by a modification of
his rapid silver impregnation method.

The processes of the nerve cell are of two varieties: the one, broad,
granular, and rapidly dividing in the vicinity of the cell body into a
number of branching subdivisions, is the tlcndron: the other, long, slen-
der, and finely but distinctly fibrillar, arises from the cell body direct, or

128

NERVOUS TISSUES

from the base of a dendron, and passing for a considerable distance from
the cell body, finally enters the nerve fiber as its axis cylinder, or termi-
nates in relation to some distant
nerve cell. This latter process is the
axon. Each cell body usually pos-
sesses a single axon and several den-
drons. Cells without an axon are
found in the retina and in the ol-
factory bulb; except for these, all
nerve cells in the body of man pos-
sess an axon and usually but one
such process. The subdivision of
nerve cells into uni-, bi-, and multi-
polar cells is, therefore, chiefly based
upon the number of their deudrons.
Dendrons (Dendrites, Protoplas-
mic Processes). The dendrons of a

FIG. 141. A NEURON (GIANT PYRAMI-
DAL CELL, OR CELL OF BET/) FROM
THE CEREBRAL CORTEX OF MAN,
SHOWING THE NEUROFIBRILS.

Bielschowsky technic. X 500.

nerve cell vary from one to a consid-
erable number. They arise from the cell body by a broad stem, and
quickly break into branches which can be traced for a considerable dis-
tance in fact, the arborization of the dendrons is usually so extensive
that it can be followed for only a short portion of its
course. Occasionally dendrons do not branch until
they have arrived at a considerable distance from
their parent cell-body.

The structure of the dendron is, to all appear-
ances, similar to that of the cell-body. The chromo-
philic substance is continued for some distance into
the arborizing dendrons, which often possess a finely
fibrillar appearance. In Golgi-stained preparations
the dendrons frequently present a thorny appearance,
due to the clustering along their borders of minute
lateral projections, the gemmules.

The terminal filaments of the deudronic arboriza-
tion are frequently in relation with the cell bodies
or axons of other neurons, less frequently with the
dendrons of other neurons. Such contact relation-
ship is known as synopsis.

Dendrons are cellulipetat processes, transmitting impulses to the cyton.

The Axon (Neuraxis, Neuraxon, Neurite, Axis Cylinder Process}.

FIG. 142. INTRA-
CELLULAR NET-
WORK (TROPHO-
SPONGIUM)
WITHIN A PUR-
KINJE CELL OF
THE CEREBELLUM
OF Strix flam-
med.

Golgi's stain. (After
Golgi.)

THE NERVE CELL

129

This process in contradistinction to the dendron, is long and slender, as
a rule does not arborize near its parent cell-body, is of smooth and regular
contour in Golgi preparations, and contains no chromophilic substance.
It arises from the cell body, or less frequently from the base of a dendron,
by a conical, clear area, the a.ron hillock or implantation cone, which,
like the process itself, is devoid of chromophilic granules. It consists of

n

FIG. 143. GOLGI CELL, TYPE I.
c, collaterals; n, axon. Golgi's stain. (After Kolliker.)

a bundle of delicate neurofibrils (axon fibrils) embedded in axopJasm.
During early developmental stages the fibrils increase in number by a
splitting of preexisting fibrils.

At some little distance from the parent cell-body the axon gives off
very fine lateral branches, the collaterals, which leave the parent stem
at the nodes of Ranvier at nearly right angles. These delicate branches,
as also the axon proper, finally terminate by a sudden end arborization,
or telodendrion, by which each axon is placed, in relation with a large

130

NEBVOUS TISSUES

number of neurons, or a considerable area of surface. The telodendrion
may terminate in minute knobs or plates, the neuropodia. The teloden-
drion is structurally apparently an efficient mechanism for mediating

FIG. 144. -GOLGI NERVE CELL, TYPE II.
a, axon; x, dendron. (After Kolliker.)

the phenomenon of 'axon reflex' (Langley). The parent stem of the axon
may be finally exhausted in its collaterals, or it may in turn end in a
terminal arborization. Collaterals are said to be more frequent in the
proximal than in the distal portion of the axon. The axon transmits
impulses away from the cell-body; it is a cellulifugal process.

THE NERVE FIBER 131

According to the length of their axons, neurons are divided by Golgi
into two types.

1. Golgi cells, Type I (Deiters' cells).

2. Golgi cells, Type II (Golgi's cells).

The cells of Type I possess a long axon which passes beyond the con-
fines of the gray matter in which it arises and usually becomes the axis
cylinder of a nerve fiber.

The cells of Type II possess a short axon which forms its terminal
arborization in the vicinity of its parent cell-body. The cells of this type
are usually association and commissural neurons; they place in conduc-
tion relation other not very remote neurons. The cells of Type I, on the
other hand, are more frequently projection neurons ; they are distributed
from the nerve centers to other and perhaps very different tissues, their
courses lying in the long projection tracts and nerve trunks of the
nervous system.

The cells of Type II are therefore most frequently intrinsic or endog-
enous neurons, their whole course lying in one division of the central
nervous system, e.g., the gray matter of the spinal cord. The cells of
Type I are more frequently extrinsic or exogenous; they arise in one
part of the nervous system to be distributed to a distant portion, e.g.,
they arise in the peripheral ganglia and enter the spinal cord to terminate
in its gray matter, or vice versa.

The size of a nerve cell is thought to bear a general relation to the
length of its axon, the larger cells possessing the longer axons. The
cells of Golgi's Type I are therefore larger than those of Type II. Like-
wise the cells of the motor tracts, whose axons are as a rule much longer
than those of the sensory tracts, are characterized by their large size
as compared witli the sensory cells.

THE NERVE FIBER

The origin of the nerve fiber and its relation to the other portions
of the neuron will be appreciated by tracing the course of the axou of a
motor nerve cell of the ventral horn of gray matter in the spinal cord.
This process, arising in the central gray matter, is at first a naked axon.
It soon leaves the gray matter to traverse the white matter and makes its
exit from the spinal cord as the axis cylinder of one of the fibers of
a ventral nerve root. On leaving the gray matter the axon acquires a

132 NEKVOUS TISSUES

cylindrical sheath of myelin substance, the medullary sheath, myelin
sheath, or white substance of Schwann.

On entering the ventral nerve root, which lies outside of the white
matter of the spinal cord, the axon receives an epithelioid membranous
sheath, the neurolemma or nucleated sheath of Schwann. The axon
retains these two sheaths until near its termination, when the sheaths
suddenly stop, the axon becoming again naked as it breaks into terminal
fibrils.

Not all nerve -fibers are medullated, nor do they all possess a neuro-
lemma. The axons of the central nervous system "are not supplied with
a neurolemma until they pierce the meninges to enter the nerve roots.
Those of the gray matter also have no appreciable medullary sheath. The
axons of the peripheral nerve trunks and ganglia are all supplied with a
neurolemma except at their terminals, as already explained. Yet some
of the peripheral axons have a medullary sheath, while others have none.
An axon with its enveloping sheaths constitutes a nerve fiber, and upon
the presence or absence of these sheaths nerve fibers may be classified as
follows :

,,. , ,, fl. With a neurolemma

A. Medullated nerve fibers { ,.,,

[2. Without a neurolemma.

B. Non-medullated nerve f 3. With a neurolemma

fibers. 1 4. Without a neurolemma alemmal.

1. Medullated Nerve Fibers with a Neurolemma. Nearly all the
nerve fibers of the cerebrospinal nerve trunks and ganglia and some of
those of the sympathetic nerves are of this type. These nerve fibers
consist essentially of three cylindrical structures : the axis cylinder, which
is the continuation of the axon of a nerve cell, and which forms the cen-
tral portion or core of the nerve fiber; the medullary sheath, which
forms a hollow cylinder inclosing the axis cylinder, and which
suffers frequent interruptions, as will be described ; and the neurolemma,
which is an extremely thin investing sheath forming an uninterrupted
envelope from the point where the nerve fiber leaves the central nervous
system to a point near the end of the fiber where the axis cylinder breaks
into its terminal fibrils. To these structures an investing sheath of con-
nective tissue, the sheath of Henle, is sometimes added. It is derived
from the connective tissue endoneurium in which the nerve fibers are
embedded. It serves to support the capillary blood-vessels destined for
the supply of the nerve fibers.

THE Axis CYLINDER. The axis cylinder presents a finely fibrillar

THE NERVE FIBER

133

structure. The nature of these fibrils is not well understood. They are
apparently continuous with the ueurofibrillar network of the cell body.
In certain nerve fibers of the lower animals these fibrils have a ten-
dency to collect into the center of the axis cylinder, leaving a peripheral
clear zone; this distribution is especially characteristic of those fibers

1 >-jjj W^8Bji2SiiE

I

\tMilr' ~

FIG. 145. ISOLATED NERVE FIBERS FROM A FROG.

The axis cylinders, the enveloping myelin sheaths, and the nodes of Ranvier are
clearly shown. Intra-vitam methylene blue stain. (Barker, after von Kolliker.)

which are not supplied with a medullary sheath. In mammals, however,
the fibrillge occupy a larger portion of the axis cylinder, the clear peri-
pheral area being correspondingly diminished until in man it can scarcely
be recognized. The fibrils of the lower animals are also coarser.

Apathy, studying chiefly the lower animals, has considered these 'ulti-
mate fibril Ice' to be the conducting element of the nerve fiber. Others,
however, lay greater stress upon the intervening clear portion, the

134

NERVOUS TISSUES

i/f/iro/ilaxiH of Schiefferdecker or a~roi>laxni, as containing the active
conducting substance of the fiber.

According to Verworn, Lenhossek and R. Goldschmidt, these elemen-
tary fibrillse (axon fibrils) in the axis cylinder are nothing else than

skeletal substance for the
support of the semi-fluid
neuroplasm. The circum-
stance that many of the
fibrils of an axis cylinder
may be sectioned without
diminution of the maximum
effect of stimulation favors
the view that the neuro-
plasm is the essential con-

FIG. 146. A SMALL PORTION OF A TRANSECTION
OF THE SCIATIC NEEVE OF A DOG.

Nerve fibers are seen in transection; their
myelin sheaths are black, their neuraxes un-
stained. Osmium tetroxid. Photo. X 700.

ducting substance.

Tashiro has demon-
strated that a living nerve
gives off a definite amount
of carbon dioxid, and that

when the nerve is stimulated the amount of carbon dioxid production is
increased. He conceives of the propagation of nerve impulses as a chemi-
cal change, the propagation being in
essence a restoration of equilibrium
in the nerve fiber disturbed at the
point of contact.

The axis cylinder is, under certain
conditions at least, found to be in-
closed by an extremely delicate mem-
brane, the axolemma of Kiihne. The
existence of this membrane as an in-
tegral part of a living axis cylinder
has been denied by others. It may
be simply a fixation artifact.

THK MEDULLARY SHEATH (\Yltile
Substance of tfcliwann, Mi/i'/i//
tf lira Hi). - The medullary slu-aili
forms a cylindrical investment for tin-
axis cylinder. Medullated fibers vary

greatly in diameter according to the amount of myelin present. It
appears to be retained in position by the neurolemma, for when the

FIG. 147. A GROUP OF LARGE MED-
ULLATED FIBERS FROM A NERVE IN
THE PERITRAOHEAL AREOLAR TIS-
SUE OF THE CAT.

Ax, axis cylinder; Nk, neurokeratin
framework; Nc, neurolemma cell and
nucleus; M, medullary sheath; N,
neurolemma. X 1000.

-

THE NERVE FIBER

135

'B

1-

n

latter is ruptured flic myelin exudes A
in the form of 'myelin drops.' The
mi/ el in, thus obtained possesses the
physical properties of a fat. It is
also capable of being blackened by
osmium tetroxid. By extraction with
ether the myelin can be removed, leav-
ing behind a supporting framework
of neurokeratin. The function of
myelin is probably nutritive, though
it has been regarded as an insulating
substance. It is thought to be present
in small a 11 101 nits even in so-called
non-medullated fibers. It seems rea-
sonable to suppose that it may have
a double function, that is, nutritive
and in part insulating.

At frequent intervals in the course
of the nerve fiber its myelin sheath

*/

suffers complete interruption, thus
forming the annular constrictions or
nodes of Eanvier. At these points the
neurolemma dips in until it is in con-
tact with the axis cylinder. Both axis
cylinder and neurolemma are contin-
ued past the node without interrup-
tion.

The successive nodes of Ranvier
divide the nerve fiber into internodal
segments. Within each internodal
segment the medullary sheath, on
blackening with osmium tetroxid,
presents clear intervals which pene-
trate the myelin sheath in such man-
ner as to give the appearance of
obliquely disposed clear lines or inci-
sions. These inciftures of tf dim id I
(Schmidt-Lantennann lines) have

not been satisfactorily explained and can not be demonstrated in the
living fiber, yet they present a constant form and are always present in
10

FIG. 148. NERVE FIBERS.

A and B, from the sciatic nerve of a
rabbit, isolated by teasing, and viewed
in profile; C, a group of nerve fibers in
transection, from the sciatic nerve of
a dog. a, axon; b, neurolemma pro-
jecting beyond the torn end of the
fiber; d, nucleus; h, endoneurium or
fibrous sheath of Henle; I, Schmidt-
Lantermann lines; n, nodes of Ran-
vier. Osmium tetroxid. A and B,
X 670; C, X 900.

136

NERVOUS TISSUES

usinic preparations. These incisures subdivide the interannular segments
of the medullary sheath into medullary segments. Schmidt originally
considered them to be the optical expression of folds in the outer fibrous
coats. Lantermann and others claim to have shown that they are within
the neurolemma. They are believed by others to represent the limits of
cones of neurokeratin. The incisures may point in different directions.
They are more probably artifacts, representing fractures in the delicate
myelin sheaths.

In preparations of fresh nerve fibers which have been treated with
silver nitrate according to the method of Banvier, the solution is found

to enter the fiber most readily
at the nodes of Ranvier, so that
if blackened by exposure to the
sunlight, minute -(like appear-
ances are seen at each node. By
prolonged maceration in weak
solutions of silver nitrate the so-
t- lution penetrates still farther

FIG. 149. CROSS AND LONGITUDINAL SEC-
TIONS OP THE SAME FUNICULUS (N)
OF NON-MEDULLATED NERVE FIBERS
(TURNED UP AT THE LEFT), SHOWING
THE PERINEURIUM (P) AND THE RELA-
TIONSHIP OF THE NEUROLEMMA NUCLEI
TO THE Axis CYLINDER BUNDLES OF
NEUROFIBRILS.

From the peritracheal areolar tissue of
the cat. X 1500.

and the blackened axis cylinder
is found to possess spiral trans-
verse markings which are quite
characteristic. The true mean-
ing of these appearances has not
been satisfactorily explained.
Because of the apparent greater
permeability of the fiber at these
points, these peculiarities have

been taken to indicate a certain relation of the annular constrictions to
the nutrition of the fiber.

THE NEUROLEMMA (Nucleated Sheaf li of Schwann). The neuro-
lemma is the outermost of the nerve fiber sheaths. It is of ectodermal
origin and makes its appearance prior to the medullary sheath. It
forms a very delicate membrane, which incloses the myelin substance,
and at each node of Eanvier comes into contact with the axis cylinder.
Attached to the inner surface of the neurolemma in each internode,
and usually but one for each internodal segment, is an oval nucleus.
The nucleus is surrounded by a minute amount of finely granular cyto-
plasm. Tli is structure is taken to indicate that the embryonal neuro-
lemma is formed by cells which became spread out over the surface of
the primitive fiber, one cell, as a rule, supplying each internodal segment ;

THE NERVE FIBER

137

and its nucleus with a minute amount of undifferentiated protoplasm is,
according to this hypothesis, considered to remain as a permanent part
of the Qeurolemma.

2. Medullated Nerve Fibers without a Neurolemma. This type
of nerve fiber composes the white matter of the central nervous system.
The axis cylinder does not, of course, differ in the least from those of
the previous variety and will need no further description.

The medullary sheath
also is similar in its finer
structure to that of the
previous type, but since
no neurolemma is pres-
ent, these fibers possess
no nodes of Eanvier. The
medullary sheath of the
fibers found in the white
matter of the brain and
spinal cord, is therefore
uninterrupted. Its sur-
face is in direct contact
with the neuroglia net-
work, which forms the
supporting tissue of these
organs, the innermost
layer being condensed
into a membrane which
simulates a neurolemma.

Pyridin-silver. X 680. (After Ranson.)

FIG. 150. CROSS-SECTION OF THE TRUNK OF THE
HUMAN VAGUS NERVE, SOME DISTANCE BELOW
THE NODOSE GANGLION, SHOWING MEDULLATED
AND NON-MEDULLATED FIBERS.

These fibers are accom-
panied by sheath cells

(Hardesty), homologues of the neurolemma cells of other fibers, which
aid in the formation and maintenance of the myelin.

3. Non-medullated Nerve Fibers with a Neurolemma (Sympor
thetic Nerve Fibers., Remak's Fibers). The most of the fibers of the
sympathetic division are of this type. The axis cylinder does not differ
from that of the previous types. The medullary sheath is entirely ab-
sent or, at most, only slightly developed in these fibers. The neuro-
lemma is perhaps incomplete at times, but exhibits frequent nuclei
along the course of the fiber. The neurolemma nuclei appear to be em-
bedded in the superficial portion of the axis cylinder. Fibers of this
type are of quite frequent occurrence also in the cerebral (cephalic;

138

NERVOUS TISSUES

cranial) nerves of the cerebrospinal division. Other cerebrospinal nerve
fibers lose their medullary sheath and finally also their neurolemma
prior to their termination.

The recent work of Ranson has shown that even in the typical medul-
lated spinal and cerebral nerves non-medullated fibers are very abundant.

In the vagus of the dog, for
example, the noil - medullated
fibers actually preponderate be-
low the diaphragm. Ranson
states that of these no consid-
erable portion can be of sympa-
thetic origin and that only a few
represent medullated fibers which
have lost their myelin distally.
The non-medullated fibers of the
vagus are said to comprise both
afferent and efferent fibers, the
latter arising from cells in the
ganglia (jugular and nodose)
connected with the vagus nerve
(Anat. Rec., 24, 1, 1914). The
spinal nerves also are shown
to contain more non-medullated
than medullated fibers (Amer.
Jour. Anat., 12, 1, 1911).

4. Non-medullated Nerve
Fibers without a Neurolemma.

-These fibers are naked axis
cylinders and as such are found
at the cytoproximal end of the
axon in the gray matter of the
central nervous system, and at
the cytoclistal end prior to the
termination of the axon in its

FIG. 151. SUCCESSIVE STAGES IN
THE DEGENERATION PROCESS EX-
HIBITED BY THE DISTAL STUMP
OF A MEDULLATED AXON (FROM
SCIATIC NERVE OF ADULT DOG)
FOLLOWING SECTION.

(1) on the second day. (2) on the
fourth day, the two fibers a and b
are at different stages of degenera-
tion, the neurolemma can be seen
bounding the unstained myelin
sheath. (3) on the eighth day, the
fragmented axon is surrounded by
an elliptical segment of myelin (a).
(4) on the nineteenth day, a, nu-
cleus, b, droplet of myelin containing
fragments of axon. (Ranson, Jour.
Comp. Neur., 22, 6, 1912.)

arborization of terminal fibrils.

In man nerve fibers are of this type throughout their entire course only
in the olfactory nerves.

All portions of the neuron, its axon and collaterals as well as its
dendrons, are dependent upon the cell body for nutrition ; hence each nerve
cell becomes the so-called trophic center for all of its processes.

THE NERVE FIBER

139

The entire nervous
system may be considered
as an enormous tangle,
formed by the interlacing
processes of an innumer-
able number of neurons
whose complex fiber paths
place all portions of the
body in communication
with all other portions.

Nerve cells are un-
equally distributed
throughout the central
division of the nervous
system ; they therefore oc-
cur in more or less dis-
tinct groups or nuclei,
from each cell of which
an axon is frequently dis-
tributed along the same
path. The larger bundles
thus formed are called
tracts; the smaller ones,
funiculi, fasciculi, or fiber
bundles.

Since each fiber of
such a tract is dependent
for nutrition upon the
nerve cell from which it
arises, the tract as a
whole must depend upon
its nucleus of origin for
its nutrition. Each nu-
cleus therefore becomes
the trophic center for the
fiber tract to which it
gives origin.

It may be readily
demonstrated that if any
such group of axons be
cut or otherwise separated
from its trophic center,
that tract will promptly

X M.tt.

t

2

,C 1

FIG. 152. REGENERATIVE STAGES IN THE PROXIMAL
STUMP OF THE CUT SCIATIC NERVE OF THE DOG,
SEVERAL MILLIMETERS ABOVE THE LEVEL OF

SECTION.

p, toward the periphery; c, toward the center.
(1) on the nineteenth day after section; a, point in
the old medullated axon from which arises an
extremely short branch which at once divides
into two. (2) on the twenty-fifth day. (3) five
protoplasmic strands down which a new axon
is growing. (Ranson.) (Pyridin-silver prepara-
tions.)

140

NERVOUS TISSUES

degenerate. If these axons happen to be the axis cylinders of medullated
nerve fibers, as is often the case, their myelin sheaths become rapidly
altered in composition and acquire a tendency to disintegrate into small
globular granules, which stain deeply with osmic acid when used according
to the method of Marchi. For the experimental demonstration of this
form of partial cell death occurring in that portion of the neuron which
has been cut off from its cell of origin, we were originally indebted to
the eminent English physiologist Waller; the resulting changes are there-
fore called WaUerian degeneration.

Obviously that portion of a neuron or of a fiber tract which, after
injury or disease involving its path, still retains its connection with its

c.reut.pesr.

me. ant.

FIG. 153. TRANSECTION OF THE SPINAL CORD OF AN EMBRYO CHICK.

c. rod. ant., axons to the ventral roots; c. rod. post., axons to the dorsal roots;
col, collateral from an axon back to the gray matter; gg, dorsal root ganglion; roc. ant.,
ventral root; roc. post., dorsal root. (After van Gehuchten.)

cell body or trophic center, will not degenerate. This part of the neuron is
called its central portion, in contradistinction to its distal portion, the latter
of which has been severed from its trophic center and is consequently

degenerated.

To the study of the various types of Wallerian degeneration we are
indebted for many of the facts by means of which the intricate tangles of
axons composing the various fiber tracts of the central nervous system
have been partially unraveled.

The contiguous relationship of different neurons within the nervous
system occurs in any one of several ways. The terminal arborizations or
telodendrions of one neuron may interlace with :

a. the telodendrions of axons belonging to other neurons,

b. the telodendrions of collaterals of other neurons,

c. the dendrons of other neurons, or

d. the terminal arborization may surround, basket-like, the cell

body of other neurons.

NEUROGLIA

141

=>:- i* -V \ " ' ' i - 'r - ...

NEUROGLIA

Both the gray and the white matter of the central nervous system
contain a peculiar supporting tissue, the neuroglia, which consists of
two elements, the glia cells and the glia filers. The latter are very
probably produced by the glia cells, of which they were formerly con-
sidered to be processes. They consist of a substance similar to, perhaps
identical with, the neurokeratin framework of myelin.

The Glia Cells. The glia cells, as seen in Golgi preparations, are
divisible into two distinct types, the ependyma cells and the astrocytes.

The EPENDYMA CELLS may
be considered as undifferen-
tiated relics of the embryonal
cells, from which both glia and
true nerve or ganglion cells
were developed. These cells
line the central canal of the
spinal cord and the ventricles
of the brain, in which latter
organ they also form the cover-
ing or outer coat of the telae
ehoroideae.

The ependyma consists of

long nucleated columnar cells

c The central H-shaped gray substance con-

wnose tree ends, in letal and sists of nerve cell bodies, dendrons, non-medul-

lated portions of axons, and neurogliar sup-
porting tissue. The enveloping white sub-
stance consists of medullated axons supported
by neuroglia. Weigert stain. X 7.

FIG. 154. TRANSECTION OF THE SPINAL CORD
OF A CHILD, FIFTH LUMBAR SEGMENT.

early life, carry a tuft of cilia ;
in adult life they are usually
non-ciliated. The attached ends
of these cells are embedded
in the surrounding gelatinous tissue, and are frequently prolonged for
some distance as a fine branched process. In this way the ependyma of
the spinal cord enters into the formation of the central gelatinous sub-
stance, in which the branched processes of its cells ramify in a glia-like
manner. In the fetus the filamentous processes extend from the central
canal all the way to the periphery of the spinal cord. In the adult the
ependyma cells are prone to so multiply as to almost occlude the central
canal; their processes have apparently become shorter, and now reach
the surface of the spinal cord only at its dorsal median sulcus.

The ASTROCTTES, when stained by the Golgi method, apparently con-
sist of a small cell body and an innumerable number of long slender

FIG. 155. PORTION OF GRAY SUBSTANCE FROM THE ANTERIOR HORN OF THE SPINAL
CORD OF MAN, SHOWING NERVE CELL BODIES, DENDRONS, MEDULLATED AND
NON-MEDULLATED PORTIONS OF AxONS, AND NETIROGLIA.

(From Salinger, after Kolliker.)

FIG. 156. TRANSVERSE SECTION THROUGH THE WHITE SUBSTANCE OF THE HUMAN

SPINAL CORD.

The dark oval bodies are cross-cut axis cylinders; the surrounding light halos
represent the myelin sheath. The coarser trabeculae are connective tissue, contin-
uous with the finer neuroglia framework. (After Salinger.)

142

NEUEOGLIA

143

processes. Two varieties of these cells are recognized : the ft/tiilrr cell
or long-rayed astrocyte, with a small cell body and very many exception-
ally long and slender processes; and the mossy cells or short-rayed

astrocytes, whose processes are shorter and somewhat thicker but de-
cidedly more varicose than those of the long-rayed type.

Eecent investigations by means of the staining methods of Weigert,
Mallory, and Benda, have demonstrated that the astrocytes, as seen in

144

NERVOUS TISSUES

the Golgi preparations, probably include two distinct structures, the
glia cells and the glia fibers.

Glia cells, as seen in sections prepared according to these methods,
appear as small cells with large and deeply staining nuclei. In the
small glia cells the cytoplasm is so slight as to form scarcely more than
a mere rim about the nucleus; in the larger cells the cytoplasm is more

FIG. 158. A LONG-RAYED ASTROCYTE.
Golgi's stain. Highly magnified. (After Berkley.)

abundant and the processes larger and more numerous. The presence
of cytoplasmic processes gives the cell an irregularly stellate appearance.

In Golgi preparations these processes can
not be distinguished from the dense net-
w r ork of glia fibers with which they are
surrounded.

The Glia Fibers. The glia fibers com-
prise numerous filiform fibrils which occur
as a dense network around the glia cells,
from which they radiate in all directions.
They pass alongside of, over, or under the
glia cells; their filaments have even been
described as passing entirely through the
cytoplasm of the cell. Nevertheless they
appear at all points to be anatomically dis-
tinct from the cell body.

The relation of the glia cells to the fibers of neuroglia is perhaps
comparable to the arrangement in fibrous or reticular tissue. The fibers

FIG. 159. A SHORT-RAYED
ASTROCYTE, OR MOSSY CELL.

Golgi's stain. Highly mag-
nified. (After Berkley.)

NEUROGLIA 145

of each of these tissues appear to be ontogenetically derived either di-
rectly or indirectly from its cells, yet when fully formed they often exist
as anatomically distinct elements.

Occurrence of Neuroglia. Xeuroglia cells and fibers occur in both
gray and white matter of the central nervous system, though perhaps
more abundant in the latter. The fibers radiate for considerable dis-
tances from their glia cells, and thus form a supporting tissue for the
nerve elements. They are frequently in intimate relation with the
blood-vessels, on the walls of which many of the glia fibers, particularly

FIG. 160. NEUROGLIA CELL WITH ADJACENT FIBERS FROM THE PINEAL BODY

OF A YEARLING SHEEP. X 1500.

the thicker or mossy variety, terminate in expanded plates, which, in
some parts, form an almost complete outer membranous coat of the
vessel.

The astrocytes are ontogenetic derivatives of the embryonic epen-
dyma cells. From their point of origin around the neural canal they
wander to all portions of the central nervous system, and even into the
optic and olfactory tracts, which are embryonic outgrowths from the
fetal cerebral vesicles. Thus neuroglia occurs throughout the brain

146

NERVOUS TISSUES

and spinal cord, and also in the olfactory nerves, the optic chiasm, and
the retina of the adult.

The supporting tissues of the central nervous system include, besides
the neuroglia, numerous bands or trabeculae of fibrous connective tissue,

' C

FIG. 161. NEUROGLIA CELLS AND FIBERS FROM THE SPINAL CORD OF AN ELEPHANT.

The letters indicate various types of neuroglia cells. /, a leukocyte. Benda's stain.
X 940. (After Hardesty.)

which push inward from the pia mater, carrying with them the vascular
branches for the supply of the nervous tissues, and which penetrate
deeply into the substances of the spinal cord and brain.

NERVE TRUNKS

Structure. The nerve fibers of the peripheral nervous system are
united into bundles to form the nerve trunks or nerves. Each nerve
is surrounded by a heavy connective tissue sheath, the epineuriuin. which
sends trabeculum-like septa into the nerve. These septa subdivide the
nerve trunk into smaller bundles of nerve fibers, the funiculi. The
funiculus forms a compact bundle of nerve fibers, and is in turn invested
with a sheath of dense connective tissue, the perineurium. Hence the

NERVE TRUNKS

147

perineurium stands in the same relation to the funiculus as does the
epineurium to the whole nerve trunk.

From the inner surface of the perineurium, septa pass into the
funiculus and break up to form a fine connective tissue fnnnrvvork, the
endoneurium, for the support of the individual nerve fibers. On sepa-
rating the fibers of a funiculus with needles a portion of this fibrous
endoneurium remains adherent to the surface of the nerve fiber and
gives the appearance of an outermost fibrous sheath, the so-called con-
nective tissue sheath of
Henle.

Nerve trunks fre-
quently branch, the
branches being formed
either by an individual
funiculus or by groups of
funiculi. In the smaller
nerve trunks the funiculi
are further subdivided.
It is by anastomosis of
the funiculi that most of
the nerve plexuses are
formed. Individual nerve The fat cells and the mye]in s h ea ths of the nerve
fibers of the medullated fibers have been blackened by osmium tetroxid. a,

type do not generally ^ at ce ^ s **> **'' D * 00( l vessels, that at b' lies within a

funiculus; c, epineurium; d, perineurium; e, coarser

branch except in those bands of the endoneurium. Osmium tetroxid. Photo,
portions which are naked X 30.
axis cylinders, viz., at the

cytoproximal portion of the axon by means of collaterals, and at the
cytodistal portion by means of end arborizations. Occasionally also col-
laterals arise at a node of Ranvier.

Vascular Supply. The nerve trunks are well supplied with blood-
vessels. The larger of these are found in the epineurium, and from
them branches of considerable size enter the septa to be distributed
throughout the perineurium to the funiculi. The coarser septa of the
endoneurium contain minute arterioles and venules. A capillary network
with elongated meshes occupies the finer divisions of the endoneurium,
its vessels being thus brought into contact with the nerve fibers.

Perivascular lymphatic vessels abound in the epineurium and its
septa, and lymphatic tissue spaces are found throughout the connective
tissue of the nerve trunk. Where the cerebrospinal nerve trunks pene-

V

FIG. 162. TRANSECTION OF THE SCIATIC NERVE
OF A DOG.

1 IS

NERVOUS TISSUES

FIG. 163. DIAGRAM OF THE ORIGIN AND RELATIONS
OF THE PERIPHERAL MOTOR AND SENSORY NEU-
RONS.

A cylindrical section of the spinal cord, with its
ventral and dorsal nerve roots, is shown, o, nerve
cell of the ventral horn whose axon passes through
the ventral nerve root, b, to its peripheral termina-
tion, c; at d is a unipolar sensory nerve cell in the
dorsal root ganglion ; its process immediately divides
into a peripheral and a central branch. The central
branch enters the spinal cord and at e divides into
an ascending, /, and a descending, g, branch from
both of which numerous collaterals, h, enter the gray
matter and terminate in fine end brushes. The
peripheral branch of the spinal ganglion cell enters
a spinal nerve and finds its way to its termination
which is here represented in the skin; it terminates
partly by free endings among the epithelial cells, i,
and partly in connection with a sensory end organ,
k, in this case a tactile corpuscle of Meissner. (After
von Lenhosse'k.)

trate the meninges these
lymphatic vessels are said
to be continuous with the
similar vessels of the
dura mater.

Minute nerve fiber
bundles, nervi nervorum,
are also found in the epi-
neurium; their fibers are
mostly, if not entirely,
distributed to the blood-
vessels.

GANGLIA

A ganglion may be
described as a group of
nerve cells occurring in
the course of a peripheral
nerve trunk. The larg-
est of the ganglia form
fusiform swellings in the
course of the nerve, which
are visible to the naked
eye. The smallest, on
the other hand, contain
not more than half a
dozen nerve cells, and
these must be sought with
the aid of the micro-
scope and can only be
found by the most care-
ful observation.

Whatever may be their
size, all ganglia appear
to have a similar struc-
ture, except for those
differences which charac-
terize the sympathetic as

GANGLIA

149

distinguished from the cerebrospinal type. The essential elements of
structure are the nerve cells, nerve fibers, and a supporting framework
of rather dense fibro-elastic connective tissue.

Many of the nerve cells of the adult mammal are unipolar in the
cerebrospinal ganglia, but are usually multipolar in the sympathetic.
The spinal ganglia of the lower vertebrates and of the embryo mammal,

FIG. 164. BIPOLAR
CELL FROM A
SPINAL GAN-
GLION.

(Barker, after
Corti.)

FIG. 165. TRANSFORMATION OF
BIPOLAR CELLS INTO UNIPOLAR
CELLS IN THE GASSERIAN GAN-
GLION OF THE PIG.

(Barker,
ten.)

after van Gehuch-

however, contain bipolar ganglion cells. In mammals the two processes
of the embryonal neuron fuse to form a single one which branches in
a Y- or T-like manner soon after leaving the parent cell body.

In the ganglia of the acoustic nerve the primitive bipolar condition
of the neuron is retained; and the cell body is not surrounded by a
capsule.

The nerve cells of all other ganglia are surrounded by a capsule of
flat epithelioid cells which form a complete investment for the nerve

150

NEKVOUS TISSUES

gfcsaa^f-^*cr:.-T7:^pc- *>/-... -^^<

^fe: II /; '-'

f|m :; -'-

^^iliift^vf

',:; "^.-w^

FIG. 166. SECTION THROUGH THE DORSAL
ROOT GANGLION OF THE FIRST THORACIC
NERVE OF A CAT.

The ganglion cells contain a large vesicu-
lar nucleus, with nucleolus, and are en-
veloped by a nucleated capsule. Several
medullated fibers appear among the gan-
glion cells. (From Barker, after Hodge.)

frequently proximally convoluted and,
after branching in .T-shape fashion,
passes out of the ganglion to become
the axis cylinder of a medullated nerve
fiber, and (2) cells with a slender axon
which breaks up within the ganglion
and whose terminal arborizations form
a pericapsular plexus around the cell
capsule; from this plexus fine end
brandies penetrate the capsule to form
a pericellular arborization about the
nerve cell itself. The cells of this lat-
ter type suggest association neurons

cell and its processes, being con-
tinuous with the neurolemma.
The capsule is not, however, as
a rule, closely applied to the
cell, but leaves a narrow inter-
val which is occupied by lymph
or 'tissue juice.'

In their structure the gang-
lionic neurons do not appear to
differ in any way from other
neurons. The large vesicular
nucleus with its distinct nucleo-
lus readily distinguishes these
cells from those of neighboring
tissues.

The studies of the ganglion
cells by Dogiel, Eanvier, and
Cajal have done much to ex-
plain the relations of these cells
to each other, especially in the
sympathetic system, where they
were formerly but little under-
stood. In the spinal ganglia
Dogiel (Anat. Anz., 1896) de-
scribed two types of ganglion
cells: (1) a unipolar cell in
which the axon is thick and

FIG. 167. A NERVE CELL FROM A
SECTION OF A HUMAN GAS-
SERIAN GANGLION.

C, capsule. Nissl's stain. X 500.

GANGLIA

151

within the ganglion. Nerve fibers from the sympathetic ganglia ;ilso enter

the spinal ganglia and form pericellular arborizations about the cells

of the second type. Dogicl

found also that, multipolar

ganglion cells occur in the

spinal ganglia of the adult as

well as of the embryo.

The more recent work of
Cajal (1905),Dogiel (1908),
and Eanson (1912) has re-
vealed a third distinct type
of cell formerly apparently
included under Dogiel's Type
I : smaller, pyriform, uni-
polar cells with non-medul-
lated axon, rarely convoluted,
dividing into a central and
a peripheral branch, the ex-
act terminations of which are
unknown ; but having accord-
ing to Kanson apparently the
same distribution as the
coarser medullated fibers of
Type I, and probably affer-
ent in nature (Jour. Comp.
Neur., vol. 22, 1911). In
cat and rat Eanson esti-
mates the number of these
cells at two-thirds that of the
total number. These are the
cells which contribute the
bulk of the very numerous
non-medullated fibers of the
spinal nerves, only a small
portion of which are believed

FIG. 168. SCHEMATIC REPRESENTATION OF THE
RELATIONS OP THE STRUCTURES COMPOSING
A SPINAL GANGLION.

A and B, ventral and dorsal spinal nerve
roots; C, a spinal nerve; D and E, its ventral
and dorsal divisions; F, its ramus communicans.
a, nerve cells of the first type, whose neuraxes
divide and form the axis cylinder of a peripheral
and a central nerve fiber; b, nerve cells of the
second type, whose neuraxes, n, end in a felt
work about the cells of the first type; s, sym-
pathetic nerve fibers which terminate in a bas-
ket work about the cell bodies of the second

to arise in sympathetic gang- type of ganglion cells. (After Dogiel.)
lia.

With the exception of relatively few cells of bi- and multipolar form,
all of the nerve cells of the spinal ganglia are unipolar in the adult
condition. In the case of the larger cells, the medullated axon before
11

152

NERVOUS TISSUES

leaving the capsule is more or less extensively convoluted over the cell
body forming in the extreme condition a so-called 'glomerulus.' These
same cells are variously modified by the presence of short, coarse and
fine intra- and extracapsular processes (both dendrons and collaterals)
frequently terminating in 'end disks' (Huber). Such processes may fuse
more or less extensively forming the 'fenestrated' variety of cells. The

FIG. 169. COMMON ATYPICAL, THOUGH PROBABLY PERFECTLY NORMAL, NERVE
CELLS FROM THE SPINAL GANGLION OF THE DOG.

a and b, cells with collaterals ending in 'end bulbs'; c, a multipolar cell; d and e,
'fenestrated' cells. (Ranson, Jour. Comp. Neur., 22, 2, 1912.)

axon, prior to its division, may split at one or several points, for longer
or shorter distances, into two or many portions, and reunite again into a
single fiber; rarely also the axon may have two or more points of
origin, probably the result of fusions of collaterals with the cell body.
These more complex atypical forms are said to predominate in man
(Eanson, Jour. Comp. Neur., 24, G, 1914). Ranson regards them to
some extent at least as transient modifications, which may return to
the simpler unipolar condition. Nageotte (1907) has suggested that

THE SYMPATHETIC DIVISION OF THE NERVOUS SYSTEM 153

the phenomena of end disks and f enestrations signify regenerative activity.
They are relatively more abundant in regenerating transplanted ganglia.
But they are abundant also in pathological ganglia (Nageotte, 1906),
and in fetal ganglia (Huber, 1913). No conclusive evidence has yet been
presented that these modified forms signify functional derangement.

THE SYMPATHETIC DIVISION OF THE NERVOUS SYSTEM

The sympathetic division of the nervous system (autonomic system)
consists essentially of three sets of ganglia: (1) the ganglionated cords
(sympathetic trunks; vertebral ganglia); (2) the prevertebral plexuses;
and (3) the visceral or terminal plexuses, including chiefly the myenteric
and submucous plexus of the alimentary canal. The ganglia of the
ganglionated cords are segmentally arranged, and interconnected trans-
versely (caudally) and longitudinally by plexuses of non-medullated fibers.
They are connected also with the spinal nerves by the white and gray rami
communicantes. Homologous ganglia in the head region, less definitely
related to the cerebral nerves, are the ciliary, sphenopalatine, submaxillary,
sublingual, parotid and otic ganglia. The prevertebral plexuses represent
fusion products of originally segmentally arranged components correspond-
ing to segments of the ganglionated cord. These plexuses contain fewer
and smaller cells, with a preponderance of fibers, e.g., cardiac, celiac
(semilunar; solar), hypogastric and pelvic plexuses. The myenteric and
submucous plexuses are located in the muscle and submucous layers re-
spectively of the esophagus, stomach and intestine. Here the cells are still
smaller and less numerous than in the prevertebral plexuses, and the fiber-
network is less dense. A plexus is a network of nerve fibers with few cells ;
where the nerve cells are relatively abundant, the plexus is known as a
ganglion. The embryonal cells (neuroblasts) which develop into sympa-
thetic neurons have migrated from the neural crest, possibly in part also
from the wall, of the primitive spinal cord.

Langley employs the term 'autonomic nervous system' for all that
portion of the peripheral nervous system not included among the cerebro-
spinal nerves, commonly designated as the 'sympathetic system.' This
comprises four components: (1) the sympathetic proper, including the
autonomic fibers arising from the thoracicolumbar regions of the spinal
cord, together with the associated vertebral ganglia and their postgang-
lionic neurons; (2) sacral autonomic, preganglionic fibers included in the
roots of the second, third and fourth sacral nerves, together with the asso-
ciated postganglionic neurons; (3) cranial autonomic, a group of fibers
arising from the midbrain and the medulla (this component is separated
from the sympathetic proper by the whole extent of the cervical region

154

NEEVOUS TISSUES

of the spinal cord, which region lacks white rami communicantes) ; (4)
enteric, including the myenteric and submucous plexuses of the digestive
tube. Langley proposes also the term 'parasympathetic' to designate the
sacral and cranial autonomic fibers, since in many parts of the body they
overlap the distribution of the sympathetic proper.

In the sympathetic (or autonomic) ganglia Dogiel (Anat. Anz., 1896)
likewise recognized two cell types, in general smaller than those of the

FIG. 170. SYMPATHETIC NEURONS.

A, in myenteric plexus, ileum of cat; B and C, in myenteric plexus, ileum of dog;
D, E, F, in submucous plexus, ileum of dog; a, axon. A corresponds to Dogiel's
Type I, a motor neuron; B and C correspond to Dogiel's Type II, probably sensory
neurons. (After Kuntz, Jour. Comp. Neur., 23, 3, 1913.)

spinal ganglia: (1) small multipolar fusiform or stellate nerve cells with
5 to 20 dendrons and an axon which enters the nerve trunks as a non-
medullated fiber, but may later acquire a thin medullary sheath motor
neurons; (2) larger spheroidal nerve cells with 1 to 16 dendrons and a

THE SYMPATHETIC DIVISION OF THE NERVOUS SYSTEM 155

single axon which also enters the nerve trunk as a non-medullated nerve
fiber, but may later acquire a very thin medullary sheath, perh;ips sen-
sory neurons. The dendrons of the second type are distinguished from
those of the first by being very long and slender and also by entering
the nerve trunks, to pass, presumably, to neighboring ganglia. The
dendrons of the first cell type on the other hand, are shorter, thicker,
and end in relation with other cells within the same ganglion. Carpen-
ter and Conel report also intermediate types in the cat.

In certain rodents (rabbit and guinea pig) many of the neurons of
the vertebral and pre vertebral autonomic ganglia are bi-nucleate (Car-
penter and Couel, Jour. Comp. Neur., 24, 3, 1914).

The ganglionic cell group is excentrically placed as regards the axis
of the nerve trunk, some funiculi apparently passing the ganglion with-
out being in any way connected with its nerve cells.

The sympathetic differ from the cerebrospinal ganglia chiefly in the
relative preponderance of non-medullated nerve fibers in the former and
of the medullated type in the latter. Just as the cerebrospinal ganglia
receive a few non-medullated sympathetic fibers, so also the sympathetic
ganglia receive, through the medium of the white rami communicantes,
a certain number of medullated nerve fibers from the cerebrospinal sys-
tem. Moreover, with the intense staining method of Weigert, very thin
medullary sheaths may now be demonstrated where formerly they were
not suspected.

The sensory and motor neurons of the cerebrospinal division show
characteristic differences in their chromophilic substance. In the cere-
bral and spinal ganglia the cell bodies of the sensory neurons contain
fine Nissl granules evenly distributed throughout the cytoplasm. The
motor cell bodies from the spinal cord contain fewer and much larger
chromophilic flakes. The sympathetic neurons likewise present a charac-
teristic and constant appearance: the chromophilic granules are inter-
mediate in size and generally massed toward the periphery (Malone;
Carpenter and Conel).

The ganglia are supplied with blood vessels and lymphatic vessels
in a manner similar to the nerve trunks in whose course they occur.

The earlier conception of the nervous system interpreted the nerve
fiber (axon) as the fusion product of a chain of cells extending from its
proximal to its distal end. The axis cylinder fibrils were regarded as
differentiation products of the cytoplasm (Schwann; Apathy; et al.). The
view which now prevails interprets the axon as the outgrowth of the cell
body to which it is attached (His; Cajal; et al.). The tissue culture

15G

NERVOUS TISSUES

FIG. 171. THE
SPROUTING OF AN
AXON BY A NEU-
ROBLAST FROM
THE SPINAL
CORD OF A FROG
EMBRYO.

From a live spec-
imen grown in
lymph; the cell
body is filled with
yolk granules; the
protoplasmic proc-
ess (axon) is of
hyaline appearance
and undergoes ame-
b o i d movements.
(Harrison.)

work of Harrison and others has established the out-
growth view upon a firm basis of observational data.
By growing small pieces of the embryonic spinal cord
of frogs in lymph, Harrison could observe the cells
sprouting an axon process (Figs. 171 and 172). He
describes the beginning of a nerve fiber as an outflow
of hyaline protoplasm from cells which were situated
within the central nervous system. The experiments of
Harrison upon frog larvae demonstrate further that the
sheath cells of the iieurolemma of motor and sensory
fibers have their origin in the ganglionic crest, there-
fore ectodermal, and that they are unessential to the
formation of the fibrils of the axis cylinder. He ex-
cised the dorsal half of the cord, including the neural
crest, and observed that in such larvse the fibers of the
motor roots did not acquire sheath cells. On the con-
trary, when he excised the ventral half of the cord,
dorsal root fibers developed normally with a iieuro-
lemma, but the sheath cells which migrated to the lo-
cation where the ventral fibers normally appear were
unable to produce

these fibers in the
absence of neuro-
blasts in the ven-
tral half of the
cord. (Anat.Rec.,
2, 9, 1908.)

The influence
which guides the
nerve along its

proper path is apparently exerted by
the tissue which is to be innervated.
The essential factors comprising this
influence are obscure; they may be of
a chemotropic nature. It must be
emphasized, however, that the con-
nection between a particular nerve
and its tissue terminal is made rela-
tively early, that is, while the two
elements are still spatially relatively
closely associated. Probably mechan-
ical stimuli, inducing thigmotropic
reactions, also play an important role
in determining the path of a nerve

0.1 Tn m

FIG. 172. THE SPROUTING OF AN
AXON BY A NEUROBLAST FROM THE
SPINAL CORD OF A FROG EMBRYO.

Two views of the same nerve fiber,
grown in lymph, taken twenty-five
minutes apart. (Harrison.)

NEURONE THEORY 157

fiber. The earlier relations are of course modified during growth; the
definitive relation between nerve and end-organ are acquired by mutual
adjustment. Kecently Harrison has contributed further experimental evi-
dence in support of the view that the growing axon is guided through a
stereotropic response (Jour. Exp. Zool., 17, 4, 1914).

By cultivating sympathetic neurons from pieces of the intestine of the
embryo chick in saline solutions, W. H. and Margaret R. Lewis (Anat. Rec.,
6, 1, 1912) have been able to demonstrate that here also the fibers arise as
outgrowths of nerve cells.

NEURONE THEORY

The work of Harrison, the Lewises and many others, including both
experimental and morphological investigations, leave scarcely any fur-
ther doubt of the accuracy of the Neurone Theory of Waldeyer (1891),
which simply applies the Cell Theory of Schleiden and Schwann (1838-
39) to the nervous system. It holds that the unit of structure is the
neuron (neurocyte), consisting of cell-body (cyton) and processes, in-
cluding one axon, and one or several dendrons. The nervous system
consists therefore of innumerable associated neurons. Neurons arise
each from a simple embryonic cell, the neuroblast, retain their independ-
ence throughout life, and make connection with each other in general
only by contact, which, however, is sufficiently intimate to insure func-
tional continuity. A neuron exhibits a structural and functional po-
larity; and constitutes a trophic unit for the maintenance of whose
metabolic activity a nucleus is necessary.

Further confirmation of the outgrowth interpretation as opposed to
that of autogenesis of the axon has recently been furnished by the experi-
ments of Clark (Jour. Comp. Neur., 24, 1, 1914) on the domestic fowl.
By prolonged exclusive feeding of polished rice he induced degeneration
in the peripheral medullated nerves. On return to an adequately nutritive
diet regeneration, accompanied by a return to normal locomotion and func-
tion, followed. The material thus gave opportunity for a microscopic study
of the steps in the nerve degeneration and regeneration. When the degen-
erative process had not been excessively prolonged a new axis cylinder grew
down the old medullary sheath, which returned to normal ; when greatly
prolonged the myelin disappeared and the nuclei of the neurolemma multi-
plied, giving an appearance very similar to that of embryonic nerve fibers
('baiidfasern' stage). Clark concludes that the function of these excessive
sheath cells is the removal of the degenerating myelin, a new medullary

158 NERVOUS TISSUES

sheath being supplied probably by joint influence of the new axis cylinder
and the neurolenima cells.

Mitochondria of granular and rod forms are abundant in the neuro-
blasts. Me>ves, Duesberg and others have claimed that these differentiate
into neurofibrils. The recent work of Cowdry (Amer. Jour. Anat., 15, 4,
1914) on chick embryos proves the unreliability of this view. Cowdry
shows that the neurofibrils arise as a differentiation of the ground substance
of the neuroblast ; and that mitochondria persist in undiminished numbers
throughout the period of neurofibril-development. Moreover, it is now
known that mitochondria are present also in adult neurons. They are ap-
parently essentially cytoplasmic constituents of a metabolically active cell.

Spinal ganglion cells of certain adult mammals (cat and rabbit) have
been kept alive in tissue cultures for as long as twenty days (Minea, Anat.
Anz., 46, 20, 1914). The ceils remain apparently normal, augment their
amount of chromophilic substance, produce new neurofibrils, develop short
processes with end-plates (neuropodia) and become fenestrated, but do not
proliferate.

CHAPTEK VI
PERIPHEEAL NERVE TERMINATIONS: END ORGANS

All peripheral nerve fibers end either as terminal fibrils or in rela-
tion to a highly specialized end organ. The function of these latter
bodies is apparently included in the changing of ordinary stimuli
mechanical, thermal, chemical, etc. into a nerve impulse, or, vice versa,
the changing of a nerve impulse to a cell stimulus which results in
motion, secretion, etc., according to the nature of the tissue cells which
are thus stimulated. Some of the nerve end organs are connected with
efferent (motor) fibers, others with afferent (sensory) fibers. Nerve
endings are found in nearly all the tissues of the body with the exception
of cartilage and the calcareous tissue of the bones.

NERVE ENDINGS IN EPITHELIUM

Intra-epithelial nerve fibrils are derived from the nerve fiber plexuses
in the subjacent connective tissue ; the epithelium usually receives a very
abundant nerve supply. The following types of intra-epithelial nerve
endings have to be considered.

1. End Fibrils. This form of nerve termination has been demon-
strated in all the varieties of epithelium. Terminal nerve fibers enter
the epithelial tissue as naked fibrils, often somewhat varicose, which form
a delicate plexus between the epithelial cells. The terminal fibrils of this
plexus frequently end in minute knoblike enlargements which are in
contact with the surface, but rarely, if ever, penetrate the interior of the
epithelial cells. The 'trefoil plates of Bethe represent unusually large
end knobs.

2. Tactile Cells (Merkel). These are modified epithelial cells,
with clear cytoplasm and a slightly vesicular nucleus, which are found
in the deeper layers of the stratified epithelium of the epidermis and
in the root sheaths of hairs. These cells are recognized by their vesicu-

159

160

PERIPHERAL, NEKVE TEEMINATIONS: END ORGANS

FIG.

173. NERVE ENDINGS IN THE EPI-
THELIUM OF THE LARYNX.

On the left a taste bud; on the right, nerve
endings in the stratified epithelium are rep-
resented. (After Retzius.)

lar character and by the fact that they occur most abundantly in the

interpapillary portions of the epidermis. The deeper surface of the

tactile cell rests in a cuplike ex-
pansion of a terminal nerve
fibril which is known as the tac-
tile meniscus.

3. Neuro-epithelium. The
cells of some types of neuro-
epithelium, e.g., the olfactory
cells, are true nerve cells ; others
are modified epithelial cells, in
relation to which the nerves ter-
minate by intercellular end fi-
brils. The neuro-epithelium of
the eye and the ear will be de-
scribed in the chapters devoted to these organs, that of the gustatory

organ forms typical nerve end organs, the taste buds.

TASTE BUDS (Gustatory Organ). These end organs appear to be

concerned with the special sense of taste. They occur in the stratified

epithelium of the base of the

tongue, uvula, soft palate,

and epiglottis. Disse has also

found similar structures in

the nasal mucous membrane.

They are most abundant on

the lateral surfaces of the cir-

cumvallate papillae of the wx&^&s*'

v ;. . V XjSi CifKjf-
>'"'VV '?**&*
^SjKSgsSf

tongue and on the walls of
the sulci in the foliate pa-
pillae which are most highly
developed in the rabbit. They
are occasionally found on the
fungiform papillae of the
tongue, where they occur in
considerable numbers in fetal
life but mostly disappear be-
fore birth, and in the lateral walls of the sulci about the circumvallate
papilla?.

Taste buds are ovoid, ellipsoidal, or spheroidal masses which occupy
almost the entire depth of the epithelial layer. Their broad base rests

m

FIG. 174. TACTILE CELLS IN THE EPITHELIUM
OF THE GROIN OF A GUINEA-PIG.

a, tactile cell; c, epithelial cell; in, tactile men-
iscus, at the end of a nerve fibril; n, nerve fiber.
Chlorid of gold. Highly magnified. (After
Ranvier.)

NEEVE ENDINGS IN EPITHELIUM

161

8* Cone.

Supporting cell.

Neuro-epit helial
cell.

' Rod cell.

upon the basement membrane, their narrower apex extends nearly to
the surface of the epithelium. The apex of the bud is thus covered by
the superficial squamous epithelial cells except for a narrow tubular
opening which overlies the superficial pole of the end organ. This
canal presents an external and an internal ostium, respectively desig-
nated the outer and inner taste pore. The inner taste pore leads into a
goblet-shaped depression in the apex of the taste bud, into which the
cuticular processes of the gustatory cells project. Composite buds with
two and three pores are
common in the foliate
papilla? of the rabbit;
Heidenhain (Anat.
Anz., 45, 16, 1914) re-
ports also buds with
four, five and six pores.
The taste buds con-
sist essentially of two
varieties of cells, the
gustatory and the sus-
tentacular. The latter
include the' broad outer
sustentacular or teg-
mental Cells at the Slir- ^EE^^^^Z^^^^J^f. Nerve fibrils.

face of the bud, the in-
ner sustentacular cells
within, and the basal
cells which lie near the
basement membrane.

The Gustatory Cells. The gustatory cells are slender neuro-epithe-
lial structures whose nucleus causes a fusiform enlargement near their
center or toward the basal end. Their cytoplasm is finely granular;
their nucleus stains deeply and is ovoid or rod-shaped. The distal end
of the cell carries a delicate, highly refractive cuticular process which
projects beyond the apices of the sustentacular cells and as far as the
inner taste pore. Their proximal end is often bifid, forked, or so flat-
tened as to form a footlike extremity which is connected with the basal
cells by fine processes. Sapid substances in solution enter the pore and
stimulate the taste cells through the hair processes.

Sustentacular Cells. The outer and inner sustentacular cells are
elongated epithelioid cells, having an ovoid or spheroidal vesicular

FIG. 175. SCHEMATIC REPRESENTATION OF A TASTE

BUD.

(After Hermann, from Bohm and von Davidoff .)

162

PERIPHEEAL NERVE TERMINATIONS: END ORGANS

nucleus which causes no bulging of the protoplasm, and a coarsely retic-
ular and frequently vacuolated cytoplasm. The distal ends of the
cells taper to blunt points which collectively form the lateral wall of
a goblet-shaped cavity at the apex of the taste bud. The proximal end

B Ez

sk

Ez

Ml*

FIG. 176. -TASTE BUD FROM THE HUMAN TONGUE.

A, in longitudinal section; B, transection through the deeper third; C, transection
through the base. Bz, basal cells; Ez, extra-bulbar cells; Gz, gustatory cell; L, leuko-
cytes, in A one of these is seen in the pore; Pg, perigemmal space; Sg, subgemmal
spaces; Sp, connective tissue of the tunica propria; Sz, sustentacular cells; x, cells of
the adjacent epithelium. (After Graberg.)

is broad, often blunt or serrated, and, like the gustatory cells, it is con-
nected with the basal cells by protoplasmic processes.

The Basal Cells. The basal cells are flattened bodies with small
ovoid vesicular nuclei and a relatively small amount of cytoplasm which
is prolonged into numerous processes that appear to be continuous with
the sustentacular and gustatory cells. These cells have been considered
as having a similar function to the sustentacular cells.

NEKVE ENDINGS IN CONNECTIVE TISSUE

1G3

The Filers. The nerve fibrils of the iasle buds are derived from a
sub-epithelial plexus which distributes terminal fibrils to the gustatory
and sustentacular cells, intragemmal fibers, and to the intervening
portions of the stratified epithelium, intergemmal fibers, where they
terminate in end fibrils. Von Lenhossek (Anat. Anz., 1892) states that
the intragemmal and intergemmal fibers are never derived from the same
nerve fiber. Circumgemmal fibers, distributed as varicose fibrils to the
surface of the taste bud, may, however, arise from the same nerve fiber
as the intragemmal branches.

Those nerve fibers which enter the taste buds form fine varicose fibrils
which are closely applied to, but are not continuous with, the gustatory
and the sustentacular cells. The terminal twigs of these fibrils end by
minute end knobs which are scarcely distinguishable from the varicosities
(Fig. 175).

NERVE ENDINGS IN CONNECTIVE TISSUE

The nerve fibers form extensive plexuses in the connective tissues
from which terminal branches are distributed to the epithelium (free
sensory endings), the walls of the blood and
lymphatic vessels (sympathetic vasomotor
endings), and to the numerous sensory end
organs (encapsulated endings) which occur
in abundance in most of the connective tis-
sues. Nerves also terminate in connective
tissue by free end fibrils some of which, as
in the epithelial tissues, possess minute end
knobs. Free nerve endings of this nature
occur in the tendons, the lungs, the stom-
achal and intestinal mucous membranes,
the meninges, and in the superficial layer
of the corium of the skin and the hair
follicles.

The following types of nerve end organs
are found in connective tissue :

1. Tactile Corpuscles (Touch Cor-
puscles of Meissner). These organs are
formed by the terminal expansion of a

nerve fiber, which forms a varicose plexus inclosed within a delicate con-
nective tissue sheath. The nerve fiber, or its primary branches, prior to

B] N N

FIG. 177. TACTILE CORPUSCLE
OF MEISSNER FROM THE SKIN
OF THE HUMAN TOE.

Bl, blood-vessel; N, medul-
lated nerve fiber. Highly
magnified. (After Schieffer-
decker.)

164

PEEIPHERAL NERVE TERMINATIONS: END ORGANS

its ultimate division makes several spiral turns about the corpuscle. The
course of the nerve fiber gives the corpuscle a peculiar spirally striated
appearance. Within the corpuscle the nerve fiber breaks into a plexus
of varicose fibrils, many of which end in knobbed extremities. The cor-

FIG. 178. TACTILE CORPUSCLE OP
MEISSNER.

b, epithelioid cells; e, nerve endings;
e, connective tissue capsule. (Maxi-
mow, after Van de Velde.)

FIG. 179. TACTILE CORPUSCLE OP

MEISSNER.

a, nerve fibrils which enter the corpuscle
and supply its nerve skein. Methylene
blue. Very highly magnified. (After
Dogiel.)

puscles also contain many flattened or cuneiform epithelioid cells which
are interspersed among the nerve fibrils.

Tactile corpuscles occur in largest numbers in the cutaneous papillce
of the finger tips, where there may be as many as twenty to the square
millimeter. They are found in considerable abundance also in other
highly sensitive regions, including especially the corium of the toe tips,
the lips, nipple, conjunctiva, glans penis and clitoris. The cutaneous
senses comprehend four different qualities of sensation : pressure, warmth,
cold and pain. These are mediated by two distinct groups of sensory
fibers ending in the skin: the one conveys the impulses for pain and
extremes of temperature (protopathic sensibility), the other for light
pressure and small changes of temperature (epicritic sensibility). The

NEEVE ENDINGS IN CONNECTIVE TISSUE

165

il

FIG. 180. RUFFINI'S END
ORGAN.

A single nerve fiber breaks
up to form the tangle of nerve
fibrils within the organ. gH,
medullary sheath; il, terminal
fibrils of the axis cylinder; L,
connective tissue capsule. (Af-
ter Ruffini.)

ally at its end. Now and
tributed to several of these

various subcutaneous endings mediate sub-
cutaneous sensibility to pressure and move-
ment.

2. Ruffini 's End Organs. These
bodies, also known as terminal cylinders,
resemble the tactile corpuscles in structure
but possess a definite, though thin, connec-
tive tissue sheath within which the ter-
minal arborization of the nerve fiber is
embedded in a granular core. They occur

FIG. 181. END BULB OF KRAUSE FROM THE MAR-
GIN OF THE OCULAR CONJUNCTIVA.

The axon forms a dense skein within the en-
capsulated bulb. Methylene blue. Highly mag-
nified. (After Dogiel.)

in the deeper part of the true skin near its
junction with the subcutaneous tissue and
in the connective tissue septa of the latter,
whereas the tactile corpuscles are found in
the papillary layer of the skin. Kuffini
(Arch. ital. de biol., 1894) states that they
occur in large numbers in the skin of the
finger tips, where they rival in number the
rather more deeply placed Pacinian cor-
puscles.

The Ruffini organs are cylindrical in
shape and their nerve fibers usually enter
at the side of the organ, though occasion-
then a single branching nerve fiber is dis-
end organs.

166

PERIPHERAL NERVE TERMINATIONS: END ORGANS

3. End Bulbs (Krause). These structures (bulbous corpuscles),
together with those which follow, form the true so-called encai

nerve end organs. In the end bulbs the nerve forms a terminal arboriza-

FIG. 182. GENITAL CORPUSCLES FROM THE CLITORIS OF A RABBIT.

A single axon from the nerve plexus enters each corpuscle. Methylene blue.
Highly magnified. (After Retzius.)

tion of the varicose and knobbed fibrils which freely anastomose (Dogiel,
Ruffini). The bulb is invested with a distinct connective tissue capsule.
On entering the bulb the nerve fiber loses its sheaths and the perineu-
rium, now represented by Henle's sheath, becomes continuous with the

B

-.--.- <v

FIG. 183. A LAMELLAR CORPUSCLE FROM THE MESENTERY OF A CAT.
A, a nearly axial section; B, a transection. Hematein and orange G. X 410.

capsule of the bulb. Within the capsule the nerve fibrils are embedded
in a granular inner bulb.

The end bulbs vary much in both size and shape. They may be
cither spheroidal, ovoid, twisted or convoluted, branched or compound, or
cylindroid. They are abundantly found in the conjunctiva, but also

NERVE ENDINGS IN CONNECTIVE TISSUE

167

occur in ilic curium of the skin. Similar, though more highly developed,
end bulbs form the so-called </rnilal corpuscles which are found in con-
siderable numbers in the connective tissue of the glans penis, prepuce,
and clitoris. In some of the smaller (cylindrical} end bulbs found in
the tendons, the mucous membranes, and in certain portions of the skin,

#

\

FIG. 184. A LAMELLAR CORPUSCLE FROM
THE PLEURA OF A CHILD.

a, lamellae; b, nerve fiber; c, nerve.
Methylene blue. Moderately magnified.
(After Dogiel.)

FIG. 185. LAMELLAR CORPUSCLE FROM
THE MESENTERY OF A KITTEN.

The nerve fiber shows lateral proc-
esses, many of which are knobbed.
Methylene blue. Moderately magni-
fied. (After Sala.)

the nerve fiber fails to divide but ends near the distal extremity of the
bulb in a small fusiform end knob.

4. Lamellar Corpuscles (Pacinian Corpuscles, Vater's Corpuscles,
Vater-Pacinian Corpuscles). These are among the largest of the nerve
end organs. In the mesentery of the cat they are of macroscopic size,
varying in length from two to three millimeters. They assume the form

of a large ovoid thickening, placed upon the end of a nerve fiber. The
12

168

PERIPHERAL NERVE TERMINATIONS: END ORGANS

Pacinian corpuscle consists of a thick lamellated connective tissue coat,
and a central granular protoplasmic core which is pierced by the nerve
fiber. The medullated nerve fiber enters the axis of the corpuscle, its
Henle's sheath becoming continuous with the superficial capsule of con-

FIG. 186. A LAMELLAR CORPUSCLE IN
LONGITUDINAL SECTION, SHOWING
A NETWORK OF SPIRAL ELASTIC
FIBERS.

Weigert's elastic tissue stain. Highly
magnified. (After Sala.)

c &..

FIG. 187. AXIAL SECTION OF A COR-
PUSCLE OF HERBST FROM A DUCK'S
TONGUE.

a, medullated nerve fiber; b, naked
axial nerve fiber with a bulbous end; c,
nuclei of the core; d, inner concentric
capsule; e, nuclei of the outer lamellated
capsule. X 380. (After Sobotta.)

nective tissue. The nerve fiber on entering the core loses its medullary
sheath, and after traversing a greater or less portion of the core divides
into two to five branches which end near the distal pole in a disk-like
expansion. In its course through the core, the nerve fiber gives off fine
lateral twigs (Sala, Retzius).

The connective tissue sheath consists of a granular protoplasm which

NERVE ENDINGS IN CONNECTIVE TISSUE

169

is permeated by densely felted spiral fibers (Sala) and is divided into
ten to fifty concentric lamellae by lines of flattened connective tissue
cells and fibers. According to Schwalbe, however, these cells form an
endothelioid coat on either surface of each lamella. Lamellar corpuscles
are occasionally compound, two or more adjacent corpuscles being sup-
plied by branches of the same nerve fiber.

Lamellar corpuscles are found in large numbers in the subcutaneous
tissue of the finger tips and of the penis, as well as in the skin of other
parts, in the mesentery and the connective
tissue of neighboring organs, e.g., the
pancreas, in the pre vertebral connective
tissue of the abdomen and mediastinum
near the walls of the large blood-vessels,
in the serous membranes, pleura, peri-
cardium, peritoneum in the periarticular
connective tissue and periosteum, in the
sheaths of the larger nerve trunks, and in
the connective tissue of the thyroid gland
and of the skeletal muscles.

5. The Corpuscles of Herbst (Key-
Retzius Corpuscles). The corpuscles of
Herbst are similar in structure to the
lamellar corpuscles except that the core
which surrounds the axial nerve fiber con-
tains cuboidal tactile cells. They occur
only in the cere of aquatic birds.

6. The Corpuscles of Grandry
(Merkel's Corpuscles}. The corpuscles
of Grandry, also found only in aquatic
birds, contain several tactile cells of ecto-
blastic origin similar to those found in

the epidermis. Each cell is in relation with a ring or meniscus formed
by the expanded end of a nerve fiber. The whole is included within a
thin connective tissue capsule and may be regarded as a compound tactile
cell occurring in connective tissue.

7. The Golgi-Mazzoni Corpuscles. The Golgi-Mazzoni corpuscles
described by Ruffini (Arch. ital. de biol., 1894) somewhat resemble the
Pacinian corpuscles in that they possess a lamellar, though relatively
very thin, connective tissue sheath and a central granular core. The core,
however, is relatively excessive in size, and the entering nerve fiber

FIG. 188. A PAPILLA OP THE
DUCK'S TONGUE, CONTAINING
A CORPUSCLE OF GRANDRY.

The corpuscle contains four
large cells, between which are the
tactile menisci of the nerve end-
ing, n, nerve. Highly magnified.
(After Merkel, from Kolliker.)

170

PERTPHEEAL NERVE TERMINATIONS: END ORGANS

breaks into a number of branches with discoid terminal expansions simi-
lar to those found in the nerve endings of Golgi in the tendons. They

FIG. 189. GOLGI-MAZZONI CORPUSCLES FROM THE SUBCUTANEOUS TISSUE OF THE

TIP OF THE FINGER. (After Ruffini.)

occur also in the corium of the skin in certain regions (e.g., the external
genitalia, finger tips), and in the conjunctiva and the periosteum.

NERVE ENDINGS IN MUSCLE AND TENDON

171

NERVE ENDINGS IN MUSCLE AND TENDON

A. STRIATED MUSCLE

1. Motor End Plates. These organs form the intramuscular end-
ings of motor axons whose cell bodies are found in the ventral horns of
the gray matter of the spinal cord. The efferent fibers reach the muscle
through the many cerebrospinal nerve trunks. On entering the muscle

i^/ ~

PSM< X X

-^^_C- :

> ' ' IMP

LllMW

-i r; r- : : ' , \ Ll ' -^ r-. J "fc=^ p X.? 1 ^! \

d C

^T^L r~K~L

^^fc*

fe

L

FIG. 190. MOTOR XERVE ENDINGS IN STRIATED MUSCLE.

.4, from a lizard; B, from the guinea-pig; C, from the hedgehog. A and C are sur-
face views; in B the end plate is seen in profile, o, muscle fiber; b, nerve fiber; c, nerve
ending in the form of a 'brush'; d, the sole plate; e, sarcolemma. A, X 160; .B, X 700;
C, X 1200. (After Bohm and von Davidoff.)

these nerves form a plexus in the perimysium from which nerve fibers
are distributed within the muscle bundles. Here they form an abundant
plexus of branching nerve fibers within the endomysium, the ultimate
branches being of sufficient number to supply one or more terminal nerve
fibers to each muscle cell.

172

PEEIPHEKAL NERVE TERMINATIONS: END ORGANS

At the surface of the muscle cell the nerve fiber loses its medullary
sheath, its neurolemma becomes continuous with the sarcolemma of the
muscle cell, and its naked axis cylinder divides into two to five branches,
which end, often after repeated subdivision, in flattened terminal disks,
distributed in mammals over a limited, in amphibians over a broad area,
but which never completely encircle the cylindrical muscle cell.

The terminal expansions of the axon rest upon a granular, slightly

raised sole plate which contains many
ovoid muscle nuclei, the sole nuclei.

2. Muscle Spindles (N euro mus-
cular Spindles, N euromuscular End
Organs). These are sensory nerve
endings which are concerned with
the so-called muscle sense. They are
especially numerous in the extrinsic
muscles of the tongue, in the small
muscles of the hand and foot, and in
the intercostal muscles ( Huber , Amer.
Jour, of Anat., 1902). They have
not been found in the muscles of the
diaphragm. A detailed description of
the developing ueuromuscular spin-
dle in the extrinsic eye muscles of the
pig has recently been given by Sutton
(Am. Jour. Anat., 18, 1, 1915). He
describes a coarsely granular 'plaque,'
different from both muscle and nerve,

FIG. 191. A MUSCLE SPINDLE FROM
THE PSOAS MAGNUS OF MAN.

1, intrafusal muscle fibers; 2, nerve
fibers; 3, axial sheath; 4, connective
tissue capsule; 5, muscle fibers of an
adjacent fasciculus; 6, peri-axial
lymphatic spaces; 7, blood-vessel.
Hematein and eosin. X 470.

which he inclines to regard as an

'intermediary structure,' perhaps a receptor substance analogous to the
sole plate of motor endings.

A muscle spindle contains from five to twenty striated muscle fibers
of small size, and an almost equal number of nerve fibers. The whole
is inclosed within a connective tissue capsule of considerable thickness.
The bundle of intrafusal muscle fibers is again surrounded by a delicate
a. rid I shcalh of connective tissue which is united to the capsule by bands
of fine fibrous tissue which span the broad peria.rinl lymphatic space.
The larger of these fibrous bands support the nerve fibers, on their way
to the intrafusal muscle cells, together with several small blood-vessels.

The muscle spindles form long fusiform bodies (from 1 to 5 milli-
meters in length) whose muscle fibers at the pole of the spindle may be

NERVE ENDINGS IN MUSCLE AND TENDON

173

connected with the tendon, or they may join other muscle fiher bundles.
The muscle spindles are usually found in the fibrous septa of the peri-
mysium. Compared with the adjacent muscle fibers, the intrafusal fibers
have a smaller diameter, are less distinctly but more coarsely striped,
and contain some centrally located nuclei.

Either one or several nerve trunks enter the spindle, usually near
its equator rather than at its poles. The nerve fibers branch repeatedly

FIG. 192. MIDDLE THIRD OF A TERMINAL PLAQUE IN THE MUSCLE SPINDLE OF AN

ADULT CAT.

A, rings; F, dendritic branchings; S, spirals. Chlorid of gold preparation. Highly
magnified. (After Ruffini.)

in the intracapsular connective tissue, and finally pierce the axial sheath
as naked processes which form a rich arborization of terminal fibrils
about the intrafusal muscle fibers. Buffini distinguishes three types of
terminal nerve fibrils: (1) annular, which form rings around the muscle
fibers; (2) spiral, which are spirally twisted about the intrafusal fibers;
and (3) dendritic branchings, in which the axons break into numerous
irregular processes with laminate expansions.

Motor end-plates for the muscle filters of the spindle as well as sym-
pathetic vasomotor nerves for its blood-vessels have also been demon-
strated within the muscle spindles.

That the muscle spindles are sensory and not motor organs has been

174

PERIPHERAL NERVE TERMINATIONS: END ORGANS

demonstrated by Sherington (Jour. PhysioL, 1894), who found that they
were not affected by the muscular atrophy following section of the pe-
ripheral motor neurones, and by Horsley ("Brain," 1897) and others who
have found that the muscle spindles are unaffected in cases of extreme
muscular atrophy in man.

3. Neurotendinous End Organs ( Golgi End Organs, Tendon Spin-
dles). These organs occur in the tendons of muscles near the junction
of the tendon bundles with the muscle fibers. They are fusiform in
shape and consist of a thin lamellar capsule of connective tissue which

f f>.

FIG. 193. NEUROTENDINOUS END ORGAN OR TENDON SPINDLE OF GOLGI.

fpt, bundle of tendon fibers; gH, medullated nerve fiber; rfnc, ribbon-like terminal
ramifications of the neuraxis; SR, node of Ranvier. Moderately magnified. (After
Ciacio.)

incloses several intrafusal tendon bundles of dense fibrous tissue. A
narrow lymphatic space intervenes between the capsule and the intra-
fusal tendon bundles.

Nerve fibers enter the spindle and give off several medullated branches
which run between the tendon bundles near the axis of the spindle.
These finally form naked end fibrils with branching end plates, which
surround the tendon bundles in an annular or spiral manner (Ciacio,
Arch. ital. de biol., 1891). Since the structure of the Golgi tendon
spindles closely resembles that of the muscle spindles, they are probably
of similar function.

4. Pacinian Corpuscles and End Bulbs of Krause. In addition
to the special motor and sensory end organs described above,
Pacinian corpuscles and end bulbs of Krause are also found in the con-
nective tissue of striated muscles.

NERVE ENDINGS IN MUSCLE AND TENDON

175

End plates of 'accessory' non-medullated, probably sympathetic,
fibers have also been described in striped muscle (Perroncito, Ihibcr ami
De Witt, and Boecke). Muscle tonus is believed to depend upon this
innervation.

B. CARDIAC AND SMOOTH MUSCLE

The nerves (sympathetic) of the heart are distributed to the cardiac
ganglia, whence non-medullated fibers pass to all portions of the organ
and form a very rich plexus in
the intermuscular connective
tissue. Fine terminal fibrils
are distributed from this plexus
to the muscle fibers, upon

whose surface they end in vari-

FIG. 194. NERVE ENDINGS IN CARDIAC
MUSCLE FROM THE HEART OF A CAT.

a, muscle cells; b, nerve fiber. Methylene
blue. Highly magnified. (After Huber and
De Witt.)

cose swellings and end knobs.
While most of these fibrils are
probably motor in function,
others which end in the inter-
muscular connective tissue are
more probably afferent (sensory). Occasional endings in cardiac muscle
resemble the simpler motor end organs of skeletal muscle.

In smooth muscle,
plexuses of sympa-
thetic nerve fibers oc-
cur in the intervals
between the bundles
of muscle fibers. Sec-
ondary plexuses of
naked fibrils are

found among the muscle cells, and from this plexus fine lateral fibrils
are distributed to the muscle cells, upon whose surface they end in small
terminal granules or end knobs. Many of the nerve fibers in smooth
muscle are undoubtedly of sensory function.

The nerve endings and the distribution of the peripheral nerve fibers
in the various organs of the body are more fully described in the several
chapters devoted to those organs.

FIG. 195. NERVE ENDINGS IN SMOOTH MUSCLE, FROM
THE INTESTINE OF A CAT.

a, muscle cell; b, nerve fiber. Methylene blue. Highly
magnified. (After Huber and De Witt.)

CHAPTER VII
THE BLOOD VASCULAK SYSTEM

This system includes the heart, arteries, capillaries, and veins.
These structures form a continuous set of branching tubes, which convey
the blood from the heart, through the arteries and capillaries, and back
again through the veins to the heart. In the capillaries a portion of the
blood plasma transudes into the tissue spaces, where it forms the tissue
juices, and from which it is returned to the blood by the lymphatic ves-
sels, the terminal branches of which empty into the subclavian veins.

This entire vascular system is completely lined by a single layer of
flattened epithelial cells, the endotlielium. The cells are united edge to
edge by an intercellular cement substance, to form a continuous mem-
brane throughout the entire system. The blood-vessels include the ar-
teries, capillaries, and veins, and these, together with the heart, will
form the subject of the present chapter. The lymphatic vessels (lymph
vascular system) will be described in connection with the lymphatic sys-
tem. The blood and lymph vessels together with their contents comprise
the vascular tissue.

ARTERIES

The arteries convey the blood from the heart to all the tissues of
the body. They are therefore almost universally present, but vary in
size from the aorta down to minute unnamed vessels of microscopic
caliber. They are divisible, according to size, into the large, medium-
sized, and small arteries, the arterioles, and what may be termed the
arterial capillaries, or precapillary arteries. The large arteries include
only the aorta and the largest of its immediate branches (innominate,
common carotids, subclavians and common iliacs), and the pulmonary
artery, the conducting arteries; the medium sized (distributing) ar-
teries comprise nearly all the remaining named arteries of the body;
small arteries, arterioles, and precapillary arteries include those un-

176

AKTUKItiS

177

named arieries which are to be found in nearly all of the organs and
tissues of the body.

Medium-sized Arteries. A medium-sized artery will be first de-
scribed, as presenting the typical arterial structure. Such a vessel con-
sists of three coats:

1. The internal coat tunica intima, or interna.

2. The middle coat tunica media.

3. The external coat tunica adventitia, or externa.

The internal coat, tunica intima, presents three layers, the innermost
being the layer of endothelial cells, the outermost a layer of elastic tissue,
the fenestrated coat of Henle, or internal elastic membrane ; between
these is a delicate fibrous
membrane or tunica pro-
pria, which constitutes the
middle layer. This layer is
regarded by some as the
product of the endothelium.

The endothelium com-
prises only a single layer of
flattened or squamous cells,
placed edge to edge to form
a continuous membrane of
simple pavement epithelium.
These cells are irregularly
polygonal in outline, with
serrated margins, and are
somewhat elongated in the
direction of the axis of
the vessel. They are loosely
attached to the elastic

membrane by the middle layer of fine fibrillar connective tissue, in whose
ground substance small branching connective tissue cells are found. The
thickness of this connective tissue layer varies proportionately to the
size of the vessel. In the largest arteries it increases in amount also
with age, becoming especially well developed in the aorta. In the smaller
arteries and in certain of the larger, e.g., external iliacs, and the main
branches of the abdominal aorta, it is so scant as to be essential-
ly lacking. The thickening of the intima in the aorta coincident
with increasing age is commonly interpreted as a compensatory
mechanism necessitated by the increasing diameter of the vessel

FIG. 196. A SMALL ARTERY FROM THE CON-
NECTIVE TISSUE OF THE ANTERIOR CERVICAL
REGION OF MAN.

a, tunica adventitia; i, tunica intima; m, tunica
media; n, a small non-medullated nerve trunk;
v, a minute venule. Hematein and eosin. X 370.

178 THE BLOOD VASCULAR. SYSTEM

due to loss of elasticity resulting from a transformation of elastin
into elacin.

The infernal elastic membrane is a layer of elastic tissue, consisting
of an intimately united fibrous mass, which completely encircles the
artery. In the smaller vessels the elastic fibers of this layer form only
a reticulated structure, but in the larger arteries they are so abundant
and so closely interwoven as to form a complete membrane, which can
be readily stripped from the subjacent tissue. If the membrane thus
prepared is examined microscopically, it will be found to present numer-
ous small openings at points where the elastic tissue is deficient. It is
this appearance which led to its description as a 'fenestrated membrane.'
The internal elastic membrane is intimately united to the tunica media,
upon which it rests; in fact, it may perhaps be better considered as the
innermost layer of this tunic, for, in the larger arteries, e.g., the aorta,
it can only with difficulty be distinguished from the adjacent layers of
elastic tissue which form a large portion of the tunica media of these
vessels.

The tunica media, or middle coat, contains smooth muscle, sheets
of elastic tissue, and a very delicate fibrous connective tissue. The pro-
portion of these elements present in any given artery varies with the
size of the vessel. Muscular tissue usually predominates, but in the
larger arteries elastic tissue is so abundant as to appear quite in excess
of the muscular ; in the smaller arteries, however, the muscular tissue is
by far the more abundant.

The smooth muscle fibers are circularly disposed in the wall of the
vessel; they are short, of irregularly serrated outline, and are intimately
united with one another. Quite frequently the muscle fibers possess short
branches which interdigitate with those of neighboring fibers. In the
larger vessels they are arranged in layers which alternate with the sheets
of elastic tissue. Small bundles of longitudinal smooth muscle fibers
are occasionally found in the outer portion of the tunica media.

The elastic tissue of the middle coat is disposed in membranous
sheets which, in the larger vessels, are embedded in a fine fibrillar con-
nective tissue. In these vessels, also, the fibro-elastic membranes thus
formed alternate with the layers of smooth muscle, throughout the entire
thickness of the tunica media. In consequence of the relaxation of the
normal arterial tone and the contraction of the muscular wall in rigor
mortis, as seen in the usual preparations, these elastic layers, as well as
the internal elastic membrane, are thrown into wavy folds.

The external coat, tunica adventitia, consists chiefly of fibrous con-

ARTERIES

179

nective tissue. Relatively few elastic fibers occur in this coat, and these
for the most part lie in its inner portion, adjoining the tunica media.
In the larger arteries, when especially abundant, the elastic fibers form
an incomplete layer, which may be termed the external elastic membrane.
Like the internal elastic membrane, this layer might well be considered as

FIG. 197. THE EXTERNAL CAROTID
ARTERY OF A CHILD.

a, tunica intima, the internal elastic
membrane is prominent; b, tunica
media, containing smooth muscle and
several wavy layers of elastic tissue;
c, tunica adventitia, containing many
transversely and obliquely cut elastic
fibers and much wavy connective tissue.
Photo. (After Magrath.)

FIG. 198. TRANSECTION OF THE WALL
OF THE AORTA OF A CHILD.

The elastic tissue is deeply stained.
1, tunica intima; 2, tunica media, 8,
tunica adventitia. Weigert's elastic
tissue stain and picro-fuchsin. Photo.
X64.

belonging to the tunica media, of which coat it would then form the
outermost stratum.

The collagenous fibers of the tunica adventitia are disposed in dense
interlacing bundles, to form a firm, unyielding coat. At the periphery
of the artery the connective tissue bundles of the adventitia intermingle
with those of the adjacent areolar connective tissue, in which the blood-
vessels are nearly always embedded, hence the outer boundary of this
coat is usually more or less ill defined.

The fibrous bundles of the adventitia are disposed somewhat obliquely
or diagonally about the artery, thus forming a closely felted connective

180

THE BLOOD VASCULAR SYSTEM

Elastica interna

Endothelial layer

Elastic J.bers

Media

f Bundles of^mooth
\ muscle cells

..Elastica externa

tissue network. Small nutrient blood-vessels, both arteries and veins
(vasa vasorum), and minute nerve trunks with occasional ganglia, occur
in this coat. From these vasa et nervi vasorum capillaries and fine nerve
fibers, both sensory and autonomic vasomotor, are distributed to the mus-
cular coat. No blood-
vessels are found in the
tunica intinia. In the
larger vessels the adven-
titia may contain also an
occasional lamellar cor-
puscle. The adventitia
contains abundant peri-
vascular lymphatics.
Nervi vasorum are said
to be lacking in the
blood-vessels of the brain
and spinal cord.

General Characteris-
tics of the Arterial Wall.
-The tunica media is
almost invariably the
thickest of the arterial
coats. In the medium-
sized vessels, e.g., the
iliac arteries, the adven-
titia is often of nearly
..Vasvasis equal thickness, but in

the smaller vessels it is
much thinner. The ar-
terial wall as a whole,
also, is very thick as
compared with the lumen
of the vessel, and is much
thicker than that of a vein of corresponding size.

The wall of the larger arteries is relatively thinner as compared with
the lumen than is the case with the arterioles; in the latter vessels
the thickness of the arterial wall often exceeds the diameter of their
lumen. In certain small arteries, e.g., those of the liver, even this ratio
may be exceeded.

The arterial wall contracts firmly in rigor mortis, hence the arteries

Adventitia

FIG. 199. PART OF A CROSS-SECTION OF THE
FEMORAL ARTERY OF A DOG. X 150. (From
Szymonowicz-MacCallum, "Histology and Mi-
croscopic Anatomy.")

ARTERIES

181

after death contain but little blood, and because of the density of the
tissues which compose their wall, these vessels retain, as a rule, their
cylindrical form.

Large Arteries. The largest arteries differ from the medium-si/ed
type in the excess of elastic tissue and relative deficiency of muscle in
their media, the extreme thinness of their adventitia, and the relative
thinness of their wall, as a whole, when compared with their lumen.
Elastic tissue is especially abundant in all of these vessels; in the media
it exceeds in volume the muscular tis-
sue, in the adventitia it forms a dense
network of elastic fibers. In the
aorta and the pulmonary artery the
elastic tissue surpasses the muscular
in the media. These vessels lack a
distinct internal and external elastic
membrane.

The adventitia of the largest ar-
teries is extremely thin, that of the
thoracic aorta being not much thicker
than its fibrous tunica intima; this
coat, therefore, forms but a small por-
tion of the vascular wall in vessels of
this type.

Small Arteries. In the small ar-
teries the elastic tissue is relatively
decreased and the smooth muscle no-
ticeably increased. The tunica iutima
of these vessels is thin, and is limited

externally by an internal elastic membrane, which stands out promi-
nently because of the relative deficiency of elastic tissue in the tunica
media.

In the tunica media of these vessels the plates of elastic tissue which
characterize the larger arteries are scarcely to be found. This coat in
the small arteries contains very little tissue other than smooth muscle.

The external elastic membrane is indistinct, and the advcutitia is
not more than one-half to two-thirds as thick as the tunica media.

Arterioles. The arterioles possess a relatively thicker wall than any
other vessel of the arterial system. Their tunica intima is thin, but little
fibrous tissue being contained within it, and the internal elastic mem-
brane is represented only by a very incomplete layer of elastic fibers.

FIG.

200. TRANSECTION OF
CELIAC Axis OF MAN.

THE

a, tunica intima with a prominent
internal elastic membrane; b, tunica
media, consisting chiefly of smooth
muscle; c, external elastic membrane
in the inner portion of the tunica ad-
ventitia. Photo. (After Magrath.)

182

THE BLOOD VASCULAK SYSTEM

The tunica media of the arteriole forms two-thirds to three-fourths of
its wall, and consists almost entirely of firmly united smooth muscle
fibers. The adventitia, much thinner than the media, contains bundles
of white fibers and delicate interlacing elastic fibrils.

Precapillary Arteries. The smallest arterioles pass into what may
be termed the precapillary arteries. In these minute vessels the wall
consists of scarcely more than the endothelial lining, about which is an
incomplete layer of circular muscle fibers, interspersed with occasional

A

r^S^^^L/S ; 3$? -V- ~ ~ ; 3??

sf^&~-'.- ^^^^^^i^^s^m F*I ( \

^^^^^^^KSM^^m

_--^-~ 1-f- ' ' . . t t ' ' . . ' JL-_-Lfa*li<- 1.* .1 ^J*l

FIG. 201. A GROUP OF SMALL BLOOD-VESSELS.

A, small arfery obliquely cut; B, arteriole and venule, the latter filled with blood;
a, fat cells. A and B are from the connective tissue of the anterior cervical region.
Hematein and eosin. A, X HO; B, X 550. C, a small arteriole near the descending
aorta of man; the internal and external elastic membranes are rendered distinct by
the stain. Hematein, Weigert's elastic tissue stain, and picro-fuchsin. X 550.

collagenous and elastic fibers. On approaching the capillaries the endo-
thelial tube is gradually laid bare. It is the smooth muscle which is
the last of the tissues to disappear from the arterial wall, whereas be-
yond the capillaries it is the fibrous tissues which are first added to
the endothelial tube to form the wall of the smallest venules (Fig. 207).

Atypical Arteries. Certain atypical arteries differ markedly from
the typical structure above described.

The umbilical arteries are almost exclusively muscular, and practically
lack elastic tissue. The muscle is arranged in two distinct layers : an inner
longitudinal, and a wide outer circular; external to these is usually a

ARTEEIES

183

MUflCLC 9COMCMT

- - AOVBNTITIA

FIG. 202. SEMI-DIA-
GRAMMATIC ILLUS-
TRATION OF SMALL
BRANCH OF PULMO-
NARY ARTERY OF
Ox.

(After Piana.) X70.

more or less complete third layer of scattered bun-
dles of longitudinally .arranged smooth muscle cells.
The umbilical vein is very similar but contains more
elastic fibers, and a distinct internal elastic mem-
brane.

The cerebral and meningeal arteries have very
thin walls and, exclusive of a relatively very well
developed internal elastic membrane, contain but
little elastic tissue.

The iliac, splenic, renal, superior mesenteric and
dorsalis penis contain scattered longitudinal bundles
of muscle in the media next the intima.

In the pulmonary arteries the media is excep-
tionally well developed. This is the case to an ex-
treme degree in the pulmonary arterioles of the cat.
The pulmonary arteries and veins are very similar
in structure. In the guinea pig and opossum the
media of the arterioles consists throughout of thick
oval segments of circularly disposed smooth muscle

alternating with narrow intervals where the muscle layer is relatively thin.
In ox, sheep and pig such segmented condition of the media is modified
in that the segmentation is spirally disposed.

The media of the roots of the aorta
and the pulmonary artery consists largely
of cardiac muscle.

In the subclavian artery the longitu-
dinal surpasses the circular ftiuscle in the
media. In the arch of the aorta and in
the upper portion of the descending aorta
longitudinal muscle bundles are found in
the intima, media and adventitia (von
Bardeleben). The common carotid, com-
mon iliac and common femoral (cruralis)
contain both longitudinally and spirally
arranged muscle fibers in the media. In
general, where large arteries are subjected
to bendings the circular muscle fibers are
reinforced by oblique (spiral) and longi-
tudinal bundles in the media. This is
conspicuously the case in the common
iliacs, the popliteal, and the brachial ar-
teries (MacCordick, Anat. Anz., 44, 11,
1913).

FIG. 203. SEMI-DIAGRAMMATIC
ILLUSTRATION OF DIVIDING
SMALL BRANCH OF PULMONARY
ARTERY OF GUINEA-PIG.

Pulmonary arterioles of opos-
sum are almost identical. X 50.

184 THE BLOOD VASCULAK SYSTEM

Comparison of Large and Small Arteries. The larger arteries are
typically elastic, the smaller typically muscular. %a the larger vessels
the elastic, tissue forms about one-half of the entire wall ; toward the
smaller arteries this tissue progressively diminishes until, in the ar-
terioles, it is limited to an incomplete internal elastic membrane, the
homologue of the complete elastic coat or fenestrated coat of Henle,
which is found only in larger vessels.

The smooth muscle, on the other hand, increases in relative amount
from the larger to the smaller arteries. While in the largest vessels it
forms not more than one-third, in the arterioles it represents about three-
fourths of the arterial wall.

In the largest arteries the adventitia is relatively very thin. That
of the medium-sized vessels is much thicker, and the ratio of connective
tissue as found in the wall of these vessels remains fairly constant down
to the arterioles. In the wall of the precapillary arteries connective
tissue is very scanty.

CAPILLARIES

The capillaries are minute tubes, 5 to 13 p, in diameter, which, in
nearly all the tissues of the body, connect the arteries with the veins.
Their wall is formed by a layer of endothelial cells which on the one
hand is continuous with the endothelial lining of the arteries, on the
other hand with that of the veins.

As a rule there are neither muscle fibers nor connective tissue in
the wall of the true capillaries ; occasionally, however, very fine isolated
circumferential elastic fibers encircle the endothelial tube. In the
minute arterioles and venules, which are about to terminate in or take
origin from the true capillaries and which have been described as pre-
capillary arterioles and venules, a very thin layer of muscle fibers or of
connective tissue is added to the endothelial wall of the capillary. On
the arterial side the muscle is the first tissue to be thus added, on the
venous side the fibrous connective tissue is the first to appear.

The endothelium of the capillary wall consists of flattened plate-
like cells which are joined edge to edge by cement substance. These
cells are somewhat elongated in the axis of the vessel, the shape of the
cell, as in the arteries and veins, depending upon the size of the vessel,
the smaller the vessel the more elongated its endothelial cells. The
margins of these cells are extremely irregular, hence they present a wavy
or serrated outline.

':

a v

FIG. 204. THE CAPILLARY NETWORK CONNECTING AN ARTERIOLE AND VENTTLB
OF THE OMENTUM OF A YOUNG RABBIT.

The blood-vessels have been injected. The discolorations at I and I are due to the
presence of lacteals beneath the endothelium ; at I' and /' these are surrounded by the
capillary network, a, arteriole; v, venule. Considerably magnified. (After Ranvier.)

FIG. 205. CAPILLARY VESSEL OF THE FROG'S MESENTERY.

Treated with nitrate of silver to show the outlines of the endot helial cells. Highly
magnified. (After Ranvier.)

13 185

186

THE BLOOD VASCULAE SYSTEM

Although the endothelial cells of the capillary wall appear to be
firmly united to one another, yet they are capable of being separated

sufficiently to permit the ready
passage of white blood-cells
through the capillary wall, by
diapedesis. The capillary wall
does not appear to be an inactive
factor in this process, for inert
pigment granules may also pene-
trate the wall of these vessels,
the endothelial cells immediately
closing the aperture which is
thus formed. Nevertheless, pure-
ly mechanical means, e.g., in-
creased blood-pressure, appear
also to favor this process. The
openings which are formed be-
tween the endothelial cells by
diapedesis of blood-cells are very
transitory; they are almost im-
mediately closed by the activity
of the endothelium. Such tran-
sitory breeches of the capillary
wall are termed stigmata.

The capillaries branch and
anastomose with one another to
form networks, the outlines of
whose meshes vary according to
the tissue in which they occur.
In such tissues as muscle and
nerve they form elongated
meshes whose long axes are
parallel to those of the muscle
or nerve fibers ; in the looser,
more areolar tissues they form

FIG. 206. Two SINUSOIDAL VESSELS PROM
THE MEDULLA OF THE HUMAN ADRENAL.

Each contains the outline of a single red
blood corpuscle for comparison of size.
At a, a small vein is shown; it is filled with
blood and possesses a much thicker wall
than that of the sinusoids. Hematein and
eosin. X 410.

large meshes of irregular form;
while in the capillary membranes, as in the walls of the pulmonary
alveoli, they are disposed in a close net, the diameter of whose meshes
scarcely exceeds that of the capillaries.

With but few exceptions capillaries occur in all the tissues of the

VEINS

187

body. In epithelium and in cartilage there are no blood-vessels of any
kind, and in the splenic pulp it is doubtful if true capillaries occur. In
certain tissues large vascular spaces occur, which are comparable to
the capillaries in that their wall consists of scarcely more than the eiido-
thelial tube, but which differ from the true capillaries in the extreme
size of their lumen. These vessels have been described by Minot (Jour.
Bost. Soc. of Med. Sc., 1900) as sinusoids. They are found in the erectile
tissues, adrenals, eoccygeal gland, parathyroids, in the maternal placenta,
and in the fetal liver, heart, pronephros, and mesonephros. They differ
from capillaries also in that they generally do not connect arteries and
veins, but are either exclusively arterial or venous. In the adult only
venous sinusoids occur. Retia mirdbilia are capillary plexuses on ar-
terioles or venules; the best example of a rete mirabile in the human
body is the arterial capillary plexus on the efferent glomerular arteriole
of the kidney.

VEINS

The blood having passed the capillaries, enters the smallest radicals
of the venous system, the precapillary venules, and passes thence through
the venules to the larger veins. The pro-
gressive increase in the caliber of these suc-
cessive vessels is accompanied by a corre-
sponding increase in the thickness of their
wall. Thus, while the endothelial tube alone
composes the capillary wall, the endothelium
of the precapillary venule is encircled by a \j

delicate connective tissue membrane. In the /

V .1 '

venule occasional smooth muscle fibers are
added to the wall of the smaller vessel, and
in the vessels of this caliber the fibrous tis-
sues have been so increased that the vascular
wall, as in the artery, can be said to possess
three coats.

Precapillary Venules. The wall of the
precapillary venule consists of the endo-
thelial lining, which is surrounded by a
very delicate connective tissue membrane
in which are very few elastic and white
fibers.

.:

/

/\

. .

/Q

i J

i

I

FIG. 207. PRECAPILLARY
VENULE AND ARTERIOLE.

The lighter nuclei are those
of the endothelium. The
darker nuclei in the venule
are in connective tissue cells;
in the arteriole they are in the
muscle cells. A, venule; B,
arteriole. Partly diagram-
matic. Highly magnified.

188

THE BLOOD VASCULAR SYSTEM

Venules. In the venule the tunica intima consists of little more
than the endothelial lining. Its media and adventitia are not as yet
distinctly differentiated, the former being distinguished only by the in-
complete layer of circularly disposed smooth muscular fibers. The ex-
tremely thin adventitia is composed almost wholly of white fibers, the
greater part of which are circularly disposed. Very few elastic fibers
occur even in vessels of this size.

Small Veins. In the small veins the three coats are fairly distinct,
the vascular wall being, however, much thinner than in the artery of
corresponding size.

The endothelium of the tunica intima is supported by a very delicate
connective tissue membrane which as yet contains but few elastic fibers.

- - - a

i

_., j

FIG. 208. TRANSECTION OF AN ARTERIOI AND VENTJLE.
X 250. (After Schafer.)

The tunica media consists of a thin layer of circularly arranged
smooth muscle fibers intermingled with a delicate fibrous tissue; elastic
fibers are relatively scarce. The adventitia, though considerably the
thickest of the three coats, is as yet a thin membrane. It consists of
fibrous connective tissue, elastic fibers being scarcely demonstrable except
by means of the specific stains for this tissue.

Larger Veins. The wall of the larger veins closely resembles that of
the corresponding artery, except that the venous wall is much thinner
and contains far less elastic tissue. The tunica intima of the medium
and lar^-e veins presents a lining endothelium, a thin layer of delicate
connective tissue fibers, and an incomplete internal elastic membrane.
The last named is never so prominent as in the artery.

VEINS

The tunica media contains smooth muscle fibers, the most of which
are circularly arranged. A somewhat smaller proportion of delicate
connective tissue completes this coat.

The media is best developed in veins of the lower extremities; it
forms a thinner layer in veins of the upper extremities, and is rela-
tively scant in the large veins of the abdominal cavity.

The adventitia of the larger veins consists of interlacing bundles of

Occa-

dense white fibers, among which is a network of fine elastic fibers.

^f^2*:a

N ' '
V ' - . '

--'' '.'; . ' - ' '

?M ' * -

1*7\ .

.

." - ' : - "

, '<tr^ . . '-

\.^~ - - : - .:,-.,.

,6

' , .

A-*--

' '^'.'' : ''^ ."-''' '-"". '

'-

Yc

X:--?-,..

FIG. 209. TRANSECTION OF THE WALL OF THE HUMAN VENA CAVA.

a, tunica intima; 6, tunica media; c, tunica adventitia. The inner portion of the
tunica adventitia contains numerous bundles of longitudinal smooth muscle fibers
which have been cut across. Hematein and eosin. X 90.

sional small bundles of longitudinal smooth muscle fibers occur in the
adventitia of the largest veins. In these vessels also, a very incomplete
external elastic membrane may be demonstrated by the specific stains for
elastic tissue.

Nerve fibers and minute blood-vessels, vasa vasorum, occur in this
coat and distribute their terminal branches to the two outer coats of the
vessel. The intima of the vein, as in the artery, is non-vascular. The
vena3 vasorum of veins empty directly into the lumen.

Atypical Veins. In certain tissues the veins present noticeable de-
partures from the typical structure. Longitudinal muscle fibers are found
in many of the larger veins of the abdominal and thoracic cavities.

190 THE BLOOD VASCULAR SYSTEM

The cephalic, basilic, mesenteric, iliac, femoral, saphenous, uterine
and the dorsalis penis veins contain small longitudinal bundles in the
intima. Certain veins, e. g., saphenous, femoral, and popliteal, contain a
layer of longitudinal muscle in the intimal portion of the media.

The adrenal veins contain, almost exclusively, longitudinal muscle
fibers, and in the renal, suprarenal, portal, splenic and phrenic veins and
the inferior vena cava these fibers form the greater portion of the tunica
adventitia.

In the pulmonary veins the circular muscle fibers are highly developed,
the tunica media of these veins almost equaling in thickness that of the
corresponding pulmonary artery. As in other large veins, however, elastic
tissue is notably deficient in the tunica media of the pulmonary veins.
The muscle of the roots is partially of the cardiac type.

The tunica media of the largest veins, e. g., the venae cavse, jugular,
innominate and subclavian, contain much fibrous and considerable elastic
tissue, the latter often forming incomplete membranous layers, which alter-
nate with the muscle, as in the arteries. Such structure is, however, limited
to the very largest of the veins. In the superior vena cava and the hepatic
vein the media is practically replaced by adventitia.

The cranial veins (cerebral and meningeal) are conspicuous for the
almost entire absence of muscle from their walls, the large meningeal
sinuses being surrounded by a dense fibrous coat derived from the dura
mater, and lined by the usual endothelium. In the veins of the retina also,
and those of bones, a media is essentially lacking.

The venous spaces of the erectile tissues have already been mentioned
as presenting to some extent the sinusoidal type of structure, these large
venous cavities possessing an extremely thin wall, in structure scarcely
more than endothelial lining. The afferent artery projects into the broad
vascular lumen, from which the efferent vein makes its exit.

Comparison of the Larger and the Smaller Veins. Comparing
the larger with the smaller veins, the excess of elastic and muscular tis-
sue in the former is most noticeable. In the absence of specific stains,
elastic tissue can scarcely be recognized in the vemiles and smaller veins.
In the medium-sized vessels it is scanty, but is present in considerable
quantity in the largest vessels.

The precapillary veins and venules contain scarcely any smooth
muscle. This tissue becomes more distinct in the small veins and
steadily increases proportionately to the size of the vessel ; in the largest
veins it is again relatively deficient.

Comparison of the Vein with the Artery of Corresponding- Size.
The lumen of any given artery is always much smaller than the total

VEINS 191

lumen of its vense comites (usually two in the case of the smaller arter-
ies, one vena comes in the case of the medium-sized), the ratio being
about one to three. Jlenee, of any two vessels in close proximity to
each oilier, the vein would more likely possess the larger caliber; the
artery, on the other hand, would have the thicker wall.

As compared with the arteries, the veins are notably deficient in elas-
tic and muscular tissue. In the wall of most veins the white fibrous is
in excess of all other tissues. For this reason the adventitia is almost
invariably the thickest of the three coats of the vein, whereas in the
artery the media is always the thickest coat.

The internal elastic membrane, which can be readily recognized even
in the smaller arteries, is limited to the large veins. Alternating layers
of elastic and muscular tissues are to be seen even in the medium-sized
arteries, but this arrangement is likewise confined to the largest of the
veins.

The wall of the vein as a whole is much thinner in proportion to its
lumen than that of the corresponding artery; it is also less rigid. For
this reason the wall of the vein is much more likely to collapse after
death than is the thicker and more rigid arterial wall. Because of the
preponderance of muscle in the wall of the artery its contraction in
rigor mortis is more powerful than that of the vein ; the vein therefore is
apt to be distended with blood while the artery contains but little. A
certain number of blood-cells can usually be found in almost any type of
blood-vessel.

Valves occur at intervals of considerable length along the course of
the larger veins. These are not found in the arteries. Each valve con-
sists of one, usually two, and occasionally more crescentic folds or redupli-
cations of the tunica intima between which is a slightly increased amount
of connective tissue, the elastic fibers of which are more abundant on the
side next the lumen. The valves therefore are suspended free in the
lumen of the vessel and are covered on either side with a layer of endo-
thelium which is continuous with that lining the vein.

The valves open with and close against the blood current. They
occur generally distal to the point of entrance of venous tributaries. They
are more abundant in the veins of the extremities and are lacking in the
superior and inferior venae cavae, in the hepatic, portal, renal, uterine,
pulmonary, umbilical, cerebral and meningeal veins, in the veins of bones,
and in veins of less than 2 millimeters diameter. They obviously assist
the flow of blood to the heart against the influence of gravity. The gen-
eral absence of valves in the veins of the abdomen and thorax, and their

192

THE BLOOD VASCULAK SYSTEM

abundance in the veins of the extremities, especially the lower, is prob-
ably to be interpreted in terms of a quadrupedal ancestral condition.

The fact should be borne in mind that it is because of their relative
infrequeucy that valves are not often met with in those transections of
the smaller veins which are seen in nearly all microscopical preparations.

y.s.

THE DEVELOPMENT OF BLOOD-VESSELS

The earliest anlage of the blood vascular system is a mesenchymalike
layer, the angioblast, which appears between the entoderm and mesoderm
at the distal pole of the yolk-sac (Fig. 210) at a very early stage of the
embryonic development (1 millimeter, Minot). In this layer appear accu-
mulations of rounded cells in the
form of anastomosing irregular
solid cords. The peripheral cells
become flattened to form an eiido-
thelial tube; the central cells sepa-
rate and scatter in the vessels as
primordial blood-cells floating in a
plasma, probably a secretion prod-
uct of the cells. This network of
primitive blood-vessels grows to-
ward the embryo in the shape of
tubes and solid nucleated sprouts
(arigioblast cords, Bremer) and,
converging to form two large ves-
sels, invades the tissue of the
embryo in the region of the de-
veloping heart as the vitelline
veins. Subsequently other ves-
sels, both arteries and veins, appear in the embryo. Such vessels are pre-
ceded by capillary plexuses, as demonstrated by Evans (Anat. Rec., 3, 9,
1909), in which the definitive vessels arise as paths in the original network
selected, enlarged, and modified under the influence of mechanical factors
incident to the flow of the main stream of the blood. There can be no
doubt that the original anlages of the blood-vessels arise by a confluence of
separate spaces (angiocysts), possibly always connected by angioblast
cords, and tubes formed in the angioblast; likewise there is no doubt that
the embryonic blood-vessels sprout as tubes and solid cords and thus grow
into adjacent regions (Fig. 211). But the features of vasculogenesis con-
cerning which there remain decided differences of opinion are (1) the
nature and origin of the angioblast, that is whether of mesodermal, ento-

FIG. 210. A 13 MM. HUMAN EMBRYO.

The chorionic vesicle is cut open, re-
vealing the embryo enveloped in the
amnion, and the yolk-sac (y.s.). X

THE DEVELOPMENT OF BLOOD-VESSELS

1:1:;

dermal or of dual origin; (2) the manner of origin of the primary vascular
stems in the embryo, whether by invasion through growth from the extra-
embryonic primitive vascular area, or by a process in the body mescnchyma
similar to that through which the primitive vessels arose in the yolk-sac
(umbilical vesicle). The evidence seems to favor the mesodermal origin
of the angioblast. The advocates of vasculogenesis by invasion (Evans,
Minot, Bremer and others) regard the original angioblast, very early differ-
entiated from mesenchyma,
as the sole future source of
endothelium, to which is
ascribed a strict specificity
throughout development. The
advocates of the in situ
method of origin (Maximow,
Huntingtoii, Schultze, Miller
and others), on the contrary,
conceive early vasculogenesis
as a process of progressive
fusion of tissue spaces and
mesenchymal cells involving
a continued differentiation of
endothelium from mesenchy-
ma.

The total evidence seems
to favor the view that in
earliest stages blood-vessels
may arise in the mesenchyma
of the embryo and that these

primitive stems may be added to by discrete anlages all of which may
fuse to form the vascular net out of which develop the future main
vessels.

The vessels of later embryonic and fetal stages probably arise solely
as sprouts from these earlier stems.

The chief point of uncertainty concerns the point in time when vascu-
logenesis passes from a process including sprouting and fusion of separate
anlages, to one where extension is exclusively by terminal growth. Both
arteries and veins have a like origin in capillary plexuses.

The final anastomosing sprouts of endothelium represent the defini-
tive capillaries. The development of the definitive wall of arteries and
veins involves the formation of extra-eiidothelial layers of muscular and
connective tissue elements from the surrounding mesenrhyiiu', and their
association into the several tunics of the various subdivisions of these
vessels.

FIG. 211. ' VASOFORMATIVE ' CELLS FROM THE
MESENTERY OF A RABBIT SEVEN DAYS OLD.

g.s., red blood cells; n, nucleus of the vascular
endothelium; p, points of growth, at which ex-
tension occurs. Highly magnified. (After Ran-
vier.)

194

THE BLOOD VASCULAR SYSTEM

The essential matters in the foregoing chapter may he summarized
in the following schemes.

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HKABT 195

HEART

The wall of the heart consists of interlacing bundles of cardiac mus-
cle fibers, the myocardium, which are covered externally by the epicar-
dium, a serous membrane which forms the visceral layer of the peri-
cardium. Internally the muscular wall of the heart is lined by the
endocardium, which resembles the serous membranes in that it consists
of pavement epithelium supported upon a layer of fibre-elastic connective
tissue. The endocardium lines all the cavities of the heart, and its endo-
thelium is directly continuous with that of those arteries and veins
which are connected with the cavity of the heart. Thus the entire
vascular system heart, arteries, capillaries, lymphatics, and veins may
be said to be lined by an uninterrupted sheet of pavement epithelial cells,
the endothelium.

Myocardium. The muscle cells of the myocardium are so disposed
as to form long fibrous bundles which by their figure-of-8 arrangement
are interwoven with one another to form a dense interlacing mass of mus-
cle bundles. (For detailed description see Mall, Amer. Jour. Anat., 11, 3,
1911.) The structure of these cardiac muscle fibers has already been
described. Because of the irregularity of their disposition, transections
of the cardiac wall present sections of muscle fibers which have been
cut in every conceivable direction.

Between the muscle fibers is a very delicate framework of fibrous
connective tissue, the endomysium, which surrounds the muscle fibers
and supports the abundant capillaries, arterioles, and venules, with
which they are supplied. The proportion of connective tissue in the
normal myocardium as compared with the muscle is, nevertheless, very
small.

In certain portions of the myocardium connective tissue is more abun-
dant. Thus it is slightly increased in the vicinity of the endocardium, in
the papillary muscles, and near the bases of the cardiac valves. At the
surface of the heart, beneath the epicardium, especially in the various
grooves on the surface of the heart, the connective tissue is still more
abundant, and may contain groups of fat cells. It is through these
accumulations of connective tissue that the larger blood-vessels are dis-
tributed to the myocardium.

Epicardium. The epicardium, like the other serous membranes,
consists of a layer of pavement cells, so joined edge to edge as to form
a complete mesothelial coat. Here and there the mesothelium presents

19G

THE BLOOD VASCULAR SYSTEM

small open! HITS at the angles between its cells; these stomata are sur-
rounded by minute, finely granular cells and are perhaps connected with
the lymphatic vessels.

The mesothelium of the epicardium is supported upon a thin layer
of dense areolar tissue in which are many small blood-vessels and
lymphatics. Fibers from the deeper surface of this layer are prolonged
into the myocardium to become continuous with its endomysial connec-
tive tissue. The larger of these connective tissue trabeculas accompany
the branches of the larger arteries and veins which are distributed to
the muscular wall of the heart.

Endocardium. The endocardium consists of a lining membrane of
polygonal endothelial cells supported upon a thin layer of delicate

fibrous connective tissue, of en-
dothelial origin (Mall). In this
membrane is a network of elas-
tic fibers, and a small amount
of smooth muscle. The en-
dothelmm of this membrane is
continuous with that of those
blood-vessels which open from
the cavities of the heart. Its

FIG. 212. THE PARIETAL LAYER OF THE
PERICARDIUM OF A CHILD.

a, mesothelium; b, connective tissue.
Hematein and eosin. Photo. X 500.

connective tissue also forms a
continuous layer with that of
the tunica intima of these ves-
sels; in fact, the three coats of the cardiac wall endocardium, myocar-
dium, and epicardium might well be compared with the corresponding
three coats of the arterial and venous walls the intima, media, and ad-
ventitia. In either organ, the inner coat consists of a lining membrane
of endothelium, and a supporting membrane of connective tissue; muscle
in large part composes the middle coat, while the outer coat is typically a
connective tissue layer.

Valves. At the cardiac orifices the entire thickness of the endocardium
is folded upon itself to form a double layer, between the folds of which
an intervening stratum of dense fibre-elastic tissue is inserted. These
endocardial folds form the cardiac valves. The number and shape of
their cusps are dependent upon the location. The semilunar valves of
the aortic and pulmonary orifices consist of three crescentic endocardial
folds; at the auriculoventricular orifices the tricuspid valve consists of
three, the bicuspid or mitral of two, folds.

The margin of the valvular cusp or fold is extremely thin ; just within

HEART

197

the margin, however, the central mass of dense fibrous tissue is somewhat
thickened to form, in each cusp, a dense rim which during valvular
closure secures the firm and accurate approximation of the free margins
of adjacent cusps. At the apex of the valvular cusp, when- the adjacent
fibrous margins of the valve meet, the dense connective tissue, particu-
larly in the semilunar valves, is considerably thickened to form a nodule,
the corpus arantii. These corpora or noduli, in the aged, are frequently
subject to calcareous infiltration.

Muscular fibers are continued from the adjacent cardiac wall into
the dense fibrous tissue at the base of the valve, except in the case of
the semilunar valves of the pulmonary and systemic aortae. This muscle

FIG. 213. THE ENDOCARDIUM.
From the ventricular wall of the heart of man. Hematein and eosin. Photo. X 469.

is generally non-striped, and probably functions as a sphincter. The
base of the valve is also surrounded by a ring of fibrous tissue, the
annulus fibrosus, whose interlacing bundles are so closely packed as to
give them an almost cartilaginous feel. At the auriculoventricular
orifices, these fibrous rings are continuous with the auriculoventricular
septum, from which the muscle bands of the myocardium take their
origin.

Chordae Tendineae. These are firm, unyielding cords, composed of
parallel bundles of dense collagenous fibers, with a few clastic lihers, and
covered with a very thin endocardium continuous with that of the ven-
tricular wall and cardiac valve. These fibrous bands unite the apices of
the papillary muscles to the ventricular surfaces of the mitral and tri-
cuspid valves. At the apex of the papillary muscle the fibrous bundles
of the chords intermingle with the muscle fibers, and are continued into
the endomysial connective tissue, which is especially abundant in those

198

THE BLOOD VASCULAR SYSTEM

portions of the myocardium. At their valvular attachment the fibrous
bundles of the chords tendineae turn almost at right angles, and spread
out, in a somewhat radial manner, to become continuous with the dense
fibrous tissue which forms the interior of the valve.

FIG. 214. RADIAL SECTIONS OF THE MITRAL VALVE, FROM THE HEART OF A MAN.

A, from the base of the valve showing the extension into it of cardiac muscle fibers
from the wall of the heart; B, from the mid-region of the valve, a, auricular endo-
cardium; b, muscle fibers; c, dense fibrous tissue; d, ventricular endocardium. Hema-
tein and eosin. Photo. X 800.

Columnse Carnee. The columns carnae are columelliform projec-
tions of the myocardium into the ventricular cavity. They consist of
cardiac muscle fibers, largely of the Purkinje fiber variety, which are dis-
posed in their long axis, and are covered by reflections and reduplications
of the endocardium. The irregular contour of the ventricular cavities
appears to be entirely due to the projecting columns carnse.

HEAET

199

These muscular columns may present any one of three modes of
attachment to the myocardium: (1) they may be attached along their
entire extent; (2) they may he attached only at their two ends, the mid-
portion being free; (3) they may he attached to the myocardium at one
end only, the other end projecting into the ventricular cavity as a papil-
lary muscle, from whose apex chordae tendinese pass to the auriculoven-

Main Bundle of His
Pulmonary Veins

Fossa Ovalis
Inf. Cavd'

Coronary Sinus
Rt'ticulum

Artery to Bundle

Tricuspid V alve

Riyht Ventricle

ChordtE Tendinete

Papillary Muscle

Sup. Cava

Aorta

Pulmonary Artery

I .1/i/-.ri</.;r Filirrs Streaming to
\ the Rctifuhirn
Right Auricle

Pars Mem. Septi
( Bi f urrnl ion uf Main Bundle into
\ Right -mil Li'ft Sept. Branches
Right Septiil Branch

Moderator Band

FIG. 215. HUMAN HEART OPENED FROM THE RIGHT TO SHOW THE ATRIOVEN-

TRICULAR BUNDLE OF His.

The illustration shows also a heart valve, the chordae tendineae, and the pap-
illary muscles. (After Curran, Anat. Rec., 3, 12, 1909.)

tricular valves. Either of the last two forms may, in transections of the
ventricles, appear as isolated islands of muscular tissue surrounded by
endocardium and lying apparently free within the cavity of the ventricle.
Columnar carna? which span the ventricular cavity constitute moderator
bands. One such hand is frequently present in the right ventricle near the
apex, and occasionally one appears in the left ventricle.

Atrioventricular Bundle. The atrioventricular bundle of His w r as
discovered in the human heart by His, Jr., in 1893. Previously in the
same year it had been noted by Kent in the heart of a number of mam-
mals. It has since been seen in every species of mammal investigated.

200

THE BLOOD VASCULAR SYSTEM

It consists of a dense meshwork of cardiac muscle fibers rich in sarco-
plasm, in the form of a band taking origin in scattered fibrils in the
posterior wall of the right atrium near the septum in the atrio ventricular
groove (sinus region; hence, sinoventricular conducting system, Eetzer,
1908), and coursing forward in the interatrial septum into the upper
anterior portion of the interventricular septum, where it divides into two
limbs which branch profusely and spread out in a complicated system

of terminal branches, the
subendocardial Purkinje
fibers. Macroscopically
the bundle has a grayish
appearance ; where it
passes from the intera-
trial to the interventricu-
lar septum (pars mem-
brauacea septi) it ex-
pands into the so-called
node. In man the right
limb is much smaller
than the left.

The bundle of the
calf's heart has been re-
constructed by De Witt
(Anat. Rec., 3, 9, 1909).
Curran (Anat. Bee., 3,
12, 1909) has described
a constant bursa or lubri-
cating mechanism in re-
lation with the bundle,

furnishing protection against friction during contraction of the heart.
He describes "its connection with all parts of both auricles through three
large trunks and a number of smaller twigs, and not, as was once
thought, merely arising in the right auricle only."

Tawara (190G) first carefully described the histology of this bun-
dle in several mammals, including man. De Witt more recently (1909)
has extended the study in this same field. "In the sheep and calf, where
the fibers are most typical and most clearly differentiated from the
myocardial fibers, the fibers are much larger than the myocardial fibers,
with fewer fibrils and much more sarcoplasm.'' She describes the bundle
as a muscular syncytium. "Connective tissue and especially elastic fibers

FIG. 216. RECONSTRUCTION OF THE SINOVEN-
TRICULAR SYSTEM (BUNDLE OF His) OF THE
CALF'S HEART.

(De Witt, Anat. Rec., 3, 9, 1909.)

HEART 201

are much more abundant than in the myocardium." The bundle con-
tains abundant ganglion cells and muscle libers. It is also very rich in
glycogen.

It would seem, on the basis of its constancy of presence and structure,
and its probably independent blood and nerve supply, that the atrioventric-
ular bundle has a function independent of the myocardium, probably of
the nature of a neuromuscular end-organ (Retzer; DeWitt), providing for
the conduction of the impulse to contraction, and the coordination of the
atrial and ventricular rhythm.

A muscle bundle of closely similar structure intimately related with
the vagus and sympathetic nerves, the ' sino-atrial node,' has been described
by Keith and Flack (1907) at the juncture of the sinus venosus and the
atrium. It is believed to be the place of origin of the impulse to the heart
beat, from which it is transmitted to the atrioventricular bundle.

Laurens (Anat. Rec., 2, 8, 1913) has described an analogous muscular
connection between auricles and ventricles in certain reptiles, where it
assumes the form of an inverted funnel-shaped tube.

Development of Heart. The anlage of the heart arises from the
fusion of a pair of parallel endothelial tubes in the paramedial angioblast,
each surrounded by primitive mesenchyma. The endothelium of the result-
ing sac differentiates into the endocardium of the definitive heart, while
the connective tissue and muscle develop from the mesenchyma in a man-
ner essentially similar to that described for the blood-vessels.

Blood- Vessels. The heart is supplied with blood through the coro-
nary arteries. The larger branches of these vessels pursue their course
beneath the epicardium in the superficial grooves of the cardiac wall.
From these large arteries, smaller branches are distributed to the epi-
cardium and to the muscular wall, the latter vessels penetrating as far
as the endocardium, in whose connective tissue they form a meager
capillary plexus.

The capillaries of the myocardium are extremely abundant. They
form elongated meshes between the muscle fibers, the circumference of
each muscle fiber being in relation with several capillary vessels. The
veins return the blood from these rich capillary plexuses and pursue a
course similar to that of the arteries, the larger veins being always found
in the broader connective tissue septa. In the right atrium certain small
veins, the vena 1 minima', empty directly into the cavity of the heart.

The lymph supply is very abundant and intimate. The lymph ves-
sels form two superficial plexuses, the endocardial and the epicardial,
both draining into the larger lymph vessels at the base of the heart.
14

202 THE BLOOD VASCULAR SYSTEM

Nerve Supply. The nerve supply of the vascular system is by means
of fine branches from the cerebrospinal and sympathetic systems. In the
heart these minute nerve trunks end in the various cardiac ganglia,
most of which are found in the connective tissue of the heart, e.g., the
coronal plexuses about the orifices of the aorta and pulmonary artery.
From these ganglia sensory nerve fibers are distributed to the endocar-
dium and epicardium, and motor fibers to the myocardium. The most of
the former are connected with the vagus, the latter with the sympathetic
trunks. Through both the vagus and the sympathetic trunks are dis-
tributed also efferent cerebrospinal fibers : the accessory nerve through
the vagus contributes 'inhibitory' fibers, the cervical spinal nerves through
the inferior cervical ganglia contribute 'acceleratory' fibers.

From the cardiac ganglia branches pass to form a coarse plexus in
the connective tissue between the muscle bundles, the perimysial plexus,
from the branches of which a fine plexus is distributed to the endo-
mysium. The terminal branches end in relation with the surface of the
muscle fibers.

The pericardium contains numerous encapsulated nerve endings
(corpuscles of Golgi and Mazzoni). According to Martynoff (Arch,
mikr. Anat., vol. 84, 191-i) unencapsulated endings also are present, of
three types : coils, dendriform terminal ramifications, and modified den-
driform endings. He describes also naked terminal filaments ending on
the bases of the mesothelial covering cells.

The Hood-vessels are similarly supplied, minute ganglia occurring
here and there in the adventitia or adjacent connective tissue. From
these ganglia sensory branches are distributed to the adventitia and in-
tima and motor branches to the tunica media. Naked nerve fibrils can bo
traced to the smallest blood-vessels, and even in the capillaries terminal
fibrillse are found in relation with the endothelial wall.

CHAPTER VIII
BLOOD

Blood may be regarded as a tissue in which the intercellular material
is a fluid, the plasma. The plasma contains fibrin in solution (fibrino-
gen) ; on exposure to air, as in case of cuts, the fibrin is precipitated in
the form of delicate needle-like crystals (Fig. 217), leaving a clear straw-
colored liquid, the serum. The active element in causing this precipita-
tion is thrombin (or prothrombin), probably liberated by the blood-
platelets on disintegration under the influence of air or the stimulus
of a roughened area on the wall of the blood-vessels. The blood-cells
become entangled in this fibrin net forming a dot or thrombus. Plasma
is very similar to, but not identical with, the lymph of the lymph
vessels.

The formed elements, or blood-cells, are of two main classes, red
and white, or erythroplastids (eryflirocytes) and leukocytes. The red
blood corpuscles or plastids owe their characteristic color to the presence
of hemoglobin. Single corpuscles have a light yellowish-green color, in
masses they appear red. The function of the hemoglobin is to carry
oxygen in weak combination as oxyhemoglobin for transportation through
the blood-vessels from the lungs to the tissues, where it is employed in
the oxidation processes upon which life depends.

THE RED BLOOD CELL

The erythroplastid is a circular biconcave disk, of 7.5 microns (a
micron is 1-1000 of a millimeter) diameter. They are present in prac-
tically all histologic preparations, hence they serve well as a ready
scale for approximate determination of size of cellular elements in the
same microscopic field. Every section ; blood preparation, as of a drop
under a cover-slip; and even the blood-vessels of living mammals, con-
tain also a larger or smaller number of cells of saucer shape (cup shape;

203

204

BLOOD

bell shape, etc.). These are believed by some (Weidenreich, Lewis, Mi-
not, and others) to be the more normal in shape; however, there remains

FIG. 217. OXALATED PLASMA OF HUMAN BLOOD CLOTTED WITH THROMBIN,
SHOWING FIBRIN NEEDLES. X 512.

(After Howell, Amer. Jour. Physiol., 35, 1, 1914.)

little doubt that the circular biconcave disk shape is the normal (origi-
nal), the saucer or cup shapes, the derived forms, the result of modifi-

THE RED BLOOD CELL

205

cation by extrinsic factors. The erythroplastid is of course a very
delicate structure, and slight tractions or tensions incident to passage
through exiguous confines, or osmotic currents set up in fixing fluids,
or the coagulation of its protoplasm, would produce modifications and
distortions. Almost any conceivable mechanical modification would of

FIG. 218. FROM A FRESHLY PREPARED, UNSTAINED SPECIMEN OF HUMAN BLOOD.

Three leukocytes, an eosinophil, a polynuclear, and a lymphocyte, are represented.
Many red blood corpuscles (erythroplastids), some on the flat, some in rouleaux
and in profile, are also shown. X 1200, but reduced somewhat in reproduction.
(After Schafer.)

necessity change a circular biconcave disk into some sort of cup-shaped
element.

The red blood element lacks a nucleus, hence the propriety of in-
sistence on the term 'plastid' or 'corpuscle' in preference to cell (cyte).
The red elements of all mammals are non-nucleated. The lower forms
have nucleated elements (erythrocytes), frequently of ellipsoidal form.
Mammalian red elements of greatly divergent sizes (2.5 /u. in musk ox;
9.4 /u, in elephant ; dog, 7.5 /u, ) are all of circular outline, except those
of the camelidge (llama, camel, etc.) which are elliptical. The erythro-
plastids are generally believed to be enclosed by a delicate membrane, and

206

BLOOD

to contain a very delicate stroma (spongioplasm) and fluid matrix (hyal-
oplasm, with hemoglobin). The red corpuscles have a tendency when ex-
posed, as in a drop mounted under a cover-slip, to arrange themselves in
rows, like coins in a pile, concave surfaces apposed, forming rouleaux.
Drop preparations show after a short time also an increasing number of
plastids with puckered or spiny surfaces, crenated corpuscles. This condi-
tion results from evaporation producing a medium of greater density than

that of the normal blood plasma. Any me-
dium of density equal to that of the plasma
of any particular blood is spoken of as an
isotonic solution for that blood. The solu-
tion in most common use for human blood
is a 0.9 per cent, solution of sodium chlorid
in distilled water. Solutions of higher den-
sity are hypertonic; these produce exosmotic
currents causing destruction leading through
crenation. Solutions of lower density, for
example, water, are Injpotonic; they produce
destruction (hemolysis) through endosmosis
causing swelling, a stage of which shows a
saucer-shaped corpuscle. This is accom-
panied by laking, or extraction of hemoglo-
bin, giving rise to A ^
Mood shadows; and
final bursting, leav-
ing a debris called FIG.
hemokonia.

The number of
red corpuscles in
the blood is subject file;
to constant varia-
tioii between wide
limits. Many
physiologic condi-
tions influence their total number, as well as the relative proportion of
red elements to the white. The average number of red corpuscles in the
adult male is about 5,000,000 per cubic millimeter. In young robust
persons the number may be considerably higher. The number may also
be much reduced by considerable hemorrhages or by the imbibition
of large quantities of fluid. Profuse perspiration tends to produce

FIG. 219. BLOOD CELLS
FROM A SPECIMEN OF
FRESHLY DRAWN UN-
STAINED HUMAN BLOOD.

A, red blood corpuscles,
deep focus, showing a light
center and dim margin; B,
the same with a higher focus;
the center, being slightly out
of focus, is dim while the
margin is light; C, crenated
red corpuscles from the mar-
gin of the preparation; a,
deep focus; 6, higher focus;
D, two polymorphonuclear
leukocytes; E, large mono-
nuclear leukocyte. X 750.

o

220. SHOWING THE
ACTION OF WATER UPON
THE RED BLOOD COR-
PUSCLE.

a, the corpuscle in pro-
b-e, various stages in
transformation which

leaves only a 'shadow' e;

diagrammatic. (After

Schafer.)

THE WHITE BLOOD CELLS

207

concentration of the blood and an apparent increase in the number
of its corpuscles. The number of red blood corpuscles in the female

FIG. 221. FIVE NUCLEATED RED CELLS
(ERYTHROCYTES) FROM THE BLOOD OF
A FROG.

Eosin-met hy lene
method.

blue. Hasting's
X 1200.

FIG. 222. THREE NU-
CLEATED RED BLOOD
CELLS (ERYTHRO-
CYTES) FROM THE
MARROW OF A HU-
MAN RIB.

Eosin - met hy lene
blue. Nocht method.
X 1200.

is slightly less than in the male, about 4.500,000 per cubic milli-
meter.

THE WHITE BLOOD CELLS

Under leukocytes are grouped the following types : ( 1 ) lymphocytes ;
(2) non-granular or monoimelear leukocytes and (3) granular leukocytes
grauulocytes. These are all nucleated elements. Leukocytes lack a
cell membrane ; all are phagocytic, especially the neutrophils ; they aver-
age about 8,000 to a cubic millimeter of blood.

Lymphocytes. The lymphocytes are perhaps the least differentiated
hlood element. They are of two main varieties, large and small, between
which are intergrades. The small lymphocyte is about the size of an
erythroplastid ; its nucleus is a dense, deeply chromatic spheroidal body:
it has a very thin, shell of very finely granular or non-granular faintly
basophilic cytoplasm. The large lymphocyte (12 to 15/u.) differs from
the small, both in somewhat larger size of nucleus and slightly wider
shell of cytoplasm. The simplest and more than likely the correct con-
ception of the relationship of large to small lymphocytes is one of growth :
that is, a large lymphocyte is a fully grown small lymphocyte, a small
lymphocyte is a daughter-cell of a large lymphocyte. They constitute
about 20 per cent, of the total white blood cell content. They are the

208

BLOOD

almost exclusive cell type of lymph. They take origin in the adult in
lymph organs, spleen and bone-marrow. In infancy their proportion is
much greater, about 50 per cent.; this increase is at the expense of the
neutrophil granulocytes.

Non-granular Leucocytes. These are characterized by a large, fre-
quently bean-shaped vesicular (clear, pale) nucleus, and an extensive

FIG. 223. A GROUP OF CELLS FROM NORMAL HUMAN BLOOD.
1, red blood corpuscles in rouleau formation; #, red blood corpuscles, surface
view; 3, lymphocyte; 4, large mononuclear leukocyte; 5, polymorphonuclear,
finely granular leukocyte; 6, eosinophil leukocyte; 7, a group of blood platelets; 8,
basophil leukocyte. Eosin-methylene blue. Hasting's method. X 1200.

shell of homogeneous faintly basophil cytoplasm. They constitute from
2 to 4 per cent, of the white cell total; they are notably phagocytic.
Occasionally a few larger neutrophilic cytoplasmic granules may be
present. Morphologically, both from the viewpoint of nucleus and cyto-
plasm, they are transitional between lymphocytes and granulocytes,
hence the use of transitional leukocijle as synonym for non-granular
or large mononuclear leukocytes. Modification of this cell, characterized

THE WHITE BLOOD CELLS 209

by great increase of nuclear and cytoplasmic constituents, gives rise to
the so-called <;I\\T CELLS. These are of two sorts, depending upon
whether the nucleus is single or multiple, the megakaryocyte and the
polyknryoi-ylt'. The latter are thought by some to be identical with the
osteoclasts of developing bone.

Megakaryocytes are practically limited to bone-marrow. They fre-
quently show long and numerous pseudopodia. These, as also the cell-
body proper, show a differentiation of the cytoplasm into a superficial
hyaline layer and a central basophilic granular core. According to
Wright, constriction and segmentation of these
pseudopods give rise to the BLOOD-PLATELETS
( plates ; plaques) . These commonly hold positions
at the center of masses of converging fibrin fibrils

in blood clots, in consequence of which they are p u; 2 24 A GROUP

supposed to be the essential elements, probably OF BLOOD PLATE-
liberating 'thrombin', in clotting, hence their LETS, FROM THE Hu-

.7. Z. . m-i i -11 MAN BLOOD.

synonym, thrombocyte. Ihis term, however, is ill-

\ery highly magni-
chosen, for these elements contain no nucleus. ec j (After Eisen.)

What simulates a nucleus is the central spheroidal

mass of basophilic granules. Blood-platelets are capable of ameboid mo-
tility. They vary in diameter from 2 to 4 microns, and in number per
cubic millimeter from 200,000 to 800,000. Analogous elements of avian,
reptilian and ichthyoid bloods are nucleated spindle cells,, or true throm-
bocytes. AYright's observations on mammalian megakaryocytes furnish
at present the best data for the genetic interpretation of blood-platelets.
However, almost every conceivable mode of origin, notably from ex-
truded nuclei of erythrocytes, and fragmenting leukocytes have had, and.
still claim, prominent supporters.

Granulocytes. The granulocytes comprise three varieties distin-
guished on the basis of their cytoplasmic granules: (1) neutrophils: (2)
eosinoplnls (o.rypliils) and (3) basopliils, or mast leukocytes. The nu-
cleus is of the polymorph type, perhaps occasionally, polynuclear. This
nuclear condition consists in a commonly crescentic chain of nuclear
masses connected by frequently extremely delicate nuclear strands.

The NEUTROPHILS are characterized by their fine cytoplasmic gran-
ules, having a neutrophil staining reaction (lilac color) in mixtures of
acid (eosin) and basic (methylene blue) dyes. They range in size
from 7.5 /u. to 10 /u, in diameter. They are predominantly phagocytic.
They constitute in normal adult life about 70 per cent, of the total white-
cell blood content.

210 BLOOD

The EOSIXOPHILS contain larger spheroidal cytoplasm ic granules
which show a special affinity for eosin. They are slightly larger than the
neutrophilic granulocytes, and comprise about 4 per cent, of the leuko-
cytes of normal blood.

The BASOPHILS are characterized by an extremely variable polymor-
phous nucleus, but especially by their spheroidal and irregular basophilic
granules of greatly varying sizes. They occur to the extent of only about
0.5 per cent, in the circulating blood. They are of approximately the
same size as the eosinophils. Their significance and genetic relationship
is uncertain, but they are usually interpreted as degenerating granulo-
cytes, the granules being variously regarded as products of nuclear frag-
mentation, and as cytoplasmic products of mucoid degeneration. Maxi-
mow (Arch. mikr. Anat, 83, 1, 1913), however, regards the 'mast cells'
of the blood as specialized kinds of granulocytes, distinct from similar
cells of the tissues, and without sign of degeneration.

Cowdry has demonstrated mitochondria, by vital staining with janus
green, in all types of leukocytes, except mast leukocytes, including plate-
lets. The lymphocytes and polymorph neutrophils contain them abun-
dantly. They are only sparsely present in eosinophils. Mitochondria are
said to be totally absent in the erythroplastids of normal adult human
blood (Intern. Monatschr. Anat. u. Physiol., 31, 4, 1914).

P. Ehrlich in a series of communications announced that by coloring
the leukocytes with various stains he was able to distinguish by their
reaction, several types of granules. These he called ( a ) oxyphil or acido-
phil, which were deeply stained by eosin, acid fuchsiii, etc.; (/?) amphophil,
which were stained both by eosin, and by dahlia and like dyes ; ( y ) baso-
phil, which were stained deeply by dahlia, thionin, etc. ; ( S ) certain cells
which neither after staining with eosin, etc., nor with dahlia, etc., could
be made to show any granules other than the nodes of cytoreticulum ; ( e )
neutrophil, which can be stained only by a due admixture of acid and basic
dyes, as of fuchsin and methylene blue, or the so-called 'triacid mixture'
of Ehrlich.

The demonstration of these characteristics presupposed a division of
dyes into three primary classes :

1. Acid e.g., eosin, orange-G, acid fuchsin, aurantia, erythrosin.

2. Basic e.g., methylene blue, dahlia, thionin, hematin.

?). X i' u I nil which are only formed by the interreaction of ex-
amples of each of the two preceding classes ; the neutral dye
is supposed to arise de novo in such mixtures, as a result of
chemical reaction.

HEMOGLOBIN

211

The application of such a classification of stains to other tissues than
the blood, has, however, been found to present considerable difficulties.

According to Kite the cytoplasm of the polymorphonuclear leukocytes
has nothing of the nature of a cell membrane, but they are completely
naked, nor do they contain a spongioplasm and hyaloplasm. "The cyto-
plasm is a jelly in which are embedded large numbers of globules." The
structures usually termed
cytoplasmic granules are of
the nature of separation
products ; they do not grade
into the surrounding cyto-
plasm. All leukocytes un-
dergo also certain definite
structural transformations,
characterized by the appear-
ance of pseudopods chang-
ing into vibratile cilia. Kite
suggests that the protoplas-
mic processes may be prom-
inently concerned in phago-
cytosis. Under certain con-
ditions erythroplastids may
be made to protrude similar
processes (Jour. Infect.
Dis., 15, 2, 1914).

FIG. 225. OUTLINE DRAWINGS OF LIVING POLY-
MORPHONUCLEAR LEUKOCYTES OF RABBIT,
FROM A DROP OF BLOOD MIXED. WITH RINGER'S
SOLUTION TO WHICH A SMALL AMOUNT OF
HIRUDIN HAD BEEN ADDED TO PREVENT COAG-
ULATION.

HEMOGLOBIN

Hemoglobin is

In the course of half an hour the cells develop
retractile undulatory processes, a, hyaline-sur-
face phase; x, hyaline layer; 6 and c, ciliated
phase; d, flagellated phase. Leukocytes of all
classes of vertebrates undergo similar changes.
(After Kite, Jour. Infectious Dis., 15, 2,
1914.)

a very

complex chemical compound
of iron with a globulin; it
gives the characteristic color
to the blood. It combines

readily with oxygen to form oxyhemoglobin, a loose chemical combina-
tion by which the oxygen is carried from the lungs to the tissues, and
which gives the brighter red color to the arterial as compared with the
venous blood. The hemoglobin is held either in solution or in unstable
chemical union by the cytoplasm of the erythroplastids. It escapes from
these corpuscles after rupture, or it may be extracted by ether, and is

212

BLOOD

then prone to crystallize on evaporation in the form of minute brownish-
yellow prisms. The crystals of the various species of any genus belong
to a crystallographic group (Reichert) but generic differences are fre-
quently striking; thus, in human blood they are long rhombohedra (Fig.
227), in guinea pig, tetrahedra, in squirrel, hexagonal plates, in rat,

FIG. 226. SECTION OF BONE MARROW FROM SKULL OF 25 MM. TURTLE EMBRYO
(CHELYDRA SERPENTINA), SHOWING THREE MAIN STAGES IN THE HEMAPOIESIS.

L, hemoblast (lymphocyte), differentiating in the mesenchyma and passing into
a blood-vessel; Me, blood mother cell (hemoblast); Mg, megaloblast ; Eb, erythro-
blast; EC, erythrocyte; E, endothelial cell; Mes, mesenchymal cell; PC, pigmented
cell. Helly fixation; Giemsa stain. X 700.

elongated six-sided plates, in hamster (a rodent), rhombohedra, and in
dog they appear as rhombic prisms which are diamond shaped in cross-
section.

Various other crystalline, and also amorphous hemoglobin derivatives
may occur as decomposition products. The iron of the coloring matter
of the hemoglobin may be thus obtained in the form of he matin, a
soluble, amorphous protein compound of a brownish-red color. If he-
matin is combined with hydrochloric acid the chlorid of hematin, hemin,
is produced. Hemiri occurs in deep brownish-red crystals, known also as
Teichmann's crystals, which differ somewhat according to the animal

HEMOGLOBIN

213

species from which they sire, obtained; those of human blood take the
form of triclinic plates (Fig. 228). Hemin crystals derive a certain
importance as a forensic test for the presence of blood, and they may
be obtained from old and dried-up specimens as readily as from fresh
blood. The procedure for testing a suspected stain consists in heating

to the boiling point in a drop
of acetic acid, a drop of a nor-
mal salt solution of the speci-
men. From fresh blood the
crystals may be produced by
heating together on a slide a
drop of blood, a grain of so-
dium chlorid, and a drop of
acetic acid. Hemin crystals
prove only that hemoglobin is
present, but give no precise in-

FIG. 227. HEMOGLOBIN CRYSTALS.

a and b, from human blood; c, from the cat;
d, from the guinea-pig; e, from the hamster; /,
from the squirrel. (After Ranvier.)

FIG. 228. CRYSTALS OF
CHLORID OF HEMATIN OR
HEMIN.

(After Ranvier.)

formation as to the species from which the blood in question came, for
the crystals obtained from many mammals are apparently identical.

Hematin may decompose also into Jiemosiderin, an iron-containing
hemoglobin derivative, in the form of light-brown granules, frequently
found in phagocytic leukocytes sis the product of cellular digestion of
effete erythroplastids. Hemosiderin granules thus appear in the spleen
and bone-marrow. Iron in the tissues, and ferruginous pigments gen-
erally, can be recognized by sipplication of the ferrocyanid test, which
stains the iron blue.

214 BLOOD

When extravasations of blood occur within the tissues of the body,
as, for example, in the corpus hemorrhagicum of the ovary, the hematin
is frequently deposited as liematoidin, an iron-free derivative of hemo-
globin which forms stellate groups of yellowish needle-like crystals. He-
matoidin is apparently identical with bilirubin, a bile pigment.

COAGULATION

According to Howell's theory of coagulation, prothrombin, probably
produced at least in part by disintegrating platelets, in the presence of
calcium becomes converted in thrombin. The latter precipitates from the
fibrinogen of the blood plasma the fibrin needles which mass to produce
a mesh in which the corpuscles become aggregated to form the thrombus
or clot. Howell has recently studied with the ultramicroscope the process
of coagulation in oxalated blood plasma and solutions of fibrinogen to
which a solution of thrombin was added. He describes clotting as pro-
ceeding after the manner of crystal formation; the crystals begin as
granules which adhere to form threads. Clotting is 'an aggregation of
the invisible particles (amicrons) to visible particles and then the further
consolidation of these particles into rigid looking needles' (Amer. Jour.
Physiol., 35, 1, 1914).

HEMAPOIESIS

A consideration of blood development involves the questions of the
sources of primary origin and the genetic relationship of the different
varieties of cells. The blood-forming or hemapoietic organs comprise (1)
the yolk-sac; (2) body mesenchyme and endothelium of primitive blood-
vessels of the embryo; (3) liver and spleen; assisted by lymph organs in
the production of lymphocytes, and finally (4) marrow of fetal and adult
bone. These several sources function in development in the order enumer-
ated, though the successive stages overlap to some extent. With the
assumption of function on the part of bone-marrow the earliest foci being
the scapular, pelvic, vertebral and costal elements the other blood-forming
organs cease activity. However, in certain diseases the spleen may possibly
be stimulated to renewed function; and lymph organs function throughout
life in the production of lymphocytes. From the standpoint of the germ
layers hemapoiesis is more probably limited to the mesoderm (mesenchyme).
This is certainly true largely at least, probably completely, of sources
outside of the yolk-sac.

EEMAPOIESIS

215

The yolk-sac wall is the earliest locus of blood-cell origin. This struc-
ture is a vesicle lined by columnar entodermal cells, invested by mesen-
chyme, the surface cells of which become arranged in the form of a mem-
brane, the mesothelium. The first anlage of blood appears in the shape
of irregular masses and cords of cells next the entoderm. These cords
anastomose at the same time that they acquire lumina through a process
which involves the peripheral
differentiation of cells into
endothelium and the appear-
ance of plasma in which the
central cells are suspended.
The very intimate spatial re-
lationship of these blood-
islands to the entoderm has
led many to incline to an en-
todermal origin of the earliest
blood anlages. The layer in
which blood first appears in
the yolk-sac has been named
angioblast, a term which does
not commit one to any view
as to primitive germ layer
origin. However, the impor-
tance of the matter of origin
seems great only when one
believes in the strict specifi-

FIG. 229. WALL OF YOLK-SAC OF A 13 MM.
HUMAN EMBRYO (Fie. 210), SHOWING A
SMALL BLOOD ISLAND (B. I.) AND SEVERAL
SMALL BLOOD VESSELS CONTAINING ERY-
THROCYTES.

The wall consists of stratified columnar and
cuboidal entodermal cells (to the right), a
middle mesenchymal layer (angioblast), and a
covering of mesothelium. X 240.

city of germ layers. Such
position is hardly tenable in
view of the fact that origin-
ally there is only one germ
layer, the ectoderm, and the
origin of the mesoderm from

the primitive streak, a phase of fusion of ectoderm and entoderm. More-
over, in certain forms, e.g., Tarsius, a primate, it is claimed by Hubrecht
that mesoderm has a double origin from ectoderm and entoderm, as well as
from primitive streak. Again in subsequent early embryonic stages it is
believed by many that blood-cells arise by process of differentiation of body
mesenchyme. In the further discussion of hemapoiesis we may take for
granted the origin of blood exclusively from mesenchymal elements.

Regarding the question of the original blood mother-cell two sharply
contrasting views are held, expressed in the monophyletic ( Unitarian) and
polyphyletic (dualistic) theories of blood-cell origin. The former holds
that all types of blood elements, red and white, have their origin directly
in one and the same primordial blood cell ('hemagonium,' hemoblast) ; the

216 BLOOD

several types are conceived to arise through process of differentiation along
distinct lines. The polyphyletic theory holds to a dual origin, from geneti-
cally distinct mother-cells, for red and, white cells; or to a multiple
origin, tracing erythrocytes and the several varieties of leukocytes each
along different lines of differentiation to different mother-cells. The later
investigations into this problem of blood-cell origin done with an admit-
tedly superior technic tend to show that the monophyletic view is correct.
This was first well supported by the work of Saxer, who gave the name

G/'

FIG. 230. LARGE BLOOD ISLAND FROM (Fie. 210), A 13 MM. HUMAN EMBRYO.

a 1 and a 2 , mesenchymal cells; a 1 is differentiating into an endothelial cell; a 3 , endo-
thelial cells becoming separated from wall to form hemoblasts ('lymphocytes');
b l and fe 2 , hemoblasts (mesameboids) ; c, megaloblasts; d l and d 2 , normoblasts; R,
binucleated giant cell. X 750.

'primary wandering cell' to the common blood-mother cell ; more recently
by the work of Maximow, who applies the name 'lymphocyte' (primary
lymphocyte) to this cell, on the ground of its resemblance to the large
lymphocyte of adult blood. This lymphocyte (hemoblast) is according to
Maximow originally a cell of the general mesenchyrna, the earliest differen-
tiation stages of which are characterized by increase of basophily of the
cytoplasm, separation from the general syncytium, and assumption of
ameboid properties. These steps involve blood-island stages.

We may now trace the steps through which the primitive blood-cell
passes in the process of attaining the adult condition of the various types
of cells. Of two daughter-cells one differentiates into an erythroblast ; the
other may remain as a primitive blood-cell to further function as a mother-
cell; at the same time primitive blood-cells may continually differentiate
in adult life from the mesenchyme of bone-marrow. An alternative view

BONE-MARROW 217

accepted by some, e.g., "Minol,- -;nul still in accord with the rnonophyletic
teaching regards the later eml>rv<mie, fetal and adult hemapoietic organs
as simply foci of proliferation and differentiation of primordial blood-cells
(hemoblasts) originally derived from the angioblast and subsequently
carried by the blood stream to these locations (red marrow, etc.) where they
persist throughout life.

We will follow first the several steps in the developmental process of the
red element, to which taken together the name 'erythrocyte' may be appro-
priately applied. According to Maximow, in the forms studied by him,
there are two lines of erythrocytes, a primitive and a definitive line; the
primitive line dies out after a brief span, and, since the definitive line
diners only in the matter of smaller size of cells, we may confine our atten-
tion to that line.

The several stages in the differentiation process are: (1) megalollast;
(2) norm.ollast; (3) erythrollast and (4) enjtliroplastld ('erythrocyte').
All except the last may multiply by mitosis. The megaloblast differs from
its progenitor, the hemoblast, in having somewhat more cytoplasm, and a
small amount of hemoglobin, which gives it a light reddish-brown color.
Its nucleus is relatively large and vesicular and contains a delicate gran-
ular network; this stage corresponds to the ichthyoid stage of Minot; a
seemingly appropriate terminology, since it calls attention to the similarity
between the adult (phylogenetic) stage of a lower form, and the embryonic
(ontogenetic) stage of a higher form. The normal/last is a daughter-cell of
the megaloblast and is of somewhat smaller size, containing more hemo-
globin, with a somewhat denser nucleus, with larger net-knots; this corre-
sponds to the sauroid stage of Minot, the significance of which term is the
same as explained above for ichthyoid. The erythroblast differs from the
normoblast in having an increased amount of hemoglobin, but mainly in
its smaller, more compact nucleus. This cell becomes an erythroplastid
through loss of nucleus. (It conduces to simplicity and clearness to regard
the megaloblast and normoblast as two developmental phases of the erythro-
blasts.) The manner by which the nucleus disappears has been much
disputed. It has been held to be absorbed (karyolysis) ; Howell has de-
scribed its extrusion either as a single or fragmented body (karyorrhexis)
in the cat; Emmel (Amer. Jour. Anat., 1<, 2, 1914) has recently de-
scribed for pig a process by which the red corpuscle arises through budding,
leaving a nucleated remnant.

Certain erythroblasts may be smaller than the average, others larger;
these dimentionally atypical forms are termed respectively microcytes and
megalocytes.

The large lymphocyte of the blood is believed to be derived from the
primitive blood-cells by slight differentiation; perhaps it represents a po-
tential hemoblast. The small lymphocyte is simply a daughter-cell of a
large; a large, a grown small lymphocyte.

218 BLOOD

The primitive blood-cell may by slight differentiation become a leuko-
l>last; according to whether the cytoplasm elaborates neutrophilic, acido-
philic, or basophilic granules, it becomes a polymorphonuclear neutrophil,
eosinophil, or basophil ('mast-cell') leukocyte. The transition stage, from

FIG. 231. DIAGRAMMATIC ILLUSTRATIONS OF SUCCESSIVE STAGES IN THE TRANS-
FORMATION OF THE MAMMALIAN ERYTHROCYTE (a) TO FORM THE EUYTHRO-
PLASTID (/).

b and c, by extrusion of the nucleus as a whole; d and e, by extrusion of the frag-
mented nucleus.

the standpoint of the nucleus, between the leucoblast with spherical nucleus
and the granulocyte with polymorphous nucleus, is the large mononuclear
leukocyte (transitional leukocyte). According to Kyes (1915), certain large
mononuclear leukocytes are derived from the reticulum of lymph nodes. Both
the reticular cells and their leukocyte derivatives are said to be phagocytic.
Giant cells are derived from the leukoblast, or perhaps primitive blood-
cell, along a separate line of differentiation, characterized by absence of cy-

FIG. 232. SUCCESSIVE STAGES IN THE ELIMINATION OF THE ERYTHROBLAST NU-
CLEUS, FROM HOMOPLASTIC CULTURES OF BLOOD OF A 32 MM. PlG EMBRYO.

This is regarded by Emmel as a 'somewhat imperfect case of constriction,' but
it illustrates the fundamental similarity between erythroplastid formation by ex-
trusion of nucleus (Howell) and by cytoplasmic constriction. (After Emmel, Amer.
Jour. Anat., 16, 2, 1914.)

toplasmic division, excessive growth, and giant or multiple nucleus. The
multinucleate condition is attained apparently by both mitotic and amitotic
division of the nucleus. From the megakaryocyte pseudopodia are derived
the blood-platelets as explained above. Blood development in marrow passes
through the same phases, the hemoblast stage here being generally known as
the myeloblast, and characterized by a considerable finely granular neutro-
philic cytoplasmic content. The above is given in outline in the following
scheme, adapted largely from the work of Maximow on hemapoiesis in the
rabbit embryo. (Arch. mikr. Anat., Bd. 73, 1909.)

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220

BLOOD

BONE-MARROW

The red variety of bone-marrow, found in the flat bones generally
and in the epiphyscs of long bones, functions as the sole hemapoietic or-
gan of later fetal and adult life. According to certain authorities it is
assisted in this function to some extent by the spleen. Besides a hema-
poietic function, red bone-marrow possesses also the capacity of de-

)> m m -&^j&/\

i rfi ^t. 1 P^^ ->

a'.-, y ^S^FT \

<Sfe5 \

&&r~*FiA -, -1.

VIG. 233. FROM A SECTION OF RED MARROW OF A HUMAN BONE.
a, giant cell; b, leukocytes; c, nucleated red blood cells; d, mitosis in a marrow
cell; e, outline of a fat cell; /, reticulum; g, mitosis in a giant cell. X 680. (After
Bohm and von Davidoff.)

stroying worn-out red blood-corpuscles. In this process it is assisted
greatly also by the spleen and lymphoid organs generally. The phago-
cytic leukocytes of these locations are largely active in this destructive
process and in the transportation of the hemoglobin debris to the liver
where as hematoidiu it is apparently appropriated in the manufacture
of the bile pigment, bilirubin.

The generic name for the specific hemogenic cells of marrow is
ntyelocyte. This includes the parent blood-cell (hemoblast) and the
intermediate developmental stages of both white (lymphocytes, mono-
nuclear leukocytes leukoblasts) and red (megaloblast, normoblast,
erythroblast stages) cells. Besides these, there are of course abundantly
present also the adult forms of blood-evils both white (eosinophil, neii-
trophil, and Iwsopliil polymorphonuclear leukocytes, and lymphocytes)
and red (erythroplastids) . Potential osteoblasts and osteoclasts are

BONE-MAEROW

221

also present, but indistinguishable from the lymphocytes and hemogenic
polykaryocytes respectively.

A description of the cells in their order of hemogenic cytomorphosis
follows :

1. Myeloblast (I'reinyelocyte; Hemoblast, Mesameboid Cell; Prim-
itive Blood Cell; 'Lymphocyte'). This is the parent blood-cell of bone-

**_*-. *.*

iy

FIG. 234. TYPES OF CELLS FROM A SMEAR PREPARATION OF THE MARROW OF A

HUMAN RIB.

1, red blood corpuscles; 2, nucleated red blood cells, erythroblasts; 3, small lympho-
cytes; 4, large mononuclear cells with neutrophil granules; -5, poly nuclear neutro-
phil; 6, eosinophil cells; 7, a basophil cell. Eosin and methylene blue. Noch's
stain. X 1200.

marrow. It produces by proliferation and slight differentiation the more
direct ancestors of both the white (leukoblast) and red (megaloblast-
erythroblast) cells. Mother- and daughter-cells are similar in their
relatively large granular nuclei, well developed cell-body, ameboid capac-
ity, and proliferative activity. The cytoplasm of the myeloblast is homo-
geneous or very finely granular and slightly basophilic; likewise the
leukoblast. The megaloblast may be distinguished by its slightly oxyphil
character due to 'the presence of a small amount of hemoglobin.

222 BLOOD

2. Lymphocytes. These include larger and smaller varieties. They
are similar to, and in part identical with, the above-described cells, the
myeloblasts. They include both cells differentiated from marrow and
cells transported by the blood stream. They are indistinguishable from
the osteoblast. In short, these several cells of similar characteristics may
be identical in their capacity to function as progenitors of blood-cells,
and may represent the parent blood-cell.

3. Large Mononuclear Leukocytes. These cells are distinguished
from the myeloblasts and lymphocytes only by their slightly modified
nucleus, and by the occasional presence of a small number of fine neu-
trophilic granules. The nucleus is oval or bean-shaped. It represents
a transition phase between the less differentiated lymphocyte stage and
the granulocytes. It contains a centrosome located usually in that por-
tion of the cytoplasm lying in the concavity of the bent nucleus. This
cell may proliferate extensively.

4. Polymorphonuclear Neutrophil Granulocytes. These include
a graded series of stages from the standpoint of shape of nucleus, and
amount of granular content. The younger stages contain a less com-
plicated nucleus, generally bean-shaped with centrosome and relatively
fewer (some basophilic, 'unripe') granules; these have a slight prolifera-
tive capacity. Older stages have progressively more complicated nuclei,
characterized by a lobulated chain (with from two to five segments) of
dense chromatin, and are no longer capable of mitotic division.

5. Eosinophil Granulocytes. These cells resemble the neutrophils
in their graded series of nuclear forms, ending in a lobulated poly-
morphous nucleus ; but differ in the matter of size and staining capacity
of the cytoplasmic granules. These granules are of fairly uniform size
and of spherical shape, but much larger than the neutrophilic granules,
and are strongly acidophilic, showing special affinity for the cytoplasmic
stain, eosin. In the younger forms the granules are basophilic. The
older types are identical with those of the blood. Again, only the less
differentiated, that is, those with oval nucleus and a centrosome, may
divide mitotically.

The commonly accepted view of the origin of neutrophilic and oxy-
philic cytoplasmic granules is that they arise intracellularly under nuclear
influence, perhaps from less differentiated nuclear extrusions or chro-
midia. Originally these granules are basophilic ('unripe'). However,
Weidenreich regards the eosinophil granules as the ingested hemoglobin
particles of degenerating and fragmenting erythroplastids. Their con-
siderable presence in red marrow and spleen where blood-cell disiutegra-

BONE-MAKROW 223

tion is extensive, lends weight to this hypothesis. Likewise Badertscher
(Amer. Jour. Anat., 15, 1, 1913) finds that eosinophil leukocytes and
free eosinophilic granules are very abundant in the vicinity of degenerat-
ing muscles in salamanders during the time when the gills atrophy, and
believes that the eosinophilic granules are ingested fragments of degener-
ated muscles and red blood-corpuscles. Eosinophils do undoubtedly in-
crease greatly in number during certain infectious diseases characterized
by extensive tissue disintegration, e.g., trirhiniasis; but disproof of intra-
cellular origin a teaching more in accord with our knowledge of cyto-
plasmic granule origin through protoplasmic activity demands direct
evidence of extensive granular ingestion, which is lacking. Moreover,
the microchemical nature of eosinophil granules differs from that of
hemoglobin ; also, they differentiate from basophilic granules and in
hemogenesis in the turtle, for example, eosinophils appear before hemo-
globin-containing cells are present. The free eosinophil granules in
degenerating tissues are more likely derived from disintegrating eosino-
phils, abundant in such regions.

6. Basophil Granulocytes(J/a,s- cells) .These are identical with
the mast leukocytes of the blood, and possibly also with the cells of this
name in connective tissue, the latter perhaps representing degenerating
phases of the former. They are characterized by a variable polymor-
phous nucleus, apparent lack of centrosome, extremely slight prolifera-
tive capacity, and presence of spheroidal non-uniform basophilic cyto-
plasmic granules. They are numerically increased in marrow and the
circulating blood and in the spleen in certain diseases.

7. Giant Cells or Myeloplaxes. These are relatively enormous
cells (of 30 to 100 microns diameter). They consist of an expansive
mass of homogeneous or finely granular slightly basophilic cytoplasm.
They may have either a single large, frequently lobulated annular, nucleus
(megakaryocyte) or several, even many, nuclei (polykaryocyte). Both
are probably derivatives of the parent lymphocyte or myeloblast. The
polylobular and multiple condition of the nucleus arises both through
mitoses (frequently multipolar) and amitoses. The polykaryocyte is
probably a later developmental stage of the megakaryocyte. These cells
are characteristic of hemopoietic foci. The polykar} T ocyte has been re-
garded as identical with the osteoclast. Nevertheless, their osteolytic
function can hardly be said to have been established ; the polykaryo-
cyte of the yolk-sac of the 10-millimeter pig embryo can be seen to
differentiate into erythrocytes, a hemoglobin-containing area developing

about the several nuclei, the whole finally breaking up into an equal num-
15

224 BLOOD

her of red cells. Giant cells are characteristic elements of all hemapoietic
organs. The megakaryocytes protrude long pseudopodia which segment
into blood- platelets (Wright), abundantly present in red marrow.

8. Erythrocytes. These cells include the several developmental
forms of red cells : (a) megaloblast, (b) normoblast, (c) erythroblast and
(d) erythroplastid. The megaloblast is very similar to the leukoblast ex-
cept that the cytoplasm contains a slight amount of hemoglobin, and
therefore gives an oxyphilic staining reaction. The nucleus is granular,
with a delicate chromatic network. This is the so-called ichthyoid stage of
Minot. Normoblast and erythroblast are closely similar stages (sauroid
stage of Minot), characterized by the relatively smaller and denser more
chromatic nucleus, and a relatively more extensive shell of cytoplasm
with increasingly more hemoglobin: The erythroplastid develops from
the erythroblast through loss of nucleus, generally by extrusion.

Evans (Amer. Jour. Physiol., 37, 2, 1915) has directed attention anew to
the phagocytic large mononuclear leukocytes, the 'macrophages' of Metsch-
nikoff (1892). On the basis of a specific response to vital azo dyes he iden-
tifies them as a group distinct from the large mononuclear elements and
lymphocytes of the blood, and includes among them certain endothelial and
reticular cells and the 'clasmatocytes' (Ranvier) or 'resting wandering cells'
(Maximow) of connective tissue,- all of which may become free macrophages.
These cells in mammals, of round or elongated shape, range in diameter
from about 10 to 30 microns; they contain a stoutly cresentic nucleus of
irregular contour and excentric position ; the . cytoplasm is weakly baso-
philic, covered with delicate pseudopods of various sizes, and frequently
filled with large vacuoles. As endothelial cells they may line the capillaries
and venules of the liver (Von Kuppfer cells'), spleen, red bone-marrow,
hemal glands, and the lymphatic sinuses of lymph nodes. They include
also reticular cells of lymph nodes, spleen pulp and bone-marrow, and the
clasmatocytes of connective tissue. As free cells they occur in the serous
cavities, lymph sinuses of lymph nodes, spleen and hepatic capillaries.
They are abundant in traiisudates and exudates in serous cavities. Only
under pathological conditions do they appear in the peripheral blood stream.
Weidenreich identified them with the large mononuclear leukocytes of the
blood and lymph. Evans' experiments, on the contrary, give no indication
that leukocytes are converted into these cells. They originate chiefly from
endothelia. They are phagocytes and are active also in the normal physio-
logical processes. They handle the blood and bile pigments, and fats and
lipoids. The protoplasm of the macrophages is characterized especially
by its response to finely particulate matter. Macrophages share the func-
tion of phagocytosis with the polymorphonuclear elements of the blood.

CHAPTER IX
THE LYMPHATIC SYSTEM

The lymphatic series includes a system of lymphatic channels which
collect the lymph from the various tissues of the body and return it
to the large veins of the neck, where it mixes with the blood. In the
course of this lymph vascular system are various aggregations of lym-
phoid or adenoid tissue which occur in the form of lymph nodules or
follicles, lymph glands or nodes, and the lymphoid organs. These or-
gans are the tonsils, thymus, and spleen. The lymphatic vessels also
stand in intimate relation if not in direct communication with the
serous and synovial membranes and the bursse.

LYMPH

Like the blood, the lymph may be considered as a primary tissue
whose intercellular elements are entirely of a fluid nature. In most
portions of the body, lymph is a colorless fluid which is scantily provided
with corpuscular elements, the lympha-lic corfjuxrlrx. The lymphatic
corpuscles are identical with the leukocytes of the blood. In the lymph
most of these cells are of the mononuclear form, the small mononuclears
or lymphocytes being the most abundant. Lymph also contains a small
proportion of polymorphonuclear cells, which not only are derived from
the lymphoid tissues, but as wandering cells find their way into the
lymphatic vessels from the tissues generally. Blood-platelets are also
present in lymph.

The cells of lymph, predominantly of the small lymphocyte type, are
derived from the numerous lymphoid masses (nodes and nodules)
through which the lymph passes on its way from the tissues to the sub-
claviaii veins. According to Dana and Carlson (Amer. Jour. Physiol.,
vol. 25, 1909) the number of lymphocytes contributed to the blood daily
may be more than the total permanently present in the blood. Since the
number in a cubic millimeter remains fairly constant, a number must

225

226 THE LYMPHATIC SYSTEM

be daily consumed in the body equal to the number added to the blood.
Many of course actually suffer destruction, but it seems probable that
a considerable number also first undergo differentiation into granulocytes,
and perhaps as potential hemoblasts may function as parent cells of
erythrocytes.

In addition to the leukocytes lymph contains fat globules and glyco-
gen. These are mostly the products of absorption from the intestinal
tract, in which process the lymphatic vessels play an important role. In
the lymphatic vessels of the intestine during absorption fat globules are
so abundant as to impart to the lymph a milky white color ; this variety
of lymph is termed the chyle. These fat globules are rapidly removed
by the lymphoid organs, since even in the presence of abundant chyle
only comparatively few fat globules escape into the general blood current.
The lymph of other portions of the body than the abdominal region,
therefore, contains relatively little fat.

The lymph, unlike the blood, circulates in but one direction, viz.,
toward the heart. It must therefore be formed in the tissues generally.
The blood plasma constantly escapes through the walls of the capillary
vessels into the surrounding lymphatic spaces of the tissues. It is these
tissue spaces which have been considered as forming the beginning of
the lymphatic system. Eecent evidence, however, goes to show that the
tissue spaces are not directly connected with the lymphatic vessels, but
that just as the plasma exudes into the tissue spaces by processes of
secretion, osmosis, and filtration, so the li.^ue juices, as the predecessors
of lymph, enter the lymphatic vessels by similar processes of secretion,
osmosis, and filtration. Lymph is also formed by absorption, which oc-
curs chiefly in the alimentary tract.

Under similar conditions the lymph as well as the blood will coagu-
late, the fibrin forming a firm, colorless clot in which the leukocytes are
entangled. Because of their tendency to adhere to the sides of the
vessel thus circulating at the periphery of the current the lymph
cells are most likely to be found at the periphery in those post-mortem
clots which occur within the lymphatic vessels.

LYMPHATIC VESSELS

(Lymphatics)

The lymphatic vessels vary in size from that of the smallest capillary
vessels up to that of the thoracic duct. The smaller vessels, lymphatic

LYMPHATIC VESSELS

227

capillaries, form anastomosing meshes in ;ill tissues where blood capil-
laries are found. They are most abundant in the perivascular connect ivc
tissues, where they form a dense plexus about the wall of the blood-ves-
sels.

The wall of the lymphatic capillary, like that of the blood capillary,

FIG. 235. SUBCUTANEOUS LYMPHATIC VESSEL, OF A FETAL PIG.

At the right is a small blood-vessel. Hematein and eosin. Highly magnified.
(After MacCallum.)

consists of a single layer of endothelium. This endothelium probably
forms a complete lining for the lymphatic capillary and is continuous
through larger and larger vessels with that of the veins, from which,
according to Sabin (Amer. Jour. Anat., 1902), the lymphatics are
originally developed.

The relation of the lymphatic capillaries to the tissue spaces is not
as yet definitely settled. It was formerly thought that these spaces were

228

THE LYMPHATIC SVSTKM

continuous with the Lymphatic capillaries, but. the more recent observa-
tions, represented by those of MacCallum (.Johns Hop. IIosp. Bull.,
1903), seem to show that the capillaries of the lymphatic system, like
those of the blood vascular system, form a series of branching channels
which are open only kward the veins. According to this conception,
therefore, the tissue juices, formerly also considered as lymph, are con-
tained within a separate series of channels, the tissue spaces and lym-
phatic canaliculi, and they enter the true lymphatics only by processes of
osmosis and the secretory activity of the lymphatic endothelia.

FIG. 236. THE GROWING END OF A DEVELOPING LYMPHATIC VESSEL IN THE SUB-
CUTANEOUS TISSUE OF A FETAL PIG.

The lumen of the vessel has been filled with a dark injection mass. Highly mag-
nified. (After MacCallum.)

The lymphatic capillaries are of rather irregular caliber, generally
greater than that of blood capillaries/ and possess frequent sinus-like
dilatations, which peculiarity is also characteristic of the larger .lym-
phatic vessels.

The lymphatic capillaries soon acquire an adventitial sheath of fibro-
elastic tissue and pass into the xnntlh-r li/m/tlniHc /vx.sc/x. On attaining
a size of from 0.2 to 0.8 millimeter their wall is differentiated into the
same three coats which are found in the veins. Except for the fact
that they contain lymph instead of blood, these vessels closely resemble
the small veins, and like some of the latter vessels they possess frequent
valves.

LYMPHATIC VESSELS 229

The tunica intima of the lymph vessel consists of an endothelial
lining with a thin delicate fibro-elastic memhrane. The tunica media is
thin and contains circular smooth muscle fibers. The adventitia is the
thickest coat of the lymph vessel. It consists of fibro-elastic connective
tissue and longitudinally disposed bundles of smooth muscle fibers.

The wall of the lymph vessels is supplied with small blood-vessels and
nerves, in the same manner as the veins. The nerves form a plexus in

FIG. 237. LYMPHATIC AND BLOOD VESSELS IN THE HILUM OF A HUMAN LYMPH-NODE.
a, lymph vessels; b, blood-vessels. Hematein and eosin. Photo. X 160.

the adventitia from which branches are distributed to the media and
intima. Kytmanof (Anat. Anz., 1901) has traced the fine nerve fibrils
to the smallest lymphatic capillaries, where, as in the intima of the
larger vessels, they end in close relation to the endothelial cells.

To summarize : the lymphatic capillaries arise by one of three
methods :

1. As lymphatic plexuses in all connective tissues; the most abun-
dant of these are the perivaseular lymphatics.

2. As dilated pouches having blind extremities, as in the villi of
the small intestine, where they are known as lacteals.

230 THE LYMPHATIC SYSTEM

3. By direct communication with the stomata of the serous mem-
branes. The presence of true stomata in the serous membranes of man
with the exception of possibly certain portions of the peritoneum is dis-
puted.

The lymph is derived from the tissue juices and by absorption from
the alimentary tract, and is conveyed by the lymphatic capillaries to

FIG. 238. LYMPHATIC CAPILLARY FROM THE SPERMATIC CORD OF A DOG, SHOWING

NERVE ENDINGS.

a, nerve fibers. Methylene blue. Highly magnified. (After Kytmanof.)

larger and larger lymph vessels, which resemble the small veins in their
structure, and which finally empty into the subclavian veins of the neck,
at their junction with the internal jugulars.

The main lymph channels are the thoracic duct on the left, and the
right lymphatic duct. Only the thoracic duct drains the abdominal
lymphatics and is thus much the larger vessel. Toward its distal end
it expands into a receptacle for the absorbed chyle, the cisterna chyli.

THE DEVELOPMENT OF LYMPH VESSELS

According to Sabin the mammalian lymphatic system has its primary
origin in two paired and one unpaired venous sprouts : the jugular, inguinal
(sciatic), and mesenteric (retroperitoneal) lymph sacs. Certain investi-
gators (Huntington, Mem. Wistar Inst., 1911; McClure, Anat. Eec., 6, 6,

THE DEVELOPMENT OF LYMPH VESSELS 231

1912, and others) interpret these sues as tho products of fusions of still
more primitive discrete lymphatic milages which arose as mcsenchymal
spaces; and their connection with the subclavian, sciatic and renal veins
as secondary unions. Sabiii and others regard the lymphatic endothelium
once having sprouted from the venous endothelium as strictly specific, and
the entire lymphatic system as a derivative by sprouting and fusion of
these three sets of anlages.

Huntington and McClure derive the definitive lymphatic system by
a progressive fusion of isolated mesenchymal spaces (mainly in the extra-
iiitimal portion of disappearing veins) and cells in the paths of the
future lymphatic trunks. According to the one school lymphatic endo-
thelium. can arise only by proliferation of preexisting endothelium ; accord-
ing to the other, endothelium can continually differentiate from young
mesenchyma.

The recent observations of Clark (Anat. Rec., 3, 4, 1909) on the
growing lymphatics in the tail of living frog tadpoles where the process
of sprouting could be clearly followed, leaves no room for doubt that
lymphatics spread through sprouting, but the material and data give no
information as to the manner of origin of the initial anlages, which is
the real question at issue. It is perhaps as yet too early to decide the mat-
ter on the basis of available evidence, but the extensive histologic data of
Huntington and McClure strongly support their claim of primary lym-
phatic origin by confluence of isolated mesenchymal spaces.

The beautiful injections of Miss Sabin which show a progressively
enlarging continuous system in pig embryos apparently flatly contradict
this hypothesis ; but the objection cannot be fairly ignored that the advo-
cates of lymphatic origin through fusion of isolated spaces base their
claims on appearances before the establishment of a continuous system
or even the several sets of lymphatic sacs, and the further fact that the
injection method is unsuitable for revealing lymphatic anlages existing
as isolated spaces. As concerns endothelium in general, Huntington
(Amer. Jour. Anat., 16, 3, 1914) regards an endothelial cell as simply
an adaptive form of a mesenchymal cell, 'modified in accordance with
definite hydrostatic and other purely mechanical factors,' resulting from
the presence of blood or lymph. On drainage of the fluid and consequent
release of pressure, the endothelial cell is believed to be capable of again
reverting to 'the type of the indifferent mesenchymal cell.' Kampmeier
(Amer. Jour. Anat., 17, 2, 1915) presents evidence from a study of sec-
tions of the young toad embryo apparently demonstrating the primary
origin of lymphatic endothelium only from venous endothelium ; but the
primary sacs and ducts arise by a confluence of these earlier discrete
venous buds. A concise discussion and summary of this subject is given by
McClure (Anat. Rec., 9, 7, 1915.)

232

THE LYMPHATIC SYSTEM

THE SEROUS MEMBRANES

The serous membranes form closed sacs which line the great cavities
of the body and are reflected over the viscera to form a double covering,
the two layers of which are freely movable over one another. Of these
two layers the one, the parietal layer, is attached to the wall of the body
cavity, the other, the visceral layer, covers the surface of the inclosed
organ.

The serous membranes consist of a mcsothelial lining and a support-
ing membrane of areolar connective tissue which is richly supplied with

capillary blood-vessels and lym-
phatics. The mesotheliurn con-
sists of large flat cells, pave-
ment epithelium, whose ser-
rated margins are firmly united
by an intercellular cement sub-
stance. Here and there mi-
nute openings are seen which
are surrounded by very small
mesothelial cells; these stomata
have been found to be in cer-
tain instances directly connect-
ed with the lymph vessels.
Some regard them as transient fenestra, others as artifacts.

Tunica Propria. The mesothelium rests upon a layer of areolar
tissue which is richly supplied with small blood-vessels and lymphatics,
forming an abundant vascular plexus beneath the mesothelium. The
serous membrane is either directly united to the wall of the cc.vity and
the surface of the organ which it envelops, or it may be attached by a
loose layer of sub mesothelial connective tissue.

The thickness of the mesothelial cells varies in different portions
of the serous membranes and is somewhat dependent upon the age of the
individual. In most portions it is no more than a pavement epithelium,
but over the surface of the functionally active ovary these cells are
much thickened and acquire a cuboidal shape ; thus it forms the 'germinal
epithelium' of the ovary. In young individuals, viz., in fetal life and
early childhood, the cuboidal cell type is found in many portions of
the peritoneum, pleura, and pericardium.

The synovial membranes resemble the serous in their structure. They

FIG. 239. TRANSECTION OF THE PERICAR-
DIUM OF A CHILD.

a-a, mesothelium; b-b, submesothelial con-
nective tissue. Hematein and eosin. Photo.
X 500.

LYMPH NODULES

are clothed by a single layer of pavement cells which is said to be in-
complete in places. Its mesothelium (meseiiehynial epithelium) is sup-
ported upon a layer of
firm fibrous tissue
richly supplied with
both lymph and blood
capillaries. In the re-
cesses of the joints the
synovial membranes
are frequently thrown
into small villous
folds, which are chief-
ly formed by the inner
portion of the fibrous
coat and are covered
with mesothelium ;
these are the synovial
villi.

The lursce and the
synovial sheaths of the
tendons are of similar
structure.

Both the serous
and the synovial mem-
branes are moistened by fluid which contains leukocytes in small num-
bers, and closely resembles the lymph and tissue juice in its composition.

FIG. 240. SECTION OF A VASCULAR SYNOVIAL VILLUS
FROM THE KNEE JOINT OF A CHILD.

Hematein and eosin. Photo. X 200.

LYMPH NODULES

(Lymph Follicles)

The lymph nodule is a structural unit of lymphoid tissue which may
exist independently, as in the solitary nodules of the intestinal tract, or
may form groups or accumulations consisting of a greater or less number
of nodular units. In this latter condition they occur in the mucous
membrane of the small intestine as Peyer's patches, in the tongue as the
lingual tonsil, in the fauces as the faucial tonsils, in the pharynx as the
pharyngeal tonsil, in the wall of the laryngeal cavity, in the spleen as
the Malpighian (splenic) corpuscles, in the lymph nodes as the peripheral

234

THE LYMPHATIC SYSTEM

lymph nodules, and in the thymus, where we may consider the lohule
of the organ as being the structural equivalent of a lymph nodule.

The lymph nodule consists of a mass of lymphoid tissue, usually of
ovoid form, which is surrounded by or embedded in connective tissue. In
those locations where it exists independently the nodule is completely

FIG. 241. A LYMPH NODULE, SOLITARY FOLLICLE, FROM THE LARGE INTESTINE OF

MAN.

In the upper part of the figure the edge of the intestinal mucosa is shown; it con-
tains many secreting tubules which have been cut in transverse or oblique section
and are lined by columnar epithelium and goblet cells. Photo. X 80.

surrounded by the connective tissue in which it lies. In other places,
as in the lymph nodes, the nodule is only partially surrounded by the
connective tissue trabeculae of the organ. Not only do fine branches
from the surrounding connective tissue bundles penetrate the periphery
of the nodule, but the reticulum of the nodule is continuous with these
trabeculae, thus forming a supporting stroma in which the lymphocytes
are embedded.

THE LYMPH NODES 235

The lymphocytes are loosely packed in the center of the nodule, and
in this portion cell division by mitosis is most active. This central por-
tion is the germinal center of Flemming. The germinal center is sur-
rounded by a denser circumferential layer of lymphoid tissue in which
cell division is less active. Between this denser portion and the sur-
rounding connective tissue the lymphocytes are again more loosely
packed, and over a greater portion of the nodule are separated from the
trabeculae by a lacuna-like space, the peripheral lymph sinus.

The nodule is usually supplied with a thin-walled artery, occasionally
two, which penetrates to the middle of the nodule to form a wide
meshed capillary plexus. The capillaries, at the periphery of the nodule,
unite to form two or more veins, which are contained in the adjacent
connective tissue.

The lymph cells are mostly of the morionuclear type of leukocyte, the
small mononuclear or lymphocyte type being the most abundant. Poly-
morphonuclear and eosinophil leukocytes are also found in the lymph
nodules, though in much smaller numbers. Mitosis is most frequently
observed in the large mononuclear type. Because of the nomadic tend-
encies of the leukocytes the boundaries of the lobule are not always
sharp, the lymph cells frequently infiltrating the surrounding connective
tissue so as to render it most difficult to distinguish the latter from the
true lymphoid tissue of the nodule.

THE LYMPH NODES

{Lymph Glands)

These structures occur in the course of the lymph circulation in vari-
ous parts of the body. They are found in the neighborhood of the
large joints, as in the axilla, the groin, the popliteal space, in the pre-
vortebral and mediastinal connective tissue of the abdominal and thoracic
cavities, and in the mesentery. They are frequently in relation with
the large arteries, e.g., the renal, internal and external carotids, etc.

Each lymph node consists of a mass of nodular lymphoid tissue in-
closed within a nbro-elastic connective tissue capsule. The capsule also
contains a little smooth muscle tissue, but this is never so abundant as to
form any considerable portion of the fibrous membrane ; in fact, as com-
pared with the somewhat similar capsule of the spleen, that of the lymph
node is notably deficient in smooth muscle.

236

THE LYMPHATIC SYSTEM

fife 4 u //>

Cor 4

AII tiff err n I h/nijili vv.s.sW, pursuing its course within tin; capsule,
enters the lymph node by a number of subdivisions which penetrate the
deeper layers of the capsule and open into a peripheral lacunar space,
the ly ni />li. N/////.S-, which separates the inner surface of the capsule from
the adjacent lymphoid tissue, but which is bridged across at frequent
intervals by the fine strands of lymph reticulum.

The lymphoid tissue, which forms the substance of the node, consists

of a dense peripheral
/essek portion, the cortex.,

for m e d by closely
packed lymph nodules,
and a looser medulla in
which are columnar ac-
cumulations of dense
lymphoid tissue, the
lymph cords.

Cortex. The nod-
ules of the cortex are
partially separated
from each other by sep-
tum - like trabeeulae
which extend inward
from the fibrous cap-

"" lp > * lld ^"S wllidl

the peripheral lymph
sinuses are continued

into the substance of the node to partially surround its lymph nodules.
Each lymph nodule is thus surrounded, except at its central pole, by
a peripheral lymph sinus, into which the afferent lymphatic vessels pour
their contents. The lymph on entering the gland is thus permitted to
enter the spaces of the reticulum and percolate through the lymph
nodules of the cortex before it can reach the looser portions of the
medulla. Each of the nodules of the cortex contains a germinal center
in which lymphocytes are actively formed by mitosis, and from which
the lymphocytes readily escape along the lymph channels of the reticu-
lum into the more open meshes of the medulla.

Medulla. The medulla occupies the center of the gland, and at
one point, the hilum, it reaches the surface. At this point a considerable
mass of fibrous trabeculae enters the medulla, carrying with it the larger
blood-vessels to be distributed to all portions of the gland. The finer

iyt>Ji fosse]

FlO. 242.-D1AOBAMMATIC ILLUSTRATION OK A LYMPH

NODE.

THE LYMPH NODES

237

ramifications of these medullary trabeculae are continuous with those
of the corfcx.

FIG. 243. TRANSECTION OF A CERVICAL LYMPH NODE OF A DOG.

The denser portions of lymphoid tissue are light in the figure, a, medullary cord
of dense lymphoid tissue; 6, looser lymphoid tissue of the cavernous medulla; c,
capsule; F, dense lymph nodule of the cortex; HF, fibrous tissue containing the large
vessels of the hilum; s, peripheral lymphatic sinus; F, blood-vessel. Magnified
several diameters. (After Ranvier.)

The lymphoid tissue of the medulla is divisible into the denser branch-
ing lymph cords, in which the lymphocytes are closely packed, and the

FIG. 244. TRANSECTION OF A MESENTERIC LYMPH NODE OF A MAN.
Hematein and eosin. Photo. X 38.

intervening pulp spaces, in which lymphocytes are less numerous, and
the reticulum of which is' continuous with that of the cortical nodules.

238

THE LYMPHATIC SYSTEM

The pulp spaces are broad channels, which are occupied by a reticu-
lum whose meshes are partially filled with lymphocytes. They are
bounded by a layer of endothelioid cells which everywhere incloses the

denser lymph cords. The function of
these cords would seem to be comparable
to that of the peripheral lymph nodules.
The pulp spaces are open toward the
cortex, whence they receive the afferent
lymph after it has percolated through the
nodules, but toward the hilum the spaces
are continued into the efferent radicles of
the lymph vessels which, in the connective
tissue of this part, unite into larger
trunks, and finally form several efferent
lymph vessels of considerable size.

The reticulum of the lymph gland is
a close-meshed network of interlacing fi-
brillar bundles, which are here and there
clasped by flattened endothelioid connec-
tive tissue cells. Eeticulum is but poorly
stained with either acid or basic dyes, is
destroyed by acids and bases, but is not
digested by pancreatin. After prolonged
action of Weigert's specific stain for elas-
tic tissue it is but slightly colored.

Lymph Cells. The great majority of
these cells are of the small mononuclear
or lymphocyte type. Large mononuclear
cells with a considerable cytoplasmic body
are also very numerous. Polymorphonu-
clear neutrophil leukocytes, though of
frequent occurrence, are less abundant
than the previous varieties. Eosinophil
cells are present in small numbers, and
large basophilic mast-cells are occasionally seen, though according to
Carlier (Jour. Anat. and Physiol., 1893) they are mostly confined to
the connective tissue. Drummond (Jour. Anat. and Physiol., 11M)0)
also found large multinuclear giant cells, megakaryocytes, similar to
those of the bone-marrow; these were, however, very rare.

Many of these cells, after proper fixation, show mitotic figures. This

FIG. 245. DIAGRAM OF THE
BLOOD-VESSELS OF A LYMPH
NODE.

A composite section of three
follicles and the medullary cords
of a mesenteric lymphatic node
of the dog. A, artery; B, medul-
lary artery; C, follicular vein; E,
artery going to the capsule; F,
capillaries in the periphery of a
cord; G, medullary vein; H, fol-
licular artery; I, arterial capil-
laries in a follicle; J, vein from
capsule; K, cord; L, trabecula;
F, vein. X 501. (After Calvert.)

HEMOLYMPH NODES 239

mitosis has been most frequently observed in the large mononuclear type,
and is most abundant in the germinal centers of the nodules. The
small mononuclear and polymorphonuclcar types have also been shown to
be capable of cell reproduction by indirect division. Reproduction by
direct division of leukocytes appears to be rare, if indeed it ever actually
occurs.

The mononuclear as well as the polymorphonuclear forms appear to
be phagocytic. Among the inclusions which have been found within
these cells are fat globules, pigment granules, red blood corpuscles in
partial disintegration, insoluble pigments, such as carbon granules, etc.,
and bacteria. The cells of the reticulum are also believed to be phago-
cytic.

Blood-vessels. The arteries enter the lymph node at its hilum, and,
following the trabeculae within which they lie, are distributed to all por-
tions of the organ. In the medulla branches are distributed to the
lymph cords, in which they form a wide-meshed capillary plexus.

The terminal branches of the primary divisions of the afferent artery
are distributed to the nodules of the cortex. A single nodular branch
(Gal vert, Anat. Anz., 1897) enters the nodule and passes straight toward
its center, where it breaks into a plexus of divergent capillaries which
unite at the surface of the nodule to form small venous radicals.

The veins follow the internodular trabeculse in their course toward the
medulla, where they enter the medullary trabeculas, are augmented by
venous radicals from the capillary plexuses of this portion of the gland,
and thence follow the trabeculse to the hilum, where they unite to form
the efferent vein.

Certain of the arteries also pass from the medulla through the inter-
nodular trabeculse to the capsule of the gland, to which they supply
a capillary plexus. The blood is returned through veins which retrace
the course of the arteries and enter the large veins of the medullary
trabeculae.

HEMOLYMPH NODES

(Hemal Nodes)

These structures, which closely resemble the lymph nodes, were first
described by H. Gibbs (Quart. Jour. Mic. Sc.), in 1884. He found
them in the connective tissue between the renal artery and vein, in the
human subject. They have since been found in the prevertebral connec-
tive tissue, and in the mediastinum and mesentery. They are larger and
16

240

THE LYMPHATIC SYSTEM

more numerous in the ruminants, ox, sheep, etc., than in man. Their
size varies from that of a millet seed to that of a pea. In color they
closely resemble a minute extravasation of blood.

These organs are essentially lymphatic structures in which the lym-
phoid tissue is arranged in the form of cords rather than in nodules. The

FIG. 246. HEMOLYMPH NODE OF THE SHEEP.

The dark areas are blood sinuses; the lighter portion within is lymphoid tissue.

Photo. X 35. (After Warthin.)

node is inclosed by a fibrous capsule, beneath which is a broad sinus filled
with blood. In this fact lies the chief distinguishing feature of these
glands.

The peripheral blood sinus, which is analogous to the peripheral
lymph sinus of a lymph node, sends into the interior of the organ a
greater or less number of secondary sinuses. Based largely upon the
abundance of these secondary sinuses, the hemolymph nodes have been
divided into two varieties, named by Warthin (Jour. Bost. Soc. Med.
Sc., 1901) the 'splenolympli glands' and the ' 'marrowlym :./:// (jhtn da.'

HEMOLYMPH NODES

241

In the splenolymph type, which is the more abundant, the node
is of small size and is well filled with secondary blood sinuses. The
lymphoid tissue is supported by a similar reticulum, and contains the
same varieties of lymph cells as in the lymph nodes.

In the marrowlymph nodes a somewhat similar structure is found.
The blood sinuses are less numerous and lymph nodules do not occur
(Vincent, Warthin). The eosinophil leukocytes are more numerous
than in the splenolymph type, and the marrowlymph nodes as a rule are
the larger.

Huntington (Amer. Jour. Anat., 16, 3, 1914) has suggested that

FIG. 247. HORIZONTAL SECTION THROUGH THE FAUCIAL TONSIL OF A CHILD.

Semi-diagrammatic, a, stratified epithelium; b, crypts; c, lymph nodule; d, mucus-
secreting gland. Hematein and eosin. X about 20.

some of the structures described as hemolymph nodes may be post-natal
hemapoietic foci, in which erythrocytes develop from the endothelium
of the lymph channels. They probably function as accessory spleens hav-
ing a combined lymphopoietic and phagocytic activity.

Intermediate types between the lymph nodes and the splenolymph
type (Vincent, Jour. Anat. and Physiol., 1897) on the one hand, and be-
tween the splenolymph node and the spleen and marrowlymph type on
the other hand, are of frequent occurrence.

Blood Supply. The afferent artery, according to Drummond (Jour.
Anat. and Physiol., 1900), enters the hilum with the connective tissue,
and through the trabeculee reaches all parts of the node. In the lymphoid

242 THE LYMPHATIC SYSTEM

tissue its branches form a capillary plexus whose vessels open into the
blood sinuses. All the sinuses, peripheral and secondary, communicate
with each other, and from them the blood is ultimately collected into
two or more thin-walled veins. In the center of the gland these vessels
unite to form an efferent vein which passes out at the hilum.

DEVELOPMENT OF LYMPH NODES

Lymph nodes arise through the invasion of primary lymphatic capillary
plexuses by lymphocytes. The first lymph nodes arise in the regions of the
axilla and groin during the third month of development. Such areas be-
come circumscribed by the development of a capsule from the surrounding
mesenchyma. The capsular tissue is continued into the developing node
in the form of trabecula?, terminating in a dense network of delicate reticu-
lar fibers. Hydrostatic conditions probably determine the formation of a
peripheral lymph sinus. The retention of certain channels (internodular
and medullary sinuses) between the peripheral sinus and the efferent lym-
phatics at the hilum is likewise probably determined mainly by the opera-
tion of like factors, brought into play through the appearance of cortical
nodules. These nodules arise as regions of proliferative activity of lympho-
cytes. The node has meanwhile early become invaded at a point which
becomes the hilum by a vascular and nerve supply. Nodules arise as ac-
cumulations of proliferating lymphocytes about the cortical arterial twigs.
Hemolymph nodes apparently arise in a manner similar to the origin of
ordinary lymph nodes, and become only secondarily modified. The reticu-
lar tissue of lymph nodes may in part arise from the capillary endotbelium.

The function of lymph nodes is the production of lymphocytes, which
become phagocytic leukocytes. Besides having a Icukopoietic role, lymph
nodes probably function also as centers for the dissolution of worn-out
blood elements, in which process phagocytosis predominates, the lympho-
cytes being in part assisted by the endotholial cells of the capillaries.
Lymphoid aggregations also serve as 'lymph filters,' the phagocytes removing
from the lymph bacteria and other noxious products.

THE TONSILS

The Faucial Tonsils (1'a/nfine Tonxils; Ai>ii/(/((<t/ir). The tonsils
consist of a mass of lymphoid tiwue which projects slightly from either
side into the cavity of the fauces, and is covered by a layer of stratified
epithelium continuous with that which lines the oral and pharyngeal

THE TONSILS

243

cavities. The lymph nodules which compose the tonsil immediately
underlie the epithelial coat, and are embedded in areolar connect ivt-
tissue.

The epithelial coat here and there penetrates the substance of the
or<:an in the form of invaginated funnel-shaped depressions, the crypts
('follicles' of the tonsils). The direction of the crypts in the upper third
of the tonsil is downward and outward (C. P. Johnson). The ducts of
many mucous glands open into the recesses of these branching crypts.
The mucus-secreting glands lie in the loose connective tissue which sur-

/T*S" SM?* <S2jy~^ ~" -JEZZ~~ 3 ^-r'

J-TC^-t: - -^~ -^'g^>>_^^ : .-^, /-'f~r$

?<2Je ^5>S? e^^GD. .^'

<Sii-t;- s -<::.'. ,v-^ ^>3

^^^^S^^^S'.^^t 'C^/fe^-i 5 '

uSs> .0,^^G2 ..-* * '*"'-" : '^~ e> ^

o.-i-^- -'./,; '-^SS^faAV^m/^^IV-T^ffl^^ja JV 9 2<SAi

/

FIG. 248. FROM A CRYPT OF A DOG'S TONSIL.

a, stratified epithelium; b, basal margin of the epithelium; c, infiltration of the epi-
thelium by leukocytes; d, spaces in the epithelium filled with leukocytes and epithelial
cells; e, blood-vessel;/, lymphoid tissue. X 150. (After Bohm and von Davidoff.)

rounds the tonsil on all but its faucial surface. The crypts are lined
throughout by a layer of stratified epithelium, which is continuous with
that on the free surface of the tonsil, but which becomes progressively
thinner as it recedes into the deeper recesses of the crypts.

Many of the lymph cells migrate into the intercellular spaces of the
epithelial layer, and even penetrate to the free surface; thus they find
their way into the oral cavity, where they are found in large numbers
in the saliva, as 'salivary corpuscles.' If such salivary corpuscles are ex-
amined in a drop of saliva, freshly prepared, the fine intracellular gran-
ules of the polymorphonuclear leukocytes will be seen to undergo an
active dancing movement, Brownian motion. The salivary corpuscles are
derived not only from the faucial tonsils but from the other lymphoid
tissue which is in relation with the oral mucous membrane, e.g., the
lingual and pharyngeal tonsils.

The passage of leukocytes through the epithelial surface of the faucial

244

THE LYMPHATIC SYSTEM

tonsil is so very active that at times the epithelium becomes completely
filled with these cells, and it is then difficult to distinguish it from the
adenoid tissue beneath. The normal tonsils atrophy after puberty.

The Lingual Tonsil. A collection of lymph nodules is also found
at the base of the tongue in the median line, between the cireumvallate
papilla3 and the epiglottis. This, because of its similarity in appearance
and in structure to the faucial tonsil, is called the lingual tonsil.

In the lingual tonsil, however, the nodules are grouped about a

FIG. 249. THE LINGUAL TONSIL OF MAN.
a, a crypt; b, von Ebner's glands. Hematein and eosin. X 45.

single wide-mouthed crypt, the foramen caecum lingui. This crypt is
frequently branched, and into it the many mucous glands of the neighbor-
ing lingual mucosa pour their secretion.

The Pharyngeal Tonsil. The posterior wall of the nasopharynx is
supplied with a similar accumulation of lymph nodules, the pharyngeal
tonsil. It lies in the median line and extends downward from between
the orifices of the auditory (Eustachian) tubes for a distance of three
centimeters (Klein). It contains a considerable number of lymph nod-
ules and several small crypts. The lateral extensions in the vicinity
of the tubal orifices are sometimes known as the tubal tonsils.

The pharyngeal tonsil is prone to hypertrophy in youth, in which

THE SPLEEN 245

case it forms the adenoid growths which are so common in strumous
children.

Viewing the several tonsils and the associated lymphoid tissue as a
whole, it will be perceived that they constitute a lymphoid ring at the
gateway to the alimentary and respiratory tracts. The function of the
lymphoid tissue is to produce phagocytic leukocytes for the protection of
the body against bacteria and other noxious products. The tonsillar crypts
offer favorable foci for the lodgment, invasion and attack of such harmful
elements. The location of this annular mass of lymphoid tissue is signifi-
cant; it is placed where it can apparently best perform a necessary func-
tion. When called upon to increase its functional activity lymphoid tissue
responds by hypertrophy; this of itself may cause inconvenience by ob-
structing the channels employed in respiration and phonation. But when
unable to respond adequately and thus successfully cope with the infecting
material, the tonsils become diseased. This is commonly considered to call
for removal of the involved lymphoid masses. But it would seem that the
excision of the tonsils would result in handicapping the organism in its
perpetual combat with bacteria, by depriving it of a means of defense;
moreover in the case of removal of the faucial tonsils, proper phonation may
also be interfered with. However, excised tonsillar tissue is probably
largely compensated for by regeneration and hypertrophy of other non-
involved lymphoid tissue. Nevertheless it has been suggested that much
could be gained through prophylactic means consisting largely perhaps in
the promotion of mouth breathing and the prevention of chronic nasal cold
in infants.

THE SPLEEN

Structure. The spleen is the largest lymphoid organ of the body.
It is located to the left and dorsally between the stomach and diaphragm,
has an irregular oval outline, measures about five inches in length and
three inches in thickness, and weighs about seven ounces. It is subject
to great variations in size and shape. It is enveloped by a thick fibro-
elastic capsule, or tunica alljuginea, containing smooth muscle in its
inner portion. External to this is also a peritoneal investment, or tunica
serosa. The capsule of the spleen of the ox is especially robust, and
rich in smooth muscle. At one point, the hilum, the capsule projects
into the spleen as a large mass of trabecular tissue. Over the entire
surface also other trabeculse project from the capsule into the paren-
chyma of the organ. These trabeculas are of similar structure to the
capsule. The supporting tissue of the parenchyma is a delicate reticu-

246

THE LYMPHATIC SYSTEM

him. This is continuous with the fibre-elastic terminal processes of the
fibromuscular trabeeulse.

The primary trabecula? divide the parenchyma imperfectly into
roughly pyramidal compartments about one millimeter in diameter, with
three trabeculse for each lobule. This lobulation is faintly indicated by
surface markings. According to Mall this unit of structure, the splenic
lobule, is further subdivided into about ten smaller compartments by

FIG. 250. PORTION OF SPLEEN OF CAT, SHOWING CAPSULE (ABOVE) AND Two
SPLENIC NODULES WITH CENTRAL ARTERIOLE.

Between the two nodules can be seen portions of a trabecula with a blood-vessel.

anastomosing septa, continuous with the primary trabecula?. This divi-
sion of the spleen into lobules, and their subdivision into lobular com-
partments has structural significance also from the viewpoint of the
blood supply. A knowledge of the microscopic structure of the spleen
is dependent upon an understanding of the distribution of the blood-
vessels.

Blood-vessels. The splenic artery enters at the hilum, associated
with the splenic vein. The larger arterial branches are located within
the coarser trabeeulse continuous with the connective tissue of the hilum
and still accompanied by the larger tributaries of the splenic vein. The

THE SPLEEN

247

smaller arteries part company with the veins when they leave the tra-
beculae and pass into the apices of the lobules. At the point of entrance
into the lobule the adventitia of the intralobular artery becomes in-
filtrated with lymphocytes, forming thus a spherical or fusiform
lymphoid mass,
the splenic nodule
( Malpighian cor-
puscle) character-
istic of the spleen.
This arterial ves-
sel gives off nu-
merous branches
to the splenic
nodule, some of
which pass beyond
the confines of the
nodule into the
splenic pulp.
Some of these
nodules contain
germ centers. In
infancy all of the
nodules are said
to contain germ
centers.

The artery
usually passes
e x c e n t r i cally
through the nod-
ule. The nod-
ules are fre-
quently situated

at the point where the artery branches and in consequence contain two
arterial vessels. Beyond the splenic nodules, the iutralobular artery
breaks into a number of twigs, one for each lobular compartment. Within
each compartment, the arteriole divides into a brush of delicate precapil-
lary arterioles, the penicilli of Euysch. On these appear an ellipsoidal
condensation of reticular tissue forming the so-called s/ilcnir r/lifixohl*.
These arterioles (six to ten microns in diameter) are known as xliettthed
arteries. The splenic pulp of the lobules can be divided into somewhat

FIG. 251. DIAGRAM OF A LOBULE OF THE SPLEEN.

A, artery lying in the center of the lobule; Am, a terminal
ampulla of the artery; C, intralobular vein; L, a splenic cor-
puscle; P, venous plexus within the pulp of the spleen; Tr,
fibromuscular trabecula within the lobule; V, interlobular
vein, lying in a large trabecula. (After Mall.)

248

THE LYMPHATIC SYSTEM

denser cords of uncertain outline, the splenic pulp cords, and slightly
looser intercordal pulp, the venous sinuses, corresponding to the sinuses
of the medulla of lymph nodes. The penicilli are located in the pulp
cords. Terminally these penicilli expand into dilatations, the ampullce
of Thoma.

The exact method of passage of the blood from the terminal arterioles
to the initial venules is uncertain and disputed. It is certain only that
blood passes freely at this point into the splenic pulp. This gives the
adenoid tissue a deeply red or purple color, in contrast to the light pink
color of ordinary lymph nodes, due to the presence of innumerable ery-

throplastids. It seems prob-
fi able that the walls of the con-

> necting capillaries and the ini-

tial venules (cavernous veins,
venous sinuses) are fenestra-
ted, permitting the free pas-
sage of blood from these vessels
into the spleen pulp.

According to some au-
thorities the blood passes
by two routes from the
arterioles to the venules;
(1) through the arterial
ampullae directly into the
venules (venous ampullae) ;
and (2) from other ter-
minal arterial twigs into
the spleen pulp, from where it is collected by the venules.

The veins thus begin as wide sinusoidal channels (pulp veins) within
the splenic pulp. At first, and for a considerable distance, they follow
an independent course through the pulp, receiving at the same time
frequent accessions of blood from other venous radicals. Finally, how-
ever, the veins enter the larger trabeculse, but are still devoid of more
complete coats than the thin membrane of fibro-elastic tissue which sur-
rounds the endothelial tube, but which is now ensheathed by the trabecu-
lar tissue. Henceforth the path of the veins lies within the trabeculaa
(interlobular veins), and is directed toward the hilum. On approaching
the hilum the larger veins acquire the usual venous coats. Having ar-
rived at the hilum, they form several efferent vessels wh